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Sample records for cancer susceptibility gene

  1. Breast Cancer Susceptibility Gene1 (BRCA1

    Directory of Open Access Journals (Sweden)

    Wasiksiri, S.

    2002-07-01

    Full Text Available Breast Cancer Susceptibility Gene1 (BRCA1 is a tumor suppressor gene for breast and ovarian cancers. The gene locates at chromosome 17q21 and encodes for 1863 amino acids protein. It is believed that BRCA1 protein is involved in many functions such as DNA repair, centrosome replication, cell cycle checkpoint and replication of other genes. More than 800 mutations have been found in the population with an increased risk of cancer incidence in their families. Germ-line mutation of BRCA1 accounts for 5-10 percent of all breast cancer cases. Epigenetic modifications also reduce the function of normal BRCA1 gene. Several methods are used for laboratory diagnosis of cancer-related mutations. The development of breast cancer in carriers at risk with BRCA1 mutations may be prevented by suitable prevention plans such as breast cancer screening, ovarian cancer screening, surgery and cancer chemotherapy.

  2. FGF receptor genes and breast cancer susceptibility

    DEFF Research Database (Denmark)

    Agarwal, D; Pineda, S; Michailidou, K;

    2014-01-01

    Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying......, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression.Results:Little evidence of association with breast cancer risk...... that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2....

  3. Hereditary Breast Cancer: The Era of New Susceptibility Genes

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    Paraskevi Apostolou

    2013-01-01

    Full Text Available Breast cancer is the most common malignancy among females. 5%–10% of breast cancer cases are hereditary and are caused by pathogenic mutations in the considered reference BRCA1 and BRCA2 genes. As sequencing technologies evolve, more susceptible genes have been discovered and BRCA1 and BRCA2 predisposition seems to be only a part of the story. These new findings include rare germline mutations in other high penetrant genes, the most important of which include TP53 mutations in Li-Fraumeni syndrome, STK11 mutations in Peutz-Jeghers syndrome, and PTEN mutations in Cowden syndrome. Furthermore, more frequent, but less penetrant, mutations have been identified in families with breast cancer clustering, in moderate or low penetrant genes, such as CHEK2, ATM, PALB2, and BRIP1. This paper will summarize all current data on new findings in breast cancer susceptibility genes.

  4. Mucin 1 Gene (MUC1 and Gastric-Cancer Susceptibility

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    Norihisa Saeki

    2014-05-01

    Full Text Available Gastric cancer (GC is one of the major malignant diseases worldwide, especially in Asia. It is classified into intestinal and diffuse types. While the intestinal-type GC (IGC is almost certainly caused by Helicobacter pylori (HP infection, its role in the diffuse-type GC (DGC appears limited. Recently, genome-wide association studies (GWAS on Japanese and Chinese populations identified chromosome 1q22 as a GC susceptibility locus which harbors mucin 1 gene (MUC1 encoding a cell membrane-bound mucin protein. MUC1 has been known as an oncogene with an anti-apoptotic function in cancer cells; however, in normal gastric mucosa, it is anticipated that the mucin 1 protein has a role in protecting gastric epithelial cells from a variety of external insults which cause inflammation and carcinogenesis. HP infection is the most definite insult leading to GC, and a protective function of mucin 1 protein has been suggested by studies on Muc1 knocked-out mice.

  5. TERT gene harbors multiple variants associated with pancreatic cancer susceptibility

    Czech Academy of Sciences Publication Activity Database

    Campa, D.; Rizzato, C.; Stolzenberg-Solomon, R.; Pacetti, P.; Vodička, Pavel; Cleary, S.P.; Capurso, G.; Bueno-de-Mesquita, H. B.; Werner, J.; Gazouli, M.; Butterbach, K.; Ivanauskas, A.; Giese, N.; Petersen, G. M.; Fogar, P.; Wang, Z.; Bassi, C.; Ryska, M.; Theodoropoulos, G.E.; Kooperberg, Ch.; Li, D.; Greenhalf, W.; Pasquali, C.; Hackert, T.; Fuchs, Ch.S.; Mohelníková-Duchoňová, B.; Sperti, C.; Funel, N.; Dieffenbach, A.K.; Wareham, N.J.; Buring, J.; Holcátová, I.; Costello, E.; Zambon, C.F.; Kupcinskas, J.; Risch, H.A.; Kraft, P.; Bracci, P.M.; Pezzilli, R.; Olson, S.H.; Sesso, H. D.; Hartge, P.; Strobel, O.; Malecka-Panas, E.; Visvanathan, K.; Arslan, A. A.; Pedrazzoli, S.; Souček, P.; Gioffreda, D.; Key, T.J.; Talar-Wojnarowska, R.; Scarpa, A.; Mambrini, A.; Jacobs, E.J.; Jamroziak, K.; Klein, A.; Tavano, F.; Bambi, F.; Landi, S.; Austin, M. A.; Vodičková, Ludmila; Brenner, H.; Chanock, S. J.; Fave, G.D.; Piepoli, A.; Cantore, M.; Zheng, W.; Wolpin, B.M.; Amundadottir, L. T.; Canzian, F.

    2015-01-01

    Roč. 137, č. 9 (2015), s. 2175-2183. ISSN 0020-7136 R&D Projects: GA ČR GAP301/12/1734 Institutional support: RVO:68378041 Keywords : pancreatic cancer * polymorphisms * telomerase * susceptibility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.085, year: 2014

  6. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility

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    Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B;

    2016-01-01

    Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and.......5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry....

  7. Functional polymorphisms in the IL-10 gene with susceptibility to esophageal, nasopharyngeal, and oral cancers.

    Science.gov (United States)

    Li, Yu-Fen; Yang, Pei-Zhen; Li, Hua-Feng

    2016-03-18

    Emerging evidence showed that functional polymorphisms in the IL-10 gene may have effects on individuals' susceptibility to nasopharyngeal, oral and esophageal cancers, yet individually published findings are inconsistent. We therefore designed the meta-analysis to investigate the correlations of IL-10 genetic polymorphisms with susceptibility to nasopharyngeal, oral and esophageal cancers. The EMBASE, MEDLINE, CINAHL, Web of Science and the Chinese Biomedical Database (CBM) databases were searched with no language restrictions. We use Comprehensive Meta-analysis 2.0 software to carry out statistical analysis. Ten case-control studies with a number of 1,883 patients and 2,857 healthy subjects were enrolled. Our results revealed that IL-10 rs1800872 T>G and rs1800896 A>G polymorphisms has a significantly association with the increased risk of esophageal cancer under the allele and dominant models; rs1800871 T>G, rs1800872 T>G and rs1800896 A>G under allele and dominant models could increase the risk of nasopharyngeal cancer; rs1800871T>G, rs1800872T>G and rs1800896 A>G SNPs under allele model were closely related to the susceptibility to oral cancer. Our findings support the point that IL-10 genetic polymorphisms may play essential role in identifying esophageal cancer, nasopharyngeal cancer and oral cancer at early stage. PMID:27002767

  8. Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

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    Nigel P S Crawford

    2007-11-01

    Full Text Available A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b, was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.

  9. Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study

    International Nuclear Information System (INIS)

    MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility. We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls) to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH). Using unconditional logistic regression we found that MLH3 (L844P, G>A) polymorphism GA (Leu/Pro) and AA (Pro/Pro) genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95) (p = 0.03) and OR = 0.62 (0.41-0.94) (p = 0.03), respectively. Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83), p = 0.01] associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49), p = 0.01], GG/AA [OR = 2.11 (1.12-3,98), p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15), p = 0.02] all associated with an increased risk for breast cancer. It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results

  10. Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility

    International Nuclear Information System (INIS)

    CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility. We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls. The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect. Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations

  11. Role of tumour necrosis factor gene polymorphisms (-308 and -238) in breast cancer susceptibility and severity

    International Nuclear Information System (INIS)

    Genetic polymorphisms in the promoter region of the tumour necrosis factor (TNF) gene can regulate gene expression and have been associated with inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter of the TNF gene (-308 G>A and -238 G>A) for their role in breast cancer susceptibility and severity by means of an allelic association study. Using a case–control study design, breast cancer patients (n = 709) and appropriate age-matched and sex-matched controls obtained from the Breast Screening Unit (n = 498) were genotyped for these TNF polymorphisms, using a high-throughput allelic discrimination method. Allele frequencies for both polymorphisms were similar in both breast cancer cases and controls. However, the -308 polymorphism was found to be associated with vascular invasion in breast tumours (P = 0.024). Comparison with other standard prognostic indices did not show any association for either genotype. We demonstrated no association between the -308G>A polymorphism and the -238G>A polymorphism in the promoter region of TNF and susceptibility to breast cancer, in a large North European population. However, the -308 G>A polymorphism was found to be associated with the presence of vascular invasion in breast tumours

  12. Endostatin gene variation and protein levels in breast cancer susceptibility and severity

    International Nuclear Information System (INIS)

    Endostatin is a potent endogenous anti-angiogenic agent which inhibits tumour growth. A non-synonymous coding polymorphism in the Endostatin gene is thought to affect Endostatin activity. We aimed to determine the role of this Endostatin polymorphism in breast cancer pathogenesis and any influence on serum Endostatin levels in healthy volunteers. Endostatin protein expression on a breast cancer micro array was also studied to determine any relationship to genotype and to breast cancer prognosis. The 4349G > A (coding non-synonymous) polymorphism in exon 42 of the Endostatin gene was genotyped in approximately 846 breast cancer cases and 707 appropriate controls. In a separate healthy cohort of 57 individuals, in addition to genotyping, serum Endostatin levels were measured using enzyme linked immunosorbant assay (ELISA). A semi-quantitative assessment of Endostatin protein expression on immunostained tissue micro arrays (TMA) constructed from breast cancer samples of patients with genotype data was performed. The rare allele (A) was significantly associated with invasive breast cancers compared to non-invasive tumours (p = 0.03), but there was no association with tumour grade, nodal status, vascular invasion or overall survival. There was no association with breast cancer susceptibility. Serum Endostatin levels and Endostatin protein expression on the tissue micro array were not associated with genotype. The Endostatin 4349A allele is associated with invasive breast cancer. The Endostatin 4349G > A polymorphism however does not appear to be associated with breast cancer susceptibility or severity in invasive disease. By studying circulating levels and tumour Endostatin protein expression, we have shown that any influence of this polymorphism is unlikely to be through an effect on the levels of protein produced

  13. Tagging single nucleotide polymorphisms in the BRIP1 gene and susceptibility to breast and ovarian cancer.

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    Honglin Song

    Full Text Available BACKGROUND: BRIP1 interacts with BRCA1 and functions in regulating DNA double strand break repair pathways. Germline BRIP1 mutations are associated with breast cancer and Fanconi anemia. Thus, common variants in the BRIP1 are candidates for breast and ovarian cancer susceptibility. METHODS: We used a SNP tagging approach to evaluate the association between common variants (minor allele frequency>or=0.05 in BRIP1 and the risks of breast cancer and invasive ovarian cancer. 12 tagging SNPs (tSNPs in the gene were identified and genotyped in up to 2,270 breast cancer cases and 2,280 controls from the UK and up to 1,513 invasive ovarian cancer cases and 2,515 controls from the UK, Denmark and USA. Genotype frequencies in cases and controls were compared using logistic regression. RESULTS: Two tSNPs showed a marginal significant association with ovarian cancer: Carriers of the minor allele of rs2191249 were at reduced risk compared with the common homozygotes (Odds Ratio (OR = 0.90 (95% CI, 0.82-1.0, P-trend = 0.045 and the minor allele of rs4988344 was associated with increased risk (OR = 1.15 (95%CI, 1.02-1.30, P-trend = 0.02. When the analyses were restricted to serous ovarian cancers, these effects became slightly stronger. These results were not significant at the 5% level after adjusting for multiple testing. None of the tSNPs was associated with breast cancer. CONCLUSIONS: It is unlikely that common variants in BRIP1 contribute significantly to breast cancer susceptibility. The possible association of rs2191249 and rs4988344 with ovarian cancer risks warrant confirmation in independent case-control studies.

  14. Mechanisms of inherited cancer susceptibility

    Institute of Scientific and Technical Information of China (English)

    Shirley HODGSON

    2008-01-01

    A small proportion of many cancers are due to inherited mutations in genes, which result in a high risk to the individual of developing specific cancers. There are several classes of genes that may be involved: tumour suppressor genes, oncogenes, genes encoding proteins involved in DNA repair and cell cycle control, and genes involved in stimulating the angiogenic pathway. Alterations in susceptibility to cancer may also be due to variations in genes involved in carcinogen metabolism. This review discusses examples of some of these genes and the associated clinical conditions caused by the inheritance of mutations in such genes.

  15. Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study

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    Pina Julieta

    2009-09-01

    Full Text Available Abstract Background MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility. Methods We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH. Results Using unconditional logistic regression we found that MLH3 (L844P, G>A polymorphism GA (Leu/Pro and AA (Pro/Pro genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95 (p = 0.03 and OR = 0.62 (0.41-0.94 (p = 0.03, respectively. Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83, p = 0.01] associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49, p = 0.01], GG/AA [OR = 2.11 (1.12-3,98, p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15, p = 0.02] all associated with an increased risk for breast cancer. Conclusion It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results.

  16. Genome-wide linkage scan for colorectal cancer susceptibility genes supports linkage to chromosome 3q

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    Velculescu Victor E

    2008-04-01

    Full Text Available Abstract Background Colorectal cancer is one of the most common causes of cancer-related mortality. The disease is clinically and genetically heterogeneous though a strong hereditary component has been identified. However, only a small proportion of the inherited susceptibility can be ascribed to dominant syndromes, such as Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Familial Adenomatous Polyposis (FAP. In an attempt to identify novel colorectal cancer predisposing genes, we have performed a genome-wide linkage analysis in 30 Swedish non-FAP/non-HNPCC families with a strong family history of colorectal cancer. Methods Statistical analysis was performed using multipoint parametric and nonparametric linkage. Results Parametric analysis under the assumption of locus homogeneity excluded any common susceptibility regions harbouring a predisposing gene for colorectal cancer. However, several loci on chromosomes 2q, 3q, 6q, and 7q with suggestive linkage were detected in the parametric analysis under the assumption of locus heterogeneity as well as in the nonparametric analysis. Among these loci, the locus on chromosome 3q21.1-q26.2 was the most consistent finding providing positive results in both parametric and nonparametric analyses Heterogeneity LOD score (HLOD = 1.90, alpha = 0.45, Non-Parametric LOD score (NPL = 2.1. Conclusion The strongest evidence of linkage was seen for the region on chromosome 3. Interestingly, the same region has recently been reported as the most significant finding in a genome-wide analysis performed with SNP arrays; thus our results independently support the finding on chromosome 3q.

  17. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors

    OpenAIRE

    Nickels, Stefan; Truong, Thérèse; Hein, Rebecca; Stevens, Kristen; Buck, Katharina; Behrens, Sabine; Eilber, Ursula; Schmidt, Martina; Häberle, Lothar; Vrieling, Alina; Gaudet, Mia; Figueroa, Jonine; Schoof, Nils; Spurdle, Amanda B.; Rudolph, Anja

    2013-01-01

    Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with ...

  18. HSD3B and gene-gene interactions in a pathway-based analysis of genetic susceptibility to bladder cancer.

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    Angeline S Andrew

    Full Text Available Bladder cancer is the 4(th most common cancer among men in the U.S. We analyzed variant genotypes hypothesized to modify major biological processes involved in bladder carcinogenesis, including hormone regulation, apoptosis, DNA repair, immune surveillance, metabolism, proliferation, and telomere maintenance. Logistic regression was used to assess the relationship between genetic variation affecting these processes and susceptibility in 563 genotyped urothelial cell carcinoma cases and 863 controls enrolled in a case-control study of incident bladder cancer conducted in New Hampshire, U.S. We evaluated gene-gene interactions using Multifactor Dimensionality Reduction (MDR and Statistical Epistasis Network analysis. The 3'UTR flanking variant form of the hormone regulation gene HSD3B2 was associated with increased bladder cancer risk in the New Hampshire population (adjusted OR 1.85 95%CI 1.31-2.62. This finding was successfully replicated in the Texas Bladder Cancer Study with 957 controls, 497 cases (adjusted OR 3.66 95%CI 1.06-12.63. The effect of this prevalent SNP was stronger among males (OR 2.13 95%CI 1.40-3.25 than females (OR 1.56 95%CI 0.83-2.95, (SNP-gender interaction P = 0.048. We also identified a SNP-SNP interaction between T-cell activation related genes GATA3 and CD81 (interaction P = 0.0003. The fact that bladder cancer incidence is 3-4 times higher in males suggests the involvement of hormone levels. This biologic process-based analysis suggests candidate susceptibility markers and supports the theory that disrupted hormone regulation plays a role in bladder carcinogenesis.

  19. Construction of label-free electrochemical immunosensor on mesoporous carbon nanospheres for breast cancer susceptibility gene

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Haixia; Zhang, Yong; Wu, Dan; Ma, Hongmin; Li, Xiaojing; Li, Yan; Wang, Huan; Li, He; Du, Bin [Key Laboratory of Chemical Sensing and Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022 (China); Wei, Qin, E-mail: sdjndxwq@163.com [Key Laboratory of Chemical Sensing and Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022 (China)

    2013-04-03

    Highlights: ► The immunosensor is designed to determine breast cancer susceptibility gene. ► Mesoporous carbon nanospheres (MCN) have great adsorption capacity. ► MCN could enhance the electroactivity of toluidine blue. ► Room temperature ionic liquid should increase the electrochemical signal. -- Abstract: In this contribution, mesoporous carbon nanospheres (MCN) were used to fabricate a label-free electrochemical immunosensor for breast cancer susceptibility gene (BRCAl). The detection platform was constructed by conjugation of anti-BRCA1 on glassy carbon electrodes which were modified by mesoporous carbon nanospheres–toluidine blue nanocomposite (MCN–TB)/room temperature ionic-liquid (RTIL) composited film. TB was adsorbed onto MCN and acted as a redox probe. The electroactivity of TB was greatly enhanced in the presence of MCN. The good conductivity of MCN and BMIM·BF{sub 4} could promote the electron transfer and thus enhance the detection sensitivity. Moreover, the large surface area of MCN and the protein-binding properties of BMIM·BF{sub 4} could greatly increase the antibody loading. The specific antibody–antigen immunoreaction on the electrode surface resulted in a decrease of amperometric signal of the electrode. Under optimized conditions, the amperometric signal decreased linearly with BRCAl concentration in the range of 0.01–15 ng mL{sup −1} with a low detection limit of 3.97 pg mL{sup −1}. The immunosensor exhibits high sensitivity, good selectivity and stability.

  20. Bioinformatics Analysis for Coding SNPs of the HLADQA1 Gene Involved in Susceptibility to Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    Yanyun Li; Jun Xing; Linsheng Zhao; Yanni Li; Yuchuan Wang; Weiming Zhang

    2006-01-01

    OBJECTIVE To analyze coding SNPs of the HLA-DQA1 gene involved in susceptibility for cervical cancer by a bioinformatics approach, and to choose some SNPs that may have an association with cervical cancer.METHODS By a SNPper tool we extracted SNPs from a public database (dbSNP), exporting them in FASTA formats suitable for subsequent use.Then we used PARSESNP as a tool for the analysis of the cSNPs.RESULTS In the cSNPs of the HLA-DQA1 gene, we find that rs9272693and rs9272703, are made up of missense mutations which convert a codon for one amino acid into a codon for a different amino acid. We chose a PSSM Difference >10 as a lower level for the scores of changes predicted to be deldterious.CONCLUSION We used a bioinformatics approach for cSNPs analysis of the HLA-DQA1 gene. This method can select the variants in a conserved region, and give a PSSM Difference score. But the results need to be verified in cervical cancer patients and a control population.

  1. Correlations between the COMT gene rs4680 polymorphism and susceptibility to ovarian cancer.

    Science.gov (United States)

    Pan, W; Liao, H

    2015-01-01

    The objective of this study was to perform a systematic review of the correlations between the single nucleotide polymorphism rs4680 in the catechol-O-methyltransferase (COMT) gene and susceptibility to ovarian cancer. A computer search was carried out for relevant case-control studies published between January 2000 to January 2014 in databases such as Ovid, EBSCO, PubMed, CNKI, CBMDISC, VIP, and WanFang Data. The literature was screened based on inclusion and exclusion criteria. A meta-analysis was performed by calculating the combined odds ratios (OR) and 95% confidence intervals (CI) using the RevMan 5.0. A total of 7 case-control studies were selected, which included 1439 cases and 2927 control subjects. Meta-analysis showed that the rs4680 polymorphism was not associated with ovarian cancer [GG vs (GA+AA): OR = 1.02, 95%CI = 0.88-1.19; G vs A allele: OR = 1.0, 95%CI = 0.90-1.11]. We, therefore, conclude that the COMT rs4680 polymorphism is not associated with susceptibility to ovarian cancer. PMID:26681027

  2. Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot"

    DEFF Research Database (Denmark)

    Johnatty, Sharon E; Beesley, Jonathan; Chen, Xiaoqing; Macgregor, Stuart; Duffy, David L; Spurdle, Amanda B; deFazio, Anna; Gava, Natalie; Webb, Penelope M; Rossing, Mary Anne; Doherty, Jennifer Anne; Goodman, Marc T; Lurie, Galina; Thompson, Pamela J; Wilkens, Lynne R; Ness, Roberta B; Moysich, Kirsten B; Chang-Claude, Jenny; Wang-Gohrke, Shan; Cramer, Daniel W; Terry, Kathryn L; Hankinson, Susan E; Tworoger, Shelley S; Garcia-Closas, Montserrat; Yang, Hannah; Lissowska, Jolanta; Chanock, Stephen J; Pharoah, Paul D; Song, Honglin; Whitemore, Alice S; Pearce, Celeste L; Stram, Daniel O; Wu, Anna H; Pike, Malcolm C; Gayther, Simon A; Ramus, Susan J; Menon, Usha; Gentry-Maharaj, Aleksandra; Anton-Culver, Hoda; Ziogas, Argyrios; Hogdall, Estrid; Kjaer, Susanne K; Hogdall, Claus; Berchuck, Andrew; Schildkraut, Joellen M; Iversen, Edwin S; Moorman, Patricia G; Phelan, Catherine M; Sellers, Thomas A; Cunningham, Julie M; Vierkant, Robert A; Rider, David N; Goode, Ellen L; Haviv, Izhak; Chenevix-Trench, Georgia

    2010-01-01

    We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs) in 173 genes in...

  3. Polymorphisms in DNA Repair Gene XRCC3 and Susceptibility to Breast Cancer in Saudi Females

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    Alaa Mohammed Ali

    2016-01-01

    Full Text Available We investigated three common polymorphisms (SNPs in the XRCC3 gene (rs861539, rs1799794, and rs1799796 in 143 Saudi females suffering from breast cancer (median age = 51.4 years and 145 age matched normal healthy controls. DNA was extracted from whole blood and genotyping was conducted using PCR-RFLP. rs1799794 showed significant association, where AA and AA+AG occurred at a significantly higher frequency in the cancer patients compared to the control group (OR: 28.1; 95% CI: 3.76–21.12; χ2: 22.82; pT and rs1799796 A>G did not show a significant difference when the results in the patients and controls were compared. However, the frequency of rs1799796 differed significantly in patients with different age of diagnosis, tumor grade, and ER and HER2 status. The wild type A allele occurred at a higher frequency in the ER− and HER2− group. Our results among Saudis suggest that some variations in XRCC3 may contribute to breast cancer susceptibility. In conclusion, the results obtained during this study suggest that rs1799794 in XRCC3 shows strong association with breast cancer development in Saudi females.

  4. An Integrated Genome-Wide Systems Genetics Screen for Breast Cancer Metastasis Susceptibility Genes.

    Science.gov (United States)

    Bai, Ling; Yang, Howard H; Hu, Ying; Shukla, Anjali; Ha, Ngoc-Han; Doran, Anthony; Faraji, Farhoud; Goldberger, Natalie; Lee, Maxwell P; Keane, Thomas; Hunter, Kent W

    2016-04-01

    Metastasis remains the primary cause of patient morbidity and mortality in solid tumors and is due to the action of a large number of tumor-autonomous and non-autonomous factors. Here we report the results of a genome-wide integrated strategy to identify novel metastasis susceptibility candidate genes and molecular pathways in breast cancer metastasis. This analysis implicates a number of transcriptional regulators and suggests cell-mediated immunity is an important determinant. Moreover, the analysis identified novel or FDA-approved drugs as potentially useful for anti-metastatic therapy. Further explorations implementing this strategy may therefore provide a variety of information for clinical applications in the control and treatment of advanced neoplastic disease. PMID:27074153

  5. Identification of New Genetic Susceptibility Loci for Breast Cancer Through Consideration of Gene-Environment Interactions

    Science.gov (United States)

    Schoeps, Anja; Rudolph, Anja; Seibold, Petra; Dunning, Alison M.; Milne, Roger L.; Bojesen, Stig E.; Swerdlow, Anthony; Andrulis, Irene; Brenner, Hermann; Behrens, Sabine; Orr, Nicholas; Jones, Michael; Ashworth, Alan; Li, Jingmei; Cramp, Helen; Connley, Dan; Czene, Kamila; Darabi, Hatef; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Knight, Julia; Glendon, Gord; Mulligan, Anna M.; Dumont, Martine; Severi, Gianluca; Baglietto, Laura; Olson, Janet; Vachon, Celine; Purrington, Kristen; Moisse, Matthieu; Neven, Patrick; Wildiers, Hans; Spurdle, Amanda; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M.; Hamann, Ute; Ko, Yon-Dschun; Dieffenbach, Aida K.; Arndt, Volker; Stegmaier, Christa; Malats, Núria; Arias Perez, JoséI.; Benítez, Javier; Flyger, Henrik; Nordestgaard, Børge G.; Truong, Théresè; Cordina-Duverger, Emilie; Menegaux, Florence; Silva, Isabel dos Santos; Fletcher, Olivia; Johnson, Nichola; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Braaf, Linde; Atsma, Femke; van den Broek, Alexandra J.; Makalic, Enes; Schmidt, Daniel F.; Southey, Melissa C.; Cox, Angela; Simard, Jacques; Giles, Graham G.; Lambrechts, Diether; Mannermaa, Arto; Brauch, Hiltrud; Guénel, Pascal; Peto, Julian; Fasching, Peter A.; Hopper, John; Flesch-Janys, Dieter; Couch, Fergus; Chenevix-Trench, Georgia; Pharoah, Paul D. P.; Garcia-Closas, Montserrat; Schmidt, Marjanka K.; Hall, Per; Easton, Douglas F.; Chang-Claude, Jenny

    2014-01-01

    Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10−07), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m2 (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m2 or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10−05). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci. PMID:24248812

  6. A systems genetics approach identifies CXCL14, ITGAX, and LPCAT2 as novel aggressive prostate cancer susceptibility genes.

    Directory of Open Access Journals (Sweden)

    Kendra A Williams

    2014-11-01

    Full Text Available Although prostate cancer typically runs an indolent course, a subset of men develop aggressive, fatal forms of this disease. We hypothesize that germline variation modulates susceptibility to aggressive prostate cancer. The goal of this work is to identify susceptibility genes using the C57BL/6-Tg(TRAMP8247Ng/J (TRAMP mouse model of neuroendocrine prostate cancer. Quantitative trait locus (QTL mapping was performed in transgene-positive (TRAMPxNOD/ShiLtJ F2 intercross males (n = 228, which facilitated identification of 11 loci associated with aggressive disease development. Microarray data derived from 126 (TRAMPxNOD/ShiLtJ F2 primary tumors were used to prioritize candidate genes within QTLs, with candidate genes deemed as being high priority when possessing both high levels of expression-trait correlation and a proximal expression QTL. This process enabled the identification of 35 aggressive prostate tumorigenesis candidate genes. The role of these genes in aggressive forms of human prostate cancer was investigated using two concurrent approaches. First, logistic regression analysis in two human prostate gene expression datasets revealed that expression levels of five genes (CXCL14, ITGAX, LPCAT2, RNASEH2A, and ZNF322 were positively correlated with aggressive prostate cancer and two genes (CCL19 and HIST1H1A were protective for aggressive prostate cancer. Higher than average levels of expression of the five genes that were positively correlated with aggressive disease were consistently associated with patient outcome in both human prostate cancer tumor gene expression datasets. Second, three of these five genes (CXCL14, ITGAX, and LPCAT2 harbored polymorphisms associated with aggressive disease development in a human GWAS cohort consisting of 1,172 prostate cancer patients. This study is the first example of using a systems genetics approach to successfully identify novel susceptibility genes for aggressive prostate cancer. Such

  7. Association of DNA repair gene XRCC1 and lung cancer susceptibility among nonsmoking Chinese women

    DEFF Research Database (Denmark)

    Yin, J.; Vogel, Ulla Birgitte; Ma, Y.;

    2009-01-01

    predisposition to cancer risk. To address this question in more detail, we conducted a hospital-based case-control study consisting of 55 lung cancer cases and 74 cancer-free controls matched on age and ethnicity among nonsmoking Chinese women. We analyzed five coding single-nucleotide polymorphisms in the XRCC1...... the haplotype encompassing the variant alleles may contribute to susceptibility of lung cancer in a Chinese population....

  8. Possible association of β2- and β3-adrenergic receptor gene polymorphisms with susceptibility to breast cancer

    OpenAIRE

    Xin-en HUANG; Hamajima, Nobuyuki; Saito, Toshiko; Matsuo, Keitaro; Mizutani, Mitsuhiro; Iwata, Hiroji; Iwase, Takuji; Miura, Shigeto; Mizuno, Tsutomu; Tokudome, Shinkan; Tajima, Kazuo

    2001-01-01

    Background The involvement of β2-adrenergic receptor (ADRB2) and β3-adrenergic receptor (ADRB3) in both adipocyte lipolysis and thermogenic activity suggests that polymorphisms in the encoding genes might be linked with interindividual variation in obesity, an important risk factor for postmenopausal breast cancer. In order to examine the hypothesis that genetic variations in ADRB2 and ADRB3 represent interindividual susceptibility factors for obesity and breast cancer, we conducted a hospita...

  9. Genotype, phenotype and cancer: Role of low penetrance genes and environment in tumour susceptibility

    Indian Academy of Sciences (India)

    Ashwin Kotnis; Rajiv Sarin; Rita Mulherkar

    2005-02-01

    Role of heredity and lifestyle in sporadic cancers is well documented. Here we focus on the influence of low penetrance genes and habits, with emphasis on tobacco habit in causing head and neck cancers. Role of such gene-environment interaction can be well studied in individuals with multiple primary cancers. Thus such a biological model may elucidate that cancer causation is not solely due to genetic determinism but also significantly relies on lifestyle of the individual.

  10. Impacts of CA9 gene polymorphisms and environmental factors on oral-cancer susceptibility and clinicopathologic characteristics in Taiwan.

    Directory of Open Access Journals (Sweden)

    Ming-Hsien Chien

    Full Text Available BACKGROUND: In Taiwan, oral cancer has causally been associated with environmental carcinogens. Carbonic anhydrase 9 (CA9 is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study explored the combined effect of CA9 gene polymorphisms and exposure to environmental carcinogens on the susceptibility of developing oral squamous cell carcinoma (OSCC and the clinicopathological characteristics of the tumors. METHODOLOGY AND PRINCIPAL FINDINGS: Four single-nucleotide polymorphisms (SNPs of the CA9 gene from 462 patients with oral cancer and 519 non-cancer controls were analyzed by a real-time polymerase chain reaction (PCR. While the studied SNPs (CA9 rs2071676, rs3829078, rs1048638 and +376 Del were not associated with susceptibility to oral cancer, the GAA haplotype of 3 CA9 SNPs (rs2071676, rs3829078, and rs1048638 was related to a higher risk of oral cancer. Moreover, the four CA9 SNPs combined with betel quid chewing and/or tobacco consumption could robustly elevate susceptibility to oral cancer. Finally, patients with oral cancer who had at least one G allele of CA9 rs2071676 were at higher risk for developing lymph-node metastasis (p = 0.022, compared to those patients homozygous for AA. CONCLUSIONS: Our results suggest that the haplotype of rs2071676, rs3829078, and rs1048638 combined has potential predictive significance in oral carcinogenesis. Gene-environment interactions of CA9 polymorphisms, smoking, and betel-quid chewing might alter oral cancer susceptibility and metastasis.

  11. Combined effects of IL-8 and CXCR2 gene polymorphisms on breast cancer susceptibility and aggressiveness

    International Nuclear Information System (INIS)

    Interleukin-8 (IL-8/CXCL-8) is a prototype of the ELR+CXC chemokines that play an important role in the promotion and progression of many human cancers including breast cancer. We have recently showed the implication of polymorphism (-251) T/A of IL-8 gene in the susceptibility and prognosis of breast carcinoma. IL-8 acts through its CXCR1 and CXCR2 receptors. CXCR2, expressed on the endothelial cells, is the receptor involved in mediating the angiogenic effects of ELR+CXC chemokines and in particular IL-8. In the current study, we investigated the susceptibility and prognostic implications of the genetic variation in CXCR2 in breast carcinoma. We also confirmed the implication of IL-8 (-251) T/A polymorphism in a larger cohort. Finally, we combined the IL-8 and CXCR2 variant alleles and analyzed their effects in breast cancer risk and prognosis. We used the allele-specific polymerase chain reaction to characterize the variation of IL-8 and CXCR2 for 409 unrelated Tunisian patients with breast carcinoma and 301 healthy control subjects. To estimate the relative risks, Odds ratios and 95% confidence intervals were calculated using unconditional logistic regression after adjusting for the known risk factors for breast cancer. Associations of the genetic marker with the rates of breast carcinoma-specific overall survival and disease-free survival were assessed using univariate and multivariate analyses. A highly significant association was found between the homozygous CXCR2 (+ 1208) TT genotype (adjusted OR = 2.89; P = 0.008) and breast carcinoma. A significantly increased risk of breast carcinoma was associated with IL-8 (-251) A allele (adjusted OR = 1.86; P = 0.001). The presence of two higher risk genotypes (the TA and TT in IL-8, and the TT in CXCR2) significantly increased the risk of developing breast carcinoma (adjusted OR = 4.15; P = 0.0004). The CXCR2 (+ 1208) T allele manifested a significant association with an aggressive phenotype of breast carcinoma as

  12. Relevance of GSTM1, GSTT1 and GSTP1 Gene Polymorphism to Breast Cancer Susceptibility in Mizoram Population, Northeast India.

    Science.gov (United States)

    Kimi, Lalro; Ghatak, Souvik; Yadav, Ravi Prakash; Chhuani, Lalhma; Lallawmzuali, Doris; Pautu, Jeremy L; Senthil Kumar, Nachimuthu

    2016-02-01

    The enzymes encoded by glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism of wide range of carcinogens that are ubiquitous in the environment. Homozygous deletions of the GSTM1 and GSTT1 genes are commonly found and result in lack of enzyme activity. This study was undertaken to evaluate the association between GSTM1, GSTT1 and GSTP1 gene polymorphism and breast cancer risk in Mizoram population. Odd ratio (OR) and 95% confidence interval (CI) from conditional logistic regression model were used to estimate the association between genetic polymorphism and breast cancer risk. The GSTM1 and GSTT1 null genotypes were associated with an increased risk of breast cancer [OR = 10.80 (95% CI 1.16-100.43)]. The risk of breast cancer associated with the GSTT1 null genotype was observed to be low among postmenopausal women. When considered together, GSTM1 and GSTT1 genotypes were found to be associated with an increased risk of breast cancer. The relationship between GSTM1 and GSTT1 gene deletions and breast cancer risk was substantially altered by consumption of Smoked Meat/Vegetable. In the present study, GSTP1Ile105Val (rs1695) polymorphism was related to breast cancer susceptibility or phenotype. Our data provides evidence for substantially increased risk of breast cancer associated with GSTM1 and/or GSTT1 homozygous gene deletions in Mizoram population. PMID:26407578

  13. The role of the breast cancer susceptibility gene 1 (BRCA1 in sporadic epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Mueller Christopher R

    2003-10-01

    Full Text Available Abstract Mutations within the BRCA1 tumor suppressor gene occur frequently in familial epithelial ovarian carcinomas but they are a rare event in the much more prevalent sporadic form of the disease. However, decreased BRCA1 expression occurs frequently in sporadic tumors, and the magnitude of this decrease has been correlated with increased disease progression. The near absence of somatic mutations consequently suggests that there are alternative mechanisms that may contribute to the observed loss of BRCA1 in sporadic tumors. Indeed, both allelic loss at the BRCA1 locus and epigenetic hypermethylation of the BRCA1 promoter play an important role in BRCA1 down-regulation; yet these mechanisms alone or in combination do not always account for the reduced BRCA1 expression. Alternatively, misregulation of specific upstream factors that control BRCA1 transcription may be a crucial means by which BRCA1 is lost. Therefore, determining how regulators of BRCA1 expression may be co-opted during sporadic ovarian tumorigenesis will lead to a better understanding of ovarian cancer etiology and it may help foster the future development of novel therapeutic strategies aimed at halting ovarian tumor progression.

  14. The application of nonsense-mediated mRNA decay inhibition to the identification of breast cancer susceptibility genes

    Directory of Open Access Journals (Sweden)

    Johnson Julie K

    2012-06-01

    Full Text Available Abstract Background Identification of novel, highly penetrant, breast cancer susceptibility genes will require the application of additional strategies beyond that of traditional linkage and candidate gene approaches. Approximately one-third of inherited genetic diseases, including breast cancer susceptibility, are caused by frameshift or nonsense mutations that truncate the protein product 1. Transcripts harbouring premature termination codons are selectively and rapidly degraded by the nonsense-mediated mRNA decay (NMD pathway. Blocking the NMD pathway in any given cell will stabilise these mutant transcripts, which can then be detected using gene expression microarrays. This technique, known as gene identification by nonsense-mediated mRNA decay inhibition (GINI, has proved successful in identifying sporadic nonsense mutations involved in many different cancer types. However, the approach has not yet been applied to identify germline mutations involved in breast cancer. We therefore attempted to use GINI on lymphoblastoid cell lines (LCLs from multiple-case, non- BRCA1/2 breast cancer families in order to identify additional high-risk breast cancer susceptibility genes. Methods We applied GINI to a total of 24 LCLs, established from breast-cancer affected and unaffected women from three multiple-case non-BRCA1/2 breast cancer families. We then used Illumina gene expression microarrays to identify transcripts stabilised by the NMD inhibition. Results The expression profiling identified a total of eight candidate genes from these three families. One gene, PPARGC1A, was a candidate in two separate families. We performed semi-quantitative real-time reverse transcriptase PCR of all candidate genes but only PPARGC1A showed successful validation by being stabilised in individuals with breast cancer but not in many unaffected members of the same family. Sanger sequencing of all coding and splice site regions of PPARGC1A did not reveal any protein

  15. The application of nonsense-mediated mRNA decay inhibition to the identification of breast cancer susceptibility genes

    International Nuclear Information System (INIS)

    Identification of novel, highly penetrant, breast cancer susceptibility genes will require the application of additional strategies beyond that of traditional linkage and candidate gene approaches. Approximately one-third of inherited genetic diseases, including breast cancer susceptibility, are caused by frameshift or nonsense mutations that truncate the protein product [1]. Transcripts harbouring premature termination codons are selectively and rapidly degraded by the nonsense-mediated mRNA decay (NMD) pathway. Blocking the NMD pathway in any given cell will stabilise these mutant transcripts, which can then be detected using gene expression microarrays. This technique, known as gene identification by nonsense-mediated mRNA decay inhibition (GINI), has proved successful in identifying sporadic nonsense mutations involved in many different cancer types. However, the approach has not yet been applied to identify germline mutations involved in breast cancer. We therefore attempted to use GINI on lymphoblastoid cell lines (LCLs) from multiple-case, non- BRCA1/2 breast cancer families in order to identify additional high-risk breast cancer susceptibility genes. We applied GINI to a total of 24 LCLs, established from breast-cancer affected and unaffected women from three multiple-case non-BRCA1/2 breast cancer families. We then used Illumina gene expression microarrays to identify transcripts stabilised by the NMD inhibition. The expression profiling identified a total of eight candidate genes from these three families. One gene, PPARGC1A, was a candidate in two separate families. We performed semi-quantitative real-time reverse transcriptase PCR of all candidate genes but only PPARGC1A showed successful validation by being stabilised in individuals with breast cancer but not in many unaffected members of the same family. Sanger sequencing of all coding and splice site regions of PPARGC1A did not reveal any protein truncating mutations. Haplotype analysis using short

  16. Polymorphisms of the Hypoxia Inducible Factor 1 and microRNA Related Genes and the Susceptibility and Survival of Lung Cancer and Upper Aero-Digestive Tract Cancers

    OpenAIRE

    Yang, Ying

    2014-01-01

    Background: Hypoxia inducible factor 1(HIF-1) and microRNAs (miRNAs) regulate transcriptional activities and contribute in several biological processes such as oxygen homeostasis, cell growth, progression and apoptosis that are important in lung and upper aero-digestive tract (UADT) cancer etiology and outcomes. Nonetheless, there are few published studies of the relationship between HIF-1 and miRNA gene polymorphisms and susceptibility and survival of lung cancer or UADT cancers. Methods: 1,...

  17. Genetic basis of interindividual susceptibility to cancer cachexia: selection of potential candidate gene polymorphisms for association studies

    Indian Academy of Sciences (India)

    N. Johns; B. H. Tan; M. Macmillan; T. S. Solheim; J. A. Ross; V. E. Baracos; S. Damaraju; K. C. H. Fearon

    2014-12-01

    Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of biological processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications and biological targets continue to evolve, there is a need for reappraisal of the literature for future candidate association studies. This review summarizes genes identified or implicated as well as putative candidate genes contributing to cachexia, identified through diverse technology platforms and model systems to further guide association studies. A systematic search covering 1986–2012 was performed for potential candidate genes / genetic polymorphisms relating to cancer cachexia. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used to reveal possible network associations between genes. Functionality of SNPs/genes was explored based on published literature, algorithms for detecting putative deleterious SNPs and interrogating the database for expression of quantitative trait loci (eQTLs). A total of 154 genes associated with cancer cachexia were identified and explored for functional polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms with functional and/or clinical significance in terms of cachexia associated with them. Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e., inflammation, loss of fat mass and/or lean mass and reduced survival). Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides a contemporary basis to select genes and/or polymorphisms for further association studies in cancer cachexia, and

  18. The breast cancer susceptibility gene BRCA1: DNA repair and other functions

    International Nuclear Information System (INIS)

    BRCA1 is a tumour suppressor gene. Germline mutations in BRCA1 confer susceptibility to breast and ovarian cancer and levels of BRCA1 mRNA and/or protein are reduced in a significant proportion of sporadic breast tumours. The product of this gene is a large multifunctional nuclear phosphoprotein that has been implicated in the regulation of cell cycle progression, apoptosis, transcription and DNA repair. Thus BRCA1 is thought to function as a genomic caretaker, responding to DNA damage by halting cell-cycle progression and activating DNA repair or cell death pathways. Evidence of a role for BRCA1 in DNA repair includes the identification of a novel C-terminal amino acid sequence motif (BRCT) common to a broad range of DNA repair proteins, the observation that the BRCA1 protein interacts with a number of DNA repair proteins, including Rad50, and the demonstration of defective double-strand break repair by homologous recombination and genetic instability in BRCA1-deficient cells. Loss of BRCA1 contributes to breast tumourigenesis by inducing genomic instability. The consistent histological phenotype of BRCA1 tumours, including their high-grade, pushing margins and syncytial appearance, together with the results of differential-expression analyses, indicate that the mutations that accumulate in these tumours are far from random. At present however the pathway between BRCA1 loss and BRCA1-mediated tumour development is poorly understood. In an attempt to address this we have studied the cellular and molecular effects of disrupting BRCA1 function. Results from this analysis and our studies on the regulation of BRCA1 expression will be presented

  19. Impacts of CA9 Gene Polymorphisms and Environmental Factors on Oral-Cancer Susceptibility and Clinicopathologic Characteristics in Taiwan

    OpenAIRE

    Chien, Ming-Hsien; Yang, Jia-Sin; Chu, Yin-Hung; Lin, Chien-huang; Wei, Lin-Hung; Yang, Shun-Fa; Lin, Chiao-Wen

    2012-01-01

    Background In Taiwan, oral cancer has causally been associated with environmental carcinogens. Carbonic anhydrase 9 (CA9) is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study explored the combined effect of CA9 gene polymorphisms and exposure to environmental carcinogens on the susceptibility of developing oral squamous cell carcinoma (OSCC) and the clinicopathological characteristics of the tumors. Methodology and Pr...

  20. Allelic variants of XRCC1 and XRCC3 repair genes and susceptibility of oral cancer in Brazilian patients

    DEFF Research Database (Denmark)

    Dos Reis, Mariana Bisarro; Losi-Guembarovski, Roberta; de Souza Fonseca Ribeiro, Enilze Maria; Cavalli, Iglenir João; Morita, Maria Celeste; Ramos, Gyl Henrique Albrecht; de Oliveira, Benedito Valdecir; Mizuno, Lauro Toyoshi; Rogatto, Silvia Regina; de Syllos Cólus, Ilce Mara

    2013-01-01

    genes have been found to be associated with oral cancer. The aim of this study was to investigate the relationship between the presence of allelic variants Arg194Trp (rs:1799782) and Arg399Gln (rs: 25487) of XRCC1 gene and Thr241Met (rs: 861539) of XRCC3 gene and susceptibility to oral cancer. We also...... variants of the XRCC1 gene within codon 194 (OR 0.82, 95% CI: 0.44-1.51) and codon 399 (OR 0.94, 95% CI: 0.59-1.50) and within the XRCC3 gene (OR 0.72; 95% CI: 0.45-1.16) were not associated with an increased risk of oral cancer. A combinational analysis of SNPs in both genes indicated no association. The......BACKGROUND: The capacity for DNA repair is essential in maintaining cellular functions and homeostasis; however, this capacity can be altered based on DNA sequence variations in DNA repair genes, which may contribute to the onset of cancer. Many single-nucleotide polymorphisms (SNPs) in repair...

  1. Allele-specific expression of mutated in colorectal cancer (MCC) gene and alternative susceptibility to colorectal cancer in schizophrenia

    Science.gov (United States)

    Wang, Yang; Cao, Yanfei; Huang, Xiaoye; Yu, Tao; Wei, Zhiyun; McGrath, John; Xu, Fei; Bi, Yan; Li, Xingwang; Yang, Fengping; Li, Weidong; Zou, Xia; Peng, Zhihai; Xiao, Yanzeng; Zhang, Yan; He, Lin; He, Guang

    2016-01-01

    Evidence has indicated that the incidence of colorectal cancer (CRC) among schizophrenia is lower than normal. To explore this potential protective effect, we employed an innovative strategy combining association study with allele-specific expression (ASE) analysis in MCC gene. We first genotyped four polymorphisms within MCC in 312 CRC patients, 270 schizophrenia patients and 270 controls. Using the MassArray technique, we performed ASE measurements in a second sample series consisting of 50 sporadic CRC patients, 50 schizophrenia patients and 52 controls. Rs2227947 showed significant differences between schizophrenia cases and controls, and haplotype analysis reported some significant discrepancies among these three subject groups. ASE values of rs2227948 and rs2227947 presented consistently differences between CRC (or schizophrenia) patients and controls. Of the three groups, highest frequencies of ASE in MCC were concordantly found in CRC group, whereas lowest frequencies of ASE were observed in schizophrenia group. Similar trends were confirmed in both haplotype frequencies and ASE frequencies (i.e. CRC > control > schizophrenia). We provide a first indication that MCC might confer alterative genetic susceptibility to CRC in individuals with schizophrenia promising to shed more light on the relationship between schizophrenia and cancer progression. PMID:27226254

  2. Further evidence for the contribution of the RAD51C gene in hereditary breast and ovarian cancer susceptibility.

    Science.gov (United States)

    Vuorela, Mikko; Pylkäs, Katri; Hartikainen, Jaana M; Sundfeldt, Karin; Lindblom, Annika; von Wachenfeldt Wäppling, Anna; Haanpää, Maria; Puistola, Ulla; Rosengren, Annika; Anttila, Maarit; Kosma, Veli-Matti; Mannermaa, Arto; Winqvist, Robert

    2011-12-01

    RAD51C, a RAD51 paralogue involved in homologous recombination, is a recently established Fanconi anemia and breast cancer predisposing factor. In the initial report, RAD51C mutations were shown to confer a high risk for both breast and ovarian tumors, but most of the replication studies published so far have failed to identify any additional susceptibility alleles. Here, we report a full mutation screening of the RAD51C gene in 147 Finnish familial breast cancer cases and in 232 unselected ovarian cancer cases originating from Finland and Sweden. In addition, in order to resolve whether common RAD51C SNPs are risk factors for breast cancer, we genotyped five tagging single nucleotide polymorphisms, rs12946522, rs304270, rs304283, rs17222691, and rs28363312, all located within the gene, from 993 Finnish breast cancer cases and 871 controls for cancer associated variants. Whereas, none of the studied common SNPs associated with breast cancer susceptibility, mutation analysis revealed two clearly pathogenic alterations. RAD51C c.-13_14del27 was observed in one familial breast cancer case and c.774delT in one unselected ovarian cancer case, thus confirming that RAD51C mutations are implicated in breast and ovarian cancer predisposition, although their overall frequency seems to be low. Independent identification of the very recently reported RAD51C c.774delT mutation in yet another patient originating from Sweden suggests that it might be a recurrent mutation in that population and should be studied further. The reliable estimation of the clinical implications of carrying a defective RAD51C allele still requires the identification of additional mutation positive families. PMID:21750962

  3. Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions

    DEFF Research Database (Denmark)

    Schoeps, Anja; Rudolph, Anja; Seibold, Petra;

    2014-01-01

    Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,47...

  4. CD44 Gene Polymorphisms and Environmental Factors on Oral Cancer Susceptibility in Taiwan

    OpenAIRE

    Chou, Ying-Erh; Hsieh, Ming-Ju; Hsin, Chung-Han; Chiang, Whei-Ling; Lai, Yi-Cheng; Lee, Yu-Hsien; Huang, Shu-Ching; Yang, Shun-Fa; Lin, Chiao-Wen

    2014-01-01

    Background Oral squamous cell carcinoma (OSCC) is the fourth leading cause of male cancer death in Taiwan. Exposure to environmental carcinogens is the primary risk factor for developing OSCC. CD44, a well-known tumor marker, plays a crucial role in tumor cell differentiation, invasion, and metastasis. This study investigated CD44 single-nucleotide polymorphisms (SNPs) with environmental risk factors to determine OSCC susceptibility and clinicopathological characteristics. Methodology/Princip...

  5. Effects of NFKB1 and NFKBIA gene polymorphisms on susceptibility to environmental factors and the clinicopathologic development of oral cancer.

    Directory of Open Access Journals (Sweden)

    Chiao-Wen Lin

    Full Text Available BACKGROUND: Oral cancer, which is the fourth most common cancer in Taiwanese men, is associated with environmental carcinogens. The possibility that genetic predisposition in nuclear factor-kappa B (NF-κB-signaling pathways activation is linked to the development of oral squamous cell carcinoma (OSCC requires investigation. The current study examines associations between polymorphisms within promoter regions of NFKB1 encoding NF-κB1 and NFKBIA encoding IkappaBalpha (IκBα with both the susceptibility to develop OSCC and the clinicopathological characteristics of the tumors. METHODOLOGY/PRINCIPAL FINDINGS: Genetic polymorphisms of NFKB1 and NFKBIA were analyzed by a real-time polymerase chain reaction (real-time PCR for 462 patients with oral cancer and 520 non-cancer controls. We found that NFKB1 -94 ATGG1/ATGG2, -94 ATGG2/ATGG2, and the combination of -94 ATGG1/ATGG2 and ATGG2/ATGG2 genotypes NFKBIA -826 T (CT+TT and -881 G (AG+GG allelic carriages, were more prevalent in OSCC patients than in non-cancer participants. Moreover, we found that NFKB1 or NFKBIA gene polymorphisms seem to be related to susceptibility to develop oral cancer linked to betel nut and tobacco consumption. Finally, patients with oral cancer who had at least one -519 T allele of the NFKBIA gene were at higher risk for developing distant metastasis (P<.05, compared with those patients CC homozygotes. CONCLUSIONS: Our results suggest that NFKB1 -94 ATTG2, NFKBIA -826 T, and -881 G alleles are associated with oral carcinogenesis. The combination of NFKB1 or NFKBIA gene polymorphisms and environmental carcinogens appears related to an increased risk of oral cancer. More importantly, the genetic polymorphism of NFKBIA -519 might be a predictive factor for the distal metastasis of OSCC in Taiwanese.

  6. Polymorphism of CYPIA1 and GSTM1 genes associated with susceptibility of gastric cancer in Shandong Province of China

    Institute of Scientific and Technical Information of China (English)

    Hao Li; Xue-Liang Chen; Hui-Qing Li

    2005-01-01

    AIM: To explore whether polymorphisms of the CYPIA1 and GSTM1 genes are associated with susceptibility of stomach cancer.METHODS: A total of 102 stomach cancer cases and 62 healthy persons were diagnosed by pathology in 1998-2000 in the Qilu Hospital of Shandong University. Gene polymorphisms were detected by the PCR using sequence-specific primers. Data analysis of the case-control study was carried out using the unconditional logistic method.RESULTS: After adjustment for age, sex, educational levels, and occupation, the risk factors for stomach cancer were shown to be smoking, Helicobacter pylori(H pylori),and presence of the CYPIM G/G and GSTM1 O/O genotypes.Interaction was observed between the combined genotypes of either CYPIA1 G/G and GSTM1 O/O or H pylori infection,or GSTM1 O/O and H pylori infection or smoking.CONCLUSION: Polymorphisms of the CYPIA1 and GSTM1 genes, H pylori infection and smoking are related to susceptibility to stomach cancer.

  7. Genetic evaluation of BRCA1-A complex genes with triple-negative breast cancer susceptibility in Chinese women

    Science.gov (United States)

    Zheng, Yi-Zi; Qiao, Feng; Yao, Ling; Cao, Zhi-Gang; Ye, Fu-Gui; Wu, Jiong; Hu, Xin; Wang, Bin; Shao, Zhi-Ming

    2016-01-01

    Background The tumor suppressor BRCA1 plays a pivotal role in maintaining genomic stability and tumor suppression. The BRCA1-A complex is required for recruitment of BRCA1 to DNA damage sites, DNA repair and cell cycle checkpoint control. Since germline mutations of BRCA1 often lead to breast tumors that are triple-negative breast cancer (TNBC) type, we aimed to investigate whether genetic deficiency in genes of the BRCA1-A complex is associated with risk to TNBC development. Results We found that rs7250266 in the promoter region of NBA1 confers a decreased risk to TNBC development, but not to non-TNBC susceptibility. In addition, the haplotypes containing two polymorphisms rs7250266 and rs2278256 are associated with a lower chance of TNBC development specifically. Our studies also showed that the protective alleles of rs7250266 (C > G) and rs2278256 (T > C) down-regulate promoter activity of NBA1 in mammary epithelial cells. Methods We investigated associations between the BRCA1-A complex genes and TNBC developing risk in first case-control study of Chinese Han Women population including 414 patients with TNBC and 354 cancer-free controls. We detected 37 common variants in ABRAXAS, RAP80, BRE, BRCC36 and NBA1/MERIT40 genes encoding the BRCA1-A complex and evaluated their genetic susceptibility to the risk of TNBC. An additional cohort with 652 other types of breast cancer (non-TNBC) cases and 890 controls was used to investigate the associations between TNBC-specific SNPs genotype and non-TNBCs susceptibility. Conclusions Genetic variants in NBA1 may be an important genetic determinant of TNBC susceptibility. Further investigation and validation of these SNPs in larger cohorts may facilitate in predication and prevention of TNBC and in counseling individuals for risk of TNBC development. PMID:26848770

  8. Cell cycle genes and ovarian cancer susceptibility: a tagSNP analysis

    DEFF Research Database (Denmark)

    Cunningham, J M; Vierkant, R A; Sellers, T A;

    2009-01-01

    BACKGROUND: Dysregulation of the cell cycle is a hallmark of many cancers including ovarian cancer, a leading cause of gynaecologic cancer mortality worldwide. METHODS: We examined single nucleotide polymorphisms (SNPs) (n=288) from 39 cell cycle regulation genes, including cyclins, cyclin...... ovarian cancer in at least one genetic model. Seven SNPs were then assessed in four additional studies with 1689 cases and 3398 controls. Association between risk of ovarian cancer and ABL1 rs2855192 found in the original population [odds ratio, OR(BB vs AA) 2.81 (1.29-6.09), P=0.01] was also observed in...... a replication population, and the association remained suggestive in the combined analysis [OR(BB vs AA) 1.59 (1.08-2.34), P=0.02]. No other SNP associations remained suggestive in the replication populations. CONCLUSION: ABL1 has been implicated in multiple processes including cell division, cell...

  9. Functional Analysis of Missense Variants in the Putative Breast Cancer Susceptibility Gene XRCC2.

    Science.gov (United States)

    Hilbers, Florentine S; Luijsterburg, Martijn S; Wiegant, Wouter W; Meijers, Caro M; Völker-Albert, Moritz; Boonen, Rick A; van Asperen, Christi J; Devilee, Peter; van Attikum, Haico

    2016-09-01

    XRCC2 genetic variants have been associated with breast cancer susceptibility. However, association studies have been complicated because XRCC2 variants are extremely rare and consist mainly of amino acid substitutions whose grouping is sensitive to misclassification by the predictive algorithms. We therefore functionally characterized variants in XRCC2 by testing their ability to restore XRCC2-DNA repair deficient phenotypes using a cDNA-based complementation approach. While the protein-truncating variants p.Leu117fs, p.Arg215*, and p.Cys217* were unable to restore XRCC2 deficiency, 19 out of 23 missense variants showed no or just a minor (<25%) reduction in XRCC2 function. The remaining four (p.Cys120Tyr, p.Arg91Trp, p.Leu133Pro, and p.Ile95Leu) had a moderate effect. Overall, measured functional effects correlated poorly with those predicted by in silico analysis. After regrouping variants from published case-control studies based on the functional effect found in this study and reanalysis of the prevalence data, there was no longer evidence for an association with breast cancer. This suggests that if breast cancer susceptibility alleles of XRCC2 exist, they are likely restricted to protein-truncating variants and a minority of missense changes. Our study emphasizes the use of functional analyses of missense variants to support variant classification in association studies. PMID:27233470

  10. Possible association of β2- and β3-adrenergic receptor gene polymorphisms with susceptibility to breast cancer

    International Nuclear Information System (INIS)

    The involvement of β2-adrenergic receptor (ADRB2) and β3-adrenergic receptor (ADRB3) in both adipocyte lipolysis and thermogenic activity suggests that polymorphisms in the encoding genes might be linked with interindividual variation in obesity, an important risk factor for postmenopausal breast cancer. In order to examine the hypothesis that genetic variations in ADRB2 and ADRB3 represent interindividual susceptibility factors for obesity and breast cancer, we conducted a hospital-based, case-control study in the Aichi Cancer Center, Japan. A self-administered questionnaire was given to 200 breast cancer patients and 182 control individuals, and pertinent information on lifestyle, family history and reproduction was collected. ADRB2 and ADRB3 genotypes were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism assessment. Twenty-five (12.4%) breast cancer patients and 32 (17.6%) control individuals were found to bear a glutamic acid (Glu) allele for the ADRB2 gene (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.38-1.18), and 60 (30.0%) breast cancer patients and 61 (33.5%) control individuals were found to bear an Arg allele for the ADRB3 gene (OR 0.85, 95% CI 0.55-1.31). A significantly lower risk was observed in those who carried the Glu ADRB2 allele and who reported first childbirth when they were younger than 25 years (OR 0.35; 95% CI 0.13-0.99). A potential association may exist between risk of breast cancer and polymorphisms in the ADRB2 and ADRB3 genes; further studies in larger samples and/or in different ethnic groups are warranted to investigate this potential association

  11. Genetic susceptibility to cancer

    International Nuclear Information System (INIS)

    The normal development and function of tissues are under the regulation of programmed expression of genes involved in the proliferation and differentiation. Tumor development can be identified as the abnormal or deregulated expression of such genes. Two distinct classes of genes have been implicated in cancer development; oncogenes and tumor-suppressor genes. Those genes are potential target for radiation carcinogenesis. However, contemporal view of mutations of oncogenes and tumor-suppressor genes in radiogenic and non-radiogenic human cancers do not match to the spectrum of radiation-induced mutation in the selected genes, and raise the question whether radiations are primarily responsible for the initiation of carcinogenesis by mutation of those genes as primary target. There is now a growing evidence for the radiation to stimulate cell growth, which is followed by suppression. Such stimulatory effects of radiation may evoke the growth-promoting and -suppressing genes, or oncogenes and tumor-suppressor genes. This may lead to a testable proposition that constitutively present gain-of-function mutations in oncogenes and/or loss-of-function mutations in tumor-suppressor genes, accumulated spontaneously or environmentally, may play a significant role in the radiation carcinogenesis. (author)

  12. Assessing SNP-SNP interactions among DNA repair, modification and metabolism related pathway genes in breast cancer susceptibility.

    Directory of Open Access Journals (Sweden)

    Yadav Sapkota

    Full Text Available Genome-wide association studies (GWASs have identified low-penetrance common variants (i.e., single nucleotide polymorphisms, SNPs associated with breast cancer susceptibility. Although GWASs are primarily focused on single-locus effects, gene-gene interactions (i.e., epistasis are also assumed to contribute to the genetic risks for complex diseases including breast cancer. While it has been hypothesized that moderately ranked (P value based weak single-locus effects in GWASs could potentially harbor valuable information for evaluating epistasis, we lack systematic efforts to investigate SNPs showing consistent associations with weak statistical significance across independent discovery and replication stages. The objectives of this study were i to select SNPs showing single-locus effects with weak statistical significance for breast cancer in a GWAS and/or candidate-gene studies; ii to replicate these SNPs in an independent set of breast cancer cases and controls; and iii to explore their potential SNP-SNP interactions contributing to breast cancer susceptibility. A total of 17 SNPs related to DNA repair, modification and metabolism pathway genes were selected since these pathways offer a priori knowledge for potential epistatic interactions and an overall role in breast carcinogenesis. The study design included predominantly Caucasian women (2,795 cases and 4,505 controls from Alberta, Canada. We observed two two-way SNP-SNP interactions (APEX1-rs1130409 and RPAP1-rs2297381; MLH1-rs1799977 and MDM2-rs769412 in logistic regression that conferred elevated risks for breast cancer (P(interaction<7.3 × 10(-3. Logic regression identified an interaction involving four SNPs (MBD2-rs4041245, MLH1-rs1799977, MDM2-rs769412, BRCA2-rs1799943 (P(permutation = 2.4 × 10(-3. SNPs involved in SNP-SNP interactions also showed single-locus effects with weak statistical significance, while BRCA2-rs1799943 showed stronger statistical significance (P

  13. Polymorphisms of the SIPA1 gene and sporadic breast cancer susceptibility

    International Nuclear Information System (INIS)

    The novel breast cancer metastasis modulator gene signal-induced proliferation-associated 1 (Sipa1) underlies the breast cancer metastasis efficiency modifier locus Mtes 1 and has been shown to influence mammary tumour metastatic efficiency in the mouse, with an ectopically expressing Sipa1 cell line developing 1.5 to 2 fold more surface pulmonary metastases. Sipa1 encodes a mitogen-inducible GTPase activating (GAP) protein for members of the Ras-related proteins; participates in cell adhesion and modulates mitogen-induced cell cycle progression. Germline SIPA1 SNPs showed association with positive lymph node metastasis and hormonal receptor status in a Caucasian cohort. We hypothesized that SIPA1 may also be correlated to breast carcinoma incidence as well as prognosis. Therefore, this study investigated the potential relationship of SIPA1 and human breast cancer incidence by a germline SNP genotype frequency association study in a case-control Caucasian cohort in Queensland, Australia. The SNPs genotyped in this study were identified in a previous study and the genotyping assays were carried out using TaqMan SNP Genotyping Assays. The data were analysed with chi-square method and the Monte Carlo style CLUMP analysis program. Results indicated significance with SIPA1 SNP rs3741378; the CC genotype was more frequently observed in the breast cancer group compared to the disease-free control group, indicating the variant C allele was associated with increased breast cancer incidence. This observation indicates SNP rs3741378 as a novel potential sporadic breast cancer predisposition SNP. While it showed association with hormonal receptor status in breast cancer group in a previous pilot study, this exonic missense SNP (Ser (S) to Phe (F)) changes a hydrophilic residue (S) to a hydrophobic residue (F) and may significantly alter the protein functions of SIPA1 in breast tumourgenesis. SIPA1 SNPs rs931127 (5' near gene), and rs746429 (synonymous (Ala (A) to Ala (A

  14. Polymorphisms of the SIPA1 gene and sporadic breast cancer susceptibility

    Directory of Open Access Journals (Sweden)

    Lintell Nicholas A

    2009-09-01

    Full Text Available Abstract Background The novel breast cancer metastasis modulator gene signal-induced proliferation-associated 1 (Sipa1 underlies the breast cancer metastasis efficiency modifier locus Mtes 1 and has been shown to influence mammary tumour metastatic efficiency in the mouse, with an ectopically expressing Sipa1 cell line developing 1.5 to 2 fold more surface pulmonary metastases. Sipa1 encodes a mitogen-inducible GTPase activating (GAP protein for members of the Ras-related proteins; participates in cell adhesion and modulates mitogen-induced cell cycle progression. Germline SIPA1 SNPs showed association with positive lymph node metastasis and hormonal receptor status in a Caucasian cohort. We hypothesized that SIPA1 may also be correlated to breast carcinoma incidence as well as prognosis. Therefore, this study investigated the potential relationship of SIPA1 and human breast cancer incidence by a germline SNP genotype frequency association study in a case-control Caucasian cohort in Queensland, Australia. Methods The SNPs genotyped in this study were identified in a previous study and the genotyping assays were carried out using TaqMan SNP Genotyping Assays. The data were analysed with chi-square method and the Monte Carlo style CLUMP analysis program. Results Results indicated significance with SIPA1 SNP rs3741378; the CC genotype was more frequently observed in the breast cancer group compared to the disease-free control group, indicating the variant C allele was associated with increased breast cancer incidence. Conclusion This observation indicates SNP rs3741378 as a novel potential sporadic breast cancer predisposition SNP. While it showed association with hormonal receptor status in breast cancer group in a previous pilot study, this exonic missense SNP (Ser (S to Phe (F changes a hydrophilic residue (S to a hydrophobic residue (F and may significantly alter the protein functions of SIPA1 in breast tumourgenesis. SIPA1 SNPs rs931127 (5

  15. Genetic polymorphisms of GSTM1,GSTP1 and GSTT1 genes and lung cancer susceptibility in the Bangladeshi population

    Institute of Scientific and Technical Information of China (English)

    Mir; Muhammad; Nasir; Uddin; Maizbha; Uddin; Ahmed; Mohammad; Safiqul; Islam; Mohammad; Siddiqul; Islam; Muhammad; Shahdaat; Bin; Sayeed; Yearul; Kabir; Abul; Hasnat

    2014-01-01

    Objective:To verify possible associations between polymorphisms of glutathione S-transferase Mu(GSTM1),glutathione S-transferase θ(GSTT1) and glutathione S-transferase Pi(GSTP1)genes and susceptibility to lung cancer.Methods:A total of 106 lung cancer patients and 116 controls were enrolled in a case-control study.The GSTM1 and GSTT1 were analyzed using PCR while GSTP1 was analyzed using PCR-restriction fragment length polymorphism.Risk of lung cancer was estimated as odds ratio at 95%confidence interval using unconditional logistic regression models adjusting for age,sex,and tobacco use.Results:GSTM1 null and GSTT1 null genotypes did not show a significant risk for developing lung cancer.A significandy elevated lung cancer risk was associated with GSTP1 heterozygous,mutant and combined heterozygous+mutant variants of rs1695.When classified by tobacco consumption status,no association with risk of lung cancer was found in case of tobacco smokers and nonsmokers carrying null and present genotypes of GSTM1 and GSTTL There is a three-fold(approximately) increase in the risk of lung cancer in case of both heterozygous(AG) and heterozygous+mutant homozygous(AG+GG) genotypes whereas there is an eightfold increase in risk of lung cancer in cases of GG with respect to AA genotype in smokers.Conclusions:Carrying the GSTM1 and GSTT1 null genotype is not a risk factor for lung cancer and GSTP1Ile105 Val is associated with elevated risk of lung cancer.

  16. Genetic polymorphisms of GSTM1, GSTP1 and GSTT1 genes and lung cancer susceptibility in the Bangladeshi population

    Institute of Scientific and Technical Information of China (English)

    Mir Muhammad Nasir Uddin; Maizbha Uddin Ahmed; Mohammad Safiqul Islam; Mohammad Siddiqul Islam; Muhammad Shahdaat Bin Sayeed; Yearul Kabir; Abul Hasnat

    2014-01-01

    To verify possible associations between polymorphisms of glutathione S-transferase Mu (GSTM1), glutathione S-transferase θ (GSTT1) and glutathione S-transferase Pi (GSTP1) genes and susceptibility to lung cancer. Methods: A total of 106 lung cancer patients and 116 controls were enrolled in a case-control study. The GSTM1 and GSTT1 were analyzed using PCR while GSTP1 was analyzed using PCR-restriction fragment length polymorphism. Risk of lung cancer was estimated as odds ratio at 95% confidence interval using unconditional logistic regression models adjusting for age, sex, and tobacco use. Results: GSTM1 null and GSTT1 null genotypes did not show a significant risk for developing lung cancer. A significantly elevated lung cancer risk was associated with GSTP1 heterozygous, mutant and combined heterozygous+mutant variants of rs1695. When classified by tobacco consumption status, no association with risk of lung cancer was found in case of tobacco smokers and nonsmokers carrying null and present genotypes of GSTM1 and GSTT1. There is a three-fold (approximately) increase in the risk of lung cancer in case of both heterozygous (AG) and heterozygous+mutant homozygous (AG+GG) genotypes whereas there is an eight-fold increase in risk of lung cancer in cases of GG with respect to AA genotype in smokers. Conclusions: Carrying the GSTM1 and GSTT1 null genotype is not a risk factor for lung cancer and GSTP1Ile105Val is associated with elevated risk of lung cancer.

  17. Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

    Science.gov (United States)

    Lawrenson, Kate; Li, Qiyuan; Kar, Siddhartha; Seo, Ji-Heui; Tyrer, Jonathan; Spindler, Tassja J.; Lee, Janet; Chen, Yibu; Karst, Alison; Drapkin, Ronny; Aben, Katja K. H.; Anton-Culver, Hoda; Antonenkova, Natalia; Bowtell, David; Webb, Penelope M.; deFazio, Anna; Baker, Helen; Bandera, Elisa V.; Bean, Yukie; Beckmann, Matthias W.; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Chen, Anne; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas T.; Edwards, Robert P.; Eilber, Ursula; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goode, Ellen L.; Goodman, Marc T.; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A. T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; James, Paul; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Kruger Kjaer, Susanne; Kelemen, Linda E.; Kellar, Melissa; Kelley, Joseph L.; Kiemeney, Lambertus A.; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F. A. G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; Nevanlinna, Heli; McNeish, Ian; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Azmi, Mat Adenan Noor; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Phelan, Catherine M.; Pike, Malcolm C.; Poole, Elizabeth M.; Ramus, Susan J.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schildkraut, Joellen M.; Schwaab, Ira; Sellers, Thomas A.; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston, Lara; Tangen, Ingvild L.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S.; van Altena, Anne M.; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A.; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna H.; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Monteiro, Alvaro; Pharoah, Paul D.; Gayther, Simon A.; Freedman, Matthew L.

    2015-01-01

    Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10−5). For three cis-eQTL associations (P<1.4 × 10−3, FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10−10 for risk variants (P<10−4) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC. PMID:26391404

  18. Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Amankwah, Ernest K; Wang, Qinggang; Schildkraut, Joellen M;

    2011-01-01

    Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among...

  19. Impacts of microRNA gene polymorphisms on the susceptibility of environmental factors leading to carcinogenesis in oral cancer.

    Directory of Open Access Journals (Sweden)

    Yin-Hung Chu

    Full Text Available BACKGROUND: MicroRNAs (miRNAs have been regarded as a critical factor in targeting oncogenes or tumor suppressor genes in tumorigenesis. The genetic predisposition of miRNAs-signaling pathways related to the development of oral squamous cell carcinoma (OSCC remains unresolved. This study examined the associations of polymorphisms with four miRNAs with the susceptibility and clinicopathological characteristics of OSCC. METHODOLOGY/PRINCIPAL FINDINGS: A total of 895 male subjects, including 425 controls and 470 male oral cancer patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and real-time PCR were used to analyze miRNA146a, miRNA196, miRNA499 and miRNA149 genetic polymorphisms between the control group and the case group. This study determined that a significant association of miRNA499 with CC genotype, as compared to the subjects with TT genotype, had a higher risk (AOR = 4.52, 95% CI = 1.24-16.48 of OSCC. Moreover, an impact of those four miRNAs gene polymorphism on the susceptibility of betel nut and tobacco consumption leading to oral cancer was also revealed. We found a protective effect between clinical stage development (AOR = 0.58, 95% CI = 0.36-0.94 and the tumor size growth (AOR = 0.47, 95% CI = 0.28-0.79 in younger patients (age<60. CONCLUSIONS: Our results suggest that genetic polymorphism of miRNA499 is associated with oral carcinogenesis, and the interaction of the miRNAs genetic polymorphism and environmental carcinogens is also related to an increased risk of oral cancer in Taiwanese.

  20. Functional promoter -31G/C variant of Survivin gene predict prostate cancer susceptibility among Chinese: a case control study

    International Nuclear Information System (INIS)

    Abnormal expression of Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5, also called as survivin), a novel member of the inhibitor of apoptosis protein (IAP) family, has implications in many types of cancer and is considered as a new therapeutic target. We suppose that genetic variant rs9904341 in the 5′ UTR region of survivin gene may be associated with the development and progression of prostate cancer (PCa) in Chinese population. TaqMan assay method was used to genotype the polymorphism in the hospital-based case–control analysis of 665 patients with PCa and 710 age-matched cancer-free controls. The genetic associations with the occurrence and progression of PCa were calculated by logistic regression. Our results indicated that compared with GG genotypes, there was a statistically significant increased risk of PCa associated with those with CC genotypes [odds ratios (ORs) = 1.57, 95%confidence intervals (CIs) = 1.17-2.13, P = 0.004]. Moreover, stratification analysis revealed that the association was more pronounced in subgroups of nondrinkers, nonsmokers and those without a family history of cancer (all P < 0.05). In addition, we observed that PSA ≥ 20 was more frequent in patients carrying GC/CC genotypes than in those with a wild type genotype. The functional survivin rs9904341 genetic variant may have a substantial influence on the PCa susceptibility and evolution

  1. Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis

    Directory of Open Access Journals (Sweden)

    Liu Jiyong

    2006-05-01

    Full Text Available Abstract Background Accumulative evidence suggests that low folate intake is associated with increased risk of breast cancer. Polymorphisms in genes involved in folate metabolism may influence DNA methylation, nucleotide synthesis, and thus individual susceptibility to cancer. Thymidylate synthase (TYMS is a key enzyme that participates in folate metabolism and catalyzes the conversion of dUMP to dTMP in the process of DNA synthesis. Two potentially functional polymorphisms [a 28-bp tandem repeat in the TYMS 5'-untranslated enhanced region (TSER and a 6-bp deletion/insertion in the TYMS 3'-untranslated region (TS 3'-UTR] were suggested to be correlated with alteration of thymidylate synthase expression and associated with cancer risk. Methods To test the hypothesis that polymorphisms of the TYMS gene are associated with risk of breast cancer, we genotyped these two polymorphisms in a case-control study of 432 incident cases with invasive breast cancer and 473 cancer-free controls in a Chinese population. Results We found that the distribution of TS3'-UTR (1494del6 genotype frequencies were significantly different between the cases and controls (P = 0.026. Compared with the TS3'-UTR del6/del6 wild-type genotype, a significantly reduced risk was associated with the ins6/ins6 homozygous variant genotype (adjusted OR = 0.58, 95% CI = 0.35–0.97 but not the del6/ins6 genotype (OR = 1.09, 95% CI = 0.82–1.46. Furthermore, breast cancer risks associated with the TS3'-UTR del6/del6 genotype were more evident in older women, postmenopausal subjects, individuals with a younger age at first-live birth and individuals with an older age at menarche. However, there was no evidence for an association between the TSER polymorphism and breast cancer risks. Conclusion These findings suggest that the TS3'-UTR del6 polymorphism may play a role in the etiology of breast cancer. Further larger population-based studies as well as functional evaluation of the

  2. Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium

    OpenAIRE

    Amankwah, E.K.; Wang, Q; Schildkraut, J.M.; Tsai, Y.Y.; Ramus, S.J.; Fridley, B L; Beesley, J.; Johnatty, S E; Webb, P. M.; Chenevix-Trench, G; Dale, L.C.; D. Lambrechts; Amant, F.; Despierre, E.; Vergote, I.

    2011-01-01

    Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among Caucasians were estimated with odds ratios (OR) among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436 cases and 1,098 controls in Australia (replication set 1) and a conso...

  3. Single nucleotide polymorphisms within interferon signaling pathway genes are associated with colorectal cancer susceptibility and survival.

    Directory of Open Access Journals (Sweden)

    Shun Lu

    Full Text Available Interferon (IFN signaling has been suggested to play an important role in colorectal carcinogenesis. Our study aimed to examine potentially functional genetic variants in interferon regulatory factor 3 (IRF3, IRF5, IRF7, type I and type II IFN and their receptor genes with respect to colorectal cancer (CRC risk and clinical outcome. Altogether 74 single nucleotide polymorphisms (SNPs were covered by the 34 SNPs genotyped in a hospital-based case-control study of 1327 CRC cases and 758 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall survival and event-free survival in a subgroup of 483 patients. Seven SNPs in IFNA1, IFNA13, IFNA21, IFNK, IFNAR1 and IFNGR1 were associated with CRC risk. After multiple testing correction, the associations with the SNPs rs2856968 (IFNAR1 and rs2234711 (IFNGR1 remained formally significant (P = 0.0015 and P<0.0001, respectively. Multivariable survival analyses showed that the SNP rs6475526 (IFNA7/IFNA14 was associated with overall survival of the patients (P = 0.041 and event-free survival among patients without distant metastasis at the time of diagnosis, P = 0.034. The hazard ratios (HRs for rs6475526 remained statistically significant even after adjustment for age, gender, grade and stage (P = 0.029 and P = 0.036, respectively, suggesting that rs6475526 is an independent prognostic marker for CRC. Our data suggest that genetic variation in the IFN signaling pathway genes may play a role in the etiology and survival of CRC and further studies are warranted.

  4. Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Li, Qiyuan; Kar, Siddhartha;

    2015-01-01

    Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions assoc...

  5. HapMap-based study of the DNA repair gene ERCC2 and lung cancer susceptibility in a Chinese population

    DEFF Research Database (Denmark)

    Yin, Jiaoyang; Vogel, Ulla Birgitte; Ma, Yegang;

    2009-01-01

    (NER) pathway. To elucidate whether common ERCC2 variants are associated with lung cancer susceptibility, we conducted a case–control study consisting of 339 cases with primary lung cancer and 358 controls matched on age, gender and ethnicity in a Chinese population. Six haplotype tagging single...... polymorphisms. Our results provide evidence to support a role for ERCC2 in lung cancer development in a Chinese population....

  6. Next generation sequencing approaches to identify novel susceptibility genes for epithelial ovarian cancer

    OpenAIRE

    Hayward, J. D.

    2014-01-01

    Ovarian cancer is the fifth most common cancer in women in developed countries and is associated with poor survival due to late diagnoses. Strategies focusing on detecting the disease in the earliest stages and/or improving risk prediction may represent effective clinical intervention reducing disease burden. Women at the greatest risk of epithelial ovarian cancer (EOC) can be offered prophylactic risk-reducing salpingo-oopherectomy (RRSO), which is currently only offered to women with mutati...

  7. Gene-expression patterns in peripheral blood classify familial breast cancer susceptibility

    OpenAIRE

    Piccolo, Stephen R; Andrulis, Irene L; Cohen, Adam L.; Conner, Thomas; Moos, Philip J.; Spira, Avrum E; Buys, Saundra S.; Johnson, W. Evan; Bild, Andrea H

    2015-01-01

    Background Women with a family history of breast cancer face considerable uncertainty about whether to pursue standard screening, intensive screening, or prophylactic surgery. Accurate and individualized risk-estimation approaches may help these women make more informed decisions. Although highly penetrant genetic variants have been associated with familial breast cancer (FBC) risk, many individuals do not carry these variants, and many carriers never develop breast cancer. Common risk varian...

  8. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors.

    Directory of Open Access Journals (Sweden)

    Stefan Nickels

    Full Text Available Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6 and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4. Overall, the per-allele odds ratio (95% confidence interval for LSP1-rs3817198 was 1.08 (1.01-1.16 in nulliparous women and ranged from 1.03 (0.96-1.10 in parous women with one birth to 1.26 (1.16-1.37 in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98 in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85 in those who drank ≥ 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 × 10(-5, with a per-allele OR of 1.14 (1.11-1.17 in parous women and 0.98 (0.92-1.05 in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.

  9. Genetic variations in DNA repair genes, radiosensitivity to cancer and susceptibility to acute tissue reactions in radiotherapy-treated cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Chistiakov, Dimitry A. (Dept. of Pathology, Univ. of Pittsburgh, Pittsburgh (US)); Voronova, Natalia V. (Dept. of Molecular Diagnostics, National Research Center GosNIIgenetika, Moscow (RU)); Chistiakov, Pavel A. (Dept. of Radiology, Cancer Research Center, Moscow (RU))

    2008-06-15

    Ionizing radiation is a well established carcinogen for human cells. At low doses, radiation exposure mainly results in generation of double strand breaks (DSBs). Radiation-related DSBs could be directly linked to the formation of chromosomal rearrangements as has been proven for radiation-induced thyroid tumors. Repair of DSBs presumably involves two main pathways, non-homologous end joining (NHEJ) and homologous recombination (HR). A number of known inherited syndromes, such as ataxia telangiectasia, ataxia-telangiectasia like-disorder, radiosensitive severe combined immunodeficiency, Nijmegen breakage syndrome, and LIG4 deficiency are associated with increased radiosensitivity and/or cancer risk. Many of them are caused by mutations in DNA repair genes. Recent studies also suggest that variations in the DNA repair capacity in the general population may influence cancer susceptibility. In this paper, we summarize the current status of DNA repair proteins as potential targets for radiation-induced cancer risk. We will focus on genetic alterations in genes involved in HR- and NHEJ-mediated repair of DSBs, which could influence predisposition to radiation-related cancer and thereby explain interindividual differences in radiosensitivity or radioresistance in a general population

  10. 'Hide-then-hit' to explain the importance of genotypic polymorphism of DNA repair genes in determining susceptibility to cancer

    Institute of Scientific and Technical Information of China (English)

    Pei-Ei Wu; Chen-Yang Shen

    2011-01-01

    Interindividual variations in DNA repair capacity/efficiency linked to the presence of polymorphisms in DNA repair-related genes have been suggested to account for different risk of developing cancers. In this review article, on the basis of breast cancer formation as a model, we propose a 'hide-then-hit' hypothesis indicating the importance of escaping checkpoint surveillance for sub-optimal DNA repair variants to cause cancer. Therefore, only cells with subtle defects in repair capacity arising from low-penetrance variants of DNA repair genes would have the opportunity to grow and accumulate the genetic changes needed for cancer formation, without triggering cell-cycle checkpoint surveillance. Furthermore, distinct from high-penetrance alleles, these polymorphic alleles of DNA repair genes would predispose carriers to a higher risk of developing cancer but would not necessarily cause cancer. To examine this,we simultaneously genotyped multiple SNPs of cell-cycle checkpoint genes and the DNA repair genes. Support for the hypothesis came from observations that breast cancer risk associated with variant genotypes of DNA repair genes became more significant in be confirmed by biological evidence in which a cause-effect relationship has to be established. However, based on this, possible gene-gene interaction is considered to play an important role in modifying the cancer risk associated with genotypic polymorphism of DNA repair gene in different study populations.

  11. Single Nucleotide Polymorphisms within Interferon Signaling Pathway Genes Are Associated with Colorectal Cancer Susceptibility and Survival

    Czech Academy of Sciences Publication Activity Database

    Lu, S.; Pardini, B.; Cheng, B.; Naccarati, A.; Huhn, S.; Vymetálková, Veronika; Vodičková, Ludmila; Buchler, T.; Hemminki, K.; Vodička, Pavel; Försti, A.

    2014-01-01

    Roč. 9, č. 10 (2014), e11161. E-ISSN 1932-6203 R&D Projects: GA ČR GAP304/10/1286; GA ČR(CZ) GAP304/12/1585 Grant ostatní: GA MŠk(CZ) COST Action BM1206 Institutional support: RVO:68378041 Keywords : colorectal cancer * interferon * nutrition Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2014

  12. Short rare hTERT-VNTR2-2nd alleles are associated with prostate cancer susceptibility and influence gene expression

    International Nuclear Information System (INIS)

    The hTERT (human telomerase reverse transcriptase) gene contains five variable number tandem repeats (VNTR) and previous studies have described polymorphisms for hTERT-VNTR2-2nd. We investigated how allelic variation in hTERT-VNTR2-2nd may affect susceptibility to prostate cancer. A case-control study was performed using DNA from 421 cancer-free male controls and 329 patients with prostate cancer. In addition, to determine whether the VNTR polymorphisms have a functional consequence, we examined the transcriptional levels of a reporter gene linked to these VNTRs and driven by the hTERT promoter in cell lines. Three new rare alleles were detected from this study, two of which were identified only in cancer subjects. A statistically significant association between rare hTERT-VNTR2-2nd alleles and risk of prostate cancer was observed [OR, 5.17; 95% confidence interval (CI), 1.09-24.43; P = 0.021]. Furthermore, the results indicated that these VNTRs inserted in the enhancer region could influence the expression of hTERT in prostate cancer cell lines. This is the first study to report that rare hTERT VNTRs are associated with prostate cancer predisposition and that the VNTRs can induce enhanced levels of hTERT promoter activity in prostate cancer cell lines. Thus, the hTERT-VNTR2-2nd locus may function as a modifier of prostate cancer risk by affecting gene expression

  13. Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Amankwah, Ernest K; Wang, Qinggang; Schildkraut, Joellen M;

    2011-01-01

    Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among...... Caucasians were estimated with odds ratios (OR) among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436 cases and 1,098 controls in Australia (replication set 1) and a consortium of 15 studies comprising 1,668 cases and 4,249 controls (replication set 2). The discovery set and...... replication set 1 (833 cases and 2,013 controls) showed statistically homogeneous (P(heterogeneity)≥0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR = 0.6 to 0.9; P(trend) = 0.001 to 0.03). Results from replication set 2 were statistically...

  14. Ancestral susceptibility to colorectal cancer

    Czech Academy of Sciences Publication Activity Database

    Huhn, S.; Pardini, Barbara; Naccarati, Alessio; Vodička, Pavel (ed.); Hemminki, K.; Försti, A.

    2012-01-01

    Roč. 27, č. 2 (2012), s. 197-204. ISSN 0267-8357 R&D Projects: GA ČR GA310/07/1430; GA ČR GAP304/10/1286 Grant ostatní: EU FP7(XE) HEALTH-F4-2007-200767 Institutional research plan: CEZ:AV0Z50390512 Keywords : cancer susceptibility * molecular epidemiology * genetic susceptibility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.500, year: 2012

  15. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

    DEFF Research Database (Denmark)

    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E;

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtype...

  16. Impact of Gene Patents and Licensing Practices on Access to Genetic Testing for Inherited Susceptibility to Cancer: Comparing Breast and Ovarian Cancers to Colon Cancers: Patents and Licensing for Breast, Ovarian and Colon Cancer Testing

    OpenAIRE

    Cook-Deegan, Robert; DeRienzo, Christopher; Carbone, Julia; Chandrasekharan, Subhashini; Heaney, Christopher; Conover, Christopher

    2010-01-01

    Genetic testing for inherited susceptibility to breast and ovarian cancer can be compared to similar testing for colorectal cancer as a “natural experiment.” Inherited susceptibility accounts for a similar fraction of both cancers and genetic testing results guide decisions about options for prophylactic surgery in both sets of conditions. One major difference is that in the United States, Myriad Genetics is the sole provider of genetic testing, because it has sole control of relevant patents...

  17. A Regulatory Polymorphism at Position -309 in PTPRCAP Is Associated with Susceptibility to Diffuse-type Gastric Cancer and Gene Expression

    Directory of Open Access Journals (Sweden)

    Hyoungseok Ju

    2009-12-01

    Full Text Available PTPRCAP (CD45-AP is a positive regulator of protein tyrosine phosphatase PTPRC (CD45, which activates Src family kinases implicated in tumorigenesis. Single-nucleotide polymorphism (SNP rs869736 located at position -309 of the PTPRCAP promoter was associated with susceptibility to diffuse-type gastric cancer in the current case-control study. The minor-allele homozygote was significantly associated with a 2.5-fold increased susceptibility to diffuse-type gastric cancer (P = .0021, n = 252, but not to intestinal-type (P = .30, n = 178, versus the major-allele homozygote, when comparing unrelated Korean patients with healthy controls (n = 406. Nine other SNPs were in nearly perfect linkage disequilibrium (r2 ≥ 0.97 with this SNP, exhibiting the same association, and spread out for 26 kb on chromosome 11q13.1 covering RPS6KB2, PTPRCAP, CORO1B, and GPR152. Among the four genes, however, only PTPRCAP expression was affected by haplotypes of the 10 SNPs. Endogenous transcript levels of PTPRCAP were linearly correlated with copy numbers (0, 1, and 2 of the risk-haplotype (P = .0060 in 12 lymphoblastoid cells derived from blood samples, but those of the other three genes were not. Furthermore, the cancer-risk, minor-allele T of rs869736 increased both promoter activity and specific nuclear protein-binding affinity than the nonrisk, major-allele G in luciferase reporter and electrophoretic mobility shift assays, respectively. Accordingly, the minor allele of rs869736 in the PTPRCAP promoter is associated with increased susceptibility to diffuse-type gastric cancer by increasing PTPRCAP expression, possibly leading to activation of the oncogenic Src family kinases.

  18. In utero exposure of rats to high-fat diets perturbs gene expression profiles and cancer susceptibility of prepubertal mammary glands.

    Science.gov (United States)

    Govindarajah, Vinothini; Leung, Yuet-Kin; Ying, Jun; Gear, Robin; Bornschein, Robert L; Medvedovic, Mario; Ho, Shuk-Mei

    2016-03-01

    Human studies suggest that high-fat diets (HFDs) increase the risk of breast cancer. The 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis rat model is commonly used to evaluate the effects of lifestyle factors such as HFD on mammary tumor risk. Past studies focused primarily on the effects of continuous maternal exposure on the risk of offspring at the end of puberty (PND50). We assessed the effects of prenatal HFD exposure on cancer susceptibility in prepubertal mammary glands and identified key gene networks associated with such disruption. During pregnancy, dams were fed AIN-93G-based diets with isocaloric high olive oil, butterfat or safflower oil. The control group received AIN-93G. Female offspring were treated with DMBA on PND21. However, a significant increase in tumor volume and a trend of shortened tumor latency were observed in rats with HFD exposure against the controls (P=.048 and P=.067, respectively). Large-volume tumors harbored carcinoma in situ. Transcriptome profiling identified 43 differentially expressed genes in the mammary glands of the HFBUTTER group as compared with control. Rapid hormone signaling was the most dysregulated pathway. The diet also induced aberrant expression of Dnmt3a, Mbd1 and Mbd3, consistent with potential epigenetic disruption. Collectively, these findings provide the first evidence supporting susceptibility of prepubertal mammary glands to DMBA-induced tumorigenesis that can be modulated by dietary fat that involves aberrant gene expression and likely epigenetic dysregulation. PMID:26895667

  19. Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer

    OpenAIRE

    Li, Donghui; Duell, Eric J.; Yu, Kai; Risch, Harvey A.; Olson, Sara H.; Kooperberg, Charles; Wolpin, Brian M.; Jiao, Li; Dong, Xiaoqun; Wheeler, Bill; Arslan, Alan A.; Bueno-De-Mesquita, H Bas; Fuchs, Charles S; Gallinger, Steven; Gross, Myron

    2012-01-01

    Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic...

  20. Ovarian Cancer in Hereditary Cancer Susceptibility Syndromes.

    Science.gov (United States)

    Nakonechny, Quentin B; Gilks, C Blake

    2016-06-01

    Hereditary breast and ovarian cancer (HBOC) syndrome and Lynch syndrome (LS) are associated with increased risk of developing ovarian carcinoma. Patients with HBOC have a lifetime risk of up to 50% of developing high-grade serous carcinoma of tube or ovary; patients with LS have a 10% lifetime risk of developing endometrioid or clear cell carcinoma of the ovary. Testing all patients with tubo-ovarian high-grade serous carcinoma for mutations associated with HBOC syndrome, and all patients presenting with endometrioid or clear cell carcinoma of the ovary for mutations associated with LS can identify patients with undiagnosed underlying hereditary cancer susceptibility syndromes. PMID:27241103

  1. A polymorphic minisatellite region of BORIS regulates gene expression and its rare variants correlate with lung cancer susceptibility

    Science.gov (United States)

    Yoon, Se-Lyun; Roh, Yun-Gil; Chu, In-Sun; Heo, Jeonghoon; Kim, Seung Il; Chang, Heekyung; Kang, Tae-Hong; Chung, Jin Woong; Koh, Sang Seok; Larionov, Vladimir; Leem, Sun-Hee

    2016-01-01

    Aberrant expression of BORIS/CTCFL (Brother of the Regulator of Imprinted Sites/CTCF-like protein) is reported in different malignancies. In this study, we characterized the entire promoter region of BORIS/CTCFL, including the CpG islands, to assess the relationship between BORIS expression and lung cancer. To simplify the construction of luciferase reporter cassettes with various-sized portions of the upstream region, genomic copies of BORIS were isolated using TAR cloning technology. We analyzed three promoter blocks: the GATA/CCAAT box, the CpG islands and the minisatellite region BORIS-MS2. Polymorphic minisatellite sequences were isolated from genomic DNA prepared from the blood of controls and cases. Of the three promoter blocks, the GATA/CCAAT box was determined to be a critical element of the core promoter, while the CpG islands and the BORIS-MS2 minisatellite region were found to act as regulators. Interestingly, the polymorphic minisatellite region BORIS-MS2 was identified as a negative regulator that repressed the expression levels of luciferase reporter cassettes less effectively in cancer cells compared with normal cells. We also examined the association between the size of BORIS-MS2 and lung cancer in a case–control study with 590 controls and 206 lung cancer cases. Rare alleles of BORIS-MS2 were associated with a statistically significantly increased risk of lung cancer (odds ratio, 2.04; 95% confidence interval, 1.02–4.08; and P=0.039). To conclude, our data provide information on the organization of the BORIS promoter region and gene regulation in normal and cancer cells. In addition, we propose that specific alleles of the BORIS-MS2 region could be used to identify the risk for lung cancer. PMID:27416782

  2. Gene by Environment Interaction Linking the Chromosome 15q25 Locus With Cigarette Consumption and Lung Cancer Susceptibility — Are African American Affected Differently?

    OpenAIRE

    Hopkins, R.J.; R. P. Young

    2016-01-01

    The majority of lung cancer cases result from complex interactions between smoking exposure, genetic susceptibility and a person's immune response to chronic inflammation or lung remodelling. Epidemiological studies confirm that susceptibility to developing chronic obstructive pulmonary disease (COPD), especially emphysema, is also closely linked to lung cancer susceptibility. Genetic epidemiology studies have consistently reported associations between the chromosome 15q25 locus with lung can...

  3. CHEK2 1100delC and polygenic susceptibility to breast cancer and colorectal cancer

    NARCIS (Netherlands)

    M. Wasielewski (Marijke)

    2009-01-01

    textabstractApproximately 15-25% of breast cancers are identified in women with a family history of breast cancer. Yet, germline mutations in the currently known breast cancer susceptibility genes account for only one-third of familial breast cancer cases. In 2002, our research group had identified

  4. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium.

    Science.gov (United States)

    Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B; Behrens, Sabine; Goode, Ellen L; Bolla, Manjeet K; Dennis, Joe; Dunning, Alison M; Easton, Douglas F; Wang, Qin; Benitez, Javier; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Fasching, Peter A; Haeberle, Lothar; Peto, Julian; Dos-Santos-Silva, Isabel; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marmé, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Nielsen, Sune F; Nordestgaard, Børge G; González-Neira, Anna; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Fagerholm, Rainer; Dörk, Thilo; Bogdanova, Natalia V; Mannermaa, Arto; Hartikainen, Jaana M; Van Dijck, Laurien; Smeets, Ann; Flesch-Janys, Dieter; Eilber, Ursula; Radice, Paolo; Peterlongo, Paolo; Couch, Fergus J; Hallberg, Emily; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Schumacher, Fredrick; Simard, Jacques; Goldberg, Mark S; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Winqvist, Robert; Grip, Mervi; Andrulis, Irene L; Glendon, Gord; García-Closas, Montserrat; Figueroa, Jonine; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Eriksson, Mikael; Hall, Per; Li, Jingmei; Cox, Angela; Cross, Simon S; Pharoah, Paul D P; Shah, Mitul; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Ademuyiwa, Foluso; Ambrosone, Christine B; Swerdlow, Anthony; Jones, Michael; Chang-Claude, Jenny

    2016-01-01

    Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry. PMID:26621531

  5. The Polymorphism of DNA Repair Gene ERCC2/XPD Arg156Arg and Susceptibility to Breast Cancer in a Chinese Population

    DEFF Research Database (Denmark)

    Yin, J. Y.; Liang, D. H.; Vogel, Ulla Birgitte;

    2009-01-01

    association between ERCC2/XPD Arg156Arg and susceptibility to breast cancer in a Chinese population, we conducted a hospital-based case-control study consisting of 129 patients with breast cancer and 205 controls matched by age, gender, and ethnicity. PCR-RFLP was used for genotyping. No associations were...... (mean age 45 years) than cases with the wild CC genotype (mean age 50 years) (P = 0.05). There were no differences in risk estimates in relation to menopause and occurrence of breast cancer. Our findings do not suggest that ERCC2/XPD Arg156Arg contributes to breast cancer susceptibility in a Chinese...

  6. Counselling framework for moderate-penetrance cancer-susceptibility mutations.

    Science.gov (United States)

    Tung, Nadine; Domchek, Susan M; Stadler, Zsofia; Nathanson, Katherine L; Couch, Fergus; Garber, Judy E; Offit, Kenneth; Robson, Mark E

    2016-09-01

    The use of multigene panels for the assessment of cancer susceptibility is expanding rapidly in clinical practice, particularly in the USA, despite concerns regarding the uncertain clinical validity for some gene variants and the uncertain clinical utility of most multigene panels. So-called 'moderate-penetrance' gene mutations associated with cancer susceptibility are identified in approximately 2-5% of individuals referred for clinical testing; some of these mutations are potentially actionable. Nevertheless, the appropriate management of individuals harbouring such moderate-penetrance genetic variants is unclear. The cancer risks associated with mutations in moderate-penetrance genes are lower and different than those reported for high-penetrance gene mutations (such as mutations in BRCA1 and BRCA2, and those associated with Lynch syndrome). The extrapolation of guidelines for the management of individuals with high-penetrance variants of cancer-susceptibility genes to the clinical care of patients with moderate-penetrance gene mutations could result in substantial harm. Thus, we provide a framework for clinical decision-making pending the development of a sufficient evidence base to document the clinical utility of the interventions for individuals with inherited moderate-penetrance gene mutations associated with an increased risk of cancer. PMID:27296296

  7. Glutathione S-transferase P1, gene-gene interaction, and lung cancer susceptibility in the Chinese population: An updated meta-analysis and review

    Directory of Open Access Journals (Sweden)

    Xue-Ming Li

    2015-01-01

    Full Text Available Aim of Study: To assess the impact of glutathione S-transferase P1 (GSTP1 Ile105Val polymorphism on the risk of lung cancer in the Chinese population, an updated meta-analysis and review was performed. Materials and Methods: Relevant studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine published through January 22, 2015. The odds ratios (ORs and 95% confidence intervals (CIs were calculated to estimate the strength of the associations. Results: A total of 13 case-control studies, including 2026 lung cancer cases and 2451 controls, were included in this meta-analysis. Overall, significantly increased lung cancer risk was associated with the variant genotypes of GSTP1 polymorphism in the Chinese population (GG vs. AA: OR = 1.36, 95% CI = 1.01-1.84. In subgroup analyses stratified by geographic area and source of controls, the significant results were found in population-based studies (GG vs. AA: OR = 1.62, 95% CI: 1.13-2.31; GG vs. AG: OR = 1.49, 95% CI: 1.03-2.16; GG vs. AA + AG: OR = 1.55, 95% CI: 1.12-2.26. A gene-gene interaction analysis showed that there was an interaction for individuals with combination of GSTM1 (or GSTT1 null genotype and GSTP1 (AG + GG mutant genotype for lung cancer risk in Chinese. Conclusion: This meta-analysis suggests that GSTP1 Ile105Val polymorphism may increase the risk of lung cancer in the Chinese population.

  8. Characterization of TRZ1, a yeast homolog of the human candidate prostate cancer susceptibility gene ELAC2 encoding tRNase Z

    Directory of Open Access Journals (Sweden)

    Chen Yuan

    2005-05-01

    Full Text Available Abstract Background In humans, mutation of ELAC2 is associated with an increased risk of prostate cancer. ELAC2 has been shown to have tRNase Z activity and is associated with the γ-tubulin complex. Results In this work, we show that the yeast homolog of ELAC2, encoded by TRZ1 (tRNase Z 1, is involved genetically in RNA processing. The temperature sensitivity of a trz1 mutant can be rescued by multiple copies of REX2, which encodes a protein with RNA 3' processing activity, suggesting a role of Trz1p in RNA processing in vivo. Trz1p has two putative nucleotide triphosphate-binding motifs (P-loop and a conserved histidine motif. The histidine motif and the putative nucleotide binding motif at the C-domain are important for Trz1p function because mutant proteins bearing changes to the critical residues in these motifs are unable to rescue deletion of TRZ1. The growth defect exhibited by trz1 yeast is not complemented by the heterologous ELAC2, suggesting that Trz1p may have additional functions in yeast. Conclusion Our results provide genetic evidence that prostate cancer susceptibility gene ELAC2 may be involved in RNA processing, especially rRNA processing and mitochondrial function.

  9. Identification of genetic polymorphisms in DNA repair xenoderma pigmentosum group D gene and its association with head and neck cancer susceptibility in rural Indian population: a hospital based case-control study from south-western Maharashtra, India

    Directory of Open Access Journals (Sweden)

    Kailas D. Datkhile

    2016-06-01

    Conclusions: This study indicates that polymorphisms in cd199 of XPD gene could play a role in modifying genetic susceptibility of individual to head and neck cancer in Maharashtra patients. Thus, the case-control study suggest that selected DNA repair genes represent genetic determinants in oral carcinogenesis along with other risk factors in the rural Indian population. [Int J Res Med Sci 2016; 4(6.000: 1997-2005

  10. Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

    DEFF Research Database (Denmark)

    Rudolph, Anja; Milne, Roger L; Truong, Thérèse;

    2015-01-01

    A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estro...

  11. 29. LACK OF ASSOCIATION OF AH RECEPTOR GENE POLYMORPHISM WITH SUSCEPTIBILITY TO BLADDER CANCER IN SHANGHAI POPULATION

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@The diversity in genetic background largely predetermine the individual susceptibility towards health risk related to xenobiotic exposure. The receptors of signal transduction mechanism are involved in the modulation of toxicological outcome of xenobiotics. The survey of distribution of different polymorphic forms of Ah receptor in Chinese population and probing into their possible association with health risk related with xenobiotic exposure will not only contribute to a better understanding of mechanism of imperilment, but also inspire a clue for a further

  12. Genetic Susceptibility to Pancreatic Cancer

    OpenAIRE

    Klein, Alison P

    2012-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. However, it has the poorest prognosis of any major tumor type, with a 5-yr survival rate of approximately 5%. Cigarette smoking, increased body mass index, heavy alcohol consumption, and a diagnosis of diabetes mellitus have all been demonstrated to increase risk of pancreatic cancer. A family history of pancreatic cancer has also been associated with increased risk suggesting inherited g...

  13. Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer

    DEFF Research Database (Denmark)

    Shen, Hui; Fridley, Brooke L; Song, Honglin; Lawrenson, Kate; Cunningham, Julie M; Ramus, Susan J; Cicek, Mine S; Tyrer, Jonathan; Stram, Douglas; Larson, Melissa C; Köbel, Martin; Ziogas, Argyrios; Zheng, Wei; Yang, Hannah P; Wu, Anna H; Wozniak, Eva L; Woo, Yin Ling; Winterhoff, Boris; Wik, Elisabeth; Whittemore, Alice S; Wentzensen, Nicolas; Weber, Rachel Palmieri; Vitonis, Allison F; Vincent, Daniel; Vierkant, Robert A; Vergote, Ignace; Van Den Berg, David; Van Altena, Anne M; Tworoger, Shelley S; Thompson, Pamela J; Tessier, Daniel C; Terry, Kathryn L; Teo, Soo-Hwang; Templeman, Claire; Stram, Daniel O; Southey, Melissa C; Sieh, Weiva; Siddiqui, Nadeem; Shvetsov, Yurii B; Shu, Xiao-Ou; Shridhar, Viji; Wang-Gohrke, Shan; Severi, Gianluca; Schwaab, Ira; Salvesen, Helga B; Rzepecka, Iwona K; Runnebaum, Ingo B; Rossing, Mary Anne; Rodriguez-Rodriguez, Lorna; Risch, Harvey A; Renner, Stefan P; Poole, Elizabeth M; Pike, Malcolm C; Phelan, Catherine M; Pelttari, Liisa M; Pejovic, Tanja; Paul, James; Orlow, Irene; Omar, Siti Zawiah; Olson, Sara H; Odunsi, Kunle; Nickels, Stefan; Nevanlinna, Heli; Ness, Roberta B; Narod, Steven A; Nakanishi, Toru; Moysich, Kirsten B; Monteiro, Alvaro N A; Moes-Sosnowska, Joanna; Modugno, Francesmary; Menon, Usha; McLaughlin, John R; McGuire, Valerie; Matsuo, Keitaro; Adenan, Noor Azmi Mat; Massuger, Leon F A G; Lurie, Galina; Lundvall, Lene; Lubi?ski, Jan; Lissowska, Jolanta; Levine, Douglas A; Leminen, Arto; Lee, Alice W; Le, Nhu D; Lambrechts, Sandrina; Lambrechts, Diether; Kupryjanczyk, Jolanta; Krakstad, Camilla; Konecny, Gottfried E; Kjaer, Susanne Krüger; Kiemeney, Lambertus A; Kelemen, Linda E; Keeney, Gary L; Karlan, Beth Y; Karevan, Rod; Kalli, Kimberly R; Kajiyama, Hiroaki; Ji, Bu-Tian; Jensen, Allan; Jakubowska, Anna; Iversen, Edwin; Hosono, Satoyo; Høgdall, Claus K; Høgdall, Estrid; Hoatlin, Maureen; Hillemanns, Peter; Heitz, Florian; Hein, Rebecca; Harter, Philipp; Halle, Mari K; Hall, Per; Gronwald, Jacek; Gore, Martin; Goodman, Marc T; Giles, Graham G; Gentry-Maharaj, Aleksandra; Garcia-Closas, Montserrat; Flanagan, James M; Fasching, Peter A; Ekici, Arif B; Edwards, Robert; Eccles, Diana; Easton, Douglas F; Dürst, Matthias; du Bois, Andreas; Dörk, Thilo; Doherty, Jennifer A; Despierre, Evelyn; Dansonka-Mieszkowska, Agnieszka; Cybulski, Cezary; Cramer, Daniel W; Cook, Linda S; Chen, Xiaoqing; Charbonneau, Bridget; Chang-Claude, Jenny; Campbell, Ian; Butzow, Ralf; Bunker, Clareann H; Brueggmann, Doerthe; Brown, Robert James (Jim); Brooks-Wilson, Angela; Brinton, Louise A; Bogdanova, Natalia; Block, Matthew S; Benjamin, Elizabeth; Beesley, Jonathan; Beckmann, Matthias W; Bandera, Elisa V; Baglietto, Laura; Bacot, François; Armasu, Sebastian M; Antonenkova, Natalia; Anton-Culver, Hoda; Aben, Katja K; Liang, Dong; Wu, Xifeng; Lu, Karen; Hildebrandt, Michelle A T; Schildkraut, Joellen M; Sellers, Thomas A; Huntsman, David; Berchuck, Andrew; Chenevix-Trench, Georgia; Gayther, Simon A; Pharoah, Paul D P; Laird, Peter W; Goode, Ellen L; Pearce, Celeste Leigh

    2013-01-01

    HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we ...

  14. A gene-wide investigation on polymorphisms in the ABCG2/BRCP transporter and susceptibility to colorectal cancer

    Czech Academy of Sciences Publication Activity Database

    Campa, D.; Pardini, Barbara; Naccarati, Alessio; Vodičková, Ludmila; Novotný, J.; Försti, A.; Hemminki, K.; Barale, R.; Vodička, Pavel; Canzian, F.

    2008-01-01

    Roč. 645, 1-2 (2008), s. 56-60. ISSN 0027-5107 R&D Projects: GA ČR GA310/07/1430 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : ABCG2 * Transporter * Colorectal cancer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.198, year: 2008

  15. Association of adiponectin receptor 1 gene −106 C > T variant with susceptibility to colorectal cancer

    Directory of Open Access Journals (Sweden)

    Touraj Mahmoudi

    2016-09-01

    Conclusions: Our findings suggest for the first time that the −106 C > T (rs2275738 variant of ADIPOR1 gene may be a genetic contributor to CRC and obesity risk in the cases with CRC. However, further studies with bigger sample size are needed to validate these findings.

  16. Association of Single Nucleotide Polymorphisms in CYP1B1 and COMT Genes with Breast Cancer Susceptibility in Indian Women

    OpenAIRE

    Sharawan Yadav; Naveen Kumar Singhal; Virendra Singh; Neeraj Rastogi; Pramod Kumar Srivastava; Mahendra Pratap Singh

    2009-01-01

    Cytochrome P450 1B1 (CYP1B1) and catechol-$O$-methyltransferase (COMT) enzymes play critical roles in estrogen metabolism. Alterations in the catalytic activity of CYP1B1 and COMT enzymes have been found associated with altered breast cancer risk in postmenopausal women in many populations. The substitution of leucine (Leu) to valine (Val) at codon 432 increases the catalytic activity of CYP1B1, however, substitution of Val to methionine (Met) at codon 158 decreases the catalytic activity of ...

  17. Single-nucleotide polymorphism in microRNA-binding site of SULF1 target gene as a protective factor against the susceptibility to breast cancer: a case-control study

    Directory of Open Access Journals (Sweden)

    Zhou Q

    2016-05-01

    Full Text Available Qiong Zhou,1–3 Yiwei Jiang,1,2,4 Wenjin Yin,1,2 Yaohui Wang,1,2,4 Jinsong Lu4 1Department of Breast Surgery, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 3Department of Gynecology, Zhejiang Cancer Hospital, Hangzhou, 4Breast Cancer Center, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China Purpose: Numerous clinical studies have suggested that chemopreventive drugs for breast cancer such as tamoxifen and exemestane can effectively reduce the incidence of estrogen receptor (ER-positive breast cancer. However, it remains unclear how to identify those who are susceptible to ER-positive breast cancer. Accordingly, there is a great demand for a probe into the predisposing factors so as to provide precise chemoprevention. Recent evidence has indicated that ERα expression can be regulated by microRNAs (miRNAs, such as miR-206, in breast cancer. We assumed that single-nucleotide polymorphisms (SNPs in the miR-206-binding sites of the target genes may be associated with breast cancer susceptibility with different ER statuses. Methods: We genotyped the SNPs that reside in and around the miR-206-binding sites of two target genes – heparan sulfatase 1 (SULF1 and RPTOR-independent companion of mammalian target of rapamycin Complex 2 (RICTOR – which were related to the progression or metastasis of breast cancer cells in 710 breast cancer patients and 294 controls by the matrix-assisted laser desorption ionization-time of flight mass spectrometry method. Modified odds ratios (ORs with their 95% confidence intervals (CIs were calculated by a multivariate logistic regression analysis to evaluate the potential association between the SNPs and breast cancer susceptibility. Results: For rs3802278, which is located in the 3'-untranslated region (3'-UTR of SULF1, the frequency of the AA genotype was less in breast cancer patients

  18. ABRAXAS (FAM175A) and Breast Cancer Susceptibility: No Evidence of Association in the Breast Cancer Family Registry

    OpenAIRE

    Anne-Laure Renault; Fabienne Lesueur; Yan Coulombe; Stéphane Gobeil; Penny Soucy; Yosr Hamdi; Sylvie Desjardins; Florence Le Calvez-Kelm; Maxime Vallée; Catherine Voegele; Hopper, John L.; Andrulis, Irene L.; Southey, Melissa C.; John, Esther M.; Jean-Yves Masson

    2016-01-01

    Approximately half of the familial aggregation of breast cancer remains unexplained. This proportion is less for early-onset disease where familial aggregation is greater, suggesting that other susceptibility genes remain to be discovered. The majority of known breast cancer susceptibility genes are involved in the DNA double-strand break repair pathway. ABRAXAS is involved in this pathway and mutations in this gene impair BRCA1 recruitment to DNA damage foci and increase cell sensitivity to ...

  19. Polymorphisms in human telomerase reverse transcriptase (hTERT) gene and susceptibility to gastric cancer in a Turkish population: Hospital-based case-control study.

    Science.gov (United States)

    Bayram, Süleyman; Ülger, Yakup; Sümbül, Ahmet Taner; Kaya, Berrin Yalinbaş; Genç, Ahmet; Rencüzoğullari, Eyyüp; Dadaş, Erdoğan

    2016-07-01

    Erosion of telomeres, tandem nucleotide repeats (TTAGGG)n that cap the end of eukaryotic chromosomes, has been related with carcinogenesis. The human telomerase reverse transcriptase (hTERT) gene is encoded the rate-limiting catalytic subunit of the telomerase complexes, which is essential for the protection of telomeric DNA length and chromosomal stability. The purpose of this study was to examine the effect of four functional single nucleotide polymorphisms (SNPs) of hTERT (rs2736109 G>A, rs2735940 T>C, rs2853669 A>G and rs2736100 T>G) on susceptibility to gastric cancer (GC) in Turkish population. The genotype frequency of hTERT rs2736109 G>A, rs2735940 T>C, rs2853669 A>G and rs2736100 T>G polymorphisms were determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and TaqMan methods in 104 subjects with GC and 209 healthy control subjects. We found that hTERT rs2736109 G>A (AA+AG vs. GG OR=1.68 95% CI=1.01-2.81, P=0.04), rs2735940 T>C (CC vs. CT+TT: OR=2.53 95% CI=1.01-6.13, P=0.03), and rs2736100 T>G (TT vs. TG+GG: OR=2.27 95% CI=1.23-4.17, P=0.006) polymorphisms were associated with risk of GC. In the haplotype analysis, hTERT Grs2736109/Trs2735940/Ars2853669/Grs2736100 haplotype was also related with an increased risk of GC (OR=1.75; 95% CI: 1.05-2.93, P=0.03). Because this is the first study regarding the hTERT rs2736109 G>A, rs2735940 T>C, rs2853669 A>G and rs2736100 T>G polymorphisms and the risk of GC susceptibility in the literature, further independent studies are needed to verify our results in a larger sample sizes, as well as in patients of different populations. PMID:27016301

  20. Genetic polymorphisms in MMP 2, 3, 7, and 9 genes and the susceptibility and clinical outcome of cervical cancer in a Chinese Han population.

    Science.gov (United States)

    Xie, Beibei; Zhang, Zhen; Wang, Hui; Chen, Zhaojie; Wang, Yongsheng; Liang, Huazheng; Yang, Gaoyuan; Yang, Xingsheng; Zhang, Haiyan

    2016-04-01

    Matrix metalloproteases (MMPs) are proteolytic enzymes that contribute to all stages of tumor progression, including the invasion and metastasis. However, there are no data about the role of MMP polymorphism in the development of cervical cancer. A hospital-based case-control study was conducted in 230 patients with cervical cancer and 230 healthy controls to investigate the possible association between the MMP2 rs243865, MMP3 rs3025058, MMP7 rs11568818, and MMP9 rs3918242 polymorphisms, respectively, and the risk of cervical cancer. Our results suggested that the MMP2 rs243865-1306 C/T was significantly associated with an increased risk of cervical cancer (CT vs. CC, OR = 1.46; 95 % CI 1.18-3.55; P = 0.032; TT vs. CC, OR = 1.72; 95 % CI 1.28-4.02; P = 0.031; CT + TT vs. CC, OR = 1.43; 95 % CI 1.21-3.44; P = 0.029). Similarly, the MMP7 rs11568818-181A/G genotypes can also elevate the risk of cervical cancer in all genetic models. However, the genotype and allele frequencies of MMP3 rs3025058 and MMP9 rs3918242 polymorphisms in cervical cancer patients were not significantly different from controls. Further analysis showed MMP2 rs243865 and MMP7 rs11568818 genotypes were associated with advanced tumor stages of cervical cancer patients. More interestingly, the MMP2 rs243865 and MMP7 rs11568818 genotype was statistically significantly associated with a poor survival in cervical cancer patients. Our results showed that the MMP2 rs243865 and MMP7 rs11568818 genotypes e were associated with increased susceptibility and development of cervical cancer in Chinese Han population. PMID:26526578

  1. Association Between Polymorphism rs678653 in Human Cyclin D1 Gene (CCND1) and Susceptibility to Cancer: A Meta-Analysis.

    Science.gov (United States)

    Dai, Xichao; Zhang, Xizhi; Wang, Buhai; Wang, Chaomin; Jiang, Jingting; Wu, Changping

    2016-01-01

    BACKGROUND To assess the association between polymorphism rs678653 in human Cyclin D1 gene (CCND1) and the risk of cancer. MATERIAL AND METHODS Multiple biomedical databases were systematically searched. Pooled odds ratios (OR) and 95% confidence intervals (95% CIs) were calculated in the appropriate model. RESULTS In total, 17 case-control studies from 14 articles were included. When combing all available data, no significant association of rs678653 with cancer risk was observed under different genetic models. Stratification by ethnicity also indicated that rs678653 was not correlated with cancer risk in Taiwanese or Indian populations. When stratified by cancer type, no significant association was found between polymorphism rs678653 and digestive tract cancer, head and neck cancer, and gynecological cancer risk. CONCLUSIONS Our comprehensive meta-analysis suggests that the polymorphism rs678653 in CCND1 has no association with cancer risk in different population and disease contexts, indicating that CCND1 rs678653 does not serve a significant biological function in predicting cancer risk. PMID:26979757

  2. Inhibition of constitutively activated phosphoinositide 3-kinase/AKT pathway enhances antitumor activity of chemotherapeutic agents in breast cancer susceptibility gene 1-defective breast cancer cells.

    Science.gov (United States)

    Yi, Yong Weon; Kang, Hyo Jin; Kim, Hee Jeong; Hwang, Jae Seok; Wang, Antai; Bae, Insoo

    2013-09-01

    Loss or decrease of wild type BRCA1 function, by either mutation or reduced expression, has a role in hereditary and sporadic human breast and ovarian cancers. We report here that the PI3K/AKT pathway is constitutively active in BRCA1-defective human breast cancer cells. Levels of phospho-AKT are sustained even after serum starvation in breast cancer cells carrying deleterious BRCA1 mutations. Knockdown of BRCA1 in MCF7 cells increases the amount of phospho-AKT and sensitizes cells to small molecule protein kinase inhibitors (PKIs) targeting the PI3K/AKT pathway. Restoration of wild type BRCA1 inhibits the activated PI3K/AKT pathway and de-sensitizes cells to PKIs targeting this pathway in BRCA1 mutant breast cancer cells, regardless of PTEN mutations. In addition, clinical PI3K/mTOR inhibitors, PI-103, and BEZ235, showed anti-proliferative effects on BRCA1 mutant breast cancer cell lines and synergism in combination with chemotherapeutic drugs, cisplatin, doxorubicin, topotecan, and gemcitabine. BEZ235 synergizes with the anti-proliferative effects of gemcitabine by enhancing caspase-3/7 activity. Our results suggest that the PI3K/AKT pathway can be an important signaling pathway for the survival of BRCA1-defective breast cancer cells and pharmacological inhibition of this pathway is a plausible treatment for a subset of breast cancers. PMID:22488590

  3. Inhibition of Constitutively Activated Phosphoinositide 3-Kinase/AKT Pathway Enhances Antitumor Activity of Chemotherapeutic Agents in Breast Cancer Susceptibility Gene 1-Defective Breast Cancer Cells

    OpenAIRE

    Yi, Yong Weon; KANG, HYO JIN; Kim, Hee Jeong; HWANG, JAE SEOK; Wang, Antai; BAE, INSOO

    2012-01-01

    Loss or decrease of wild type BRCA1 function, by either mutation or reduced expression, has a role in hereditary and sporadic human breast and ovarian cancers. We report here that the PI3K/AKT pathway is constitutively active in BRCA1-defective human breast cancer cells. Levels of phospho-AKT are sustained even after serum starvation in breast cancer cells carrying deleterious BRCA1 mutations. Knockdown of BRCA1 in MCF7 cells increases the amount of phospho-AKT and sensitizes cells to small m...

  4. Genetic susceptibility to breast and endometrial cancer

    OpenAIRE

    Wedrén, Sara

    2004-01-01

    Hormones are central in the carcinogenic process in the breast and in the uterine epithelium. Individual genetically determined variation in the response to hormonal influence may alter susceptibility to breast and endometrial cancers. Many small studies of this hypothesis have generated inconclusive results. Since the effect of any genetic variant is expected to be modest, large studies are needed to draw reliable conclusions. Also, there may be interaction between genetic ...

  5. Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results.

    NARCIS (Netherlands)

    Plon, S.E.; Eccles, D.M.; Easton, D.; Foulkes, W.D.; Genuardi, M.; Greenblatt, M.S.; Hogervorst, F.B.; Hoogerbrugge, N.; Spurdle, A.B.; Tavtigian, S.V.

    2008-01-01

    Genetic testing of cancer susceptibility genes is now widely applied in clinical practice to predict risk of developing cancer. In general, sequence-based testing of germline DNA is used to determine whether an individual carries a change that is clearly likely to disrupt normal gene function. Genet

  6. C766T low-density lipoprotein receptor-related protein 1 (LRP1) gene polymorphism and susceptibility to breast cancer

    International Nuclear Information System (INIS)

    Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor with an important role in regulating the activity of proteinases in extracellular matrix. Several studies have also described its role in intracellular signaling. Previous studies showed that the expression of LRP1 is related to invasiveness of cancer cells. However, recent data on LRP1 suggest that this receptor can also be involved in tumor establishment and progression. We investigated an association between the C766T polymorphism of the third exon of the LRP1 gene and breast cancer in a sample of women of Caucasian origin. Allele and genotype frequencies of this polymorphism were assessed in 164 women with breast cancer and in 183 age-compatible women without a history of any cancer disease. An increase in LRP1 T allele frequency in subjects with breast cancer was observed compared with controls (0.21 versus 0.15, P = 0.01963). A significant excess of genotypes with the T allele (homozygotes plus heterozygotes) was also observed (odds ratio 1.743, 95% confidence interval 1.112–2.732). The T allele of the C766T polymorphism in the LRP1 gene is associated with an increased risk of breast cancer development in women of Caucasian origin

  7. Cancer gene therapy

    OpenAIRE

    Mitrović Tatjana; Radulović Siniša

    2005-01-01

    Cancer gene therapy can be defined as transfer of nucleic acids into tumor or normal cells with aim to eradicate or reduce tumor mass by direct killing of cells, immunomodulation or correction of genetic errors, and reversion of malignant status. Initially started with lots of optimism and enthusiasm, cancer gene therapy has shown limited success in treatment of patients. This review highlights current limitations and almost endless possibilities of cancer gene therapy. The major difficulty i...

  8. Artificial neural network-based exploration of gene-nutrient interactions in folate and xenobiotic metabolic pathways that modulate susceptibility to breast cancer.

    Science.gov (United States)

    Naushad, Shaik Mohammad; Janaki Ramaiah, M; Pavithrakumari, Manickam; Jayapriya, Jaganathan; Hussain, Tajamul; Alrokayan, Salman A; Gottumukkala, Suryanarayana Raju; Digumarti, Raghunadharao; Kutala, Vijay Kumar

    2016-04-15

    In the current study, an artificial neural network (ANN)-based breast cancer prediction model was developed from the data of folate and xenobiotic pathway genetic polymorphisms along with the nutritional and demographic variables to investigate how micronutrients modulate susceptibility to breast cancer. The developed ANN model explained 94.2% variability in breast cancer prediction. Fixed effect models of folate (400μg/day) and B12 (6μg/day) showed 33.3% and 11.3% risk reduction, respectively. Multifactor dimensionality reduction analysis showed the following interactions in responders to folate: RFC1 G80A×MTHFR C677T (primary), COMT H108L×CYP1A1 m2 (secondary), MTR A2756G (tertiary). The interactions among responders to B12 were RFC1G80A×cSHMT C1420T and CYP1A1 m2×CYP1A1 m4. ANN simulations revealed that increased folate might restore ER and PR expression and reduce the promoter CpG island methylation of extra cellular superoxide dismutase and BRCA1. Dietary intake of folate appears to confer protection against breast cancer through its modulating effects on ER and PR expression and methylation of EC-SOD and BRCA1. PMID:26784656

  9. Association of cancer stem cell markers genetic variants with gallbladder cancer susceptibility, prognosis, and survival.

    Science.gov (United States)

    Yadav, Anu; Gupta, Annapurna; Rastogi, Neeraj; Agrawal, Sushma; Kumar, Ashok; Kumar, Vijay; Mittal, Balraj

    2016-02-01

    Genes important to stem cell progression have been involved in the genetics and clinical outcome of cancers. We investigated germ line variants in cancer stem cell (CSC) genes to predict susceptibility and efficacy of chemoradiotherapy treatment in gallbladder cancer (GBC) patients. In this study, we assessed the effect of SNPs in CSC genes (surface markers CD44, ALCAM, EpCAM, CD133) and (molecular markers NANOG, SOX-2, LIN-28A, ALDH1A1, OCT-4) with GBC susceptibility and prognosis. Total 610 GBC patients and 250 controls were genotyped by using PCR-RFLP, ARMS-PCR, and TaqMan allelic discrimination assays. Chemotoxicity graded 2-4 in 200 patients and tumor response was recorded in 140 patients undergoing neoadjuvant chemotherapy (NACT). Differences in genotype and haplotype frequency distributions were calculated by binary logistic regression. Gene-gene interaction model was analyzed by generalized multifactor dimensionality reduction (GMDR). Overall survival was assessed by Kaplan-Meier survival curve and multivariate Cox-proportional methods. ALCAM Ars1157Crs10511244 (P = 0.0035) haplotype was significantly associated with GBC susceptibility. In GMDR analysis, ALCAM rs1157G>A, EpCAM rs1126497T>C emerged as best significant interaction model with GBC susceptibility and ALDH1A1 rs13959T>G with increased risk of grade 3-4 hematological toxicity. SOX-2 rs11915160A>C, OCT-4 rs3130932T>G, and NANOG rs11055786T>C were found best gene-gene interaction model for predicting response to NACT. In both Cox-proportional and recursive partitioning ALCAM rs1157GA+AA genotype showed higher mortality and hazard ratio. ALCAM gene polymorphisms associated with GBC susceptibility and survival while OCT-4, SOX-2, and NANOG variants showed an interactive role with treatment response. PMID:26318430

  10. BRCA1基因多态性与宫颈癌发生关系的研究%Study on the polymorphism of breast cancer susceptibility gene 1 (BRCA1) and risk of cervical cancer

    Institute of Scientific and Technical Information of China (English)

    李利玲

    2011-01-01

    Objective; To study the polymorphism of breast cancer susceptibility gene 1 ( BRCA1) and the correlation with cervical cancer. Methods; A population based case -control study was conducted in 68 healthy controls and 71 cervical cancer patients. The BRCA1 Pro871 Leu polymorphism was detected by PCR - restriction fragment length polymorphism ( PCR - RFLP). Results; For the BRCA1 871 C>T polymorphism, individuals with C/T, C/C, C/T + T/T genotype significantly decreased the risk of developing cervical cancer compared with those harboring CyC genotype (C/T: OR (95% CI) =0.29 (0.13-0.68), T/T: OR (95% CI) = 0.29 (0.12-0.69), C/T + T/T; OR (95%CI) =0.29 (0.14-0.61). Conclusion: This study confirms the close relationship between BRCA1 polymorphism and cervical cancer. Mutation of BRCA1 Pro871Leu is a protective factor of inhibiting generation of cervical cancer.%目的 探讨人乳腺癌易感基因1(BRCA1)基因多态性与宫颈癌发生的关系.方法 采用病例对照研究,运用多聚酶链式反应-限制性片段长度多态性(PCR-RFLP)法检测71例宫颈癌患者和68例健康人BRCA1 871 C>T单核苷酸多态性,比较上述各组基因型和等位基因频率分布有无差异.结果 BRCA1 871T/T,C/T,C/T+T/T基因型相对于C/C基因型显著降低了宫颈癌发生的风险(C/T:OR(95%CI)=0.29(0.13-0.68),T/T:OR(95%CI)=0.29(0.12-0.69),C/T+T/T:OR(95%CI)=0.29(0.14-0.61);结论BRCA1基因突变与宫颈癌密切相关,BRCA1 871C>T降低了宫颈癌发生的风险.

  11. A Functional Variant at the miR-214 Binding Site in the Methylenetetrahydrofolatereductase Gene Alters Susceptibility to Gastric Cancer in a Chinese Han Population

    Directory of Open Access Journals (Sweden)

    Qiaoyun Chen

    2015-05-01

    Full Text Available Background and Aims: Single nucleotide polymorphisms in miRNA binding sites, which are located in mRNA 3' untranslated regions (3'-UTRs, were recently found to influence microRNA-target interactions. Specifically, such polymorphisms can modulatebinding affinity or create or destroy miRNA-binding sites; such variants have also been found to be associated with cancer risk. In this study, we explored the effect of a functional variant at the miR-214 binding site in the methylenetetrahydrofolate reductase gene (rs114673809 on gastric cancer (GC risk in a hospital-based case-control study in a Chinese Han population. Methods and Results: We genotyped the rs114673809 polymorphism in 345 gastric cancer patients and 376 cancer-free controls using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP technique. The functions of rs114673809 were investigated using a luciferase activity assay and validated by immunoblotting. We found that participants carrying the rs114673809 AA genotype or A allele had a significantly increased risk of gastric cancer (OR = 1.667, 95% CI = 1.044-2.660, P = 0.034; OR = 1.261, 95% CI = 1.017-1.563, P = 0.037, respectively compared to those carrying the GG genotype and G allele. In addition, rs114673809 modified the binding of hsa-miR-214 to MTHFR as well as MTHFR protein levels in gastric cancer patients. Conclusion: Our data suggested that rs114673809, which is located at the miR-214 binding site in the 3'-UTR of MTHFR, may play an important role in the development of gastric cancer in a Chinese Han population.

  12. Inherited susceptibility to cancer and other factors influencing occurrence of cancer

    International Nuclear Information System (INIS)

    The types of defects and polymorphisms leading to hereditary susceptibility to cancer include proneness to increased DNA damage, recessive syndromes of faulty DNA repair and differentiation, as well as dominant mutations of cell cycle and control proliferation. The cancer susceptibility syndromes inherited in a dominant fashion are caused by mutations in tumor suppressor genes. These genes are recessive in relation to wild type alleles. In two syndromes of hereditary mutations in tumor suppressor genes (Rb and WT2), their expression 'in vivo' may be influenced by the sex of the transmitting parent, what points to modulation by imprinting. Genetic heterogeneity of the population in susceptibility to genotoxic agents is related to the individual variation in acceptable levels of exposure to agents and factors, such as products of incomplete combustion (PIC), UV ('xeroderma pigmentosum') and ionizing radiation ('ataxia telangiectasia'). DNA damage and adducts are considered to be indicative of genotoxic exposure and its effect as well as modulation of carcinogenic damage by genetic polymorphisms. Gene and protein polymorphisms are considered as markers of increased individual risk. Since environmental factors are considered to be able to control, the individual susceptibility to enhanced DNA damage and environmentally induced cancers could be counteracted by decreasing the levels of contamination or exposure. This explains the wide interest in markers of this individual sensitivity. Most of the postulated markers of sensitivity to PIV do not, however, prove to be generally applicable in that sense. Their prognostic value is limited either by low amplitude of the effect, or by their character specific either to the population or to the cancer type. The polymorphisms most relevant to cancers induced by PIC exposures may be those of inductibility of benzopyrene hydroxylase, and some other DNA polymorphisms concerning the CYP1A1 gene. (author). 24 refs, 1 fig., 3 tabs

  13. Intracisternal A particle genes: Distribution in the mouse genome, active subtypes, and potential roles as species-specific mediators of susceptibility to cancer.

    Science.gov (United States)

    Qin, Chunhua; Wang, Zhibin; Shang, Jin; Bekkari, Kavitha; Liu, Rong; Pacchione, Stephen; McNulty, Kathleen A; Ng, Alan; Barnum, John E; Storer, Richard D

    2010-01-01

    Rodents, mice and rats in particular, are the species of choice for evaluating chemical carcinogenesis. However, different species and strains often respond very differently, undermining the logic of extrapolation of animal results to humans and complicating risk assessment. Intracisternal A particles (IAPs), endogenous retroviral sequences, are an important class of transposable elements that induce genomic mutations and cell transformation by disrupting gene expression. Several lines of evidence support a role of IAPs as mouse-specific genetic factors in responses to toxicity and expression of disease phenotypes. Since multiple subtypes and copies of IAPs are present in the mouse genome, their activity and locations relative to functional genes are of critical importance. This study identified the major "active" subtypes of IAPs (subtype 1/1a) that are responsible for newly transposed IAP insertions described in the literature, and confirmed that (1) polymorphisms for IAP insertions exist among different mouse strains and (2) promoter activity of the LTRs can be modulated by chemicals. This study further identified all the genes in the C57BL/6 mouse genome with IAP subtype 1 and 1a sequences inserted in their proximity, and the major biofunctional categories and cellular signaling networks of those genes. Since many "IAP-associated genes" play important roles in the regulation of cell proliferation, cell cycle, and cell death, the associated IAPs, upon activation, can affect cellular responses to xenobiotics and disease processes, especially carcinogenesis. This systemic analysis provides a solid foundation for further investigations of the role of IAPs as species- and strain-specific disease susceptibility factors. PMID:20025072

  14. Association of interferon regulatory factor 4 gene polymorphisms rs12203592 and rs872071 with skin cancer and haematological malignancies susceptibility: a meta-analysis of 19 case–control studies

    International Nuclear Information System (INIS)

    Research has indicated that the rs12203592 and rs872071 interferon regulatory factor 4 (IRF4) gene polymorphisms correlate with the risk of cancer, especially skin cancer and haematological malignancies, but the results remain controversial. To understand better the effects of these two polymorphisms on skin cancer and haematological malignancies susceptibility, a cumulative meta-analysis was performed. We conducted a search using the PubMed and Web of Science databases for relevant case-control studies published before April 2014. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using fixed- or random-effects models where appropriate. Heterogeneity test, publication bias test, and sensitivity analysis were also performed. In total, 11 articles comprised of 19 case–control studies were identified; five focused on the rs12203592 polymorphism with 7,992 cases and 8,849 controls, and six were on the rs872071 polymorphism with 3108 cases and 8300 controls. As for rs12203592, a significant correlation with overall skin cancer and haematological malignancies risk was found with the homozygote comparison model (OR = 1.566, 95% CI 1.087-2.256) and recessive model (OR = 1.526, 95% CI 1.107-2.104). For rs872071, a significantly elevated haematological malignancies risk was observed in all genetic models (homozygote comparison: OR = 1.805, 95% CI 1.402-2.323; heterozygote comparison: OR = 1.427, 95% CI 1.203-1.692; dominant: OR = 1.556, 95% CI 1.281-1.891; recessive: OR = 1.432, 95% CI 1.293-1.587; additive: OR = 1.349, 95% CI 1.201-1.515). Similarly, increased skin cancer and haematological malignancies risk was also identified after stratification of the SNP data by cancer type, ethnicity and source of controls for both polymorphisms. Our meta-analysis indicated that the rs12203592 and rs872071 IRF4 gene polymorphisms are associated with individual susceptibility to skin cancer and haematological malignancies. Moreover, the effect

  15. Gene Therapy of Cancerous Diseases

    OpenAIRE

    Valenčáková, A.; Dziaková, A.; Hatalová, E.

    2015-01-01

    Gene therapy of cancerous diseases provides new means of curing patients with oncologic illnesses. There are several approaches in treating cancer by gene therapy. Most commonly used methods are: cancer immunogene therapy, suicide gene therapy, application of tumor-suppressor genes, antiangiogenic therapy, mesenchymal stem cells used as vectors, gene directed enzyme/prodrug therapy and bacteria used as anti-cancer agents. Cancer gene immunotherapy uses several immunologic agents for the purp...

  16. ESR1 is co-expressed with closely adjacent uncharacterised genes spanning a breast cancer susceptibility locus at 6q25.1.

    Directory of Open Access Journals (Sweden)

    Anita K Dunbier

    2011-04-01

    Full Text Available Approximately 80% of human breast carcinomas present as oestrogen receptor α-positive (ER+ve disease, and ER status is a critical factor in treatment decision-making. Recently, single nucleotide polymorphisms (SNPs in the region immediately upstream of the ER gene (ESR1 on 6q25.1 have been associated with breast cancer risk. Our investigation of factors associated with the level of expression of ESR1 in ER+ve tumours has revealed unexpected associations between genes in this region and ESR1 expression that are important to consider in studies of the genetic causes of breast cancer risk. RNA from tumour biopsies taken from 104 postmenopausal women before and after 2 weeks treatment with an aromatase (oestrogen synthase inhibitor was analyzed on Illumina 48K microarrays. Multiple-testing corrected Spearman correlation revealed that three previously uncharacterized open reading frames (ORFs located immediately upstream of ESR1, C6ORF96, C6ORF97, and C6ORF211 were highly correlated with ESR1 (Rs =  0.67, 0.64, and 0.55 respectively, FDR<1 × 10(-7. Publicly available datasets confirmed this relationship in other groups of ER+ve tumours. DNA copy number changes did not account for the correlations. The correlations were maintained in cultured cells. An ERα antagonist did not affect the ORFs' expression or their correlation with ESR1, suggesting their transcriptional co-activation is not directly mediated by ERα. siRNA inhibition of C6ORF211 suppressed proliferation in MCF7 cells, and C6ORF211 positively correlated with a proliferation metagene in tumours. In contrast, C6ORF97 expression correlated negatively with the metagene and predicted for improved disease-free survival in a tamoxifen-treated published dataset, independently of ESR1. Our observations suggest that some of the biological effects previously attributed to ER could be mediated and/or modified by these co-expressed genes. The co-expression and function of these genes may be

  17. Mapping and localization of susceptible genes in asthma

    Institute of Scientific and Technical Information of China (English)

    GU Ming-liang; ZHAO Jing

    2011-01-01

    Objective To elucidate the development of mapping and localization of susceptible genes on chromosomes to asthma related phenotypes.Data sources Published articles about susceptibility genes for asthma related phenotypes were selected using PubMed.Study selection Using methods of candidate gene positional clone and genome-wide scan with linkage and association analysis to determine the location in the genome of susceptibility genes to asthma and asthma related phenotypes.Results There are multiple regions in the genome harboring susceptibility genes to asthma and asthma relatedphenotypes, including chromosomes 5, 11, 12, 6, 2, 3, 13, 7, 14, 9, 19 and 17. Many of these regions contain candidate genes involved in asthma development and progression. Some susceptible genes may affect the phenotype expression or response to therapy. In addition, the interaction of multiple genes with the environment may contribute to the susceptibility to asthma.Conclusions As an essential step toward cloning the susceptible genes to asthma, fine mapping and localization onchromosomes are definitely needed. Novel powerful tools for gene discovery and the integration of genetics, biology and bioinformatics should be pursued.

  18. A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24

    DEFF Research Database (Denmark)

    Goode, Ellen L; Chenevix-Trench, Georgia; Song, Honglin;

    2010-01-01

    Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with foll...

  19. Polygenic susceptibility to breast cancer: current state-of-the-art

    Science.gov (United States)

    Ghoussaini, Maya; Pharoah, Paul DP

    2016-01-01

    Breast cancer is the most commonly occurring invasive cancer among women and its estimated incidence rate worldwide is approximately 1 million cases annually. Although several breast cancer susceptibility genes have been identified over the past two decades, it is likely that many genes with modest effects are yet to be found. In this review, we discuss the progress that has been recently made with the emergence of empirical genome-wide association studies for breast cancer and the identification of several common, low-penetrance disease alleles at loci that had not been previously implicated as candidates for breast cancer susceptibility. We also discuss the implications of these recent findings for risk prediction, targeted screening and public health interventions, and conclude by discussing the strengths and weaknesses of these studies, and the strategies required to identify additional risk factors for breast cancer. PMID:19519208

  20. Association of Breast Cancer Susceptibility Variants with Risk of Pancreatic Cancer

    Science.gov (United States)

    Couch, Fergus J.; Wang, Xianshu; McWilliams, Robert R.; Bamlet, William R.; de Andrade, Mariza; Petersen, Gloria M.

    2011-01-01

    Background A number of susceptibility genes are common to breast and pancreatic cancer. Recently, several breast cancer susceptibility loci have been identified through genome-wide association studies. Here we evaluated possible associations between these single nucleotide polymorphisms (SNPs) and pancreatic cancer risk. Methods Ten SNPs from FGFR2, TOX3, MAP3K1, H19, LSP1, chromosome 8q24, CASP8 and LUM were investigated for associations with pancreatic cancer risk following genotyping in 1143 caucasian individuals with pancreatic adenocarcinoma and 1097 unaffected controls from a clinic-based pancreatic cancer case-control study. Results CASP8 rs1045485 (Odds ratio (OR)= 0.78; 95% confidence interval (95%CI), 0.65-0.9; p=0.005) and MAP3K1 rs889312 (OR= 0.85; 95%CI, 0.74-0.97; p=0.017)) showed evidence of association with risk of pancreatic cancer. The CASP8 rs1045485 association was evident in ever-smokers (p=0.002), but not in non-smokers (p=0.55), and the effect was strongest in heavy smokers (OR, 0.52; 95% CI, 0.29- 0.93; p=0.03). In contrast the MAP3K1 rs889312 association was only evident in non-smokers (OR, 0.78; 95%CI, 0.64-0.95; p=0.01). In addition, evaluation of the influence of the ten SNPs on survival detected significant associations between outcome for locally advanced pancreatic cancer cases and both 8q rs6983561 (p=0.045) and LUM rs2268578 (p=0.02). Conclusion Association studies in a large pancreatic case-control study indicates that SNPs associated with breast cancer may also be associated with pancreatic cancer susceptibility and survival. PMID:19843670

  1. Identification of genes associated with multiple cancers via integrative analysis

    Directory of Open Access Journals (Sweden)

    Huang Jian

    2009-11-01

    Full Text Available Abstract Background Advancement in gene profiling techniques makes it possible to measure expressions of thousands of genes and identify genes associated with development and progression of cancer. The identified cancer-associated genes can be used for diagnosis, prognosis prediction, and treatment selection. Most existing cancer microarray studies have been focusing on the identification of genes associated with a specific type of cancer. Recent biomedical studies suggest that different cancers may share common susceptibility genes. A comprehensive description of the associations between genes and cancers requires identification of not only multiple genes associated with a specific type of cancer but also genes associated with multiple cancers. Results In this article, we propose the Mc.TGD (Multi-cancer Threshold Gradient Descent, an integrative analysis approach capable of analyzing multiple microarray studies on different cancers. The Mc.TGD is the first regularized approach to conduct "two-dimensional" selection of genes with joint effects on cancer development. Simulation studies show that the Mc.TGD can more accurately identify genes associated with multiple cancers than meta analysis based on "one-dimensional" methods. As a byproduct, identification accuracy of genes associated with only one type of cancer may also be improved. We use the Mc.TGD to analyze seven microarray studies investigating development of seven different types of cancers. We identify one gene associated with six types of cancers and four genes associated with five types of cancers. In addition, we also identify 11, 9, 18, and 17 genes associated with 4 to 1 types of cancers, respectively. We evaluate prediction performance using a Leave-One-Out cross validation approach and find that only 4 (out of 570 subjects cannot be properly predicted. Conclusion The Mc.TGD can identify a short list of genes associated with one or multiple types of cancers. The identified genes

  2. Clues to the Function of the Tumour Susceptibility Gene BRCA2

    Directory of Open Access Journals (Sweden)

    Simon A. Gayther

    1998-01-01

    Full Text Available The breast cancer susceptibility gene BRCA2 was isolated in 1995. BRCA2 is a large gene comprising 10,254 nucleotides and 26 coding exons. Neither the nucleotide nor the predicted protein sequences (comprising 3,418 amino acids have provided substantial clues about its function. As a result, researchers have been trying to elucidate the function using a combination of cell biological and biochemical methods and the construction of animal models using gene targeting in mice. Recent data suggest that BRCA2 may participate in pathways associated with recombination or double-strand DNA break repair and may act by either sensing or responding to DNA damage. In addition, there is evidence to suggest that BRCA2 functions in a manner similar to the previously isolated breast cancer susceptibility gene BRCA1.

  3. Childhood indicators of susceptibility to subsequent cervical cancer

    OpenAIRE

    Montgomery, S M; Ehlin, A G C; Sparén, P.; Björkstén, B; Ekbom, A.

    2002-01-01

    Common warts could indicate cervical cancer susceptibility, as both are caused by human papillomavirus (HPV). Eczema was also investigated, as atopic eczema has been negatively associated with warts, but non-atopic eczema may be associated with compromised host defences, as observed in patients with HIV, suggesting increased susceptibility to HPV infection and cervical cancer. ‘Cervical cancer’ was self-reported during an interview by 87 of 7594 women members of two longitudinal British birth...

  4. ABRAXAS (FAM175A and Breast Cancer Susceptibility: No Evidence of Association in the Breast Cancer Family Registry.

    Directory of Open Access Journals (Sweden)

    Anne-Laure Renault

    Full Text Available Approximately half of the familial aggregation of breast cancer remains unexplained. This proportion is less for early-onset disease where familial aggregation is greater, suggesting that other susceptibility genes remain to be discovered. The majority of known breast cancer susceptibility genes are involved in the DNA double-strand break repair pathway. ABRAXAS is involved in this pathway and mutations in this gene impair BRCA1 recruitment to DNA damage foci and increase cell sensitivity to ionizing radiation. Moreover, a recurrent germline mutation was reported in Finnish high-risk breast cancer families. To determine if ABRAXAS could be a breast cancer susceptibility gene in other populations, we conducted a population-based case-control mutation screening study of the coding exons and exon/intron boundaries of ABRAXAS in the Breast Cancer Family Registry. In addition to the common variant p.Asp373Asn, sixteen distinct rare variants were identified. Although no significant difference in allele frequencies between cases and controls was observed for the identified variants, two variants, p.Gly39Val and p.Thr141Ile, were shown to diminish phosphorylation of gamma-H2AX in MCF7 human breast adenocarcinoma cells, an important biomarker of DNA double-strand breaks. Overall, likely damaging or neutral variants were evenly represented among cases and controls suggesting that rare variants in ABRAXAS may explain only a small proportion of hereditary breast cancer.

  5. ABRAXAS (FAM175A) and Breast Cancer Susceptibility: No Evidence of Association in the Breast Cancer Family Registry

    Science.gov (United States)

    Renault, Anne-Laure; Lesueur, Fabienne; Coulombe, Yan; Gobeil, Stéphane; Soucy, Penny; Hamdi, Yosr; Desjardins, Sylvie; Le Calvez-Kelm, Florence; Vallée, Maxime; Voegele, Catherine; Hopper, John L.; Andrulis, Irene L.; Southey, Melissa C.; John, Esther M.; Masson, Jean-Yves; Tavtigian, Sean V.; Simard, Jacques

    2016-01-01

    Approximately half of the familial aggregation of breast cancer remains unexplained. This proportion is less for early-onset disease where familial aggregation is greater, suggesting that other susceptibility genes remain to be discovered. The majority of known breast cancer susceptibility genes are involved in the DNA double-strand break repair pathway. ABRAXAS is involved in this pathway and mutations in this gene impair BRCA1 recruitment to DNA damage foci and increase cell sensitivity to ionizing radiation. Moreover, a recurrent germline mutation was reported in Finnish high-risk breast cancer families. To determine if ABRAXAS could be a breast cancer susceptibility gene in other populations, we conducted a population-based case-control mutation screening study of the coding exons and exon/intron boundaries of ABRAXAS in the Breast Cancer Family Registry. In addition to the common variant p.Asp373Asn, sixteen distinct rare variants were identified. Although no significant difference in allele frequencies between cases and controls was observed for the identified variants, two variants, p.Gly39Val and p.Thr141Ile, were shown to diminish phosphorylation of gamma-H2AX in MCF7 human breast adenocarcinoma cells, an important biomarker of DNA double-strand breaks. Overall, likely damaging or neutral variants were evenly represented among cases and controls suggesting that rare variants in ABRAXAS may explain only a small proportion of hereditary breast cancer. PMID:27270457

  6. Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD.

    Directory of Open Access Journals (Sweden)

    Robert P Young

    Full Text Available Epidemiological studies show that approximately 20-30% of chronic smokers develop chronic obstructive pulmonary disease (COPD while 10-15% develop lung cancer. COPD pre-exists lung cancer in 50-90% of cases and has a heritability of 40-77%, much greater than for lung cancer with heritability of 15-25%. These data suggest that smokers susceptible to COPD may also be susceptible to lung cancer. This study examines the association of several overlapping chromosomal loci, recently implicated by GWA studies in COPD, lung function and lung cancer, in (n = 1400 subjects sub-phenotyped for the presence of COPD and matched for smoking exposure. Using this approach we show; the 15q25 locus confers susceptibility to lung cancer and COPD, the 4q31 and 4q22 loci both confer a reduced risk to both COPD and lung cancer, the 6p21 locus confers susceptibility to lung cancer in smokers with pre-existing COPD, the 5p15 and 1q23 loci both confer susceptibility to lung cancer in those with no pre-existing COPD. We also show the 5q33 locus, previously associated with reduced FEV(1, appears to confer susceptibility to both COPD and lung cancer. The 6p21 locus previously linked to reduced FEV(1 is associated with COPD only. Larger studies will be needed to distinguish whether these COPD-related effects may reflect, in part, associations specific to different lung cancer histology. We demonstrate that when the "risk genotypes" derived from the univariate analysis are incorporated into an algorithm with clinical variables, independently associated with lung cancer in multivariate analysis, modest discrimination is possible on receiver operator curve analysis (AUC = 0.70. We suggest that genetic susceptibility to lung cancer includes genes conferring susceptibility to COPD and that sub-phenotyping with spirometry is critical to identifying genes underlying the development of lung cancer.

  7. Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer

    DEFF Research Database (Denmark)

    Kabisch, Maria; Lorenzo Bermejo, Justo; Dünnebier, Thomas;

    2015-01-01

    The chromosomal passenger complex (CPC) plays a pivotal role in the regulation of cell division. Therefore, inherited CPC variability could influence tumor development. The present candidate gene approach investigates the relationship between single nucleotide polymorphisms (SNPs) in genes encodi...

  8. Genes that modulate susceptibility for alcohol dependence

    OpenAIRE

    Caio Cesar Silva de Cerqueira; Domingos Lázaro Souza Rios

    2008-01-01

    The pathways for the metabolism of the alcohol are complex and modulated by some genes that promote response to this substance. The genes that codify the enzyme alcohol dehydrogenase (os genes ADH1B or ADH2) act in the conversion of ethanol in acetaldehyde; the enzyme aldehyde dehydrogenase (ALDH2) that converts the aldehyde into ascetic acid, and the gene that codifies the enzyme cytochrome P450, isoform 2E1 (CYP2E1), that acts generating free radicals of great importance in the induced hepa...

  9. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

    DEFF Research Database (Denmark)

    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E;

    2011-01-01

    were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations......Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes.......016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor...

  10. Gene therapy of liver cancer

    OpenAIRE

    Hernandez-Alcoceba, R. (Rubén); B. Sangro; Prieto, J.

    2006-01-01

    The application of gene transfer technologies to the treatment of cancer has led to the development of new experimental approaches like gene directed enzyme/pro-drug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor genes. In addition, gene therapy has a big impact on other fields like cancer immunotherapy, anti-angiogenic therapy and virotherapy. These strategies are being evaluated for the treatment of primary and metastatic liver cancer and some of them have reac...

  11. Polymorphisms of CYP1A1*4 and GST as Susceptibility and Prognostic Genes for Acute Myeloid Leukemia

    OpenAIRE

    Sheriff, E.; Ahmed, A.; Heba, M

    2010-01-01

    Associations between polymorphisms for genes encoding enzymes involved in biotransformation of xenobiotics and susceptibility to several cancers have been shown in several studies. The aim of the study is to investigate the influence of cytochromes P450 (CYP1A1*4) and Glutathione S-transferases (GSTs) (T1 and M1) gene polymorphisms in susceptibility to acute myeloid leukemia (AML) as well as their prognostic role for the treatment outcome in AML patients. Material and Methods: This study incl...

  12. Is COMT a Susceptibility Gene for Schizophrenia?

    OpenAIRE

    Williams, Hywel J.; Owen, Michael J; O'Donovan, Michael C.

    2007-01-01

    Catechol-O-methyl transferase (COMT) is a catabolic enzyme involved in the degradation of a number of bioactive molecules; of principal interest to psychiatry, these include dopamine. The enzyme is encoded by the COMT gene. COMT is located (along with 47 other genes) in a fragment of chromosome 22q11 which when deleted results in a complex syndrome, the psychiatric manifestations of which include schizophrenia and other psychoses. These 2 observations have placed COMT near the top of a rather...

  13. Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity.

    OpenAIRE

    Ahmed, M.; Dorling, L.; Kerns, S.; Fachal, L; Elliott, R.; Partliament, M.; Rosenstein, B S; Vega, A; Gómez-Caamaño, A.; Barnett, G.; Dearnaley, D. P.; Hall, E.; Sydes, M; Burnet, N.; Pharoah, P. D.

    2016-01-01

    BACKGROUND: Numerous germline single-nucleotide polymorphisms increase susceptibility to prostate cancer, some lying near genes involved in cellular radiation response. This study investigated whether prostate cancer patients with a high genetic risk have increased toxicity following radiotherapy. METHODS: The study included 1560 prostate cancer patients from four radiotherapy cohorts: RAPPER (n=533), RADIOGEN (n=597), GenePARE (n=290) and CCI (n=150). Data from genome-wide association studie...

  14. Interactions between Environmental Factors and Melatonin Receptor Type 1A Polymorphism in Relation to Oral Cancer Susceptibility and Clinicopathologic Development

    OpenAIRE

    Lin, Feng-Yan; Lin, Chiao-Wen; Yang, Shun-Fa; Lee, Wei-Jiunn; Lin, Yung-Wei; Lee, Liang-Ming; Chang, Junn-Liang; Weng, Wei-chun; Lin, Chien-Huang; Chien, Ming-Hsien

    2015-01-01

    Background The purpose of this study was to explore the combined effect of melatonin receptor type 1A (MTNR1A) gene polymorphisms and exposure to environmental carcinogens on the susceptibility and clinicopathological characteristics of oral cancer. Methodology and Principal Findings Three polymorphisms of the MTNR1A gene from 618 patients with oral cancer and 560 non-cancer controls were analyzed by real-time polymerase chain reaction (PCR). The CTA haplotype of the studied MTNR1A polymorphi...

  15. A gene-wide investigation on polymorphisms in the taste receptor 2R14 (TAS2R14) and susceptibility to colorectal cancer

    Czech Academy of Sciences Publication Activity Database

    Campa, D.; Vodička, Pavel; Pardini, Barbara; Naccarati, Alessio; Carrai, M.; Vodičková, Ludmila; Novotný, J.; Hemminki, K.; Försti, A.; Barale, R.; Canzian, F.

    2010-01-01

    Roč. 11, č. 1 (2010), s. 88-93. ISSN 1471-2350 R&D Projects: GA ČR GA310/05/2626 Institutional research plan: CEZ:AV0Z50390512 Keywords : colorectal cancer * TAS2R14 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.439, year: 2010

  16. Gene therapy of liver cancer

    Institute of Scientific and Technical Information of China (English)

    Ruben Hernandez-Alcoceba; Bruno Sangro; Jesus Prieto

    2006-01-01

    The application of gene transfer technologies to the treatment of cancer has led to the development of new experimental approaches like gene directed enzyme/prodrug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor genes. In addition,gene therapy has a big impact on other fields like cancer immunotherapy, anti-angiogenic therapy and virotherapy.These strategies are being evaluated for the treatment of primary and metastatic liver cancer and some of them have reached clinical phases. We present a review on the basis and the actual status of gene therapy approaches applied to liver cancer.

  17. Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci

    OpenAIRE

    Shen, Changbing; Gao, Jing; Sheng, Yujun; Dou, Jinfa; Zhou, Fusheng; Zheng, Xiaodong; Ko, Randy; Tang, Xianfa; Zhu, Caihong; Yin, Xianyong; Sun, Liangdan; Cui, Yong; Zhang, Xuejun

    2016-01-01

    Vitiligo is an autoimmune disease with a strong genetic component, characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Genetic factors are known to play key roles in vitiligo through discoveries in association studies and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Recently, our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wid...

  18. The Role of Methylation in Breast Cancer Susceptibility and Treatment.

    Science.gov (United States)

    Pouliot, Marie-Christine; Labrie, Yvan; Diorio, Caroline; Durocher, Francine

    2015-09-01

    DNA methylation is a critical mechanism of epigenetic modification involved in gene expression programming, that can promote the development of several cancers, including breast cancer. The methylation of CpG islands by DNA methyltransferases is reversible and has been shown to modify the transcriptional activity of key proliferation genes or transcription factors involved in suppression or promotion of cell growth. Indeed, aberrant methylation found in gene promoters is a hallmark of cancer that could be used as non-intrusive biomarker in body fluids such as blood and plasma for early detection of breast cancer. Many biomarker genes have been evaluated for breast cancer detection. However, in the absence of a unique biomarker having the sufficient specificity and sensitivity, a panel of multiple genes should be used. Treatments targeting aberrant methylation by DNA methyltransferase inhibitors, which trigger re-expression of silenced genes, are now available and allow for better treatment efficiency. PMID:26254344

  19. Selenoprotein S (SEPS1) gene -105G>A promoter polymorphism influences the susceptibility to gastric cancer in the Japanese population

    OpenAIRE

    Nagasaka Mitsuo; Nakamura Masakatsu; Kamiya Yoshio; Fujita Hiroshi; Maruyama Naoko; Yoshioka Daisuke; Ohkubo Masaaki; Tahara Tomomitsu; Arisawa Tomiyasu; Shibata Tomoyuki; Iwata Masami; Takahama Kazuya; Watanabe Makoto; Hirata Ichiro

    2009-01-01

    Abstract Background Inflammation is a key factor in the process of carcinogenesis from chronic gastritis induced by Helicobacter pylori. Selenoprotein S (SEPS1) is involved in the control of the inflammatory response in the endoplasmic reticulum (ER). Recently the -105G>A polymorphism in the promoter of SEPS1 was shown to increase pro-inflammatory cytokine expression. We examined the association between this polymorphism and the risk of gastric cancer. Methods We took stomach biopsies during ...

  20. Risk allelic load in Th2 and Th3 cytokines genes as biomarker of susceptibility to HPV-16 positive cervical cancer: a case control study

    OpenAIRE

    K. Torres-Poveda; A. I. Burguete-García; Bahena-Román, M.; Méndez-Martínez, R.; Zurita-Díaz, M. A.; López-Estrada, G.; Delgado-Romero, K.; Peralta-Zaragoza, O.; Bermúdez-Morales, V. H.; Cantú, D; García-Carrancá, A.; Madrid-Marina, V.

    2016-01-01

    Background Alterations in the host cellular immune response allow persistent infections with High-Risk Human Papillomavirus (HR-HPV) and development of premalignant cervical lesions and cervical cancer (CC). Variations of immunosuppressive cytokine levels in cervix are associated with the natural history of CC. To assess the potential role of genetic host immunity and cytokines serum levels in the risk of developing CC, we conducted a case–control study paired by age. Methods Peripheral blood...

  1. Selenoprotein S (SEPS1 gene -105G>A promoter polymorphism influences the susceptibility to gastric cancer in the Japanese population

    Directory of Open Access Journals (Sweden)

    Nagasaka Mitsuo

    2009-01-01

    Full Text Available Abstract Background Inflammation is a key factor in the process of carcinogenesis from chronic gastritis induced by Helicobacter pylori. Selenoprotein S (SEPS1 is involved in the control of the inflammatory response in the endoplasmic reticulum (ER. Recently the -105G>A polymorphism in the promoter of SEPS1 was shown to increase pro-inflammatory cytokine expression. We examined the association between this polymorphism and the risk of gastric cancer. Methods We took stomach biopsies during endoscopies of 268 Japanese gastric cancer patients (193 males and 75 females, average age 65.3, and 306 control patients (184 males and 122 females, average age 62.7 and extracted the DNA from the biopsy specimens. All subjects provided written informed consent. For the genotyping of the SEPS1 promoter polymorphism at position -105G>A, PCR-RFLP methods were used and the PCR products were digested with PspGI. Logistic-regression analysis was used to estimate odds ratios (OR and 95% confidence intervals (CI, adjusting for age, sex, and H. pylori infection status. Results Among cases, the distribution of genotypes was as follows: 88.4% were GG, 11.2% were GA, and 0.4% were AA. Among controls, the distribution was as follows: 92.5% were GG, 7.2% were GA, and 0.3% were AA. Among males, carrying the A allele was associated with an increased odds of gastric cancer, compared with the GG genotype (OR: 2.0, 95% CI 1.0–4.1, p = 0.07. Compared with the GG genotype, carrying the A allele was significantly associated with increased risks of intestinal type gastric cancer (OR: 2.0, 95%CI 1.0–3.9, p Conclusion The -105G>A promoter polymorphism of SEPS1 was associated with the intestinal type of gastric cancer. This polymorphism may influence the inflammatory conditions of gastric mucosa. Larger population-based studies are needed for clarifying the relation between inflammatory responses and SEPS1 polymorphism.

  2. Gene Therapy of Cancerous Diseases

    Directory of Open Access Journals (Sweden)

    Valenčáková, A.

    2015-11-01

    Full Text Available Gene therapy of cancerous diseases provides new means of curing patients with oncologic illnesses. There are several approaches in treating cancer by gene therapy. Most commonly used methods are: cancer immunogene therapy, suicide gene therapy, application of tumor-suppressor genes, antiangiogenic therapy, mesenchymal stem cells used as vectors, gene directed enzyme/prodrug therapy and bacteria used as anti-cancer agents. Cancer gene immunotherapy uses several immunologic agents for the purpose of explaining effective anti-tumor immune response. Another method is suicide gene therapy, based on introducing viral or bacterial agents to tumor cells, allowing the conversion of a non-toxic compound to a lethal medication. The application of intact suppressor genes to cancer cells will avert their neoplastic behavior and will induce tumor regression. Inhibition of angiogenesis is also a promising strategy for treating oncologic patients. Mesenchymal stem cells can also be used as vectors in targeted gene therapy. An increasing list of experimental evidence shows, that therapeutically modified mesenchymal stem cells in “gene directed enzyme/prodrug therapy” can attack cancer tissue can kill tumor cells, cancer stem cells included. Bacteria are used as anti-cancer agents independently of in combination with conventional therapeutic methods.

  3. A genomics approach to identify susceptibilities of breast cancer cells to “fever-range” hyperthermia

    International Nuclear Information System (INIS)

    Preclinical and clinical studies have shown for decades that tumor cells demonstrate significantly enhanced sensitivity to “fever range” hyperthermia (increasing the intratumoral temperature to 42-45°C) than normal cells, although it is unknown why cancer cells exhibit this distinctive susceptibility. To address this issue, mammary epithelial cells and three malignant breast cancer lines were subjected to hyperthermic shock and microarray, bioinformatics, and network analysis of the global transcription changes was subsequently performed. Bioinformatics analysis differentiated the gene expression patterns that distinguish the heat shock response of normal cells from malignant breast cancer cells, revealing that the gene expression profiles of mammary epithelial cells are completely distinct from malignant breast cancer lines following this treatment. Using gene network analysis, we identified altered expression of transcripts involved in mitotic regulators, histones, and non-protein coding RNAs as the significant processes that differed between the hyperthermic response of mammary epithelial cells and breast cancer cells. We confirmed our data via qPCR and flow cytometric analysis to demonstrate that hyperthermia specifically disrupts the expression of key mitotic regulators and G2/M phase progression in the breast cancer cells. These data have identified molecular mechanisms by which breast cancer lines may exhibit enhanced susceptibility to hyperthermic shock

  4. Low-risk susceptibility alleles in 40 human breast cancer cell lines

    International Nuclear Information System (INIS)

    Low-risk breast cancer susceptibility alleles or SNPs confer only modest breast cancer risks ranging from just over 1.0 to1.3 fold. Yet, they are common among most populations and therefore are involved in the development of essentially all breast cancers. The mechanism by which the low-risk SNPs confer breast cancer risks is currently unclear. The breast cancer association consortium BCAC has hypothesized that the low-risk SNPs modulate expression levels of nearby located genes. Genotypes of five low-risk SNPs were determined for 40 human breast cancer cell lines, by direct sequencing of PCR-amplified genomic templates. We have analyzed expression of the four genes that are located nearby the low-risk SNPs, by using real-time RT-PCR and Human Exon microarrays. The SNP genotypes and additional phenotypic data on the breast cancer cell lines are presented. We did not detect any effect of the SNP genotypes on expression levels of the nearby-located genes MAP3K1, FGFR2, TNRC9 and LSP1. The SNP genotypes provide a base line for functional studies in a well-characterized cohort of 40 human breast cancer cell lines. Our expression analyses suggest that a putative disease mechanism through gene expression modulation is not operative in breast cancer cell lines

  5. Identifying cancer genes from cancer mutation profiles by cancer functions

    Institute of Scientific and Technical Information of China (English)

    LI YanHui; GUO Zheng; PENG ChunFang; LIU Qing; MA WenCai; WANG Jing; YAO Chen; ZHANG Min; ZHU Jing

    2008-01-01

    It is of great importance to identify new cancer genes from the data of large scale genome screenings of gene mutations in cancers. Considering the alternations of some essential functions are indispensable for oncogenesis, we define them as cancer functions and select, as their approximations, a group of detailed functions in GO (Gene Ontology) highly enriched with known cancer genes. To evaluate the efficiency of using cancer functions as features to identify cancer genes, we define, in the screened genes, the known protein kinase cancer genes as gold standard positives and the other kinase genes as gold standard negatives. The results show that cancer associated functions are more efficient in identifying cancer genes than the selection pressure feature. Furthermore, combining cancer functions with the number of non-silent mutations can generate more reliable positive predictions. Finally, with precision 0.42, we suggest a list of 46 kinase genes as candidate cancer genes which are annotated to cancer functions and carry at least 3 non-silent mutations.

  6. Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study.

    Science.gov (United States)

    Childs, Erica J; Chaffee, Kari G; Gallinger, Steven; Syngal, Sapna; Schwartz, Ann G; Cote, Michele L; Bondy, Melissa L; Hruban, Ralph H; Chanock, Stephen J; Hoover, Robert N; Fuchs, Charles S; Rider, David N; Amundadottir, Laufey T; Stolzenberg-Solomon, Rachael; Wolpin, Brian M; Risch, Harvey A; Goggins, Michael G; Petersen, Gloria M; Klein, Alison P

    2016-07-01

    Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e., BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (iCOGS) array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR = 1.36; 95% CI, 1.13-1.63; P = 9.29 × 10(-4); 7p13, rs17688601: OR = 0.76; 95% CI, 0.63-0.93; P = 6.59 × 10(-3)). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (P pancreatic cancer for SNPs at HDAC9 (7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 25(7); 1185-91. ©2016 AACR. PMID:27197284

  7. Epidermal characteristics related to skin cancer susceptibility

    International Nuclear Information System (INIS)

    We have compared the basal cell labeling index and cellular architecture in samples of epidermis removed by vacuum blistering from people with or without a personal history of skin cancer. Donors with no family history of skin cancer showed a basal cell labeling index of 5.5% with a standard deviation of 1.3%. Those not personally affected but with a family history gave 4.1% +/- 0.4% but among cancer patients the value was approximately doubled to 11.5% +/- 2.7%. The proportion of cells replicating was reduced after ultraviolet irradiation, with a D0 of 40 J/m2 for UVB but no difference could be demonstrated between individuals with or without a history of skin cancer

  8. Gene therapy in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Xu Chang-tai; Guo Xue-gang; Pan Bo-rong

    2003-01-01

    @@ 1 Introduction We have reviewed the gene therapy in gastrointestinal diseases[1]. Gastric cancer is common in China[2~20] ,and its early diagnosis andtreatment are still difficult up to now[13~36]. The expression of anexogenous gene introduced by gene therapy into patients with gliomascan be monitored non- invasively by positron- emission tomography[4]. In recent years, gene study in cancer is a hotspot, and great progress hasbeen achieved[33~41].

  9. Breast Tissue Composition and Susceptibility to Breast Cancer

    OpenAIRE

    Boyd, Norman F.; Lisa J Martin; Bronskill, Michael; Martin J. Yaffe; Duric, Neb; Minkin, Salomon

    2010-01-01

    Breast density, as assessed by mammography, reflects breast tissue composition. Breast epithelium and stroma attenuate x-rays more than fat and thus appear light on mammograms while fat appears dark. In this review, we provide an overview of selected areas of current knowledge about the relationship between breast density and susceptibility to breast cancer. We review the evidence that breast density is a risk factor for breast cancer, the histological and other risk factors that are associat...

  10. Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease

    OpenAIRE

    Escott-Price, Valentina; Bellenguez, Celine; Wang, Li-San; Choi, Seung-Hoan; Harold, Denise; Jones, Lesley; Holmans, Peter; Gerrish, Amy; Vedernikov, Alexey; Richards, Alexander; Destefano, Anita L.; Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A; Naj, Adam C.; Sims, Rebecca

    2014-01-01

    Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes fr...

  11. Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease

    OpenAIRE

    Yong-Gang Yao; Valentina Escott-Price; Céline Bellenguez; Li-San Wang; Seung-Hoan Choi; Denise Harold; Lesley Jones; Peter Holmans; Amy Gerrish; Alexey Vedernikov; Alexander Richards; Destefano, Anita L.; Jean-Charles Lambert; Ibrahim-Verbaas, Carla A; Naj, Adam C.

    2014-01-01

    Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Al...

  12. Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease

    OpenAIRE

    Escott-Price, Valentina; Bellenguez, Céline; Wang, Lisan; Choi, Seunghoan; Harold, Denise H.; Jones, Lesley A.; Holmans, Peter A.; Gerrish, Amy; Vedernikov, Alexey; Richards, Alexander L.; Destefano, Anita L.; Lambert, Jean Charles; Ibrahim-Verbaas, Carla A; Naj, Adam C.; Sims, Rebecca J.A.

    2014-01-01

    Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes fr...

  13. Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

    OpenAIRE

    Escott-Price, V.; Bellenguez, C; Wang, L.; Choi, S.; Harold, D.; Jones, L.; Holmans, P.; Gerrish, A; Vedernikov, A.; Richards, A.; DeStefano, A.L.; Lambert, J.; Ibrahim-Verbaas, C.A.; Naj, A. C.; Sims, R.

    2014-01-01

    PUBLISHED BACKGROUND: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over...

  14. Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci.

    Science.gov (United States)

    Shen, Changbing; Gao, Jing; Sheng, Yujun; Dou, Jinfa; Zhou, Fusheng; Zheng, Xiaodong; Ko, Randy; Tang, Xianfa; Zhu, Caihong; Yin, Xianyong; Sun, Liangdan; Cui, Yong; Zhang, Xuejun

    2016-01-01

    Vitiligo is an autoimmune disease with a strong genetic component, characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Genetic factors are known to play key roles in vitiligo through discoveries in association studies and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Recently, our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wide association study (GWAS). More than 40 robust susceptible loci have been identified and confirmed to be associated with vitiligo by using GWAS. Most of these associated genes participate in important pathways involved in the pathogenesis of vitiligo. Many susceptible loci with unknown functions in the pathogenesis of vitiligo have also been identified, indicating that additional molecular mechanisms may contribute to the risk of developing vitiligo. In this review, we summarize the key loci that are of genome-wide significance, which have been shown to influence vitiligo risk. These genetic loci may help build the foundation for genetic diagnosis and personalize treatment for patients with vitiligo in the future. However, substantial additional studies, including gene-targeted and functional studies, are required to confirm the causality of the genetic variants and their biological relevance in the development of vitiligo. PMID:26870082

  15. Identification of candidate genes for dyslexia susceptibility on chromosome 18.

    Directory of Open Access Journals (Sweden)

    Thomas S Scerri

    Full Text Available Six independent studies have identified linkage to chromosome 18 for developmental dyslexia or general reading ability. Until now, no candidate genes have been identified to explain this linkage. Here, we set out to identify the gene(s conferring susceptibility by a two stage strategy of linkage and association analysis.Linkage analysis: 264 UK families and 155 US families each containing at least one child diagnosed with dyslexia were genotyped with a dense set of microsatellite markers on chromosome 18. Association analysis: Using a discovery sample of 187 UK families, nearly 3000 SNPs were genotyped across the chromosome 18 dyslexia susceptibility candidate region. Following association analysis, the top ranking SNPs were then genotyped in the remaining samples. The linkage analysis revealed a broad signal that spans approximately 40 Mb from 18p11.2 to 18q12.2. Following the association analysis and subsequent replication attempts, we observed consistent association with the same SNPs in three genes; melanocortin 5 receptor (MC5R, dymeclin (DYM and neural precursor cell expressed, developmentally down-regulated 4-like (NEDD4L.Along with already published biological evidence, MC5R, DYM and NEDD4L make attractive candidates for dyslexia susceptibility genes. However, further replication and functional studies are still required.

  16. Prioritisation and network analysis of Crohn's disease susceptibility genes.

    Directory of Open Access Journals (Sweden)

    Daniele Muraro

    Full Text Available Recent Genome-Wide Association Studies (GWAS have revealed numerous Crohn's disease susceptibility genes and a key challenge now is in understanding how risk polymorphisms in associated genes might contribute to development of this disease. For a gene to contribute to disease phenotype, its risk variant will likely adversely communicate with a variety of other gene products to result in dysregulation of common signaling pathways. A vital challenge is to elucidate pathways of potentially greatest influence on pathological behaviour, in a manner recognizing how multiple relevant genes may yield integrative effect. In this work we apply mathematical analysis of networks involving the list of recently described Crohn's susceptibility genes, to prioritise pathways in relation to their potential development of this disease. Prioritisation was performed by applying a text mining and a diffusion based method (GRAIL, GPEC. Prospective biological significance of the resulting prioritised list of proteins is highlighted by changes in their gene expression levels in Crohn's patients intestinal tissue in comparison with healthy donors.

  17. Replication of Breast Cancer Susceptibility Loci in Whites and African Americans Using a Bayesian Approach

    OpenAIRE

    O'Brien, Katie M.; Cole, Stephen R.; Poole, Charles; Bensen, Jeannette T.; Herring, Amy H.; Engel, Lawrence S.; Millikan, Robert C.

    2013-01-01

    Genome-wide association studies (GWAS) and candidate gene analyses have led to the discovery of several dozen genetic polymorphisms associated with breast cancer susceptibility, many of which are considered well-established risk factors for the disease. Despite attempts to replicate these same variant-disease associations in African Americans, the evaluable populations are often too small to produce precise or consistent results. We estimated the associations between 83 previously identified ...

  18. Postgenomics, uncertain futures, and the familiarization of susceptibility genes

    Science.gov (United States)

    Chilibeck, Gillian; Lock, Margaret; Sehdev, Megha

    2016-01-01

    This paper draws on empirical findings from interview studies in the USA and Canada to interrogate the idea that expanding practices of genetic testing are likely to transform kin and family relations in fundamental ways. We argue that in connection with common adult onset disorders in which susceptibility genes with low predictive power are implicated it is unlikely that family relationships will be radically altered as a result of learning about either individual or family genotypes. Rather, pre-existing family dynamics and ideas about family susceptibilities for disease may be reinforced. The case of the ApoE gene and its relationship to Alzheimer’s disease is used as an illustrative example. We found that “postgenomic” thinking, in which complexity of disease causation is emphasized, is readily apparent in informant narratives. PMID:20570031

  19. Gene therapy for thyroid cancer

    International Nuclear Information System (INIS)

    Gene therapy for thyroid cancer include immunotherapy, suicide gene therapy, tumor suppressor replacement, 131I therapy by sodium/iodide symporter and antisense therapy and so on. Gene therapy has wide perspectives, but there are many problems need to be solved for clinical application

  20. Gene Susceptibility in Iranian Asthmatic Patients: A Narrative Review

    OpenAIRE

    Alizadeh-Navaei, R; A Rafiei; Hedayatizadeh-Omran, A; I Mohammadzadeh; Arabi, M.

    2014-01-01

    As environmental factors are important in the development of asthma, genetic factors could have a critical role in the expression of the disease. Hence, we carried out a systematic review to assess the susceptible genes for asthma in Iranian population. We conducted a literature search by using the electronic database PubMed, Biological Abstracts Web of Science, Current Contents Connect, Cinahl, ScienceDirect, Scopus, IranMedex, and Scientific Information Database to identify articles that ev...

  1. AN EPIDEMIOLOGY AND MOLECULAR GENETIC STUDY ON BREAST CANCER SUSCEPTIBILITY

    Institute of Scientific and Technical Information of China (English)

    贾卫华; 王继先; 李本孝; 李征

    2000-01-01

    Objectives. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-based case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel art and Falconer methods were used to analyze the segregation ratio and heritability. Polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significartly, OR is 3.905 ( 95 % CI = 1.079 ~ 14.13), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 9.99%, which is larger than that in second, third degree and non-blood relatives. Segregation ratio is 0.021, heritability among first degree relatives is 35.6 ± 5.8%. Frequencies of LOH at BRCA1 and BRCA2 loci in sporadic breast cancer are 6.12% and 5.77% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome aberrations were observed. Conclusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.

  2. AN EPIDEMIOLOGY AND MOLECULAR GENETIC STUDY ON BREAST CANCER SUSCEPTIBILITY

    Institute of Scientific and Technical Information of China (English)

    贾卫华; 王继先; 李本孝; 李征

    2000-01-01

    Obieaites. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-besed case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel-Gart and Falconer methods were used to analyze the segregation ratio and heritability. Polymemse chain reaction (PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significantly, OR is 3.905(95% CI = 1.079—14.13), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 9.99%, which is larger than that in second, third degree and non-blnod relatives. Segregation ratio is 0.021, heritability among first degree relatives is 35.6 ± 5.8%. Frequencies of LDH at BRCA1 and BRCA2 loci in sporadic breast cancer are 6.12% and 5.77% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome abermtions were observed.Condusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.

  3. HOX genes in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Kelly Zoë L

    2011-09-01

    Full Text Available Abstract The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development. Here we review a number of recent studies showing that HOX genes are strongly expressed in ovarian cancer, and that in some cases the expression of specific HOX genes is sufficient to confer a particular identity and phenotype upon cancer cells. We also review the recent advances in elucidating the different functions of HOX genes in ovarian cancer. A literature search was performed using the search terms HOX genes (including specific HOX genes, ovarian cancer and oncogenesis. Articles were accessed through searches performed in ISI Web of Knowledge, PubMed and ScienceDirect. Taken together, these studies have shown that HOX genes play a role in the oncogenesis of ovarian cancer and function in the inhibition of apoptosis, DNA repair and enhanced cell motility. The function of HOX genes in ovarian cancer oncogenesis supports their potential role as prognostic and diagnostic markers, and as therapeutic targets in this disease.

  4. MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis

    Directory of Open Access Journals (Sweden)

    Wu Wei

    2011-05-01

    Full Text Available Abstract Background The tumor suppressor gene p53 is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. In the last decade it has been demonstrated that the single nucleotide polymorphism (SNP at codon 72 of the p53 gene is associated with the risk for development of various neoplasms. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the MDM2 gene promoter. From the time that this well-characterized functional polymorphism was identified, a variety of case-control studies have been published that investigate the possible association between MDM2 SNP309 and cancer risk. However, the results of the published studies, as well as the subsequent meta-analyses, remain contradictory. Methods To investigate whether currently published epidemiological studies can clarify the potential interaction between MDM2 SNP309 and the functional genetic variant in p53 codon72 (Arg72Pro and p53 mutation status, we performed a meta-analysis of the risk estimate on 27,813 cases with various tumor types and 30,295 controls. Results The data we reviewed indicated that variant homozygote 309GG and heterozygote 309TG were associated with a significant increased risk of all tumor types (homozygote comparison: odds ratio (OR = 1.25, 95% confidence interval (CI = 1.13-1.37; heterozygote comparison: OR = 1.10, 95% CI = 1.03-1.17. We also found that the combination of GG and Pro/Pro, TG and Pro/Pro, GG and Arg/Arg significantly increased the risk of cancer (OR = 3.38, 95% CI = 1.77-6.47; OR = 1.88, 95% CI = 1.26-2.81; OR = 1.96, 95% CI = 1.01-3.78, respectively. In a stratified analysis by tumor location, we also found a significant increased risk in brain, liver, stomach and uterus cancer (OR = 1.47, 95% CI = 1.06-2.03; OR = 2.24, 95%CI = 1.57-3.18; OR = 1.54, 95%CI = 1.04-2.29; OR = 1.34, 95%CI = 1.07-1.29, respectively. However, no association was seen between MDM2 SNP309 and tumor susceptibility

  5. MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis

    International Nuclear Information System (INIS)

    The tumor suppressor gene p53 is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. In the last decade it has been demonstrated that the single nucleotide polymorphism (SNP) at codon 72 of the p53 gene is associated with the risk for development of various neoplasms. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the MDM2 gene promoter. From the time that this well-characterized functional polymorphism was identified, a variety of case-control studies have been published that investigate the possible association between MDM2 SNP309 and cancer risk. However, the results of the published studies, as well as the subsequent meta-analyses, remain contradictory. To investigate whether currently published epidemiological studies can clarify the potential interaction between MDM2 SNP309 and the functional genetic variant in p53 codon72 (Arg72Pro) and p53 mutation status, we performed a meta-analysis of the risk estimate on 27,813 cases with various tumor types and 30,295 controls. The data we reviewed indicated that variant homozygote 309GG and heterozygote 309TG were associated with a significant increased risk of all tumor types (homozygote comparison: odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.13-1.37; heterozygote comparison: OR = 1.10, 95% CI = 1.03-1.17). We also found that the combination of GG and Pro/Pro, TG and Pro/Pro, GG and Arg/Arg significantly increased the risk of cancer (OR = 3.38, 95% CI = 1.77-6.47; OR = 1.88, 95% CI = 1.26-2.81; OR = 1.96, 95% CI = 1.01-3.78, respectively). In a stratified analysis by tumor location, we also found a significant increased risk in brain, liver, stomach and uterus cancer (OR = 1.47, 95% CI = 1.06-2.03; OR = 2.24, 95%CI = 1.57-3.18; OR = 1.54, 95%CI = 1.04-2.29; OR = 1.34, 95%CI = 1.07-1.29, respectively). However, no association was seen between MDM2 SNP309 and tumor susceptibility in the stratified analysis by p53 mutation status

  6. Cancer susceptibility and reproductive trade-offs: a model of the evolution of cancer defences.

    Science.gov (United States)

    Boddy, Amy M; Kokko, Hanna; Breden, Felix; Wilkinson, Gerald S; Aktipis, C Athena

    2015-07-19

    The factors influencing cancer susceptibility and why it varies across species are major open questions in the field of cancer biology. One underexplored source of variation in cancer susceptibility may arise from trade-offs between reproductive competitiveness (e.g. sexually selected traits, earlier reproduction and higher fertility) and cancer defence. We build a model that contrasts the probabilistic onset of cancer with other, extrinsic causes of mortality and use it to predict that intense reproductive competition will lower cancer defences and increase cancer incidence. We explore the trade-off between cancer defences and intraspecific competition across different extrinsic mortality conditions and different levels of trade-off intensity, and find the largest effect of competition on cancer in species where low extrinsic mortality combines with strong trade-offs. In such species, selection to delay cancer and selection to outcompete conspecifics are both strong, and the latter conflicts with the former. We discuss evidence for the assumed trade-off between reproductive competitiveness and cancer susceptibility. Sexually selected traits such as ornaments or large body size require high levels of cell proliferation and appear to be associated with greater cancer susceptibility. Similar associations exist for female traits such as continuous egg-laying in domestic hens and earlier reproductive maturity. Trade-offs between reproduction and cancer defences may be instantiated by a variety of mechanisms, including higher levels of growth factors and hormones, less efficient cell-cycle control and less DNA repair, or simply a larger number of cell divisions (relevant when reproductive success requires large body size or rapid reproductive cycles). These mechanisms can affect intra- and interspecific variation in cancer susceptibility arising from rapid cell proliferation during reproductive maturation, intrasexual competition and reproduction. PMID:26056364

  7. Genome-wide association study of susceptibility loci for breast cancer in Sardinian population

    International Nuclear Information System (INIS)

    Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p < 10−6 level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10−5, we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16x10−5), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population. The online version of this article (doi:10.1186/s12885-015-1392-9) contains supplementary material, which is available to authorized users

  8. Interactions between environmental factors and melatonin receptor type 1A polymorphism in relation to oral cancer susceptibility and clinicopathologic development.

    Directory of Open Access Journals (Sweden)

    Feng-Yan Lin

    Full Text Available The purpose of this study was to explore the combined effect of melatonin receptor type 1A (MTNR1A gene polymorphisms and exposure to environmental carcinogens on the susceptibility and clinicopathological characteristics of oral cancer.Three polymorphisms of the MTNR1A gene from 618 patients with oral cancer and 560 non-cancer controls were analyzed by real-time polymerase chain reaction (PCR. The CTA haplotype of the studied MTNR1A polymorphisms (rs2119882, rs13140012, rs6553010 was related to a higher risk of oral cancer. Moreover, MTNR1A gene polymorphisms exhibited synergistic effects of environmental factors (betel quid and tobacco use on the susceptibility of oral cancer. Finally, oral-cancer patients with betel quid-chewing habit who had T/T allele of MTNR1A rs13140012 were at higher risk for developing an advanced clinical stage and lymph node metastasis.These results support gene-environment interactions of MTNR1A polymorphisms with smoking and betel quid-chewing habits possibly altering oral-cancer susceptibility and metastasis.

  9. Genetic susceptibility loci, pesticide exposure and prostate cancer risk.

    Directory of Open Access Journals (Sweden)

    Stella Koutros

    Full Text Available Uncovering SNP (single nucleotide polymorphisms-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs and 95% confidence intervals (CIs. Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1 SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44-8.15 (P-interaction= 0.003. Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41 (P-interaction= 0.006. In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.

  10. Haplotypes of nine single nucleotide polymorphisms on chromosome 19q13.2-3 associated with susceptibility of lung cancer in a Chinese population

    DEFF Research Database (Denmark)

    Yin, Jiaoyang; Vogel, Ulla Birgitte; Ma, Yegang;

    2008-01-01

    To evaluate the joint effect of nine single nucleotide polymorphisms for three DNA repair genes in the region of chromosome 19q13.2-3 on susceptibility of lung cancer in a Chinese population, we conducted a hospital-based case-control study consisting of 247 lung cancer cases and 253 cancer...

  11. Prostate Cancer Susceptibility Polymorphism rs2660753 Is Not Associated with Invasive Ovarian Cancer

    DEFF Research Database (Denmark)

    Amankwah, Ernest K; Kelemen, Linda E; Wang, Qinggang;

    2011-01-01

    BACKGROUND: We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC; OR = 1.2, 95% CI=1.0-1.4, P(trend) = 0.01) that showed a stronger association with the serous histological subtype (OR = 1.3, 95% CI = 1.......0-1.2, P(trend) = 0.11). There was no evidence for statistical heterogeneity in ORs across the studies. CONCLUSIONS: Although rs2660753 is a strong prostate cancer susceptibility polymorphism, the association with another hormonally related cancer, invasive EOC, is not supported by this replication study.......1-1.5, P(trend) = 0.003). METHODS: We sought to replicate this association in 12 other studies comprising 4,482 cases and 6,894 controls of white non-Hispanic ancestry in the Ovarian Cancer Association Consortium. RESULTS: No evidence for an association with all cancers or serous cancers was observed in a...

  12. The multidrug resistance 1 (MDR1) gene polymorphism G-rs3789243-A is not associated with disease susceptibility in Norwegian patients with colorectal adenoma and colorectal cancer; a case control study

    DEFF Research Database (Denmark)

    Andersen, V.; Agerstjerne, L.; Jensen, D.;

    2009-01-01

    Background: Smoking, dietary factors, and alcohol consumption are known life style factors contributing to gastrointestinal carcinogenesis. Genetic variations in carcinogen handling may affect cancer risk. The multidrug resistance 1(MDR1/ABCB1) gene encodes the transport protein P-glycoprotein (a...

  13. Progress in Gene Therapy for Prostate Cancer

    OpenAIRE

    KamranAliAhmed; BrianJamesDavis; TorrenceMWilson; GregoryAWiseman; MarkJFederspiel; JohnCMorris

    2012-01-01

    Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our...

  14. Gene Therapy in Human Breast Cancer

    OpenAIRE

    Abaan, Ogan D.

    2002-01-01

    Gene therapy, being a novel treatment for many diseases, is readily applicable for the treatment of cancer patients. Breast cancer is the most common cancer among women. There are many clinical protocols for the treatment of breast cancer, and gene therapy is now being considered within current protocols. This review will focus on the basic concepts of cancer gene therapy strategies (suicide gene, tumor suppressor gene, anti-angiogenesis, immunotherapy, oncolytic viruses and ribozyme/antisens...

  15. Lack of Replication of Seven Pancreatic Cancer Susceptibility Loci Identified in Two Asian Populations

    Czech Academy of Sciences Publication Activity Database

    Campa, D.; Rizzato, C.; Bauer, A. S.; Werner, J.; Capurso, G.; Costello, E.; Talar-Wojnarowska, R.; Jamroziak, K.; Pezzilli, R.; Gazouli, M.; Khaw, K. T.; Key, T. J.; Bambi, F.; Mohelníková-Duchoňová, B.; Heller, A.; Landi, S.; Vodičková, Ludmila; Theodoropoulos, G.; Burget, P.; Vodička, Pavel; Hoheisel, J. D.; Delle Fave, G.; Neoptolemos, J. P.; Souček, P.; Buechler, M. W.; Giese, N.; Canzian, F.

    2013-01-01

    Roč. 22, č. 2 (2013), s. 320-323. ISSN 1055-9965 Institutional support: RVO:68378041 Keywords : cancer growth * cancer risk * cancer susceptibility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.324, year: 2013

  16. SNP-SNP interactions in breast cancer susceptibility

    Directory of Open Access Journals (Sweden)

    Wang Yuanyuan

    2006-05-01

    Full Text Available Abstract Background Breast cancer predisposition genes identified to date (e.g., BRCA1 and BRCA2 are responsible for less than 5% of all breast cancer cases. Many studies have shown that the cancer risks associated with individual commonly occurring single nucleotide polymorphisms (SNPs are incremental. However, polygenic models suggest that multiple commonly occurring low to modestly penetrant SNPs of cancer related genes might have a greater effect on a disease when considered in combination. Methods In an attempt to identify the breast cancer risk conferred by SNP interactions, we have studied 19 SNPs from genes involved in major cancer related pathways. All SNPs were genotyped by TaqMan 5'nuclease assay. The association between the case-control status and each individual SNP, measured by the odds ratio and its corresponding 95% confidence interval, was estimated using unconditional logistic regression models. At the second stage, two-way interactions were investigated using multivariate logistic models. The robustness of the interactions, which were observed among SNPs with stronger functional evidence, was assessed using a bootstrap approach, and correction for multiple testing based on the false discovery rate (FDR principle. Results None of these SNPs contributed to breast cancer risk individually. However, we have demonstrated evidence for gene-gene (SNP-SNP interaction among these SNPs, which were associated with increased breast cancer risk. Our study suggests cross talk between the SNPs of the DNA repair and immune system (XPD-[Lys751Gln] and IL10-[G(-1082A], cell cycle and estrogen metabolism (CCND1-[Pro241Pro] and COMT-[Met108/158Val], cell cycle and DNA repair (BARD1-[Pro24Ser] and XPD-[Lys751Gln], and within carcinogen metabolism (GSTP1-[Ile105Val] and COMT-[Met108/158Val] pathways. Conclusion The importance of these pathways and their communication in breast cancer predisposition has been emphasized previously, but their

  17. SNP-SNP interactions in breast cancer susceptibility

    International Nuclear Information System (INIS)

    Breast cancer predisposition genes identified to date (e.g., BRCA1 and BRCA2) are responsible for less than 5% of all breast cancer cases. Many studies have shown that the cancer risks associated with individual commonly occurring single nucleotide polymorphisms (SNPs) are incremental. However, polygenic models suggest that multiple commonly occurring low to modestly penetrant SNPs of cancer related genes might have a greater effect on a disease when considered in combination. In an attempt to identify the breast cancer risk conferred by SNP interactions, we have studied 19 SNPs from genes involved in major cancer related pathways. All SNPs were genotyped by TaqMan 5'nuclease assay. The association between the case-control status and each individual SNP, measured by the odds ratio and its corresponding 95% confidence interval, was estimated using unconditional logistic regression models. At the second stage, two-way interactions were investigated using multivariate logistic models. The robustness of the interactions, which were observed among SNPs with stronger functional evidence, was assessed using a bootstrap approach, and correction for multiple testing based on the false discovery rate (FDR) principle. None of these SNPs contributed to breast cancer risk individually. However, we have demonstrated evidence for gene-gene (SNP-SNP) interaction among these SNPs, which were associated with increased breast cancer risk. Our study suggests cross talk between the SNPs of the DNA repair and immune system (XPD-[Lys751Gln] and IL10-[G(-1082)A]), cell cycle and estrogen metabolism (CCND1-[Pro241Pro] and COMT-[Met108/158Val]), cell cycle and DNA repair (BARD1-[Pro24Ser] and XPD-[Lys751Gln]), and within carcinogen metabolism (GSTP1-[Ile105Val] and COMT-[Met108/158Val]) pathways. The importance of these pathways and their communication in breast cancer predisposition has been emphasized previously, but their biological interactions through SNPs have not been described

  18. Heuristic modeling of carcinogenesis for the population with dichotomous susceptibility to cancer: a pancreatic cancer example.

    Directory of Open Access Journals (Sweden)

    Tengiz Mdzinarishvili

    Full Text Available At present, carcinogenic models imply that all individuals in a population are susceptible to cancer. These models either ignore a fall of the cancer incidence rate at old ages, or use some poorly identifiable parameters for its accounting. In this work, a new heuristic model is proposed. The model assumes that, in a population, only a small fraction (pool of individuals is susceptible to cancer and decomposes the problem of the carcinogenic modeling on two sequentially solvable problems: (i determination of the age-specific hazard rate in individuals susceptible to cancer (individual hazard rate from the observed hazard rate in the population (population hazard rate; and (ii modelling of the individual hazard rate by a chosen "up" of the theoretical hazard function describing cancer occurrence in individuals in time (age. The model considers carcinogenesis as a failure of individuals susceptible to cancer to resist cancer occurrence in aging and uses, as the theoretical hazard function, the three-parameter Weibull hazard function, often utilized in a failure analysis. The parameters of this function, providing the best fit of the modeled and observed individual hazard rates (determined from the population hazard rates, are the outcomes of the modeling. The model was applied to the pancreatic cancer data. It was shown that, in the populations stratified by gender, race and the geographic area of living, the modeled and observed population hazard rates of pancreatic cancer occurrence have similar turnovers at old ages. The sizes of the pools of individuals susceptible to this cancer: (i depend on gender, race and the geographic area of living; (ii proportionally influence the corresponding population hazard rates; and (iii do not influence the individual hazard rates. The model should be further tested using data on other types of cancer and for the populations stratified by different categorical variables.

  19. Identification of Pseudomonas aeruginosa genes associated with antibiotic susceptibility

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Pseudomonas aeruginosa causes acute and chronic infections in humans and these infections are difficult to treat due to the bacteria’s high-level of intrinsic and acquired resistance to antibiotics. To address this problem, it is crucial to investigate the molecular mechanisms of antibiotic resistance in this organism. In this study, a P. aeruginosa transposon insertion library of 17000 clones was constructed and screened for altered susceptibility to seven antibiotics. Colonies grown on agar plates con- taining antibiotics at minimum inhibitory concentrations (MICs) and those unable to grow at ? MIC were collected. The transposon-disrupted genes in 43 confirmed mutants that showed at least a three-fold increase or a two-fold decrease in suscep- tibility to at least one antibiotic were determined by semi-random PCR and subsequent sequencing analysis. In addition to nine genes known to be associated with antibiotic resistance, including mexI, mexB and mexR, 24 new antibiotic resis- tance-associated genes were identified, including a fimbrial biogenesis gene pilY1 whose disruption resulted in a 128-fold in- crease in the MIC of carbenicillin. Twelve of the 43 genes identified were of unknown function. These genes could serve as targets to control or reverse antibiotic resistance in this important human pathogen.

  20. Targeted Next-Generation Sequencing Identifies a Recurrent Mutation in MCPH1 Associating with Hereditary Breast Cancer Susceptibility.

    Directory of Open Access Journals (Sweden)

    Tuomo Mantere

    2016-01-01

    Full Text Available Breast cancer is strongly influenced by hereditary risk factors, a majority of which still remain unknown. Here, we performed a targeted next-generation sequencing of 796 genes implicated in DNA repair in 189 Finnish breast cancer cases with indication of hereditary disease susceptibility and focused the analysis on protein truncating mutations. A recurrent heterozygous mutation (c.904_916del, p.Arg304ValfsTer3 was identified in early DNA damage response gene, MCPH1, significantly associating with breast cancer susceptibility both in familial (5/145, 3.4%, P = 0.003, OR 8.3 and unselected cases (16/1150, 1.4%, P = 0.016, OR 3.3. A total of 21 mutation positive families were identified, of which one-third exhibited also brain tumors and/or sarcomas (P = 0.0007. Mutation carriers exhibited significant increase in genomic instability assessed by cytogenetic analysis for spontaneous chromosomal rearrangements in peripheral blood lymphocytes (P = 0.0007, suggesting an effect for MCPH1 haploinsufficiency on cancer susceptibility. Furthermore, 40% of the mutation carrier tumors exhibited loss of the wild-type allele. These findings collectively provide strong evidence for MCHP1 being a novel breast cancer susceptibility gene, which warrants further investigations in other populations.

  1. Targeted Next-Generation Sequencing Identifies a Recurrent Mutation in MCPH1 Associating with Hereditary Breast Cancer Susceptibility

    Science.gov (United States)

    Mantere, Tuomo; Winqvist, Robert; Kauppila, Saila; Grip, Mervi; Jukkola-Vuorinen, Arja; Tervasmäki, Anna; Rapakko, Katrin; Pylkäs, Katri

    2016-01-01

    Breast cancer is strongly influenced by hereditary risk factors, a majority of which still remain unknown. Here, we performed a targeted next-generation sequencing of 796 genes implicated in DNA repair in 189 Finnish breast cancer cases with indication of hereditary disease susceptibility and focused the analysis on protein truncating mutations. A recurrent heterozygous mutation (c.904_916del, p.Arg304ValfsTer3) was identified in early DNA damage response gene, MCPH1, significantly associating with breast cancer susceptibility both in familial (5/145, 3.4%, P = 0.003, OR 8.3) and unselected cases (16/1150, 1.4%, P = 0.016, OR 3.3). A total of 21 mutation positive families were identified, of which one-third exhibited also brain tumors and/or sarcomas (P = 0.0007). Mutation carriers exhibited significant increase in genomic instability assessed by cytogenetic analysis for spontaneous chromosomal rearrangements in peripheral blood lymphocytes (P = 0.0007), suggesting an effect for MCPH1 haploinsufficiency on cancer susceptibility. Furthermore, 40% of the mutation carrier tumors exhibited loss of the wild-type allele. These findings collectively provide strong evidence for MCHP1 being a novel breast cancer susceptibility gene, which warrants further investigations in other populations. PMID:26820313

  2. The diabetes susceptibility gene Clec16a regulates mitophagy

    OpenAIRE

    Soleimanpour, Scott A.; Gupta, Aditi; Bakay, Marina; Ferrari, Alana M.; Groff, David N.; Fadista, João; Spruce, Lynn A; Kushner, Jake A.; Groop, Leif; Seeholzer, Steven H.; Kaufman, Brett A; Hakonarson, Hakon; Stoffers, Doris A.

    2014-01-01

    Clec16a has been identified as a disease susceptibility gene for type 1 diabetes, multiple sclerosis and adrenal dysfunction, but its function is unknown. Here we report that Clec16a is a membrane-associated endosomal protein that interacts with E3 ubiquitin ligase Nrdp1. Loss of Clec16a leads to an increase in the Nrdp1 target Parkin, a master regulator of mitophagy. Islets from mice with pancreas-specific deletion of Clec16a have abnormal mitochondria with reduced oxygen consumption and ATP...

  3. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder;

    2002-01-01

    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each...... high frequency of loss of heterozygosity. The genes and ESTs presented in this study encode new potential tumor markers as well as potential novel therapeutic targets for prevention or therapy of CRC....

  4. Gene therapy in pancreatic cancer

    OpenAIRE

    Liu, Si-Xue; Xia, Zhong-Sheng; Zhong, Ying-Qiang

    2014-01-01

    Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC...

  5. Study on the relationship between polymorphisms of XPA gene and susceptibility of esophageal cancer%XPA基因多态性与食管癌易感性关系的研究

    Institute of Scientific and Technical Information of China (English)

    冯向先; 段培芬; 王丽冰; 张建斌; 卢祖洵

    2008-01-01

    目的 探讨长治地区食管癌高发的主要环境危险因素和参与DNA损伤修复的XPA基因多态性与食管癌易感性的关系,以及与环境因素之间对食管癌发生的交互作用.方法 采用病例对照研究,对196例食管癌患者和201例对照者进行食管癌相关因素的问卷调查,应用PCR-RFLP技术对XPA 23G多态性基因型检测,采用SPSS 12.0统计软件对研究结果进行分析.结果病例组携带突变(G)等位基因的频率明显低于对照组(X2=18.31,P<0.01);XPA基因三种基因型在两组间差异有统计学意义(X2=16.56,P<0.01),且携带有xPA突变杂合子(A/G)和突变纯合子(G/G)的个体发生食管癌的危险性比携带野生纯合子(A/A)个体低[OR值(95%CI)分别为0.58(0.37~0.91)和0.32(0.18~0.56)].携带XPA突变基因G与经常食用腌制食品之间存在负交互作用(S=0.04,API=-0.77).结论 XPA 23G多态性可能与长治地区食管癌的发生有一定关系,携带XPA突变基因G可抑制食用腌制食品对食管癌的发生.%Objective To explore the relationships between the polyrnorphisms of xeroderma pigmentosum A(XPA) and the susceptibility of esophageal cancer (EC),as well as its interaction with environmental factors-gene in Changzhi area,Shanxi province. Methods A case-control study was conducted,including 196 cases of EC and 201 controls.XPA 23G polymorphisms were determined with polymerase chain-restriction on fragment length polymorphism (PCR-RFLP).Results The risk of EC was significantly degraded in the individuals who had been carrying the XPA heterozygote (A/G) and mutation genotype (G/G),compared to those with wild genotype (X2=16.21,P<0.01) and the ORs were 0.58 (0.37-0.91) and 0.32 (0.18-0.56),respectively.There was negative interaction between XPA 23G mutation genotype and the consumption of pickled food (S=0.04,API=-0.77).Conclusion Genetic polymorphism in the XPA 23G might be associated with esophageal cancer in Changzhi area,and there was a

  6. Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

    OpenAIRE

    Wold, William S.M.; Toth, Karoly

    2013-01-01

    Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vector...

  7. Contribution of environment and genetics to pancreatic cancer susceptibility.

    Directory of Open Access Journals (Sweden)

    Barbara A Hocevar

    Full Text Available Several risk factors have been identified as potential contributors to pancreatic cancer development, including environmental and lifestyle factors, such as smoking, drinking and diet, and medical conditions such as diabetes and pancreatitis, all of which generate oxidative stress and DNA damage. Oxidative stress status can be modified by environmental factors and also by an individual's unique genetic makeup. Here we examined the contribution of environment and genetics to an individual's level of oxidative stress, DNA damage and susceptibility to pancreatic cancer in a pilot study using three groups of subjects: a newly diagnosed pancreatic cancer group, a healthy genetically-unrelated control group living with the case subject, and a healthy genetically-related control group which does not reside with the subject. Oxidative stress and DNA damage was evaluated by measuring total antioxidant capacity, direct and oxidative DNA damage by Comet assay, and malondialdehyde levels. Direct DNA damage was significantly elevated in pancreatic cancer patients (age and sex adjusted mean ± standard error: 1.00 ± 0.05 versus both healthy unrelated and related controls (0.70 ± 0.06, pA and ERCC4 R415Q polymorphisms. These results suggest that measurement of DNA damage, as well as select SNPs, may provide an important screening tool to identify individuals at risk for development of pancreatic cancer.

  8. Polymorphisms in autophagy genes and susceptibility to tuberculosis.

    Directory of Open Access Journals (Sweden)

    Mario Songane

    Full Text Available Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana. We compared 22 polymorphisms of 14 autophagy genes between 1022 Indonesian TB patients and 952 matched controls, and between patients infected with different M. tuberculosis genotypes, as determined by spoligotyping. The same autophagy polymorphisms were studied in correlation with ex-vivo production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 in healthy volunteers. No association was found between TB and polymorphisms in the genes ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1, LAMP3, P2RX7, WIPI1, MTOR and ATG4C. Associations were found between polymorphisms in LAMP1 (p = 0.02 and MTOR (p = 0.02 and infection with the successful M. tuberculosis Beijing genotype. The polymorphisms examined were not associated with M. tuberculosis induced cytokines, except for a polymorphism in ATG10, which was linked with IL-8 production (p = 0.04. All associations found lost statistical significance after correction for multiple testing. This first examination of a broad set of polymorphisms in autophagy genes fails to show a clear association with TB, with M. tuberculosis Beijing genotype infection or with ex-vivo pro-inflammatory cytokine production.

  9. Genetic susceptibility to HPV infection and cervical cancer

    Directory of Open Access Journals (Sweden)

    P.C. Maciag

    1999-07-01

    Full Text Available Squamous cell carcinoma of the cervix (SCCC is one of the leading causes of death in developing countries. Infection with high-risk human papillomavirus (HPV is the major risk factor to develop malignant lesions in the cervix. Polymorphisms of the MHC and p53 genes seem to influence the outcome of HPV infection and progression to SCCC, although controversial data have been reported. MHC are highly polymorphic genes that encode molecules involved in antigen presentation, playing a key role in immune regulation, while p53 is a tumor suppressor gene that regulates cell proliferation. The HPV E6 protein from high-risk types binds p53 and mediates its degradation by the ubiquitin pathway. The role of these polymorphisms in genetic susceptibility to HPV infection and to SCCC remains under investigation.

  10. Genetic and genomic analysis modeling of germline c-MYC overexpression and cancer susceptibility

    Directory of Open Access Journals (Sweden)

    Nunes Virginia

    2008-01-01

    Full Text Available Abstract Background Germline genetic variation is associated with the differential expression of many human genes. The phenotypic effects of this type of variation may be important when considering susceptibility to common genetic diseases. Three regions at 8q24 have recently been identified to independently confer risk of prostate cancer. Variation at 8q24 has also recently been associated with risk of breast and colorectal cancer. However, none of the risk variants map at or relatively close to known genes, with c-MYC mapping a few hundred kilobases distally. Results This study identifies cis-regulators of germline c-MYC expression in immortalized lymphocytes of HapMap individuals. Quantitative analysis of c-MYC expression in normal prostate tissues suggests an association between overexpression and variants in Region 1 of prostate cancer risk. Somatic c-MYC overexpression correlates with prostate cancer progression and more aggressive tumor forms, which was also a pathological variable associated with Region 1. Expression profiling analysis and modeling of transcriptional regulatory networks predicts a functional association between MYC and the prostate tumor suppressor KLF6. Analysis of MYC/Myc-driven cell transformation and tumorigenesis substantiates a model in which MYC overexpression promotes transformation by down-regulating KLF6. In this model, a feedback loop through E-cadherin down-regulation causes further transactivation of c-MYC. Conclusion This study proposes that variation at putative 8q24 cis-regulator(s of transcription can significantly alter germline c-MYC expression levels and, thus, contribute to prostate cancer susceptibility by down-regulating the prostate tumor suppressor KLF6 gene.

  11. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium.

    OpenAIRE

    van der Lei, J.; Rudolph, A; Moysich, KB; Behrens, S; Goode, EL.; Bolla, MK; Dennis, J; Dunning, AM; Easton, DF; Wang, Q.; Benitez, J; Hopper, JL; Southey, MC; Schmidt, MK; Broeks, A

    2015-01-01

    Funding for the iCOGS infrastructure came from: the European Community?s Seventh Framework Programme under grant agreement number 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (NIH, CA128978, CA122443) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112?the GAME-ON initiative), the Department of Defence (W81...

  12. Gene therapy for prostate cancer.

    LENUS (Irish Health Repository)

    Tangney, Mark

    2012-01-31

    Cancer remains a leading cause of morbidity and mortality. Despite advances in understanding, detection, and treatment, it accounts for almost one-fourth of all deaths per year in Western countries. Prostate cancer is currently the most commonly diagnosed noncutaneous cancer in men in Europe and the United States, accounting for 15% of all cancers in men. As life expectancy of individuals increases, it is expected that there will also be an increase in the incidence and mortality of prostate cancer. Prostate cancer may be inoperable at initial presentation, unresponsive to chemotherapy and radiotherapy, or recur following appropriate treatment. At the time of presentation, patients may already have metastases in their tissues. Preventing tumor recurrence requires systemic therapy; however, current modalities are limited by toxicity or lack of efficacy. For patients with such metastatic cancers, the development of alternative therapies is essential. Gene therapy is a realistic prospect for the treatment of prostate and other cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. Therapeutics can act directly (eg, by inducing tumor cells to produce cytotoxic agents) or indirectly by upregulating the immune system to efficiently target tumor cells or by destroying the tumor\\'s vasculature. However, technological difficulties must be addressed before an efficient and safe gene medicine is achieved (primarily by developing a means of delivering genes to the target cells or tissue safely and efficiently). A wealth of research has been carried out over the past 20 years, involving various strategies for the treatment of prostate cancer at preclinical and clinical trial levels. The therapeutic efficacy observed with many of these approaches in patients indicates that these treatment modalities will serve as an important component of urological malignancy treatment in the clinic, either in isolation or

  13. Gene therapy for prostate cancer.

    Science.gov (United States)

    Tangney, Mark; Ahmad, Sarfraz; Collins, Sara A; O'Sullivan, Gerald C

    2010-05-01

    Cancer remains a leading cause of morbidity and mortality. Despite advances in understanding, detection, and treatment, it accounts for almost one-fourth of all deaths per year in Western countries. Prostate cancer is currently the most commonly diagnosed noncutaneous cancer in men in Europe and the United States, accounting for 15% of all cancers in men. As life expectancy of individuals increases, it is expected that there will also be an increase in the incidence and mortality of prostate cancer. Prostate cancer may be inoperable at initial presentation, unresponsive to chemotherapy and radiotherapy, or recur following appropriate treatment. At the time of presentation, patients may already have metastases in their tissues. Preventing tumor recurrence requires systemic therapy; however, current modalities are limited by toxicity or lack of efficacy. For patients with such metastatic cancers, the development of alternative therapies is essential. Gene therapy is a realistic prospect for the treatment of prostate and other cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. Therapeutics can act directly (eg, by inducing tumor cells to produce cytotoxic agents) or indirectly by upregulating the immune system to efficiently target tumor cells or by destroying the tumor's vasculature. However, technological difficulties must be addressed before an efficient and safe gene medicine is achieved (primarily by developing a means of delivering genes to the target cells or tissue safely and efficiently). A wealth of research has been carried out over the past 20 years, involving various strategies for the treatment of prostate cancer at preclinical and clinical trial levels. The therapeutic efficacy observed with many of these approaches in patients indicates that these treatment modalities will serve as an important component of urological malignancy treatment in the clinic, either in isolation or

  14. Prioritization of Susceptibility Genes for Ectopic Pregnancy by Gene Network Analysis.

    Science.gov (United States)

    Liu, Ji-Long; Zhao, Miao

    2016-01-01

    Ectopic pregnancy is a very dangerous complication of pregnancy, affecting 1%-2% of all reported pregnancies. Due to ethical constraints on human biopsies and the lack of suitable animal models, there has been little success in identifying functionally important genes in the pathogenesis of ectopic pregnancy. In the present study, we developed a random walk-based computational method named TM-rank to prioritize ectopic pregnancy-related genes based on text mining data and gene network information. Using a defined threshold value, we identified five top-ranked genes: VEGFA (vascular endothelial growth factor A), IL8 (interleukin 8), IL6 (interleukin 6), ESR1 (estrogen receptor 1) and EGFR (epidermal growth factor receptor). These genes are promising candidate genes that can serve as useful diagnostic biomarkers and therapeutic targets. Our approach represents a novel strategy for prioritizing disease susceptibility genes. PMID:26840308

  15. 'Sunscreen' Gene May Guard Against Skin Cancer

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_158935.html 'Sunscreen' Gene May Guard Against Skin Cancer Researchers hope their ... say they've identified a so-called "sunscreen" gene that may help protect against skin cancer. They ...

  16. 'Sunscreen' Gene May Guard Against Skin Cancer

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_158935.html 'Sunscreen' Gene May Guard Against Skin Cancer Researchers hope their ... say they've identified a so-called "sunscreen" gene that may help protect against skin cancer. They ...

  17. Five New Genes Linked to Colon Cancer

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_159556.html Five New Genes Linked to Colon Cancer But researchers say it's ... 2016 (HealthDay News) -- Scientists have identified five new gene mutations that may be tied to colon cancer. ...

  18. Gene Tied to Breast Cancer Raises Uterine Cancer Risk Too

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159652.html Gene Tied to Breast Cancer Raises Uterine Cancer Risk ... June 30, 2016 (HealthDay News) -- Women with a gene mutation known as BRCA1 have an increased risk ...

  19. CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Bo [Jiangsu Cancer Hospital, Department of Medical Oncology, Nanjing, Jiangsu Province (China); Zhu, Qun [Second Affiliated Hospital, Nanjing Medical University, Department of Endocrinology, Nanjing, Jiangsu Province (China); Zheng, Ma-Qing [College of Pharmacy, Nanjing University of Technology, Nanjing, Jiangsu Province (China); Chen, Jia; Shi, Mei-Qi; Feng, Ji-Feng [Jiangsu Cancer Hospital, Department of Medical Oncology, Nanjing, Jiangsu Province (China)

    2013-01-11

    Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P < 0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals.

  20. CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population

    International Nuclear Information System (INIS)

    Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P < 0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals

  1. Gene Therapy Used in Cancer Treatment

    OpenAIRE

    Thomas Wirth; Seppo Ylä-Herttuala

    2014-01-01

    Cancer has been, from the beginning, a target of intense research for gene therapy approaches. Currently, more than 60% of all on-going clinical gene therapy trials worldwide are targeting cancer. Indeed, there is a clear unmet medical need for novel therapies. This is further urged by the fact that current conventional cancer therapies are frequently troubled by their toxicities. Different gene therapy strategies have been employed for cancer, such as pro-drug activating suicide gene therapy...

  2. Gensko zdravljenje raka: Cancer gene therapy:

    OpenAIRE

    Serša, Gregor; Čemažar, Maja; KOČEVAR, NINA

    2010-01-01

    Gene therapy uses genes to treat diseases. Large amount of research is based on cancer because current methods for cancer treatment have limited efficiencyand unwanted side effects. In the following article we first presentthe basic principles of gene therapy. Next, we describe the main delivery systems, which are viral and non-viral, and then the main therapeuticstrategies of cancer gene therapy. These can be divided into immunological, where we take advantage of the immune system for cancer...

  3. The multidrug resistance 1 (MDR1) gene polymorphism G-rs3789243-A is not associated with disease susceptibility in Norwegian patients with colorectal adenoma and colorectal cancer; a case control study

    DEFF Research Database (Denmark)

    Andersen, V.; Agerstjerne, L.; Jensen, D.;

    2009-01-01

    Background: Smoking, dietary factors, and alcohol consumption are known life style factors contributing to gastrointestinal carcinogenesis. Genetic variations in carcinogen handling may affect cancer risk. The multidrug resistance 1(MDR1/ABCB1) gene encodes the transport protein P-glycoprotein (a...... inflammation, and may thereby affect the risk of malignity. Hence, genetic variations that modify the function of P-glycoprotein may be associated with the risk of colorectal cancer (CRC). We have previously found an association between the MDR1 intron 3 G-rs3789243-A polymorphism and the risk of CRC in a...... Danish study population. The aim of this study was to investigate if this MDR1 polymorphism was associated with risk of colorectal adenoma (CA) and CRC in the Norwegian population. Methods: Using a case-control design, the association between the MDR1 intron 3 G-rs3789243-A polymorphism and the risk of...

  4. Gene therapy for gastric cancer: A review

    Institute of Scientific and Technical Information of China (English)

    Chao Zhang; Zhan-Kui Liu

    2003-01-01

    Gastric cancer is common in China, and its early diagnosis and treatment are difficult. In recent years great progress has been achieved in gene therapy, and a wide array of gene therapy systems for gastric cancer has been investigated. The present article deals with the general principles of gene therapy and then focuses on how these principles may be applied to gastric cancer.

  5. Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Valentina Escott-Price

    Full Text Available Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6 and 14 (IGHV1-67 p = 7.9×10-8 which indexed novel susceptibility loci.The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

  6. Gene-network analysis identifies susceptibility genes related to glycobiology in autism.

    Directory of Open Access Journals (Sweden)

    Bert van der Zwaag

    Full Text Available The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci. We applied this approach to autism spectrum disorder (ASD, and identified the copy-number changes in the DNA of 105 ASD patients and 267 healthy individuals with Illumina Humanhap300 Beadchips. Subsequently, we used a human reconstructed gene-network, Prioritizer, to rank candidate genes in the segmental gains and losses in our autism cohort. This analysis highlighted several candidate genes already known to be mutated in cognitive and neuropsychiatric disorders, including RAI1, BRD1, and LARGE. In addition, the LARGE gene was part of a sub-network of seven genes functioning in glycobiology, present in seven copy-number changes specifically identified in autism patients with limited co-morbidity. Three of these seven copy-number changes were de novo in the patients. In autism patients with a complex phenotype and healthy controls no such sub-network was identified. An independent systematic analysis of 13 published autism susceptibility loci supports the involvement of genes related to glycobiology as we also identified the same or similar genes from those loci. Our findings suggest that the occurrence of genomic gains and losses of genes associated with glycobiology are important contributors to the development of ASD.

  7. IL18 Gene Variants Influence the Susceptibility to Chagas Disease

    Science.gov (United States)

    Leon Rodriguez, Daniel A; Carmona, F. David; Echeverría, Luis Eduardo; González, Clara Isabel; Martin, Javier

    2016-01-01

    Chagas disease is a parasitic disorder caused by the infection with the flagellated protozoan Trypanosoma cruzi. According to the World Health Organization, more than six million people are currently infected in endemic regions. Genetic factors have been proposed to influence predisposition to infection and development of severe clinical phenotypes like chronic Chagas cardiomyopathy (CCC). Interleukin 18 (IL18) encodes a proinflammatory cytokine that has been proposed to be involved in controlling T. cruzi infection. In this study, we analyzed the possible role of six IL18 gene variants (rs5744258, rs360722, rs2043055, rs187238, rs1946518 and rs360719), which cover most of the variation within the locus, in the susceptibility to infection by T. cruzi and/or CCC. In total, 1,171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and CCC (n = 401), were genotyped using TaqMan probes. Significant associations with T. cruzi infection were observed when comparing seronegative and seropositive individuals for rs187238 (P = 2.18E-03, OR = 0.77), rs360719 (P = 1.49E-03, OR = 0.76), rs2043055 (P = 2.52E-03, OR = 1.29), and rs1946518 (P = 0.0162, OR = 1.22). However, dependence analyses suggested that the association was mainly driven by the polymorphism rs360719. This variant is located within the promoter region of the IL18 gene, and it has been described that it creates a binding site for the transcription factor OCT-1 affecting IL-18 expression levels. In addition, no evidence of association was observed between any of the analyzed IL18 gene polymorphisms and the development of CCC. In summary, our data suggest that genetic variation within the promoter region of IL18 is directly involved in the susceptibility to infection by T. cruzi, which provides novel insight into disease pathophysiology and adds new perspectives to achieve a more effective disease control. PMID:27027876

  8. 核苷酸切除修复通路基因多态性与肺癌易感性%Gene polymorphisms in the nucleotide excision repair pathway and lung cancer susceptibility

    Institute of Scientific and Technical Information of China (English)

    钱莹莹; 束永前

    2013-01-01

    Nucleotide excision repair (NER) pathway is one of the principal ways of the repair of DNA damage.The single nucleotide polymorphisms (SNP) of its key genes such as xeroderma pigmentosum group A (XPA) gene,excision repair cross complementingl (ERCC1) gene and xeroderma pigmentosum group D (XPD) gene may be associated with differences in the DNA repair capacity and may influence an individual's risk of lung cancer,because the variant genotype in those polymorphisms might destroy or alter repair function.%核苷酸切除修复(NER)通路是修复DNA损伤的主要途径之一,其中着色性于皮病A型(XPA)基因、核苷酸切除修复交叉互补1(ERCC1)基因和着色性干皮病D型(XPD)基因的单核苷酸多态性(SNP)改变了NER通路中重要酶与蛋白的修复功能,引起DNA损伤修复能力的差异,最终导致个体肺癌易感性不同.

  9. Mutation analysis of breast cancer gene BRCA among breast cancer Jordanian females

    International Nuclear Information System (INIS)

    To screen mutations of the tumor suppressor breast cancer susceptibility gene 1 (BRCA1) within 3 exons among Jordanian breast cancer females. A total of 135 Jordanian breast cancer females were genetically analyzed by denaturing gradient electrophoresis (DGGE) for mutation detection in 3 BRCA1 exons (2, 11 and 20) between 2000-2002 in Al-Basheer Hospital, Amman, Jordan. Of the studied patients 50 had a family history of breast cancer, 28 had a family history of cancer other than breast cancer, and 57 had no family history of any cancer. Five germline mutations were detected among breast cancer females with a family history of breast cancers (one in exon 2 and 4 mutations in exon 11). Another germline mutation (within exon 11) was detected among breast cancer females with family history of cancer other than breast cancer, and no mutation was detected among breast cancer females with no family history of any cancer or among normal control females. Screening mutations within exon 2, exon 11 and exon 20 showed that most screened mutations were within BRCA1 exon 11 among breast cancer Jordanian families with a family history of breast cancer. (author)

  10. RCDB: Renal Cancer Gene Database

    Directory of Open Access Journals (Sweden)

    Ramana Jayashree

    2012-05-01

    Full Text Available Abstract Background Renal cell carcinoma or RCC is one of the common and most lethal urological cancers, with 40% of the patients succumbing to death because of metastatic progression of the disease. Treatment of metastatic RCC remains highly challenging because of its resistance to chemotherapy as well as radiotherapy, besides surgical resection. Whereas RCC comprises tumors with differing histological types, clear cell RCC remains the most common. A major problem in the clinical management of patients presenting with localized ccRCC is the inability to determine tumor aggressiveness and accurately predict the risk of metastasis following surgery. As a measure to improve the diagnosis and prognosis of RCC, researchers have identified several molecular markers through a number of techniques. However the wealth of information available is scattered in literature and not easily amenable to data-mining. To reduce this gap, this work describes a comprehensive repository called Renal Cancer Gene Database, as an integrated gateway to study renal cancer related data. Findings Renal Cancer Gene Database is a manually curated compendium of 240 protein-coding and 269 miRNA genes contributing to the etiology and pathogenesis of various forms of renal cell carcinomas. The protein coding genes have been classified according to the kind of gene alteration observed in RCC. RCDB also includes the miRNAsdysregulated in RCC, along with the corresponding information regarding the type of RCC and/or metastatic or prognostic significance. While some of the miRNA genes showed an association with other types of cancers few were unique to RCC. Users can query the database using keywords, category and chromosomal location of the genes. The knowledgebase can be freely accessed via a user-friendly web interface at http://www.juit.ac.in/attachments/jsr/rcdb/homenew.html. Conclusions It is hoped that this database would serve as a useful complement to the existing public

  11. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array

    DEFF Research Database (Denmark)

    Eeles, Rosalind A; Olama, Ali Amin Al; Benlloch, Sara;

    2013-01-01

    Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the internationa...

  12. 19p13.1 is a triple-negative-specific breast cancer susceptibility locus

    DEFF Research Database (Denmark)

    Stevens, Kristen N; Fredericksen, Zachary; Vachon, Celine M;

    2012-01-01

    The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone recepto...

  13. Clinical application of micronucleus test: a case-control study on the prediction of breast cancer risk/susceptibility.

    Directory of Open Access Journals (Sweden)

    Claudia Bolognesi

    Full Text Available The micronucleus test is a well-established DNA damage assay in human monitoring. The test was proposed as a promising marker of cancer risk/susceptibility mainly on the basis of studies on breast cancer. Our recent meta-analysis showed that the association between micronuclei frequency, either at baseline or after irradiation, and breast cancer risk or susceptibility, has been evaluated in few studies of small size, with inconsistent results. The aim of the present study is to investigate the role of micronucleus assay in evaluating individual breast cancer susceptibility. Two-hundred and twenty untreated breast cancer patients and 295 female controls were enrolled in the study. All women were characterized for cancer family history and 155 subjects were evaluated for the presence of BRCA mutations. Micronuclei frequency was evaluated at baseline and after irradiation with 1-Gy gamma rays from a 137Cs source. The results show a non significant increase of frequency of micronucleated binucleated lymphocytes in cancer patients compared with the controls at baseline (Mean (S.E.: 16.8 (0.7 vs 15.7 (0.5, but not after irradiation (Mean (S.E.: 145.8 (3.0 vs 154.0 (2.6. Neither a family history of breast cancer nor the presence of a pathogenic mutation in BRCA1/2 genes were associated with an increased micronuclei frequency. Our results do not support a significant role of micronucleus frequency as a biomarker of breast cancer risk/susceptibility.

  14. Experience of parental cancer in childhood is a risk factor for psychological distress during genetic cancer susceptibility testing

    NARCIS (Netherlands)

    van Oostrom, I.; Meijers-Heijboer, H.; Duivenvoorden, H. J.; Brocker-Vriends, A. H. J. T.; van Asperen, C. J.; Sijmons, R. H.; Seynaeve, C.; Van Gool, A. R.; Klijn, J. G. M.; Tibben, A.

    2006-01-01

    Background: This study explores the effect of age at the time of parental cancer diagnosis or death on psychological distress and cancer risk perception in individuals undergoing genetic testing for a specific cancer susceptibility. Patients and methods: Cancer-related distress, worry and risk perce

  15. Epigenetic Regulation of Cancer-Associated Genes in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Mi Jeong Kwon

    2011-01-01

    Full Text Available The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, most studies have focused on the epigenetic inactivation of tumor suppressor genes during tumorigenesis and little is known about the epigenetic activation of cancer-associated genes, except for the DNA hypomethylation of some genes. Recently, we reported that the overexpression of cancer-promoting genes in ovarian cancer is associated with the loss of repressive histone modifications. This discovery suggested that epigenetic derepression may contribute to ovarian tumorigenesis by constituting a possible mechanism for the overexpression of oncogenes or cancer-promoting genes in tumors. The emerging importance of epigenetic aberrations in tumor initiation and in the regulation of cancer-initiating cells, suggests that epigenetically regulated genes may be promising therapeutic targets and biomarkers. Given that the current challenges in ovarian cancer include the identification of biomarkers for early cancer detection and the discovery of novel therapeutic targets for patients with recurrent malignancies undergoing chemotherapy, understanding the epigenetic changes that occur in ovarian cancer is crucial. This review looks at epigenetic mechanisms involved in the regulation of cancer-associated genes, including the contribution of epigenetic derepression to the activation of cancer-associated genes in ovarian cancer. In addition, possible epigenetic therapies targeting epigenetically dysregulated genes are discussed. A better understanding of the epigenetic changes in ovarian cancer will contribute to the improvement of patient outcomes.

  16. Impacts of CA9 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan.

    Directory of Open Access Journals (Sweden)

    Shian-Shiang Wang

    Full Text Available BACKGROUND: Carbonic anhydrase 9 (CA9 is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study explored the effect of CA9 gene polymorphisms on the susceptibility of developing urothelial cell carcinoma (UCC and the clinicopathological status. METHODOLOGY AND PRINCIPAL FINDINGS: A total of 442 participants, including 221 healthy people and 221 patients with UCC, were recruited for this study. Four single-nucleotide polymorphisms (SNPs of the CA9 gene were assessed by a real-time PCR with the TaqMan assay. After adjusting for other co-variants, the individuals carrying at least one A allele at CA9 rs1048638 had a 2.303-fold risk of developing UCC than did wild-type (CC carriers. Furthermore, UCC patients who carried at least one A allele at rs1048638 had a higher invasive stage risk (p< 0.05 than did patients carrying the wild-type allele. Moreover, among the UCC patients with smoker, people with at least one A allele of CA9 polymorphisms (rs1048638 had a 4.75-fold (95% CI = 1.204-18.746 increased risk of invasive cancer. CONCLUSION: The rs1048638 polymorphic genotypes of CA9 might contribute to the prediction of susceptibility to and pathological development of UCC. This is the first study to provide insight into risk factors associated with CA9 variants in carcinogenesis of UCC in Taiwan.

  17. Development and analytical validation of a 25-gene next generation sequencing panel that includes the BRCA1 and BRCA2 genes to assess hereditary cancer risk

    OpenAIRE

    Judkins, Thaddeus; Leclair, Benoît; Bowles, Karla; Gutin, Natalia; Trost, Jeff; McCulloch, James; Bhatnagar, Satish; Murray, Adam; Craft, Jonathan; Wardell, Bryan; Bastian, Mark; Mitchell, Jeffrey; Jian CHEN; Tran, Thanh; Williams, Deborah

    2015-01-01

    Background Germline DNA mutations that increase the susceptibility of a patient to certain cancers have been identified in various genes, and patients can be screened for mutations in these genes to assess their level of risk for developing cancer. Traditional methods using Sanger sequencing focus on small groups of genes and therefore are unable to screen for numerous genes from several patients simultaneously. The goal of the present study was to validate a 25-gene panel to assess genetic r...

  18. Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

    DEFF Research Database (Denmark)

    Song, H.; Koessler, T.; Ahmed, S.; Ramus, S.J.; Kjaer, S.K.; DiCioccio, R.A.; Wozniak, E.; Whittemore, A.S.; McGuire, V.; Ponder, B.A.; Turnbull, C.; Hines, S.; Rahman, N.; Eeles, R.A.; Easton, D.F.; Gayther, S.A.; Dunning, A.M.; Pharoah, P.D.; Høgdall, Estrid Vilma Solyom

    2008-01-01

    Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive...... ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary...... cancer [per minor allele OR, 1.19; 95% confidence interval (95% CI), 1.04-1.37; P(trend) = 0.012]. This association was stronger for the serous histologic subtype (OR, 1.29; 95% CI, 1.09-1.53; P = 0.003). SNP rs7931342 (chromosome 11q13) showed some evidence of association with breast cancer (per minor...

  19. 环境因素和CYP2E1基因 rs8192775位点的交互作用与汉族人群胃癌的关系%Relationship between CYP2 E1 gene rs8192775 polymorphism and interaction of gene-environment and susceptibility of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    蒋林; 王佳; 任晓峰; 颜小銮; 王凡; 沈孝兵

    2013-01-01

    Objective:To determine the association of CYP2E1 gene rs8192775 polymorphism and interaction of gene-environment with the susceptibility of gastric cancer in Han nationality .Methods:A case-control study was conducted to collect 330 new cases of primary gastric cancer and control of epidemiological data and clinical pathology .To apply conditional Logistic regression analysis for environment influence factors in Han population of Nanjing city, multiple heat ligase detection reaction technology (iMLDR) was applied to detect rs8192775, using crossover analysis method to analyse the interaction of SNPs locus and the environment risk factors .Results: The environmental risk factors concluded history of digestive disease , family history of cancer , irregular meals , smoked fried foods and mental depression , fresh fruits were protective factors .The differences of genotype frequency between two groups were statistically significant ( P <0.05 ) . The environment factors with rs 8192775 had significant interaction in the occurrence of gastric cancer (Pint <0.05).Conclusion:The interaction of rs8192775 polymorphism and environmental risk factors happens in gastric cancer .%目的:探讨环境因素和CYP2 E1基因rs8192775位点以及二者交互作用与汉族人群胃癌的关系。方法:采用1∶1病例对照研究,选择经病理确诊的汉族原发性胃癌新发患者330例及其对照进行流行病学资料调查。应用多重高温连接酶检测反应技术( iMLDR)检测rs8192775位点基因型并分析环境因素、rs8192775位点多态性及其基因-环境的交互作用与胃癌的关系。结果:胃癌的环境危险因素为消化系统疾病史、肿瘤家族史、三餐不定时、喜食烟熏煎炸食品和精神压抑,保护因素为喜食新鲜水果。病例、对照组之间基因型频率的差异有统计学意义( P<0.05)。环境因素与rs8192775在胃癌的发生中均存在显著的交互作用( Pint <0.05)。

  20. Susceptibility

    Czech Academy of Sciences Publication Activity Database

    Petrovský, Eduard

    Dordrecht: Springer, 2007 - (Gubbins, D.; Herrero-Bervera, E.), s. 931-933. (Encyclopedia of Earth sciences series). ISBN 978-1-4020-3992-8 Institutional research plan: CEZ:AV0Z30120515 Keywords : magnetic susceptibility * magnetic field * magnetization curve Subject RIV: DE - Earth Magnetism, Geodesy, Geography

  1. Relationship of insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) gene polymorphism with the susceptibility to development of prostate cancer and influence on serum levels of IGF-I, and IGFBP-3.

    Science.gov (United States)

    Safarinejad, Mohammad Reza; Shafiei, Nayyer; Safarinejad, Shiva

    2011-06-01

    The bioavailability of IGF-I is controlled by the binding protein, IGF binding protein-3 (IGFBP-3). In addition, IGFBP-3 is a strong anti-proliferative protein that provokes apoptosis and inhibits cell proliferation in prostate cancer. We conducted this study to investigate the association between IGFBP-3 gene polymorphism and serum levels of IGF-I and IGFBP-3 and the incidence of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). DNA isolation was performed in peripheral blood samples obtained from all participants. Required areas were amplified with polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique by using proper primers belonging to this gene area. We also measured serum IGF-I and IGFBP-3 levels. The IGFBP-3 -202 A/C polymorphism genotype frequencies showed a significant difference between PCa patients and controls (χ(2)=6.27, df=2.0, P=0.026), as well as between BPH patients and controls (χ(2)=11.57, df=4.0, P=0.014). The AA genotype frequency was significantly decreased in PCa and BPH patients compared to control group and the risk of PCa and BPH occurrence of this genotype was decreased accordingly (PCa; OR=0.28, 95% CI=0.17-0.44, P=0.0001; BPH: OR=0.48, 95% CI=0.29-0.77, P=0.001). Age-adjusted mean serum IGFBP-3 concentrations were highest in the individuals with the AA genotype and diminished significantly in a stepwise manner in the presence of 1 or 2 copies of the C allele (4577 ng/ml, 3929 ng/ml and 3349 ng/ml, respectively). Patients with PCa and BPH had lower serum IGF-1 (P=0.001, and P=0.01, respectively) and IGFBP-3 levels (P=0.001, and P=0.01, respectively) compared with controls. The AA genotype at IGFBP-3 gene polymorphism is associated with reduced risks of PCa and BPH. Both IGF-I and IGFBP-3 concentrations, are associated with modified risks of PCa and BPH. PMID:21536469

  2. American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility.

    Science.gov (United States)

    2003-06-15

    As the leading organization representing cancer specialists involved in patient care and clinical research, the American Society of Clinical Oncology (ASCO) reaffirms its commitment to integrating cancer risk assessment and management, including molecular analysis of cancer predisposition genes, into the practice of oncology and preventive medicine. The primary goal of this effort is to foster expanded access to, and continued advances in, medical care provided to patients and families affected by hereditary cancer syndromes. The 1996 ASCO Statement on Genetic Testing for Cancer Susceptibility set forth specific recommendations relating to clinical practice, research needs, educational opportunities, requirement for informed consent, indications for genetic testing, regulation of laboratories, and protection from discrimination, as well as access to and reimbursement for cancer genetics services. In updating this Statement, ASCO endorses the following principles: Indications for Genetic Testing: ASCO recommends that genetic testing be offered when 1) the individual has personal or family history features suggestive of a genetic cancer susceptibility condition, 2) the test can be adequately interpreted, and 3) the results will aid in diagnosis or influence the medical or surgical management of the patient or family members at hereditary risk of cancer. ASCO recommends that genetic testing only be done in the setting of pre- and post-test counseling, which should include discussion of possible risks and benefits of cancer early detection and prevention modalities. Special Issues in Testing Children for Cancer Susceptibility: ASCO recommends that the decision to offer testing to potentially affected children should take into account the availability of evidence-based risk-reduction strategies and the probability of developing a malignancy during childhood. Where risk-reduction strategies are available or cancer predominantly develops in childhood, ASCO believes that

  3. Cancer survivorship--genetic susceptibility and second primary cancers: research strategies and recommendations.

    OpenAIRE

    Travis, Lois B.; Rabkin, Charles S.; Brown, Linda Morris; Allan, James M.; Alter, Blanche P.; Ambrosone, Christine B.; Begg, Colin B.; Caporaso, Neil; Chanock, Stephen; DeMichele, Angela; Figg, William Douglas; Mary K Gospodarowicz; Hall, Eric J.; Hisada, Michie; Inskip, Peter

    2006-01-01

    KEYWORDS - CLASSIFICATION: adverse effects;Antineoplastic Agents;biomarkers of individual susceptibility: validation;Biotechnology;cancer epidemiology;chemically induced;Carcinogens;Case-Control Studies;Clinical Trials;Cohort Studies;Congresses;drug therapy;epidemiology;etiology;genetics;Genetic Predisposition to Disease;Humans;methods;mortality;Medical Informatics;Multicenter Studies;Neoplasms;Neoplasms,Radiation-Induced;Neoplasms,Second Primary;radiotherapy;Radiotherapy;Registries;Research;...

  4. The role of germline alterations in the DNA damage response genes BRIP1 and BRCA2 in melanoma susceptibility.

    Science.gov (United States)

    Tuominen, Rainer; Engström, Pär G; Helgadottir, Hildur; Eriksson, Hanna; Unneberg, Per; Kjellqvist, Sanela; Yang, Muyi; Lindén, Diana; Edsgärd, Daniel; Hansson, Johan; Höiom, Veronica

    2016-07-01

    We applied a targeted sequencing approach to identify germline mutations conferring a moderately to highly increased risk of cutaneous and uveal melanoma. Ninety-two high-risk melanoma patients were screened for inherited variation in 120 melanoma candidate genes. Observed gene variants were filtered based on frequency in reference populations, cosegregation with melanoma in families and predicted functional effect. Several novel or rare genetic variants in genes involved in DNA damage response, cell-cycle regulation and transcriptional control were identified in melanoma patients. Among identified genetic alterations was an extremely rare variant (minor allele frequency of 0.00008) in the BRIP1 gene that was found to cosegregate with the melanoma phenotype. We also found a rare nonsense variant in the BRCA2 gene (rs11571833), previously associated with cancer susceptibility but not with melanoma, which showed weak association with melanoma susceptibility in the Swedish population. Our results add to the growing knowledge about genetic factors associated with melanoma susceptibility and also emphasize the role of DNA damage response as an important factor in melanoma etiology. © 2016 Wiley Periodicals, Inc. PMID:27074266

  5. Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

    Science.gov (United States)

    Kuchenbaecker, Karoline B; Ramus, Susan J; Tyrer, Jonathan; Lee, Andrew; Shen, Howard C; Beesley, Jonathan; Lawrenson, Kate; McGuffog, Lesley; Healey, Sue; Lee, Janet M; Spindler, Tassja J; Lin, Yvonne G; Pejovic, Tanja; Bean, Yukie; Li, Qiyuan; Coetzee, Simon; Hazelett, Dennis; Miron, Alexander; Southey, Melissa; Terry, Mary Beth; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Neuhausen, Susan L; Ding, Yuan Chun; Hansen, Thomas V O; Jønson, Lars; Gerdes, Anne-Marie; Ejlertsen, Bent; Barrowdale, Daniel; Dennis, Joe; Benitez, Javier; Osorio, Ana; Garcia, Maria Jose; Komenaka, Ian; Weitzel, Jeffrey N; Ganschow, Pamela; Peterlongo, Paolo; Bernard, Loris; Viel, Alessandra; Bonanni, Bernardo; Peissel, Bernard; Manoukian, Siranoush; Radice, Paolo; Papi, Laura; Ottini, Laura; Fostira, Florentia; Konstantopoulou, Irene; Garber, Judy; Frost, Debra; Perkins, Jo; Platte, Radka; Ellis, Steve; Godwin, Andrew K; Schmutzler, Rita Katharina; Meindl, Alfons; Engel, Christoph; Sutter, Christian; Sinilnikova, Olga M; Damiola, Francesca; Mazoyer, Sylvie; Stoppa-Lyonnet, Dominique; Claes, Kathleen; De Leeneer, Kim; Kirk, Judy; Rodriguez, Gustavo C; Piedmonte, Marion; O'Malley, David M; de la Hoya, Miguel; Caldes, Trinidad; Aittomäki, Kristiina; Nevanlinna, Heli; Collée, J Margriet; Rookus, Matti A; Oosterwijk, Jan C; Tihomirova, Laima; Tung, Nadine; Hamann, Ute; Isaccs, Claudine; Tischkowitz, Marc; Imyanitov, Evgeny N; Caligo, Maria A; Campbell, Ian G; Hogervorst, Frans B L; Olah, Edith; Diez, Orland; Blanco, Ignacio; Brunet, Joan; Lazaro, Conxi; Pujana, Miquel Angel; Jakubowska, Anna; Gronwald, Jacek; Lubinski, Jan; Sukiennicki, Grzegorz; Barkardottir, Rosa B; Plante, Marie; Simard, Jacques; Soucy, Penny; Montagna, Marco; Tognazzo, Silvia; Teixeira, Manuel R; Pankratz, Vernon S; Wang, Xianshu; Lindor, Noralane; Szabo, Csilla I; Kauff, Noah; Vijai, Joseph; Aghajanian, Carol A; Pfeiler, Georg; Berger, Andreas; Singer, Christian F; Tea, Muy-Kheng; Phelan, Catherine M; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Mulligan, Anna Marie; Tchatchou, Sandrine; Andrulis, Irene L; Glendon, Gord; Toland, Amanda Ewart; Jensen, Uffe Birk; Kruse, Torben A; Thomassen, Mads; Bojesen, Anders; Zidan, Jamal; Friedman, Eitan; Laitman, Yael; Soller, Maria; Liljegren, Annelie; Arver, Brita; Einbeigi, Zakaria; Stenmark-Askmalm, Marie; Olopade, Olufunmilayo I; Nussbaum, Robert L; Rebbeck, Timothy R; Nathanson, Katherine L; Domchek, Susan M; Lu, Karen H; Karlan, Beth Y; Walsh, Christine; Lester, Jenny; Hein, Alexander; Ekici, Arif B; Beckmann, Matthias W; Fasching, Peter A; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Lambrechts, Sandrina; Dicks, Ed; Doherty, Jennifer A; Wicklund, Kristine G; Rossing, Mary Anne; Rudolph, Anja; Chang-Claude, Jenny; Wang-Gohrke, Shan; Eilber, Ursula; Moysich, Kirsten B; Odunsi, Kunle; Sucheston, Lara; Lele, Shashi; Wilkens, Lynne R; Goodman, Marc T; Thompson, Pamela J; Shvetsov, Yurii B; Runnebaum, Ingo B; Dürst, Matthias; Hillemanns, Peter; Dörk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Leminen, Arto; Pelttari, Liisa M; Butzow, Ralf; Modugno, Francesmary; Kelley, Joseph L; Edwards, Robert P; Ness, Roberta B; du Bois, Andreas; Heitz, Florian; Schwaab, Ira; Harter, Philipp; Matsuo, Keitaro; Hosono, Satoyo; Orsulic, Sandra; Jensen, Allan; Kjaer, Susanne Kruger; Hogdall, Estrid; Hasmad, Hanis Nazihah; Azmi, Mat Adenan Noor; Teo, Soo-Hwang; Woo, Yin-Ling; Fridley, Brooke L; Goode, Ellen L; Cunningham, Julie M; Vierkant, Robert A; Bruinsma, Fiona; Giles, Graham G; Liang, Dong; Hildebrandt, Michelle A T; Wu, Xifeng; Levine, Douglas A; Bisogna, Maria; Berchuck, Andrew; Iversen, Edwin S; Schildkraut, Joellen M; Concannon, Patrick; Weber, Rachel Palmieri; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Tworoger, Shelley S; Bandera, Elisa V; Orlow, Irene; Olson, Sara H; Krakstad, Camilla; Salvesen, Helga B; Tangen, Ingvild L; Bjorge, Line; van Altena, Anne M; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Kellar, Melissa; Brooks-Wilson, Angela; Kelemen, Linda E; Cook, Linda S; Le, Nhu D; Cybulski, Cezary; Yang, Hannah; Lissowska, Jolanta; Brinton, Louise A; Wentzensen, Nicolas; Hogdall, Claus; Lundvall, Lene; Nedergaard, Lotte; Baker, Helen; Song, Honglin; Eccles, Diana; McNeish, Ian; Paul, James; Carty, Karen; Siddiqui, Nadeem; Glasspool, Rosalind; Whittemore, Alice S; Rothstein, Joseph H; McGuire, Valerie; Sieh, Weiva; Ji, Bu-Tian; Zheng, Wei; Shu, Xiao-Ou; Gao, Yu-Tang; Rosen, Barry; Risch, Harvey A; McLaughlin, John R; Narod, Steven A; Monteiro, Alvaro N; Chen, Ann; Lin, Hui-Yi; Permuth-Wey, Jenny; Sellers, Thomas A; Tsai, Ya-Yu; Chen, Zhihua; Ziogas, Argyrios; Anton-Culver, Hoda; Gentry-Maharaj, Aleksandra; Menon, Usha; Harrington, Patricia; Lee, Alice W; Wu, Anna H; Pearce, Celeste L; Coetzee, Gerry; Pike, Malcolm C; Dansonka-Mieszkowska, Agnieszka; Timorek, Agnieszka; Rzepecka, Iwona K; Kupryjanczyk, Jolanta; Freedman, Matt; Noushmehr, Houtan; Easton, Douglas F; Offit, Kenneth; Couch, Fergus J; Gayther, Simon; Pharoah, Paul P; Antoniou, Antonis C; Chenevix-Trench, Georgia

    2015-02-01

    Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers. PMID:25581431

  6. Refining Breast Cancer Risk Stratification: Additional Genes, Additional Information.

    Science.gov (United States)

    Kurian, Allison W; Antoniou, Antonis C; Domchek, Susan M

    2016-01-01

    Recent advances in genomic technology have enabled far more rapid, less expensive sequencing of multiple genes than was possible only a few years ago. Advances in bioinformatics also facilitate the interpretation of large amounts of genomic data. New strategies for cancer genetic risk assessment include multiplex sequencing panels of 5 to more than 100 genes (in which rare mutations are often associated with at least two times the average risk of developing breast cancer) and panels of common single-nucleotide polymorphisms (SNPs), combinations of which are generally associated with more modest cancer risks (more than twofold). Although these new multiple-gene panel tests are used in oncology practice, questions remain about the clinical validity and the clinical utility of their results. To translate this increasingly complex genetic information for clinical use, cancer risk prediction tools are under development that consider the joint effects of all susceptibility genes, together with other established breast cancer risk factors. Risk-adapted screening and prevention protocols are underway, with ongoing refinement as genetic knowledge grows. Priority areas for future research include the clinical validity and clinical utility of emerging genetic tests; the accuracy of developing cancer risk prediction models; and the long-term outcomes of risk-adapted screening and prevention protocols, in terms of patients' experiences and survival. PMID:27249685

  7. Gene Therapy Used in Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Thomas Wirth

    2014-04-01

    Full Text Available Cancer has been, from the beginning, a target of intense research for gene therapy approaches. Currently, more than 60% of all on-going clinical gene therapy trials worldwide are targeting cancer. Indeed, there is a clear unmet medical need for novel therapies. This is further urged by the fact that current conventional cancer therapies are frequently troubled by their toxicities. Different gene therapy strategies have been employed for cancer, such as pro-drug activating suicide gene therapy, anti-angiogenic gene therapy, oncolytic virotherapy, gene therapy-based immune modulation, correction/compensation of gene defects, genetic manipulation of apoptotic and tumor invasion pathways, antisense, and RNAi strategies. Cancer types, which have been targeted with gene therapy, include brain, lung, breast, pancreatic, liver, colorectal, prostate, bladder, head and neck, skin, ovarian, and renal cancer. Currently, two cancer gene therapy products have received market approval, both of which are in China. In addition, the stimulation of the host’s immune system, using gene therapeutic approaches, has gained vast interest. The intention of this review is to point out the most commonly viral and non-viral vectors and methods used in cancer gene therapy, as well as highlight some key results achieved in clinical trials.

  8. Methylenetetrahydrofolate Reductase Genotypes, Dietary Habits and Susceptibility to Stomach Cancer

    Institute of Scientific and Technical Information of China (English)

    ChangmingGao; TakezakiToshiro; JianzhongWu; JianhuoDing; YantingLiu; SupingLi; PingSu; XuHu; TianliongXu; HamajimaNobuyuki; TajimaKazuo

    2004-01-01

    OBJECTIVE To study the relation among methylenetetrahydrofolate reductase (MTHFR) C677T genotypes, dietary habits and the risk of stomach cancer (SC).METHODS A case-control study was conducted with 107 cases of SC and 200 population-based controls in Chuzhou district, Huaian, Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects..MTHFR genotypes were detected by PCR-RFLP. RESULTS (1) The prevalence of the MTHFR C/T or T/T genotypes was found to be significantly different between controls (68.5%) and SC cases (79.4%,P=0.0416), the increased risk had an adjusted OR of 1.79 (95%C1:1.01-3.19). (2) Among subjects who had a low intake of garlic or Chinese onion, MTHFR C/T or T/T genotypes significantly increased the risk of developing SC. Among non-tea drinkers or among subjects who had a frequent intakeof meat, the carriers of the MTHFR C/T or T/T genotypes had a higher risk of SC than individuals with the C/C type MTHFR. CONCLUSION The polymorphism of MTHFR C677T was associated with increased risk of developing SC, and that individuals with differing genotypes may have different susceptibilities to SC, based on their exposure level to environmental factors.

  9. Polymorphisms and Plasma Levels of Tissue Inhibitor of Metalloproteinase-3: Impact on Genetic Susceptibility and Clinical Outcome of Oral Cancer.

    Science.gov (United States)

    Su, Chun-Wen; Huang, Yi-Wen; Chen, Mu-Kuan; Su, Shih-Chi; Yang, Shun-Fa; Lin, Chiao-Wen

    2015-11-01

    Oral cancer, the fourth most common cancer among men in Taiwan, is associated with environmental carcinogens. Tissue inhibitor of metalloproteinase-3 (TIMP3), a member of the TIMP family, is the only protein that binds to the extracellular matrix for suppressing cancer cell growth, angiogenesis, migration, and invasion. The association of TIMP3 polymorphism with oral cancer susceptibility, however, has not yet been reported. In this study, 1947 participants-1200 healthy male controls and 747 male patients with oral cancer-were recruited. Allelic discrimination of TIMP3 -1296 T > C (rs9619311), TIMP3 C > T (rs9862), and TIMP3 C > T (rs11547635) polymorphisms were assessed through real-time polymerase chain reaction. The authors discovered that individuals carrying the polymorphic rs9862 allele are more susceptible to oral cancer [odds ratio (OR), 1.5; 95% confidence interval (CI), 1.2-1.9; adjusted OR (AOR), 1.6; 95% CI, 1.2-2.1] after adjustment for betel quid chewing, alcohol, and tobacco consumption. Among 601 betel quid chewers, the TIMP3 polymorphism rs9862 T/T carriers had a 32.2-fold (95% CI, 20.2-51.3) increased oral cancer risk compared with those carrying C/C and not chewing betel quid. In addition, the authors observed a significant association between rs9862 variants and large tumors (OR, 1.5; 95% CI, 1.0-2.3) development. Moreover, TIMP3 plasma levels significantly increased in oral cancer patients who have large tumor or carry T allele rs9862 polymorphism. In conclusion, these results suggest that gene-environment interactions between the TIMP3 rs9862 polymorphisms and betel quid may alter oral cancer susceptibility and tumor growth in Taiwanese men. PMID:26579821

  10. Genome-wide association analysis identifies three new breast cancer susceptibility loci

    DEFF Research Database (Denmark)

    Ghoussaini, Maya; Fletcher, Olivia; Michailidou, Kyriaki;

    2012-01-01

    Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ...

  11. Mapping of Mcs30, a new mammary carcinoma susceptibility quantitative trait locus (QTL30 on rat chromosome 12: identification of fry as a candidate Mcs gene.

    Directory of Open Access Journals (Sweden)

    Xuefeng Ren

    Full Text Available Rat strains differ dramatically in their susceptibility to mammary carcinogenesis. On the assumption that susceptibility genes are conserved across mammalian species and hence inform human carcinogenesis, numerous investigators have used genetic linkage studies in rats to identify genes responsible for differential susceptibility to carcinogenesis. Using a genetic backcross between the resistant Copenhagen (Cop and susceptible Fischer 344 (F344 strains, we mapped a novel mammary carcinoma susceptibility (Mcs30 locus to the centromeric region on chromosome 12 (LOD score of ∼8.6 at the D12Rat59 marker. The Mcs30 locus comprises approximately 12 Mbp on the long arm of rat RNO12 whose synteny is conserved on human chromosome 13q12 to 13q13. After analyzing numerous genes comprising this locus, we identified Fry, the rat ortholog of the furry gene of Drosophila melanogaster, as a candidate Mcs gene. We cloned and determined the complete nucleotide sequence of the 13 kbp Fry mRNA. Sequence analysis indicated that the Fry gene was highly conserved across evolution, with 90% similarity of the predicted amino acid sequence among eutherian mammals. Comparison of the Fry sequence in the Cop and F344 strains identified two non-synonymous single nucleotide polymorphisms (SNPs, one of which creates a putative, de novo phosphorylation site. Further analysis showed that the expression of the Fry gene is reduced in a majority of rat mammary tumors. Our results also suggested that FRY activity was reduced in human breast carcinoma cell lines as a result of reduced levels or mutation. This study is the first to identify the Fry gene as a candidate Mcs gene. Our data suggest that the SNPs within the Fry gene contribute to the genetic susceptibility of the F344 rat strain to mammary carcinogenesis. These results provide the foundation for analyzing the role of the human FRY gene in cancer susceptibility and progression.

  12. Progress in gene therapy for prostate cancer

    Directory of Open Access Journals (Sweden)

    KamranAliAhmed

    2012-11-01

    Full Text Available Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our institution attempts to address this deficiency. The sodium-iodide symporter (NIS is responsible for the ability of the thyroid gland to transport and concentrate iodide. The characteristics of the NIS gene suggest that it could represent an ideal therapeutic gene for cancer therapy. Published results from Mayo Clinic researchers have indicated several important successes with the use of the NIS gene and prostate gene therapy. Studies have demonstrated that transfer of the human NIS gene into prostate cancer using adenovirus vectors in vitro and in vivo results in efficient uptake of radioactive iodine and significant tumor growth delay with prolongation of survival. Preclinical successes have culminated in the opening of a phase I trial for patients with advanced prostate disease which is currently accruing patients. Further study will reveal the clinical promise of NIS gene therapy in the treatment of prostate as well as other malignancies.

  13. Variants of MUC5B minisatellites and the susceptibility of bladder cancer.

    Science.gov (United States)

    Ahn, Eun-Kyung; Kim, Wun-Jae; Kwon, Jeong-Ah; Choi, Phil-Jo; Kim, Woo Jin; Sunwoo, Yangil; Heo, Jeonghoon; Leem, Sun-Hee

    2009-04-01

    The human MUC5B gene, which is primarily expressed in the tracheobronchial tract, is clustered to chromosome 11p15.5 with three other secreted gel-forming mucins, MUC6, MUC2, and MUC5AC. In this study, we identified seven variable number of tandem repeats (VNTRs; minisatellites) from the entire MUC5B region. Six (MUC5B-MS1, -MS2, -MS3, -MS4, -MS5, and -MS7) of the seven minisatellites evaluated in this study were novel minisatellites, but the MUC5B-MS6 minisatellite was described in a previous study. These minisatellites of MUC5B were analyzed in genomic DNA extracted from controls, cancer patients, and multigenerational families. Three (MUC5B-MS3, -MS6, and -MS7) of the seven minisatellites were found to be polymorphic and transmitted through meiosis following Mendelian inheritance in seven families; therefore, these minisatellite polymorphisms could be useful as markers for paternity mapping and DNA fingerprinting. In addition, we evaluated allelic variation in these minisatellites to determine if such variation affected the susceptibility to various carcinomas. To accomplish this, we conducted a case-control study in which the genomic DNA of 789 cancer-free controls and cancer patients with five types of cancer were compared. A statistically significant association between the long rare MUC5B-MS6 alleles and the occurrence of bladder cancer was identified in the younger group (<60; odds ratio, 4.54; 95% confidence interval, 1.0-20.7; p=0.03). This observation suggests that the long rare MUC5B-MS6 alleles evaluated in this study could be used to identify the risk of bladder cancer. PMID:19191526

  14. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array

    Science.gov (United States)

    Eeles, Rosalind A; Olama, Ali Amin Al; Benlloch, Sara; Saunders, Edward J; Leongamornlert, Daniel A; Tymrakiewicz, Malgorzata; Ghoussaini, Maya; Luccarini, Craig; Dennis, Joe; Jugurnauth-Little, Sarah; Dadaev, Tokhir; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Muir, Ken; Giles, Graham G; Severi, Gianluca; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schumacher, Fredrick; Henderson, Brian; Le Marchand, Loic; Lindstrom, Sara; Kraft, Peter; Hunter, David J; Gapstur, Susan; Chanock, Stephen J; Berndt, Sonja I; Albanes, Demetrius; Andriole, Gerald; Schleutker, Johanna; Weischer, Maren; Canzian, Federico; Riboli, Elio; Key, Tim J; Travis, Ruth; Campa, Daniele; Ingles, Sue A; John, Esther M; Hayes, Richard B; Pharoah, Paul DP; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet; Ostrander, Elaine A; Signorello, Lisa B; Thibodeau, Stephen N; Schaid, Dan; Maier, Christiane; Vogel, Walther; Kibel, Adam S; Cybulski, Cezary; Lubinski, Jan; Cannon-Albright; Brenner, Hermann; Park, Jong Y; Kaneva, Radka; Batra, Jyotsna; Spurdle, Amanda B; Clements, Judith A; Teixeira, Manuel R; Dicks, Ed; Lee, Andrew; Dunning, Alison; Baynes, Caroline; Conroy, Don; Maranian, Melanie J; Ahmed, Shahana; Govindasami, Koveela; Guy, Michelle; Wilkinson, Rosemary A; Sawyer, Emma J; Morgan, Angela; Dearnaley, David P; Horwich, Alan; Huddart, Robert A; Khoo, Vincent S; Parker, Christopher C; Van As, Nicholas J; Woodhouse, J; Thompson, Alan; Dudderidge, Tim; Ogden, Chris; Cooper, Colin; Lophatananon, Artitaya; Cox, Angela; Southey, Melissa; Hopper, John L; English, Dallas R; Aly, Markus; Adolfsson, Jan; Xu, Jiangfeng; Zheng, Siqun; Yeager, Meredith; Kaaks, Rudolf; Diver, W Ryan; Gaudet, Mia M; Stern, Mariana; Corral, Roman; Joshi, Amit D; Shahabi, Ahva; Wahlfors, Tiina; Tammela, Teuvo J; Auvinen, Anssi; Virtamo, Jarmo; Klarskov, Peter; Nordestgaard, Børge G; Røder, Andreas; Nielsen, Sune F; Bojesen, Stig E; Siddiq, Afshan; FitzGerald, Liesel; Kolb, Suzanne; Kwon, Erika; Karyadi, Danielle; Blot, William J; Zheng, Wei; Cai, Qiuyin; McDonnell, Shannon K; Rinckleb, Antje; Drake, Bettina; Colditz, Graham; Wokolorczyk, Dominika; Stephenson, Robert A; Teerlink, Craig; Muller, Heiko; Rothenbacher, Dietrich; Sellers, Thomas A; Lin, Hui-Yi; Slavov, Chavdar; Mitev, Vanio; Lose, Felicity; Srinivasan, Srilakshmi; Maia, Sofia; Paulo, Paula; Lange, Ethan; Cooney, Kathleen A; Antoniou, Antonis; Vincent, Daniel; Bacot, François; Tessier; Kote-Jarai, Zsofia; Easton, Douglas F

    2013-01-01

    Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10−8). More than 70 prostate cancer susceptibility loci, explaining ~30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies. PMID:23535732

  15. Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.

    Science.gov (United States)

    Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Lorsch, Zachary S; Walker, Deena M; Wang, Junshi; Huang, Xiaojie; Schlüter, Oliver M; Maze, Ian; Peña, Catherine J; Heller, Elizabeth A; Issler, Orna; Wang, Minghui; Song, Won-Min; Stein, Jason L; Liu, Xiaochuan; Doyle, Marie A; Scobie, Kimberly N; Sun, Hao Sheng; Neve, Rachael L; Geschwind, Daniel; Dong, Yan; Shen, Li; Zhang, Bin; Nestler, Eric J

    2016-06-01

    Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. PMID:27181059

  16. Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2

    DEFF Research Database (Denmark)

    Orr, Nick; Dudbridge, Frank; Dryden, Nicola;

    2015-01-01

    We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further...

  17. Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility.

    Science.gov (United States)

    Piccolo, Stephen R; Hoffman, Laura M; Conner, Thomas; Shrestha, Gajendra; Cohen, Adam L; Marks, Jeffrey R; Neumayer, Leigh A; Agarwal, Cori A; Beckerle, Mary C; Andrulis, Irene L; Spira, Avrum E; Moos, Philip J; Buys, Saundra S; Johnson, William Evan; Bild, Andrea H

    2016-03-01

    The signaling events that drive familial breast cancer (FBC) risk remain poorly understood. While the majority of genomic studies have focused on genetic risk variants, known risk variants account for at most 30% of FBC cases. Considering that multiple genes may influence FBC risk, we hypothesized that a pathway-based strategy examining different data types from multiple tissues could elucidate the biological basis for FBC. In this study, we performed integrated analyses of gene expression and exome-sequencing data from peripheral blood mononuclear cells and showed that cell adhesion pathways are significantly and consistently dysregulated in women who develop FBC. The dysregulation of cell adhesion pathways in high-risk women was also identified by pathway-based profiling applied to normal breast tissue data from two independent cohorts. The results of our genomic analyses were validated in normal primary mammary epithelial cells from high-risk and control women, using cell-based functional assays, drug-response assays, fluorescence microscopy, and Western blotting assays. Both genomic and cell-based experiments indicate that cell-cell and cell-extracellular matrix adhesion processes seem to be disrupted in non-malignant cells of women at high risk for FBC and suggest a potential role for these processes in FBC development. PMID:26969729

  18. The SPINK gene family and celiac disease susceptibility

    NARCIS (Netherlands)

    Wapenaar, Martin C.; Monsuur, Alienke J.; Poell, Jos; Slot, Ruben Van 't; Meijer, Jos W. R.; Meijer, Gerrit A.; Mulder, Chris J.; Mearin, Maria Luisa; Wijmenga, Cisca

    2007-01-01

    The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was deter

  19. Genome-wide transcriptome directed pathway analysis of maternal pre-eclampsia susceptibility genes.

    Directory of Open Access Journals (Sweden)

    Hannah E J Yong

    Full Text Available Preeclampsia (PE is a serious hypertensive pregnancy disorder with a significant genetic component. Numerous genetic studies, including our own, have yielded many susceptibility genes from distinct functional groups. Additionally, transcriptome profiling of tissues at the maternal-fetal interface has likewise yielded many differentially expressed genes. Often there is little overlap between these two approaches, although genes identified in both approaches are significantly associated with PE. We have thus taken a novel integrative bioinformatics approach of analysing pathways common to the susceptibility genes and the PE transcriptome.Using Illumina Human Ht12v4 and Wg6v3 BeadChips, transcriptome profiling was conducted on n = 65 normotensive and n = 60 PE decidua basalis tissues collected at delivery. The R software package libraries lumi and limma were used to preprocess transcript data for pathway analysis. Pathways were analysed and constructed using Pathway Studio. We examined ten candidate genes, which are from these functional groups: activin/inhibin signalling-ACVR1, ACVR1C, ACVR2A, INHA, INHBB; structural components-COL4A1, COL4A2 and M1 family aminopeptidases-ERAP1, ERAP2 and LNPEP.Major common regulators/targets of these susceptibility genes identified were AGT, IFNG, IL6, INHBA, SERPINE1, TGFB1 and VEGFA. The top two categories of pathways associated with the susceptibility genes, which were significantly altered in the PE decidual transcriptome, were apoptosis and cell signaling (p < 0.001. Thus, susceptibility genes from distinct functional groups share similar downstream pathways through common regulators/targets, some of which are altered in PE. This study contributes to a better understanding of how susceptibility genes may interact in the development of PE. With this knowledge, more targeted functional analyses of PE susceptibility genes in these key pathways can be performed to examine their contributions to the pathogenesis

  20. NRAMP1 and VDR Gene Polymorphisms in Susceptibility to Tuberculosis in Venezuelan Population

    OpenAIRE

    Mercedes Fernández-Mestre; Ángel Villasmil; Howard Takiff; Zhenia Fuentes Alcalá

    2015-01-01

    Natural resistance-associated macrophage protein (Nramp1) and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis, and associations between susceptibility to tuberculosis and polymorphisms in the genes NRAMP and VDR have been sought in geographically diverse populations. We investigated associations of NRAMP1 and VDR gene polymorphisms with susceptibility to TB in the Venezuelan population. The results suggest the absence ...

  1. Lung cancer susceptibility model based on age, family history and genetic variants.

    Directory of Open Access Journals (Sweden)

    Robert P Young

    Full Text Available BACKGROUND: Epidemiological and pedigree studies suggest that lung cancer results from the combined effects of age, smoking, impaired lung function and genetic factors. In a case control association study of healthy smokers and lung cancer cases, we identified genetic markers associated with either susceptibility or protection to lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: We screened 157 candidate single nucleotide polymorphisms (SNP in a discovery cohort of 439 subjects (200 controls and 239 lung cancer cases and identified 30 SNPs associated with either the healthy smokers (protective or lung cancer (susceptibility phenotype. After genotyping this 30 SNP panel in a validation cohort of 491 subjects (248 controls and 207 lung cancers and, using the same protective and susceptibility genotypes from our discovery cohort, a 20 SNP panel was selected based on replication of SNP associations in the validation cohort. Following multivariate logistic regression analyses, including the selected SNPs from runs 1 and 2, we found age and family history of lung cancer to be significantly and independently associated with lung cancer. Numeric scores were assigned to both the SNP and demographic data, and combined to form a simple algorithm of risk. CONCLUSIONS/SIGNIFICANCE: Significant differences in the distribution of the lung cancer susceptibility score was found between normal controls and lung cancer cases, which remained after accounting for differences in lung function. Validation in other case-control and prospective cohorts are underway to further define the potential clinical utility of this model.

  2. Genetic polymorphisms of DNA double-strand break repair pathway genes and glioma susceptibility

    International Nuclear Information System (INIS)

    Genetic variations in DNA double-strand break repair genes can influence the ability of a cell to repair damaged DNA and alter an individual’s susceptibility to cancer. We studied whether polymorphisms in DNA double-strand break repair genes are associated with an increased risk of glioma development. We genotyped 10 potentially functional single nucleotide polymorphisms (SNPs) in 7 DNA double-strand break repair pathway genes (XRCC3, BRCA2, RAG1, XRCC5, LIG4, XRCC4 and ATM) in a case–control study including 384 glioma patients and 384 cancer-free controls in a Chinese Han population. Genotypes were determined using the OpenArray platform. In the single-locus analysis there was a significant association between gliomas and the LIG4 rs1805388 (Ex2 +54C>T, Thr9Ile) TT genotype (adjusted OR, 3.27; 95% CI, 1.87-5.71), as well as the TC genotype (adjusted OR, 1.62; 95% CI, 1.20-2.18). We also found that the homozygous variant genotype (GG) of XRCC4 rs1805377 (IVS7-1A>G, splice-site) was associated with a significantly increased risk of gliomas (OR, 1.77; 95% CI, 1.12-2.80). Interestingly, we detected a significant additive and multiplicative interaction effect between the LIG4 rs1805388 and XRCC4 rs1805377 polymorphisms with an increasing risk of gliomas. When we stratified our analysis by smoking status, LIG4 rs1805388 was associated with an increased glioma risk among smokers. These results indicate for the first time that LIG4 rs1805388 and XRCC4 rs1805377, alone or in combination, are associated with a risk of gliomas

  3. Do variants associated with susceptibility to pancreatic cancer and type 2 diabetes reciprocally affect risk?

    Directory of Open Access Journals (Sweden)

    Lang Wu

    Full Text Available Although type 2 diabetes mellitus is a known risk factor for pancreatic cancer, the existence of shared genetic susceptibility is largely unknown. We evaluated whether any reported genetic risk variants of either disease found by genome-wide association studies reciprocally confer susceptibility.Data that were generated in previous genome-wide association studies (GENEVA Type 2 Diabetes; PanScan were obtained through the National Institutes of Health database of Genotypes and Phenotypes (dbGaP. Using the PanScan datasets, we tested for association of 38 variants within 37 genomic regions known to be susceptibility factors for type 2 diabetes. We further examined whether type 2 diabetes variants predispose to pancreatic cancer risk stratified by diabetes status. Correspondingly, we examined the association of fourteen pancreatic cancer susceptibility variants within eight genomic regions in the GENEVA Type 2 Diabetes dataset.Four plausible associations of diabetes variants and pancreatic cancer risk were detected at a significance threshold of p = 0.05, and one pancreatic cancer susceptibility variant was associated with diabetes risk at threshold of p = 0.05, but none remained significant after correction for multiple comparisons.Currently identified GWAS susceptibility variants are unlikely to explain the potential shared genetic etiology between Type 2 diabetes and pancreatic cancer.

  4. Family Matters: Adjustment to genetic cancer susceptibility testing

    NARCIS (Netherlands)

    I.I.H. van Oostrom (Iris)

    2006-01-01

    textabstractCancer is generally feared because it is associated with death and severe physical suffering. It is one of the most common causes of death in the Netherlands. Breast and colon cancer are the most prevalent types of cancer among women. Frequently occurring types in men are cancer of colon

  5. Sequence divergence of Mus spretus and Mus musculus across a skin cancer susceptibility locus

    Directory of Open Access Journals (Sweden)

    Balmain Allan

    2008-12-01

    Full Text Available Abstract Background Mus spretus diverged from Mus musculus over one million years ago. These mice are genetically and phenotypically divergent. Despite the value of utilizing M. musculus and M. spretus for quantitative trait locus (QTL mapping, relatively little genomic information on M. spretus exists, and most of the available sequence and polymorphic data is for one strain of M. spretus, Spret/Ei. In previous work, we mapped fifteen loci for skin cancer susceptibility using four different M. spretus by M. musculus F1 backcrosses. One locus, skin tumor susceptibility 5 (Skts5 on chromosome 12, shows strong linkage in one cross. Results To identify potential candidate genes for Skts5, we sequenced 65 named and unnamed genes and coding elements mapping to the peak linkage area in outbred spretus, Spret/EiJ, FVB/NJ, and NIH/Ola. We identified polymorphisms in 62 of 65 genes including 122 amino acid substitutions. To look for polymorphisms consistent with the linkage data, we sequenced exons with amino acid polymorphisms in two additional M. spretus strains and one additional M. musculus strain generating 40.1 kb of sequence data. Eight candidate variants were identified that fit with the linkage data. To determine the degree of variation across M. spretus, we conducted phylogenetic analyses. The relatedness of the M. spretus strains at this locus is consistent with the proximity of region of ascertainment of the ancestral mice. Conclusion Our analyses suggest that, if Skts5 on chromosome 12 is representative of other regions in the genome, then published genomic data for Spret/EiJ are likely to be of high utility for genomic studies in other M. spretus strains.

  6. Reevaluation of RINT1 as a breast cancer predisposition gene.

    Science.gov (United States)

    Li, Na; Thompson, Ella R; Rowley, Simone M; McInerny, Simone; Devereux, Lisa; Goode, David; Investigators, LifePool; Wong-Brown, Michelle W; Scott, Rodney J; Trainer, Alison H; Gorringe, Kylie L; James, Paul A; Campbell, Ian G

    2016-09-01

    Rad50 interactor 1 (RINT1) has recently been reported as an intermediate-penetrance (odds ratio 3.24) breast cancer susceptibility gene, as well as a risk factor for Lynch syndrome. The coding regions and exon-intron boundaries of RINT1 were sequenced in 2024 familial breast cancer cases previously tested negative for BRCA1, BRCA2, and PALB2 mutations and 1886 population-matched cancer-free controls using HaloPlex Targeted Enrichment Assays. Only one RINT1 protein-truncating variant was detected in a control. No excess was observed in the total number of rare variants (truncating and missense) (28, 1.38 %, vs. 27, 1.43 %. P > 0.999) or in the number of variants predicted to be pathogenic by various in silico tools (Condel, Polyphen2, SIFT, and CADD) in the cases compared to the controls. In addition, there was no difference in the incidence of classic Lynch syndrome cancers in RINT1 rare variant-carrying families compared to RINT1 wild-type families. This study had 90 % power to detect an odds ratio of at least 2.06, and the results do not provide any support for RINT1 being a moderate-penetrance breast cancer susceptibility gene, although larger studies will be required to exclude more modest effects. This study emphasizes the need for caution before designating a cancer predisposition role for any gene based on very rare truncating variants and in silico-predicted missense variants. PMID:27544226

  7. Genetic Variation in Cell Cycle Regulatory Gene AURKA and Association With Intrinsic Breast Cancer Subtype

    OpenAIRE

    Taylor, Nicholas J.; Bensen, Jeannette T.; Poole, Charles; Troester, Melissa A.; Gammon, Marilie D.; Luo, Jingchun; Millikan, Robert C.; Olshan, Andrew F.

    2014-01-01

    AURKA is a putative low-penetrance tumor susceptibility gene due to its prominent role in cell cycle regulation and centrosomal function. Germline variation in AURKA was evaluated for association with breast cancer and intrinsic breast cancer subtypes in the Carolina Breast Cancer Study (CBCS), a population-based case-control study of African Americans (AA) and Caucasians (Cau). Tag and candidate single nucleotide polymorphisms (SNPs) on AURKA were genotyped in 1946 cases and 1747 controls. I...

  8. P2X7 receptor-deficient mice are susceptible to bone cancer pain

    DEFF Research Database (Denmark)

    Hansen, RR; Nielsen, CK; Nasser, A; Thomsen, SI; Eghorn, LF; Pham, Y; Schulenburg, C; Syberg, S; Ding, Ming; Stojilkovic, SS; Jorgensen, NR; Heegaard, AM

    2011-01-01

    were susceptible to bone cancer pain and moreover had an earlier onset of pain-related behaviours compared with cancer-bearing, wild-type mice. Furthermore, acute treatment with the selective P2X7 receptor antagonist, A-438079, failed to alleviate pain-related behaviours in models of bone cancer pain...... with and without astrocyte activation (BALB/cJ or C3H mice inoculated with 4T1 mammary cancer cells or NCTC 2472 osteosarcoma cells, respectively), suggesting that astrocytic P2X7 receptors play a negligible role in bone cancer pain. The results support the hypothesis that bone cancer pain is a...

  9. HOX Genes in Pancreatic Development and Cancer

    OpenAIRE

    Sophie Gray; Hardev S Pandha; Agnieszka Michael; Richard Morgan; Gary Middleton

    2011-01-01

    The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are subsequently re-expressed in many types of cancer. Some recent studies have shown that HOX genes may have key roles both in pancreatic development and in adult diseases of the pancreas, including cancer. In this review we consider recent advances in elucidating the role of HOX genes in these processes, how they may connect early developmental events to s...

  10. Network of Cancer Genes (NCG 3.0): integration and analysis of genetic and network properties of cancer genes

    OpenAIRE

    D'Antonio, Matteo; Pendino, Vera; Sinha, Shruti; Ciccarelli, Francesca D.

    2011-01-01

    The identification of a constantly increasing number of genes whose mutations are causally implicated in tumor initiation and progression (cancer genes) requires the development of tools to store and analyze them. The Network of Cancer Genes (NCG 3.0) collects information on 1494 cancer genes that have been found mutated in 16 different cancer types. These genes were collected from the Cancer Gene Census as well as from 18 whole exome and 11 whole-genome screenings of cancer samples. For each...

  11. Matrix metalloproteinase 3 polymorphisms as a potential marker of enhanced susceptibility to lung cancer in chronic obstructive pulmonary disease subjects

    Directory of Open Access Journals (Sweden)

    Kamil Brzóska

    2014-09-01

    Full Text Available [b]Introduction and objective[/b]. Chronic obstructive pulmonary disease (COPD is often accompanied by lung cancer. Among the genes that may play a role in the occurrence of COPD and lung cancer are those encoding the proteolytic enzymes, such as matrix metalloproteinases (MMPs and their tissue inhibitors. The objective of this study was to find MMPs-associated markers useful in the identification of COPD subjects with increased susceptibility to developing lung cancer. [b]Materials and methods[/b]. We compared the frequency of single nucleotide polymorphisms in genes coding for matrix proteinases ([i]MMP1, MMP2, MMP3, MMP9, MMP12[/i] as well as tissue inhibitor of metalloproteinases ([i]TIMP1[/i] in two groups of subjects: COPD patients (54 subjects and COPD patients diagnosed for lung cancer occurrence (53 subjects.The levels of the respective proteins in blood serum were also analyzed. [b]Results[/b]. The frequencies of 2 genotypes, [i]MMP3[/i] rs3025058 and MMP3 rs678815, were significantly different between the studied groups. In both cases, more heterozygotes and less homozygotes (both types were observed in the COPD group than in the COPD + cancer group. A significantly higher TIMP1 level in blood serum was observed in the COPD + cancer group than in the COPD group. There were no statistically significant differences in[i] MMPs[/i] blood levels between the studied groups. In addition, no genotype-associated differences in [i]TIMP1[/i] or[i] MMPs[/i] blood levels were observed. [b]Conclusions[/b]. Homozygocity for [i]MMP3[/i] rs3025058 and rs678815 polymorphisms is a potential marker of enhanced susceptibility to lung cancer development among COPD subjects.

  12. Importance of TP53 codon 72 and intron 3 duplication 16bp polymorphisms in prediction of susceptibility on breast cancer

    International Nuclear Information System (INIS)

    TP53 is one of major tumour suppressor genes being essential in preservation of genome integrity. Two very common polymorphisms have been demonstrated to contribute to cancer susceptibility and tumour behaviour. The purpose of this study was to evaluate the role of Arg72Pro and PIN3 Ins16bp polymorphisms in TP53 gene as genetic susceptibility and predictive markers to breast cancer. We analysed DNA samples from 264 breast cancer patients and 440 controls, for TP53 Arg72Pro and PIN3 Ins16bp polymorphisms using PCR-RFLP. We observed that women with A2A2 genotype have increased risk for developing breast cancer, either in women with or without familial history (FH) of the disease (OR = 4.40, 95% CI 1.60–12.0; p = 0.004; OR = 3.88, 95% CI 1.18–12.8; p = 0.026, respectively). In haplotype analysis, statistically significant differences were found between TP53 Arg-A2 haplotype frequencies and familial breast cancer cases and the respective control group (OR = 2.10, 95% CI 1.08–4.06; p = 0.028). Furthermore, both TP53 polymorphisms are associated with higher incidence of lymph node metastases. Our findings suggest TP53 PIN3 Ins16bp polymorphism as a real risk modifier in breast cancer disease, either in sporadic and familial breast cancer. Furthermore, both TP53 polymorphisms are associated with higher incidence of lymph node metastases

  13. Vitamin D receptor gene polymorphisms, dietary promotion of insulin resistance, and colon and rectal cancer.

    OpenAIRE

    Maureen A Murtaugh; Sweeney, Carol; Ma, Khe-Ni; Potter, John D.; Caan, Bette J.; Wolff, Roger K.; Slattery, Martha L.

    2006-01-01

    Biomarkers of individual susceptibility: field studies. Biomarker: vitamin D receptor (VDR) gene polymorphisms Effect studied: colon and rectal cancer risk. Tissue/biological material/sample size: colon, rectum. Method of analysis: genotyping of the VDR gene Study design: case-control studyStudy size: colon cancer (1,698 cases and 1,861 controls); rectal cancer (752 cases and 960 controls) Impact on outcome (including dose-response): The lowest colon cancer risk was observed with the Ff/ff Fo...

  14. 11q13 is a Susceptibility Locus for Hormone Receptor Positive Breast Cancer

    DEFF Research Database (Denmark)

    Lambrechts, Diether; Truong, Therese; Justenhoven, Christina;

    2012-01-01

    A recent two-stage genome-wide association study (GWAS) identified five novel breast cancer susceptibility loci on chromosomes 9, 10 and 11. To provide more reliable estimates of the relative risk associated with these loci and investigate possible heterogeneity by subtype of breast cancer, we ge...

  15. Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

    DEFF Research Database (Denmark)

    Kote-Jarai, Zsofia; Olama, Ali Amin Al; Giles, Graham G;

    2011-01-01

    Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of st...

  16. Methylated genes as new cancer biomarkers.

    LENUS (Irish Health Repository)

    Duffy, M J

    2012-02-01

    Aberrant hypermethylation of promoter regions in specific genes is a key event in the formation and progression of cancer. In at least some situations, these aberrant alterations occur early in the formation of malignancy and appear to be tumour specific. Multiple reports have suggested that measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2 for predicting outcome in lymph node-negative breast cancer patients and methylated MGMT in predicting benefit from alkylating agents in patients with glioblastomas. However, prior to clinical utilisation, these findings require validation in prospective clinical studies. Furthermore, assays for measuring gene methylation need to be standardised, simplified and evaluated in external quality assurance programmes. It is concluded that methylated genes have the potential to provide a new generation of cancer biomarkers.

  17. DNA repair genotypes and phenotypes and cancer susceptibility

    Institute of Scientific and Technical Information of China (English)

    Qingyi Wei

    2008-01-01

    @@ The role of DNA repair in the etiology of cancers has been well illustrated in several hereditary syndromes, in which an inherited defect in DNA repair and related biological processes is associated with extraordinarily high incidence of cancer.

  18. Fluconazole susceptibility and ERG11 gene expression in vaginal candida species isolated from Lagos Nigeria.

    Science.gov (United States)

    Pam, Victoria K; Akpan, Juliet U; Oduyebo, Oyinlola O; Nwaokorie, Francisca O; Fowora, Muinah A; Oladele, Rita O; Ogunsola, Folasade T; Smith, Stella I

    2012-01-01

    Fluconazole resistance is an important type of resistance in Candida because in most countries, fluconazole is the drug of choice for vulvovaginal candidiasis. Candida species resist fluconazole by various mechanisms but there is paucity of data on these in our environment. Such mechanisms include among others, over-expression of the ERG11 gene, which codes for synthesis of the target enzymes in the fungus. The aim of this study was to screen Candida spp. resistant to fluconazole for the expression of ERG11 gene. Fluconazole susceptibility test was performed on 28 clinical strains of Candida species previously obtained from students of a School of Nursing in Lagos, Nigeria. They were identified by API Candida, CHROMagar candida and germ tube test. Using 25 mcg discs, fluconazole susceptibility was determined by the disc diffusion method and results were interpreted in accordance with the Clinical Laboratory Standard Institute (CLSI) criteria; sensitive (S), resistant (R) and susceptible dose dependent (SDD). The R and SDD isolates were subsequently evaluated for the presence of ERG11 gene. Of the 28 clinical isolates, 14 were identified as C. albicans and six as C. tropicalis. The remaining isolates were identified as C. glabrata (2), C. famata (2) C. kefyr (2) one each of C. parapsilosis and C. guilliermondii respectively. In this study, 18 were susceptible (S) to fluconazole, eight were SDD and two were resistant to the antifungal agent. Out of the 14 C. albicans isolates, 12 were susceptible, one showed high level resistance and similar number showed susceptible dose dependence. ERG11 was detected in three susceptible dose dependent Candida species. This analysis demonstrates that susceptible dose dependence should not be overlooked as it may be associated with the presence of ERG11 gene and resistance to fluconazole. There is a need to consider routine antifungal susceptibility testing for Candida species causing vulvovaginitis. PMID:22493755

  19. Genetic susceptibility to pancreatic cancer and its functional characterisation: The PANcreatic Disease ReseArch (PANDoRA) consortium

    Czech Academy of Sciences Publication Activity Database

    Campa, D.; Rizzato, C.; Capurso, G.; Giese, N.; Funel, N.; Greenhalf, W.; Souček, P.; Gazouli, M.; Pezzilli, R.; Pasquali, C.; Talar-Wojnarowska, R.; Cantore, M.; Andriulli, A.; Scarpa, A.; Jamroziak, K.; Delle Fave, G.; Costello, E.; Khaw, K. T.; Heller, A.; Key, T. K.; Theodoropoulos, G.; Malecka-Panas, E.; Mambrini, A.; Bambi, F.; Landi, S.; Pedrazzoli, S.; Bassi, C.; Pacetti, P.; Piepoli, A.; Tavano, F.; di Sebastiano, P.; Vodičková, Ludmila; Basso, D.; Plebani, M.; Fogar, P.; Buechler, M. W.; Bugert, P.; Vodička, Pavel; Boggi, U.; Neoptolemos, J. P.; Werner, J.; Canzian, F.

    2013-01-01

    Roč. 45, č. 2 (2013), s. 95-99. ISSN 1590-8658 Institutional support: RVO:68378041 Keywords : cancer susceptibility * genetic polymorphisms * genetic susceptibility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.889, year: 2013

  20. The role of genetic breast cancer susceptibility variants as prognostic factors.

    Science.gov (United States)

    Fasching, Peter A; Pharoah, Paul D P; Cox, Angela; Nevanlinna, Heli; Bojesen, Stig E; Karn, Thomas; Broeks, Annegien; van Leeuwen, Flora E; van't Veer, Laura J; Udo, Renate; Dunning, Alison M; Greco, Dario; Aittomäki, Kristiina; Blomqvist, Carl; Shah, Mitul; Nordestgaard, Børge G; Flyger, Henrik; Hopper, John L; Southey, Melissa C; Apicella, Carmel; Garcia-Closas, Montserrat; Sherman, Mark; Lissowska, Jolanta; Seynaeve, Caroline; Huijts, Petra E A; Tollenaar, Rob A E M; Ziogas, Argyrios; Ekici, Arif B; Rauh, Claudia; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Andrulis, Irene L; Ozcelik, Hilmi; Mulligan, Anna-Marie; Glendon, Gord; Hall, Per; Czene, Kamila; Liu, Jianjun; Chang-Claude, Jenny; Wang-Gohrke, Shan; Eilber, Ursula; Nickels, Stefan; Dörk, Thilo; Schiekel, Maria; Bremer, Michael; Park-Simon, Tjoung-Won; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Hooning, Maartje J; Martens, John W M; Jager, Agnes; Kriege, Mieke; Lindblom, Annika; Margolin, Sara; Couch, Fergus J; Stevens, Kristen N; Olson, Janet E; Kosel, Matthew; Cross, Simon S; Balasubramanian, Sabapathy P; Reed, Malcolm W R; Miron, Alexander; John, Esther M; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Chenevix-Trench, Georgia; Lambrechts, Diether; Dieudonne, Anne-Sophie; Hatse, Sigrid; van Limbergen, Erik; Benitez, Javier; Milne, Roger L; Zamora, M Pilar; Pérez, José Ignacio Arias; Bonanni, Bernardo; Peissel, Bernard; Loris, Bernard; Peterlongo, Paolo; Rajaraman, Preetha; Schonfeld, Sara J; Anton-Culver, Hoda; Devilee, Peter; Beckmann, Matthias W; Slamon, Dennis J; Phillips, Kelly-Anne; Figueroa, Jonine D; Humphreys, Manjeet K; Easton, Douglas F; Schmidt, Marjanka K

    2012-09-01

    Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 (8q24), rs3817198 (LSP1), rs889312 (MAP3K1), rs3803662 (TOX3), rs13387042 (2q35), rs4973768 (SLC4A7), rs6504950 (COX11) and rs10941679 (5p12) were genotyped for 25 853 BC patients with the available follow-up; 62 other SNPs, which have been suggested as BC risk SNPs by a GWAS or as candidate SNPs from individual studies, were genotyped for replication purposes in subsets of these patients. Cox proportional hazard models were used to test the association of these SNPs with overall survival (OS) and BC-specific survival (BCS). For the confirmed loci, we performed an accessory analysis of publicly available gene expression data and the prognosis in a different patient group. One of the 11 SNPs, rs3803662 (TOX3) and none of the 62 candidate/GWAS SNPs were associated with OS and/or BCS at PBreast tumor expression of these genes was not associated with prognosis. With the exception of rs3803662 (TOX3), there was no evidence that any of the SNPs associated with BC susceptibility were associated with the BC survival. Survival may be influenced by a distinct set of germline variants from those influencing susceptibility. PMID:22532573

  1. Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review

    International Nuclear Information System (INIS)

    Interleukins and cytokines play an important role in the pathogenesis of many solid cancers. Several single nucleotide polymorphisms (SNPs) identified in cytokine genes are thought to influence the expression or function of these proteins and many have been evaluated for their role in inflammatory disease and cancer predisposition. The aim of this study was to evaluate any role of specific SNPs in the interleukin genes IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 in predisposition to breast cancer susceptibility and severity. Candidate single nucleotide polymorphisms (SNPs) in key cytokine genes were genotyped in breast cancer patients and in appropriate healthy volunteers who were similar in age, race and sex. Genotyping was performed using a high throughput allelic discrimination method. Data on clinico-pathological details and survival were collected. A systematic review of Medline English literature was done to retrieve previous studies of these polymorphisms in breast cancer. None of the polymorphisms studied showed any overall predisposition to breast cancer susceptibility, severity or to time to death or occurrence of distant metastases. The results of the systematic review are summarised. Polymorphisms within key interleukin genes (IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 do not appear to play a significant overall role in breast cancer susceptibility or severity

  2. [Gene therapy with cytokines against cervical cancer].

    Science.gov (United States)

    Bermúdez-Morales, Victor Hugo; Peralta-Zaragoza, Oscar; Madrid-Marina, Vicente

    2005-01-01

    Gene therapy is an excellent alternative for treatment of many diseases. Capacity to manipulate the DNA has allowed direct the gene therapy to correct the function of an altered gene, to increase the expression of a gene and to favour the activation of the immune response. This way, it can intend the use of the DNA like medication able to control, to correct or to cure many diseases. Gene therapy against cancer has an enormous potential, and actually the use of the DNA has increased to control diverse cancer in animal models, with very encouraging results that have allowed its applications in experimental protocols in human. This work concentrates a review of the foundations of the gene therapy and its application on cervical cancer, from the point of view of the alterations of the immune system focused on the tumour micro-environment, and the use of the cytokines as immunomodulators. PMID:16983992

  3. IL-1α -889 C/T polymorphism and cancer susceptibility: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Cheng D

    2014-11-01

    Full Text Available Daye Cheng, Yiwen Hao, Wenling Zhou Department of Transfusion, First Hospital of China Medical University, Shenyang, People's Republic of China Abstract: The -889 C/T polymorphism in the interleukin-1α (IL-1α gene has been implicated in the risk of cancer, but the results are inconclusive. The present meta-analysis aimed to investigate the association between the -889 C/T polymorphism and cancer risk. A literature search in PubMed, Embase™, Web of Science™, Science Direct®, SpringerLink, EBSCO, Wanfang, and Chinese National Knowledge Infrastructure (CNKI databases was carried out to identify studies investigating the association between IL-1α -889 C/T polymorphism and cancer risk. The odds ratio (OR with 95% confidence interval (CI were used to assess the strength of association. A total of 20 publications, involving 6,782 cases and 7,767 controls, were included in this meta-analysis. Combined analysis revealed a significant association between -889 C/T polymorphism and cancer risk under an allele model (OR =1.12, 95% CI =1.02–1.24, P=0.02, recessive model (OR =1.34, 95% CI =1.06–1.68, P=0.01, and homozygous comparison (OR =1.38, 95% CI =1.10–1.74, P<0.01. Subgroup analysis by ethnicity showed there was significant association between cancer risk and IL-1a -889C/T polymorphism in Asian populations under a recessive model (OR =2.57, 95% CI =1.11–5.98, P=0.03 and homozygous comparison (OR =2.60, 95% CI =1.12–6.04, P=0.03. Moreover, a subgroup analysis was conducted by source of control, and a statistically increased cancer risk was found in the hospital-based group, under a recessive model (OR =1.62, 95% CI =1.03–2.56, P=0.04 and homozygous comparison (OR =1.67, 95% CI =1.04–2.68, P=0.03. This meta-analysis suggests that IL-1α -889 C/T polymorphism contributes to cancer susceptibility. Further large and well-designed studies are needed to confirm this association. Keywords: neoplasma, biomarker, cytokine, systematic review

  4. Association of Wnt signaling pathway genetic variants in gallbladder cancer susceptibility and survival.

    Science.gov (United States)

    Yadav, Anu; Gupta, Annapurna; Yadav, Saurabh; Rastogi, Neeraj; Agrawal, Sushma; Kumar, Ashok; Kumar, Vijay; Misra, Sanjeev; Mittal, Balraj

    2016-06-01

    Gallbladder cancer (GBC) is the most common malignancy of the biliary tract with adverse prognosis and poor survival. Wnt signaling plays an important role in embryonic development and regeneration of tissues in all the species. Deregulation of expression and mutations in this pathway may lead to disease state such as cancer. In this study, we assessed the association of common germline variants of Wnt pathway genes (SFRP2, SFRP4, DKK2, DKK3, WISP3, APC, β-catenin, AXIN-2, GLI-1) to evaluate their contribution in predisposition to GBC and treatment outcomes. The study included 564 GBC patients and 250 controls. Out of 564, 200 patients were followed up for treatment response and survival. Tumor response (RECIST 1.1) was recorded in 116 patients undergoing non-adjuvant chemotherapy (NACT). Survival was assessed by Kaplan-Meier curve and Cox-proportional hazard regression. Single locus analysis showed significant association of SFRP4 rs1802073G > T [p value = 0.0001], DKK2 rs17037102C > T [p value = 0.0001], DKK3 rs3206824C > T [p value = 0.012], APC rs4595552 A/T [p value = 0.021], APC rs11954856G > T [p value = 0.047], AXIN-2 rs4791171C > T [p value = 0.001], β-catenin rs4135385A > G [p value = 0.031], and GLI-1 rs222826C > G [p value = 0.001] with increased risk of GBC. Gene-gene interaction using GMDR analysis predicted APC rs11954856 and AXIN2 rs4791171 as significant in conferring GBC susceptibility. Cox-proportional hazard model showed GLI-1 rs2228226 CG/GG and AXIN-2 rs4791171 TT genotype higher hazard ratio. In recursive partitioning, AXIN-2 rs4791171 TT genotype showed higher mortality and hazard. Most of studied genetic variants influence GBC susceptibility. APC rs11954856, GLI-1 rs2228226, and AXIN-2 rs4791171 were found to be associated with poor survival in advanced GBC patients. PMID:26715268

  5. Bimodal gene expression patterns in breast cancer

    OpenAIRE

    Nikolsky Yuri; Bugrim Andrej; Shi Weiwei; Kirillov Eugene; Bessarabova Marina; Nikolskaya Tatiana

    2010-01-01

    Abstract We identified a set of genes with an unexpected bimodal distribution among breast cancer patients in multiple studies. The property of bimodality seems to be common, as these genes were found on multiple microarray platforms and in studies with different end-points and patient cohorts. Bimodal genes tend to cluster into small groups of four to six genes with synchronised expression within the group (but not between the groups), which makes them good candidates for robust conditional ...

  6. Topological Features In Cancer Gene Expression Data

    OpenAIRE

    Lockwood, Svetlana; Krishnamoorthy, Bala

    2014-01-01

    We present a new method for exploring cancer gene expression data based on tools from algebraic topology. Our method selects a small relevant subset from tens of thousands of genes while simultaneously identifying nontrivial higher order topological features, i.e., holes, in the data. We first circumvent the problem of high dimensionality by dualizing the data, i.e., by studying genes as points in the sample space. Then we select a small subset of the genes as landmarks to construct topologic...

  7. DTNBP1, a schizophrenia susceptibility gene, affects kinetics of transmitter release

    OpenAIRE

    Chen, Xiao-Wei; Feng, Ya-Qin; Hao, Chan-Juan; Guo, Xiao-Li; He, Xin; Zhou, Zhi-Yong; Guo, Ning; Huang, Hong-Ping; Xiong, Wei; Zheng, Hui; Zuo, Pan-Li; Zhang, Claire Xi; Li, Wei; Zhou, Zhuan

    2008-01-01

    Schizophrenia is one of the most debilitating neuropsychiatric disorders, affecting 0.5–1.0% of the population worldwide. Its pathology, attributed to defects in synaptic transmission, remains elusive. The dystrobrevin-binding protein 1 (DTNBP1) gene, which encodes a coiled-coil protein, dysbindin, is a major susceptibility gene for schizophrenia. Our previous results have demonstrated that the sandy (sdy) mouse harbors a spontaneously occurring deletion in the DTNBP1 gene and expresses no dy...

  8. Genome-Wide Transcriptome Directed Pathway Analysis of Maternal Pre-Eclampsia Susceptibility Genes

    OpenAIRE

    Yong, Hannah E. J.; Melton, Phillip E.; Johnson, Matthew P.; Freed, Katy A.; Kalionis, Bill; Murthi, Padma; Brennecke, Shaun P.; Keogh, Rosemary J.; Moses, Eric K.

    2015-01-01

    Background Preeclampsia (PE) is a serious hypertensive pregnancy disorder with a significant genetic component. Numerous genetic studies, including our own, have yielded many susceptibility genes from distinct functional groups. Additionally, transcriptome profiling of tissues at the maternal-fetal interface has likewise yielded many differentially expressed genes. Often there is little overlap between these two approaches, although genes identified in both approaches are significantly associ...

  9. Contribution of rare germline copy number variations and common susceptibility loci in Lynch syndrome patients negative for mutations in the mismatch repair genes

    DEFF Research Database (Denmark)

    Villacis, Rolando A R; Miranda, Priscila M; Gomy, Israel; Santos, Erika M M; Carraro, Dirce M; Achatz, Maria I; Rossi, Benedito M; Rogatto, Silvia R

    2016-01-01

    silico molecular analysis revealed that 61% (41/67) of the genes covered by rare CNVs were associated with cancer, mainly colorectal (17 genes). Ten common SNPs, previously associated with CRC, were genotyped in 39 index patients and 100 sporadic CRC cases. Although no significant, an increased number of...... risk alleles was detected in the index cases compared with the sporadic CRC patients. None of the SNPs were covered by CNVs, suggesting an independent effect of each alteration in cancer susceptibility. In conclusion, rare germline CNVs and common SNPs may contribute to an increased risk for hereditary...

  10. Women’s perceived susceptibility to and utilisation of cervical cancer screening services in Malawi

    Directory of Open Access Journals (Sweden)

    Melanie Y. Hami

    2014-10-01

    Full Text Available Background: Malawi provides cervical cancer screening services free of charge at some public health facilities. Few women make use of these cancer screening services in Malawi and many women continue to be diagnosed with cervical cancer only during the late inoperable stages of the condition. Objectives: The purpose of this study was to discover whether the perceived susceptibility to cervical cancer, amongst Malawian women aged 42 and older, influenced their intentions to utilise the available free cervical cancer screening services. Method: A quantitative, cross-sectional descriptive study design was adopted. Structured interviews were conducted with 381 women who visited 3 health centres in the Blantyre District of Malawi. Results: A statistically-significant association existed between women’s intentions to be screened for cervical cancer and their knowledge about cervical cancer (X² = 8.9; df = 1; p = 0.003 and with having heard about HPV infection (X² = 4.2; df = 1; p = 0.041 at the 5% significance level. Cervical cancer screening services are provided free of charge in government health institutions in Malawi. Nevertheless, low perceived susceptibility to cervical cancer amongst women, aged 42 and older, might contribute to limited utilisation of cervical screening services, explaining why 80% of cervical cancer patients in Malawi were diagnosed during the late inoperable stages. Conclusion: Malawian women lacked awareness regarding their susceptibility to cervical cancer and required information about the available cervical cancer screening services. Malawi’s women, aged 42 and older, must be informed about the advantages of cervical cancer screening and about the importance of effective treatment if an early diagnosis has been made. Women aged 42 and older rarely attend antenatal, post-natal, well baby or family-planning clinics, where health education about cervical cancer screening is often provided. Consequently, these women

  11. Combinations of FUT2 gene polymorphisms and environmental factors are associated with oral cancer risk.

    Science.gov (United States)

    Su, Kuo-Jung; Ho, Chuan-Chen; Lin, Chiao-Wen; Chen, Mu-Kuan; Su, Shih-Chi; Yu, Yung-Luen; Yang, Shun-Fa

    2016-05-01

    In humans, fucosyltransferase-2 (FUT2) plays an important role in α1,2- linkage of fucose and participates in complex cellular processes such as fertilization, embryogenesis, and immune responses. However, little information is available concerning the FUT2 expression in tumorigenesis. The aim of this work was to investigate the combined effect of FUT2 gene polymorphisms and exposure to environmental carcinogens on the susceptibility and clinic pathological characteristics of oral cancer. Four SNPs of the FUT2 gene (rs281377, rs1047781, rs601338, and rs602662) from 1200 non-cancer controls and 700 oral squamous cell carcinoma (OSCC) patients were analyzed by real-time polymerase chain reaction (PCR). The samples were further analyzed to clarify the associations between these gene polymorphisms and the risk of OSCC, and the impact of these SNPs on the susceptibility and clinic pathological characteristics of OSCC. After adjusting for other covariant, we observed that betel quid chewing among 1255 smokers who carrying at least one C genotype (TC and CC) at rs281377 and least one T genotype (TA and TT) at rs1047781 were exhibited synergistic effects of environmental factors (betel quid and cigarette use) on the susceptibility of oral cancer. Taken together, our results support gene-environment interactions of FUT2 polymorphisms with smoking and betel quid chewing habits possibly altering oral cancer susceptibility. Furthermore, to our knowledge, this is the first study of association between FUT2 gene variants and OSCC risk. PMID:26646561

  12. Circadian gene variants and susceptibility to type 2 diabetes: a pilot study.

    Directory of Open Access Journals (Sweden)

    M Ann Kelly

    Full Text Available BACKGROUND: Disruption of endogenous circadian rhythms has been shown to increase the risk of developing type 2 diabetes, suggesting that circadian genes might play a role in determining disease susceptibility. We present the results of a pilot study investigating the association between type 2 diabetes and selected single nucleotide polymorphisms (SNPs in/near nine circadian genes. The variants were chosen based on their previously reported association with prostate cancer, a disease that has been suggested to have a genetic link with type 2 diabetes through a number of shared inherited risk determinants. METHODOLOGY/PRINCIPAL FINDINGS: The pilot study was performed using two genetically homogeneous Punjabi cohorts, one resident in the United Kingdom and one indigenous to Pakistan. Subjects with (N = 1732 and without (N = 1780 type 2 diabetes were genotyped for thirteen circadian variants using a competitive allele-specific polymerase chain reaction method. Associations between the SNPs and type 2 diabetes were investigated using logistic regression. The results were also combined with in silico data from other South Asian datasets (SAT2D consortium and white European cohorts (DIAGRAM+ using meta-analysis. The rs7602358G allele near PER2 was negatively associated with type 2 diabetes in our Punjabi cohorts (combined odds ratio [OR] = 0.75 [0.66-0.86], p = 3.18 × 10(-5, while the BMAL1 rs11022775T allele was associated with an increased risk of the disease (combined OR = 1.22 [1.07-1.39], p = 0.003. Neither of these associations was replicated in the SAT2D or DIAGRAM+ datasets, however. Meta-analysis of all the cohorts identified disease associations with two variants, rs2292912 in CRY2 and rs12315175 near CRY1, although statistical significance was nominal (combined OR = 1.05 [1.01-1.08], p = 0.008 and OR = 0.95 [0.91-0.99], p = 0.015 respectively. CONCLUSIONS/SIGNIFICANCE: None of the selected circadian gene variants was associated with type

  13. Association studies on susceptibility genes in Alzheimer disease

    OpenAIRE

    Björk, Behnosh Fakhri

    2008-01-01

    Alzheimer disease (AD) is the most common form of dementia in the elderly. Due to the complexity of AD, it has been difficult to find genetic risk factors predisposing to disease. To date, three genes (APP, PSEN1 and PSEN2) with disease causing genetic variants have been reported for the rare early onset monogenic forms of AD. For the more prevalent, late onset Alzheimer disease (LOAD), the epsilon4 allele of the APOE gene, is the only confirmed genetic risk factor. However,...

  14. Identification of novel hereditary cancer genes by whole exome sequencing.

    Science.gov (United States)

    Sokolenko, Anna P; Suspitsin, Evgeny N; Kuligina, Ekatherina Sh; Bizin, Ilya V; Frishman, Dmitrij; Imyanitov, Evgeny N

    2015-12-28

    Whole exome sequencing (WES) provides a powerful tool for medical genetic research. Several dozens of WES studies involving patients with hereditary cancer syndromes have already been reported. WES led to breakthrough in understanding of the genetic basis of some exceptionally rare syndromes; for example, identification of germ-line SMARCA4 mutations in patients with ovarian hypercalcemic small cell carcinomas indeed explains a noticeable share of familial aggregation of this disease. However, studies on common cancer types turned out to be more difficult. In particular, there is almost a dozen of reports describing WES analysis of breast cancer patients, but none of them yet succeeded to reveal a gene responsible for the significant share of missing heritability. Virtually all components of WES studies require substantial improvement, e.g. technical performance of WES, interpretation of WES results, mode of patient selection, etc. Most of contemporary investigations focus on genes with autosomal dominant mechanism of inheritance; however, recessive and oligogenic models of transmission of cancer susceptibility also need to be considered. It is expected that the list of medically relevant tumor-predisposing genes will be rapidly expanding in the next few years. PMID:26427841

  15. GWAS-identified colorectal cancer susceptibility loci associated with clinical outcomes

    OpenAIRE

    Dai, Jingyao; Gu, Jian; Huang, Maosheng; Eng, Cathy; Kopetz, E. Scott; Ellis, Lee M.; Hawk, Ernest; Wu, Xifeng

    2012-01-01

    Recent genome-wide association studies (GWAS) have identified several common susceptibility loci associated with the risk of colorectal cancer (CRC). However, whether these loci affect clinical outcomes of CRC is not clear. In this study, we genotyped 26 single nucleotide polymorphisms (SNPs) in 10 GWAS-identified CRC susceptibility regions and evaluated their associations with survival and recurrence in 285 stage II and III patients receiving fluorouracil-based adjuvant chemotherapy. Only on...

  16. Do Variants Associated with Susceptibility to Pancreatic Cancer and Type 2 Diabetes Reciprocally Affect Risk?

    OpenAIRE

    Wu, Lang; Rabe, Kari G.; Petersen, Gloria M.

    2015-01-01

    Objectives Although type 2 diabetes mellitus is a known risk factor for pancreatic cancer, the existence of shared genetic susceptibility is largely unknown. We evaluated whether any reported genetic risk variants of either disease found by genome-wide association studies reciprocally confer susceptibility. Methods Data that were generated in previous genome-wide association studies (GENEVA Type 2 Diabetes; PanScan) were obtained through the National Institutes of Health database of Genotypes...

  17. American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility.

    Science.gov (United States)

    Robson, Mark E; Bradbury, Angela R; Arun, Banu; Domchek, Susan M; Ford, James M; Hampel, Heather L; Lipkin, Stephen M; Syngal, Sapna; Wollins, Dana S; Lindor, Noralane M

    2015-11-01

    The American Society of Clinical Oncology (ASCO) has long affirmed that the recognition and management of individuals with an inherited susceptibility to cancer are core elements of oncology care. ASCO released its first statement on genetic testing in 1996 and updated that statement in 2003 and 2010 in response to developments in the field. In 2014, the Cancer Prevention and Ethics Committees of ASCO commissioned another update to reflect the impact of advances in this area on oncology practice. In particular, there was an interest in addressing the opportunities and challenges arising from the application of massively parallel sequencing-also known as next-generation sequencing-to cancer susceptibility testing. This technology introduces a new level of complexity into the practice of cancer risk assessment and management, requiring renewed effort on the part of ASCO to ensure that those providing care to patients with cancer receive the necessary education to use this new technology in the most effective, beneficial manner. The purpose of this statement is to explore the challenges of new and emerging technologies in cancer genetics and provide recommendations to ensure their optimal deployment in oncology practice. Specifically, the statement makes recommendations in the following areas: germline implications of somatic mutation profiling, multigene panel testing for cancer susceptibility, quality assurance in genetic testing, education of oncology professionals, and access to cancer genetic services. PMID:26324357

  18. Schizophrenia susceptibility genes on chromosome 13q32

    Institute of Scientific and Technical Information of China (English)

    胡颖; 许琪; 鞠桂芝; 刘树铮; 史杰萍; 于雅琴; 尉军

    2004-01-01

    @@Schizophrenia is a complex mental disorder affecting approximately 1% of the general population worldwide.1 It has a high incidence in the general population, a poor prognosis and a poor outcome, in that it has become a major social problem. Family, twin, and adoption studies have clearly shown that a genetic component is quite likely to play an important role in determining susceptibility to schizophrenia. The genome-wide scan indicates that several chromosomal regions are linked to schizophrenia, some of which have been replicated independently including 6p21-24, 8p21-22, 13q14-33 and 22q11-12.2,3 This study was designed to detect two single nucleotide polymorphisms (SNPs) located in the 13q14-33 region, rs188608 at the STK24 locus and rs2892679 at the GPC6 locus, among Chinese population.

  19. Association between single nucleotide polymorphisms of ER β gene and susceptibility of breast cancer in Xinjiang Uygur%雌激素受体β基因单核苷酸多态性与新疆维吾尔族乳腺癌易感性的关系

    Institute of Scientific and Technical Information of China (English)

    班哓辉; 杜露; 李涌涛; 杨亮; 张明帅; 艾司克尔·阿尤甫; 朱丽萍

    2014-01-01

    目的 探讨雌激素受体(ER)β基因Rsa Ⅰ位点单核苷酸多态性(SNP)与新疆维吾尔族乳腺癌易感性的关系.方法 采用病例-对照研究,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测112例维吾尔族女性乳腺癌患者(病例组)和139例维吾尔族体检健康女性(对照组)ERβ基因RsaⅠ (G/A)位点基因型,比较该位点基因型分布与维吾尔族女性乳腺癌发病风险的关系.结果 病例组和对照组中ERβ基因Rsa Ⅰ(G/A)位点的GG、GA基因型频率分别为83.0%、17.0%和73.4%、26.6%,G、A等位基因频率分别为91.5%、8.5%和86.7%、13.3%,差异均无统计学意义(/x2=3.335,P=0.068; x2=2.917,P=0.088).有无雌激素暴露史的两组基因型分布分别为74.2%、25.8%和86.4%、13.6%;有无肿瘤家族史的两组基因型分布100%、O和72.8%、27.2%,差异均有统计学意义(P=0.046、P=0.001).非条件Logistic回归分析显示,以GG型为对照,有雌激素暴露史和无肿瘤家族史的GA型发生乳腺癌危险性降低(OR=0.385,95%CI0.148~0.999; OR=0.285,95%CI 0.134~0.605).结论 ERβ基因Rsa Ⅰ位点SNP与雌激素暴露和无肿瘤家族史因素下的乳腺癌有关,GA基因型可能为维吾尔族女性乳腺癌保护因素.%Obiective To investigate the association between single nucleotide polymorphisms (SNPs) of ER β gene and susceptibility of breast cancer in Uygur women in Xinjiang.Methods A case-control study was designed to explore the genotypes of Rsa Ⅰ (G/A) of ER β gene,detected by PCR-restriction fragment length polymorphism (PCR-RFLP) assay,in 112 breast cancer cases of Uygur women and 139 medical health cases of Uygur women.The association between SNPs of ER β gene and risk of breast cancer in Uygur women was analyzed by unconditional Logistic regression model.Results The frequencies of genotypes of Rsa Ⅰ (G/A) of ER β gene in cancer group and control group were 83.0 % and 17.0 %,73.4

  20. Susceptibility to breast cancer Cuban families and intervention strategy proposal

    International Nuclear Information System (INIS)

    In breast cancer, as in most cancers, mutations usually occur in somatic cells, but sometimes occur in germ cells. The carriers of these mutations germ have up to 80% risk of having the disease course of their lives and pass it on to their offspring, they are called hereditary cancers. In this work studied 50 tested history relatives of this neoplasm from consulting advice genetic hereditary breast cancer. The tree was made pedigree of the family of each test and been classified risk using the criteria of Hampel et al. Other malignancies were identified through the analysis of pedigrees and performed syndromic classification of families. It develops an algorithm for the care of breast cancer families hereditary and plotted strategies identified by risk taking that each category implies a different intervention. It recommended to continue studying the value of marking lesions subclinical and train staff to perform this technique for its widespread use in the country. (Author)

  1. Chromosomal Abnormalities and Putative Susceptibility Genes in Autism Spectrum Disorders

    DEFF Research Database (Denmark)

    Nielsen, Mette Gilling

    Autism spectrum disorders (ASDs) is a heterogeneous group of neurodevelopmental disorders with a significant genetic component as shown by family and twin studies. However, only a few genes have repeatedly been shown to be involved in the development of ASDs. The aim of this study has been to...

  2. Influence of doxorubicin on fluconazole susceptibility and efflux pump gene expression of Candida dubliniensis.

    LENUS (Irish Health Repository)

    Schulz, Bettina

    2012-05-01

    The effect of doxorubicin (DOX) on the fluconazole (FLU) susceptibility of C. dubliniensis was investigated. Isolates were exposed to DOX and FLU in a chequerboard assay and resistance gene expressions were analysed after DOX exposure. The susceptibility of the yeast to FLU was decreased in the presence of DOX in the chequerboard assay with FIC indices suggesting an antagonistic effect. Gene expression analyses showed an overexpression of CdCDR2. Hence, DOX was found to have an impact on resistance mechanisms in C. dubliniensis isolates.

  3. An overview of gene therapy in head and neck cancer

    OpenAIRE

    Amit Bali; Deepika Bali; Ashutosh Sharma

    2013-01-01

    Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatment approaches for cancer gene therapy; gene addition therapy, immunotherapy, gene therapy using oncolytic viruses, antisense ribonucleic acid (RNA) and RNA interference-based gene therapy. Clinical trials to date in head and neck cancer have shown evidence of gene transduction...

  4. The bystander effect of cancer gene therapy

    International Nuclear Information System (INIS)

    Cancer gene therapy is a new, promising therapeutic agent. In the clinic, it should be used in combination with existing modalities, such as tumour irradiation. First, we summarise the most important fields of cancer gene therapy: gene directed enzyme pro-drug therapy; the activation of an anti-tumour immune attack; restoration of the wild type p53 status; the application of new, replication competent and oncolytic viral vectors; tumour specific, as well as radiation- and hypoxia-induced gene expression. Special emphasizes are put on the combined effect of these modalities with local tumour irradiation. Using the available vector systems, only a small portion of the cancer cells will contain the therapeutic genes under therapeutic situations. Bystander cell killing might contribute to the success of various gene therapy protocols. We summarise the evidences that lethal bystander effects may occur during cancer gene therapy. Bystander effects are especially important in the gene directed enzyme pro-drug therapy. There, bystander cell killing might have different routes: cell communication through gap junction intercellular contacts; release of toxic metabolites into the neighbourhood or to larger distances; phagocytosis of apoptotic bodies; and the activation of the immune system. Bystander cell killing can be enhanced by the introduction of gap junction proteins into the cells, by further activating the immune system with immune-stimulatory molecules, or by introducing genes into the cells that help the transfer of cytotoxic genes and / or metabolites into the bystander cells. In conclusion, there should be additional improvements in cancer gene therapy for the more efficient clinical application. (orig.)

  5. The bystander effect of cancer gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lumniczky, K.; Safrany, G. (Department of Molecular and Tumour Radiobiology, National Research Institute for Radiobiology and Radiohygiene, Budapest (Hungary))

    2008-12-15

    Cancer gene therapy is a new, promising therapeutic agent. In the clinic, it should be used in combination with existing modalities, such as tumour irradiation. First, we summarise the most important fields of cancer gene therapy: gene directed enzyme pro-drug therapy; the activation of an anti-tumour immune attack; restoration of the wild type p53 status; the application of new, replication competent and oncolytic viral vectors; tumour specific, as well as radiation- and hypoxia-induced gene expression. Special emphasizes are put on the combined effect of these modalities with local tumour irradiation. Using the available vector systems, only a small portion of the cancer cells will contain the therapeutic genes under therapeutic situations. Bystander cell killing might contribute to the success of various gene therapy protocols. We summarise the evidences that lethal bystander effects may occur during cancer gene therapy. Bystander effects are especially important in the gene directed enzyme pro-drug therapy. There, bystander cell killing might have different routes: cell communication through gap junction intercellular contacts; release of toxic metabolites into the neighbourhood or to larger distances; phagocytosis of apoptotic bodies; and the activation of the immune system. Bystander cell killing can be enhanced by the introduction of gap junction proteins into the cells, by further activating the immune system with immune-stimulatory molecules, or by introducing genes into the cells that help the transfer of cytotoxic genes and / or metabolites into the bystander cells. In conclusion, there should be additional improvements in cancer gene therapy for the more efficient clinical application. (orig.)

  6. Methylated genes as new cancer biomarkers

    DEFF Research Database (Denmark)

    Brunner, Nils; Duffy, M.J; Napieralski, R.;

    2009-01-01

    measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2 for...... predicting outcome in lymph node-negative breast cancer patients and methylated MGMT in predicting benefit from alkylating agents in patients with glioblastomas. However, prior to clinical utilisation, these findings require validation in prospective clinical studies. Furthermore, assays for measuring gene...

  7. PTPN22 gene polymorphisms in autoimmune diseases with special reference to systemic lupus erythematosus disease susceptibility

    Directory of Open Access Journals (Sweden)

    Pradhan V

    2010-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a prototype autoimmune disease. SLE is a result of one or more immune mechanisms, like autoantibody production, complement activation, multiple inflammation and immune complex deposition leading to organ tissue damage. SLE affected patients are susceptible to common and opportunistic infections. There are several reports suggesting that Mycobacterium tuberculosis infection precipitates SLE in patients from endemic areas. Genetic factors and environmental factors also play an important role in the overall susceptibility to SLE pathophysiology. Recently, protein tyrosine phosphatase, non-receptor type 22 (PTPN22 gene, has been found to be associated with several autoimmune diseases like SLE, Grave′s disease and Hashimoto thyroiditis. The missense R620W polymorphism, rs 2476601, in PTPN22 gene at the nucleotide 1858 in codon 620 (620Arg > Trp has been associated with autoimmune diseases. The PTPN22 locus is also found to be responsible for development of pulmonary tuberculosis in certain populations. The PTPN22 1858C/T gene locus will be ideal to look for SLE susceptibility to tuberculosis in the Indian population. In this review, we focus on human PTPN22 gene structure and function as well as the association of PTPN22 gene polymorphisms with SLE susceptibility

  8. Multi-locus association study of schizophrenia susceptibility genes with a posterior probability method

    Institute of Scientific and Technical Information of China (English)

    SUN; Xiangqing; JIA; Yanbin; ZHANG; Xuegong; XU; Qi; SHEN

    2005-01-01

    Schizophrenia is a serious neuropsychiatric illness affecting about 1% of the world's population. It is considered a complex inheritance disorder. A number of genes are involved in combination in the etiology of the disorder. Evidence implicates the altered dopaminergic transmission in schizophrenia. In the present study, in order to identify susceptibility genes for schizophrenia in dopaminergic metabolism, we analyzed 59 single nucleotide polymorphisms (SNPs) in 24 genes of the dopaminergic pathway among 82 unrelated patients with schizophrenia and 108 matched normal controls. Considering that traditional single-locus association studies ignore the multigenic nature of complex diseases and do not take into account possible interactions between susceptibility genes, we proposed a multi-locus analysis method, using the posterior probability of morbidity as a measure of absolute disease risk for a multi-locus genotype combination, and developed an algorithm based on perturbation and average to detect the susceptibility multi-locus genotype combinations, as well as to repress noise and avoid false positive results at our best. A three-locus SNP genotype combination involved in the interactions of COMTand ALDH3B1 genes was detected to be significantly susceptible to schizophrenia.

  9. The role of ERBB2 gene polymorphisms in leprosy susceptibility

    Directory of Open Access Journals (Sweden)

    Jamile Leão Rêgo

    2015-04-01

    Full Text Available Mycobacterium lepraeinfects skin and peripheral nerves causing deformities and disability. The M. lepraebacterium binds to ErbB2 on the Schwann cell surface causing demyelination and favoring spread of the bacilli and causing nerve injury. Polymorphisms at the ERBB2 gene were previously investigated as genetic risk factors for leprosy in two Brazilian populations but with inconsistent results. Herein we extend the analysis of ERBB2 variants to a third geographically distinct population in Brazil. Our results show that there is no association between the genotyped SNPs and the disease (p> 0.05 in this population. A gene set or pathway analysis under the genomic region of ERBB2 will be necessary to clarify its regulation under M. lepraestimulus.

  10. Ischemic stroke susceptibility gene in a Northern Han Chinese population

    OpenAIRE

    Wang, Haiping; Shi, Shujuan; Yan, Wenjing; Song, Yan; Zhan, Jingjing; Zhang, Chen; Wang, Haiji

    2013-01-01

    Interleukin-18 gene promoter polymorphisms are potential risk factors for ischemic cerebrovascular disease, and the –607C allele may increase ischemic stroke risk in the Han Chinese population. In the present study, we recruited 291 patients with ischemic cerebrovascular disease from the Affiliated Hospital of Qingdao University Medical College, China, and 226 healthy controls. Both patients and controls were from the Han population in northern China. Immunoresonance scattering assays detecte...

  11. Genetic variation in the NBS1, MRE11, RAD50 and BLM genes and susceptibility to non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    Gascoyne Randy D

    2009-11-01

    Full Text Available Abstract Background Translocations are hallmarks of non-Hodgkin lymphoma (NHL genomes. Because lymphoid cell development processes require the creation and repair of double stranded breaks, it is not surprising that disruption of this type of DNA repair can cause cancer. The members of the MRE11-RAD50-NBS1 (MRN complex and BLM have central roles in maintenance of DNA integrity. Severe mutations in any of these genes cause genetic disorders, some of which are characterized by increased risk of lymphoma. Methods We surveyed the genetic variation in these genes in constitutional DNA of NHL patients by means of gene re-sequencing, then conducted genetic association tests for susceptibility to NHL in a population-based collection of 797 NHL cases and 793 controls. Results 114 SNPs were discovered in our sequenced samples, 61% of which were novel and not previously reported in dbSNP. Although four variants, two in RAD50 and two in NBS1, showed association results suggestive of an effect on NHL, they were not significant after correction for multiple tests. Conclusion These results suggest an influence of RAD50 and NBS1 on susceptibility to diffuse large B-cell lymphoma and marginal zone lymphoma. Larger association and functional studies could confirm such a role.

  12. Targeting Gene-Virotherapy for Cancer

    Institute of Scientific and Technical Information of China (English)

    Xin-Yuan LIU; Jing-Fa GU; Wen-Fang SHI

    2005-01-01

    Gene therapy and viral therapy for cancer have therapeutic effects, but there has been no significant breakthrough in these two forms of therapy. Therefore, a new strategy called "targeting genevirotherapy", which combines the advantages of gene therapy and viral therapy, has been formulated. This new therapy has stronger antitumor effects than either gene therapy or viral therapy. A tumor-specific replicative adenovirus vector ZD55 (E1B55KD deleted Adv.) was constructed and various single therapeutic genes were inserted into ZD55 to form ZD55-gene. These are the targeting gene-virotherapy genes. But experiments showed that a single gene was not effective in eliminating the tumor mass, and therefore two genes were separately inserted into ZD55. This strategy is called "targeting dual gene-virotherapy" (with PCT patent). Better results were obtained with this strategy, and all the xenograft tumor masses were completely eliminated in all mice when two suitable genes producing a synergetic or compensative effect were chosen. Twenty-six papers on these strategies have been published by researchers in our laboratory.Furthermore, an adenoviral vector with two targeting promoters harboring two antitumor genes has been constructed for cancer therapy. Promising results have been obtained with this adenoviral vectorand another patent has been applied for. This antitumor strategy can be used to kill tumor cells completely with minimum damage to normal cells.

  13. HOX Genes in Pancreatic Development and Cancer

    Directory of Open Access Journals (Sweden)

    Sophie Gray

    2011-05-01

    Full Text Available The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are subsequently re-expressed in many types of cancer. Some recent studies have shown that HOX genes may have key roles both in pancreatic development and in adult diseases of the pancreas, including cancer. In this review we consider recent advances in elucidating the role of HOX genes in these processes, how they may connect early developmental events to subsequent adult disease, and their potential both as diagnostic markers and therapeutic targets.

  14. Colorectal cancer risk genes are functionally enriched in regulatory pathways

    OpenAIRE

    Lu, Xi; Cao, Mingming; Han, Su; Yang, Youlin; Zhou, Jin

    2016-01-01

    Colorectal cancer (CRC) is a common complex disease caused by the combination of genetic variants and environmental factors. Genome-wide association studies (GWAS) have been performed and reported some novel CRC susceptibility variants. However, the potential genetic mechanisms for newly identified CRC susceptibility variants are still unclear. Here, we selected 85 CRC susceptibility variants with suggestive association P 

  15. Targeting Radiotherapy to Cancer by Gene Transfer

    OpenAIRE

    R. J. Mairs; Boyd, M.

    2003-01-01

    Targeted radionuclide therapy is an alternative method of radiation treatment which uses a tumor-seeking agent carrying a radioactive atom to deposits of tumor, wherever in the body they may be located. Recent experimental data signifies promise for the amalgamation of gene transfer with radionuclide targeting. This review encompasses aspects of the integration of gene manipulation and targeted radiotherapy, highlighting the possibilities of gene transfer to assist the targeting of cancer ...

  16. Gene expression profiling analysis of ovarian cancer

    Science.gov (United States)

    YIN, JI-GANG; LIU, XIAN-YING; WANG, BIN; WANG, DAN-YANG; WEI, MAN; FANG, HUA; XIANG, MEI

    2016-01-01

    As a gynecological oncology, ovarian cancer has high incidence and mortality. To study the mechanisms of ovarian cancer, the present study analyzed the GSE37582 microarray. GSE37582 was downloaded from Gene Expression Omnibus and included data from 74 ovarian cancer cases and 47 healthy controls. The differentially-expressed genes (DEGs) were screened using linear models for microarray data package in R and were further screened for functional annotation. Next, Gene Ontology and pathway enrichment analysis of the DEGs was conducted. The interaction associations of the proteins encoded by the DEGs were searched using the Search Tool for the Retrieval of Interacting Genes, and the protein-protein interaction (PPI) network was visualized by Cytoscape. Moreover, module analysis of the PPI network was performed using the BioNet analysis tool in R. A total of 284 DEGs were screened, consisting of 145 upregulated genes and 139 downregulated genes. In particular, downregulated FBJ murine osteosarcoma viral oncogene homolog (FOS) was an oncogene, while downregulated cyclin-dependent kinase inhibitor 1A (CDKN1A) was a tumor suppressor gene and upregulated cluster of differentiation 44 (CD44) was classed as an ‘other’ gene. The enriched functions included collagen catabolic process, stress-activated mitogen-activated protein kinases cascade and insulin receptor signaling pathway. Meanwhile, FOS (degree, 15), CD44 (degree, 9), B-cell CLL/lymphoma 2 (BCL2; degree, 7), CDKN1A (degree, 7) and matrix metallopeptidase 3 (MMP3; degree, 6) had higher connectivity degrees in the PPI network for the DEGs. These genes may be involved in ovarian cancer by interacting with other genes in the module of the PPI network (e.g., BCL2-FOS, BCL2-CDKN1A, FOS-CDKN1A, FOS-CD44, MMP3-MMP7 and MMP7-CD44). Overall, BCL2, FOS, CDKN1A, CD44, MMP3 and MMP7 may be correlated with ovarian cancer. PMID:27347159

  17. A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility

    DEFF Research Database (Denmark)

    Damotte, V; Guillot-Noel, L; Patsopoulos, N A; Madireddy, L; El Behi, M; De Jager, P L; Baranzini, S E; Cournu-Rebeix, I; Fontaine, B; Sørensen, Per Soelberg

    2014-01-01

    interaction with other genes as a group. Pathway analysis is an alternative way to highlight such group of genes. Using SNP association P-values from eight multiple sclerosis (MS) GWAS data sets, we performed a candidate pathway analysis for MS susceptibility by considering genes interacting in the cell...... adhesion molecule (CAMs) biological pathway using Cytoscape software. This network is a strong candidate, as it is involved in the crossing of the blood-brain barrier by the T cells, an early event in MS pathophysiology, and is used as an efficient therapeutic target. We drew up a list of 76 genes...

  18. Employment of Salmonella in Cancer Gene Therapy.

    Science.gov (United States)

    Lee, Che-Hsin

    2016-01-01

    One of the primary limitations of cancer gene therapy is lack of selectivity of the therapeutic gene to tumor cells. Current efforts are focused on discovering and developing tumor-targeting vectors that selectively target only cancer cells but spare normal cells to improve the therapeutic index. The use of preferentially tumor-targeting bacteria as vectors is one of the innovative approaches for the treatment of cancer. This is based on the observation that some obligate or facultative-anaerobic bacteria are capable of multiplying selectively in tumors and inhibiting their growth. In this study, we exploited attenuated Salmonella as a tumoricidal agent and a vector to deliver genes for tumor-targeted gene therapy. Attenuated Salmonella, carrying a eukaryotic expression plasmid encoding an anti-angiogenic gene, was used to evaluate its' ability for tumor targeting and gene delivery in murine tumor models. We also investigated the use of a polymer to modify or shield Salmonella from the pre-existing immune response in the host in order to improve gene delivery to the tumor. These results suggest that tumor-targeted gene therapy using Salmonella carrying a therapeutic gene, which exerts tumoricidal and anti-angiogenic activities, represents a promising strategy for the treatment of tumors. PMID:26846804

  19. Analysis on the Susceptibility Genes in Two Chinese Pedigrees with Familial Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Changshui Xu

    2010-01-01

    Full Text Available Objective. To screen the susceptibility genes in Chinese pedigrees with early-onset familial Parkinson's disease (FPD. Methods. Fifty-one genomic DNA samples extracted from two Chinese pedigrees with FPD, the alpha-synuclein genes (SNCA, the leucine-rich repeat kinase 2(LRRK2, PINK1(PTEN-induced putative kinase 1, PARK7(Protein DJ1, PARK2(Parkinson juvenile disease protein 2, the glucocerebrosidase (GBA, and ATP(Ezrin-binding protein PACE-1, were sequenced by the use of polymerase chain reaction (PCR technique. The gene dose of SNCA was checked. Results. There were only two missense mutations observed, respectively, at exon 5 of LRRK2 and exon 10 of PARK2, and both were enrolled in SNPs. Conclusion. No meaningful mutations could be detected, and other susceptibility genes should be detected in FDP patients in China.

  20. Dopaminergic genes predict individual differences in susceptibility to confirmation bias.

    Science.gov (United States)

    Doll, Bradley B; Hutchison, Kent E; Frank, Michael J

    2011-04-20

    The striatum is critical for the incremental learning of values associated with behavioral actions. The prefrontal cortex (PFC) represents abstract rules and explicit contingencies to support rapid behavioral adaptation in the absence of cumulative experience. Here we test two alternative models of the interaction between these systems, and individual differences thereof, when human subjects are instructed with prior information about reward contingencies that may or may not be accurate. Behaviorally, subjects are overly influenced by prior instructions, at the expense of learning true reinforcement statistics. Computational analysis found that this pattern of data is best accounted for by a confirmation bias mechanism in which prior beliefs--putatively represented in PFC--influence the learning that occurs in the striatum such that reinforcement statistics are distorted. We assessed genetic variants affecting prefrontal and striatal dopaminergic neurotransmission. A polymorphism in the COMT gene (rs4680), associated with prefrontal dopaminergic function, was predictive of the degree to which participants persisted in responding in accordance with prior instructions even as evidence against their veracity accumulated. Polymorphisms in genes associated with striatal dopamine function (DARPP-32, rs907094, and DRD2, rs6277) were predictive of learning from positive and negative outcomes. Notably, these same variants were predictive of the degree to which such learning was overly inflated or neglected when outcomes are consistent or inconsistent with prior instructions. These findings indicate dissociable neurocomputational and genetic mechanisms by which initial biases are strengthened by experience. PMID:21508242

  1. Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in African Americans

    OpenAIRE

    Chen, Fang; Chen, Gary K.; Millikan, Robert C.; John, Esther M; Ambrosone, Christine B.; Bernstein, Leslie; Zheng, Wei; Jennifer J Hu; Ziegler, Regina G.; Deming, Sandra L.; Bandera, Elisa V.; Nyante, Sarah; Palmer, Julie R.; Rebbeck, Timothy R.; Sue A Ingles

    2011-01-01

    Genome-wide association studies (GWAS) have revealed 19 common genetic variants that are associated with breast cancer risk. Testing of the index signals found through GWAS and fine-mapping of each locus in diverse populations will be necessary for characterizing the role of these risk regions in contributing to inherited susceptibility. In this large study of breast cancer in African-American women (3016 cases and 2745 controls), we tested the 19 known risk variants identified by GWAS and re...

  2. Custom genotyping for substance addiction susceptibility genes in Jordanians of Arab descent

    OpenAIRE

    AL-Eitan Laith N; Jaradat Saied A; Hulse Gary K; Tay Guan K

    2012-01-01

    Abstract Background Both environmental and genetic factors contribute to individual susceptibility to initiation of substance use and vulnerability to addiction. Determining genetic risk factors can make an important contribution to understanding the processes leading to addiction. In order to identify gene(s) and mechanisms associated with substance addiction, a custom platform array search for a genetic association in a case/control of homogenous Jordanian Arab population was undertaken. Pa...

  3. The SH2D2A gene and susceptibility to multiple sclerosis

    DEFF Research Database (Denmark)

    Lorentzen, A.R.; Smestad, C.; Lie, B.A.;

    2008-01-01

    We previously reported an association between the SH2D2A gene encoding TSAd and multiple sclerosis (MS). Here a total of 2128 Nordic MS patients and 2004 controls were genotyped for the SH2D2A promoter GA repeat polymorphism and rs926103 encoding a serine to asparagine substitution at amino acid...... SH2D2A gene may contribute to susceptibility to MS Udgivelsesdato: 2008/7/15...

  4. Base excision repair mechanisms and relevance to cancer susceptibility

    International Nuclear Information System (INIS)

    The base excision repair (BER) pathway is considered the predominant DNA repair system in mammalian cells for eliminating small DNA lesions generated at DNA bases either exogenously by environmental agents or endogenously by normal cellular metabolic processes (e.g. production of oxyradical species, alkylating agents, etc). The main goal of this project is the understanding of the involvement of BER in genome stability and in particular in sporadic cancer development associated with inflammation such as gastric cancer (GC). A major risk factor of GC is the infection by Helicobacter pylori, which causes oxidative stress. Oxidative DNA damage is mainly repaired by BER

  5. Mapping the genes for susceptibility and response to Leishmania tropica in mouse

    Czech Academy of Sciences Publication Activity Database

    Sohrabi, Yahya; Havelková, Helena; Kobets, Tetyana; Šíma, Matyáš; Volkova, Valeriya; Grekov, Igor; Jarošíková, T.; Kurey, Irina; Vojtíšková, Jarmila; Svobodová, M.; Demant, P.; Lipoldová, Marie

    2013-01-01

    Roč. 7, č. 7 (2013), s. 1-17. ISSN 1935-2735 R&D Projects: GA ČR GA310/08/1697; GA MŠk LH12049 Institutional support: RVO:68378050 Keywords : Leishmania tropica * gene controlling susceptibility * host-parasite interactions * leishmaniasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.489, year: 2013

  6. Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis

    NARCIS (Netherlands)

    Rosentul, D.C.; Delsing, C.E.; Jaeger, M.; Plantinga, T.S.; Oosting, M.; Costantini, I.; Venselaar, H.; Joosten, L.A.B.; Meer, J.W.M. van der; Dupont, B.; Kullberg, B.J.; Sobel, J.D.; Netea, M.G.

    2014-01-01

    OBJECTIVE: Approximately 5% of women suffer from recurrent vulvovaginal candidiasis (RVVC). It has been hypothesized that genetic factors play an important role in the susceptibility to RVVC. The aim of this study was to assess the effect of genetic variants of genes encoding for pattern recognition

  7. Detection of vanC 1 gene transcription in vancomycin-susceptible Enterococcus faecalis

    Directory of Open Access Journals (Sweden)

    Tiane Martin de Moura

    2013-06-01

    Full Text Available Here we report the presence and expression levels of the vanC 1 and vanC 2/3 genes in vancomycin-susceptible strains of Enterococcus faecalis. The vanC 1 and vanC 2/3 genes were located in the plasmid DNA and on the chromosome, respectively. Specific mRNA of the vanC 1 gene was detected in one of these strains. Additionally, analysis of the vanC gene sequences showed that these genes are related to the vanC genes of Enterococcus gallinarum and Enterococcus casseliflavus. The presence of vanC genes is useful for the identification of E. gallinarum and E. casseliflavus. Moreover, this is the first report of vanC mRNA in E. faecalis.

  8. 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer

    DEFF Research Database (Denmark)

    Warren, Helen; Dudbridge, Frank; Fletcher, Olivia;

    2012-01-01

    Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686).......Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686)....

  9. Differential gene expression of two extreme honey bee (Apis mellifera) colonies showing varroa tolerance and susceptibility.

    Science.gov (United States)

    Jiang, S; Robertson, T; Mostajeran, M; Robertson, A J; Qiu, X

    2016-06-01

    Varroa destructor, an ectoparasitic mite of honey bees (Apis mellifera), is the most serious pest threatening the apiculture industry. In our honey bee breeding programme, two honey bee colonies showing extreme phenotypes for varroa tolerance/resistance (S88) and susceptibility (G4) were identified by natural selection from a large gene pool over a 6-year period. To investigate potential defence mechanisms for honey bee tolerance to varroa infestation, we employed DNA microarray and real time quantitative (PCR) analyses to identify differentially expressed genes in the tolerant and susceptible colonies at pupa and adult stages. Our results showed that more differentially expressed genes were identified in the tolerant bees than in bees from the susceptible colony, indicating that the tolerant colony showed an increased genetic capacity to respond to varroa mite infestation. In both colonies, there were more differentially expressed genes identified at the pupa stage than at the adult stage, indicating that pupa bees are more responsive to varroa infestation than adult bees. Genes showing differential expression in the colony phenotypes were categorized into several groups based on their molecular functions, such as olfactory signalling, detoxification processes, exoskeleton formation, protein degradation and long-chain fatty acid metabolism, suggesting that these biological processes play roles in conferring varroa tolerance to naturally selected colonies. Identification of differentially expressed genes between the two colony phenotypes provides potential molecular markers for selecting and breeding varroa-tolerant honey bees. PMID:26919127

  10. Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

    DEFF Research Database (Denmark)

    Song, Honglin; Ramus, Susan J; Kjaer, Susanne Krüger;

    2009-01-01

    Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive.......01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast...... ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially...

  11. Gene Expression Analysis of Plum pox virus (Sharka Susceptibility/Resistance in Apricot (Prunus armeniaca L..

    Directory of Open Access Journals (Sweden)

    Manuel Rubio

    Full Text Available RNA-Seq has proven to be a very powerful tool in the analysis of the Plum pox virus (PPV, sharka disease/Prunus interaction. This technique is an important complementary tool to other means of studying genomics. In this work an analysis of gene expression of resistance/susceptibility to PPV in apricot is performed. RNA-Seq has been applied to analyse the gene expression changes induced by PPV infection in leaves from two full-sib apricot genotypes, "Rojo Pasión" and "Z506-7", resistant and susceptible to PPV, respectively. Transcriptomic analyses revealed the existence of more than 2,000 genes related to the pathogen response and resistance to PPV in apricot. These results showed that the response to infection by the virus in the susceptible genotype is associated with an induction of genes involved in pathogen resistance such as the allene oxide synthase, S-adenosylmethionine synthetase 2 and the major MLP-like protein 423. Over-expression of the Dicer protein 2a may indicate the suppression of a gene silencing mechanism of the plant by PPV HCPro and P1 PPV proteins. On the other hand, there were 164 genes involved in resistance mechanisms that have been identified in apricot, 49 of which are located in the PPVres region (scaffold 1 positions from 8,050,804 to 8,244,925, which is responsible for PPV resistance in apricot. Among these genes in apricot there are several MATH domain-containing genes, although other genes inside (Pleiotropic drug resistance 9 gene or outside (CAP, Cysteine-rich secretory proteins, Antigen 5 and Pathogenesis-related 1 protein; and LEA, Late embryogenesis abundant protein PPVres region could also be involved in the resistance.

  12. Gene Expression Analysis of Plum pox virus (Sharka) Susceptibility/Resistance in Apricot (Prunus armeniaca L.).

    Science.gov (United States)

    Rubio, Manuel; Ballester, Ana Rosa; Olivares, Pedro Manuel; Castro de Moura, Manuel; Dicenta, Federico; Martínez-Gómez, Pedro

    2015-01-01

    RNA-Seq has proven to be a very powerful tool in the analysis of the Plum pox virus (PPV, sharka disease)/Prunus interaction. This technique is an important complementary tool to other means of studying genomics. In this work an analysis of gene expression of resistance/susceptibility to PPV in apricot is performed. RNA-Seq has been applied to analyse the gene expression changes induced by PPV infection in leaves from two full-sib apricot genotypes, "Rojo Pasión" and "Z506-7", resistant and susceptible to PPV, respectively. Transcriptomic analyses revealed the existence of more than 2,000 genes related to the pathogen response and resistance to PPV in apricot. These results showed that the response to infection by the virus in the susceptible genotype is associated with an induction of genes involved in pathogen resistance such as the allene oxide synthase, S-adenosylmethionine synthetase 2 and the major MLP-like protein 423. Over-expression of the Dicer protein 2a may indicate the suppression of a gene silencing mechanism of the plant by PPV HCPro and P1 PPV proteins. On the other hand, there were 164 genes involved in resistance mechanisms that have been identified in apricot, 49 of which are located in the PPVres region (scaffold 1 positions from 8,050,804 to 8,244,925), which is responsible for PPV resistance in apricot. Among these genes in apricot there are several MATH domain-containing genes, although other genes inside (Pleiotropic drug resistance 9 gene) or outside (CAP, Cysteine-rich secretory proteins, Antigen 5 and Pathogenesis-related 1 protein; and LEA, Late embryogenesis abundant protein) PPVres region could also be involved in the resistance. PMID:26658051

  13. Mutation Analysis in the BRCA1 Gene in Chinese Breast Cancer Families

    Institute of Scientific and Technical Information of China (English)

    WUZhengyan; ZHENLinlin; FANPing

    2003-01-01

    Objective: To study the mutation of BRCA1 gene in Chinese breast cancer families. Methods:Fifteen families were selected, involving 41 members, consisting of 23 breast cancer patients. Using poly-merase chain reaction and single stranded conformation polymorphism (PCR-SSCP), and subsequent DNA sequencing, the mutation of BRCA1 genes were analyzed. Results: Four mutations were found in all fam-ilies, and the proportion of mutation was 26.7% (4/15) in breast cancer families. One of the 4 mutations was 2228 insC, resulting in chain termination at codon 711. The remaining 3 mutations were 1884A→T and 3232A→G, resulting in single amino acid change respectively. Conclusion: BRCA1 is a breast cancer susceptibility gene. The relatively low proportion and frequency of BRCA1 mutations in our study hints additional BRCA genes existed.

  14. Fetal radiation exposure induces testicular cancer in genetically susceptible mice.

    Directory of Open Access Journals (Sweden)

    Gunapala Shetty

    Full Text Available The prevalence of testicular germ cell tumors (TGCT, a common solid tissue malignancy in young men, has been annually increasing at an alarming rate of 3%. Since the majority of testicular cancers are derived from germ cells at the stage of transformation of primordial germ cell (PGC into gonocytes, the increase has been attributed to maternal/fetal exposures to environmental factors. We examined the effects of an estrogen (diethylstilbestrol, DES, an antiandrogen (flutamide, or radiation on the incidence of testicular germ cell tumors in genetically predisposed 129.MOLF-L1 (L1 congenic mice by exposing them to these agents on days 10.5 and 11.5 of pregnancy. Neither flutamide nor DES produced noticeable increases in testis cancer incidence at 4 weeks of age. In contrast, two doses of 0.8-Gy radiation increased the incidence of TGCT from 45% to 100% in the offspring. The percentage of mice with bilateral tumors, weights of testes with TGCT, and the percentage of tumors that were clearly teratomas were higher in the irradiated mice than in controls, indicating that irradiation induced more aggressive tumors and/or more foci of initiation sites in each testis. This radiation dose did not disrupt spermatogenesis, which was qualitatively normal in tumor-free testes although they were reduced in size. This is the first proof of induction of testicular cancer by an environmental agent and suggests that the male fetus of women exposed to radiation at about 5-6 weeks of pregnancy might have an increased risk of developing testicular cancer. Furthermore, it provides a novel tool for studying the molecular and cellular events of testicular cancer pathogenesis.

  15. Analysis of a p53 Mutation Associated with Cancer Susceptibility for Biochemistry and Genetic Laboratory Courses

    Science.gov (United States)

    Soto-Cruz, Isabel; Legorreta-Herrera, Martha

    2009-01-01

    We have devised and implemented a module for an upper division undergraduate laboratory based on the amplification and analysis of a p53 polymorphism associated with cancer susceptibility. First, students collected a drop of peripheral blood cells using a sterile sting and then used FTA cards to extract the genomic DNA. The p53 region is then PCR…

  16. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

    DEFF Research Database (Denmark)

    Pharoah, Paul D P; Tsai, Ya-Yu; Ramus, Susan J;

    2013-01-01

    Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24...

  17. Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2

    DEFF Research Database (Denmark)

    Ahmed, Shahana; Thomas, Gilles; Ghoussaini, Maya; Healey, Catherine S; Humphreys, Manjeet K; Platte, Radka; Morrison, Jonathan; Maranian, Melanie; Pooley, Karen A; Luben, Robert; Eccles, Diana; Evans, D Gareth; Fletcher, Olivia; Johnson, Nichola; dos Santos Silva, Isabel; Peto, Julian; Stratton, Michael R; Rahman, Nazneen; Jacobs, Kevin; Prentice, Ross; Anderson, Garnet L; Rajkovic, Aleksandar; Curb, J David; Ziegler, Regina G; Berg, Christine D; Buys, Saundra S; McCarty, Catherine A; Feigelson, Heather Spencer; Calle, Eugenia E; Thun, Michael J; Diver, W Ryan; Bojesen, Stig; Nordestgaard, Børge G; Flyger, Henrik; Dörk, Thilo; Schürmann, Peter; Hillemanns, Peter; Karstens, Johann H; Bogdanova, Natalia V; Antonenkova, Natalia N; Zalutsky, Iosif V; Bermisheva, Marina; Fedorova, Sardana; Khusnutdinova, Elza; Kang, Daehee; Yoo, Keun-Young; Noh, Dong Young; Ahn, Sei-Hyun; Devilee, Peter; van Asperen, Christi J; Tollenaar, R A E M; Seynaeve, Caroline; Garcia-Closas, Montserrat; Lissowska, Jolanta; Brinton, Louise; Peplonska, Beata; Nevanlinna, Heli; Heikkinen, Tuomas; Aittomäki, Kristiina; Blomqvist, Carl; Hopper, John L; Southey, Melissa C; Smith, Letitia; Spurdle, Amanda B; Schmidt, Marjanka K; Broeks, Annegien; van Hien, Richard R; Cornelissen, Sten; Milne, Roger L; Ribas, Gloria; González-Neira, Anna; Benitez, Javier; Schmutzler, Rita K; Burwinkel, Barbara; Bartram, Claus R; Meindl, Alfons; Brauch, Hiltrud; Justenhoven, Christina; Hamann, Ute; Chang-Claude, Jenny; Hein, Rebecca; Wang-Gohrke, Shan; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Kataja, Vesa; Olson, Janet E; Wang, Xianshu; Fredericksen, Zachary; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; English, Dallas R; Hankinson, Susan E; Cox, David G; Kraft, Peter; Vatten, Lars J; Hveem, Kristian; Kumle, Merethe; Sigurdson, Alice; Doody, Michele; Bhatti, Parveen; Alexander, Bruce H; Hooning, Maartje J; van den Ouweland, Ans M W; Oldenburg, Rogier A; Schutte, Mieke; Hall, Per; Czene, Kamila; Liu, Jianjun; Li, Yuqing; Cox, Angela; Elliott, Graeme; Brock, Ian; Reed, Malcolm W R; Shen, Chen-Yang; Yu, Jyh-Cherng; Hsu, Giu-Cheng; Chen, Shou-Tung; Anton-Culver, Hoda; Ziogas, Argyrios; Andrulis, Irene L; Knight, Julia A; Beesley, Jonathan; Goode, Ellen L; Couch, Fergus; Chenevix-Trench, Georgia; Hoover, Robert N; Ponder, Bruce A J; Hunter, David J; Pharoah, Paul D P; Dunning, Alison M; Chanock, Stephen J; Easton, Douglas F

    2009-01-01

    Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage...

  18. Association studies of ERCC1 polymorphisms with lung cancer susceptibility: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jinhong Zhu

    Full Text Available BACKGROUND: Excision repair cross-complimentary group 1 (ERCC1 is an essential component of the nucleotide excision repair system that is responsible for repairing damaged DNA. Functional genetic variations in the ERCC1 gene may alter DNA repair capacity and modulate cancer risk. The putative roles of ERCC1 gene polymorphisms in lung cancer susceptibility have been widely investigated. However, the results remain controversial. OBJECTIVES: An updated meta-analysis was conducted to explore whether lung cancer risk could be attributed to the following ERCC1 polymorphisms: rs11615 (T>C, rs3212986 (C>A, rs3212961 (A>C, rs3212948 (G>C, rs2298881 (C>A. METHODS: Several major databases (MEDLINE, EMBASE and Scopus and the Chinese Biomedical database were searched for eligible studies. Crude odds ratios (ORs with 95% confidence intervals (CIs were used to measure the strength of associations. RESULTS: Sixteen studies with 10,106 cases and 13,238 controls were included in this meta-analysis. Pooled ORs from 11 eligible studies (8,215 cases vs. 11,402 controls suggested a significant association of ERCC1 rs11615 with increased risk for lung cancer (homozygous: CC versus TT, OR = 1.24, 95% CI: 1.04-1.48, P = 0.02. However, such an association was disproportionately driven by a single study. Removal of that study led to null association. Moreover, initial analyses suggested that ERCC1 rs11615 exerts a more profound effect on the susceptibility of non-smokers to lung cancer than that of smokers. Moreover, no statistically significant association was found between remaining ERCC1 polymorphisms of interest and lung cancer risk, except for rs3212948 variation (heterozygous: CG vs.GG, OR = 0.78, 95% CI: 0.67-0.90, P = 0.001; dominant: CG/CC vs.GG, OR = 0.79, 95% CI: 0.69-0.91, P = 0.001. CONCLUSION: Overall, this meta-analysis suggests that ERCC1 rs3212948 G>C, but not others, is a lung cancer risk-associated polymorphism. Carefully

  19. Gene Therapy in Oral Cancer: A Review

    OpenAIRE

    Kumar, M. Sathish; Masthan, K.M.K.; Babu, N. Aravindha; Dash, Kailash Chandra

    2013-01-01

    Gene therapy is the use of DNA as an agent to treat disease. Gene therapy aims at the insertion of a functional gene into the cells of a patient for the correction of an inborn error of metabolism, to alter or repair an acquired genetic abnormality, and to provide new function to the cell. Many experiments have been done with respect to its application in various diseases.Today, most of the gene therapy studies are aimed at cancer and hereditary diseases which are linked to genetic defects. C...

  20. Transcriptionally targeted gene therapy to detect and treat cancer

    OpenAIRE

    Wu, Lily; Johnson, Mai; Sato, Makoto

    2003-01-01

    The greatest challenge in cancer treatment is to achieve the highest levels of specificity and efficacy. Cancer gene therapy could be designed specifically to express therapeutic genes to induce cancer cell destruction. Cancer-specific promoters are useful tools to accomplish targeted expression; however, high levels of gene expression are needed to achieve therapeutic efficacy. Incorporating an imaging reporter gene in tandem with the therapeutic gene will allow tangible proof of principle t...

  1. Association between single nucleotide polymorphisms of BARD1 gene and susceptibility of early-onset breast cancer in Uygur women in Xinjiang%BARD1基因单核苷酸多态性与新疆维吾尔族妇女早发性乳腺癌的相关性研究

    Institute of Scientific and Technical Information of China (English)

    孙刚; 王江涛; 马斌林; 耿中利; 任光辉; 单美慧; 马斌; 马莉莉; 王岩

    2012-01-01

    目的 探讨BARD1基因Pro24Ser(C/T)、Arg378Ser(G/C)和Val507Met( G/A)单核苷酸多态性(SNPa)与新疆维吾尔族妇女早发性乳腺癌易感性的关系.方法 采用病例-对照研究,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测新疆地区144例维吾尔族妇女早发性乳腺癌(年龄≤40岁)和136例维吾尔族健康女性BARD1基因Pr024Ser (C/T)、Arg378 Ser( G/C)和Val507Met (G/A)位点基因型,比较各位点基因型分布与维吾尔族妇女早发性乳腺癌发病风险的关系.结果 初潮年龄早、初产年龄晚和肿瘤家族史可能是新疆地区维吾尔族早发性乳腺癌患者发病的高危因素.在维吾尔族早发性乳腺癌组和健康对照组中,BARD1基因Pro24Ser (C/T)、Arg378Ser(G/C)和Val507Met( G/A)位点的各基因型频率差异有统计学意义(P<0.05).Logistic同归分析表明,Pro24Ser(C/T)位点TT(OR =0.117,95% CI为0.058~0.236)及显性模型CT+ TT( OR=0.279,95%CI为0.157~0.494)、Arg378Ser( G/C)位点CC(OR=0.348,95%CI为0.145~0.834)和Val507 Met( G/A)位点AA(OR=0.359,95% CI为0.167~0.774)的改变,可以显著降低维吾尔族早发性乳腺癌发病风险,并且各位点之间存在协同作用;同时,显性模型CT+TT、GC +CC、GA +AA间的交互作用可以降低52.1%的乳腺癌发病风险(OR=0.479,95% CI为0.230~0.995).分层分析结果显示,Pro24Ser(C/T)和Arg378Ser( G/C)位点基因突变型的保护作用在初潮年龄早和肿瘤家族史阴性患者中更为明显.随着患者初潮年龄的增加,这种保护作用逐渐降低.结论 BARD1基因Pr24Ser(C/T)、Arg378Ser(G/C)和Val507Met( G/A)位点的SNPs变化,能够显著降低新疆地区维吾尔族妇女早发性乳腺癌的发病风险,初潮年龄早和无肿瘤家族史可以增加突变等位基因的保护作用.%Objective To investigate the association between single nucleotide polymorphisms (SNPs) of BARD1 gene and susceptibility of early-onset breast cancer in

  2. Gene Polymorphisms in Pattern Recognition Receptors and Susceptibility to Idiopathic Recurrent Vulvovaginal Candidiasis

    Directory of Open Access Journals (Sweden)

    Diana eRosentul

    2014-09-01

    Full Text Available Objective. Approximately 5% of women suffer from recurrent vulvovaginal candidiasis (RVVC. It has been hypothesized that genetic factors play an important role in the susceptibility to RVVC. The aim of this study was to assess the effect of genetic variants of genes encoding for Pattern Recognition Receptors (PRRs on susceptibility to RVVC.Study design. For the study, 119 RVVC patients and 263 healthy controls were recruited. Prevalence of polymorphisms in five PRRs involved in recognition of Candida were investigated in patients and controls. In silico and functional studies were performed to assess their functional effects. Results. Single nucleotide polymorphisms (SNPs in TLR1, TLR4, CLEC7A and CARD9 did not affect the susceptibility to RVVC. In contrast, a non-synonymous polymorphism in TLR2 (rs5743704, Pro631His increased the susceptibility to RVVC almost 3-fold. Furthermore, the TLR2 rs5743704 SNP had deleterious effects on protein function as assessed by in-silico analysis, and in-vitro functional assays suggested that it reduces production of IL-17 and IFN upon stimulation of peripheral blood mononuclear cells with C. albicans. No effects were observed on serum MBL concentrations.Conclusion. Genetic variation in TLR2 may significantly enhance susceptibility to RVVC by modulating host defense mechanisms against Candida. Additional studies are warranted to assess systematically the role of host genetic variation for susceptibility to RVVC.

  3. Adenoviral gene therapy in gastric cancer: A review

    Institute of Scientific and Technical Information of China (English)

    Nima Khalighinejad; Hesammodin Hariri; Omid Behnamfar; Arash Yousefi; Amir Momeni

    2008-01-01

    Gastric cancer is one of the most common malignancies worldwide. With current therapeutic approaches the prognosis of gastric cancer is very poor, as gastric cancer accounts for the second most common cause of death in cancer related deaths. Gastric cancer like almost all other cancers has a molecular genetic basis which relies on disruption in normal cellular regulatory mechanisms regarding cell growth, apoptosis and cell division. Thus novel therapeutic approaches such as gene therapy promise to become the alternative choice of treatment in gastric cancer. In gene therapy, suicide genes, tumor suppressor genes and anti-angiogenesis genes among many others are introduced to cancer cells via vectors.Some of the vectors widely used in gene therapy are Adenoviral vectors. This review provides an update of the new developments in adenoviral cancer gene therapy including strategies for inducing apoptosis, inhibiting metastasis and targeting the cancer cells.

  4. Whole exome sequencing suggests much of non-BRCA1/BRCA2 familial breast cancer is due to moderate and low penetrance susceptibility alleles.

    Directory of Open Access Journals (Sweden)

    Francisco Javier Gracia-Aznarez

    Full Text Available The identification of the two most prevalent susceptibility genes in breast cancer, BRCA1 and BRCA2, was the beginning of a sustained effort to uncover new genes explaining the missing heritability in this disease. Today, additional high, moderate and low penetrance genes have been identified in breast cancer, such as P53, PTEN, STK11, PALB2 or ATM, globally accounting for around 35 percent of the familial cases. In the present study we used massively parallel sequencing to analyze 7 BRCA1/BRCA2 negative families, each having at least 6 affected women with breast cancer (between 6 and 10 diagnosed under the age of 60 across generations. After extensive filtering, Sanger sequencing validation and co-segregation studies, variants were prioritized through either control-population studies, including up to 750 healthy individuals, or case-control assays comprising approximately 5300 samples. As a result, a known moderate susceptibility indel variant (CHEK2 1100delC and a catalogue of 11 rare variants presenting signs of association with breast cancer were identified. All the affected genes are involved in important cellular mechanisms like DNA repair, cell proliferation and survival or cell cycle regulation. This study highlights the need to investigate the role of rare variants in familial cancer development by means of novel high throughput analysis strategies optimized for genetically heterogeneous scenarios. Even considering the intrinsic limitations of exome resequencing studies, our findings support the hypothesis that the majority of non-BRCA1/BRCA2 breast cancer families might be explained by the action of moderate and/or low penetrance susceptibility alleles.

  5. Glutathione S-transferase M1, T1 and P1 polymorphisms: susceptibility and outcome in lung cancer patients.

    Science.gov (United States)

    Sreeja, Leelakumari; Syamala, Vani; Hariharan, Sreedharan; Syamala, Volga S; Raveendran, Praveenkumar B; Sivanandan, C D; Madhavan, Jayaprakash; Ankathil, Ravindran

    2008-01-01

    The glutathione S-transferases (GSTs) are a superfamily of genes whose products are phase II enzymes, catalyzing the conjugation of reactive intermediates to soluble glutathione. Some of the GSTs are polymorphic and may play a role in lung cancer susceptibility. We investigated whether genetic polymorphisms of GSTM1, GSTP1 and GSTT1 genes modulated lung cancer risk and affect survival among lung cancer patients. We determined the GST genotypes in 422 study subjects, using polymerase chain reaction (PCR) and reverse PCR and restriction fragment length polymorphism (RFLP). Logistic Regression analysis was carried out to find the association of various polymorphisms and GSTs and lung cancer. The influence of the genetic polymorphisms on patient survival was estimated using the method of Kaplan-Meier survival function. Cox Proportional Hazard models were used to estimate hazard ratios (HR) for deaths. GSTT1 -/- genotype conferred a higher odds ratio of 2.9 (P = 0.001) compared to the GSTT1+/+. So also, the GSTP1 GG genotype too had higher risk compared to the GSTP1 AA genotype (OR = 2.3, P = 0.033). When the combined GST M1, GSTT1 and GSTP1 genotypes were examined, patients with the combinations GSTM1 null and GSTT1 null had a significant OR of 3.6. So also the combinations GSTT1-/- GSTP1 AA (P = 0.005) and GSTT1-/- GSTP1 AG/GG (P = 0.001) came out to be significant. There were some significant interactions between GST genotypes with tobacco smoking and also for clinicopathological factors. Regarding survival analysis, no association of GSTM1 or GSTP1 genes with survival was noted. The GSTT1 -/- genotype along with stage was significantly associated with overall survival and found to be an independent prognostic factors for shorter lung cancer survival. PMID:18472644

  6. Transcriptional Targeting in Cancer Gene Therapy

    OpenAIRE

    Tracy Robson; David G. Hirst

    2003-01-01

    Cancer gene therapy has been one of the most exciting areas of therapeutic research in the past decade. In this review, we discuss strategies to restrict transcription of transgenes to tumour cells. A range of promoters which are tissue-specific, tumour-specific, or inducible by exogenous agents are presented. Transcriptional targeting should prevent normal tissue toxicities associated with other cancer treatments, such as radiation and chemotherapy. In addition, the specificity of these stra...

  7. Genome-wide association study of colorectal cancer identifies six new susceptibility loci

    Science.gov (United States)

    Schumacher, Fredrick R.; Schmit, Stephanie L.; Jiao, Shuo; Edlund, Christopher K.; Wang, Hansong; Zhang, Ben; Hsu, Li; Huang, Shu-Chen; Fischer, Christopher P.; Harju, John F.; Idos, Gregory E.; Lejbkowicz, Flavio; Manion, Frank J.; McDonnell, Kevin; McNeil, Caroline E.; Melas, Marilena; Rennert, Hedy S.; Shi, Wei; Thomas, Duncan C.; Van Den Berg, David J.; Hutter, Carolyn M.; Aragaki, Aaron K.; Butterbach, Katja; Caan, Bette J.; Carlson, Christopher S.; Chanock, Stephen J.; Curtis, Keith R.; Fuchs, Charles S.; Gala, Manish; Giovannucci, Edward L.; Gogarten, Stephanie M.; Hayes, Richard B.; Henderson, Brian; Hunter, David J.; Jackson, Rebecca D.; Kolonel, Laurence N.; Kooperberg, Charles; Küry, Sébastien; LaCroix, Andrea; Laurie, Cathy C.; Laurie, Cecelia A.; Lemire, Mathieu; Levine, David; Ma, Jing; Makar, Karen W.; Qu, Conghui; Taverna, Darin; Ulrich, Cornelia M.; Wu, Kana; Kono, Suminori; West, Dee W.; Berndt, Sonja I.; Bezieau, Stéphane; Brenner, Hermann; Campbell, Peter T.; Chan, Andrew T.; Chang-Claude, Jenny; Coetzee, Gerhard A.; Conti, David V.; Duggan, David; Figueiredo, Jane C.; Fortini, Barbara K.; Gallinger, Steven J.; Gauderman, W. James; Giles, Graham; Green, Roger; Haile, Robert; Harrison, Tabitha A.; Hoffmeister, Michael; Hopper, John L.; Hudson, Thomas J.; Jacobs, Eric; Iwasaki, Motoki; Jee, Sun Ha; Jenkins, Mark; Jia, Wei-Hua; Joshi, Amit; Li, Li; Lindor, Noralene M.; Matsuo, Keitaro; Moreno, Victor; Mukherjee, Bhramar; Newcomb, Polly A.; Potter, John D.; Raskin, Leon; Rennert, Gad; Rosse, Stephanie; Severi, Gianluca; Schoen, Robert E.; Seminara, Daniela; Shu, Xiao-Ou; Slattery, Martha L.; Tsugane, Shoichiro; White, Emily; Xiang, Yong-Bing; Zanke, Brent W.; Zheng, Wei; Le Marchand, Loic; Casey, Graham; Gruber, Stephen B.; Peters, Ulrike

    2016-01-01

    Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E-08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies. PMID:26151821

  8. Identification of seven new prostate cancer susceptibility loci through a genome-wide association study

    Science.gov (United States)

    Eeles, Rosalind A.; Kote-Jarai, Zsofia; Olama, Ali Amin Al; Giles, Graham G.; Guy, Michelle; Severi, Gianluca; Muir, Kenneth; Hopper, John L.; Henderson, Brian E.; Haiman, Christopher A.; Schleutker, Johanna; Hamdy, Freddie C.; Neal, David E.; Donovan, Jenny L.; Stanford, Janet L.; Ostrander, Elaine A.; Ingles, Sue A.; John, Esther M.; Thibodeau, Stephen N.; Schaid, Daniel; Park, Jong Y.; Spurdle, Amanda; Clements, Judith; Dickinson, Joanne L.; Maier, Christiane; Vogel, Walther; Dörk, Thilo; Rebbeck, Timothy R.; Cooney, Kathleen A.; Cannon-Albright, Lisa; Chappuis, Pierre O.; Hutter, Pierre; Zeegers, Maurice; Kaneva, Radka; Zhang, Hong-Wei; Lu, Yong-Jie; Foulkes, William D.; English, Dallas R.; Leongamornlert, Daniel A.; Tymrakiewicz, Malgorzata; Morrison, Jonathan; Ardern-Jones, Audrey T.; Hall, Amanda L.; O’Brien, Lynne T.; Wilkinson, Rosemary A.; Saunders, Edward J.; Page, Elizabeth C.; Sawyer, Emma J.; Edwards, Stephen M.; Dearnaley, David P.; Horwich, Alan; Huddart, Robert A.; Khoo, Vincent S.; Parker, Christopher C.; Van As, Nicholas; Woodhouse, Christopher J.; Thompson, Alan; Christmas, Tim; Ogden, Chris; Cooper, Colin S.; Southey, Melissa C.; Lophatananon, Artitaya; Liu, Jo-Fen; Kolonel, Laurence N.; Le Marchand, Loic; Wahlfors, Tiina; Tammela, Teuvo L.; Auvinen, Anssi; Lewis, Sarah J.; Cox, Angela; FitzGerald, Liesel M.; Koopmeiners, Joseph S.; Karyadi, Danielle M.; Kwon, Erika M.; Stern, Mariana C.; Corral, Roman; Joshi, Amit D.; Shahabi, Ahva; McDonnell, Shannon K.; Sellers, Thomas A; Pow-Sang, Julio; Chambers, Suzanne; Aitken, Joanne; Gardiner, R.A. (Frank); Batra, Jyotsna; Kedda, Mary Anne; Lose, Felicity; Polanowski, Andrea; Patterson, Briony; Serth, Jürgen; Meyer, Andreas; Luedeke, Manuel; Stefflova, Klara; Ray, Anna M.; Lange, Ethan M.; Farnham, Jim; Khan, Humera; Slavov, Chavdar; Mitkova, Atanaska; Cao, Guangwen; Easton, Douglas F.

    2010-01-01

    Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. To identify common PrCa susceptibility alleles, we have previously conducted a genome-wide association study in which 541, 129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and 1,894 controls. We have now evaluated promising associations in a second stage, in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls, and a third stage, involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to previously identified loci, we identified a further seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11, and 22 (P=1.6×10−8 to P=2.7×10−33). PMID:19767753

  9. Lateral organ boundaries 1 is a disease susceptibility gene for citrus bacterial canker disease.

    Science.gov (United States)

    Hu, Yang; Zhang, Junli; Jia, Hongge; Sosso, Davide; Li, Ting; Frommer, Wolf B; Yang, Bing; White, Frank F; Wang, Nian; Jones, Jeffrey B

    2014-01-28

    Citrus bacterial canker (CBC) disease occurs worldwide and incurs considerable costs both from control measures and yield losses. Bacteria that cause CBC require one of six known type III transcription activator-like (TAL) effector genes for the characteristic pustule formation at the site of infection. Here, we show that Xanthomonas citri subspecies citri strain Xcc306, with the type III TAL effector gene pthA4 or with the distinct yet biologically equivalent gene pthAw from strain XccA(w), induces two host genes, CsLOB1 and CsSWEET1, in a TAL effector-dependent manner. CsLOB1 is a member of the Lateral Organ Boundaries (LOB) gene family of transcription factors, and CsSWEET1 is a homolog of the SWEET sugar transporter and rice disease susceptibility gene. Both TAL effectors drive expression of CsLOB1 and CsSWEET1 promoter reporter gene fusions when coexpressed in citrus or Nicotiana benthamiana. Artificially designed TAL effectors directed to sequences in the CsLOB1 promoter region, but not the CsSWEET1 promoter, promoted pustule formation and higher bacterial leaf populations. Three additional distinct TAL effector genes, pthA*, pthB, and pthC, also direct pustule formation and expression of CsLOB1. Unlike pthA4 and pthAw, pthB and pthC do not promote the expression of CsSWEET1. CsLOB1 expression was associated with the expression of genes associated with cell expansion. The results indicate that CBC-inciting species of Xanthomonas exploit a single host disease susceptibility gene by altering the expression of an otherwise developmentally regulated gene using any one of a diverse set of TAL effector genes in the pathogen populations. PMID:24474801

  10. Relation between interleukin-13 gene polymorphisms and susceptibility to brucellosis in Iranian population

    Directory of Open Access Journals (Sweden)

    Sayed-Jalal-Aladin Ashraf-Mansuri

    2016-03-01

    Full Text Available Brucella is an intracellular Gram-negative bacterium. Previous reports showed that gene polymorphisms of cytokines can affect resistance or susceptibility to Brucella infection. Interleukin-13, a cytokine secreted by Th2 lymphocytes, has an important role in immune responses against established infections. In this study, we investigated the association of three polymorphic sites of IL-13 with susceptibility to brucellosis in Iranian population. In this study 169 patients with brucellosis and 71 healthy controls were included. DNA was extracted and genotyped for three bi-allelic polymorphisms of IL-13 gene at positions -1512A/C, -1055C/T, and +2044G/A by polymerase chain reaction-restriction fragment length polymorphism method. None of the studied alleles and genotypes of IL-13 gene (-1512A/C, -1055C/T, and +2044G/A showed significant relationship with susceptibility to brucellosis. However, among eight haplotypes, the distribution of TCG and CAA haplotypes were significantly higher in the patients compared with those in the controls (P=0.002 and P=0.034, respectively. Although, the later did not tolerate Bonferoni correction. On the contrary, the distribution of TCA haplotype was higher in the controls compared to that in the patients (P=0.01. Furthermore, TAG/TCA haplogenotypes were significantly higher among controls compared to the brucellosis patients (P=0.025. P value resulted from TCA and TAG/TCA did not tolerate Bonferroni correction. There is no association between the inheritance of different alleles and genotypes of interleukin-13 gene and susceptibility to brucellosis. However, it seems that the inheritance of some haplotypes and haplogenotypes of IL-13 can impact the susceptibility to brucellosis.

  11. Translational Approaches towards Cancer Gene Therapy: Hurdles and Hopes

    OpenAIRE

    Yadollah Omidi; Jaleh Barar

    2012-01-01

    Introduction: Of the cancer gene therapy approaches, gene silencing, suicide/apoptosis inducing gene therapy, immunogene therapy and targeted gene therapy are deemed to sub­stantially control the biological consequences of genomic changes in cancerous cells. Thus, a large number of clinical trials have been conducted against various malignancies. In this review, we will discuss recent translational progresses of gene and cell therapy of cancer. Methods: Essential information on gene therapy o...

  12. Heat induces gene amplification in cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► This study discovered that heat exposure (hyperthermia) results in gene amplification in cancer cells. ► Hyperthermia induces DNA double strand breaks. ► DNA double strand breaks are considered to be required for the initiation of gene amplification. ► The underlying mechanism of heat-induced gene amplification is generation of DNA double strand breaks. -- Abstract: Background: Hyperthermia plays an important role in cancer therapy. However, as with radiation, it can cause DNA damage and therefore genetic instability. We studied whether hyperthermia can induce gene amplification in cancer cells and explored potential underlying molecular mechanisms. Materials and methods: (1) Hyperthermia: HCT116 colon cancer cells received water-submerged heating treatment at 42 or 44 °C for 30 min; (2) gene amplification assay using N-(phosphoacetyl)-L-aspartate (PALA) selection of cabamyl-P-synthetase, aspartate transcarbarmylase, dihydro-orotase (cad) gene amplified cells; (3) southern blotting for confirmation of increased cad gene copies in PALA-resistant cells; (4) γH2AX immunostaining to detect γH2AX foci as an indication for DNA double strand breaks. Results: (1) Heat exposure at 42 or 44 °C for 30 min induces gene amplification. The frequency of cad gene amplification increased by 2.8 and 6.5 folds respectively; (2) heat exposure at both 42 and 44 °C for 30 min induces DNA double strand breaks in HCT116 cells as shown by γH2AX immunostaining. Conclusion: This study shows that heat exposure can induce gene amplification in cancer cells, likely through the generation of DNA double strand breaks, which are believed to be required for the initiation of gene amplification. This process may be promoted by heat when cellular proteins that are responsible for checkpoints, DNA replication, DNA repair and telomere functions are denatured. To our knowledge, this is the first study to provide direct evidence of hyperthermia induced gene amplification.

  13. Heat induces gene amplification in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Bin, E-mail: yanbin@mercyhealth.com [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39213 (United States); Mercy Cancer Center, Mercy Medical Center-North Iowa, Mason City, IA 50401 (United States); Ouyang, Ruoyun [Department of Respiratory Medicine, The Second Xiangya Hospital, Xinagya School of Medicine, Central South University, Changsha 410011 (China); Huang, Chenghui [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39213 (United States); Department of Oncology, The Third Xiangya Hospital, Xinagya School of Medicine, Central South University, Changsha 410013 (China); Liu, Franklin [Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710 (United States); Neill, Daniel [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39213 (United States); Li, Chuanyuan [Dermatology, Duke University Medical Center, Durham, NC 27710 (United States); Dewhirst, Mark [Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710 (United States)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer This study discovered that heat exposure (hyperthermia) results in gene amplification in cancer cells. Black-Right-Pointing-Pointer Hyperthermia induces DNA double strand breaks. Black-Right-Pointing-Pointer DNA double strand breaks are considered to be required for the initiation of gene amplification. Black-Right-Pointing-Pointer The underlying mechanism of heat-induced gene amplification is generation of DNA double strand breaks. -- Abstract: Background: Hyperthermia plays an important role in cancer therapy. However, as with radiation, it can cause DNA damage and therefore genetic instability. We studied whether hyperthermia can induce gene amplification in cancer cells and explored potential underlying molecular mechanisms. Materials and methods: (1) Hyperthermia: HCT116 colon cancer cells received water-submerged heating treatment at 42 or 44 Degree-Sign C for 30 min; (2) gene amplification assay using N-(phosphoacetyl)-L-aspartate (PALA) selection of cabamyl-P-synthetase, aspartate transcarbarmylase, dihydro-orotase (cad) gene amplified cells; (3) southern blotting for confirmation of increased cad gene copies in PALA-resistant cells; (4) {gamma}H2AX immunostaining to detect {gamma}H2AX foci as an indication for DNA double strand breaks. Results: (1) Heat exposure at 42 or 44 Degree-Sign C for 30 min induces gene amplification. The frequency of cad gene amplification increased by 2.8 and 6.5 folds respectively; (2) heat exposure at both 42 and 44 Degree-Sign C for 30 min induces DNA double strand breaks in HCT116 cells as shown by {gamma}H2AX immunostaining. Conclusion: This study shows that heat exposure can induce gene amplification in cancer cells, likely through the generation of DNA double strand breaks, which are believed to be required for the initiation of gene amplification. This process may be promoted by heat when cellular proteins that are responsible for checkpoints, DNA replication, DNA repair and

  14. Genes Expressed Differentially in Hessian Fly Larvae Feeding in Resistant and Susceptible Plants

    Science.gov (United States)

    Chen, Ming-Shun; Liu, Sanzhen; Wang, Haiyan; Cheng, Xiaoyan; El Bouhssini, Mustapha; Whitworth, R. Jeff

    2016-01-01

    The Hessian fly, Mayetiola destructor, is a destructive pest of wheat worldwide and mainly controlled by deploying resistant cultivars. In this study, we investigated the genes that were expressed differentially between larvae in resistant plants and those in susceptible plants through RNA sequencing on the Illumina platform. Informative genes were 11,832, 14,861, 15,708, and 15,071 for the comparisons between larvae in resistant versus susceptible plants for 0.5, 1, 3, and 5 days, respectively, after larvae had reached the feeding site. The transcript abundance corresponding to 5401, 6902, 8457, and 5202 of the informative genes exhibited significant differences (p ≤ 0.05) in the respective paired comparisons. Overall, genes involved in nutrient metabolism, RNA and protein synthesis exhibited lower transcript abundance in larvae from resistant plants, indicating that resistant plants inhibited nutrient metabolism and protein production in larvae. Interestingly, the numbers of cytochrome P450 genes with higher transcript abundance in larvae from resistant plants were comparable to, or higher than those with lower transcript abundance, indicating that toxic chemicals from resistant plants may have played important roles in Hessian fly larval death. Our study also identified several families of genes encoding secreted salivary gland proteins (SSGPs) that were expressed at early stage of 1st instar larvae and with more genes with higher transcript abundance in larvae from resistant plants. Those SSGPs are candidate effectors with important roles in plant manipulation. PMID:27529231

  15. Antiangiogenic gene therapy of cancer: recent developments

    OpenAIRE

    Libutti Steven K; Blazer Dan G; Tandle Anita

    2004-01-01

    Abstract With the role of angiogenesis in tumor growth and progression firmly established, considerable effort has been directed to antiangiogenic therapy as a new modality to treat human cancers. Antiangiogenic agents have recently received much widespread attention but strategies for their optimal use are still being developed. Gene therapy represents an attractive alternative to recombinant protein administration for several reasons. This review evaluates the potential advantages of gene t...

  16. Multifunctional Delivery Systems for Cancer Gene Therapy

    OpenAIRE

    McErlean, Emma M.; McCrudden, Cian M; McCarthy, Helen O.

    2015-01-01

    This chapter examines key concepts with respect to cancer gene therapy and the current issues with respect to non-viral delivery. The biological and molecular barriers that need to be overcome before effective non-viral delivery systems can be appropriately designed for oncology applications are highlighted and ways to overcome these are discussed. Strategies developed to evade the immune response are also described and targeted gene delivery is examined with the most effective strategies hig...

  17. Gene Tests May Improve Therapy for Endometrial Cancer

    Science.gov (United States)

    ... External link, please review our exit disclaimer . Subscribe Gene Tests May Improve Therapy for Endometrial Cancer By analyzing genes in hundreds of endometrial tumors, scientists identified details ...

  18. Analysis of the novel fanconi anemia gene SLX4/FANCP in familial breast cancer cases.

    Science.gov (United States)

    Bakker, Janine L; van Mil, Saskia E; Crossan, Gerry; Sabbaghian, Nelly; De Leeneer, Kim; Poppe, Bruce; Adank, Muriel; Gille, Hans; Verheul, Henk; Meijers-Heijboer, Hanne; de Winter, Johan P; Claes, Kathleen; Tischkowitz, Marc; Waisfisz, Quinten

    2013-01-01

    SLX4/FANCP is a recently discovered novel disease gene for Fanconi anemia (FA), a rare recessive disorder characterized by chromosomal instability and increased cancer susceptibility. Three of the 15 FA genes are breast cancer susceptibility genes in heterozygous mutation carriers--BRCA2, PALB2, and BRIP1. To investigate if defects in SLX4 also predispose to breast cancer, the gene was sequenced in a cohort of 729 BRCA1/BRCA2-negative familial breast cancer cases. We identified a single splice site mutation (c.2013+2T>A), which causes a frameshift by skipping of exon 8. We also identified 39 missense variants, four of which were selected for functional testing in a Mitomycin C-induced growth inhibition assay, and appeared indistinguishable from wild type. Although this is the first study that describes a truncating SLX4 mutation in breast cancer patients, our data indicate that germline mutations in SLX4 are very rare and are unlikely to make a significant contribution to familial breast cancer. PMID:22911665

  19. Two Genes Might Help Predict Breast Cancer Survival

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_160503.html Two Genes Might Help Predict Breast Cancer Survival Research suggests ... 18, 2016 (HealthDay News) -- The activity of two genes may help predict certain breast cancer patients' chances ...

  20. Role of key-regulator genes in melanoma susceptibility and pathogenesis among patients from South Italy

    International Nuclear Information System (INIS)

    Several genetic alterations have been demonstrated to contribute to the development and progression of melanoma. In this study, we further investigated the impact of key-regulator genes in susceptibility and pathogenesis of such a disease. A large series (N = 846) of sporadic and familial cases originating from South Italy was screened for germline mutations in p16CDKN2A, BRCA2, and MC1R genes by DHPLC analysis and automated DNA sequencing. Paired primary melanomas and lymph node metastases from same patients (N = 35) as well as melanoma cell lines (N = 18) were analyzed for somatic mutations in NRAS, BRAF, and p16CDKN2A genes. For melanoma susceptibility, investigations at germline level indicated that p16CDKN2A was exclusively mutated in 16/545 (2.9%) non-Sardinian patients, whereas BRCA2 germline mutations were observed in 4/91 (4.4%) patients from North Sardinia only. Two MC1R germline variants, Arg151Cys and Asp294His, were significantly associated with melanoma in Sardinia. Regarding genetic events involved in melanoma pathogenesis at somatic level, mutually-exclusive mutations of NRAS and BRAF genes were observed at quite same rate (about two thirds) in cultured and in vivo melanomas (either primary or metastatic lesions). Conversely, p16CDKN2A gene alterations were observed at increased rates moving from primary to metastatic melanomas and melanoma cell lines. Activation of the ERK gene product was demonstrated to be consistently induced by a combination of molecular alterations (NRAS/BRAF mutations and p16CDKN2A silencing). Our findings further clarified that: a) mutation prevalence in melanoma susceptibility genes may vary within each specific geographical area; b) multiple molecular events are accumulating during melanomagenesis

  1. Gene Variants Are Associated with PCOS Susceptibility and Hyperandrogenemia in Young Korean Women

    Directory of Open Access Journals (Sweden)

    Do Kyeong Song

    2014-08-01

    Full Text Available BackgroundThe fat mass and obesity-associated (FTO gene is associated with obesity and type 2 diabetes mellitus. Obesity and insulin resistance are also common features of polycystic ovary syndrome (PCOS. Therefore, the FTO gene might be a candidate gene for PCOS susceptibility. The aim of the present study was to evaluate the effects of FTO gene variants on PCOS susceptibility and metabolic and reproductive hormonal parameters.MethodsWe recruited 432 women with PCOS (24±5 years and 927 healthy women with regular menstrual cycles (27±5 years and performed a case-control association study. We genotyped the single nucleotide polymorphisms rs1421085, rs17817449, and rs8050136 in the FTO gene and collected metabolic and hormonal measurements.ResultsLogistic regression revealed that the G/G genotype (rs1421085, 1.6%, the C/C genotype (rs17817449, 1.6%, and the A/A genotype (rs8050136, 1.6% were strongly associated with an increased risk of PCOS (odds ratio, 2.551 to 2.559; all P<0.05. The strengths of these associations were attenuated after adjusting for age and BMI. The women with these genotypes were more obese and exhibited higher free androgen indices (P<0.05 and higher free testosterone levels (P=0.053 to 0.063 compared to the other genotypes. However the significant differences disappeared after adjusting for body mass index (BMI. When we analyzed the women with PCOS and the control groups separately, there were no significant differences in the metabolic and reproductive hormonal parameters according to the FTO gene variants.ConclusionThe rs1421085, rs17817449, and rs8050136 variants of the FTO gene were associated with PCOS susceptibility and hyperandrogenemia in young Korean women. These associations may be mediated through an effect of BMI.

  2. Integrative analysis of cancer genes in a functional interactome

    Science.gov (United States)

    Ung, Matthew H.; Liu, Chun-Chi; Cheng, Chao

    2016-01-01

    The post-genomic era has resulted in the accumulation of high-throughput cancer data from a vast array of genomic technologies including next-generation sequencing and microarray. As such, the large amounts of germline variant and somatic mutation data that have been generated from GWAS and sequencing projects, respectively, show great promise in providing a systems-level view of these genetic aberrations. In this study, we analyze publicly available GWAS, somatic mutation, and drug target data derived from large databanks using a network-based approach that incorporates directed edge information under a randomized network hypothesis testing procedure. We show that these three classes of disease-associated nodes exhibit non-random topological characteristics in the context of a functional interactome. Specifically, we show that drug targets tend to lie upstream of somatic mutations and disease susceptibility germline variants. In addition, we introduce a new approach to measuring hierarchy between drug targets, somatic mutants, and disease susceptibility genes by utilizing directionality and path length information. Overall, our results provide new insight into the intrinsic relationships between these node classes that broaden our understanding of cancer. In addition, our results align with current knowledge on the therapeutic actionability of GWAS and somatic mutant nodes, while demonstrating relationships between node classes from a global network perspective. PMID:27356765

  3. Breast cancer susceptibility relationship in NQO1 gene C609T polymorphism and environmental factors%NQO1基因C6O9T多态性和环境因素与乳腺癌遗传易感性的关系

    Institute of Scientific and Technical Information of China (English)

    汪满金; 俸瑞发; 刘晓萌; 陈威; 谭盛葵

    2015-01-01

    目的 探讨醌氧化还原酶1 (quinone oxido-reductase 1,NQO1)基因C609T多态性和环境因素与乳腺癌遗传易感性的关系.方法 采用以医院为基础的病例对照研究收集桂林医学院附属医院2012-10-15-2014-02-15共248例女性乳腺癌患者和该院2013-03-01-2013-12-30共284名女性健康体检者的人口学和环境暴露资料等,并采用TaqManMGB荧光定量聚合酶链反应技术和多因素非条件Logistic回归模型分析NQO1基因C609T在两组中分布频率的差异,以及与环境因素的交互作用.结果 病例组NQO1基因位点CC、CT和TT各基因型频率分别为27.42%、49.60%和22.98%,对照组中基因型频率分别为34.51%、50.35%和15.14%,差异有统计学意义,x2 =6.48,P=0.039.多因素Logistic回归分析表明,与CC基因型相比,CT或TT基因型的个体罹患乳腺癌的风险OR值分别为1.33和2.92.病例组等位基因T频率(47.78%)较对照组(40.32%)增高(x2=6.00,P=0.014),携带T等位基因者患乳腺癌的危险性是C等位基因携带者的1.36倍.交互作用分析表明,NQO1基因C609T多态性与经常熬夜、被动吸烟、精神创伤、睡觉佩戴胸罩、性格和体育锻炼等之间均存在交互作用(P<0.05),其OR值分别为2.45、3.96、2.40、1.98、0.33和0.52.结论 NQO1基因C609T多态性可能为乳腺癌发病的遗传易感因素,且与环境因素具有协同致癌作用.%OBJECTIVE To investigate the relationship between the quinone oxidoreductase 1 (NQO1) C609T gene polymorphism and environmental factors and genetic susceptibility of breast cancer.METHODS Demographic and environmental exposure information in 248 cases of female breast cancer patients in 2012-10-15-2014-02-15 and 284 cases of healthy women in 2013-03-01-2013-12-30 in our hospital were collected using hospital-based case-control study,and the differences of frequency distribution of NQO1 gene C609T in two groups as well as interaction with environmental factors were

  4. Analysis of Fractal Nature of Cancer Genes

    Directory of Open Access Journals (Sweden)

    Piyushi Singh, James Rohit Runda, Devanshu Umredkar & Rahul Shrivatava - See more at: http://sciencebeingjournal.com/octa-journal-biosciences/analysis-fractal-nature-cancer-genes#sthash.cDBXfyAw.dpuf

    2013-05-01

    Full Text Available This paper is aimed to predict the fractal natures of genes of two different cancers in Homo sapiens. The cancers whose properties were studied include the cancer of Lung and Skin. Two important genes that are responsible for each of these cancers were acquired to analyze their fractal nature. Wavelet transformation had been extensively used in the process of determining the fractal nature.The mRNA sequences were collected from the NCBI database and were then pre-processed efficiently. DNA walk plots were generated for each of these sequences using an in-house program written in MATLAB language. The data so obtained was checked for fractal property using wavelet transformations using an in-house program written in Matlab. All the sequences were checked for quadratic variations with the use of Daubechies-2(DB2 wavelets. The parameters were then plotted and the nature of each cancer was obtained from the plots. We have found that the gene sequences are exhibiting multifractal nature.

  5. Association of polymorphisms in non-classic MHC genes with susceptibility to autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    JieTang; ChengZhou; Zhi-JunZhang; Shu-SenZheng

    2012-01-01

    BACKGROUND: Autoimmune hepatitis is a chronic, generally progressive inflammatory disorder of the liver, of which the cause is unclear. It was demonstrated that genetic factors are involved in its pathogenesis. Previous studies showed that human leukocyte antigen in the major histocompatibility complex (MHC) is associated with susceptibility to autoimmune hepatitis. Current genome scanning studies suggest that genes outside the MHC also play a critical role in autoimmune disorders. This article focuses on our current understanding of the polymorphisms of these genes and their roles in the pathogenesis of autoimmune hepatitis. DATA  SOURCES: Studies were identified by searching MEDLINE and PubMed for articles using the keywords autoimmune hepatitis, polymorphism, CTLA-4, Fas, TNF-α, TGF-β1, TBX21 and VDR up to May 2011. Additional papers were identified by a manual search of the references from key articles. RESULTS:  According to the case-control studies on genetic polymorphisms, at least six genes (CTLA-4, Fas, TNF-α, TGF-β1, TBX21 and VDR) are involved in autoimmune hepatitis besides HLA. So far, there has been no agreement about gene susceptibility and the actual clinical significance of these genes is still controversial. CONCLUSION: Studies on gene polymorphisms outside the MHC and knowledge of genetic predispositions for autoimmune hepatitis may not only elucidate pathogenic mechanisms, but also provide new targets for therapy in the future.

  6. Clinical adenoviral gene therapy for prostate cancer

    Czech Academy of Sciences Publication Activity Database

    Schenk, E.; Essand, M.; Bangma, Ch. H.; Barber, Ch.; Behr, J.-P.; Briggs, S.; Carlisle, R.; Cheng, W.-S.; Danielsson, A.; Dautzenberg, I. J. C.; Dzojic, H.; Erbacher, P.; Fisher, K.; Frazier, A.; Georgopoulos, L. J.; Hoeben, R.; Kochanek, S.; Koppers-Lalic, D.; Kraaij, R.; Kreppel, F.; Lindholm, L.; Magnusson, M.; Maitland, N.; Neuberg, P.; Nilsson, B.; Ogris, M.; Remy, J.-S.; Scaife, M.; Schooten, E.; Seymour, L.; Totterman, T.; Uil, T. G.; Ulbrich, Karel; Veldhoven-Zweistra, J. L. M.; de Vrij, J.; van Weerden, W.; Wagner, E.; Willemsen, R.

    2010-01-01

    Roč. 21, č. 7 (2010), s. 807-813. ISSN 1043-0342 EU Projects: European Commission(XE) 512087 - GIANT Keywords : adenovirus * gene delivery * prostate cancer Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.829, year: 2010

  7. Gene sensitizes cancer cells to chemotherapy drugs

    Science.gov (United States)

    NCI scientists have found that a gene, Schlafen-11 (SLFN11), sensitizes cells to substances known to cause irreparable damage to DNA.  As part of their study, the researchers used a repository of 60 cell types to identify predictors of cancer cell respons

  8. Gene variant linked to lung cancer risk

    Science.gov (United States)

    A variation of the gene NFKB1, called rs4648127, is associated with an estimated 44 percent reduction in lung cancer risk. When this information, derived from samples obtained as part of a large NCI-sponsored prevention clinical trial, was compared with d

  9. Matrix metalloproteinase gene polymorphisms and periodontitis susceptibility: a meta-analysis involving 6,162 individuals

    Science.gov (United States)

    Weng, Hong; Yan, Yan; Jin, Ying-Hui; Meng, Xiang-Yu; Mo, Yuan-Yuan; Zeng, Xian-Tao

    2016-01-01

    We aimed to systematically investigate the potential association of matrix metalloproteinase (MMP)-9, -3, -2, and -8 gene polymorphisms with susceptibility to periodontitis using meta-analysis. A literature search in PubMed, Embase, and Web of Sciencewas conducted to obtain relevant publications. Finally a total of 16 articles with 24 case-control studies (nine on MMP-9-1562 C/T, seven on MMP-3-1171 A5/A6, four on MMP-2-753C/T, and four on MMP-8-799 C/T) were considered in this meta-analysis. The results based on 2,724 periodontitis patients and 3,438 controls showed that MMP-9-1562C/T, MMP-3-1171 A5/A6, and MMP-8-799C/T polymorphisms were associated with periodontitis susceptibility. No significant association was found between MMP-2-753 C/T and periodontitis susceptibility. Subgroup analyses suggested that the MMP-9-1562 C/T polymorphism reduced chronic periodontitis susceptibility and MMP-3-1171 A5/A6polymorphism increased chronic periodontitis susceptibility. In summary, current evidence demonstrated that MMP-9-753 C/Tpolymorphism reduced the risk of periodontitis, MMP-3-1171 5A/6A and MMP-8-799 C/Tpolymorphisms increased the risk of periodontitis, and MMP-2-753 C/T was not associated with risk of periodontitis. PMID:27095260

  10. Gene Prospector: An evidence gateway for evaluating potential susceptibility genes and interacting risk factors for human diseases

    Directory of Open Access Journals (Sweden)

    Khoury Muin J

    2008-12-01

    Full Text Available Abstract Background Millions of single nucleotide polymorphisms have been identified as a result of the human genome project and the rapid advance of high throughput genotyping technology. Genetic association studies, such as recent genome-wide association studies (GWAS, have provided a springboard for exploring the contribution of inherited genetic variation and gene/environment interactions in relation to disease. Given the capacity of such studies to produce a plethora of information that may then be described in a number of publications, selecting possible disease susceptibility genes and identifying related modifiable risk factors is a major challenge. A Web-based application for finding evidence of such relationships is key to the development of follow-up studies and evidence for translational research. We developed a Web-based application that selects and prioritizes potential disease-related genes by using a highly curated and updated literature database of genetic association studies. The application, called Gene Prospector, also provides a comprehensive set of links to additional data sources. Results We compared Gene Prospector results for the query "Parkinson" with a list of 13 leading candidate genes (Top Results from a curated, specialty database for genetic associations with Parkinson disease (PDGene. Nine of the thirteen leading candidate genes from PDGene were in the top 10th percentile of the ranked list from Gene Prospector. In fact, Gene Prospector included more published genetic association studies for the 13 leading candidate genes than PDGene did. Conclusion Gene Prospector provides an online gateway for searching for evidence about human genes in relation to diseases, other phenotypes, and risk factors, and provides links to published literature and other online data sources. Gene Prospector can be accessed via http://www.hugenavigator.net/HuGENavigator/geneProspectorStartPage.do.

  11. Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Steve P. Crampton

    2014-09-01

    Full Text Available Systemic lupus erythematosus (SLE represents a challenging autoimmune disease from a clinical perspective because of its varied forms of presentation. Although broad-spectrum steroids remain the standard treatment for SLE, they have many side effects and only provide temporary relief from the symptoms of the disease. Thus, gaining a deeper understanding of the genetic traits and biological pathways that confer susceptibility to SLE will help in the design of more targeted and effective therapeutics. Both human genome-wide association studies (GWAS and investigations using a variety of mouse models of SLE have been valuable for the identification of the genes and pathways involved in pathogenesis. In this Review, we link human susceptibility genes for SLE with biological pathways characterized in mouse models of lupus, and discuss how the mechanistic insights gained could advance drug discovery for the disease.

  12. Gene therapy in head and neck cancer: a review

    OpenAIRE

    Chisholm, E; Bapat, U.; Chisholm, C; Alusi, G.; Vassaux, G

    2007-01-01

    Gene therapy for cancer is a rapidly evolving field with head and neck squamous cell cancer being one of the more frequently targeted cancer types. The number of clinical trials in the UK is growing and there is already a commercially available agent in China. Various gene therapy strategies along with delivery mechanisms for targeting head and neck cancer are reviewed.

  13. Expression and Significance of MAGE Genes in Human Lung Cancer

    OpenAIRE

    Guangxu LI; Song, Pingping; ZHANG, BAIJIANG

    2013-01-01

    Lung cancer is one of the common malignancies with an extremely poor prognosis, because of the current diagnostic techniques are not easy to find micrometastases. Melanoma associated antigens genes (MAGE) are tumor specific antigen genes, closely related to the occurrence, development and prognosis of lung cancer. The research of MAGE genes provide a new direction for the diagnosis and treatment of lung cancer.

  14. Investigations of the potential schizophrenia susceptibility gene Kinase Interacting with Stathmin (KIS)

    OpenAIRE

    Bristow, Greg; Harrison, Paul J; Eastwood, Sharon L.

    2010-01-01

    Single nucleotide polymorphisms (SNPs) within the gene encoding the serine threonine kinase KIS (Kinase Interacting with Stathmin, also known as UHMK1) have recently been associated with schizophrenia. However, little is known about the neurobiology of KIS or the mechanisms through which disease-associated SNPs may increase susceptibility to schizophrenia. The studies presented in this thesis focus on the distribution of KIS and its mRNA, address the mechanisms through which KIS may confer su...

  15. SCAR Markers Assisted Selection for a Bentazon Susceptible Lethality Gene (ben) in Rice

    Institute of Scientific and Technical Information of China (English)

    XIANG; Tai-he; YANG; Jian-bo; YANG; Qian-jin; ZHU; Qi-sheng; LI; Li; HUANG; Da-nian

    2003-01-01

    In progenies resulting from crosses involving rice cultivar Norin 8m susceptible to bentazon as the donor of ben gene, SCARs tightly linked to ben were utilized for selection of ben. The homozygous and heterozygous genotypes with ben could be identified with the SCARs. The molecular markers offer a powerful tool for indirect selection of ben and can accelerate the introgression of ben into current rice cultivars.

  16. Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain

    OpenAIRE

    Richards, Alexander L.; Jones, Lesley; Moskvina, Valentina; Kirov, George; Gejman, Pablo V.; Levinson, Douglas F.; Sanders, Alan R; Purcell, Shaun; Visscher, Peter M.; Craddock, Nick; Owen, Michael J.; Holmans, Peter; O’Donovan, Michael C

    2011-01-01

    It is widely thought that alleles that influence susceptibility to common diseases, including schizophrenia, will frequently do so through effects on gene expression. Since only a small proportion of the genetic variance for schizophrenia has been attributed to specific loci, this remains an unproven hypothesis. The International Schizophrenia Consortium (ISC) recently reported a substantial polygenic contribution to that disorder, and that schizophrenia risk alleles are enriched among SNPs s...

  17. Brain and blood gene expression pathways associated with susceptibility to PTSD

    OpenAIRE

    Daskalakis, Nikolaos P.; Joseph Buxbaum; Flory, Janine D.; Guiqing Cai; Li Shen; Linda M. Bierer; Hagit Cohen; Rachel Yehuda

    2012-01-01

    Background : The identification of molecular post-traumatic stress disorder (PTSD) susceptibility pathways associated with different patterns of behavioral response to trauma is essential to an understanding of the neurobiology of PTSD and can pave the design for new treatments. Although several genes have been reported to be differentially expressed in PTSD, methodological constraints have limited the interpretation, for example, variation in the type or magnitude of trauma exposure, inter-i...

  18. Effects of disruption of heat shock genes on susceptibility of Escherichia coli to fluoroquinolones

    Directory of Open Access Journals (Sweden)

    Morioka Mizue

    2003-08-01

    Full Text Available Abstract Background It is well known that expression of certain bacterial genes responds rapidly to such stimuli as exposure to toxic chemicals and physical agents. It is generally believed that the proteins encoded in these genes are important for successful survival of the organism under the hostile conditions. Analogously, the proteins induced in bacterial cells exposed to antibiotics are believed to affect the organisms' susceptibility to these agents. Results We demonstrated that Escherichia coli cells exposed to levofloxacin (LVFX, a fluoroquinolone (FQ, induce the syntheses of heat shock proteins and RecA. To examine whether the heat shock proteins affect the bactericidal action of FQs, we constructed E. coli strains with mutations in various heat shock genes and tested their susceptibility to FQs. Mutations in dnaK, groEL, and lon increased this susceptibility; the lon mutant exhibited the greatest effects. The increased susceptibility of the lon mutant was corroborated by experiments in which the gene encoding the cell division inhibitor, SulA, was subsequently disrupted. SulA is induced by the SOS response and degraded by the Lon protease. The findings suggest that the hypersusceptibility of the lon mutant to FQs could be due to abnormally high levels of SulA protein resulting from the depletion of Lon and the continuous induction of the SOS response in the presence of FQs. Conclusion The present results show that the bactericidal action of FQs is moderately affected by the DnaK and GroEL chaperones and strongly affected by the Lon protease. FQs have contributed successfully to the treatment of various bacterial infections, but their widespread use and often misuse, coupled with emerging resistance, have gradually compromised their utility. Our results suggest that agents capable of inhibiting the Lon protease have potential for combination therapy with FQs.

  19. Novel single nucleotide polymorphisms in lactoferrin gene and their association with mastitis susceptibility in Holstein cattle

    OpenAIRE

    Ateya A.I.; El-Seady Y.Y.; Atwa S.M.; Merghani B.H.; Sayed N.A.

    2016-01-01

    Since lactoferrin is acute phase protein and has an exceptional role in defense mechanism of mammary gland, it is considered a candidate gene for mastitis susceptibility in dairy cattle. In this study, blood samples were collected for DNA extraction from fifty Holstein dairy cows in the third lactation season reared under Egyptian conditions assigned into three groups mastitis (n=15), subclinical mastitis (n=20) and healthy (n=15) based on California mastit...

  20. Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia.

    NARCIS (Netherlands)

    Lan, Q.; Hsiung, C.A.; Matsuo, K.; Hong, Y.C.; Seow, A.; Wang, Z.; Hosgood, H.D.; Chen, K.; Wang, J.C.; Chatterjee, N.; Hu, W.; Wong, M.P.; Zheng, W.; Caporaso, N.; Park, J.Y.; Chen, C.J.; Kim, Y.H.; Kim, Y.T.; Landi, M.T.; Shen, H.; Lawrence, C.; Burdett, L.; Yeager, M.; Yuenger, J.; Jacobs, K.B.; Chang, I.S.; Mitsudomi, T.; Kim, H.N.; Chang, G.C.; Bassig, B.A.; Tucker, M.; Wei, F.; Yin, Y.; Wu, C.; An, S.J.; Qian, B.; Lee, V.H.; Lu, D.; Liu, J.; Jeon, H.S.; Hsiao, C.F.; Sung, J.S.; Kim, J.H.; Gao, Y.T.; Tsai, Y.H.; Jung, Y.J.; Guo, H.; Hu, Z.; Hutchinson, A.; Wang, W.C.; Klein, R.; Chung, C.C.; Oh, I.J.; Chen, K.Y.; Berndt, S.I.; He, X.; Wu, W.; Chang, J.; Zhang, X.C.; Huang, M.S.; Zheng, H.; Wang, J.; Zhao, X.; Li, Y.; Choi, J.E.; Su, W.C.; Park, K.H.; Sung, S.W.; Shu, X.O.; Chen, Y.M.; Liu, L.; Kang, C.H.; Hu, L.; Chen, C.H.; Pao, W.; Kim, Y.C.; Yang, T.Y.; Xu, J.; Guan, P.; Tan, W.; Su, J.; Wang, C.L.; Li, H.; Sihoe, A.D.; Zhao, Z.; Chen, Y.; Choi, Y.Y.; Hung, J.Y.; Kim, J.S.; Yoon, H.I.; Cai, Q.; Lin, C.C.; Park, I.K.; Xu, P.; Dong, J.; Kim, C.; He, Q; Perng, R.P.; Kohno, T.; Kweon, S.S.; Chen, C.Y.; Vermeulen, R.; Wu, J.; Lim, W.Y.; Chen, K.C.; Chow, W.H.; Ji, B.T.; Chan, J.K.; Chu, M.; Li, Y.J.; Yokota, J.; Li, J.; Chen, H.; Xiang, Y.B.; Yu, C.J.; Kunitoh, H.; Wu, G.; Jin, L.; Lo, Y.L.; Shiraishi, K.; Chen, Y.H.; Lin, H.C.; Wu, T.; WU, Y.; Yang, P.C.; Zhou, B.; Shin, M.H.; Fraumeni, J.F.; Lin, D.; Chanock, S.J.; Rothman, N.

    2012-01-01

    To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland Ch

  1. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

    DEFF Research Database (Denmark)

    Al Olama, Ali Amin; Kote-Jarai, Zsofia; Berndt, Sonja I;

    2014-01-01

    Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer...

  2. From Identification to Characterization of the Multiple Sclerosis Susceptibility Gene CLEC16A

    Directory of Open Access Journals (Sweden)

    Tone Berge

    2013-02-01

    Full Text Available Multiple sclerosis (MS is an inflammatory, demyelinating disorder of the central nervous system that develops in genetically susceptible individuals, probably triggered by common environmental factors. Human leukocyte antigen (HLA loci were early shown to confer the strongest genetic associations in MS. Now, more than 50 non-HLA MS susceptibility loci are identified, of which the majority are located in immune-regulatory genes. Single nucleotide polymorphisms (SNPs in the C-type lectin-like domain family 16A (CLEC16A gene were among the first non-HLA genetic variants that were confirmed to be associated with MS. Fine-mapping has indicated a primary association in MS and also other autoimmune diseases to intronic CLEC16A SNPs. Here, we review the identification of MS susceptibility variants in the CLEC16A gene region, functional studies of the CLEC16A molecule and the recent progress in understanding the implications thereof for MS development. This may serve as an example of the importance for further molecular investigation of the loci identified in genetic studies, with the aim to translate this knowledge into the clinic.

  3. Analysis on the Susceptibility Genes in Two Chinese Pedigrees with Familial Parkinson's Disease

    OpenAIRE

    Changshui Xu; Jun Xu; Yanmin Zhang; Jianjun Ma; Hideshi Kawakami; Hirofumi Maruyama; Masaki Kamada

    2010-01-01

    Objective. To screen the susceptibility genes in Chinese pedigrees with early-onset familial Parkinson's disease (FPD). Methods. Fifty-one genomic DNA samples extracted from two Chinese pedigrees with FPD, the alpha-synuclein genes (SNCA), the leucine-rich repeat kinase 2(LRRK2), PINK1(PTEN-induced putative kinase 1), PARK7(Protein DJ1), PARK2(Parkinson juvenile disease protein 2), the glucocerebrosidase (GBA), and ATP(Ezrin-binding protein PACE-1), were sequenced by the use of polymerase ch...

  4. BoLA-DRB3 gene polymorphism and FMD resistance or susceptibility in Wanbei cattle

    OpenAIRE

    Wei LEI; Liang, Qinglong; Jing, Luo; Wang, Chengmin; Wu, Xiaobing; He, Hongxuan

    2012-01-01

    For the further characterization of foot-and-mouth disease virus (FMDV)-induced foot-and-mouth disease, we investigated the association between polymorphism of BoLA-DRB3 gene and FMD resistance/susceptibility of Wanbei cattle challenged with FMDV. One hundred cattle were challenged with FMDV and exon 2 of BoLA-DRB3 genes was amplified by hemi-nested polymerase chain reaction from asymptomatic animals and from animals with FMD. PCR products were characterized by the RFLP technique using restri...

  5. TOP2 gene disruption reduces drug susceptibility by increasing intracellular ergosterol biosynthesis in Candida albicans.

    Science.gov (United States)

    Zheng, Hao; Jiang, Yuan-Ying; Wang, Yan; Jia, Xin-Ming; Yan, Tian-Hua; Gao, Ping-Hui; Yan, Lan; Jiang, Ling-Huo; Ji, Hui; Cao, Yong-Bing

    2010-07-01

    In this study the role of the TOP2 gene in fungal drug susceptibility was investigated by disrupting and overexpressing the gene in Candida albicans. MIC determination and a spot assay showed that a top2Delta/Delta null mutant (strain T2bc) was more resistant to the antifungals tested than the wild-type (strain CAI4). Real-time RT-PCR and rhodamine 6G efflux examination showed that TOP2 did not influence the activity of drug efflux pumps. Sterol analysis with GC/high-resolution MS indicated that the intracellular ergosterol composition of the top2Delta/Delta mutant was significantly increased. Subsequently, fluorescence polarization measurements also revealed that Top2-deprived cells displayed a decrease in membrane fluidity, resulting in enhanced passive diffusion of the drugs. Quantitative real-time RT-PCR analysis further confirmed that the ERG11 gene, an essential gene in ergosterol biosynthesis, was upregulated. These results demonstrate a close relationship between the TOP2 gene and drug susceptibility in C. albicans. PMID:20223895

  6. 着色性干皮病基因组D和胞苷脱氨酶基因单核苷酸多态性与肺癌易感性的关系%Relationship between single nucleotide polymorphisms of xeroderma pigmentosum complementary group D and cytidine deaminase gene and susceptibility to lung cancer

    Institute of Scientific and Technical Information of China (English)

    周敏; 戎霞君; 高蓓莉; 丁永杰; 万欢英

    2011-01-01

    Objective To investigate the relationship between single nucleotide polymorphisms of xeroderma pigmentosum complementary group D ( XPD) and cytidine deaminase ( CDA) gene and susceptibility to lung cancer, and explore the influence of the interaction between smoking and gene polymorphisms on the risk of development of lung cancer. Methods Case-control study was performed on 103 patients with lung cancer and 103 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) was employed to determine the genotype distribution of XPD exon 10 G→A (Asp312Asn) and 23A→C (.Lys751Gln) and that of CDA exon 79A→ C ( Lys27Gln) and 208G→ A (Ala70 Thr). Results There was no significant difference in genotype distribution of XPD312 and XPD751 between two groups (P > 0.05). However, smoking in combination with mutation at locus 751 of XPD increased the risk of development of lung cancer (P =0.044), and the risk of development of lung cancer increased 6. 13 times with mutations at both loci 312 and 751 of XPD (P =0. 047). There was no significant difference in genotype distribution of CDA Lys27Gln and CDA Ala70 Thr between two groups (P > 0. 05). There was no significant difference in genotype distribution of XPD and CDA among different pathological types. Conclusion Smoking in combination with mutation at locus 751 of XPD may increase the risk of development of lung cancer, and mutation' at both loci 312 and locus 751 of XPD may increase the risk of development of lung cancer.%目的 探讨着色性干皮病基因组D( XPD)和胞苷脱氨酶(CDA)基因单核苷酸多态性与肺癌易感性及其病理类型的关系,并探讨吸烟与基因多态性的交互作用对肺癌发病风险的影响.方法 采用病例-对照研究方法纳入肺癌患者和健康对照者各103人,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法分析两组人群XPD基因外显子10G→A (Asp312Asn)、23 A→C( Lys751 Gln

  7. Association of CYP1A1 and GSTM1 Polymorphisms With Oral Cancer Susceptibility

    OpenAIRE

    Liu, Haitao; Jia, Jinlin; Mao, Xuemei; Lin, Zhiyong

    2015-01-01

    Abstract Our meta-analysis was aimed to evaluate the association of CYP1A1 and glutathione-S-transferase M1 (GSTM1) polymorphisms with oral cancer susceptibility. The related articles were searched in PubMed, Embase, and CNKI databases. Fifty eligible studies were included in our meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the relationship of CYP1A1 (rs4646903 and rs1048943) and GSTM1 polymorphisms with oral cancer risk. A random-effects model or...

  8. Identification of six new susceptibility loci for invasive epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Kuchenbaecker, Karoline B; Ramus, Susan J; Tyrer, Jonathan;

    2015-01-01

    Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed...... associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded...

  9. Genetic polymorphism of the OPG gene associated with breast cancer

    International Nuclear Information System (INIS)

    The receptor activator of NF-κB (RANK), its ligand (RANKL) and osteoprotegerin (OPG) have been reported to play a role in the pathophysiological bone turnover and in the pathogenesis of breast cancer. Based on this we investigated the role of single nucleotide polymorphisms (SNPs) within RANK, RANKL and OPG and their possible association to breast cancer risk. Genomic DNA was obtained from Caucasian participants consisting of 307 female breast cancer patients and 396 gender-matched healthy controls. We studied seven SNPs in the genes of OPG (rs3102735, rs2073618), RANK (rs1805034, rs35211496) and RANKL (rs9533156, rs2277438, rs1054016) using TaqMan genotyping assays. Statistical analyses were performed using the χ2-tests for 2 x 2 and 2 x 3 tables. The allelic frequencies (OR: 1.508 CI: 1.127-2.018, p=0.006) and the genotype distribution (p=0.019) of the OPG SNP rs3102735 differed significantly between breast cancer patients and healthy controls. The minor allele C and the corresponding homo- and heterozygous genotypes are more common in breast cancer patients (minor allele C: 18.4% vs. 13.0%; genotype CC: 3.3% vs. 1.3%; genotype CT: 30.3% vs. 23.5%). No significantly changed risk was detected in the other investigated SNPs. Additional analysis showed significant differences when comparing patients with invasive vs. non-invasive tumors (OPG rs2073618) as well as in terms of tumor localization (RANK rs35211496) and body mass index (RANKL rs9533156 and rs1054016). This is the first study reporting a significant association of the SNP rs3102735 (OPG) with the susceptibility to develop breast cancer in the Caucasian population

  10. Fine mapping of chromosome 15q25.1 lung cancer susceptibility in African-Americans

    OpenAIRE

    Hansen, Helen M.; Xiao, Yuanyuan; Rice, Terri; Bracci, Paige M.; Wrensch, Margaret R.; Sison, Jennette D.; Chang, Jeffery S.; Smirnov, Ivan V.; Patoka, Joseph; Seldin, Michael F; Quesenberry, Charles P.; Kelsey, Karl T.; Wiencke, John K.

    2010-01-01

    Several genome-wide association studies identified the chr15q25.1 region, which includes three nicotinic cholinergic receptor genes (CHRNA5-B4) and the cell proliferation gene (PSMA4), for its association with lung cancer risk in Caucasians. A haplotype and its tagging single nucleotide polymorphisms (SNPs) encompassing six genes from IREB2 to CHRNB4 were most strongly associated with lung cancer risk (OR = 1.3; P < 10−20). In order to narrow the region of association and identify potential c...

  11. Association of single nucleotide polymorphisms in Wnt signaling pathway genes with breast cancer in Saudi patients.

    Directory of Open Access Journals (Sweden)

    Mohammad Saud Alanazi

    Full Text Available Breast cancer is a complex heterogeneous disease involving genetic and epigenetic alterations in genes encoding proteins that are components of various signaling pathways. Candidate gene approach have identified association of genetic variants in the Wnt signaling pathway genes and increased susceptibility to several diseases including breast cancer. Due to the rarity of somatic mutations in key genes of Wnt pathway, we investigated the association of genetic variants in these genes with predisposition to breast cancers. We performed a case-control study to identify risk variants by examining 15 SNPs located in 8 genes associated with Wnt signaling. Genotypic analysis of individual locus showed statistically significant association of five SNPs located in β-catenin, AXIN2, DKK3, SFRP3 and TCF7L2 with breast cancers. Increased risk was observed only with the SNP in β-catenin while the other four SNPs conferred protection against breast cancers. Majority of these associations persisted after stratification of the cases based on estrogen receptor status and age of on-set of breast cancer. The rs7775 SNP in exon 6 of SFRP3 gene that codes for either arginine or glycine exhibited very strong association with breast cancer, even after Bonferroni's correction. Apart from these five variants, rs3923086 in AXIN2 and rs3763511 in DKK4 that did not show any association in the overall population were significantly associated with early on-set and estrogen receptor negative breast cancers, respectively. This is the first study to utilize pathway based approach to identify association of risk variants in the Wnt signaling pathway genes with breast cancers. Confirmation of our findings in larger populations of different ethnicities would provide evidence for the role of Wnt pathway as well as screening markers for early detection of breast carcinomas.

  12. Alcohol-related cancers and genetic susceptibility in Europe: the ARCAGE project: study samples and data collection.

    LENUS (Irish Health Repository)

    Lagiou, Pagona

    2009-02-01

    Cancers of the upper aerodigestive tract (UADT) include those of the oral cavity, pharynx (other than nasopharynx), larynx, and esophagus. Tobacco smoking and consumption of alcoholic beverages are established causes of UADT cancers, whereas reduced intake of vegetables and fruits are likely causes. The role of genetic predisposition and possible interactions of genetic with exogenous factors, however, have not been adequately studied. Moreover, the role of pattern of smoking and drinking, as well as the exact nature of the implicated dietary variables, has not been clarified. To address these issues, the International Agency for Research on Cancer initiated in 2002 the alcohol-related cancers and genetic susceptibility (ARCAGE) in Europe project, with the participation of 15 centers in 11 European countries. Information and biological data from a total of 2304 cases and 2227 controls have been collected and will be used in a series of analyses. A total of 166 single nucleotide polymorphisms of 76 genes are being studied for genetic associations with UADT cancers. We report here the methodology of the ARCAGE project, main demographic and lifestyle characteristics of the cases and controls, as well as the distribution of cases by histology and subsite. About 80% of cases were males and fewer than 20% of all cases occurred before the age of 50 years. Overall, the most common subsite was larynx, followed by oral cavity, oropharynx, esophagus and hypopharynx. Close to 90% of UADT cancers were squamous cell carcinomas. A clear preponderance of smokers and alcohol drinkers among UADT cases compared with controls was observed.

  13. Microarray Analysis of Gene Expression Profiles of Schistosoma japonicum Derived from Less-Susceptible Host Water Buffalo and Susceptible Host Goat

    OpenAIRE

    Jianmei Yang; Yang Hong; Chunxiu Yuan; Zhiqiang Fu; Yaojun Shi; Min Zhang; Liuhong Shen; Yanhui Han; Chuangang Zhu; Hao Li; Ke Lu; Jinming Liu; Xingang Feng; Jiaojiao Lin

    2013-01-01

    BACKGROUND: Water buffalo and goats are natural hosts for S. japonicum in endemic areas of China. The susceptibility of these two hosts to schistosome infection is different, as water buffalo are less conducive to S. japonicum growth and development. To identify genes that may affect schistosome development and survival, we compared gene expression profiles of schistosomes derived from these two natural hosts using high-throughput microarray technology. RESULTS: The worm recovery rate was low...

  14. Antimicrobial Susceptibility of Bordetella bronchiseptica Isolates from Swine and Companion Animals and Detection of Resistance Genes.

    Directory of Open Access Journals (Sweden)

    Sandra Prüller

    Full Text Available Bordetella bronchiseptica causes infections of the respiratory tract in swine and other mammals and is a precursor for secondary infections with Pasteurella multocida. Treatment of B. bronchiseptica infections is conducted primarily with antimicrobial agents. Therefore it is essential to get an overview of the susceptibility status of these bacteria. The aim of this study was to comparatively analyse broth microdilution susceptibility testing according to CLSI recommendations with an incubation time of 16 to 20 hours and a longer incubation time of 24 hours, as recently proposed to obtain more homogenous MICs. Susceptibility testing against a panel of 22 antimicrobial agents and two fixed combinations was performed with 107 porcine isolates from different farms and regions in Germany and 43 isolates obtained from companion animals in Germany and other European countries. Isolates with increased MICs were investigated by PCR assays for the presence of resistance genes. For ampicillin, all 107 porcine isolates were classified as resistant, whereas only a single isolate was resistant to florfenicol. All isolates obtained from companion animals showed elevated MICs for β-lactam antibiotics and demonstrated an overall low susceptibility to cephalosporines. Extension of the incubation time resulted in 1-2 dilution steps higher MIC50 values of porcine isolates for seven antimicrobial agents tested, while isolates from companion animals exhibited twofold higher MIC50/90 values only for tetracycline and cefotaxime. For three antimicrobial agents, lower MIC50 and MIC90 values were detected for both, porcine and companion animal isolates. Among the 150 isolates tested, the resistance genes blaBOR-1 (n = 147, blaOXA-2, (n = 4, strA and strB (n = 17, sul1 (n = 10, sul2 (n = 73, dfrA7 (n = 3 and tet(A (n = 8 were detected and a plasmid localisation was identified for several of the resistance genes.

  15. Comparison of gene activation by two TAL effectors from Xanthomonas axonopodis pv. manihotis reveals candidate host susceptibility genes in cassava.

    Science.gov (United States)

    Cohn, Megan; Morbitzer, Robert; Lahaye, Thomas; Staskawicz, Brian J

    2016-08-01

    Xanthomonas axonopodis pv. manihotis (Xam) employs transcription activator-like (TAL) effectors to promote bacterial growth and symptom formation during infection of cassava. TAL effectors are secreted via the bacterial type III secretion system into plant cells, where they are directed to the nucleus, bind DNA in plant promoters and activate the expression of downstream genes. The DNA-binding activity of TAL effectors is carried out by a central domain which contains a series of repeat variable diresidues (RVDs) that dictate the sequence of bound nucleotides. TAL14Xam668 promotes virulence in Xam strain Xam668 and has been shown to activate multiple cassava genes. In this study, we used RNA sequencing to identify the full target repertoire of TAL14Xam668 in cassava, which includes over 50 genes. A subset of highly up-regulated genes was tested for activation by TAL14CIO151 from Xam strain CIO151. Although TAL14CIO151 and TAL14Xam668 differ by only a single RVD, they display differential activation of gene targets. TAL14CIO151 complements the TAL14Xam668 mutant defect, implying that shared target genes are important for TAL14Xam668 -mediated disease susceptibility. Complementation with closely related TAL effectors is a novel approach to the narrowing down of biologically relevant susceptibility genes of TAL effectors with multiple targets. This study provides an example of how TAL effector target activation by two strains within a single species of Xanthomonas can be dramatically affected by a small change in RVD-nucleotide affinity at a single site, and reflects the parameters of RVD-nucleotide interaction determined using designer TAL effectors in transient systems. PMID:26575863

  16. Identifying Driver Genes in Cancer by Triangulating Gene Expression, Gene Location, and Survival Data

    Science.gov (United States)

    Rouam, Sigrid; Miller, Lance D; Karuturi, R Krishna Murthy

    2014-01-01

    Driver genes are directly responsible for oncogenesis and identifying them is essential in order to fully understand the mechanisms of cancer. However, it is difficult to delineate them from the larger pool of genes that are deregulated in cancer (ie, passenger genes). In order to address this problem, we developed an approach called TRIAngulating Gene Expression (TRIAGE through clinico-genomic intersects). Here, we present a refinement of this approach incorporating a new scoring methodology to identify putative driver genes that are deregulated in cancer. TRIAGE triangulates – or integrates – three levels of information: gene expression, gene location, and patient survival. First, TRIAGE identifies regions of deregulated expression (ie, expression footprints) by deriving a newly established measure called the Local Singular Value Decomposition (LSVD) score for each locus. Driver genes are then distinguished from passenger genes using dual survival analyses. Incorporating measurements of gene expression and weighting them according to the LSVD weight of each tumor, these analyses are performed using the genes located in significant expression footprints. Here, we first use simulated data to characterize the newly established LSVD score. We then present the results of our application of this refined version of TRIAGE to gene expression data from five cancer types. This refined version of TRIAGE not only allowed us to identify known prominent driver genes, such as MMP1, IL8, and COL1A2, but it also led us to identify several novel ones. These results illustrate that TRIAGE complements existing tools, allows for the identification of genes that drive cancer and could perhaps elucidate potential future targets of novel anticancer therapeutics. PMID:25949096

  17. Analysis of large deletions in BRCA1, BRCA2 and PALB2 genes in Finnish breast and ovarian cancer families

    Directory of Open Access Journals (Sweden)

    Sólyom Szilvia

    2008-05-01

    Full Text Available Abstract Background BRCA1 and BRCA2 are the two most important genes associated with familial breast and ovarian cancer susceptibility. In addition, PALB2 has recently been identified as a breast cancer susceptibility gene in several populations. Here we have evaluated whether large genomic rearrangement in these genes could explain some of Finnish breast and/or ovarian cancer families. Methods Altogether 61 index patients of Northern Finnish breast and/or ovarian cancer families were analyzed by Multiplex ligation-dependent probe amplification (MLPA method in order to identify exon deletions and duplications in BRCA1, BRCA2 and PALB2. The families have been comprehensively screened for germline mutation in these genes by conventional methods of mutation analysis and were found negative. Results We identified one large deletion in BRCA1, deleting the most part of the gene (exon 1A-13 in one family with family history of ovarian cancer. No large genomic rearrangements were identified in either BRCA2 or PALB2. Conclusion In Finland, women eligible for BRCA1 or BRCA2 mutation screening, when found negative, could benefit from screening for large genomic rearrangements at least in BRCA1. On the contrary, the genomic rearrangements in PALB2 seem not to contribute to the hereditary breast cancer susceptibility.

  18. Analysis of large deletions in BRCA1, BRCA2 and PALB2 genes in Finnish breast and ovarian cancer families

    International Nuclear Information System (INIS)

    BRCA1 and BRCA2 are the two most important genes associated with familial breast and ovarian cancer susceptibility. In addition, PALB2 has recently been identified as a breast cancer susceptibility gene in several populations. Here we have evaluated whether large genomic rearrangement in these genes could explain some of Finnish breast and/or ovarian cancer families. Altogether 61 index patients of Northern Finnish breast and/or ovarian cancer families were analyzed by Multiplex ligation-dependent probe amplification (MLPA) method in order to identify exon deletions and duplications in BRCA1, BRCA2 and PALB2. The families have been comprehensively screened for germline mutation in these genes by conventional methods of mutation analysis and were found negative. We identified one large deletion in BRCA1, deleting the most part of the gene (exon 1A-13) in one family with family history of ovarian cancer. No large genomic rearrangements were identified in either BRCA2 or PALB2. In Finland, women eligible for BRCA1 or BRCA2 mutation screening, when found negative, could benefit from screening for large genomic rearrangements at least in BRCA1. On the contrary, the genomic rearrangements in PALB2 seem not to contribute to the hereditary breast cancer susceptibility

  19. Gene expression profiles in irradiated cancer cells

    International Nuclear Information System (INIS)

    Knowledge of the molecular and genetic mechanisms underlying cellular response to radiation may provide new avenues to develop innovative predictive tests of radiosensitivity of tumours and normal tissues and to improve individual therapy. Nowadays very few studies describe molecular changes induced by hadrontherapy treatments, therefore this field has to be explored and clarified. High-throughput methodologies, such as DNA microarray, allow us to analyse mRNA expression of thousands of genes simultaneously in order to discover new genes and pathways as targets of response to hadrontherapy. Our aim is to elucidate the molecular networks involved in the sensitivity/resistance of cancer cell lines subjected to hadrontherapy treatments with a genomewide approach by using cDNA microarray technology to identify gene expression profiles and candidate genes responsible of differential cellular responses

  20. Whole-exome sequencing for the identification of susceptibility genes of Kashin-Beck disease.

    Directory of Open Access Journals (Sweden)

    Zhenxing Yang

    Full Text Available OBJECTIVE: To identify and investigate the susceptibility genes of Kashin-Beck disease (KBD in Chinese population. METHODS: Whole-exome capturing and sequencing technology was used for the detection of genetic variations in 19 individuals from six families with high incidence of KBD. A total of 44 polymorphisms from 41 genes were genotyped from a total of 144 cases and 144 controls by using MassARRAY under the standard protocol from Sequenom. Association was applied on the data by using PLINK1.07. RESULTS: In the sequencing stage, each sample showed approximately 70-fold coverage, thus covering more than 99% of the target regions. Among the single nucleotide polymorphisms (SNPs used in the transmission disequilibrium test, 108 had a p-value of <0.01, whereas 1056 had a p-value of <0.05. Kyoto Encyclopedia of Genes and Genomes(KEGG pathway analysis indicates that these SNPs focus on three major pathways: regulation of actin cytoskeleton, focal adhesion, and metabolic pathways. In the validation stage, single locus effects revealed that two of these polymorphisms (rs7745040 and rs9275295 in the human leukocyte antigen (HLA-DRB1 gene and one polymorphism (rs9473132 in CD2-associated protein (CD2AP gene have a significant statistical association with KBD. CONCLUSIONS: HLA-DRB1 and CD2AP gene were identified to be among the susceptibility genes of KBD, thus supporting the role of the autoimmune response in KBD and the possibility of shared etiology between osteoarthritis, rheumatoid arthritis, and KBD.

  1. Transcription factor SP4 is a susceptibility gene for bipolar disorder.

    Directory of Open Access Journals (Sweden)

    Xianjin Zhou

    Full Text Available The Sp4 transcription factor plays a critical role for both development and function of mouse hippocampus. Reduced expression of the mouse Sp4 gene results in a variety of behavioral abnormalities relevant to human psychiatric disorders. The human SP4 gene is therefore examined for its association with both bipolar disorder and schizophrenia in European Caucasian and Chinese populations respectively. Out of ten SNPs selected from human SP4 genomic locus, four displayed significant association with bipolar disorder in European Caucasian families (rs12668354, p = 0.022; rs12673091, p = 0.0005; rs3735440, p = 0.019; rs11974306, p = 0.018. To replicate the genetic association, the same set of SNPs was examined in a Chinese bipolar case control sample. Four SNPs displayed significant association (rs40245, p = 0.009; rs12673091, p = 0.002; rs1018954, p = 0.001; rs3735440, p = 0.029, and two of them (rs12673091, rs3735440 were shared with positive SNPs from European Caucasian families. Considering the genetic overlap between bipolar disorder and schizophrenia, we extended our studies in Chinese trios families for schizophrenia. The SNP7 (rs12673091, p = 0.012 also displayed a significant association. The SNP7 (rs12673091 was therefore significantly associated in all three samples, and shared the same susceptibility allele (A across all three samples. On the other hand, we found a gene dosage effect for mouse Sp4 gene in the modulation of sensorimotor gating, a putative endophenotype for both schizophrenia and bipolar disorder. The deficient sensorimotor gating in Sp4 hypomorphic mice was partially reversed by the administration of dopamine D2 antagonist or mood stabilizers. Both human genetic and mouse pharmacogenetic studies support Sp4 gene as a susceptibility gene for bipolar disorder or schizophrenia. The studies on the role of Sp4 gene in hippocampal development may provide novel insights for the contribution of hippocampal abnormalities in these

  2. Variants of the SFTPA1 and SFTPA2 genes and susceptibility to tuberculosis in Ethiopia.

    Science.gov (United States)

    Malik, S; Greenwood, C M T; Eguale, T; Kifle, A; Beyene, J; Habte, A; Tadesse, A; Gebrexabher, H; Britton, S; Schurr, E

    2006-02-01

    Lungs are the central organ affected and targeted by Mycobacterium tuberculosis and immune processes in the lung are of critical importance in the pathogenesis of tuberculosis. A major lung defense against invading pathogens is provided by surfactant protein A, a multi-chain protein encoded by the SFTPA1 and SFTPA2 genes. Here, we investigated polymorphisms in the SFTPA1 and SFTPA2 genes for association with tuberculosis in 181 Ethiopian families comprising 226 tuberculosis cases. Four polymorphisms, SFTPA1 307A, SFTPA1 776T, SFTPA2 355C, and SFTPA2 751C, were associated with tuberculosis (P=0.00008; P=0.019, P=0.029 and P=0.042, respectively). Additional subgroup analysis in male, female and more severely affected patients provided evidence for SFTPA1/2-covariate interaction. Finally, out of five intragenic haplotypes identified in the SFTPA1 gene and nine identified in the SFTPA2 gene, 1A(3) was most significantly associated with tuberculosis susceptibility (P=0.026). These findings suggest that SFTPA1 and SFTPA2 modify the risk of tuberculosis susceptibility and that this risk is influenced by additional covariates. PMID:16292672

  3. Lung Cancer Susceptibility and hOGG1 Ser326Cys Polymorphism: A Meta-Analysis

    International Nuclear Information System (INIS)

    Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly being studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. In this study, we tried to assess reported studies of association between polymorphism of human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys and lung cancer. We conducted MEDLINE, Current Contents and Web of Science searches using 'hOGG1', 'lung cancer' and 'polymorphism' as keywords to search for papers published (from January 1995 through August 2010). Data were combined using both a fixed effects (the inverse variance-weighted method) and a random effects (DerSimonian and Laird method) models. The Cochran Q test was used for the assessment of heterogeneity. Publication bias was assessed by both Begg’s and Egger’s tests. We identified 20 case-control studies in 21 different ethnic populations. As two studies were not in the Hardy-Weinberg equilibrium, 18 case-control studies in 19 different ethnic populations (7,792 cases and 9,358 controls) were included in our meta-analysis. Summary frequencies of the Cys allele among Caucasians and Asians based on the random effects model were 20.9% (95% confidence interval (CI) = 18.9–22.9) and 46.1% (95% CI = 40.2–52.0), respectively. The distribution of the Cys allele was significantly different between Asians and Caucasians (P < 0.001). The Cys/Cys genotype was significantly associated with lung cancer risk in Asian populations (odds ratio = 1.27, 95% CI = 1.09–1.48) but not in Caucasian populations. This ethnic difference in lung cancer risk may be due to environmental factors such as cigarette smoking and dietary factors. Although the summary risk for developing lung cancer may not be large, lung cancer is such a common malignancy that even a small increase

  4. Linkage analysis in a large Swedish family supports the presence of a susceptibility locus for adenoma and colorectal cancer on chromosome 9q22.32-31.1

    DEFF Research Database (Denmark)

    Skoglund, J; Djureinovic, T; Zhou, X-L;

    2006-01-01

    dominantly inherited colorectal cancer risk. Recently, a locus on chromosome 9q22.2-31.2 was identified by linkage analysis in sib pairs with colorectal cancer or adenoma. METHODS: Linkage analysis for the suggested locus on chromosome 9 was carried out in an extended Swedish family. This family had...... previously been investigated but following the identification of adenomas in several previously unaffected family members, these subjects were now considered to be gene carriers. RESULTS: In the present study, we found linkage of adenoma and colorectal cancer to chromosome 9q22.32-31.1 with a multipoint LOD...... score of 2.4. We were also able to define the region for this locus to 7.9 cM between the markers D9S280 and D9S277. CONCLUSIONS: Our result supports the presence of a susceptibility locus predisposing to adenoma and colorectal cancer in this chromosomal region....

  5. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer.

    Science.gov (United States)

    Couch, Fergus J; Kuchenbaecker, Karoline B; Michailidou, Kyriaki; Mendoza-Fandino, Gustavo A; Nord, Silje; Lilyquist, Janna; Olswold, Curtis; Hallberg, Emily; Agata, Simona; Ahsan, Habibul; Aittomäki, Kristiina; Ambrosone, Christine; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K; Arver, Brita; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Beckmann, Lars; Beckmann, Matthias W; Benitez, Javier; Blank, Stephanie V; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Buys, Saundra S; Caldes, Trinidad; Caligo, Maria A; Canzian, Federico; Carpenter, Jane; Chang-Claude, Jenny; Chanock, Stephen J; Chung, Wendy K; Claes, Kathleen B M; Cox, Angela; Cross, Simon S; Cunningham, Julie M; Czene, Kamila; Daly, Mary B; Damiola, Francesca; Darabi, Hatef; de la Hoya, Miguel; Devilee, Peter; Diez, Orland; Ding, Yuan C; Dolcetti, Riccardo; Domchek, Susan M; Dorfling, Cecilia M; Dos-Santos-Silva, Isabel; Dumont, Martine; Dunning, Alison M; Eccles, Diana M; Ehrencrona, Hans; Ekici, Arif B; Eliassen, Heather; Ellis, Steve; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Försti, Asta; Fostira, Florentia; Foulkes, William D; Friebel, Tara; Friedman, Eitan; Frost, Debra; Gabrielson, Marike; Gammon, Marilie D; Ganz, Patricia A; Gapstur, Susan M; Garber, Judy; Gaudet, Mia M; Gayther, Simon A; Gerdes, Anne-Marie; Ghoussaini, Maya; Giles, Graham G; Glendon, Gord; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Greene, Mark H; Gronwald, Jacek; Guénel, Pascal; Gunter, Marc; Haeberle, Lothar; Haiman, Christopher A; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Healey, Sue; Heikkinen, Tuomas; Henderson, Brian E; Herzog, Josef; Hogervorst, Frans B L; Hollestelle, Antoinette; Hooning, Maartje J; Hoover, Robert N; Hopper, John L; Humphreys, Keith; Hunter, David J; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Jones, Michael; Kabisch, Maria; Kar, Siddhartha; Karlan, Beth Y; Khan, Sofia; Khaw, Kay-Tee; Kibriya, Muhammad G; Knight, Julia A; Ko, Yon-Dschun; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kwong, Ava; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Lee, Eunjung; Le Marchand, Loic; Lester, Jenny; Lindblom, Annika; Lindor, Noralane; Lindstrom, Sara; Liu, Jianjun; Long, Jirong; Lubinski, Jan; Mai, Phuong L; Makalic, Enes; Malone, Kathleen E; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Martens, John W M; McGuffog, Lesley; Meindl, Alfons; Miller, Austin; Milne, Roger L; Miron, Penelope; Montagna, Marco; Mazoyer, Sylvie; Mulligan, Anna M; Muranen, Taru A; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nordestgaard, Børge G; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Osorio, Ana; Park, Sue K; Peeters, Petra H; Peissel, Bernard; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M; Pilarski, Robert; Poppe, Bruce; Pylkäs, Katri; Radice, Paolo; Rahman, Nazneen; Rantala, Johanna; Rappaport, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Romieu, Isabelle; Rudolph, Anja; Rutgers, Emiel J; Sanchez, Maria-Jose; Santella, Regina M; Sawyer, Elinor J; Schmidt, Daniel F; Schmidt, Marjanka K; Schmutzler, Rita K; Schumacher, Fredrick; Scott, Rodney; Senter, Leigha; Sharma, Priyanka; Simard, Jacques; Singer, Christian F; Sinilnikova, Olga M; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Swerdlow, Anthony; Szabo, Csilla I; Tamimi, Rulla; Tapper, William; Teixeira, Manuel R; Teo, Soo-Hwang; Terry, Mary B; Thomassen, Mads; Thompson, Deborah; Tihomirova, Laima; Toland, Amanda E; Tollenaar, Robert A E M; Tomlinson, Ian; Truong, Thérèse; Tsimiklis, Helen; Teulé, Alex; Tumino, Rosario; Tung, Nadine; Turnbull, Clare; Ursin, Giski; van Deurzen, Carolien H M; van Rensburg, Elizabeth J; Varon-Mateeva, Raymonda; Wang, Zhaoming; Wang-Gohrke, Shan; Weiderpass, Elisabete; Weitzel, Jeffrey N; Whittemore, Alice; Wildiers, Hans; Winqvist, Robert; Yang, Xiaohong R; Yannoukakos, Drakoulis; Yao, Song; Zamora, M Pilar; Zheng, Wei; Hall, Per; Kraft, Peter; Vachon, Celine; Slager, Susan; Chenevix-Trench, Georgia; Pharoah, Paul D P; Monteiro, Alvaro A N; García-Closas, Montserrat; Easton, Douglas F; Antoniou, Antonis C

    2016-01-01

    Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction. PMID:27117709

  6. P2X7 receptor-deficient mice are susceptible to bone cancer pain

    DEFF Research Database (Denmark)

    Hansen, Rikke Rie; Nielsen, Christian K.; Nasser, Arafat;

    2011-01-01

    The purinergic P2X7 receptor is implicated in both neuropathic and inflammatory pain, and has been suggested as a possible target in pain treatment. However, the specific role of the P2X7 receptor in bone cancer pain is unknown. We demonstrated that BALB/cJ P2X7 receptor knockout (P2X7R KO) mice...... were susceptible to bone cancer pain and moreover had an earlier onset of pain-related behaviours compared with cancer-bearing, wild-type mice. Furthermore, acute treatment with the selective P2X7 receptor antagonist, A-438079, failed to alleviate pain-related behaviours in models of bone cancer pain...... with and without astrocyte activation (BALB/cJ or C3H mice inoculated with 4T1 mammary cancer cells or NCTC 2472 osteosarcoma cells, respectively), suggesting that astrocytic P2X7 receptors play a negligible role in bone cancer pain. The results support the hypothesis that bone cancer pain is a...

  7. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

    Science.gov (United States)

    Couch, Fergus J.; Kuchenbaecker, Karoline B.; Michailidou, Kyriaki; Mendoza-Fandino, Gustavo A.; Nord, Silje; Lilyquist, Janna; Olswold, Curtis; Hallberg, Emily; Agata, Simona; Ahsan, Habibul; Aittomäki, Kristiina; Ambrosone, Christine; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K.; Arver, Brita; Barile, Monica; Barkardottir, Rosa B.; Barrowdale, Daniel; Beckmann, Lars; Beckmann, Matthias W.; Benitez, Javier; Blank, Stephanie V.; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Buys, Saundra S.; Caldes, Trinidad; Caligo, Maria A.; Canzian, Federico; Carpenter, Jane; Chang-Claude, Jenny; Chanock, Stephen J.; Chung, Wendy K.; Claes, Kathleen B. M.; Cox, Angela; Cross, Simon S.; Cunningham, Julie M.; Czene, Kamila; Daly, Mary B.; Damiola, Francesca; Darabi, Hatef; de la Hoya, Miguel; Devilee, Peter; Diez, Orland; Ding, Yuan C.; Dolcetti, Riccardo; Domchek, Susan M.; Dorfling, Cecilia M.; dos-Santos-Silva, Isabel; Dumont, Martine; Dunning, Alison M.; Eccles, Diana M.; Ehrencrona, Hans; Ekici, Arif B.; Eliassen, Heather; Ellis, Steve; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Försti, Asta; Fostira, Florentia; Foulkes, William D.; Friebel, Tara; Friedman, Eitan; Frost, Debra; Gabrielson, Marike; Gammon, Marilie D.; Ganz, Patricia A.; Gapstur, Susan M.; Garber, Judy; Gaudet, Mia M.; Gayther, Simon A.; Gerdes, Anne-Marie; Ghoussaini, Maya; Giles, Graham G.; Glendon, Gord; Godwin, Andrew K.; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Greene, Mark H.; Gronwald, Jacek; Guénel, Pascal; Gunter, Marc; Haeberle, Lothar; Haiman, Christopher A.; Hamann, Ute; Hansen, Thomas V. O.; Hart, Steven; Healey, Sue; Heikkinen, Tuomas; Henderson, Brian E.; Herzog, Josef; Hogervorst, Frans B. L.; Hollestelle, Antoinette; Hooning, Maartje J.; Hoover, Robert N.; Hopper, John L.; Humphreys, Keith; Hunter, David J.; Huzarski, Tomasz; Imyanitov, Evgeny N.; Isaacs, Claudine; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M.; Jones, Michael; Kabisch, Maria; Kar, Siddhartha; Karlan, Beth Y.; Khan, Sofia; Khaw, Kay-Tee; Kibriya, Muhammad G.; Knight, Julia A.; Ko, Yon-Dschun; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kwong, Ava; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Lee, Eunjung; Le Marchand, Loic; Lester, Jenny; Lindblom, Annika; Lindor, Noralane; Lindstrom, Sara; Liu, Jianjun; Long, Jirong; Lubinski, Jan; Mai, Phuong L.; Makalic, Enes; Malone, Kathleen E.; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Martens, John W. M.; McGuffog, Lesley; Meindl, Alfons; Miller, Austin; Milne, Roger L.; Miron, Penelope; Montagna, Marco; Mazoyer, Sylvie; Mulligan, Anna M.; Muranen, Taru A.; Nathanson, Katherine L.; Neuhausen, Susan L.; Nevanlinna, Heli; Nordestgaard, Børge G.; Nussbaum, Robert L.; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Osorio, Ana; Park, Sue K.; Peeters, Petra H.; Peissel, Bernard; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M.; Pilarski, Robert; Poppe, Bruce; Pylkäs, Katri; Radice, Paolo; Rahman, Nazneen; Rantala, Johanna; Rappaport, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Romieu, Isabelle; Rudolph, Anja; Rutgers, Emiel J.; Sanchez, Maria-Jose; Santella, Regina M.; Sawyer, Elinor J.; Schmidt, Daniel F.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Schumacher, Fredrick; Scott, Rodney; Senter, Leigha; Sharma, Priyanka; Simard, Jacques; Singer, Christian F.; Sinilnikova, Olga M.; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Swerdlow, Anthony; Szabo, Csilla I.; Tamimi, Rulla; Tapper, William; Teixeira, Manuel R.; Teo, Soo-Hwang; Terry, Mary B.; Thomassen, Mads; Thompson, Deborah; Tihomirova, Laima; Toland, Amanda E.; Tollenaar, Robert A. E. M.; Tomlinson, Ian; Truong, Thérèse; Tsimiklis, Helen; Teulé, Alex; Tumino, Rosario; Tung, Nadine; Turnbull, Clare; Ursin, Giski; van Deurzen, Carolien H. M.; van Rensburg, Elizabeth J.; Varon-Mateeva, Raymonda; Wang, Zhaoming; Wang-Gohrke, Shan; Weiderpass, Elisabete; Weitzel, Jeffrey N.; Whittemore, Alice; Wildiers, Hans; Winqvist, Robert; Yang, Xiaohong R.; Yannoukakos, Drakoulis; Yao, Song; Zamora, M Pilar; Zheng, Wei; Hall, Per; Kraft, Peter; Vachon, Celine; Slager, Susan; Chenevix-Trench, Georgia; Pharoah, Paul D. P.; Monteiro, Alvaro A. N.; García-Closas, Montserrat; Easton, Douglas F.; Antoniou, Antonis C.

    2016-01-01

    Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction. PMID:27117709

  8. A comprehensive review on host genetic susceptibility to human papillomavirus infection and progression to cervical cancer

    Directory of Open Access Journals (Sweden)

    Koushik Chattopadhyay

    2011-01-01

    Full Text Available Cervical cancer is the second most common cancer in women worldwide. This is caused by oncogenic types of human papillomavirus (HPV infection. Although large numbers of young sexually active women get HPV-infected, only a small fraction develop cervical cancer. This points to different co-factors for regression of HPV infection or progression to cervical cancer. Host genetic factors play an important role in the outcome of such complex or multifactor diseases such as cervical cancer and are also known to regulate the rate of disease progression. The aim of this review is to compile the advances in the field of host genetics of cervical cancer. MEDLINE database was searched using the terms, ′HPV′, ′cervical′, ′CIN′, ′polymorphism(s′, ′cervical′ + FNx01the name of the geneFNx01 and ′HPV′ + FNx01the name of the geneFNx01. This review focuses on the major host genes reported to affect the progression to cervical cancer in HPV infected individuals.

  9. Absence of linkage between MHC and a gene involved in susceptibility to human schistosomiasis

    Directory of Open Access Journals (Sweden)

    Chiarella J.M.

    1998-01-01

    Full Text Available Six hundred million people are at risk of infection by Schistosoma mansoni. MHC haplotypes have been reported to segregate with susceptibility to schistosomiasis in murine models. In humans, a major gene related to susceptibility/resistance to infection by S. mansoni (SM1 and displaying the mean fecal egg count as phenotype was detected by segregation analysis. This gene displayed a codominant mode of inheritance with an estimated frequency of 0.20-0.25 for the deleterious allele and accounted for more than 50% of the variance of infection levels. To determine if the SM1 gene segregates with the human MHC chromosomal region, we performed a linkage study by the lod score method. We typed for HLA-A, B, C, DR and DQ antigens in 11 informative families from an endemic area for schistosomiasis in Bahia, Brazil, by the microlymphocytotoxicity technique. HLA-DR typing by the polymerase chain reaction with sequence-specific primers (PCR-SSP and HLA-DQ were confirmed by PCR-sequence-specific oligonucleotide probes (PCR-SSOP. The lod scores for the different q values obtained clearly indicate that there is no physical linkage between HLA and SM1 genes. Thus, susceptibility or resistance to schistosomiasis, as defined by mean fecal egg count, is not primarily dependent on the host's HLA profile. However, if the HLA molecule plays an important role in specific immune responses to S. mansoni, this may involve the development of the different clinical aspects of the disease such as granuloma formation and development of hepatosplenomegaly.

  10. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

    Science.gov (United States)

    Michailidou, Kyriaki; Beesley, Jonathan; Lindstrom, Sara; Canisius, Sander; Dennis, Joe; Lush, Michael; Maranian, Mel J; Bolla, Manjeet K; Wang, Qin; Shah, Mitul; Perkins, Barbara J; Czene, Kamila; Eriksson, Mikael; Darabi, Hatef; Brand, Judith S; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Nielsen, Sune F; Rahman, Nazneen; Turnbull, Clare; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; dos-Santos-Silva, Isabel; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Eilber, Ursula; Behrens, Sabine; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Aaltonen, Kirsimari; Ahsan, Habibul; Kibriya, Muhammad G; Whittemore, Alice S; John, Esther M; Malone, Kathleen E; Gammon, Marilie D; Santella, Regina M; Ursin, Giske; Makalic, Enes; Schmidt, Daniel F; Casey, Graham; Hunter, David J; Gapstur, Susan M; Gaudet, Mia M; Diver, W Ryan; Haiman, Christopher A; Schumacher, Fredrick; Henderson, Brian E; Le Marchand, Loic; Berg, Christine D; Chanock, Stephen; Figueroa, Jonine; Hoover, Robert N; Lambrechts, Diether; Neven, Patrick; Wildiers, Hans; van Limbergen, Erik; Schmidt, Marjanka K; Broeks, Annegien; Verhoef, Senno; Cornelissen, Sten; Couch, Fergus J; Olson, Janet E; Hallberg, Emily; Vachon, Celine; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A; van der Luijt, Rob B; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Yoo, Keun-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Guénel, Pascal; Truong, Thérèse; Mulot, Claire; Sanchez, Marie; Burwinkel, Barbara; Marme, Frederik; Surowy, Harald; Sohn, Christof; Wu, Anna H; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O; González-Neira, Anna; Benitez, Javier; Zamora, M Pilar; Perez, Jose Ignacio Arias; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S; Reed, Malcolm WR; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Lindblom, Annika; Margolin, Sara; Teo, Soo Hwang; Yip, Cheng Har; Taib, Nur Aishah Mohd; TAN, Gie-Hooi; Hooning, Maartje J; Hollestelle, Antoinette; Martens, John WM; Collée, J Margriet; Blot, William; Signorello, Lisa B; Cai, Qiuyin; Hopper, John L; Southey, Melissa C; Tsimiklis, Helen; Apicella, Carmel; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Hou, Ming-Feng; Kristensen, Vessela N; Nord, Silje; Alnaes, Grethe I Grenaker; Giles, Graham G; Milne, Roger L; McLean, Catriona; Canzian, Federico; Trichopoulos, Dmitrios; Peeters, Petra; Lund, Eiliv; Sund, Malin; Khaw, Kay-Tee; Gunter, Marc J; Palli, Domenico; Mortensen, Lotte Maxild; Dossus, Laure; Huerta, Jose-Maria; Meindl, Alfons; Schmutzler, Rita K; Sutter, Christian; Yang, Rongxi; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Chan, Ching Wan; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Haeberle, Lothar; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J; Swerdlow, Anthony J; Brinton, Louise; Garcia-Closas, Montserrat; Zheng, Wei; Halverson, Sandra L; Shrubsole, Martha; Long, Jirong; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bernard, Loris; Bogdanova, Natalia V; Dörk, Thilo; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Devilee, Peter; Tollenaar, Robert AEM; Seynaeve, Caroline; Van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Huzarski, Tomasz; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Kabisch, Maria; Torres, Diana; Neuhausen, Susan L; Anton-Culver, Hoda; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Simard, Jacques; Pharoah, Paul PDP; Kraft, Peter; Dunning, Alison M; Chenevix-Trench, Georgia; Hall, Per; Easton, Douglas F

    2015-01-01

    Genome wide association studies (GWAS) and large scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ~14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS comprising of 15,748 breast cancer cases and 18,084 controls, and 46,785 cases and 42,892 controls from 41 studies genotyped on a 200K custom array (iCOGS). Analyses were restricted to women of European ancestry. Genotypes for more than 11M SNPs were generated by imputation using the 1000 Genomes Project reference panel. We identified 15 novel loci associated with breast cancer at P<5×10−8. Combining association analysis with ChIP-Seq data in mammary cell lines and ChIA-PET chromatin interaction data in ENCODE, we identified likely target genes in two regions: SETBP1 on 18q12.3 and RNF115 and PDZK1 on 1q21.1. One association appears to be driven by an amino-acid substitution in EXO1. PMID:25751625

  11. Association of cellular and molecular responses in the rat mammary gland to 17β-estradiol with susceptibility to mammary cancer

    International Nuclear Information System (INIS)

    We are using ACI and BN rats, which differ markedly in their susceptibility to 17β-estradiol (E2)-induced mammary cancer, to identify genetic variants and environmental factors that determine mammary cancer susceptibility. The objective of this study was to characterize the cellular and molecular responses to E2 in the mammary glands of ACI and BN rats to identify qualitative and quantitative phenotypes that associate with and/or may confer differences in susceptibility to mammary cancer. Female ACI and BN rats were treated with E2 for 1, 3 or 12 weeks. Mammary gland morphology and histology were examined by whole mount and hematoxylin and eosin (H&E) staining. Cell proliferation and epithelial density were evaluated by quantitative immunohistochemistry. Apoptosis was evaluated by quantitative western blotting and flow cytometry. Mammary gland differentiation was examined by immunohistochemistry. Gene expression was evaluated by microarray, qRT-PCR and quantitative western blotting assays. Extracellular matrix (ECM) associated collagen was evaluated by Picrosirius Red staining and Second Harmonic Generation (SHG) microscopy. The luminal epithelium of ACI rats exhibited a rapid and sustained proliferative response to E2. By contrast, the proliferative response exhibited by the mammary epithelium of BN rats was restrained and transitory. Moreover, the epithelium of BN rats appeared to undergo differentiation in response to E2, as evidenced by production of milk proteins as well as luminal ectasia and associated changes in the ECM. Marked differences in expression of genes that encode proteins with well-defined roles in mammary gland development (Pgr, Wnt4, Tnfsf11, Prlr, Stat5a, Areg, Gata3), differentiation and milk production (Lcn2, Spp1), regulation of extracellular environment (Mmp7, Mmp9), and cell-cell or cell-ECM interactions (Cd44, Cd24, Cd52) were observed. We propose that these cellular and molecular phenotypes are heritable and may underlie, at least in

  12. Relative susceptibilities of male germ cells to genetic defects induced by cancer chemotherapies

    Energy Technology Data Exchange (ETDEWEB)

    Wyrobek, A J; Schmid, T E; Marchetti, F

    2004-06-15

    Some chemotherapy regimens include agents that are mutagenic or clastogenic in model systems. This raises concerns that cancer survivors, who were treated before or during their reproductive years, may be at increased risks for abnormal reproductive outcomes. However, the available data from offspring of cancer survivors are limited, representing diverse cancers, therapies, time-to-pregnancies, and reproductive outcomes. Rodent breeding data after paternal exposures to individual chemotherapeutic agents illustrate the complexity of factors that influence the risk for transmitted genetic damage including agent, dose, endpoint, and the germ-cell susceptibility profiles that vary across agents. Direct measurements of chromosomal abnormalities in sperm of mice and humans by sperm FISH have corroborated the differences in germ-cell susceptibilities. The available evidence suggests that the risk of producing chromosomally defective sperm is highest during the first few weeks after the end of chemotherapy, and decays with time. Thus, sperm samples provided immediately after the initiation of cancer therapies may contain treatment-induced genetic defects that will jeopardize the genetic health of offspring.

  13. Nanoparticle-based targeted gene therapy for lung cancer

    OpenAIRE

    Lee, Hung-Yen; Mohammed, Kamal A; Nasreen, Najmunnisa

    2016-01-01

    Despite striking insights on lung cancer progression, and cutting-edge therapeutic approaches the survival of patients with lung cancer, remains poor. In recent years, targeted gene therapy with nanoparticles is one of the most rapidly evolving and extensive areas of research for lung cancer. The major goal of targeted gene therapy is to bring forward a safe and efficient treatment to cancer patients via specifically targeting and deterring cancer cells in the body. To achieve high therapeuti...

  14. 15q12 Variants, Sputum Gene Promoter Hypermethylation, and Lung Cancer Risk: A GWAS in Smokers

    Science.gov (United States)

    Leng, Shuguang; Liu, Yushi; Weissfeld, Joel L.; Thomas, Cynthia L.; Han, Younghun; Picchi, Maria A.; Edlund, Christopher K.; Willink, Randall P.; Gaither Davis, Autumn L.; Do, Kieu C.; Nukui, Tomoko; Zhang, Xiequn; Burki, Elizabeth A.; Van Den Berg, David; Romkes, Marjorie; Gauderman, W. James; Crowell, Richard E.; Tesfaigzi, Yohannes; Stidley, Christine A.; Amos, Christopher I.; Siegfried, Jill M.; Gilliland, Frank D.

    2015-01-01

    Background: Lung cancer is the leading cause of cancer-related mortality worldwide. Detection of promoter hypermethylation of tumor suppressor genes in exfoliated cells from the lung provides an assessment of field cancerization that in turn predicts lung cancer. The identification of genetic determinants for this validated cancer biomarker should provide novel insights into mechanisms underlying epigenetic reprogramming during lung carcinogenesis. Methods: A genome-wide association study using generalized estimating equations and logistic regression models was conducted in two geographically independent smoker cohorts to identify loci affecting the propensity for cancer-related gene methylation that was assessed by a 12-gene panel interrogated in sputum. All statistical tests were two-sided. Results: Two single nucleotide polymorphisms (SNPs) at 15q12 (rs73371737 and rs7179575) that drove gene methylation were discovered and replicated with rs73371737 reaching genome-wide significance (P = 3.3×10–8). A haplotype carrying risk alleles from the two 15q12 SNPs conferred 57% increased risk for gene methylation (P = 2.5×10–9). Rs73371737 reduced GABRB3 expression in lung cells and increased risk for smoking-induced chronic mucous hypersecretion. Furthermore, subjects with variant homozygote of rs73371737 had a two-fold increase in risk for lung cancer (P = .0043). Pathway analysis identified DNA double-strand break repair by homologous recombination (DSBR-HR) as a major pathway affecting susceptibility for gene methylation that was validated by measuring chromatid breaks in lymphocytes challenged by bleomycin. Conclusions: A functional 15q12 variant was identified as a risk factor for gene methylation and lung cancer. The associations could be mediated by GABAergic signaling that drives the smoking-induced mucous cell metaplasia. Our findings also substantiate DSBR-HR as a critical pathway driving epigenetic gene silencing. PMID:25713168

  15. CGMD: An integrated database of cancer genes and markers

    OpenAIRE

    Jangampalli Adi Pradeepkiran; Sri Bhashyam Sainath; Konidala Kramthi Kumar; Lokanada Balasubramanyam; Kodali Vidya Prabhakar; Matcha Bhaskar

    2015-01-01

    Integrating cancer genes and markers with experimental evidence might provide valuable information for the further investigation of crosstalk between tumor genes and markers in cancer biology. To achieve this objective, we developed a database known as the Cancer Gene Marker Database (CGMD), which integrates data on tumor genes and markers based on experimental evidence. The major goal of CGMD is to provide the following: 1) current systematic treatment approaches and recent advances in diffe...

  16. Genetic variant in CD44 confer susceptibility to acute skin reaction in breast cancer patients undergoing radiotherapy

    International Nuclear Information System (INIS)

    Heterogeneity in toxicity to normal tissue is observed in 10% of cancer patients after radiotherapy (RT) which limits the therapeutic outcome. Response to RT is manifested from alterations in gene of vivid pathways involving DNA damage-repair, inflammatory cytokine, cell cycle regulation, antioxidant response etc. Therefore, the common sequence variants in these radioresponsive genes may modify the severity of normal tissue toxicity and identification of the same may have clinical relevance as a predictive biomarker. The present study was aimed to evaluate the potential modifying role of genetic variants in NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A, LIG3, SH3GL1, BAXS, XRCC1, MAD2L2 and TGFBR3 on the individual susceptibility to RT induced acute skin reactions. All the 132 breast cancer patients were treated with a total dose of 50 Gy in case of mastectomy and 60 Gy in breast conservation surgery. The severity of skin damage was scored according to the Radiation Therapy Oncology Group (RTOG) criteria and the toxicity scores were dichotomized as non-over-responders (NOR; RTOG<2) and over-responders (NOR;RTOG>2) for analysis. Out of the 132 subjects, 44 were ORs. Among the 20 studied SNPs of indicated genes, the rs8193 (CD44) polymorphism lying in the miRNA binding site was significantly (p<0.05) associated with the RT induced adverse skin reactions. The non-coding CD44 3'-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed. Therefore, though the role of CD44 in radiosensitivity is unknown, the change in the miRNA binding to CD44mRNA transcripts may regulate expression of several genes involved in pathophysiology of normal tissue radiosensitivity leading to the observed outcome. (author)

  17. Association between the XPG gene Asp1104His polymorphism and lung cancer risk.

    Science.gov (United States)

    Zhou, B; Hu, X M; Wu, G Y

    2016-01-01

    It has been suggested that the xeroderma pigmentosum complementation group G (XPG) gene Asp1104His polymorphism is linked to susceptibility to lung cancer. However, the results from the published studies are contradictory rather than conclusive. With this meta-analysis, we aimed to achieve a better understanding of the effects of the XPG gene Asp1104His polymorphism on lung cancer risk. We identified six eligible studies from five publications that included a total of 2293 lung cancer patients and 2586 controls. There was a significant association between the XPG gene Asp1104His polymorphism and lung cancer (His/His vs Asp/Asp: OR = 1.24, 95%CI = 1.04-1.48; Asp/His vs Asp/Asp: OR = 1.17, 95%CI = 1.03-1.34; the dominant model: OR = 1.18, 95%CI = 1.04-1.33; the recessive model: OR = 1.10, 95%CI = 0.94-1.28). In a subgroup analysis by nationality, we found a significant association between the XPG gene Asp1104His polymorphism and lung cancer risk in Asians. No publication bias was found in this study. The results from this meta-analysis indicate that the XPG gene Asp1104His polymorphism is associated with lung cancer risk, especially in Asians. PMID:27323149

  18. Global lung cancer risk from PAH exposure highly depends on emission sources and individual susceptibility

    Science.gov (United States)

    Shen, Huizhong; Tao, Shu; Liu, Junfeng; Huang, Ye; Chen, Han; Li, Wei; Zhang, Yanyan; Chen, Yuanchen; Su, Shu; Lin, Nan; Xu, Yinyin; Li, Bengang; Wang, Xilong; Liu, Wenxin

    2014-10-01

    The health impacts of polycyclic aromatic hydrocarbons (PAHs), the most concerning organic pollutants, depend not only on the locations and strengths of emission sources, but also on individual susceptibility. Moreover, trans-boundary transport makes them a global concern. In this study, a comprehensive analysis of the global health impacts of polycyclic aromatic hydrocarbons (PAHs) in ambient air is presented. Model resolution is critical in exposure modelling. Globally, incremental lifetime lung cancer risk (ILCR) induced by ambient PAH exposure is 3.1 × 10-5. If the individual susceptibility was not taken into consideration, the overall risk would be underestimated by 55% and the proportion of highly vulnerable population would be underestimated by more than 90%. Emphasizing on individual susceptibility, our study provides an instrumental revision of current risk assessment methodology. In terms of lung cancer risk, the most important sources are combustion of biomass fuels (40%) and fossil fuels (14%) in the residential/commercial sector, coke (13%) and aluminium (12%) production, and motor vehicles (9%). PAHs can travel long distance globally especially within the Eurasian continent. Still, the risk is dominantly contributed by local.

  19. Mutation analysis of the PALB2 gene in unselected pancreatic cancer patients in the Czech Republic.

    Science.gov (United States)

    Borecka, M; Zemankova, P; Vocka, M; Soucek, P; Soukupova, J; Kleiblova, P; Sevcik, J; Kleibl, Z; Janatova, M

    2016-05-01

    Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis among common solid cancer diagnoses. It has been shown that up to 10% of PDAC cases have a familial component. Characterization of PDAC-susceptibility genes could reveal high-risk individuals and patients that may benefit from tailored therapy. Hereditary mutations in PALB2 (Partner and Localizer of BRCA2) gene has been shown to predispose, namely to PDAC and breast cancers; however, frequencies of mutations vary among distinct geographical populations. Using the combination of sequencing, high-resolution melting and multiplex ligation-dependent probe amplification analyses, we screened the entire PALB2 gene in 152 unselected Czech PDAC patients. Truncating mutations were identified in three (2.0%) patients. Genotyping of found PALB2 variants in 1226 control samples revealed one carrier of PALB2 truncating variant (0.08%; P = 0.005). The mean age at PDAC diagnosis was significantly lower among PALB2 mutation carriers (51 years) than in non-carriers (63 years; P = 0.016). Only one patient carrying germline PALB2 mutation had a positive family breast cancer history. Our results indicate that hereditary PALB2 mutation represents clinically considerable genetic factor increasing PDAC susceptibility in our population and that analysis of PALB2 should be considered not only in PDAC patients with familial history of breast or pancreatic cancers but also in younger PDAC patients without family cancer history. PMID:27106063

  20. Cytotoxic T-lymphocyte antigen 4 gene polymorphisms and susceptibility to chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Amir Houshang Mohammad Alizadeh; Mehrdad Hajilooi; Mitra Ranjbar; Farahnaz Fallahian; Seyed Mohsen Mousavi

    2006-01-01

    AIM: To assess the three polymorphism regions within cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene, a C/T base exchange in the promoter region-318 (CTLA-4 -318C/T), an A/G substitution in the exon 1 position 49 (CTLA-4 49A/G), a T/C substitution in 1172 (CTLA-4 -1172T/C) in patients with chronic hepatitis B.METHODS: Fifty-one patients with chronic hepatitis B virus infection and 150 healthy subjects were recruited sequentially as they presented to the hepatic clinic. Classification of chronic hepatitis B virus (HBV)-infected patients was as asymptomatic carrier state (26 patients) and chronic hepatitis B (25 patients). Genomic DNA was isolated from anti-coagulated peripheral blood Buffy coat using Miller's salting-out method. The presence of the CTLA-4 gene polymorphisms was determined using polymerase chain reaction amplification refractory mutation system (ARMS).RESULTS: We observed a significant association between -318 genotypes frequency (T+C-, T+C+, T-C+) and susceptibility to chronic hepatitis B (P=0.012,OR=0.49, 95%CI: 0.206-1.162). However, we did not observe a significant association for +49 genotype frequency (T+C+, T+C- T-C+) and -1172 genotype frequency (C+T+, T+C- C+T-) and state of disease.CONCLUSION: Our results suggest that CTLA-4 gene polymorphisms may partially be involved in the susceptibility to chronic hepatitis B.

  1. LOD score exclusion analyses for candidate disease susceptibility genes using case-parents design

    Institute of Scientific and Technical Information of China (English)

    DENG Hongwen; GAO Guimin

    2006-01-01

    The focus of almost all the association studies of candidate genes is to test for their importance. We recently developed a LOD score approach that can be used to test against the importance of candidate genes for complex diseases and quantitative traits in random samples. As a complementary method to regular association analyses, our LOD score approach is powerful but still affected by the population admixture, though it is more conservative. To control the confounding effect of population heterogeneity, we develop here a LOD score exclusion analysis using case-parents design, the basic design of the transmission disequilibrium test (TDT) approach that is immune to population admixture. In the analysis, specific genetic effects and inheritance models at candidate genes can be analyzed and if a LOD score is ≤ - 2.0, the locus can be excluded from having an effect larger than that specified. Simulations show that this approach has reasonable power to exclude a candidate gene having small genetic effects if it is not a disease susceptibility locus (DSL) with sample size often employed in TDT studies. Similar to association analyses with the TDT in nuclear families, our exclusion analyses are generally not affected by population admixture. The exclusion analyses may be implemented to rule out candidate genes with no or minor genetic effects as supplemental analyses for the TDT. The utility of the approach is illustrated with an application to test the importance of vitamin D receptor (VDR) gene underlying the differential risk to osteoporosis.

  2. Mutation analysis of BRCA1 and BRCA2 cancer predisposition genes in radiation hypersensitive cancer patients

    International Nuclear Information System (INIS)

    Purpose: The dose intensity of radiotherapy (RT) used in cancer treatment is limited in rare individuals who display severe normal tissue reactions after standard RT treatments. Novel predictive assays are required to identify these individuals prior to treatment. The mechanisms responsible for such reactions are unknown, but may involve dysfunction of genes involved in the sensing and response of cells to DNA damage. The breast cancer susceptibility genes BRCA1 and BRCA2 are implicated in DNA damage repair and the control of genome stability. The purpose of this study was to determine if clinical radiation hypersensitivity is related to mutations of the BRCA1 and BRCA2 genes. Such information is of potential use in the clinical management of BRCA mutation carriers and their families. Methods and Materials: Twenty-two cancer patients who developed severe normal tissue reactions after RT were screened for mutations of BRCA1 and BRCA2, using various methods including protein truncation testing, direct DNA sequencing, and a PCR-based BRCA1 exon 13 duplication test. Results: No mutations were detected in the 22 patients tested, despite screening for the majority of commonly described types of mutations of BRCA1 and BRCA2. Conclusion: These early results suggest that genes other than BRCA1 and BRCA2 probably account for most cases of clinical radiation hypersensitivity, and that screening for mutations of BRCA1 and BRCA2 is unlikely to be useful in predicting response to radiotherapy. However, it has not been excluded that some BRCA1 or BRCA2 heterozygotes might experience unexpected RT toxicity; further BRCA mutation screening on radiation sensitive individuals is warranted

  3. Matrix metalloproteinase gene polymorphisms and periodontitis susceptibility: a meta-analysis involving 6,162 individuals

    OpenAIRE

    Hong Weng; Yan Yan; Ying-Hui Jin; Xiang-Yu Meng; Yuan-Yuan Mo; Xian-Tao Zeng

    2016-01-01

    We aimed to systematically investigate the potential association of matrix metalloproteinase (MMP)-9, -3, -2, and -8 gene polymorphisms with susceptibility to periodontitis using meta-analysis. A literature search in PubMed, Embase, and Web of Sciencewas conducted to obtain relevant publications. Finally a total of 16 articles with 24 case-control studies (nine on MMP-9-1562 C/T, seven on MMP-3-1171 A5/A6, four on MMP-2-753C/T, and four on MMP-8-799 C/T) were considered in this meta-analysis....

  4. Adenoviral gene therapy in gastric cancer: A review

    OpenAIRE

    Khalighinejad, Nima; Hariri, Hesammodin; Behnamfar, Omid; Yousefi, Arash; Momeni, Amir

    2008-01-01

    Gastric cancer is one of the most common malignancies worldwide. With current therapeutic approaches the prognosis of gastric cancer is very poor, as gastric cancer accounts for the second most common cause of death in cancer related deaths. Gastric cancer like almost all other cancers has a molecular genetic basis which relies on disruption in normal cellular regulatory mechanisms regarding cell growth, apoptosis and cell division. Thus novel therapeutic approaches such as gene therapy promi...

  5. Highly parallel identification of essential genes in cancer cells

    OpenAIRE

    Luo, Biao; Cheung, Hiu Wing; Subramanian, Aravind; Sharifnia, Tanaz; Okamoto, Michael; Yang, Xiaoping; Hinkle, Greg; Boehm, Jesse S.; Beroukhim, Rameen; Weir, Barbara A.; Mermel, Craig; Barbie, David A; Awad, Tarif; Zhou, Xiaochuan; Nguyen, Tuyen Van

    2008-01-01

    More complete knowledge of the molecular mechanisms underlying cancer will improve prevention, diagnosis and treatment. Efforts such as The Cancer Genome Atlas are systematically characterizing the structural basis of cancer, by identifying the genomic mutations associated with each cancer type. A powerful complementary approach is to systematically characterize the functional basis of cancer, by identifying the genes essential for growth and related phenotypes in different cancer cells. Such...

  6. Cell Targeting in Anti-Cancer Gene Therapy

    OpenAIRE

    Lila, Mohd Azmi Mohd; Siew, John Shia Kwong; Zakaria, Hayati; Saad, Suria Mohd; Ni, Lim Shen; Abdullah, Jafri Malin

    2004-01-01

    Gene therapy is a promising approach towards cancer treatment. The main aim of the therapy is to destroy cancer cells, usually by apoptotic mechanisms, and preserving others. However, its application has been hindered by many factors including poor cellular uptake, non-specific cell targeting and undesirable interferences with other genes or gene products. A variety of strategies exist to improve cellular uptake efficiency of gene-based therapies. This paper highlights advancements in gene th...

  7. Gene network-based cancer prognosis analysis with sparse boosting

    OpenAIRE

    Ma, Shuangge; Huang, Yuan; Huang, Jian; Fang, Kuangnan

    2012-01-01

    High-throughput gene profiling studies have been extensively conducted, searching for markers associated with cancer development and progression. In this study, we analyse cancer prognosis studies with right censored survival responses. With gene expression data, we adopt the weighted gene co-expression network analysis (WGCNA) to describe the interplay among genes. In network analysis, nodes represent genes. There are subsets of nodes, called modules, which are tightly connected to each othe...

  8. Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

    International Nuclear Information System (INIS)

    Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value < 0.05 in EPICOLON stage 1 [rs698 in ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive), rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive), rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant), and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1

  9. Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

    Directory of Open Access Journals (Sweden)

    Moreno Victor

    2011-08-01

    Full Text Available Abstract Background Colorectal cancer (CRC is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. Methods CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. Results None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive, rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive, rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant, and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive. In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1

  10. Epigenetic modulation of cancer-germline antigen gene expression in tumorigenic human mesenchymal stem cells: implications for cancer therapy.

    Science.gov (United States)

    Gjerstorff, Morten; Burns, Jorge S; Nielsen, Ole; Kassem, Moustapha; Ditzel, Henrik

    2009-07-01

    Cancer-germline antigens are promising targets for cancer immunotherapy, but whether such therapies will also eliminate the primary tumor stem cell population remains undetermined. We previously showed that long-term cultures of telomerized adult human bone marrow mesenchymal stem cells can spontaneously evolve into tumor-initiating, mesenchymal stem cells (hMSC-TERT20), which have characteristics of clinical sarcoma cells. In this study, we used the hMSC-TERT20 tumor stem cell model to investigate the potential of cancer-germline antigens to serve as tumor stem cell targets. We found that tumorigenic transformation of hMSC-TERT20 cells induced the expression of members of several cancer-germline antigen gene families (ie, GAGE, MAGE-A, and XAGE-1), with promoter hypomethylation and histone acetylation of the corresponding genes. Both in vitro cultures and tumor xenografts derived from tumorigenic hMSC-TERT20 single cell subclones exhibited heterogeneous expression of both GAGE and MAGE-A proteins, and similar patterns of expression were observed in clinical sarcomas. Importantly, histone deacetylase and DNA methyltransferase inhibitors were able to induce more ubiquitous expression levels of cancer-germline antigens in hMSC-TERT20 cells, while their expression levels in primary human mesenchymal stem cells remained unaffected. The expression pattern of cancer-germline antigens in tumorigenic mesenchymal stem cells and sarcomas, plus their susceptibility to enhancement by epigenetic modulators, makes them promising targets for immunotherapeutic approaches to cancer treatment. PMID:19498007

  11. Protective and Susceptible HLA Class I Genes in Patients with End-Stage Renal Disease

    Directory of Open Access Journals (Sweden)

    2008-01-01

    Full Text Available The role of the HLA system in the pathophysiology of primary renal disease is intriguing, but not completely resolved. According to the results of studies links between HLA haplotype and renal failure has been reported. This study was conducted to determine protective and susceptible role of HLA class I genes in end stage renal disease patients. Subjects of this study were 77 individuals from Azerbaijan republic referred to Iran Red Crescent Society clinic in Baku of which were assigned into 2 group, case and control, based on renal disease. Case group were 26 patients with end stage renal disease candidate for renal transplant and controls were 51 healthy subjects. Typing of HLA class I was performed by serologic method. There was no significant difference in age and sex between control and patient groups. The most frequent detected HLA antigens were A2 (41.6%, A3(28.6%, A24(26% from A loci and B35 (46.8%, B51 (29.9%, B18 (13% from B loci. Significant association was found between susceptibility to ESRD and HLA-A33, A11, B49 (p<0.05. The findings support the idea that polymorphism of HLA class I may influence the susceptibility to ESRD. We suggested HLA antigen distribution will identify the high-risk patients who are candidates for transplantation.

  12. Association of rs6983267 Polymorphism and Thyroid Cancer Susceptibility: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Li, Jingdong; Wang, Xiaofei; Dong, Jiahong

    2016-01-01

    BACKGROUND Recent genome-wide association studies have identified rs6983267 polymorphism as a key locus in the 8q24 region associated with multisite cancers. However, the information on its association with thyroid cancer is inconclusive. The aim of this study was to determine whether this locus is a risk factor for susceptibility to thyroid cancer by conducting a meta-analysis. MATERIAL AND METHODS Relevant studies were identified by searching PubMed and Embase databases. The pooled odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated. RESULTS A total of 4 studies including 2825 cases and 9684 controls were enrolled to this meta-analysis. The pooled data showed the G allele of the rs6983267 polymorphism is a risk factor for susceptibility to thyroid cancer (OR=1.08, 95%CI: 1.02-1.16, P=0.01). Significant associations were also found in homozygote comparison (GG vs. TT: OR=1.17, 95%CI: 1.03-1.33, P=0.02) and dominant model (GG+GT vs. TT: OR=1.13, 95%CI: 1.01-1.26, P=0.03). Borderline significant associations in similar directions were found in the recessive model (GG vs. GT+TT: OR=1.10, 95%CI: 0.99-1.22, P=0.07) and heterozygote comparison (GT vs. TT: OR=1.10, 95%CI: 0.99-1.24, P=0.09). CONCLUSIONS Our meta-analysis shows that the rs6983267 G>T polymorphism might be associated with higher risk of thyroid cancer. Further research with larger sample sizes and full investigation of confounding risk factors is needed to confirm or revise our conclusions. PMID:27251952

  13. Discovering cancer genes by integrating network and functional properties

    Directory of Open Access Journals (Sweden)

    Davis David P

    2009-09-01

    Full Text Available Abstract Background Identification of novel cancer-causing genes is one of the main goals in cancer research. The rapid accumulation of genome-wide protein-protein interaction (PPI data in humans has provided a new basis for studying the topological features of cancer genes in cellular networks. It is important to integrate multiple genomic data sources, including PPI networks, protein domains and Gene Ontology (GO annotations, to facilitate the identification of cancer genes. Methods Topological features of the PPI network, as well as protein domain compositions, enrichment of gene ontology categories, sequence and evolutionary conservation features were extracted and compared between cancer genes and other genes. The predictive power of various classifiers for identification of cancer genes was evaluated by cross validation. Experimental validation of a subset of the prediction results was conducted using siRNA knockdown and viability assays in human colon cancer cell line DLD-1. Results Cross validation demonstrated advantageous performance of classifiers based on support vector machines (SVMs with the inclusion of the topological features from the PPI network, protein domain compositions and GO annotations. We then applied the trained SVM classifier to human genes to prioritize putative cancer genes. siRNA knock-down of several SVM predicted cancer genes displayed greatly reduced cell viability in human colon cancer cell line DLD-1. Conclusion Topological features of PPI networks, protein domain compositions and GO annotations are good predictors of cancer genes. The SVM classifier integrates multiple features and as such is useful for prioritizing candidate cancer genes for experimental validations.

  14. A novel functional TagSNP Rs7560488 in the DNMT3A1 promoter is associated with susceptibility to gastric cancer by modulating promoter activity.

    Directory of Open Access Journals (Sweden)

    Huazhang Wu

    Full Text Available DNA-methyltransferase (DNMT-3A which contains DNMT3A1 and DNMT3A2 isoforms have been suggested to play a crucial role in carcinogenesis and showed aberrant expression in most cancers. Accumulated evidences also indicated that single nucleotide polymorphisms (SNP in DNMT genes were associated with susceptibility to different tumors. We hypothesized that genetic variants in DNMT3A1 promoter region are associated with gastric cancer risk. We selected the tagSNPs from the HapMap database for the Chinese and genotyped in a case-control study to evaluate the association with gastric cancer (GC in a Chinese population. We identified that the functional tagSNP rs7560488 T>C associated with a significantly increased risk of GC. In vitro functional analysis by luciferase reporter assay and EMSA indicated that the tagSNP rs7560488 T>C substantially altered transcriptional activity of DNMT3A1 gene via influencing the binding of some transcriptional factors, although a definite transcriptional factor remains to be established. Compared with TT homozygotes, subjects who were TC heterozygotes and CC homozygotes exhibited a reduced expression of DNMT3A1. Furthermore, stratified analysis showed that individuals who harbor TC or CC genotypes less than 60 years old were more susceptible to GC. Our results suggest that the genetic variations in the DNMT3A1 promoter contribute to the susceptibility to GC and also provide an insight that tagSNP rs7560488 T>C may be a promising biomarker for predicting GC genetic susceptibility and a valuable information in GC pathogenesis.

  15. HLA-D region genes and rheumatoid arthritis (RA): importance of DR and DQ genes in conferring susceptibility to RA.

    Science.gov (United States)

    Singal, D P; Green, D; Reid, B; Gladman, D D; Buchanan, W W

    1992-01-01

    The distribution of HLA-D region antigens was studied in three groups (I, IIa, and IIb) of patients with rheumatoid arthritis (RA): group I comprised 43 patients with mild, non-progressive RA, controlled by non-steroidal anti-inflammatory drugs without progression or erosions; group II comprised 94 patients with severe disease, who had earlier been treated with non-steroidal anti-inflammatory drugs and all had incomplete response requiring treatment with gold (sodium aurothiomalate). Of these, 46 patients (group IIa) responded to gold and the disease was well controlled, and the remaining 48 patients (group IIb) did not respond to gold and developed gold induced toxic reactions, including thrombocytopenia or proteinuria, or both. HLA-D region antigens were defined by serological and molecular (Southern blot analysis and oligonucleotide typing) techniques. The results show that DR4 was significantly increased in all three groups of patients. The prevalence of DR1, or DR1 in DR4 negative patients, and DR3 and DR4 associated DQw7 specificities, however, showed differences in these three groups of patients. The prevalence of DR1 and of DR1 in DR4 negative patients was increased only in patients with mild (group I) RA, but not in patients with severe (groups IIa and IIb) disease. On the other hand, the prevalence of DR4 associated DQw7 was significantly increased in patients with severe disease, but not in patients with mild RA. In addition, DR3 was significantly increased only in patients with severe disease who developed gold induced toxic reactions (group IIb). These data suggest that the HLA-D region genes which cause susceptibility to mild RA may be different from those causing susceptibility to severe RA. The results suggest that both DR and DQ (A, B) genes may be important in conferring susceptibility to RA: DR in mild disease and DQ in severe RA. Images PMID:1371662

  16. An overview of gene therapy in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Amit Bali

    2013-01-01

    Full Text Available Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatment approaches for cancer gene therapy; gene addition therapy, immunotherapy, gene therapy using oncolytic viruses, antisense ribonucleic acid (RNA and RNA interference-based gene therapy. Clinical trials to date in head and neck cancer have shown evidence of gene transduction and expression, mediation of apoptosis and clinical response including pathological complete responses. The objective of this article is to provide an overview of the current available gene therapies for head and neck cancer.

  17. Study on relationship of apolipoprotein E gene polymorphism and genetic susceptibility of stress urinary incontinence

    Institute of Scientific and Technical Information of China (English)

    Tong Jia-li; Lang Jing-he; Zhu lan

    2010-01-01

    Objective: To explore the relationship between apolipoprotein E (ApoE) gene polymorphism and susceptibility of stress urinary incontinence (SUI).Methods: ApoE genotypes were examined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) technique in 99 patients with SUI and 101 asymptomatic controls. Results: The frequency of allele e3 of ApoE was slightly lower in patients with anatomic SUI than that in controls (79.44% vs. 81.68%), while the frequency of allele e4 of ApoE was slightly higher in patients with anatomic SUI than that in controls (10.00% vs. 9.90%). No significant difference was found in frequency of allele e3 or e4 between SUI patients and controls (χ2=0.523, P=0.770).Conclusion: The gene polymorphism of ApoE is not independently involved in the development of SUI.

  18. Identification of a novel asthma susceptibility gene on chromosome 1qter and its functional evaluation

    DEFF Research Database (Denmark)

    White, Julia H; Chiano, Mathias; Wigglesworth, Mark;

    2008-01-01

    , through a series of genotyping screens. Further screening using the pedigree-based association test (PBAT) identified polymorphisms in the OPN3 and CHML genes as being associated with asthma and atopic asthma after correcting for multiple comparisons. We observed that polymorphisms flanking the OPN3 and......Asthma is a multifactorial disease, in which the intricate interplay between genetic and environmental factors underlies the overall phenotype of the disease. Using a genome-wide scan for linkage in a population comprising of Danish families, we identified a novel linked locus on chromosome 1qter...... (LOD 3.6, asthma) and supporting evidence for this locus was identified for both asthma and atopic-asthma phenotypes in the GAIN (Genetics of Asthma International Network) families. The putative susceptibility gene was progressively localized to a 4.5 Mb region on chromosome 1q adjacent to the telomere...

  19. Association of Genetic Polymorphism in the Interleukin-8 Gene with Risk of Oral Cancer and Its Correlation with Pain.

    Science.gov (United States)

    Singh, Prithvi Kumar; Chandra, Girish; Bogra, Jaishri; Gupta, Rajni; Kumar, Vijay; Hussain, Syed Rizwan; Jain, Amita; Mahdi, Abbas Ali; Ahmad, Mohammad Kaleem

    2016-02-01

    Oral cancer is a multifactorial disease process and involves complex interactions between gene to gene and gene to environmental factors. Interleukin 8 (IL-8), a pro-inflammatory cytokine, having angiogenic activity with elevated expression in tumor cells, is reported to play an essential role in oral cancer development. This study was conducted with the aim to investigate the role of IL-8 (-A251T) gene polymorphism in susceptibility, progression, and self-reporting pain in oral cancer. The single nucleotide polymorphisms of the IL-8 (-A251T) gene were screened in 300 patients with oral cancer and 300 healthy controls, by polymerase chain reaction-restriction fragment length polymorphism. Genotype and allele frequencies were evaluated by chi-square test and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. The results of the study demonstrated that IL-8 (-A251T) gene polymorphism was significantly associated with susceptibility of oral cancer, whereas its correlation with clinico-pathological status or pain due to oral cancer could not be established. The AT heterozygous (OR 5.31; CI 3.38-8.34; p 0.0001) and AA homozygous (OR 2.89; CI 1.76-4.75; p 0.0001) had a greater risk for oral cancer compared to TT homozygous. Furthermore, significantly increased values of A allele frequencies compared to T allele were observed in all patients (OR 1.56; CI 1.24-1.96; p 0.0002). Tobacco chewing and smoking were also found to influence the development of oral cancer and increased the incidence of pain in oral cancer patients. The findings of this study suggest that the IL-8 (-A251T) gene polymorphism may be associated with increased risk of oral cancer. PMID:26660080

  20. Tagging single-nucleotide polymorphisms in candidate oncogenes and susceptibility to ovarian cancer

    DEFF Research Database (Denmark)

    Quaye, L; Song, H; Ramus, S J;

    2009-01-01

    Low-moderate risk alleles that are relatively common in the population may explain a significant proportion of the excess familial risk of ovarian cancer (OC) not attributed to highly penetrant genes. In this study, we evaluated the risks of OC associated with common germline variants in five onc...

  1. MGMT Leu84Phe polymorphism contributes to cancer susceptibility: evidence from 44 case-control studies.

    Directory of Open Access Journals (Sweden)

    Jun Liu

    Full Text Available BACKGROUND: O(6-methylguanine-DNA methyltransferase is one of the few proteins to directly remove alkylating agents in the human DNA direct reversal repair pathway. A large number of case-control studies have been conducted to explore the association between MGMT Leu84Phe polymorphism and cancer risk. However, the results were not consistent. METHODS: We carried out a meta-analysis of 44 case-control studies to clarify the association between the Leu84Phe polymorphism and cancer risk. RESULTS: Overall, significant association of the T allele with cancer susceptibility was verified with meta-analysis under a recessive genetic model (P<0.001, OR=1.30, 95%CI 1.24-1.50 and TT versus CC comparison (P=0.001, OR=1.29, 95% CI 1.12-1.50. In subgroup analysis, a significant increased risk was found for lung cancer (TT versus CC, P=0.027, OR=1.67, 95% CI 1.06-2.63; recessive genetic model, P=0.32, OR=1.64, 95% CI 1.04-2.58, whereas risk of colorectal cancer was significantly low under a dominant genetic model (P=0.019, OR=0.84, 95% CI 0.72-0.97. Additionally, a significant association between TT genetic model and total cancer risk was found in the Caucasian population (TT versus CC, P=0.014, OR=1.29, 95% CI 1.05-1.59; recessive genetic model, P=0.009, OR=1.31, 95% CI 1.07-1.61, but not in the Asian population. An increased risk for lung cancer was also verified in the Caucasian population (TT versus CC, P=0.035, OR=1.62, 95% CI 1.04-2.53; recessive genetic model, P=0.048, OR=1.57, 95% CI 1.01-2.45. CONCLUSIONS: These results suggest that MGMT Leu84Phe polymorphism might contribute to the susceptibility of certain cancers.

  2. MGMT Leu84Phe Polymorphism Contributes to Cancer Susceptibility: Evidence from 44 Case-Control Studies

    Science.gov (United States)

    Yu, Cuicui; Sun, Yan; Jia, Chuanliang; Zhang, Lijing; Salahuddin, Taufiq; Li, Xiaodong; Lang, Juntian; Song, Xicheng

    2013-01-01

    Background O6-methylguanine-DNA methyltransferase is one of the few proteins to directly remove alkylating agents in the human DNA direct reversal repair pathway. A large number of case-control studies have been conducted to explore the association between MGMT Leu84Phe polymorphism and cancer risk. However, the results were not consistent. Methods We carried out a meta-analysis of 44 case-control studies to clarify the association between the Leu84Phe polymorphism and cancer risk. Results Overall, significant association of the T allele with cancer susceptibility was verified with meta-analysis under a recessive genetic model (P<0.001, OR=1.30, 95%CI 1.24-1.50) and TT versus CC comparison (P=0.001, OR=1.29, 95% CI 1.12-1.50). In subgroup analysis, a significant increased risk was found for lung cancer (TT versus CC, P=0.027, OR=1.67, 95% CI 1.06-2.63; recessive genetic model, P=0.32, OR=1.64, 95% CI 1.04-2.58), whereas risk of colorectal cancer was significantly low under a dominant genetic model (P=0.019, OR=0.84, 95% CI 0.72-0.97). Additionally, a significant association between TT genetic model and total cancer risk was found in the Caucasian population (TT versus CC, P=0.014, OR=1.29, 95% CI 1.05-1.59; recessive genetic model, P=0.009, OR=1.31, 95% CI 1.07-1.61), but not in the Asian population. An increased risk for lung cancer was also verified in the Caucasian population (TT versus CC, P=0.035, OR=1.62, 95% CI 1.04-2.53; recessive genetic model, P=0.048, OR=1.57, 95% CI 1.01-2.45). Conclusions These results suggest that MGMT Leu84Phe polymorphism might contribute to the susceptibility of certain cancers. PMID:24086516

  3. Programmed cell death 1 gene (PDCD1 polymorphism and pemphigus foliaceus (fogo selvagem disease susceptibility

    Directory of Open Access Journals (Sweden)

    Karin Braun-Prado

    2007-03-01

    Full Text Available Pemphigus foliaceus, also known as fogo selvagem, is an autoimmune disease of the epidermis characterized by superficial blisters and antibodies against desmoglein 1. It is a multifactorial disease and genetic susceptibility is oligogenic or polygenic. Considering the crucial function of the programmed cell death 1 molecule (PD-1 in the immune response, the aim of this study was to verify if variants of the PDCD1 gene influence susceptibility and resistance to pemphigus foliaceus, in a case - control disease association study. We analyzed patients (n = 154 and unaffected control individuals (n = 325 of the Brazilian population, in respect to the PD1.3(G,A PD1.5(C,T and PD1.6(A,G single nucleotide polymorphisms (SNPs and also investigated, for the first time, the exon 5 PDCD1 microsatellite (CTGn. The patient and control samples were divided into strata, according to the predominant ancestry of the individuals (African or European. The PD1.5 genotype distribution in the patients sample was almost indistinguishable from that in the control sample, in both population strata. A possible negative association between pemphigus foliaceus and allele PD1.3A was observed in the total African and European ancestry population sample (odds ratio (OR = 0.55, p = 0.066 and should be investigated in forthcoming studies. The PD1.6A allele was over-represented among the patients of predominantly European ancestry due to an increase of both the G/A and the A/A genotypes (OR = 2.12 and 1.74, respectively; p = 0.035. We conclude that polymorphisms of the PDCD1 gene may influence susceptibility to pemphigus foliaceus, at least in Brazilians of predominantly European ancestry.

  4. Identification of candidate methylation-responsive genes in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Dickerson Erin B

    2007-01-01

    Full Text Available Abstract Background Aberrant methylation of gene promoter regions has been linked to changes in gene expression in cancer development and progression. Genes associated with CpG islands (CGIs are especially prone to methylation, but not all CGI-associated genes display changes in methylation patterns in cancers. Results In order to identify genes subject to regulation by methylation, we conducted gene expression profile analyses of an ovarian cancer cell line (OVCAR-3 before and after treatment with the demethylating agent 5-aza-deoxycytidine (5-aza-dC. An overlapping subset of these genes was found to display significant differences in gene expression between normal ovarian surface epithelial cells and malignant cells isolated from ovarian carcinomas. While 40% of all human genes are associated with CGIs, > 94% of the overlapping subset of genes is associated with CGIs. The predicted change in methylation status of genes randomly selected from the overlapping subset was experimentally verified. Conclusion We conclude that correlating genes that are upregulated in response to 5-aza-dC treatment of cancer cell lines with genes that are down-regulated in cancer cells may be a useful method to identify genes experiencing epigenetic-mediated changes in expression over cancer development.

  5. Gene Expression Profiling Predicts the Development of Oral Cancer

    OpenAIRE

    Saintigny, Pierre; Zhang, Li; Fan, You-Hong; El-Naggar, Adel K.; Papadimitrakopoulou, Vali; Feng, Lei; Lee, J. Jack; Kim, Edward S.; Hong, Waun Ki; Mao, Li

    2011-01-01

    Patients with oral preneoplastic lesion (OPL) have high risk of developing oral cancer. Although certain risk factors such as smoking status and histology are known, our ability to predict oral cancer risk remains poor. The study objective was to determine the value of gene expression profiling in predicting oral cancer development. Gene expression profile was measured in 86 of 162 OPL patients who were enrolled in a clinical chemoprevention trial that used the incidence of oral cancer develo...

  6. Quantitative DNA Methylation Analysis of Candidate Genes in Cervical Cancer

    OpenAIRE

    Erin M Siegel; Riggs, Bridget M; Delmas, Amber L.; Koch, Abby; Hakam, Ardeshir; Brown, Kevin D.

    2015-01-01

    Aberrant DNA methylation has been observed in cervical cancer; however, most studies have used non-quantitative approaches to measure DNA methylation. The objective of this study was to quantify methylation within a select panel of genes previously identified as targets for epigenetic silencing in cervical cancer and to identify genes with elevated methylation that can distinguish cancer from normal cervical tissues. We identified 49 women with invasive squamous cell cancer of the cervix and ...

  7. DETECTION OF GENE MUTATION IN SPUTUM OF LUNG CANCER PATIENT

    Institute of Scientific and Technical Information of China (English)

    ZHANG He-long; WANG Wen-liang; CUI Da-xiang

    1999-01-01

    @@ Lung cancer is a common malignant tumor, which has ahigh incidence and mortality rate. Therefore, it is necessary to seek a new method for the diagnosis, especially the early diagnosis of lung cancer. The development of molecular biology makes the gene diagnosis of lung cancer possible.PCR-SSCP was applied to detect p53 gene mutation of lung cancer patients' sputum cells and we have achieved good results.

  8. Expression and Significance of MAGE Genes in Human Lung Cancer

    Directory of Open Access Journals (Sweden)

    Guangxu LI

    2013-06-01

    Full Text Available Lung cancer is one of the common malignancies with an extremely poor prognosis, because of the current diagnostic techniques are not easy to find micrometastases. Melanoma associated antigens genes (MAGE are tumor specific antigen genes, closely related to the occurrence, development and prognosis of lung cancer. The research of MAGE genes provide a new direction for the diagnosis and treatment of lung cancer.

  9. Fine mapping of chromosome 15q25.1 lung cancer susceptibility in African-Americans.

    Science.gov (United States)

    Hansen, Helen M; Xiao, Yuanyuan; Rice, Terri; Bracci, Paige M; Wrensch, Margaret R; Sison, Jennette D; Chang, Jeffery S; Smirnov, Ivan V; Patoka, Joseph; Seldin, Michael F; Quesenberry, Charles P; Kelsey, Karl T; Wiencke, John K

    2010-09-15

    Several genome-wide association studies identified the chr15q25.1 region, which includes three nicotinic cholinergic receptor genes (CHRNA5-B4) and the cell proliferation gene (PSMA4), for its association with lung cancer risk in Caucasians. A haplotype and its tagging single nucleotide polymorphisms (SNPs) encompassing six genes from IREB2 to CHRNB4 were most strongly associated with lung cancer risk (OR = 1.3; P < 10(-20)). In order to narrow the region of association and identify potential causal variations, we performed a fine-mapping study using 77 SNPs in a 194 kb segment of the 15q25.1 region in a sample of 448 African-American lung cancer cases and 611 controls. Four regions, two SNPs and two distinct haplotypes from sliding window analyses, were associated with lung cancer. CHRNA5 rs17486278 G had OR = 1.28, 95% CI 1.07-1.54 and P = 0.008, whereas CHRNB4 rs7178270 G had OR = 0.78, 95% CI 0.66-0.94 and P = 0.008 for lung cancer risk. Lung cancer associations remained significant after pack-year adjustment. Rs7178270 decreased lung cancer risk in women but not in men; gender interaction P = 0.009. For two SNPs (rs7168796 A/G and rs7164594 A/G) upstream of PSMA4, lung cancer risks for people with haplotypes GG and AA were reduced compared with those with AG (OR = 0.56, 95% CI 0.38-0.82; P = 0.003 and OR = 0.73, 95% CI 0.59-0.90, P = 0.004, respectively). A four-SNP haplotype spanning CHRNA5 (rs11637635 C, rs17408276 T, rs16969968 G) and CHRNA3 (rs578776 G) was associated with increased lung cancer risk (P = 0.002). The identified regions contain SNPs predicted to affect gene regulation. There are multiple lung cancer risk loci in the 15q25.1 region in African-Americans. PMID:20587604

  10. Vitamin D Receptor Gene Polymorphisms and Breast Cancer Risk in Kazakhstan

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    Ainur Akilzhanova

    2014-01-01

    Full Text Available Introduction: The steroid hormone 1,25-dihydroxyvitamin D3 is thought to protect against breast cancer. The activity of 1,25-dihydroxyvitamin D3 is mediated via the vitamin D receptor (VDR, and a number of polymorphisms in the VDR gene have been identified. These result in distinct genotypes, some of which may alter susceptibility to breast cancer. Two common single nucleotide polymorphisms (SNP in the VDR gene (VDR, rs1544410 (BsmI and rs2228570 (FokI, have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokI ff genotype, which encodes a less transcriptionally active isoform of VDR. A reduced risk has been reported for the BsmI BB genotype which may influence VDR mRNA stability. Aim: We have investigated whether specific VDR gene polymorphisms are associated with breast cancer risk in Kazakhstan women. Material and Methods: In a case–control study, female breast cancer patients (315 and a female control group (n=604 were tested for two VDR polymorphisms. Statistical analysis was conducted using SPSS19.0. Results: The VDR rs2228570 (FokI polymorphism was associated with an increased occurence of BC [rs2228570 (folk ff vs. FF genotype: OR=1.71; 95% CI=1.21-2.43]. No association was noted between rs1544410 (BsmI BB and breast cancer risk [OR=0.68; 95% CI=0.49-0.95]. Conclusion: Although the factors that increase breast cancer susceptibility remain uncertain, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status. Additional testing on the effect of varying genotypes on the functional mechanisms of the VDR could help to improve future testing and treatment of woman at risk for breast cancer.

  11. Polymorphisms in the Human Cytochrome P450 and Arylamine N-Acetyltransferase: Susceptibility to Head and Neck Cancers

    Directory of Open Access Journals (Sweden)

    Rim Khlifi

    2013-01-01

    Full Text Available The occurrence of head and neck cancer (HNC is associated with smoking and alcohol drinking. Tobacco smoking exposes smokers to a series of carcinogenic chemicals. Cytochrome P450 enzymes (CYP450s, such as CYP1A1, CYP1B1, and CYP2D6, usually metabolize carcinogens to their inactive derivatives, but they occasionally convert the chemicals to more potent carcinogens. In addition, via CYP450 (CYP2E1 oxidase, alcohol is metabolized to acetaldehyde, a highly toxic compound, which plays an important role in carcinogenesis. Furthermore, two N-acetyltransferase isozymes (NATs, NAT1 and NAT2, are polymorphic and catalyze both N-acetylation and O-acetylation of aromatic and heterocyclic amine carcinogens. Genetic polymorphisms are associated with a number of enzymes involved in the metabolism of carcinogens important in the induction of HNC. It has been suggested that such polymorphisms may be linked to cancer susceptibility. In this paper, we select four cytochrome P450 enzymes (CYP1A1, CYP1BA1, CYP2D6, and CYP2E1, and two N-acetyltransferase isozymes (NAT1 and NAT2 in order to summarize and analyze findings from the literature related to HNC risk by focusing on (i the interaction between these genes and the environment, (ii the impact of genetic defect on protein activity and/or expression, and (iii the eventual involvement of race in such associations.

  12. Experience with breast cancer, pre-screening perceived susceptibility and the psychological impact of screening

    DEFF Research Database (Denmark)

    Absetz, Pilvikki; Aro, Arja R; Sutton, Stephen R

    2003-01-01

    This prospective study examined whether the psychological impact of organized mammography screening is influenced by women's pre-existing experience with breast cancer and perceived susceptibility (PS) to the disease. From a target population of 16,886, a random sample of women with a normal...... screening finding and all women with a false positive or a benign biopsy finding were included (N=1942). Data were collected with postal questionnaires 1-month before screening invitation and 2 and 12 months after screening. Response rate was 63% at baseline; 86, and 80% of the baseline participants...... responded to the follow-ups. Psychological impact was measured as anxiety (STAI-S), depression (BDI), health-related concerns (IAS), and breast cancer-specific beliefs and concerns. Data was analyzed with repeated measures analyses of variance, with estimates of effect size based on Eta-squared. Women with...

  13. Regularized gene selection in cancer microarray meta-analysis

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    Huang Jian

    2009-01-01

    Full Text Available Abstract Background In cancer studies, it is common that multiple microarray experiments are conducted to measure the same clinical outcome and expressions of the same set of genes. An important goal of such experiments is to identify a subset of genes that can potentially serve as predictive markers for cancer development and progression. Analyses of individual experiments may lead to unreliable gene selection results because of the small sample sizes. Meta analysis can be used to pool multiple experiments, increase statistical power, and achieve more reliable gene selection. The meta analysis of cancer microarray data is challenging because of the high dimensionality of gene expressions and the differences in experimental settings amongst different experiments. Results We propose a Meta Threshold Gradient Descent Regularization (MTGDR approach for gene selection in the meta analysis of cancer microarray data. The MTGDR has many advantages over existing approaches. It allows different experiments to have different experimental settings. It can account for the joint effects of multiple genes on cancer, and it can select the same set of cancer-associated genes across multiple experiments. Simulation studies and analyses of multiple pancreatic and liver cancer experiments demonstrate the superior performance of the MTGDR. Conclusion The MTGDR provides an effective way of analyzing multiple cancer microarray studies and selecting reliable cancer-associated genes.

  14. Expression of phosphoenolpyruvate carboxykinase linked to chemoradiation susceptibility of human colon cancer cells

    International Nuclear Information System (INIS)

    Resistance to 5-fluorouracil (5-FU) in patients with colorectal cancer prevents effective treatment and leads to unnecessary and burdensome chemotherapy. Therefore, prediction of 5-FU resistance is imperative. To identify the proteins linked to 5-FU resistance, two-dimensional gel electrophoresis-based proteomics was performed using the human colon cancer cell line SNU-C4R with induced 5-FU resistance. Proteins showing altered expression in SNU-C4R were identified by matrix-associated laser desorption/ionization–time-of-flight analysis, and their roles in susceptibility to 5-FU or radiation were evaluated in various cell lines by transfection of specific siRNA or creation of overexpression constructs. Changes in cellular signaling and expression of mitochondrial apoptotic factors were investigated by Western Blot analysis. A mitochondrial membrane potential probe (JC-1 dye) and a flow cytometry system were employed to determine the mitochondrial membrane potential. Finally, protein levels were determined by Western Blot analysis in tissues from 122 patients with rectal cancer to clarify whether each identified protein is a useful predictor of a chemoradiation response. We identified mitochondrial phosphoenolpyruvate carboxykinase (mPEPCK) as a candidate predictor of 5-FU resistance. PEPCK was downregulated in SNU-C4R compared with its parent cell line SNU-C4. Overexpression of mPEPCK did not significantly alter the susceptibility to either 5-FU or radiation. Suppression of mPEPCK led to a decrease in both the cellular level of phosphoenolpyruvate and the susceptibility to 5-FU and radiation. Furthermore, the cellular levels of phosphoenolpyruvate (an end product of PEPCK and a substrate of pyruvate kinase), phosphorylated AKT, and phosphorylated 4EBP1 were decreased significantly secondary to the mPEPCK suppression in SNU-C4. However, mPEPCK siRNA transfection induced changes in neither the mitochondrial membrane potential nor the expression levels of

  15. Functional variants of sphingosine-1-phosphate receptor 1 gene associate with asthma susceptibility

    Science.gov (United States)

    Sun, Xiaoguang; Ma, Shwu-Fan; Wade, Michael S.; Flores, Carlos; Pino-Yanes, Maria; Moitra, Jaideep; Ober, Carole; Kittles, Rick; Husain, Aliya N.; Ford, Jean G.; Garcia, Joe G. N.

    2012-01-01

    Background The genetic mechanisms underlying asthma remain unclear. Increased permeability of the microvasculature is a feature of asthma and the sphingosine-1-phosphate receptor, S1PR1, is an essential participant regulating lung vascular integrity and responses to lung inflammation. Objective We explored the contribution of polymorphisms in the S1PR1 gene (S1PR1) to asthma susceptibility. Methods A combination of gene re-sequencing for SNP discovery, case-control association, functional evaluation of associated SNPs, and protein immunochemistry studies was utilized. Results Immunohistochemistry studies demonstrated significantly decreased S1PR1 protein expression in pulmonary vessels in asthmatic lungs compared to non-asthmatic individuals (p<0.05). Direct DNA sequencing of 27 multiethnic samples identified 39 S1PR1 variants (18 novel SNPs). Association studies were performed based on genotyping results from cosmopolitan tagging SNPs in three case-control cohorts from Chicago and New York totaling 1061 subjects (502 cases and 559 controls). Promoter SNP rs2038366 (−1557G/T) was found to be associated with asthma (p=0.03) in European Americans. In African Americans, an association was found for both asthma and severe asthma for intronic SNP rs3753194 (c.−164+170A/G) (p=0.006 and p=0.040, respectively) and for promoter SNP rs59317557 (−532C/G) with severe asthma (p=0.028). Consistent with predicted in silico functionality, alleles of promoter SNPs rs2038366 (−1557G/T) and rs59317557 (−532C/G) influenced the activity of a luciferase S1PR1 reporter vector in transfected endothelial cells exposed to growth factors (EGF, PDGF, VEGF) known to be increased in asthmatic airways. Conclusion These data provide strong support for a role for S1PR1 gene variants in asthma susceptibility and severity. Clinical Implications Our results indicate S1PR1 is a novel asthma candidate gene and an attractive target for future therapeutic strategies. Capsule summary This study

  16. Pleiotropy of cancer susceptibility variants on the risk of non-Hodgkin lymphoma: the PAGE consortium.

    Directory of Open Access Journals (Sweden)

    Unhee Lim

    Full Text Available BACKGROUND: Risk of non-Hodgkin lymphoma (NHL is higher among individuals with a family history or a prior diagnosis of other cancers. Genome-wide association studies (GWAS have suggested that some genetic susceptibility variants are associated with multiple complex traits (pleiotropy. OBJECTIVE: We investigated whether common risk variants identified in cancer GWAS may also increase the risk of developing NHL as the first primary cancer. METHODS: As part of the Population Architecture using Genomics and Epidemiology (PAGE consortium, 113 cancer risk variants were analyzed in 1,441 NHL cases and 24,183 controls from three studies (BioVU, Multiethnic Cohort Study, Women's Health Initiative for their association with the risk of overall NHL and common subtypes [diffuse large B-cell lymphoma (DLBCL, follicular lymphoma (FL, chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL] using an additive genetic model adjusted for age, sex and ethnicity. Study-specific results for each variant were meta-analyzed across studies. RESULTS: The analysis of NHL subtype-specific GWAS SNPs and overall NHL suggested a shared genetic susceptibility between FL and DLBCL, particularly involving variants in the major histocompatibility complex region (rs6457327 in 6p21.33: FL OR=1.29, p=0.013; DLBCL OR=1.23, p=0.013; NHL OR=1.22, p=5.9 × E-05. In the pleiotropy analysis, six risk variants for other cancers were associated with NHL risk, including variants for lung (rs401681 in TERT: OR per C allele=0.89, p=3.7 × E-03; rs4975616 in TERT: OR per A allele=0.90, p=0.01; rs3131379 in MSH5: OR per T allele=1.16, p=0.03, prostate (rs7679673 in TET2: OR per C allele=0.89, p=5.7 × E-03; rs10993994 in MSMB: OR per T allele=1.09, p=0.04, and breast (rs3817198 in LSP1: OR per C allele=1.12, p=0.01 cancers, but none of these associations remained significant after multiple test correction. CONCLUSION: This study does not support strong pleiotropic effects of non

  17. GENE TECHNOLOGY: A NEW WAY TO TREAT CANCER

    Directory of Open Access Journals (Sweden)

    Prajapati P M.

    2012-06-01

    Full Text Available Gene therapy is the process of introducing genetic material RNA or DNA into a person's cells to fight disease. Gene therapy treats disease by either replacing damaged or missing genes with normal ones, or by providing new genes. The concept of gene therapy was born more than thirty years ago; however, new technology is opening the door to dramatically new possibilities in the treatment of cancers of all kinds. The long-term goal of cancer gene therapy is to develop treatments that attack only cancer cells, thereby eliminating adverse effects on the body and improving the possibility to cure disease. Gene therapy may someday soon make cancer a manageable disease with nominal side effects to the patients. Furthermore, since gene therapy has potential for other diseases such as cystic fibrosis, hemophilia, sickle-cell anemia, muscular dystrophy and Parkinson's, the value of research and discovery has broad applications.

  18. Gene Test May Spare Some Breast Cancer Patients from Chemo

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_157730.html Gene Test May Spare Some Breast Cancer Patients From ... researchers report. The test is called the 21-gene recurrence score (Oncotype DX). Among women that the ...

  19. Interactions between breast cancer susceptibility loci and menopausal hormone therapy in relationship to breast cancer in the Breast and Prostate Cancer Cohort Consortium.

    Science.gov (United States)

    Gaudet, Mia M; Barrdahl, Myrto; Lindström, Sara; Travis, Ruth C; Auer, Paul L; Buring, Julie E; Chanock, Stephen J; Eliassen, A Heather; Gapstur, Susan M; Giles, Graham G; Gunter, Marc; Haiman, Christopher; Hunter, David J; Joshi, Amit D; Kaaks, Rudolf; Khaw, Kay-Tee; Lee, I-Min; Le Marchand, Loic; Milne, Roger L; Peeters, Petra H M; Sund, Malin; Tamimi, Rulla; Trichopoulou, Antonia; Weiderpass, Elisabete; Yang, Xiaohong R; Prentice, Ross L; Feigelson, Heather Spencer; Canzian, Federico; Kraft, Peter

    2016-02-01

    Current use of menopausal hormone therapy (MHT) has important implications for postmenopausal breast cancer risk, and observed associations might be modified by known breast cancer susceptibility loci. To provide the most comprehensive assessment of interactions of prospectively collected data on MHT and 17 confirmed susceptibility loci with invasive breast cancer risk, a nested case-control design among eight cohorts within the NCI Breast and Prostate Cancer Cohort Consortium was used. Based on data from 13,304 cases and 15,622 controls, multivariable-adjusted logistic regression analyses were used to estimate odds ratios (OR) and 95 % confidence intervals (CI). Effect modification of current and past use was evaluated on the multiplicative scale. P values <1.5 × 10(-3) were considered statistically significant. The strongest evidence of effect modification was observed for current MHT by 9q31-rs865686. Compared to never users of MHT with the rs865686 GG genotype, the association between current MHT use and breast cancer risk for the TT genotype (OR 1.79, 95 % CI 1.43-2.24; P interaction = 1.2 × 10(-4)) was less than expected on the multiplicative scale. There are no biological implications of the sub-multiplicative interaction between MHT and rs865686. Menopausal hormone therapy is unlikely to have a strong interaction with the common genetic variants associated with invasive breast cancer. PMID:26802016

  20. Increased gene dosage of Ink4a/Arf results in cancer resistance and normal aging

    OpenAIRE

    Matheu, Ander; Pantoja, Cristina; Efeyan, Alejo; Criado, Luis M.; Martín-Caballero, Juan; Flores, Juana M.; Klatt, Peter; Serrano, Manuel

    2004-01-01

    Mammalian genes frequently present allelic variants that differ in their expression levels and that, in the case of tumor suppressor genes, can be of relevance for cancer susceptibility and aging. We report here the characterization of a novel mouse model with increased activity for the Ink4a and Arf tumor suppressors. We have generated a “super Ink4a/Arf” mouse strain carrying a transgenic copy of the entire Ink4a/Arf locus. Cells derived from super Ink4a/Arf mice have increased resistance t...

  1. Multiple sclerosis susceptibility in a Brazilian sample, HLA and CIITA genes

    Directory of Open Access Journals (Sweden)

    Eduardo Ribeiro Paradela

    2014-06-01

    Full Text Available Introduction: The multiple sclerosis (MS is a chronic disease of the central nervous system that affects mainly young adults. This disease is characterized by the spread of demyelinating lesions in time and space. This condition may be influenced by genetic factors as heterogeneity, incomplete penetrance, polygenic inheritance and epigenetic factors, which makes this complex disease a challenge for geneticists. Objectives: The aim of this study was to investigate the association between HLA alleles from DQA1, DQB1 and DRB1 loci (6p21.3, genetic polymorphisms -168A/G (rs3087456 and +1614 G/C (rs4774 in the CIITA gene (16p13 and susceptibility to MS in a miscegenated sample from Rio de Janeiro state, RJ, Brazil. Method: DNA samples from 52 patients with relapsing remitting multiple sclerosis (MSRR [21 males (40.38% and 31 females (59.62%] and 116 healthy controls [46 males (39.65% and 70 females (60.35%] matched by race, sex and age were analyzed by techniques of PCR, SSP-PCR, electrophoresis and DNA sequencing. Results: A significant association between MS and HLA-DRB1*15:01 allele was observed [p value=.002; Odds Ratio (OR=3.2], especially in women (p=.001; OR=4.9, which remained statistically significant after Bonferroni correction. Furthermore, it was observed that the polymorphism +1614 G/C, “C/C” profile, in association with the allele DRB1*15:01 influences the increased susceptibility to MS in women (p=.029; OR=5.6. In addition, it was observed that the "G/G" profile in CIITA polymorphism +1614G/C may be associated with the resistance to MS (p=.02; OR=0.23, as well as HLA-DRB1*11:02 (p=.02, OR=0.5. The HLA-DQB1*06:02 allele also has been implicated as a possible susceptibility factor for MS (p=.02; OR=1.8, data not confirmed after Bonferronís correction. Conclusion: Together, these results reinforce the polygenic nature of MS, and proposed that the CIITA gene, which is the regulator of the expression of HLA-D, is an additive factor to

  2. Bacteriological profile and antibiotic susceptibility patterns of clinical isolates in a tertiary care cancer center

    Directory of Open Access Journals (Sweden)

    Vivek Bhat

    2016-01-01

    Full Text Available Introduction: This increased risk of bacterial infections in the cancer patient is further compounded by the rising trends of antibiotic resistance in commonly implicated organisms. In the Indian setting this is particularly true in case of Gram negative bacilli such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. Increasing resistance among Gram positive organisms is also a matter of concern. The aim of this study was to document the common organisms isolated from bacterial infections in cancer patients and describe their antibiotic susceptibilities. Methods: We conducted a 6 month study of all isolates from blood, urine, skin/soft tissue and respiratory samples of patients received from medical and surgical oncology units in our hospital. All samples were processed as per standard microbiology laboratory operating procedures. Isolates were identified to species level and susceptibility tests were performed as per Clinical Laboratory Standards Institute (CLSI guidelines -2012. Results: A total of 285 specimens from medical oncology (114 and surgical oncology services (171 were cultured. Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Acinetobacter spp. were most commonly encountered. More than half of the Acinetobacter strains were resistant to carbapenems. Resistance in Klebsiella pneumoniae to cephalosporins, fluoroquinolones and carbapenems was >50%. Of the Staphylococcus aureus isolates 41.67% were methicillin resistant. Conclusion: There is, in general, a high level of antibiotic resistance among gram negative bacilli, particularly E. coli, Klebsiella pneumoniae and Acinetobacter spp. Resistance among Gram positives is not as acute, although the MRSA incidence is increasing.

  3. The methylenetetrahydrofolate reductase gene variant C677T influences susceptibility to migraine with aura

    Directory of Open Access Journals (Sweden)

    Sundholm James

    2004-02-01

    Full Text Available Abstract Background The C677T variant in the methylenetetrahydrofolate reductase (MTHFR gene is associated with increased levels of circulating homocysteine and is a mild risk factor for vascular disease. Migraine, with and without aura (MA and MO, is a prevalent and complex neurovascular disorder that may also be affected by genetically influenced hyperhomocysteinaemia. To determine whether the C677T variant in the MTHFR gene is associated with migraine susceptibility we utilised unrelated and family-based case-control study designs. Methods A total of 652 Caucasian migraine cases were investigated in this study. The MTHFR C677T variant was genotyped in 270 unrelated migraine cases and 270 controls as well as 382 affected subjects from 92 multiplex pedigrees. Results In the unrelated case-control sample we observed an over-representation of the 677T allele in migraine patients compared to controls, specifically for the MA subtype (40% vs. 33% (χ2 = 5.70, P = 0.017. The Armitage test for trend indicated a significant dosage effect of the risk allele (T for MA (χ2 = 5.72, P = 0.017. This linear trend was also present in the independent family-based sample (χ2 = 4.25, Padjusted = 0.039. Overall, our results indicate that the T/T genotype confers a modest, yet significant, increase in risk for the MA subtype (odds ratio: 2.0 – 2.5. No increased risk for the MO subtype was observed (P > 0.05. Conclusions In Caucasians, the C677T variant in the MTHFR gene influences susceptibility to MA, but not MO. Investigation into the enzyme activity of MTHFR and the role of homocysteine in the pathophysiology of migraine is warranted.

  4. Gene therapy for gastric cancer: Is it promising?

    OpenAIRE

    Sutter, Andreas P; Fechner, Henry

    2006-01-01

    Gastric cancer is one of the most common tumors worldwide. The therapeutic outcome of conventional therapies is inefficient. Thus, new therapeutic strategies are urgently needed. Gene therapy is a promising molecular alternative in the treatment of gastric cancer, including the replacement of defective tumor suppressor genes, the inactivation of oncogenes, the introduction of suicide genes, genetic immunotherapy, anti-angiogenetic gene therapy, and virotherapy. Improved molecular biological t...

  5. Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers : Implications for Risk Prediction

    NARCIS (Netherlands)

    Antoniou, Antonis C.; Beesley, Jonathan; McGuffog, Lesley; Sinilnikova, Olga M.; Healey, Sue; Neuhausen, Susan L.; Ding, Yuan Chun; Rebbeck, Timothy R.; Weitzel, Jeffrey N.; Lynch, Henry T.; Isaacs, Claudine; Ganz, Patricia A.; Tomlinson, Gail; Olopade, Olufunmilayo I.; Couch, Fergus J.; Wang, Xianshu; Lindor, Noralane M.; Pankratz, Vernon S.; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Barile, Monica; Viel, Alessandra; Allavena, Anna; Dall'Olio, Valentina; Peterlongo, Paolo; Szabo, Csilla I.; Zikan, Michal; Claes, Kathleen; Poppe, Bruce; Foretova, Lenka; Mai, Phuong L.; Greene, Mark H.; Rennert, Gad; Lejbkowicz, Flavio; Glendon, Gord; Ozcelik, Hilmi; Andrulis, Irene L.; Thomassen, Mads; Gerdes, Anne-Marie; Sunde, Lone; Cruger, Dorthe; Jensen, Uffe Birk; Caligo, Maria; Friedman, Eitan; Kaufman, Bella; Laitman, Yael; Milgrom, Roni; Dubrovsky, Maya; Cohen, Shimrit; Borg, Ake; Jernstroem, Helena; Lindblom, Annika; Rantala, Johanna; Stenmark-Askmalm, Marie; Melin, Beatrice; Nathanson, Kate; Domchek, Susan; Jakubowska, Ania; Lubinski, Jan; Huzarski, Tomasz; Osorio, Ana; Lasa, Adriana; Duran, Mercedes; Tejada, Maria-Isabel; Godino, Javier; Benitez, Javier; Hamann, Ute; Kriege, Mieke; Hoogerbrugge, Nicoline; van der Luijt, Rob B.; van Asperen, Christi J.; Devilee, Peter; Meijers-Heijboer, E. J.; Blok, Marinus J.; Aalfs, Cora M.; Hogervorst, Frans; Rookus, Matti; Cook, Margaret; Oliver, Clare; Frost, Debra; Conroy, Don; Evans, D. Gareth; Lalloo, Fiona; Pichert, Gabriella; Davidson, Rosemarie; Cole, Trevor; Cook, Jackie; Paterson, Joan; Hodgson, Shirley; Morrison, Patrick J.; Porteous, Mary E.; Walker, Lisa; Kennedy, M. John; Dorkins, Huw; Peock, Susan; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; de Pauw, Antoine; Mazoyer, Sylvie; Bonadona, Valerie; Lasset, Christine; Dreyfus, Helene; Leroux, Dominique; Hardouin, Agnes; Berthet, Pascaline; Faivre, Laurence; Loustalot, Catherine; Noguchi, Tetsuro; Sobol, Hagay; Rouleau, Etienne; Nogues, Catherine; Frenay, Marc; Venat-Bouvet, Laurence; Hopper, John L.; Daly, Mary B.; Terry, Mary B.; John, Esther M.; Buys, Saundra S.; Yassin, Yosuf; Miron, Alexander; Goldgar, David; Singer, Christian F.; Dressler, Anne Catharina; Gschwantler-Kaulich, Daphne; Pfeiler, Georg; Hansen, Thomas V. O.; Jnson, Lars; Agnarsson, Bjarni A.; Kirchhoff, Tomas; Offit, Kenneth; Devlin, Vincent; Dutra-Clarke, Ana; Piedmonte, Marion; Rodriguez, Gustavo C.; Wakeley, Katie; Boggess, John F.; Basil, Jack; Schwartz, Peter E.; Blank, Stephanie V.; Toland, Amanda Ewart; Montagna, Marco; Casella, Cinzia; Imyanitov, Evgeny; Tihomirova, Laima; Blanco, Ignacio; Lazaro, Conxi; Ramus, Susan J.; Sucheston, Lara; Karlan, Beth Y.; Gross, Jenny; Schmutzler, Rita; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Lochmann, Magdalena; Arnold, Norbert; Heidemann, Simone; Varon-Mateeva, Raymonda; Niederacher, Dieter; Sutter, Christian; Deissler, Helmut; Gadzicki, Dorothea; Preisler-Adams, Sabine; Kast, Karin; Schoenbuchner, Ines; Caldes, Trinidad; de la Hoya, Miguel; Aittomaeki, Kristiina; Nevanlinna, Heli; Simard, Jacques; Spurdle, Amanda B.; Holland, Helene; Chen, Xiaoqing; Platte, Radka; Chenevix-Trench, Georgia; Easton, Douglas F.

    2010-01-01

    The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 i

  6. Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction

    DEFF Research Database (Denmark)

    Antoniou, Antonis C; Beesley, Jonathan; McGuffog, Lesley;

    2010-01-01

    The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs650495...

  7. Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: Implications for risk prediction

    NARCIS (Netherlands)

    A.C. Antoniou (Antonis); J. Beesley (Jonathan); L. McGuffog (Lesley); O. Sinilnikova (Olga); S. Healey (Sue); S.L. Neuhausen (Susan); Y.C. Ding (Yuan); R. Rebbeck (Timothy); J.N. Weitzel (Jeffrey); H. Lynch (Henry); C. Isaacs (Claudine); P.A. Ganz (Patricia); G. Tomlinson (Gail); O.I. Olopade (Olofunmilayo); F.J. Couch (Fergus); X. Wang (Xing); N.M. Lindor (Noralane); V.S. Pankratz (Shane); P. Radice (Paolo); S. Manoukian (Siranoush); B. Peissel (Bernard); D. Zaffaroni (D.); M. Barile (Monica); A. Viel (Alessandra); A. Allavena (Anna); V. Dall'Olio (Valentina); P. Peterlongo (Paolo); C. Szabo (Csilla); M. Zikan (Michal); K. Claes (Kathleen); B. Poppe (Bruce); L. Foretova (Lenka); P.L. Mai (Phuong); M.H. Greene (Mark); G. Rennert (Gad); F. Lejbkowicz (Flavio); G. Glendon (Gord); H. Ozcelik (Hilmi); I.L. Andrulis (Irene); M. Thomassen (Mads); A-M. Gerdes (Anne-Marie); L. Sunde (Lone); D. Cruger (Dorthe); U.B. Jensen; M.A. Caligo (Maria); E. Friedman (Eitan); B. Kaufman (Bella); Y. Laitman (Yael); R. Milgrom (Roni); M. Dubrovsky (Maya); S. Cohen (Shimrit); Å. Borg (Åke); H. Jernström (H.); A. Lindblom (Annika); J. Rantala (Johanna); M. Stenmark-Askmalm (M.); B. Melin (Beatrice); K.L. Nathanson (Katherine); S.M. Domchek (Susan); A. Jakubowska (Anna); J. Lubinski (Jan); T. Huzarski (Tomasz); A. Osorio (Ana); A. Lasa (Adriana); M. Durán (Mercedes); M.I. Tejada; J. Godino (Javier); J. Benitez (Javier); U. Hamann (Ute); M. Kriege (Mieke); N. Hoogerbrugge (Nicoline); R.B. van der Luijt (Rob); C.J. van Asperen (Christi); P. Devilee (Peter); E.J. Meijers-Heijboer (Hanne); M.J. Blok (Marinus); C.M. Aalfs (Cora); F.B.L. Hogervorst (Frans); M.A. Rookus (Matti); M. Cook (Margaret); C.T. Oliver (Clare); D. Frost (Debra); D. Conroy (Don); D.G. Evans (Gareth); F. Lalloo (Fiona); G. Pichert (Gabriella); R. Davidson (Rosemarie); T.J. Cole (Trevor); J. Paterson (Joan); S.V. Hodgson (Shirley); P.J. Morrison (Patrick); M.E. Porteous (Mary); L.J. Walker (Lisa); M.J. Kennedy (John); H. Dorkins (Huw); S. Peock (Susan); A.K. Godwin (Andrew); D. Stoppa-Lyonnet (Dominique); A. de Pauw (Antoine); S. Mazoyer (Sylvie); V. Bonadona (Valérie); C. Lasset (Christine); H. Dreyfus (Hélène); D. Leroux (Dominique); A. hardouin (Agnès); P. Berthet (Pascaline); L. Faivre (Laurence); C. Loustalot (Catherine); T. Noguchi (Tetsuro); H. Sobol (Hagay); E. Rouleau (Etienne); C. Nogues (Catherine); M. Frenay (Marc); L. Vénat-Bouvet (Laurence); J. Hopper (John); M.J. Daly (Mark); M-B. Terry (Mary-beth); E.M. John (Esther); S.S. Buys (Saundra); Y. Yassin (Yosuf); A. Miron (Alexander); D. Goldgar (David); C.F. Singer (Christian); C. Dressler (Catherina); D. Gschwantler-Kaulich (Daphne); G. Pfeiler (Georg); T.V.O. Hansen (Thomas); L. Jnson (Lars); B.A. Agnarsson (Bjarni); T. Kircchoff (Tomas); K. Offit (Kenneth); V. Devlin (Vincent); A. Dutra-Clarke (Ana); M. Piedmonte (Marion); G.C. Rodriguez (Gustavo); K. Wakeley (Katie); J.F. Boggess (John); J. Basil (Jack); P.E. Schwartz (Peter); S.V. Blank (Stephanie); A.E. Toland (Amanda); M. Montagna (Marco); C. Casella (Cinzia); E.N. Imyanitov (Evgeny); L. Tihomirova (Laima); I. Blanco (Ignacio); C. Lazaro (Conxi); S.J. Ramus (Susan); L. Sucheston (Lara); B.Y. Karlan (Beth); J. Gross (Jenny); R.K. Schmutzler (Rita); B. Wapenschmidt (Barbara); C. Engel (Christoph); A. Meindl (Alfons); M. Lochmann (Magdalena); N. Arnold (Norbert); S. Heidemann (Simone); R. Varon-Mateeva (Raymonda); D. Niederacher (Dieter); C. Sutter (Christian); H. Deissler (Helmut); D. Gadzicki (Dorothea); S. Preisler-Adams (Sabine); K. Kast (Karin); I. Schönbuchner (Ines); T. Caldes (Trinidad); M. de La Hoya (Miguel); K. Aittomäki (Kristiina); H. Nevanlinna (Heli); J. Simard (Jacques); A.B. Spurdle (Amanda); H. Holland (Helene); G. Chenevix-Trench (Georgia); R. Platte (Radka); D.F. Easton (Douglas)

    2010-01-01

    textabstractThe known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10,

  8. Gene expression profiling in the lungs of pigs with different susceptibilities to Glässer's disease

    OpenAIRE

    Wilkinson, Jamie M; Sargent, Carole A.; Galina-Pantoja, Lucina; Tucker, Alexander W

    2010-01-01

    Background Haemophilus parasuis is the causative agent of Glässer's disease in pigs. Currently, little is known about the molecular mechanisms that contribute to disease susceptibility. This study used a porcine oligonucleotide microarray to identify genes that were differentially expressed (DE) in the lungs of colostrum-deprived animals previously characterized as being either 'Fully Resistant' (FR) or 'Susceptible' to infection by H. parasuis in a bacterial challenge experiment. Results Gen...

  9. Gene expression profiling in the lungs of pigs with different susceptibilities to Glässer's disease

    OpenAIRE

    Sargent Carole A; Wilkinson Jamie M; Galina-Pantoja Lucina; Tucker Alexander W

    2010-01-01

    Abstract Background Haemophilus parasuis is the causative agent of Glässer's disease in pigs. Currently, little is known about the molecular mechanisms that contribute to disease susceptibility. This study used a porcine oligonucleotide microarray to identify genes that were differentially expressed (DE) in the lungs of colostrum-deprived animals previously characterized as being either 'Fully Resistant' (FR) or 'Susceptible' to infection by H. parasuis in a bacterial challenge experiment. Re...

  10. The multiple sclerosis susceptibility genes TAGAP and IL2RA are regulated by vitamin D in CD4+ T cells

    OpenAIRE

    T. Berge; Leikfoss, I S; Brorson, I S; Bos, S.D.; Page, C. M.; Gustavsen, M W; Bjølgerud, A; Holmøy, T; Celius, E. G.; Damoiseaux, J; Smolders, J; Harbo, H.F.; Spurkland, A

    2016-01-01

    Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system that develops in genetically susceptible individuals. The majority of the MS-associated gene variants are located in genetic regions with importance for T-cell differentiation. Vitamin D is a potent immunomodulator, and vitamin D deficiency has been suggested to be associated with increased MS disease susceptibility and activity. In CD4+ T cells, we have analyzed in vitro vitamin D responsiveness ...

  11. Mutation analysis of the ATR gene in breast and ovarian cancer families

    International Nuclear Information System (INIS)

    Mutations in BRCA1, BRCA2, ATM, TP53, CHK2 and PTEN account for only 20–30% of the familial aggregation of breast cancer, which suggests the involvement of additional susceptibility genes. The ATR (ataxia-telangiectasia- and Rad3-related) kinase is essential for the maintenance of genomic integrity. It functions both in parallel and cooperatively with ATM, but whereas ATM is primarily activated by DNA double-strand breaks induced by ionizing radiation, ATR has been shown to respond to a much broader range of DNA damage. Upon activation, ATR phosphorylates several important tumor suppressors, including p53, BRCA1 and CHK1. Based on its central function in the DNA damage response, ATR is a plausible candidate gene for susceptibility to cancer. We screened the entire coding region of the ATR gene for mutations in affected index cases from 126 Finnish families with breast and/or ovarian cancer, 75 of which were classified as high-risk and 51 as moderate-risk families, by using conformation sensitive gel electrophoresis and direct sequencing. A large number of novel sequence variants were identified, four of which – Glu254Gly, Ser1142Gly, IVS24-48G>A and IVS26+15C>T – were absent from the tested control individuals (n = 300). However, the segregation of these mutations with the cancer phenotype could not be confirmed, partly because of the lack of suitable DNA samples. The present study does not support a major role for ATR mutations in hereditary susceptibility to breast and ovarian cancer

  12. Gene delivery for the treatment of prostate cancer

    OpenAIRE

    Fitzgerald, Kathleen A.

    2016-01-01

    Prostate cancer is one of the most common cancers diagnosed in men. Whilst treatments for early-stage disease are largely effective, current therapies for metastatic prostate cancer, particularly for bone metastasis, offer only a few months increased lifespan at best. Hence new treatments are urgently required. Small interfering RNA (siRNA) has been investigated for the treatment of prostate cancer where it can ‘silence’ specific cancer-related genes. However the clinical application of siRNA...

  13. Association of two mutations in the CHEK2 gene with breast cancer

    International Nuclear Information System (INIS)

    Cell-cycle checkpoint kinase 2 (CHEK2) is a central mediator of cellular responses to DNA damage. Ionizing radiation activates the CHEK2 protein via ATM-mediated phosphorylation and activated CHEK2 kinase can phosphorylate several substrates, including Cdc25A, p53 and E2F1, which mediate cell cycle arrest and apoptosis. CHEK2 phosphorylation of the breast cancer susceptibility protein BRCA1 regulates DNA double-strand break repair, and deletion of CHEK2 potentiate the incidence of mammary carcinomas in BRCA1 conditional mutant mice. A truncating variant of CHEK2, the 1100 delC mutation, has been identified as a low-penetrance breast-cancer susceptibility allele. Heterozygous 1100 delC carriers have an approximately 2-fold increased risk for breast cancer. The role of variants in CHEK2 other than 1100 delC is less clear. To assess the role of these CHEK2 variants in breast cancer, we conducted an association study of the I157T and IVS211G>A mutations in breast cancer case-control settings from the Belarus populations. Our series consisted of 424 breast cancer patients and 307 population controls. The missense substitution I157T was identified in 24/424 cases (5.7%) vs. 4/307 controls (1.3%; OR 54.5, 95% CI 1.6-13.2, p 5 0.005) in investigated cohorts. The splicing mutation IVS211G > A was infrequent, being observed 4/424 patients (0.9%). Heterozygous CHEK2 mutation carriers tended to be diagnosed at an earlier age, but these differences did not reach statistical significance. Family history of breast cancer did not differ between carriers and non carriers. Our data indicate that the I157T allele, and possibly the IVS211G > A allele, of the CHEK2 gene contribute to inherited breast cancer susceptibility. (authors)

  14. Gene Expression Correlation for Cancer Diagnosis: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Binbing Ling

    2014-01-01

    Full Text Available Poor prognosis for late-stage, high-grade, and recurrent cancers has been motivating cancer researchers to search for more efficient biomarkers to identify the onset of cancer. Recent advances in constructing and dynamically analyzing biomolecular networks for different types of cancer have provided a promising novel strategy to detect tumorigenesis and metastasis. The observation of different biomolecular networks associated with normal and cancerous states led us to hypothesize that correlations for gene expressions could serve as valid indicators of early cancer development. In this pilot study, we tested our hypothesis by examining whether the mRNA expressions of three randomly selected cancer-related genes PIK3C3, PIM3, and PTEN were correlated during cancer progression and the correlation coefficients could be used for cancer diagnosis. Strong correlations (0.68≤r≤1.0 were observed between PIK3C3 and PIM3 in breast cancer, between PIK3C3 and PTEN in breast and ovary cancers, and between PIM3 and PTEN in breast, kidney, liver, and thyroid cancers during disease progression, implicating that the correlations for cancer network gene expressions could serve as a supplement to current clinical biomarkers, such as cancer antigens, for early cancer diagnosis.

  15. BRCA1 and BRCA2 Gene Mutations Screening In Sporadic Breast Cancer Patients In Kazakhstan.

    Directory of Open Access Journals (Sweden)

    Ainur R. Akilzhanova

    2013-05-01

    Full Text Available Background: A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Kazakhstan women. Aim: To evaluate the role of BRCA1/2 mutations in Kazakhstan women presenting with sporadic breast cancer. Methods: We investigated the distribution and nature of polymorphisms in BRCA1 and BRCA2 entire coding regions in 156 Kazakhstan sporadic breast cancer cases and 112 age-matched controls using automatic direct sequencing. Results: We identified 22 distinct variants, including 16 missense mutations and 6 polymorphisms in BRCA1/2 genes. In BRCA1, 9 missense mutations and 3 synonymous polymorphisms were observed. In BRCA2, 7 missense mutations and 3 polymorphisms were detected. There was a higher prevalence of observed mutations in Caucasian breast cancer cases compared to Asian cases (p<0.05; higher frequencies of sequence variants were observed in Asian controls. No recurrent or founder mutations were observed in BRCA1/2 genes. There were no statistically significant differences in age at diagnosis, tumor histology, size of tumor, and lymph node involvement between women with breast cancer with or without the BRCA sequence alterations. Conclusions: Considering the majority of breast cancer cases are sporadic, the present study will be helpful in the evaluation of the need for the genetic screening of BRCA1/2 mutations and reliable genetic counseling for Kazakhstan sporadic breast cancer patients. Evaluation of common polymorphisms and mutations and breast cancer risk in families with genetic predisposition to breast cancer is ongoing in another current investigation. 

  16. Microarray analysis of gene expression profiles of Schistosoma japonicum derived from less-susceptible host water buffalo and susceptible host goat.

    Directory of Open Access Journals (Sweden)

    Jianmei Yang

    Full Text Available BACKGROUND: Water buffalo and goats are natural hosts for S. japonicum in endemic areas of China. The susceptibility of these two hosts to schistosome infection is different, as water buffalo are less conducive to S. japonicum growth and development. To identify genes that may affect schistosome development and survival, we compared gene expression profiles of schistosomes derived from these two natural hosts using high-throughput microarray technology. RESULTS: The worm recovery rate was lower and the length and width of worms from water buffalo were smaller compared to those from goats following S. japonicum infection for 7 weeks. Besides obvious morphological difference between the schistosomes derived from the two hosts, differences were also observed by scanning and transmission electron microscopy. Microarray analysis showed differentially expressed gene patterns for parasites from the two hosts, which revealed that genes related to lipid and nucleotide metabolism, as well as protein folding, sorting, and degradation were upregulated, while others associated with signal transduction, endocrine function, development, immune function, endocytosis, and amino acid/carbohydrate/glycan metabolism were downregulated in schistosomes from water buffalo. KEGG pathway analysis deduced that the differentially expressed genes mainly involved lipid metabolism, the MAPK and ErbB signaling pathways, progesterone-mediated oocyte maturation, dorso-ventral axis formation, reproduction, and endocytosis, etc. CONCLUSION: The microarray gene analysis in schistosomes derived from water buffalo and goats provide a useful platform to disclose differences determining S. japonicum host compatibility to better understand the interplay between natural hosts and parasites, and identify schistosome target genes associated with susceptibility to screen vaccine candidates.

  17. Expression patterns of esophageal cancer deregulated genes in C57BL/6J mouse embryogenesis

    Institute of Scientific and Technical Information of China (English)

    Jian Zhang; Fu-Lu Gao; Hui-Ying Zhi; Ai-Ping Luo; Fang Ding; Min Wu; Zhi-Hua Liu

    2004-01-01

    development may serve as candidate susceptibility genes for inherited esophageal cancer disorders as well as for various heritable disorders of embryonic development.

  18. Gene Therapy of Cancer: Induction of Anti-Tumor Immunity

    Institute of Scientific and Technical Information of China (English)

    Cheng Qian; Jesus Prieto

    2004-01-01

    Many malignancies lack satisfactory treatment and new therapeutic options are urgently needed. Gene therapy is a new modality to treat both inherited and acquired diseases based on the transfer of genetic material to the tissues. Different gene therapy strategies against cancers have been developed. A considerable number of preclinical studies indicate that a great variety of cancers are amenable to gene therapy. Among these strategies,induction of anti-tumorimmunity is the most promising approach. Gene therapy with cytokines has reached unprecedented success in preclinical models of cancer. Synergistic rather than additive effects have beendemonstrated by combination of gene transfer of cytokines/chemokines, costimulatory molecules or adoptive cell therapy. Recent progress in vector technology and in imaging techniques allowing in vivo assessment of gene expression will facilitate the development of clinical applications of gene therapy, a procedure which may have a notorious impact in the management of cancers lacking effective treatment.

  19. Gene therapy for gastric cancer: Is it promising?

    Institute of Scientific and Technical Information of China (English)

    Andreas P Sutter; Henry Fechner

    2006-01-01

    Gastric cancer is one of the most common tumors worldwide. The therapeutic outcome of conventional therapies is inefficient. Thus, new therapeutic strategies are urgently needed. Gene therapy is a promising molecular alternative in the treatment of gastric cancer,including the replacement of defective tumor suppressor genes, the inactivation of oncogenes, the introduction of suicide genes, genetic immunotherapy, anti-angiogenetic gene therapy, and virotherapy. Improved molecular biological techniques and a better understanding of gastric carcinogenesis have allowed us to validate a variety of genes as molecular targets for gene therapy.This review provides an update of the new developments in cancer gene therapy, new principles, techniques,strategies and vector systems, and shows how they may be applied in the treatment of gastric cancer.

  20. Suicide genes or p53 gene and p53 target genes as targets for cancer gene therapy by ionizing radiation

    International Nuclear Information System (INIS)

    Radiotherapy has some disadvantages due to the severe side-effect on the normal tissues at a curative dose of ionizing radiation (IR). Similarly, as a new developing approach, gene therapy also has some disadvantages, such as lack of specificity for tumors, limited expression of therapeutic gene, potential biological risk. To certain extent, above problems would be solved by the suicide genes or p53 gene and its target genes therapies targeted by ionizing radiation. This strategy not only makes up the disadvantage from radiotherapy or gene therapy alone, but also promotes success rate on the base of lower dose. By present, there have been several vectors measuring up to be reaching clinical trials. This review focused on the development of the cancer gene therapy through suicide genes or p53 and its target genes mediated by IR. (authors)

  1. Immuno-isolation in cancer gene therapy.

    Science.gov (United States)

    Cirone, Pasquale; Potter, Murray; Hirte, Hal; Chang, Patricia

    2006-04-01

    The implantation of genetically-modified non-autologous cells in immuno-protected microcapsules is an alternative to ex vivo gene therapy. Such cells delivering a recombinant therapeutic product are isolated from the host's immune system by being encapsulated within permselective microcapsules. This approach has been successful in pre-clinical animal studies involving delivery of hormone or enzymes to treat dwarfism, lysosomal storage disease, or hemophilia B. Recently, this platform technology has shown promise in the treatment for more complex diseases such as cancer. One of the earliest strategy was to augment the chemotherapeutic effect of a prodrug by implanting encapsulated cells that can metabolise prodrugs into cytotoxic products in close proximity to the cancer cells. More recent approaches include enhancing tumor cell death through immunotherapy, or suppressing tumor cell proliferation through anti-angiogenesis. These can be achieved by delivering single molecules of cytokines or angiostatin, respectively, by implanting microencapsulated cells engineered to secrete these recombinant products. Recent refinements of these approaches include genetic fusion of cytokines or angiostatin to additional functional groups with tumor targeting or tumor cell killing properties, thus enhancing the potency of the recombinant products. Furthermore, a COMBO strategy of implanting microencapsulated cells to deliver multiple products targeted to diverse pathways in tumor suppression also showed much promise. This review will summarise the application of microencapsulation of genetically-modified cells to cancer treatment in animal models, the efficacy of such approaches, and how these studies have led to better understanding of the biology of cancer treatment. The flexibility of this modular system involving molecular engineering, cellular genetic modification, and polymer chemistry provides potentially a huge range of application modalities, and a tremendous multi

  2. 大规模单核苷酸多态性分析与肿瘤易感性%Large-scale Single Nucleotide Polymorphism Analysis and Cancer Susceptibility

    Institute of Scientific and Technical Information of China (English)

    王娟

    2007-01-01

    单核苷酸多态性(SNPs)是人类基因组中最常见的变异形式.作为第三代遗传标记,SNP在基因定位、克隆、遗传多态性方面具有广泛应用,特别是作为基因诊断标记在预防医学中具有十分重要的作用.近年来,随着人类基因组计划的发展,数以百万计的SNP被陆续发现,并可在公共数据库中免费获得.SNP数量的快速增加和SNP检测方法的发展,为其在肿瘤易感性领域的应用提供了可能.在本综述中,我们介绍了几种高通量检测SNP的分析方法,总结了大规模SNP分析技术在肿瘤易感性中的应用,介绍了目前人们对于不同人群中的SNP分析、肿瘤易感基因、个体肿瘤易感性的理解,以及研究SNP标记与肿瘤易感性关系时存在的难点.%Single nucleotide polymorphisms (SNPs) are the most common sources of variation between humans. As a kind of new genetic marker, SNPs are used extensively in gene location, clone and genetic polymorphisms. Specially, as diagnostic markers, the genetic SNPs play an important role in preventive medicine. In recent years, with the development of human genome project, millions of SNPs are reported and freely available in public databases. The rapid increase of SNP number and the development of detection methods for SNPs provide probability for the analysis of cancer susceptibility. In this review, we described main methods for high-throughput SNP analysis technologies. We summarized the application of SNPs analysis by large-scale analytic technologies in cancer susceptibility, the current understanding of SNP analysis in the different populations, tumor susceptibility genes and individual cancer susceptibility, as well as the obstacles in discovering the relationship between SNP analysis and cancer susceptibility underlying complex human traits.

  3. Optimal search-based gene subset selection for gene array cancer classification.

    Science.gov (United States)

    Li, Jiexun; Su, Hua; Chen, Hsinchun; Futscher, Bernard W

    2007-07-01

    High dimensionality has been a major problem for gene array-based cancer classification. It is critical to identify marker genes for cancer diagnoses. We developed a framework of gene selection methods based on previous studies. This paper focuses on optimal search-based subset selection methods because they evaluate the group performance of genes and help to pinpoint global optimal set of marker genes. Notably, this paper is the first to introduce tabu search (TS) to gene selection from high-dimensional gene array data. Our comparative study of gene selection methods demonstrated the effectiveness of optimal search-based gene subset selection to identify cancer marker genes. TS was shown to be a promising tool for gene subset selection. PMID:17674622

  4. Patterns and functional implications of rare germline variants across 12 cancer types

    OpenAIRE

    Lu, Charles; Xie, Mingchao; Wendl, Michael C; Wang, Jiayin; McLellan, Michael D; Mark D M Leiserson; Huang, Kuan-lin; Wyczalkowski, Matthew A.; Jayasinghe, Reyka; Banerjee, Tapahsama; Ning, Jie; Tripathi, Piyush; Zhang, Qunyuan; Niu, Beifang; Ye, Kai

    2015-01-01

    Large-scale cancer sequencing data enable discovery of rare germline cancer susceptibility variants. Here we systematically analyse 4,034 cases from The Cancer Genome Atlas cancer cases representing 12 cancer types. We find that the frequency of rare germline truncations in 114 cancer-susceptibility-associated genes varies widely, from 4% (acute myeloid leukaemia (AML)) to 19% (ovarian cancer), with a notably high frequency of 11% in stomach cancer. Burden testing identifies 13 cancer genes w...

  5. Relationship between Polymorphism of HLA-DP Gene and Susceptibility Hepatitis C Infection

    Institute of Scientific and Technical Information of China (English)

    WANG Jia; XIAO Rong-rong; SHEN Hong-bing

    2015-01-01

    Objective:To assess the relationship between HLA-DP gene polymorphism and the susceptibility of HCV infection among high-risk populations in Jiangsu Province. Methods: Three HLA-DP variants of rs3077, rs9277535 and rs2395309 were genotyped in 1653 subjects including 268 self-limited HCV infection subjects, 401 persistent HCV infection subjects and 984 healthy control people using Taqman- MGB. Results: The frequencies of rs3077, rs9277535 and rs2395309 mutant genotype in HCV infected group were much higher than in control group (Prs3077<0.010;Prs9277535=0.043;Prs2395309<0.010); The frequencies of rs3077 TC and rs2395309 AG heterozygous genotypes were much higher than control group (Prs3077=0.033,Prs2395309=0.037). And the frequency of rs9277535 GA heterozygous genotype in HCV persistent infection group was higher than in spontaneous clearance group (P= 0.044). Conclusion: These variants in the HLA-DP locus are associated with the susceptibility of HCV infection.

  6. Converging findings from linkage and association analyses on susceptibility genes for smoking and other addictions.

    Science.gov (United States)

    Yang, J; Li, M D

    2016-08-01

    Experimental approaches to genetic studies of complex traits evolve with technological advances. How do discoveries using different approaches advance our knowledge of the genetic architecture underlying complex diseases/traits? Do most of the findings of newer techniques, such as genome-wide association study (GWAS), provide more information than older ones, for example, genome-wide linkage study? In this review, we address these issues by developing a nicotine dependence (ND) genetic susceptibility map based on the results obtained by the approaches commonly used in recent years, namely, genome-wide linkage, candidate gene association, GWAS and targeted sequencing. Converging and diverging results from these empirical approaches have elucidated a preliminary genetic architecture of this intractable psychiatric disorder and yielded new hypotheses on ND etiology. The insights we obtained by putting together results from diverse approaches can be applied to other complex diseases/traits. In sum, developing a genetic susceptibility map and keeping it updated are effective ways to keep track of what we know about a disease/trait and what the next steps may be with new approaches. PMID:27166759

  7. Search of type 2 diabetes susceptibility gene on chromosome 20q

    International Nuclear Information System (INIS)

    Significant evidence of linkage to type 2 diabetes (T2D) has been shown in a relatively broad region on chromosome 20q, where the hepatocyte nuclear factor-4α (HNF4A) has been noted as a positional candidate. To systematically evaluate genetic susceptibility to T2D in the relevant region, we examined the disease association by using 1145 SNPs in two-step screening in the Japanese population. The marker screening enabled us to identify significant disease association in the lipopolysaccharide binding protein (LBP) but not in the HNF4A locus. In a 17.7-Mb interval screened, the strongest association was identified for a SNP, rs2232592, located in the intron of LBP, with an estimated odds ratio of 1.73 (95% CI 1.30-2.31) (P 0.0002) in the whole study panel involving 675 case and 474 control subjects. Our data suggest that the LBP gene may confer genetic susceptibility to T2D and this warrants further replication study

  8. Identification of genes involved in breast cancer and breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Apostolou P

    2015-07-01

    Full Text Available Panagiotis Apostolou, Maria Toloudi, Ioannis Papasotiriou Research and Development Department, Research Genetic Cancer Centre Ltd, Florina, Greece Abstract: Breast cancer is the most frequent type of cancer in women. Great progress has been made in its treatment but relapse is common. One hypothesis to account for the high recurrence rates is the presence of cancer stem cells (CSCs, which have the ability to self-renew and differentiate into multiple malignant cell types. This study aimed to determine genes that are expressed in breast cancer and breast CSCs and to investigate their correlation with stemness. RNA was extracted from established breast cancer cell lines and from CSCs derived from five different breast cancer patients. DNA microarray analysis was performed and any upregulated genes were also studied in other cancer types, including colorectal and lung cancer. For genes that were expressed only in breast cancer, knockdown-based experiments were performed. Finally, the gene expression levels of stemness transcription factors were measured. The outcome of the analysis indicated a group of genes that were aberrantly expressed mainly in breast cancer cells with stemness properties. Knockdown experiments confirmed the impact of several of these on NANOG, OCT3/4, and SOX2 transcription factors. It seems that several genes that are not directly related with hormone metabolism and basic signal transduction pathways might have an important role in relapse and disease progression and, thus, can be targeted for new treatment approaches for breast cancer. Keywords: breast cancer, cancer stem cells, stemness, DNA microarray

  9. Mutational analysis of the BRCA1 gene in 30 Czech ovarian cancer patients

    Indian Academy of Sciences (India)

    M. Zikan; P. Pohlreich; J. Stribrna

    2005-04-01

    Ovarian cancer is one of the most severe of oncological diseases. Inherited mutations in cancer susceptibility genes play a causal role in 5–10% of newly diagnosed tumours. BRCA1 and BRCA2 gene alterations are found in the majority of these cases. The aim of this study was to analyse the BRCA1 gene in the ovarian cancer risk group to characterize the spectrum of its mutations in the Czech Republic. Five overlapping fragments amplified on both genomic DNA and cDNA were used to screen for the whole protein-coding sequence of the BRCA1 gene. These fragments were analysed by the protein truncation test (PTT) and direct sequencing. Three inactivating mutations were identified in the group of 30 Czech ovarian cancer patients: the 5382insC mutation in two unrelated patients and a deletion of exons 21 and 22 in another patient. In addition, we have found an alternatively spliced product lacking exon 5 in two other unrelated patients. The 5382insC is the most frequent alteration of the BRCA1 gene in Central and Eastern Europe. The deletion of exons 21 and 22 affects the BRCT functional domain of the BRCA1 protein. Although large genomic rearragements are known to be relatively frequent in Western European populations, no analyses have been performed in our region yet.

  10. Oxytocin receptor gene variation and differential susceptibility to family environment in predicting youth borderline symptoms.

    Science.gov (United States)

    Hammen, Constance; Bower, Julienne E; Cole, Steven W

    2015-04-01

    Oxytocin appears to be centrally involved in socioemotional functioning, and is hypothesized to be relevant to the severe disruption in close relationships characteristic of borderline personality pathology. We examined whether a polymorphism of the oxytocin receptor gene (OXTR rs53576) interacts with quality of family functioning to predict borderline personality disorder (BPD) symptomatology in a sample of youth at age 20. A total of 385 youth from a longitudinal study of offspring of depressed or nondepressed mothers who were well characterized with respect to their family conditions and BPD symptomatology provided DNA for genotyping. Analyses revealed a significant moderation of the link between early family quality and later BPD symptoms by OXTR rs53576, and the pattern was consistent with differential susceptibility (plasticity). Whereas A-allele carriers had high levels of BPD symptoms under negative family conditions and low levels under positive conditions, GG homozygotes had average levels of BPD symptoms regardless of their family quality. PMID:25102084

  11. Gene expression profile differences in gastric cancer, pericancerous epithelium and normal gastric mucosa by gene chip

    Institute of Scientific and Technical Information of China (English)

    Chuan-Ding Yu; Shen-Hua Xu; Hang-Zhou Mou; Zhi-Ming Jiang; Chi-Hong Zhu; Xiang-Lin Liu

    2005-01-01

    AIM: To study the difference of gene expression in gastric cancer (T), pericancerous epithelium (P) and normal tissue of gastric mucosa (C), and to screen an associated novel gene in early gastric carcinogenesis by oligonudeotide microarray.METHODS: U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T, P and C, respectively. Bioinformatics was used to analyze the detected results.RESULTS: When gastric cancer was compared with normal gastric mucosa, 766 genes were found, with a difference of more than four times in expression levels. Of the 766 genes,530 were up-regulated (Signal Log Ratio [SLR]>2), and 236 were down-regulated (SLR<-2). When pericancerous epithelium was compared with normal gastric mucosa, 64genes were found, with a difference of more than four times in expression levels. Of the 64 genes, 50 were up-regulated (SLR>2), and 14 were down-regulated (SLR<-2). Compared with normal gastric mucosa, a total of 143 genes with a difference in expression levels (more than four times, either in cancer or in pericancerous epithelium) were found in gastric cancer (T) and pericancerous epithelium (P). Of the 143 genes, 108 were up-regulated (SLR>2), and 35were down-regulated (SLR<-2).CONCLUSION: To apply a gene chip could find 143 genes associated with the genes of gastric cancer in pericancerous epithelium, although there were no pathological changes in the tissue slices. More interesting, six genes of pericancerous epithelium were up-regulated in comparison with genes of gastric cancer and three genes were down-regulated in comparison with genes of gastric cancer. It is suggested that these genes may be related to the carcinogenesis and development of early gastric cancer.

  12. Genome-wide search for gene-gene interactions in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Shuo Jiao

    Full Text Available Genome-wide association studies (GWAS have successfully identified a number of single-nucleotide polymorphisms (SNPs associated with colorectal cancer (CRC risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG is considered to be one source of the missing heritability. To address this, we performed a genome-wide search for pair-wise GxG associated with CRC risk using 8,380 cases and 10,558 controls in the discovery phase and 2,527 cases and 2,658 controls in the replication phase. We developed a simple, but powerful method for testing interaction, which we term the Average Risk Due to Interaction (ARDI. With this method, we conducted a genome-wide search to identify SNPs showing evidence for GxG with previously identified CRC susceptibility loci from 14 independent regions. We also conducted a genome-wide search for GxG using the marginal association screening and examining interaction among SNPs that pass the screening threshold (p<10(-4. For the known locus rs10795668 (10p14, we found an interacting SNP rs367615 (5q21 with replication p = 0.01 and combined p = 4.19×10(-8. Among the top marginal SNPs after LD pruning (n = 163, we identified an interaction between rs1571218 (20p12.3 and rs10879357 (12q21.1 (nominal combined p = 2.51×10(-6; Bonferroni adjusted p = 0.03. Our study represents the first comprehensive search for GxG in CRC, and our results may provide new insight into the genetic etiology of CRC.

  13. Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease

    International Nuclear Information System (INIS)

    Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD

  14. NAT2 polymorphisms combining with smoking associated with breast cancer susceptibility: a meta-analysis.

    Science.gov (United States)

    Zhang, Jian; Qiu, Li-Xin; Wang, Zhong-Hua; Wang, Jia-Lei; He, Shuang-Shuang; Hu, Xi-Chun

    2010-10-01

    To derive a more precise estimation of the relationship between the slow or rapid acetylation resulting from N-acetyltransferase 2 (NAT2) polymorphisms and breast cancer risk, a meta-analysis was performed. PubMed, Medline, Embase, and Web of Science were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess strength of association. The pooled ORs were performed for slow versus rapid acetylation genotypes. A total of 26 studies including 9,215 cases and 10,443 controls were included in the meta-analysis. Overall, no significantly elevated breast cancer risk was associated with NAT2 slow genotypes when all studies were pooled into the meta-analysis (OR = 1.026, 95% CI = 0.968-1.087). In the subgroup analysis by ethnicity, increased risks were not found for either Caucasians (OR = 1.001, 95% CI = 0.938-1.068) or Asians (OR = 1.155, 95% CI = 0.886-1.506). When stratified by study design, statistically significantly elevated risk associated with NAT2 slow genotypes was only found among hospital-based studies (OR = 1.178, 95% CI = 1.037-1.339). In the subgroup analysis by menopausal status, no statistically significantly increased risk was found in either premenopausal (OR = 1.053, 95% CI = 0.886-1.252) or postmenopausal women (OR = 0.965, 95% CI = 0.844-1.104). When stratified by cumulative smoking exposure, in the subgroup of smokers with high pack-years, NAT2 slow genotypes were significantly associated with increased breast cancer risk (OR = 1.400, 95% CI = 1.099-1.784). In conclusion, this meta-analysis suggested that there is overall lack of association between NAT2 genotypes and breast cancer risk, however, NAT2 polymorphisms when combining with heavy smoking history may contribute to breast cancer susceptibility. PMID:20180012

  15. Hormone-dependent effects of FGFR2 and MAP3K1 in breast cancer susceptibility in a population-based sample of post-menopausal African-American and European-American women

    OpenAIRE

    Timothy R Rebbeck; DeMichele, Angela; Tran, Teo V.; Panossian, Saarene; Bunin, Greta R.; Troxel, Andrea B.; Strom, Brian L

    2008-01-01

    FGFR2 and MAP3K1 are members of the RAS/RAF/MEK/ERK-signaling pathway and have been identified from genome-wide association studies to be breast cancer susceptibility genes. Potential interactions of these genes and their role with respect to tumor markers, hormonal factors and race on breast cancer risk have not been explored. We examined FGFR2 and MAP3K1 variants, breast tumor characteristics and hormone exposures in a population-based case–control sample of 1225 European-American (EA) and ...

  16. Men with Advanced Prostate Cancer Might Consider Gene Test

    Science.gov (United States)

    ... whether abnormal DNA repair genes could help predict disease outcomes, the scientists said. The study team consisted of researchers from Memorial Sloan Kettering Cancer Center, Fred Hutchinson Cancer Research Center in Seattle, Dana-Farber Cancer Institute in Boston, the University of Washington ...

  17. Bacteriophage-Derived Vectors for Targeted Cancer Gene Therapy

    Directory of Open Access Journals (Sweden)

    Md Zahidul Islam Pranjol

    2015-01-01

    Full Text Available Cancer gene therapy expanded and reached its pinnacle in research in the last decade. Both viral and non-viral vectors have entered clinical trials, and significant successes have been achieved. However, a systemic administration of a vector, illustrating safe, efficient, and targeted gene delivery to solid tumors has proven to be a major challenge. In this review, we summarize the current progress and challenges in the targeted gene therapy of cancer. Moreover, we highlight the recent developments of bacteriophage-derived vectors and their contributions in targeting cancer with therapeutic genes following systemic administration.

  18. Targeting p53 and its domains for cancer gene therapy

    OpenAIRE

    Karina Julia Matissek

    2014-01-01

    The tumor suppressor p53 is one of the most frequently mutated proteins in human cancer and has been extensively targeted for cancer therapy. This resulted in wild type p53 gene therapeutic approval for the treatment of head and neck cancer in China. p53 mainly functions as a transcription factor and stimulates a variety of genes involved in the intrinsic and extrinsic apoptotic pathway by binding to p53 responsive elements as a t...

  19. Stem Cell Based Gene Therapy in Prostate Cancer

    OpenAIRE

    Jae Heon Kim; Hong Jun Lee; Yun Seob Song

    2014-01-01

    Current prostate cancer treatment, especially hormone refractory cancer, may create profound iatrogenic outcomes because of the adverse effects of cytotoxic agents. Suicide gene therapy has been investigated for the substitute modality for current chemotherapy because it enables the treatment targeting the cancer cells. However the classic suicide gene therapy has several profound side effects, including immune-compromised due to viral vector. Recently, stem cells have been regarded as a new ...

  20. Genetic Polymorphisms of TGFB1, TGFBR1, SNAI1 and TWIST1 Are Associated with Endometrial Cancer Susceptibility in Chinese Han Women

    Science.gov (United States)

    Yang, Li; Wang, Ya-Jun; Zheng, Li-Yuan; Jia, Yu-Mian; Chen, Yi-Lin; Chen, Lan; Liu, Dong-Ge; Li, Xiang-Hong; Guo, Hong-Yan; Sun, Ying-Li; Tian, Xin-Xia; Fang, Wei-Gang

    2016-01-01

    Endometrial cancer (EC) is a complex disease involving multiple gene-gene and gene–environment interactions. TGF-β signaling plays pivotal roles in EC development. This study aimed to investigate whether the genetic polymorphisms of TGF-β signaling related genes TGFB1, TGFBR1, SNAI1 and TWIST1 contribute to EC susceptibility. Using the TaqMan Genotyping Assay, 19 tagging-SNPs of these four genes were genotyped in 516 EC cases and 707 controls among Chinese Han women. Logistic regression (LR) showed that the genetic variants of TGFB1 rs1800469, TGFBR1 rs6478974 and rs10733710, TWIST1 rs4721745 were associated with decreased EC risk, and these four loci showed a dose-dependent effect (Ptrend pregnancy intervals (˃11 years) and BMI˂24 (aOR = 0.39, 95% CI = 0.17–0.90, P = 0.0275). These results suggest that polymorphisms in TGFB1, TGFBR1, SNAI1 and TWIST1 may modulate EC susceptibility, both separately and corporately. PMID:27171242

  1. ANALYSES ON DIFFERENTIALLY EXPRESSED GENES ASSOCIATED WITH HUMAN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    MENG Xu-li; DING Xiao-wen; XU Xiao-hong

    2006-01-01

    Objective: To investigate the molecular etiology of breast cancer by way of studying the differential expression and initial function of the related genes in the occurrence and development of breast cancer. Methods: Two hundred and eighty-eight human tumor related genes were chosen for preparation of the oligochips probe. mRNA was extracted from 16 breast cancer tissues and the corresponding normal breast tissues, and cDNA probe was prepared through reverse-transcription and hybridized with the gene chip. A laser focused fluorescent scanner was used to scan the chip. The different gene expressions were thereafter automatically compared and analyzed between the two sample groups. Cy3/Cy5>3.5 meant significant up-regulation. Cy3/Cy5<0.25 meant significant down-regulation. Results: The comparison between the breast cancer tissues and their corresponding normal tissues showed that 84 genes had differential expression in the Chip. Among the differently expressed genes, there were 4 genes with significant down-regulation and 6 with significant up-regulation. Compared with normal breast tissues, differentially expressed genes did partially exist in the breast cancer tissues. Conclusion: Changes in multi-gene expression regulations take place during the occurrence and development of breast cancer; and the research on related genes can help understanding the mechanism of tumor occurrence.