Mellon, Suzanne; Gold, Robin; Janisse, James; Cichon, Michelle; Tainsky, Michael A; Simon, Michael S.; Korczak, Jeannette
While families at increased risk for familial breast/ovarian cancer continue to overestimate their cancer risk with increased cancer worries about the future, few studies have examined factors that affect inherited cancer risk perception and cancer worries in both survivors and unaffected female relatives. The purpose of this study was to examine variables that may affect cancer worries and risk perceptions from a family-based perspective in a racially diverse, community-based, random sample ...
Koifman Rosalina Jorge
Full Text Available Antecedents of familial aggregation of breast and ovarian cancer are observed in only 5-8% of all breast cancer cases. Nevertheless, this variable displays one of the highest risk ratios associated to breast cancer outcome. Despite recent identification of genetic mutations associated with familial aggregation of these tumors, mainly at BRCA1 and BRCA2 genes, knowledge on the interaction between environmental agents in these families remains quite unclear. In this paper we ascertained the correlation among ages of the onset of breast/ovarian cancer in 260 Brazilian families with those cancer aggregation. Further we estimated the median age of the onset of breast cancer among four generations. We observed that the higher the number of family cancer cases, the highest is the correlation of ages for the onset of breast cancer. We also observed a 8-10 year decline in the mean age-of-onset of breast/ovarian cancer from one generation to another in the studied families. If these results could be confirmed elsewhere, we believe that the hypothesis of interaction between environmental risks factors in families indeed showing breast/ovarian cancer aggregation is reinforced.
Gutiérrez-Enríquez, Sara; de la Hoya, Miguel; Martínez-Bouzas, Cristina; Sanchez de Abajo, Ana; Ramón y Cajal, Teresa; Llort, Gemma; Blanco, Ignacio; Beristain, Elena; Díaz-Rubio, Eduardo; Alonso, Carmen; Tejada, María-Isabel; Caldés, Trinidad; Diez, Orland
Germ-line mutations in BRCA1 and BRCA2 are responsible for about 30-60% of the hereditary breast and ovarian cancer (HBOC). A large number of point mutations have been described in both genes. However, large deletions and duplications that disrupt one or more exons are overlooked by point mutation detection approaches. Over the past years several rearrangements have been identified in BRCA1, while few studies have been designed to screen this type of mutations in BRCA2. Our aim was to estimate the prevalence of large genomic rearrangements in the BRCA2 gene in Spanish breast/ovarian cancer families. The multiplex ligation-dependent probe amplification (MLPA) was employed to search gross deletions or duplications of BRCA2 in 335 Spanish moderate to high-risk breast/ovarian cancer families previously screened negative for point mutations by conventional methods. Four different and novel large genomic alterations were consistently identified by MLPA in five families, respectively: deletions of exon 2, exons 10-12 and exons 15-16 and duplication of exon 20 (in two families). RT-PCR experiments confirmed the deletion of exons 15-16. All patients harbouring a genomic rearrangement were members of high-risk families, with three or more breast/ovarian cancer cases or the presence of breast cancer in males. We provide evidence that the BRCA2 rearrangements seem to account for a relatively small proportion of familial breast cancer cases in Spanish population. The screening for these alterations as part of the comprehensive genetic testing can be recommended, especially in multiple case breast/ovarian families and families with male breast cancer cases. PMID:17063271
Full Text Available Background: BRCA1 and BRCA2 germline mutations predispose heterozygous carriers to hereditary breast/ovarian cancer. However, unclassified variants (UVs (variants with unknown clinical significance and missense polymorphisms in BRCA1 and BRCA2 genes pose a problem in genetic counseling, as their impact on risk of breast and ovarian cancer is still unclear. The objective of our study was to identify UVs and missense polymorphisms in Algerian breast/ovarian cancer patients and relatives tested previously for BRCA1 and BRCA2 genes germline mutations analysis.
de la Hoya, Miguel; Osorio, Ana; Diez, Orland; Miramar, María Dolores; Infante, Mar; Martinez-Bouzas, Cristina; Torres, Asunción; Lasa, Adriana; Llort, Gemma; Brunet, Joan; Graña, Begoña; Perez Segura, Pedro; Garcia, María José; Gutiérrez-Enríquez, Sara; Carracedo, Ángel; Tejada, María-Isabel; Velasco, Eladio A.; Calvo, María-Teresa; Balmaña, Judith; Benitez, Javier; Caldés, Trinidad
Background The PALB2 gene, also known as FANCN, forms a bond and co-localizes with BRCA2 in DNA repair. Germline mutations in PALB2 have been identified in approximately 1% of familial breast cancer and 3–4% of familial pancreatic cancer. The goal of this study was to determine the prevalence of PALB2 mutations in a population of BRCA1/BRCA2 negative breast cancer patients selected from either a personal or family history of pancreatic cancer. Methods 132 non-BRCA1/BRCA2 breast/ovarian cancer families with at least one pancreatic cancer case were included in the study. PALB2 mutational analysis was performed by direct sequencing of all coding exons and intron/exon boundaries, as well as multiplex ligation-dependent probe amplification. Results Two PALB2 truncating mutations, the c.1653T>A (p.Tyr551Stop) previously reported, and c.3362del (p.Gly1121ValfsX3) which is a novel frameshift mutation, were identified. Moreover, several PALB2 variants were detected; some of them were predicted as pathological by bioinformatic analysis. Considering truncating mutations, the prevalence rate of our population of BRCA1/2-negative breast cancer patients with pancreatic cancer is 1.5%. Conclusions The prevalence rate of PALB2 mutations in non-BRCA1/BRCA2 breast/ovarian cancer families, selected from either a personal or family pancreatic cancer history, is similar to that previously described for unselected breast/ovarian cancer families. Future research directed towards identifying other gene(s) involved in the development of breast/pancreatic cancer families is required. PMID:23935836
Abstract Inherited breast-ovarian cancer was described in 1866. The underlying genetic defects in BRCA1/2 were demonstrated 128 years later. We now have 10 years of experience with genetic testing in BRCA kindreds. The majority of breast cancer kindreds (familial breast cancer) do not demonstrate ovarian cancer and are not associated with BRCA mutations. The effect of early diagnosis and treatment is monitored through international collaborations. BRCA1-associated breast cancer is biologicall...
Ataxia telangiectasia-mutated and Rad3-related (ATR) is a member of the PIK-related family which plays, along with ATM, a central role in cell-cycle regulation. ATR has been shown to phosphorylate several tumor suppressors like BRCA1, CHEK1 and TP53. ATR appears as a good candidate breast cancer susceptibility gene and the current study was designed to screen for ATR germline mutations potentially involved in breast cancer predisposition. ATR direct sequencing was performed using a fluorescent method while widely available programs were used for linkage disequilibrium (LD), haplotype analyses, and tagging SNP (tSNP) identification. Expression analyses were carried out using real-time PCR. The complete sequence of all exons and flanking intronic sequences were analyzed in DNA samples from 54 individuals affected with breast cancer from non-BRCA1/2 high-risk French Canadian breast/ovarian families. Although no germline mutation has been identified in the coding region, we identified 41 sequence variants, including 16 coding variants, 3 of which are not reported in public databases. SNP haplotypes were established and tSNPs were identified in 73 healthy unrelated French Canadians, providing a valuable tool for further association studies involving the ATR gene, using large cohorts. Our analyses led to the identification of two novel alternative splice transcripts. In contrast to the transcript generated by an alternative splicing site in the intron 41, the one resulting from a deletion of 121 nucleotides in exon 33 is widely expressed, at significant but relatively low levels, in both normal and tumoral cells including normal breast and ovarian tissue. Although no deleterious mutations were identified in the ATR gene, the current study provides an haplotype analysis of the ATR gene polymorphisms, which allowed the identification of a set of SNPs that could be used as tSNPs for large-scale association studies. In addition, our study led to the characterization of a
Full Text Available Abstract Background Ataxia telangiectasia-mutated and Rad3-related (ATR is a member of the PIK-related family which plays, along with ATM, a central role in cell-cycle regulation. ATR has been shown to phosphorylate several tumor suppressors like BRCA1, CHEK1 and TP53. ATR appears as a good candidate breast cancer susceptibility gene and the current study was designed to screen for ATR germline mutations potentially involved in breast cancer predisposition. Methods ATR direct sequencing was performed using a fluorescent method while widely available programs were used for linkage disequilibrium (LD, haplotype analyses, and tagging SNP (tSNP identification. Expression analyses were carried out using real-time PCR. Results The complete sequence of all exons and flanking intronic sequences were analyzed in DNA samples from 54 individuals affected with breast cancer from non-BRCA1/2 high-risk French Canadian breast/ovarian families. Although no germline mutation has been identified in the coding region, we identified 41 sequence variants, including 16 coding variants, 3 of which are not reported in public databases. SNP haplotypes were established and tSNPs were identified in 73 healthy unrelated French Canadians, providing a valuable tool for further association studies involving the ATR gene, using large cohorts. Our analyses led to the identification of two novel alternative splice transcripts. In contrast to the transcript generated by an alternative splicing site in the intron 41, the one resulting from a deletion of 121 nucleotides in exon 33 is widely expressed, at significant but relatively low levels, in both normal and tumoral cells including normal breast and ovarian tissue. Conclusion Although no deleterious mutations were identified in the ATR gene, the current study provides an haplotype analysis of the ATR gene polymorphisms, which allowed the identification of a set of SNPs that could be used as tSNPs for large-scale association
Steffensen, Ane Y; Jønson, Lars; Ejlertsen, Bent; Gerdes, Anne-Marie; Nielsen, Finn C; Hansen, Thomas V O
Mutations in the two breast cancer susceptibility genes BRCA1 and BRCA2 are associated with increased risk of breast and ovarian cancer. Patients with mutations in both genes are rarely reported and often involve Ashkenazi founder mutations. Here we report the first identification of a Danish...... breast and ovarian cancer family heterozygote for mutations in the BRCA1 and BRCA2 genes. The BRCA1 nucleotide 5215G > A/c.5096G > A mutation results in the missense mutation Arg1699Gln, while the BRCA2 nucleotide 859 + 4A > G/c.631 + 4A > G is novel. Exon trapping experiments and reverse transcriptase...... (RT)-PCR analysis revealed that the BRCA2 mutation results in skipping of exon 7, thereby introducing a frameshift and a premature stop codon. We therefore classify the mutation as disease causing. Since the BRCA1 Arg1699Gln mutation is also suggested to be disease-causing, we consider this family...
Abdelilah Laraqui, Nancy Uhrhammer, Idriss Lahlou-Amine, Hicham EL Rhaffouli, Jamila El Baghdadi, Mohamed Dehayni, Rahali Driss Moussaoui, Mohamed Ichou, Yassir Sbitti, Abderrahman Al Bouzidi, Said Amzazi, Yves-Jean Bignon
Full Text Available Worldwide variation in the distribution of BRCA mutations is well recognised, and for the Moroccan population no comprehensive studies about BRCA mutation spectra or frequencies have been published. We therefore performed mutation analysis of the BRCA1 gene in 121 Moroccan women diagnosed with breast cancer. All cases completed epidemiology and family history questionnaires and provided a DNA sample for BRCA testing. Mutation analysis was performed by direct DNA sequencing of all coding exons and flanking intron sequences of the BRCA1 gene. 31.6 % (6/19 of familial cases and 1 % (1/102 of early-onset sporadic (< 45 years were found to be associated with BRCA1 mutations. The pathogenic mutations included two frame-shift mutations (c.798_799delTT, c.1016dupA, one missense mutation (c.5095C>T, and one nonsense mutation (c.4942A>T. The c.798_799delTT mutation was also observed in Algerian and Tunisian BC families, suggesting the first non-Jewish founder mutation to be described in Northern Africa. In addition, ten different unclassified variants were detected in BRCA1, none of which were predicted to affect splicing. Most unclassified variants were placed in Align-GVGD classes suggesting neutrality. c.5117G>C involves a highly conserved amino acid suggestive of interfering with function (Align-GVGD class C55, but has been observed in conjunction with a deleterious mutation in a Tunisian family. These findings reflect the genetic heterogeneity of the Moroccan population and are relevant to genetic counselling and clinical management. The role of BRCA2 in BC is also under study.
Vos, Joel; Menko, Fred H.; Oosterwijk, Jan C.; van Asperen, Christi J.; Stiggelbout, Anne M.; Tibben, Aad
Background Many cancer-patients undergo DNA testing in the BRCA1/2 genes to receive information about the likelihood that cancer is heritable. Previous nonsystematic studies suggested that DNA testing often does not fulfill the counselees' needs for certainty. We explored the balance between the cou
Hansen, Thomas v O; Jønson, Lars; Albrechtsen, Anders;
BRCA1 and BRCA2 germ-line mutations predispose to breast and ovarian cancer. Large genomic rearrangements of BRCA1 account for 0-36% of all disease causing mutations in various populations, while large genomic rearrangements in BRCA2 are more rare. We examined 642 East Danish breast and/or ovarian...
Infante, M; Durán, M; Acedo, A; Pérez-Cabornero, L; Sanz, D J; García-González, M; Beristain, E; Esteban-Cardeñosa, E; de la Hoya, M; Teulé, A; Vega, A; Tejada, M-I; Lastra, E; Miner, C; Velasco, E A
The distribution of BRCA1 and BRCA2 germ line mutations in breast/ovarian cancer families varies among different populations, which typically present a wide spectrum of unique mutations. Splicing mutation 5272-1G>A of BRCA1 and frameshift mutation 5374delTATG of BRCA2 are highly prevalent mutations in Castilla-León (Spain), accounting for 18.4% and 13.6% of BRCA1 and BRCA2 positive families, respectively. To test the presence of founder effects, 9 Spanish 5272-1G>A and 13 5374delTATG families were genotyped with polymorphic markers linked to BRCA1 or BRCA2. All the 5272-1G>A families shared a common haplotype in eight markers (1.1 Mb region) and the mutation age was estimated in 15 generations (approximately 380 years). A conserved haplotype associated to 5374delTATG was observed in four markers (0.82 Mb). The mutation occurred approximately 48 generations ago (approximately 1200 years). Each mutation likely arose from a common ancestor that could be traced to a small area of Castilla-León and expanded to other Spanish regions. They can have a significant impact on the clinical management of asymptomatic carriers as well as on the genetic screening strategy to be followed in populations with Spanish ancestries. PMID:19912264
Full Text Available Abstract This paper discusses the presentation I held at the symposium on genetics during the 4th European Breast Cancer Conference held in Hamburg in March 2004. Primarily, the goals and working methods of the advocacy group specialised in Hereditary Breast/Ovarian Cancer of the Dutch Breast Cancer Patient Organisation known as BorstkankerVereniging Nederland (BVN are explained. Furthermore, some specific individual problems that mutation carriers might encounter before and after BRCA1/2 susceptibility testing are discussed. These include: dilemmas in choosing preventive interventions, dealing with the psychological impact of knowing you are a mutation carrier, dealing with the social implications of being genetically at risk, an example of insurance discrimination. In addition, some controversial social and ethical issues that are currently under debate are highlighted, such as the issue of the European patenting of the breast cancer susceptibility genes BRCA1 and BRCA2. Since this topic could also become relevant for other gene-related diseases, society as a whole has to consider the ethical and social implications related to the patenting of human genes in general. Another ethical area of debate is the controversial issue of prenatal BRCA testing and the choice of pregnancy termination. Finally, the Working Party pleads for the international co-operation and exchange of data and experience among professionals as well as patients. It appears that professionals in different European countries tend to advise on different risk management strategies and treatments and as such, the Working Party strongly advocates the international standardisation of risk management and treatment of mutation carriers. In this respect, specific attention should be given to a group that has had a non-informative or negative BRCA test result, because this group is still considered to be at high risk to develop the disease.
Germline mutations in BRCA1 and BRCA2 are associated with susceptibility hereditary to breast (CM) and ovarian cancer (OC). The proportion of high risk families carrying mutations in BRCA1 / 2 (20% -70%) and the spectrum of mutations are variable and dependent on the location and type of families studied. In this communication we update our results on the frequency and type of mutations in BRCA1 / 2 families in Uruguayan breast / ovarian cancer. Patients and methods. 39 selected families were included in the study from patients referred to the Unit of the Hospital de Clinicas Oncogene tics for genetic risk assessment and who had at least 3 cases of CM (at least one diagnosed before age 50) or 2 cases with any of the following sub: Parental transmittance, bilateral breast cancer, breast cancer male, ovarian cancer. Results. 8 8 families different mutations (20%), 6 were identified in BRCA1 and BRCA2 2, all resulting in premature termination codon. Regarding family history, 33 families had history of CM and 6 remaining history of CM and CO. Among the first 6 mutations diagnosed (Five in BRCA1 and one in BRCA2) and between the latter 2 mutations (1 in BRCA1 and 1 in BRCA2). Regarding the index cases, all BRCA2 mutations were detected in patients in whom the disease was diagnosed before the 50, 5 of them carrying CM and CO. The BRCA1 were found in a patient with CO diagnosed at age 55 and a patient with CM diagnosed before 50 years. Conclusions. The proportion of flamilies with BRCA1 / 2 is of agreement with that reported in previous studies involving selected families based on similar criteria, but the relative frequency of engagement
Full Text Available Abstract Inherited breast-ovarian cancer was described in 1866. The underlying genetic defects in BRCA1/2 were demonstrated 128 years later. We now have 10 years of experience with genetic testing in BRCA kindreds. The majority of breast cancer kindreds (familial breast cancer do not demonstrate ovarian cancer and are not associated with BRCA mutations. The effect of early diagnosis and treatment is monitored through international collaborations. BRCA1-associated breast cancer is biologically different from other breast cancers, including a worse prognosis. BRCA2-associated breast cancer is, beside early onset, in many ways similar to sporadic breast cancer. Mammography screening of the high risk groups aiming at early diagnosis and treatment, seems promising for familial breast cancer and for BRCA2-associated breast cancer, but numbers included for BRCA2 carriers are limited. BRCA1-carriers have worse prognosis, and the potential benefit of MRI for early diagnosis is now being explored. Early diagnosis and treatment of ovarian cancer does not substantially improve survival, and prophylactic oophorectomy at the end of childbearing ages is advocated. Prophylactic mastectomy is debated, and we may await the results of MRI trials before recommending this option. Familial breast cancer and BRCA2-associated breast cancers are often oestrogen receptor positive, and may be prevented by oestrogen blockers/inhibitors. Oophorectomy prevents ovarian cancer, and may possibly prevent both receptor positive and receptor negative breast cancer as well, also while using HRT. Oral contraceptives may reduce ovarian cancer risk and increase breast cancer risk, irrespective of initial risk and genetic subgroup.
Jouali, Farah; Laarabi, Fatima-Zahra; Marchoudi, Nabila; Ratbi, Ilham; Elalaoui, Siham Chafai; Rhaissi, Houria; Fekkak, Jamal; Sefiani, Abdelaziz
At present, breast cancer is the most common type of cancer in females. The majority of cases are sporadic, but 5–10% are due to an inherited predisposition to develop breast and ovarian cancers, which are transmitted as an autosomal dominant form with incomplete penetrance. The beneficial effects of clinical genetic testing, including next generation sequencing (NGS) for BRCA1/2 mutations, is major; in particular, it benefits the care of patients and the counseling of relatives that are at risk of breast cancer, in order to reduce breast cancer mortality. BRCA genetic testing was performed in 15 patients with breast cancer and a family with positivity for the heterozygous c.6428C>A mutation of the BRCA2 gene. Informed consent was obtained from all the subjects. Genomic DNAs were extracted and the NGS for genes was performed using the Ion Torrent Personal Genome Machine (PGM) with a 316 chip. The reads were aligned with the human reference HG19 genome to elucidate variants in the BRCA1 and BRCA2 genes. Mutations detected by the PGM platform were confirmed by target direct Sanger sequencing on a second patient DNA sample. In total, 4 BRCA variants were identified in 6 families by NGS. Of these, 3 mutations had been previously reported: c.2126insA of BRCA1, and c.1310_1313delAAGA and c.7235insG of BRCA2. The fourth variant, c.3453delT in BRCA1, has, to the best of our knowledge, never been previously reported. The present study is the first to apply NGS of the BRCA1 and BRCA2 genes to a Moroccan population, prompting additional investigation into local founder mutations and variant characteristics in the region. The variants with no clear clinical significance may present a diagnostic challenge when performing targeted resequencing. These results confirm that an NGS approach based on Ampliseq libraries and PGM sequencing is a highly efficient, speedy and high-throughput mutation detection method, which may be preferable in lower income countries.
Tercyak, Kenneth P.; DeMarco, Tiffani A.; Mars, Bryn D.; Peshkin, Beth N.
Women who participate in BRCA1/2 cancer genetic counseling do so for a variety of reasons, including learning quantitative risk information about their chances of developing hereditary breast-ovarian cancer at some point during their lifetimes. For these women, obtaining pre-test and disclosure genetic counseling with a professional affords them numerous potential benefits, including adequate preparation for, and accurate interpretation of, their test results. In consequence, women commonly r...
Casey, Murray Joseph; Colanta, Agnes B
More than 40 years ago Lynch et al. described several multigenerational breast cancer family pedigrees which demonstrated autosomal dominant inheritance of a trait(s) that increased risks for both breast and ovarian cancers. Mutation carriers in at least 90 % of these hereditary breast ovarian cancer (HBOC) syndrome families have been linked to cancer-associated mutations in the genes BRCA1 and BRCA2. This review focuses on the contributions of Lynch, colleagues and collaborators and pertinent literature, toward defining the HBOC syndrome, the cancer risks that the inherited adverse mutations convey, the gynecologic tissues and organs from which the malignancy may arise to disseminate throughout the pelvic and abdominal organs and peritoneum and how this information can be used to reduce the risk and morbidities of intra-abdominal carcinomatosis in effected individuals. PMID:26875157
Mazoyer, S.; Lalle, P.; Narod, S A; Bignon, Y J; Courjal, F.; Jamot, B; Dutrillaux, B; Stoppa-Lyonnett, D; Sobol, H
Nineteen French breast and breast-ovarian cancer families were tested for linkage with five chromosome 17q markers. The five breast-ovarian cancer families as a group give positive evidence for linkage, whereas the 14 breast cancer-only families do not. Heterogeneity of linkage of breast and breast-ovarian cancers is significant in France and supports the existence of more than one susceptibility gene.
Bodurka Diane C
Full Text Available Abstract Background Women with BRCA1 or BRCA2 mutations have a substantially increased risk of breast and ovarian cancer compared with the general population. Therefore, prophylactic mastectomy (PM and bilateral salpingo-oophorectomy (BSO have been proposed as risk-reduction strategies for BRCA1/2 mutation carriers. We aimed to assess the feasibility of coordinated PM and BSO in hereditary breast-ovarian cancer syndrome. Methods High risk women for breast and ovarian cancer who underwent coordinated PM and BSO were included in this study. Clinical characteristics and surgical and oncologic outcomes were retrospectively reviewed. Results Twelve patients underwent coordinated PM and BSO. Ten had history of previous breast cancer. Autologous breast reconstruction was performed in ten patients. The mean age at surgery was 43 (range 34–65. Mean operating time was 9.3 hours (range 3–16 with a mean postoperative hospitalization of 5.4 days (range 4–8. Intraoperatively, there were no major surgical complications. Postoperatively, one patient developed an abdominal wound dehiscence, another reoperation for flap congestion; one had umbilical superficial epidermolysis, and one patient developed aspiration pneumonia. At a mean follow-up of 84 months, 10 of patients were cancer-free. Although no patients developed a new primary cancer, two developed a distant recurrence. Conclusion Coordinated PM and BSO is a feasible procedure with acceptable morbidity in selected high-risk patients that desire to undergo surgery at one operative setting.
Peters, June A; Hoskins, Lindsey; Prindiville, Sheila; Kenen, Regina; Greene, Mark H
The CEGRM was initially conceived as a simple, concise, visual representation of the social interaction domains of information, tangible services and emotional exchanges (Kenen, R., & Peters, J. (2001). J Genet Counsel, 10, 289-309). A blend of the genetic pedigree, genogram, and ecomap, the CEGRM was developed to facilitate contemporary genetic counseling goals. An exploratory pilot study of 20 subjects showed that it was feasible, comfortable and efficiently accomplished, and that the process was useful both for assessment and as an intervention with study participants (Peters, J. A., Kenen, R., Giusti, R., Loud, J., Weissman, N., & Greene, M. H. (2004). Am J Med Genet Part A, 130A, 258-264). Subsequently, we have extended the CEGRM to 150 women from hereditary breast/ovarian cancer (HBOC) families; three different investigators have successfully administered this tool. The preliminary findings from the exploratory study were confirmed in the larger sample. Engaging in the interactive, insight-promoting CEGRM process provides a novel tool for assessing the social context of genetic testing, and helping high-risk women better understand and integrate genetic information into their personal and family identities, health beliefs, and decisions. PMID:17111216
Tonin, P.; Vivier, A.; Morgan, K.; Narod, S.; Pollack, M. (McGill Univ., Montreal (Canada)); Ehrenborg, E.; Zazzi, H.; Luthman, H.; Larsson, C. (Karolinska Hospital, Stockholm (Sweden)); Lenoir, G. (International Agency for Research on Cancer, Lyon (France)) (and others)
The gene for insulin-like growth factor-binding protein 4 (IGFBP4) codes for a serum protein that binds to the family of insulin-like growth factors and modulates their activity. It has been mapped by in situ hybridization to chromosome region 17q12-q21.1. The authors have developed a CA-repeat polymorphism from a cosmid clone containing IGFBP4. By linkage analysis, IGFBP4 maps to the chromosome 17q interval THRA1-D17S579. This interval also contains the gene for hereditary breast-ovarian cancer, BRCA1. Genetic recombination between IGFBP4 and BRCA1 places IGFBP4 centromeric to the cancer susceptibility gene and effectively excludes it as a candidate gene for BRCA1. IGFBP4 is, however, one of the closest known centromeric markers for BRCA1; the estimated recombination fraction is 0.015. IGFBP4 and D17S579 together define a 2.8-cM interval that contains BRCA1. 18 refs., 3 figs., 1 tab.
Thomassen, Mads; Hansen, Thomas V O; Borg, Ake;
A national study of BRCA1 and BRCA2 mutations in Danish HBOC (Hereditary Breast Ovarian Cancer) families revealed a total number of 322 mutation positive families, 206 (64%) BRCA1 and 116 (36%) BRCA2 positive families from a population of 5.5 million inhabitants. Seven hundred and twenty six muta...
Phelps, Ceri; Bennett, Paul; Brain, Kate
This study explored whether Smith and Lazarus' (1990, 1993) cognitive theory of emotion could predict emotional responses to an emotionally ambiguous real-life situation. Questionnaire data were collected from 145 women upon referral for cancer genetic risk assessment. These indicated a mixed emotional reaction of both positive and negative emotions to the assessment. Hierarchical regression analyses revealed that the hypothesised models explained between 20% and 33% of the variance of anxiety, hope and gratitude scores, but only 10% of the variance for challenge scores. For the previously unmodelled emotion of relief, 31% of the variance was explained by appraisals and core relational themes. The findings help explain why emotional responses to cancer genetic risk assessment vary and suggest that improving the accuracy of individuals' beliefs and expectations about the assessment process may help subsequent adaptation to risk information. PMID:18942008
Bernatsky, S; Ramsey-Goldman, R; Foulkes, W D; Gordon, C; A E Clarke
Background: An increased lymphoma risk is well documented in systemic lupus (SLE). Less attention has been focused on women's cancers, even though SLE affects mostly females. Our objective was to estimate the risk of breast, ovarian, and endometrial cancers in SLE, relative to the general population. Methods: Data were included from five recent studies of large SLE cohorts. The number of cancers observed was determined for each cancer type. The expected number of malignancies was ascertained ...
Pinto, Pedro; Peixoto, Ana; Santos, Catarina; Rocha, Patrícia; Pinto, Carla; Pinheiro, Manuela; Leça, Luís; Martins, Ana Teresa; Ferreira, Verónica; Bartosch, Carla; Teixeira, Manuel R
BRCA1 and BRCA2 mutations are responsible for hereditary breast and ovarian cancer, but they also confer an increased risk for the development of rarer cancers associated with this syndrome, namely, cancer of the pancreas, male breast, peritoneum, and fallopian tube. The objective of this work was to quantify the contribution of the founder mutations BRCA2 c.156_157insAlu and BRCA1 c.3331_3334del for cancer etiology in unselected hospital-based cohorts of Portuguese patients diagnosed with these rarer cancers, by using a strategy that included testing of archival tumor tissue. A total of 102 male breast, 68 pancreatic and 33 peritoneal/fallopian tube carcinoma cases were included in the study. The BRCA2 c.156_157insAlu mutation was observed with a frequency of 7.8% in male breast cancers, 3.0% in peritoneal/fallopian tube cancers, and 1.6% in pancreatic cancers, with estimated total contributions of germline BRCA2 mutations of 14.3%, 5.5%, and 2.8%, respectively. No carriers of the BRCA1 c.3331_3334del mutation were identified. During our study, a patient with an ampulla of Vater carcinoma was incidentally found to carry the BRCA2 c.156_157insAlu mutation, so we decided to test a consecutive series of additional 15 ampullary carcinomas for BRCA1/BRCA2 mutations using a combination of direct founder mutation testing and full gene analysis with next generation sequencing. BRCA2 mutations were observed with a frequency of 14.3% in ampulla of Vater carcinomas. In conclusion, taking into account the implications for both the individuals and their family members, we recommend that patients with these neoplasias should be offered BRCA1/BRCA2 genetic testing and we here show that it is feasible to test for founder mutations in archival tumor tissue. Furthermore, we identified for the first time a high frequency of germline BRCA2 mutations in ampullary cancers. PMID:27532258
Carus, Andreas; Donskov, Frede; Gebski, Val;
Background: In some solid cancers a survival benefit has been observed for patients who had chemotherapy-induced neutropenia. The prognostic impact of baseline and nadir blood neutrophils was assessed in the present study. Methods: Data on patients with breast cancer st.I-IV, ovarian cancer st.......Survival data were updated 2010. Results: A total of 819 patients were identified, comprising 507 patients with breast cancer, 118 patients with ovarian cancer, 115 patients with NSCLC and 79 patients with SCLC. Median survival for ovarian cancer patients obtaining nadir neutropenia below 2.0 x 109/l was 56...... months. In contrast, median survival for ovarian cancer patients who had nadir neutropenia above 2.0 was 27 months. In a multivariate analysis, adjusting for well-known prognostic features, nadir neutropenia below 2.0 was statistically significant (HR 1.73;p=0.03). In patients with NSCLC, baseline...
van der Luijt, R. B.; van Zon, P. H A; Jansen, R.; van der Sijs-Bos, C. J M; Warlam-Rodenhuis, C.; Ausems, M.
Germline mutations in either of the two major breast cancer predisposition genes, BRCA1 and BRCA2, account for a significant proportion of hereditary breast/ovarian cancer. Identification of breast cancer patients carrying mutations of these genes is primarily based on a positive family history of breast/ovarian cancer or early onset of the disease or both. In the course of mutation screening of the BRCA1 and BRCA2 genes in a hospital based series of patients with risk factors for hereditary ...
Burford, B; Gentry-Maharaj, A; Graham, R;
Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoanti...
Dhillon, P.K.; Yeole, B. B.; Dikshit, R; Kurkure, A P; Bray, F.
Background: Demographic, socioeconomic and cultural changes in India have increased longevity, delayed childbearing, decreased parity and resulted in a more westernised lifestyle, contributing to the increasing burden of cancer, especially among women. Methods: We evaluated secular changes in the incidence of breast, cervical and ovarian cancer in Mumbai women aged 30–64 between 1976 and 2005. Age-standardised incidence rates were calculated and presented by site and calendar period. An age–p...
Piao, B K; Wang, Y X; Xie, G R; Mansmann, U; Matthes, H; Beuth, J; Lin, H S
Standardized aqueous mistletoe extracts have been applied to cancer patients for several decades as complementary medicine. A multicentric, randomized, open, prospective clinical trial was conducted in three oncological centers in the People's Republic of China in Bejing, Shenyang and Tianjin. Following the guidelines of "Good Clinical Practice" (GCP) this study was performed to get information on efficacy safety and side-effects of the standardized mistletoe extract (sME). Two hundred and thirty-three patients with breast (n=68), ovarian (n=71) and non-small cell lung cancer (NSCLC; n=94) were enrolled into this study. Two hundred and twenty-four patients fulfilled the requirements for final analysis (n=115 treated with sME HELIXOR A; n=109 comprising the control group being treated with the approved immunomodulating phytopharmacon Lentinan). All patients were provided with standard tumor-destructive treatment schedules and complementarily treated with sME or Lentinan during chemotherapy according to treatment protocol. Biometrically, the patients of the control and sME treatment group were comparable regarding distribution, clinical classification (WHO) and treatment protocols. Analysis was performed according to the "Intention to treat principle". Quality of life (QoL) was significantly (pcontrol group. Additionally, the occurrence of adverse events (AEs) was less frequent in the sME than in the control group (total number of AEs 52 versus 90 and number of serious AEs 5 versus 10 in study and control group, most of them due to chemotherapy). Only one serious AE was allocated to complementary treatment in each group (1 angioedema in sME group). All other side-effects of the sME (7 harmless local inflammatory reactions at subcutaneous injection site, 4 cases with fever) were self-limiting and did not demand therapeutic intervention. This study showed that complementary treatment with sME can beneficially reduce the side-effects of chemotherapy in cancer patients
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
Cook-Deegan, Robert; DeRienzo, Christopher; Carbone, Julia; Chandrasekharan, Subhashini; Heaney, Christopher; Conover, Christopher
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...
Phipps, R. F.; Perry, P M
Familial breast cancer is important because of all the known risk factors associated with developing the disease. The one with the most predictability is a positive family history. It is also important because a family history causes anxiety in the families concerned, and young women will often ask their chance of developing the disease. This form of breast cancer accounts for 10% of causes and has factors that distinguish it from the sporadic variety. Relatives of familial breast cancer pati...
Hayat Roshanai, Afsaneh
The overall aims of this thesis were to investigate psychological and behavioral effects of receiving cancer genetic counseling for breast, ovarian and colorectal cancer and/or with a family history of these cancer types and to determine whether counselees’ informational needs were met. Study I was performed 3-7 years post-counseling. Participants (n=214) reported a relatively high level of anxiety but a low level of depression compared to cancer patients in general. However, there was no ind...
Differences in the frequency and distribution of BRCA1 and BRCA2 mutations in breast/ovarian cancer cases from the Basque country with respect to the Spanish population: implications for genetic counselling.
Beristain, E; Martínez-Bouzas, C; Guerra, I; Viguera, N; Moreno, J; Ibañez, E; Díez, J; Rodríguez, F; Mallabiabarrena, G; Luján, S; Gorostiaga, J; De Pablo, J L; Mendizabal, J L; Tejada, M I
The prevalence of unique and recurrent BRCA1 and BRCA2 pathogenic mutations and unclassified variants varies among different populations. Two hundred and thirty-six breast and/or ovarian cancer patients were analysed to clarify the role of these genes in the Basque Country. We also studied 130 healthy women from the general population from the same region. Fifteen different pathological mutations were found in 16 index cases: 10 truncating mutations, 4 missense mutations and 1 splicing mutation. c.3002_3003insT and c.5788_5789delGT, both in exon 11 of BRCA2 have not previously been described. No pathological mutations were found in cases of sporadic juvenile breast cancer. There are no recurrent mutations in our population; apart from the mutation c.9254_9258del5, which appears in only two index cases. We have also found a lot of variants whose effect is unknown. From these variants, 17 have not previously been described: 6 missenses, 6 synonymous and 5 alterations in intronic regions. We would like to highlight the fact that 14.3% of patients with 3 or more cases of breast cancer in the family, and 16.7% of patients with family history of breast and ovarian cancer, present a pathological mutation in BRCA1 or BRCA2. This manuscript demonstrates that each population can have different mutations and due to this, Genetic Counselling and selection criteria must be different for each population. Furthermore, this article describes for the first time some new mutations and unclassified variants found in our population. PMID:17262179
Kelly, Kimberly M.; Ellington, Lee; Schoenberg, Nancy; Agarwal, Parul; Jackson, Thomas; Dickinson, Stephanie; Abraham, Jame; Paskett, Electra D.; Leventhal, Howard; Andrykowski, Michael
Few studies have linked actual genetic counseling content to short-term outcomes. Using the Self-regulation Model, the impact of cognitive and affective content in genetic counseling on short-term outcomes was studied in individuals at elevated risk of familial breast-ovarian cancer. Surveys assessed dependent variables: distress, perceived risk, and 6 knowledge measures (Meaning of Positive Test; Meaning of Negative Test; Personal Behavior; Practitioner Knowledge; Mechanisms of Cancer Inheri...
Stephen J. Lanspa
Full Text Available Pancreatic cancer’s high mortality rate equates closely with its incidence, thereby showing the need for development of biomarkers of its increased risk and a better understanding of its genetics, so that high-risk patients can be better targeted for screening and early potential lifesaving diagnosis. Its phenotypic and genotypic heterogeneity is extensive and requires careful scrutiny of its pattern of cancer associations, such as malignant melanoma associated with pancreatic cancer, in the familial atypical multiple mole melanoma syndrome, due to the CDKN2A germline mutation. This review is designed to depict several of the hereditary pancreatic cancer syndromes with particular attention given to the clinical application of this knowledge into improved control of pancreatic cancer.
Full Text Available Abstract Background Both recurrent and population specific mutations have been found in different areas of the world and more specifically in ethnically defined or isolated populations. The population of Slovenia has over several centuries undergone limited mixing with surrounding populations. The current study was aimed at establishing the mutation spectrum of BRCA1/2 in the Slovenian breast/ovarian cancer families taking advantage of a complete cancer registration database. A second objective was to determine the cancer phenotype of these families. Methods The original population database was composed of cancer patients from the Institute of Oncology Ljubljana in Slovenia which also includes current follow-up status on these patients. The inclusion criteria for the BRCA1/2 screening were: (i probands with at least two first degree relatives with breast and ovarian cancer; (ii probands with only two first degree relatives of breast cancer where one must be diagnosed less than 50 years of age; and (iii individual patients with breast and ovarian cancer, bilateral breast cancer, breast cancer diagnosed before the age of 40 and male breast cancer without any other cancer in the family. Results Probands from 150 different families met the inclusion criteria for mutation analysis of which 145 consented to testing. A BRCA1/2 mutation was found in 56 (39%. Two novel large deletions covering consecutive exons of BRCA1 were found. Five highly recurrent specific mutations were identified (1806C>T, 300T>G, 300T>A, 5382insC in the BRCA1 gene and IVS16-2A>G in the BRCA2 gene. The IVS16-2A>G in the BRCA2 gene appears to be a unique founder mutation in the Slovenian population. A practical implication is that only 4 PCR fragments can be used in a first screen and reveal the cancer predisposing mutation in 67% of the BRCA1/2 positive families. We also observed an exceptionally high frequency of 4 different pathogenic missense mutations, all affecting one of
Rustgi, Anil K.
This review by Rustgi elaborates on the known genetic syndromes that underlie familial pancreatic cancer. It aims to delineate the subtypes of syndromic hereditary pancreatic cancer in which germline genetic mutations have been identified and nonsyndromic familial pancreatic cancer in which genetic information is emerging.
Tartrate-resistant acid phosphatase (TRAP) is a metalloprotein enzyme that belongs to the acid phosphatases and is known to be expressed by osteoclasts. It has already been investigated as a marker of bone metastases in cancer patients. In this study, which examined the value of serum TRAP concentrations as a marker of bone disease in breast cancer patients, we observed high concentrations of TRAP even in patients without bone metastases. To elucidate this phenomenon, we examined the expression of TRAP in breast cancer cells and the cells of several other malignancies. TRAP concentrations in the serum of tumor patients were determined by ELISA. The expression of TRAP in breast, ovarian, and cervical cancer and malignant melanoma was analyzed by immunohistochemistry. RT-PCR and immunocytology were used to evaluate TRAP expression in cultured tumor cells. A marked increase in serum TRAP concentrations was observed in patients with breast and ovarian cancer, regardless of the presence or absence of bone disease. TRAP expression was found in breast and ovarian cancers and malignant melanoma, while cervical cancer showed only minimal expression of TRAP. Expression of TRAP was absent in benign tissue or was much less marked than in the corresponding malignant tissue. TRAP expression was also demonstrated in cultured primary cancer cells and in commercially available cell lines. Overexpression of TRAP was detected in the cells of various different tumors. TRAP might be useful as a marker of progression of malignant disease. It could also be a potential target for future cancer therapies
Full Text Available Abstract Background A substantial minority of individuals who initially apply for genetic counselling for breast/ovarian cancer withdraw at an early stage from the counselling process. This study investigated the self-reported reasons for early withdrawal and the factors associated significantly with such withdrawal. Methods Self-report questionnaires were mailed to 83 women who had applied for genetic counselling for breast/ovarian cancer but who subsequently withdrew from the counselling process (the "withdrawers". A comparison group of 105 women who had completed the genetic counselling (the "attendees" received a similar questionnaire. The questionnaire assessed sociodemographic characteristics, reasons for applying for genetic counselling, general distress (MHI-5, cancer-specific distress (IES, and cancer worries. For those women who discontinued the counselling, reasons for withdrawal were also assessed. Results The primary reasons given for withdrawing from counselling were difficulties in anticipating the consequences of genetic counselling (28%, and worries about being unable to adequately cope with an unfavourable test result (20%. Compared to the attendees, the withdrawers were significantly younger, more frequently asymptomatic, more often the first and only member of the family to apply for counselling, and less worried about cancer. Current levels of cancer-specific distress and general distress were comparable between the two groups. Conclusion Younger women, those without a history of cancer, and those who are first in their family to apply are more likely to withdraw prematurely from genetic counselling for breast/ovarian cancer. These withdrawers have no elevated levels of distress. However, a substantial percentage of individuals discontinue counselling due to concerns about their (inability to cope with a possible unfavourable test outcome. This suggests that greater attention should be paid to ways of coping with test
Muhamad, Mazanah; Afshari, Mojgan; Kazilan, Fitrisehara
This paper raises issues about the role of family members in providing support for breast cancer survivors. Data were collected from 400 breast cancer survivors in Peninsular Malaysia through a custom-designed questionnaire fielded at hospitals and support group meetings. The data were analyzed using descriptive statistics. The analyses show that all family members could be supportive, especially in decision making and help with emotional issues. The spouse was the main support provider among the family members (others were children, parents, siblings and more distant relatives). The results also indicated that a significant percentage practiced collaborative decision-making. Breast cancer survivors needed their family members' support for information on survivorship strategies such as managing emotions, health, life style and dietary practice. The family members' supportive role may be linked to the Malaysian strong family relationship culture. For family members to contribute more adequately to cancer survivorship, it is suggested that appropriate educational intervention also be provided to them. PMID:22126470
Baumgart, Leigh A; Postula, Kristen J Vogel; Knaus, William A
Personal and family health histories remain important independent risk factors for cancer; however they are currently not being well collected or used effectively. Health Heritage was designed to address this need. The purpose of this study was to validate the ability of Health Heritage to identify patients appropriate for further genetic evaluation and to accurately stratify cancer risk. A retrospective chart review was conducted on 100 random patients seen at an adult genetics clinic presenting with concern for an inherited predisposition to cancer. Relevant personal and family history obtained from the patients' medical records was entered into Health Heritage. Recommendations by Health Heritage were compared to national guidelines of eligibility for genetic evaluation. Agreement between Health Heritage referral for genetic evaluation and guideline eligibility for genetic evaluation was 97 % (sensitivity 98 % and specificity 88 %). Risk stratification for cancer was also compared between Health Heritage and those documented by a geneticist. For patients at increased risk for breast, ovarian, or colorectal cancer as determined by the geneticist, risk stratification by Health Heritage agreed 90, 93, and 75 %, respectively. Discordances in risk stratification were attributed to both complex situations better handled by the geneticist and Health Heritage's adherence to incorporating all information into its algorithms. Health Heritage is a clinically valid tool to identify patients appropriate for further genetic evaluation and to encourage them to confirm the assessment and management recommendations with cancer genetic experts. Health Heritage also provides an estimate of cancer risk that is complementary to a genetics team. PMID:26711915
Dominguez-Valentin, Mev; Therkildsen, Christina; Da Silva, Sabrina;
Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic...... features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) syndrome with the aim to delineate tumor characteristics that may contribute to refined diagnostics and optimized tumor prevention....
The Breast Cancer Family Registry and the Colon Cancer Family Registry were established by the National Cancer Institute as a resource for investigators to use in conducting studies on the genetics and molecular epidemiology of breast and colon cancer.
Full Text Available Background. Except for smoking and certain occupational exposures, the etiology of bladder cancer is largely unknown. Several case reports have described familial aggregation of transitional cell carcinoma of the bladder. Although the majority of patients with bladder cancer do not have family history of transitional cell carcinoma of the urinary tract, the study of familial transitional cell carcinoma may lead to the knowledge on the pathogenesis of this disease. The purpose of this study was to describe three cases of urinary bladder cancer in a single three-member family, i.e. in two generations (mother and son and a family member related by marriage (the patient’s wife. Case report. Three cases of urinary bladder cancer occurred in a three-member family within the interval of 5 years. The following common characteristics were detected in our patients: old age (over 60, working as farmers for more than 50 years, negative personal medical history on relevant health disorders, place of birth - village, place of residence - village, the same water supply, similar nutrition, positive family history on urinary bladder cancer or other malignant tumors, the first sign of illness was macroscopic hematuria in all the patients and the same pathohistological type of cancer - carcinoma papillare transitiocellulare. Conclusion. The stated common characteristics in our cases indicate, above all, the impact of exposure to external surrounding factors on the occurrence of urinary bladder cancer.
Full Text Available Abstract Background Tartrate-resistant acid phosphatase (TRAP is a metalloprotein enzyme that belongs to the acid phosphatases and is known to be expressed by osteoclasts. It has already been investigated as a marker of bone metastases in cancer patients. In this study, which examined the value of serum TRAP concentrations as a marker of bone disease in breast cancer patients, we observed high concentrations of TRAP even in patients without bone metastases. To elucidate this phenomenon, we examined the expression of TRAP in breast cancer cells and the cells of several other malignancies. Methods TRAP concentrations in the serum of tumor patients were determined by ELISA. The expression of TRAP in breast, ovarian, and cervical cancer and malignant melanoma was analyzed by immunohistochemistry. RT-PCR and immunocytology were used to evaluate TRAP expression in cultured tumor cells. Results A marked increase in serum TRAP concentrations was observed in patients with breast and ovarian cancer, regardless of the presence or absence of bone disease. TRAP expression was found in breast and ovarian cancers and malignant melanoma, while cervical cancer showed only minimal expression of TRAP. Expression of TRAP was absent in benign tissue or was much less marked than in the corresponding malignant tissue. TRAP expression was also demonstrated in cultured primary cancer cells and in commercially available cell lines. Conclusion Overexpression of TRAP was detected in the cells of various different tumors. TRAP might be useful as a marker of progression of malignant disease. It could also be a potential target for future cancer therapies.
Full Text Available Abstract Background Individuals who carry deleterious BRCA mutations face significantly elevated risks of breast, ovarian, and other cancers. These individuals are also responsible for informing relatives of their increased risk for carrying the family BRCA mutation. Few interventions have been developed to facilitate this family communication process. Methods We developed the Sharing Risk Information Tool (ShaRIT, a personalized educational intervention, to support BRCA carriers as they discuss BRCA positive results and their implications with relatives. We conducted a pilot study of 19 BRCA carriers identified through the University of California San Francisco Cancer Risk Program. Our study had two aims: 1 to assess the feasibility and acceptability of ShaRIT, and 2 describe characteristics associated with increased family communication and BRCA testing. Participants in our study were divided into two groups: those who had not received ShaRIT as part of their genetic counseling protocol (control group, n = 10 and those who received ShaRIT (n = 9. Results All 9 women who received ShaRIT reported that it was a useful resource. Characteristics associated with increased sharing and testing included: female gender, degree of relationship, and frequency of communication. Increased pedigree knowledge showed a trend toward higher rates of sharing. Conclusions Both participants and genetic counselors considered ShaRIT a well-received, comprehensive tool for disseminating individual risk information and clinical care guidelines to Hereditary Breast and Ovarian Cancer Syndrome families. Because of this, ShaRIT has been incorporated as standard of care at our institution. In the future we hope to evaluate the effects of ShaRIT on family communication and family testing in larger populations of BRCA positive families.
Ihab Shafek Atta
Full Text Available We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner’s, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A.
Atta, Ihab Shafek; AlQahtani, Fahd Nasser
We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner's, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A. PMID:27087812
Atta, Ihab Shafek; AlQahtani, Fahd Nasser
We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner's, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A. PMID:27087812
Full Text Available Dysregulated lipid metabolism contributes to cancer progression. Our previous study indicates that long-chain fatty acyl-Co A synthetase (ACSL 3 is essential for lipid upregulation induced by endoplasmic reticulum stress. In this report, we aimed to identify the role of ACSL family in cancer with systematic analysis and in vitro experiment. We explored the ACSL expression using Oncomine database to determine the gene alteration during carcinogenesis and identified the association between ACSL expression and the survival of cancer patient using PrognoScan database. ACSL1 may play a potential oncogenic role in colorectal and breast cancer and play a potential tumor suppressor role in lung cancer. Co-expression analysis revealed that ACSL1 was coexpressed with MYBPH, PTPRE, PFKFB3, SOCS3 in colon cancer and with LRRFIP1, TSC22D1 in lung cancer. In accordance with PrognoScan analysis, downregulation of ACSL1 in colon and breast cancer cell line inhibited proliferation, migration, and anchorage-independent growth. In contrast, increase of oncogenic property was observed in lung cancer cell line by attenuating ACSL1. High ACSL3 expression predicted a better prognosis in ovarian cancer; in contrast, high ACSL3 predicted a worse prognosis in melanoma. ACSL3 was coexpressed with SNUPN, TRIP13, and SEMA5A in melanoma. High expression of ACSL4 predicted a worse prognosis in colorectal cancer, but predicted better prognosis in breast, brain and lung cancer. ACSL4 was coexpressed with SERPIN2, HNRNPCL1, ITIH2, PROCR, LRRFIP1. High expression of ACSL5 predicted good prognosis in breast, ovarian, and lung cancers. ACSL5 was coexpressed with TMEM140, TAPBPL, BIRC3, PTPRE, and SERPINB1. Low ACSL6 predicted a worse prognosis in acute myeloid leukemia. ACSL6 was coexpressed with SOX6 and DARC. Altogether, different members of ACSLs are implicated in diverse types of cancer development. ACSL-coexpressed molecules may be used to further investigate the role of ACSL
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
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
Rodríguez, Vivian M; Corona, Rosalie; Bodurtha, Joann N; Quillin, John M
Family health history about cancer is an important prevention and health promotion tool. Yet few studies have identified family context factors that promote such discussions. We explored relations among family context (cohesion, flexibility, and openness), self-efficacy, and cancer communication (gathering family history, sharing cancer risk information, and frequency) in a diverse group of women enrolled in a randomized control trial. Baseline survey data for 472 women were analyzed. The women's average age was 34 years, 59% identified as Black, 31% had graduated high school, and 75% reported a family history of any cancer. Results showed that greater family cohesion and flexibility were related to higher communication frequency and sharing cancer information. Women who reported greater self-efficacy were more likely to have gathered family history, shared cancer risk information, and communicated more frequently with relatives. Openness was not associated with communication but was related to greater family cohesion and flexibility. Adjusting for demographic variables, self-efficacy, and family cohesion significantly predicted communication frequency. Women with higher self-efficacy were also more likely to have gathered family health history about cancer and shared cancer risk information. Future research may benefit from considering family organization and self-efficacy when developing psychosocial theories that in turn inform cancer prevention interventions. PMID:26735646
Pelttari, Liisa M.
Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possi...
Full Text Available Abstract Approximately 10% of gastric cancer cases show familial clustering but only 1-3% of gastric carcinomas arise as a result of inherited gastric cancer predisposition syndromes. Direct proof that Hereditary Gastric Cancer a genetic disease with a germline gene defect has come from the demonstration of co-segregation of germline E-cadherin (CDH1 mutations with early onset diffuse gastric cancer in families with an autosomal dominant pattern of inheritance (HDGC. E-cadherin is a transmembrane calcium-dependent cell-adhesion molecule involved in cell-junction formation and the maintenance of epithelial integrity. In this review, we describe frequency and type of CDH1 mutations in sporadic and familial gastric cancer. Further we demonstrate the functional significance of some CDH1 germline missense mutations found in HDGC. We also discuss the CDH1 polymorphisms that have been associated to gastric cancer. We report other types of malignancies associated to HDGC, besides diffuse gastric cancer. Moreover, we review the data available on putative alternative candidate genes screened in familial gastric cancer. Finally, we briefly discuss the role of low-penetrance genes and Helicobacter pylori in gastric cancer. This knowledge is a fundamental step towards accurate genetic counselling, in which a highly specialised pre-symptomatic therapeutic intervention should be offered.
Swerdlow, A J; Huttly, S. R.; Smith, P.G.
In a case-control study of testis cancer 259 cases with testicular cancer, 238 controls treated at radiotherapy centres and 251 non-radiotherapy hospital in-patient controls were interviewed about some possible prenatal and familial risk factors for the tumour. For firstborn men, the risk of testis cancer increased significantly according to maternal age at the subject's birth, and this effect was most marked for seminoma. The association with maternal age was not apparent for cases other tha...
P H Pestonjamasp; I Mittra
The involvement of the familial breast-ovarian cancer gene (BRCA1) in the molecular pathogenesis of breast cancer among Indian women is unknown. We have used a set of microsatellite polymorphisms to examine the frequency of allele loss at the BRCA1 region on chromosome 17q21, in a panel of 80 human breast tumours. Tumour and blood leukocyte/normal tissue DNA from a series of 80 patients with primary breast cancer was screened by PCR-amplified microsatellite length polymorphisms to detect deletions at three polymorphic BRCA1 loci. PCR-allelotype was valuable in examining allele losses from archival and small tumour samples. Loss of alleles at BRCA1 in the patient set, confirmed a noteworthy role of this gene in the molecular pathogenesis of breast cancer and was in accordance with its well-documented tumour suppressive function.
Vujovic, S; Vujosevic, S; Kavaric, S; Sopta, J; Ivovic, M; Saveanu, A; Brue, T; Korbonits, M; Popovic, V
People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient's mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies. PMID:26886902
Pelttari, Liisa M.; Khan, Sofia; Vuorela, Mikko; Kiiski, Johanna I.; Vilske, Sara; Nevanlinna, Viivi; Ranta, Salla; Schleutker, Johanna; Winqvist, Robert; Kallioniemi, Anne; Dörk, Thilo; Bogdanova, Natalia V.; Figueroa, Jonine; Pharoah, Paul D. P.; Schmidt, Marjanka K.; Dunning, Alison M.; García-Closas, Montserrat; Bolla, Manjeet K.; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Hopper, John L.; Southey, Melissa C.; Rosenberg, Efraim H.; Fasching, Peter A.; Beckmann, Matthias W.; Peto, Julian; dos-Santos-Silva, Isabel; Sawyer, Elinor J.; Tomlinson, Ian; Burwinkel, Barbara; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E.; Nordestgaard, Børge G.; Benitez, Javier; González-Neira, Anna; Neuhausen, Susan L.; Anton-Culver, Hoda; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Brüning, Thomas; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Van Dyck, Laurien; Janssen, Hilde; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Peterlongo, Paolo; Hallberg, Emily; Olson, Janet E.; Giles, Graham G.; Milne, Roger L.; Haiman, Christopher A.; Schumacher, Fredrick; Simard, Jacques; Dumont, Martine; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Grip, Mervi; Andrulis, Irene L.; Glendon, Gord; Devilee, Peter; Seynaeve, Caroline; Hooning, Maartje J.; Collée, Margriet; Cox, Angela; Cross, Simon S.; Shah, Mitul; Luben, Robert N.; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Couch, Fergus J.; Yannoukakos, Drakoulis; Orr, Nick; Swerdlow, Anthony; Darabi, Hatef; Li, Jingmei; Czene, Kamila; Hall, Per; Easton, Douglas F.; Mattson, Johanna; Blomqvist, Carl; Aittomäki, Kristiina; Nevanlinna, Heli
Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk. PMID:27149063
Liisa M Pelttari
Full Text Available Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC that were genotyped on a custom chip (iCOGS. We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259 and population controls (n = 3586 from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR: 1.15, 95% confidence interval (CI: 1.11-1.19, P = 8.88 x 10-16 and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11, compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.
Giglia, Matthew D; Chu, Daniel I
While most colorectal cancers (CRCs) originate from nonhereditary spontaneous mutations, one-third of cases are familial or hereditary. Hereditary CRCs, which account for discovery that certain genotypes can lead to development of CRC, thousands of mutations have now been implicated in CRC. These new findings have enhanced our ability to identify at-risk patients, initiate better surveillance, and take preventative measures. Given the large number of genes now associated with hereditary and familial CRCs, clinicians should be familiar with the alphabet soup of genes to provide the highest quality of care for patients and families. PMID:27582643
... Does Breast or Ovarian Cancer Run in Your Family? Language: English Español (Spanish) Recommend on Facebook Tweet ... get ovarian cancer by age 70. Does Your Family Health History Put You At Risk? Tell your ...
The HER family of receptors plays a major role in a variety of cancers including breast cancer. Several researchers have shown that HER family overexpression in breast cancer is a significant prognostic factor, especially for survival and relapse. Therefore, many therapeutics are being developed to test the impact of HER family blockade in breast cancer. Although numerous therapies have been developed, many have not been very successful in the clinic. This is often a consequence of cancer cel...
Vinaykumar Kontham; Susanna von Holst; Annika Lindblom
Family history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the predisposing genes are known but numerous families have been tested without finding the predisposing gene. We performed a genome wide linkage analysis in 121 colorectal families with an increased ...
Lynch, Henry T; Kosoko-Lasaki, Omofolasade; Leslie, Stephen W; Rendell, Marc; Shaw, Trudy; Snyder, Carrie; D'Amico, Anthony V; Buxbaum, Sarah; Isaacs, William B; Loeb, Stacy; Moul, Judd W; Powell, Isaac
Prostate cancer (PC) has the highest degree of genetic transmission of any form of malignancy. In some families, the hereditary pattern is so strong as to mimic an autosomal dominance trait. We reviewed the known predisposing genetic markers to assess possible strategies for screening of families at risk. We carried out a systematic literature search using the Pubmed service of the National Center for Biotechnology Information (NCBI) and several gene libraries, including the NCBI SNP Library, the Online Mendelian Inheritance in Man® Catalog of Human Genes and Genetic Disorders (OMIM) and SNPedia to obtain known gene loci, SNPs and satellite markers associated with PC. We further cross referenced information on identified loci comparing data from different articles and gene reference sites. Whenever possible, we recorded the odds ratio (OR) for the allele associated with PC. In multiple different linkage studies, many independent PC associated loci have been identified on separate chromosomes. Genome-wide association studies have added many more markers to the set derived from linkage investigations. A subset of the alleles is associated with early onset and aggressive cancer. Due to the great heterogeneity, the OR for any one allele predicting future development of this malignancy is low. The strongest predictors are the BRCA2 mutations, and the highly penetrant G84E mutation in HOXB13. The presence of multiple risk alleles is more highly predictive than a single allele. Technical limitations on screening large panels of alleles are being overcome. It is appropriate to begin supplementing prostate specific antigen testing with alleles, such as BRCA2 and HOXB13, disclosed by targeted genomic analysis in families with an unfavorable family cancer history. Future population studies of PC should include genomic sequencing protocols, particularly in families with a history of PC and other malignancies. PMID:26638190
Full Text Available Differentiated non-medullary thyroid cancer (NMTC is mostly sporadic, but the recurrence of familial form of the disease has been reported. Short or dysfunctional telomeres have been associated with familial benign diseases and familial breast cancer. We aimed to study the telomere-telomerase complex in familial NMTC (FNMTC. The genetic analysis included the measurement in the peripheral blood of relative telomere length (RTL, telomerase reverse transcriptase (hTERT gene amplification, hTERT mRNA expression, telomerase protein activity and search of hTERT or TERC (telomerase RNA component gene mutations. We, also, studied telomeric fusions and associations as well as other chromosomal fragility features by conventional and molecular cytogenetic analyses, in phytohemagglutinin stimulated T-lymphocytes from familial patients, unaffected family members, sporadic PTC patients and healthy subjects. We found that, telomere lenght was significantly shorter in the blood of familial patients compared to sporadic PTCs, healthy subjects, nodular goiter and unaffected siblings. hTERT gene amplification was significantly higher in FNMTC patients compared to the other groups and, in particular, it was significantly greater in offspring with respect to parents. hTERT mRNA expression as well as telomerase activity were significantly higher in FNMTC patients compared to sporadic In addition, we demonstrated that familial patients have a significant increase in spontaneous telomeric associations and telomeric fusions compared to healthy subjects and sporadic cases. Q-FISH analysis demonstrated that familial cases display a significant decrease in the telomeric PNA-FISH signal intensity in metaphase chromsome. Our study demonstrates that patients with FNMTC display an imbalance of the telomeretelomerase complex in the peripheral blood.
Boilesen, Astrid Elisabeth Bruun; Bisgaard, Marie Luise; Bernstein, Inge
OBJECTIVE: Women in hereditary non-polyposis colorectal cancer (HNPCC) families have an elevated risk of endometrial and ovarian cancer. The risk in Lynch syndrome families with known mutations in mismatch repair genes (MMR genes) seems to be higher than in familial colorectal cancer (CRC) famili...
Carroll, J. C.; Heisey, R. E.; Warner, E.; V Goel; McCready, D R
OBJECTIVES: To outline the psychosocial issues in hereditary breast cancer (HBC) assessment and discuss the role of family physicians. QUALITY OF EVIDENCE: A literature search using MEDLINE, CINAHL, CancerLit, and HealthStar databases was conducted from January 1990 to April 1998, using the key words breast cancer or neoplasm and familial or hereditary, genetic testing or screening, primary care or family physician or counseling, genetic counseling, psychosocial or psychological. We found onl...
An article about an educational program at the City of Hope Cancer Center intended to provide health professionals with the tools and information needed to help family caregivers care for themselves and their loved ones with cancer.
Bladder cancer is the seventh most common cancer in men in the world, it is the second most seen cancer after lung cancer and the first in urogenital tumours in Turkey. Many molecular epidemiologic studies have been reported to investigate the associations between the MTHFR C677T and A1298C polymorphisms and bladder cancer risk. In this report, a family with transitional bladder cancer have also MTHFR A1298C heterozygosity which supports the association between MTHFR variants and bladder canc...
Folsom, A.R.; Chen, P.L.; Sellers, T.A. [Univ. of Minnesota, Minneapolis, MN (United States)] [and others
A majority of breast and ovarian cancer families and half of the early-onset breast cancer families are linked to markers on 17q (BRCA1). While linkage has been demonstrated in families with premenopausal disease, few studies have tested these markers in families with postmenopausal breast cancer. In the Iowa Women`s Health Study, a population-based study of over 42,000 women, an association of waist-to-hip ratio (WHR) with the risk of postmenopausal breast cancer was found predominantly in women with a positive family history -- this interaction was associated with a 3.2-fold elevated risk. This effect was even more pronounced when the definition of family history included breast and ovarian cancer, known to be linked to 17q markers. We evaluated evidence for linkage with D17S579, a BRCA-1-linked marker, in 13 families in which the index case had postmenopausal breast cancer. Genotyping for alleles at D17S579 was performed on 84 blood samples. Linkage analysis assumed that the breast cancer trait had an autosomal dominant mode of inheritance with a penetrance of 80%. For the 13 families studied, the maximum lod score was 0.29 at a theta of 0.27. There was significant evidence against tight linkage of breast cancer with D17S579 (theta<0.4). Heterogeneity analysis suggested evidence for the presence of both linked and unlinked families. Partitioning informative families on WHR of the index case suggested heterogeneity. These data suggest that, in a subset of families identified by a postmenopausal breast cancer proband, risk of breast cancer may be mediated by BRCA1, with heterogeneity defined by WHR.
Radina, M. Elise
An estimated 20% of breast cancer survivors face the chronic condition of breast cancer-related lymphedema. This study explored the ways in which women with this condition experienced changes in their participation in family leisure as one indicator of family functioning. Participants (N = 27) were interviewed regarding lifestyles before and after…
Long, Kristin A.; Marsland, Anna L.
This systematic review integrates qualitative and quantitative research findings regarding family changes in the context of childhood cancer. Twenty-eight quantitative, 42 qualitative, and one mixed-method studies were reviewed. Included studies focused on family functioning, marital quality, and/or parenting in the context of pediatric cancer,…
Chen, Mei-Chih; Hsu, Shih-Lan; Lin, Ho; Yang, Tsung-Ying
Retinoic acid which belongs to the retinoid class of chemical compounds is an important metabolite of vitamin A in diets. It is currently understood that retinoic acid plays important roles in cell development and differentiation as well as cancer treatment. Lung, prostate, breast, ovarian, bladder, oral, and skin cancers have been demonstrated to be suppressed by retinoic acid. Our results also show that low doses and high doses of retinoic acid may respectively cause cell cycle arrest and a...
Barrisford, Glen W.; Singer, Eric A; Rosner, Inger L.; Marston Linehan, W.; Gennady Bratslavsky
Familial renal cancer (FRC) is a heterogeneous disorder comprised of a variety of subtypes. Each subtype is known to have unique histologic features, genetic alterations, and response to therapy. Through the study of families affected by hereditary forms of kidney cancer, insights into the genetic basis of this disease have been identified. This has resulted in the elucidation of a number of kidney cancer gene pathways. Study of these pathways has led to the development of novel targeted mole...
Full Text Available Bladder cancer is the seventh most common cancer in men in the world, it is the second most seen cancer after lung cancer and the first in urogenital tumours in Turkey. Many molecular epidemiologic studies have been reported to investigate the associations between the MTHFR C677T and A1298C polymorphisms and bladder cancer risk. In this report, a family with transitional bladder cancer have also MTHFR A1298C heterozygosity which supports the association between MTHFR variants and bladder cancer. This %uFB01nding should be further validated by prospective and larger studies with more diverse ethnic groups.
Scott Rodney J
Full Text Available Abstract Mutations in BRCA1 account for the majority of familial aggregations of early onset breast and ovarian cancer (~70% and about 1/5 of all early onset breast cancer families; in contrast, mutations in BRCA2 account for a smaller proportion of breast/ovarian cancer families and a similar proportion of early onset breast cancer families. BRCA2 has also been shown to be associated with a much more pleiotropic disease spectrum compared to BRCA1. Since the identification of both BRCA1 and BRCA2 investigations into the functions of these genes have revealed that both are associated with the maintenance of genomic integrity via their apparent roles in cellular response to DNA damage, especially their involvement in the process of double strand DNA break repair. This review will focus on the specific roles of both genes and how functional differences may account for the diverse clinical findings observed between families that harbour BRCA1 or BRCA2 mutations.
L N Lyubchenko; N. I. Pospelova; A. A. Parokonnaya; A. A. Luzhnikova; E. M. Chevkina
The problems in the early diagnosis, primary and secondary prevention of family cancer of the breast and/or ovaries are successfully solved within medical genetic counseling at a cancer clinic. Its genetic diagnosis is confirmed, individual risks for breast and/or ovarian cancer are calculated, risk-modifying factors are studied, and treatment, family planning, and childbirth are discussed during clinicogenetic studies.
Kluijt, Irma; Sijmons, Rolf H; Hoogerbrugge, Nicoline; Plukker, John T.; de Jong, Daphne; van Krieken, J. Han; van Hillegersberg, Richard; Ligtenberg, Marjolijn; Bleiker, Eveline; Cats, Anemieke
Hereditary diffuse gastric cancer (HDGC) is a relatively rare disorder, with a mutated CDH1 gene as the only known cause. Carriers of a germline mutation in CDH1 have a lifetime risk of > 80% of developing diffuse gastric cancer. As periodic gastric surveillance is of limited value in detecting early stages of HDGC, prophylactic gastrectomy is advised for this patient group. Little is known about other types of familial gastric cancer. The Dutch working group on hereditary gastric cancer has ...
Dworkind, M.; Shvartzman, P; Adler, P. S.; Franco, E. D.
Members in the Department of Family Medicine of a university teaching hospital were surveyed to find out their involvement in caring for cancer patients. Respondents indicated that many cancer patients were followed, but few cancer support services in the hospital and the community were used. The desire to take on new cancer patients was lacking, yet an interest in continuing medical education existed. Feedback from the department will help guide our Education Committee to develop continuing ...
Lovat, Francesca; Bitto, Alessandro; Xu, Shi-Qiong; Fassan, Matteo; Goldoni, Silvia; Metalli, David; Wubah, Vera; McCue, Peter; Serrero, Ginette; Gomella, Leonard G.; Baffa, Raffaele; Iozzo, Renato V.; Morrione, Andrea
The growth factor proepithelin functions as an important regulator of proliferation and motility. Proepithelin is overexpressed in a great variety of cancer cell lines and clinical specimens of breast, ovarian and renal cancer, as well as glioblastomas. Using recombinant proepithelin on 5637 transitional cell carcinoma-derived cells, we have shown previously that proepithelin plays a critical role in bladder cancer by promoting motility of bladder cancer cells. In this study, we used the ONCO...
Breast cancer is the most common cancer affecting European women and the leading cause of cancer-related death. A total of 15-20% of women who develop breast cancer have a family history and 5-10% a true genetic predisposition. The identification and screening of women at increased risk may allow early detection of breast cancer and improve prognosis. We established a family risk assessment clinic in May 2005 to assess and counsel women with a family history of breast cancer, to initiate surveillance, and to offer risk-reducing strategies for selected high-risk patients. Patients at medium or high risk of developing breast cancer according to NICE guidelines were accepted. Family history was determined by structured questionnaire and interview. Lifetime risk of developing breast cancer was calculated using Claus and Tyrer-Cuzick scoring. Risk of carrying a breast cancer-related gene mutation was calculated using the Manchester system. One thousand two hundred and forty-three patients have been referred. Ninety-two percent were at medium or high risk of developing breast cancer. Formal assessment of risk has been performed in 368 patients, 73% have a high lifetime risk of developing breast cancer, and 72% a Manchester score >or=16. BRCA1\\/2 mutations have been identified in 14 patients and breast cancer diagnosed in two. Our initial experience of family risk assessment has shown there to be a significant demand for this service. Identification of patients at increased risk of developing breast cancer allows us to provide individuals with accurate risk profiles, and enables patients to make informed choices regarding their follow-up and management.
Son, Yedong; Lim, Myong Cheol; Seo, Sang Soo; Kang, Sokbom; Park, Sang-yoon
Objective To investigate the completeness of pedigree and of number of pedigree analysis to know the acceptable familial history in Korean women with ovarian cancer. Methods Interview was conducted in 50 ovarian cancer patients for obtaining familial history three times over the 6 weeks. The completeness of pedigree is estimated in terms of familial history of disease (cancer), health status (health living, disease and death), and onset age of disease and death. Results The completion of pedi...
Austin, Melissa A.; Kuo, Elena; Van Den Eeden, Stephen K; Mandelson, Margaret T.; Brentnall, Teresa A.; Kamineni, Aruna; Potter, John D.
Genetic association studies have identified more than a dozen genes associated with risk of pancreatic cancer. Given this genetic heterogeneity, family history can be useful for identifying individuals at high-risk for this disease. The goal of this analysis was to evaluate associations of family history of diabetes and family history of pancreatic cancer with risk of pancreatic cancer. PACIFIC is a case-control study based in two large health plans. Cases were diagnosed wit...
Expert-reviewed information summary about the challenges faced by family caregivers of cancer patients. This summary focuses on typical caregiver roles and concerns, and helpful interventions for caregivers.
Andersson, Ulrika; Wibom, Carl; Cederquist, Kristina;
BACKGROUND: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several can...... colon cancer. CONCLUSIONS: Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.......BACKGROUND: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several...... cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. METHODS: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation...
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)
Brittain, Kelly; Taylor, Jacquelyn Y.; Loveland-Cherry, Carol; Northouse, Laurel; Caldwell, Cleopatra H.
Colorectal cancer (CRC) is the third leading cause of cancer death among African Americans. Less than 50% of African Americans have had CRC screening. This study examined the relationships between family support and influence, cultural identity, CRC beliefs, and a screening informed decision among 129 urban African Americans. Family support (p < .01) significantly predicted CRC beliefs and CRC beliefs significantly predicted informed decision (p < .01). Based on study results, practitioners s...
Young, D; McLeish, L; Sullivan, F.; Pitkethly, M; M. Reis; Goudie, D; Vysny, H; Ozakinci, G; Steel, M
Up to 40% of referrals from primary care to ‘breast cancer family clinics' prove to be of women whose assessed risk falls below the guidelines' threshold for management in secondary or tertiary care, despite recommendations that they should be screened out at primary care level. A randomised trial, involving 87 such women referred to the Tayside Familial Breast Cancer Service compared two ways of communicating risk information, letter or personal interview. Both were found to be acceptable to...
Madlensky, Lisa; Bousman, Chad A.
Introduction The prevalence of cigarette smoking in the United States has decreased, but current rates remain above nationally set objectives. A family history of lung cancer may motivate adult smokers to quit and contribute to further reductions in smoking prevalence. Methods We surveyed adult smokers (N = 838) interviewed as part of the 2005 Health Information National Trends Survey. We examined the association between family history of lung cancer and smoking cessation precontemplation (no...
Weigl, Stefania; Paradiso, Angelo; Tommasi, Stefania
Mitochondrial genome and functional alterations are related to various diseases including cancer. In all cases, the role of these organelles is associated with defects in oxidative energy metabolism and control of tumor-induced oxidative stress. The present study examines the involvement of mitochondrial DNA in cancer and in particular in breast cancer. Furthermore, since mitochondrial DNA is maternally inherited, hereditary breast cancer has been focused on.
Kelly, Kimberly M.; Love, Margaret M.; Pearce, Kevin A.; Porter, Kyle; Barron, Mary A.; Andrykowski, Michael
Context: Challenges to the identification of hereditary cancer in primary care may be more pronounced in rural Appalachia, a medically underserved region. Purpose: To examine primary care physicians' identification of hereditary cancers. Methods: A cross-sectional survey was mailed to family physicians in the midwestern and southeastern United…
Full Text Available Family history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the predisposing genes are known but numerous families have been tested without finding the predisposing gene. We performed a genome wide linkage analysis in 121 colorectal families with an increased risk of colorectal cancer. The families were ascertained from the department of clinical genetics at the Karolinska University Hospital in Stockholm, Sweden and were considered negative for Familial Polyposis and Lynch syndrome. In total 600 subjects were genotyped using single nucleotide polymorphism array chips. Parametric- and non-parametric linkage analyses were computed using MERLIN in all and subsets of families. No statistically significant result was seen, however, there were suggestive positive HLODs above two in parametric linkage analysis. This was observed in a recessive model for high-risk families, at locus 9q31.1 (HLOD=2.2, rs1338121 and for moderate-risk families, at locus Xp22.33 (LOD=2.2 and HLOD=2.5, rs2306737. Using families with early-onset, recessive analysis suggested one locus on 4p16.3 (LOD=2.2, rs920683 and one on 17p13.2 (LOD/HLOD=2.0, rs884250. No NPL score above two was seen for any of the families. Our linkage study provided additional support for the previously suggested region on chromosome 9 and suggested additional loci to be involved in colorectal cancer risk. Sequencing of genes in the regions will be done in future studies.
Kontham, Vinaykumar; von Holst, Susanna; Lindblom, Annika
Family history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the predisposing genes are known but numerous families have been tested without finding the predisposing gene. We performed a genome wide linkage analysis in 121 colorectal families with an increased risk of colorectal cancer. The families were ascertained from the department of clinical genetics at the Karolinska University Hospital in Stockholm, Sweden and were considered negative for Familial Polyposis and Lynch syndrome. In total 600 subjects were genotyped using single nucleotide polymorphism array chips. Parametric- and non-parametric linkage analyses were computed using MERLIN in all and subsets of families. No statistically significant result was seen, however, there were suggestive positive HLODs above two in parametric linkage analysis. This was observed in a recessive model for high-risk families, at locus 9q31.1 (HLOD=2.2, rs1338121) and for moderate-risk families, at locus Xp22.33 (LOD=2.2 and HLOD=2.5, rs2306737). Using families with early-onset, recessive analysis suggested one locus on 4p16.3 (LOD=2.2, rs920683) and one on 17p13.2 (LOD/HLOD=2.0, rs884250). No NPL score above two was seen for any of the families. Our linkage study provided additional support for the previously suggested region on chromosome 9 and suggested additional loci to be involved in colorectal cancer risk. Sequencing of genes in the regions will be done in future studies. PMID:24349560
Kelly, Kimberly M; Shedlosky-Shoemaker, Randi; Porter, Kyle; Remy, Amber; DeSimone, Philip; Andrykowski, Michael A
Family history is one the greatest risk factors for disease and one of the most important informational tools in medical genetics for the purpose of diagnosis, risk assessment, prevention and treatment. However, research is needed on the comparability of different methods of cancer family history assessment and the influence of psychosocial factors in family history reports. The purpose of this study was to determine if individuals had discrepancies between written and interview reports of cancer family history and the role of psychosocial factors in these discrepancies. Oncology patients (n=104) were administered a survey to assess psychosocial factors (i.e., information-seeking, worry, perceived risk, and health literacy) and were asked to provide family history in a written and an interview form. Randomization determined which form individuals received first. No differences in the amount of missing data or the amount of unspecified data were noted between the written and interview method. Psychosocial factors did not differentiate between those who had discrepancies in family history reports and those who did not have discrepancies in family history reports; although there was a trend for those with lower literacy and those who were blunters to be more discrepant on type of cancer diagnosis. In sum, this preliminary study indicates that written and interview methods of family history assessment for first degree relatives may be used interchangeably. The ability to use written methods will facilitate collection of basic family history information in the oncology clinic. PMID:17318453
Laufey T Amundadottir
Full Text Available BACKGROUND: The contribution of low-penetrant susceptibility variants to cancer is not clear. With the aim of searching for genetic factors that contribute to cancer at one or more sites in the body, we have analyzed familial aggregation of cancer in extended families based on all cancer cases diagnosed in Iceland over almost half a century. METHODS AND FINDINGS: We have estimated risk ratios (RRs of cancer for first- and up to fifth-degree relatives both within and between all types of cancers diagnosed in Iceland from 1955 to 2002 by linking patient information from the Icelandic Cancer Registry to an extensive genealogical database, containing all living Icelanders and most of their ancestors since the settlement of Iceland. We evaluated the significance of the familial clustering for each relationship separately, all relationships combined (first- to fifth-degree relatives and for close (first- and second-degree and distant (third- to fifth-degree relatives. Most cancer sites demonstrate a significantly increased RR for the same cancer, beyond the nuclear family. Significantly increased familial clustering between different cancer sites is also documented in both close and distant relatives. Some of these associations have been suggested previously but others not. CONCLUSION: We conclude that genetic factors are involved in the etiology of many cancers and that these factors are in some cases shared by different cancer sites. However, a significantly increased RR conferred upon mates of patients with cancer at some sites indicates that shared environment or nonrandom mating for certain risk factors also play a role in the familial clustering of cancer. Our results indicate that cancer is a complex, often non-site-specific disease for which increased risk extends beyond the nuclear family.
Amundadottir Laufey T
Full Text Available Background The contribution of low-penetrant susceptibility variants to cancer is not clear. With the aim of searching for genetic factors that contribute to cancer at one or more sites in the body, we have analyzed familial aggregation of cancer in extended families based on all cancer cases diagnosed in Iceland over almost half a century. Methods and Findings We have estimated risk ratios (RRs of cancer for first- and up to fifth-degree relatives both within and between all types of cancers diagnosed in Iceland from 1955 to 2002 by linking patient information from the Icelandic Cancer Registry to an extensive genealogical database, containing all living Icelanders and most of their ancestors since the settlement of Iceland. We evaluated the significance of the familial clustering for each relationship separately, all relationships combined (first- to fifth-degree relatives and for close (first- and second-degree and distant (third- to fifth-degree relatives. Most cancer sites demonstrate a significantly increased RR for the same cancer, beyond the nuclear family. Significantly increased familial clustering between different cancer sites is also documented in both close and distant relatives. Some of these associations have been suggested previously but others not. Conclusion We conclude that genetic factors are involved in the etiology of many cancers and that these factors are in some cases shared by different cancer sites. However, a significantly increased RR conferred upon mates of patients with cancer at some sites indicates that shared environment or nonrandom mating for certain risk factors also play a role in the familial clustering of cancer. Our results indicate that cancer is a complex, often non-site-specific disease for which increased risk extends beyond the nuclear family.
Full Text Available ... That Affect Risk Breast Density on a Mammogram Family History of Breast, Ovarian or Prostate Cancer Inherited ... Symptoms Having Children After Breast Cancer Concern for Family Members Questions to Ask Your Doctor - Survivorship Staying ...
Harinck, Femme; Kluijt, Irma; van der Stoep, Nienke; Oldenburg, Rogier A.; Wagner, Anja; Aalfs, Cora M.; Sijmons, Rolf H.; Poley, Jan-Werner; Kuipers, Ernst J.; Fockens, Paul; van Os, Theo A. M.; Bruno, Marco J.
Background CDKN2A-mutation carriers run a high risk of developing melanomas and have an increased risk of developing pancreatic cancer (PC). Familial PC (FPC) patients with a personal history or family history of melanomas are therefore offered CDKN2A-mutation analysis. In contrast, CDKN2A testing i
Westman, J; Hampel, H.; Bradley, T.
OBJECTIVE—A computer based touchscreen family cancer history questionnaire was developed and implemented to facilitate the provision of cancer risk assessments for the ambulatory and outpatient populations of a free standing cancer hospital. METHODS—A questionnaire consisting of a series of branched point decision making screens was developed which enables the participant to enter demographic data, personal cancer history, and cancer histories for first and second degree relatives. A freestan...
Hazelwood, Daniela Maria; Koeck, Sabine; Wallner, Martin; Anderson, Kathryn Hoehn; Mayer, Hanna
People are diagnosed with cancer sooner nowadays thanks to increased awareness and improvements in cancer screenings. Patients are able to live longer due to cancer treatment regimens; however, they suffer the consequences of living with cancer and therapy-related symptoms. Symptom management is challenging for both patients and family caregivers. Therefore, family members must be integrated in the patient’s care plan. For this review, a literature search was conducted to determine what types...
Howell, Lisa A; Sinicrope, Pamela S.; Brockman, Tabetha A; Patten, Christi A.; Decker, Paul A.; Ehlers, Shawna L.; Nadeau, Ashley; Rabe, Kari G.; Breitkopf, Carmen Radecki; Petersen, Gloria M.
Background Cancer is a shared family experience that might provide an opportunity for lifestyle change among at-risk family members. The purpose of this study was to assess receptivity and preferences for cancer risk reduction programs among at-risk family members with two or more relatives affected with pancreas cancer. Methods We surveyed 401 at-risk family members in an existing pancreatic cancer family registry. Participants completed a mailed survey which examined demographic, medical, a...
L. N. Lyubchenko
Full Text Available The problems in the early diagnosis, primary and secondary prevention of family cancer of the breast and/or ovaries are successfully solved within medical genetic counseling at a cancer clinic. Its genetic diagnosis is confirmed, individual risks for breast and/or ovarian cancer are calculated, risk-modifying factors are studied, and treatment, family planning, and childbirth are discussed during clinicogenetic studies.
Siegfried, Jill M.; Hershberger, Pamela A.; Stabile, Laura P.
Lung cancer has long been thought of as a cancer that mainly affects men, but over the past several decades, because of the high increase in tobacco use by women, there has been a corresponding dramatic increase in lung cancer among women. Since 1998, lung cancer deaths in women have surpassed those caused by breast cancer in the United States. Annual lung cancer deaths among women in the US also currently surpass those caused by breast, ovarian, and cervical cancers combined. Women are more ...
Sheppard, Vanessa B.; Graves, Kristi D.; Christopher, Juleen; Hurtado-de-Mendoza, Alejandra; Talley, Costellia; Williams, Karen Patricia
Genetic counseling and testing for hereditary breast cancer have the potential benefit of early detection and early interventions in African American women. However, African American women have low use of these services compared to White women. We conducted two focus groups with African American women diagnosed with breast cancer (affected group, n=13) and women with at least one first-degree relative with breast/ovarian cancer (unaffected group, n= 8). A content analysis approach was employe...
Walid Shaib; Frederick Lansigan; Daniel Cornfeld; Kostas Syrigos; Muhammad Wasif Saif
Context Gemcitabine is a pyrimidine antimetabolite with activity in a number of cancers. Gemcitabine is the accepted standard for the adjuvant and metastatic treatment of pancreatic cancer, however, it also has indications in breast, ovarian, and non-small cell lung cancers. The most common side effect is myelosuppression. Dyspnea is reported in 23% and bronchospasm occurs in less than 2% of subjects. Acute respiratory distress syndrome is rare with single agent use or in combination. Case re...
Mack, W.; Langholz, B; Thomas, D. C.
It has recently been shown that the relative risks of the order of 2 to 4 that are frequently found for cancer among relatives of affected cases are unlikely to be explainable by shared environmental risk factors. Classical methods of epidemiological analysis are not well suited to such analysis because they assume that the outcomes of each individual are independent. Classical methods of genetic analysis, on the other hand, are limited in their handling of environmental factors and variable ...
Full Text Available While PCTAIRE1/PCTK1/Cdk16 is overexpressed in malignant cells and is crucial in tumorigenesis, its function in apoptosis remains unclear. Here we investigated the role of PCTAIRE1 in apoptosis, especially in the extrinsic cell death pathway. Gene-knockdown of PCTAIRE1 sensitized prostate cancer PPC1 and Du145 cells, and breast cancer MDA-MB-468 cells to TNF-family cytokines, including TNF-related apoptosis-inducing ligand (TRAIL. Meanwhile, PCTAIRE1-knockdown did not sensitize non-malignant cells, including diploid fibroblasts IMR-90 and the immortalized prostate epithelial cell line 267B1. PCTAIRE1-knockdown did not up-regulate death receptor expression on the cell surface or affect caspase-8, FADD and FLIP expression levels. PCTAIRE1-knockdown did promote caspase-8 cleavage and RIPK1 degradation, while RIPK1 mRNA knockdown sensitized PPC1 cells to TNF-family cytokines. Furthermore, the kinase inhibitor SNS-032, which inhibits PCTAIRE1 kinase activity, sensitized PPC1 cells to TRAIL-induced apoptosis. Together these results suggest that PCTAIRE1 contributes to the resistance of cancer cell lines to apoptosis induced by TNF-family cytokines, which implies that PCTAIRE1 inhibitors could have synergistic effects with TNF-family cytokines for cytodestruction of cancer cells.
Greeff, Abraham P.; Thiel, Colleen
This study identifies qualities associated with the successful adaptation of families with a husband diagnosed with prostate cancer. Both qualitative and quantitative measures were used in this cross-sectional survey research design. Twenty-one husbands and their spouses independently completed six questionnaires and a biographical questionnaire,…
Mokuau, Noreen; Braun, Kathryn L.; Daniggelis, Ephrosine
Native Hawaiian women have the highest breast cancer incidence and mortality rates when compared with other large ethnic groups in Hawai'i. Like other women, they rely on the support of their families as co-survivors. This project explored the feasibility and effects of a culturally tailored educational intervention designed to build family…
Perea del Pozo, E.; Ramirez Plaza, C.; J. Padillo Ruiz; J.M. Martos Martínez
Background: Familial adenomatous polyposis (FAP) is an autosomal dominant cancer predisposition syndrome characterised by the progressive development of multiple colorectal adenomatous polyps and an increased incidence of colorectal carcinoma. It is often accompanied by other benign or malignant extracolonic manifestations, including gastric and duodenal tumours, osteomas, desmoid tumours, retinal pigmentation, and thyroid and adrenocortical tumours Methods and results: We report the case ...
van der Kolk, Dorina M.; de Bock, Geertruida H.; Leegte, Beike K.; Schaapveld, Michael; Mourits, Marian J. E.; de Vries, J; van der Hout, Annemieke H.; Oosterwijk, Jan C.
Accurate estimations of lifetime risks of breast and ovarian cancer are crucial for counselling women from BRCA1/2 families. We therefore determined breast and ovarian cancer penetrance in BRCA1/2 mutation families in the northern Netherlands and compared them with the incidence of cancers in the ge
... If Breast or Ovarian Cancer Runs in Your Family Browse Sections The Basics Overview Counseling and Testing ... Checkups The Basics The Basics: Overview If your family has a history of breast or ovarian cancer, ...
Bouchardy Magnin, Christine; Rapiti Aylward, Elisabetta; Fioretta, Gérald; Schubert, Hyma; Chappuis, Pierre; Vlastos, Georges; Benhamou, Simone
Male breast cancer patients have a higher risk of developing a second primary cancer, but whether this risk differs according to the family history of breast or ovarian cancers remains to be elucidated. We aimed to determine the effect of a positive family history among men diagnosed with breast cancer on tumour characteristics, treatment, second cancer occurrence and overall survival.
Biglia, Nicoletta; Sgandurra, Paola; Bounous, Valentina Elisabetta; Maggiorotto, Furio; Piva, Eleonora; Pivetta, Emanuele; Ponzone, Riccardo; Pasini, Barbara
Objectives To compare clinical–pathological characteristics and outcome between sporadic ovarian cancer and ovarian cancer in patents with hereditary breast and ovarian cancer syndrome (HBOC). Methods Twenty-four patients with ovarian cancer treated between 2000 and 2009 who tested positive for BRCA1/2 mutation (BRCA+) and a control group of 64 age-matched patients with no family history of breast/ovarian cancer (controls) were enrolled. Clinical–pathological characteristics, surgical outcome, overall (OS), and progression-free survival (PFS) were compared between the two groups. Results The high-grade serous histotype was more represented in BRCA+ than in controls (70.8% versus 53.1%) (p > 0.05). BRCA+ cancers were more frequently diagnosed at stage II than controls (20.83% versus 4.69%) (p = 0.024). Radical primary surgery was performed in 70% of women in both groups, with no difference in debulking results. In patients undergoing surgery after neoadjuvant chemotherapy, in all BRCA+ patients, optimal cytoreduction was achieved (versus 70% of the controls). PFS was significantly longer for BRCA+ patients compared to controls (60 months versus 22 months; p = 0.039). No significant difference was observed in OS between BRCA+ patients and controls. Conclusions At a median follow-up time of 46 months, BRCA+ patients have a better prognosis than controls in terms of PFS. Higher chemosensitivity of BRCA+ tumours was observed. PMID:27350785
Silverman, D.T. (Debra T.); Schiffman, M; Everhart, J; Goldstein, A.; Lillemoe, K D; Swanson, G.M.; Schwartz, A. G.; Brown, L.M.; Greenberg, R S; Schoenberg, J. B.; Pottern, L M; Hoover, R. N.; Fraumeni, J. F.
In a population-based case-control study of pancreatic cancer conducted in three areas of the USA, 484 cases and 2099 controls were interviewed to evaluate the aetiologic role of several medical conditions/interventions, including diabetes mellitus, cholecystectomy, ulcer/gastrectomy and allergic states. We also evaluated risk associated with family history of cancer. Our findings support previous studies indicating that diabetes is a risk factor for pancreatic cancer, as well as a possible c...
Siminoff, Laura A.; Wilson-Genderson, Maureen; Baker, Sherman
Objective This study investigated depressive symptomatology in lung cancer patients and their identified caregiver. Methods We conducted semi-structured interviews and administered measures of family environment, depressive symptomatology, and the extent to which the caregiver blamed the cancer on the patient not having taken better care of him/herself to 190 patient-caregiver dyads. Multivariate two-level models were used to estimate the unique effects for each dyad member and cross-partner effects while controlling for interdependencies in the data. Results More than half of patients (55%) were male but 74% of caregivers were female. The majority (57.4%) were spouses, followed by offspring and other family or friends The baseline model with covariates showed that younger caregivers, spouse caregivers, and caregivers who blamed the patient for the cancer had higher depressive symptom scores. When examining the unique effect for each dyad member, with the exception of patient report of familial conflict, patient and caregiver reports of lower familial cohesion and expressiveness and higher conflict were associated with higher depression scores for patient and caregiver respectively. When examining cross-partner effects, patient reports of lower cohesion, lower expressiveness and greater conflict were associated with higher caregiver depression scores. Offspring caregivers reported less depression than non-offspring caregivers. Conclusion The family environment and blaming the patient during times of illness can affect both patient and caregiver depression. Findings suggest that quality of the family dynamic is important for patients but may be particularly influential for caregivers. Future research should aid clinicians' assessment of family environment when making treatment plans. PMID:20119935
Chau, Rowena; Jenkins, Mark A; Buchanan, Daniel D; Ait Ouakrim, Driss; Giles, Graham G; Casey, Graham; Gallinger, Steven; Haile, Robert W; Le Marchand, Loic; Newcomb, Polly A; Lindor, Noralane M; Hopper, John L; Win, Aung Ko
This study was aimed to characterize the distribution of colorectal cancer risk using family history of cancers by data mining. Family histories for 10,066 colorectal cancer cases recruited to population cancer registries of the Colon Cancer Family Registry were analyzed using a data mining framework. A novel index was developed to quantify familial cancer aggregation. Artificial neural network was used to identify distinct categories of familial risk. Standardized incidence ratios (SIRs) and corresponding 95 % confidence intervals (CIs) of colorectal cancer were calculated for each category. We identified five major, and 66 minor categories of familial risk for developing colorectal cancer. The distribution the major risk categories were: (1) 7 % of families (SIR = 7.11; 95 % CI 6.65-7.59) had a strong family history of colorectal cancer; (2) 13 % of families (SIR = 2.94; 95 % CI 2.78-3.10) had a moderate family history of colorectal cancer; (3) 11 % of families (SIR = 1.23; 95 % CI 1.12-1.36) had a strong family history of breast cancer and a weak family history of colorectal cancer; (4) 9 % of families (SIR = 1.06; 95 % CI 0.96-1.18) had strong family history of prostate cancer and weak family history of colorectal cancer; and (5) 60 % of families (SIR = 0.61; 95 % CI 0.57-0.65) had a weak family history of all cancers. There is a wide variation of colorectal cancer risk that can be categorized by family history of cancer, with a strong gradient of colorectal cancer risk between the highest and lowest risk categories. The risk of colorectal cancer for people with the highest risk category of family history (7 % of the population) was 12-times that for people in the lowest risk category (60 %) of the population. Data mining was proven an effective approach for gaining insight into the underlying cancer aggregation patterns and for categorizing familial risk of colorectal cancer. PMID:26681340
Amin, Dhara N.; Campbell, Marcia R.; Moasser, Mark M.
Many types of human cancer are characterized by deregulation of the human epidermal growth factor receptor (HER) family of tyrosine kinase receptors. In some cancers, genomic events causing overactivity of individual HER family members are etiologically linked with the pathogenesis of these cancers, and constitute the driving signaling function underlying their tumorigenic behavior. HER3 stands out among this family as the only member lacking catalytic kinase function. Cancers with driving HE...
Valentin, Mev; Therkildsen, Christina; Veerla, Srinivas; Jönsson, Mats; Bernstein, Inge; Borg, Ake; Nilbert, Mef
Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects....
Fiederling, Jonas; Shams, Ahmad Zia; Haug, Ulrike
Evidence regarding validity of self-reported family history of cancer (FHC) has been reviewed only for breast, colorectal, prostate, ovarian, endometrial and uterine cancer. We aimed to systematically review studies assessing validity of self-reported family history for the remaining cancer sites. We searched the Medline database for relevant studies published by January 2016. We extracted information on the study design and the positive predictive value (PPV) of self-reported FHC, defined as the proportion of reported cancer diagnoses among relatives that was confirmed by a reference standard (as a measure of over-reporting). We also extracted information on sensitivity of self-reported FHC (as a measure of underreporting). Overall, 21 studies were included that provided information on the PPV of self-reported FHC for relevant cancers and four studies also provided information on sensitivity. The PPV was highest (mostly >70%) for pancreatic, lung, thyroid and urinary system cancers and for leukemia and lymphoma, while it was lowest for stomach and liver cancer. Sensitivity was highest (>70%) for pancreatic cancer, lung cancer, brain cancer, melanoma, leukemia and lymphoma. For several cancers, sample sizes were low and the number of studies limited, particularly regarding sensitivity of self-reported FHC. In conclusion, for some cancers (e.g., pancreatic cancer, lung cancer, leukemia, lymphoma) self-reported FHC can be considered sufficiently valid to be useful, for example, in preventive counseling. For several cancers, it is not sufficiently studied or the pattern is inconsistent. This needs to be taken into account when using self-reported information about FHC in clinical practice or epidemiological research. PMID:27222437
Full Text Available p53 is an important tumor suppressor gene, which is stimulated by cellular stress like ionizing radiation, hypoxia, carcinogens and oxidative stress. Upon activation p53 leads to cell cycle arrest and promotes DNA repair or induces apoptosis via several pathways. p63 and p73 are structural homologs of p53 that can act similarly to the protein but also hold functions distinct from p53. Today more than forty different isoforms of the p53 family members are known. They result from transcription via different promoters and alternative splicing. Some isoforms have carcinogenic properties and mediate resistance to chemotherapy. Therefore, expression patterns of the p53 family genes can offer prognostic information in several malignant tumors. Furthermore, the p53 family constitutes a potential target for cancer therapy. Small molecules (e.g. Nutlins, RITA, PRIMA-1, and MIRA-1 among others have been objects of intense research interest in recent years. They restore pro-apoptotic wild-type p53 function and were shown to break chemotherapeutic resistance. Due to p53 family interactions small molecules also influence p63 and p73 activity. Thus, the members of the p53 family are key players in the cellular stress response in cancer and are expected to grow in importance as therapeutic targets.
Full Text Available TP53, TP63, and TP73 genes comprise the p53 family. Each gene produces protein isoforms through multiple mechanisms including extensive alternative mRNA splicing. Accumulating evidence shows that these isoforms play a critical role in the regulation of many biological processes in normal cells. Their abnormal expression contributes to tumorigenesis and has a profound effect on tumor response to curative therapy. This paper is an overview of isoform diversity in the p53 family and its role in cancer.
Li, Jenny; Hart, Tae L; Aronson, Melyssa; Crangle, Cassandra; Govindarajan, Anand
Currently, there is a lack of evidence evaluating the psychological impact of cancer-related risk perception and worry in individuals at high risk for gastric cancer. We examined the relationships between perceived risk, cancer worry and screening behaviors among first-degree relatives (FDRs) of patients with familial gastric cancer. FDRs of patients diagnosed with familial gastric cancer with a non-informative genetic analysis were identified and contacted. Participants completed a telephone interview that assessed socio-demographic information, cancer risk perception, cancer worry, impact of worry on daily functioning, and screening behaviors. Twenty-five FDRs completed the telephone interview. Participants reported high levels of comparative and absolute cancer risk perception, with an average perceived lifetime risk of 54 %. On the other hand, cancer-related worry scores were low, with a significant minority (12 %) experiencing high levels of worry. Study participants exhibited high levels of confidence (median = 70 %) in the effectiveness of screening at detecting a curable cancer. Participants that had undergone screening in the past showed significantly lower levels of cancer-related worry compared to those that had never undergone screening. In conclusion, individuals at high-risk for gastric cancer perceived a very high personal risk of cancer, but reported low levels of cancer worry. This paradoxical result may be attributed to participants' high levels of confidence in the effectiveness of screening. These findings highlight the importance for clinicians to discuss realistic risk appraisals and expectations towards screening with unaffected members of families at risk for gastric cancer, in an effort to help mitigate anxiety and help with coping. PMID:26493173
Jacobs, Eric J.; Chanock, Stephen J.; Fuchs, Charles S; LaCroix, Andrea; McWilliams, Robert R.; Steplowski, Emily; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Bueno-De-Mesquita, H Bas; Gross, Myron; Helzlsouer, Kathy; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Allen, Naomi E.
A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e. ovarian, breast, and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of five types of cancer (pancreas, prostate, ovarian, br...
Gage-Bouchard, Elizabeth A.; Devine, Katie A.; Heckler, Charles E.
The factors that influence caregiver coping mechanism preferences after a child’s diagnosis with cancer are not fully understood. This study examines the relationship between caregivers’ socio-demographic characteristics and the coping strategies they use to adapt to childhood cancer. Sixty caregivers of pediatric cancer patients completed a socio-demographic questionnaire, the Family Environment Scale, and the COPE inventory. There were no significant differences in family environment by inc...
Sokolowski, Ineta; Kjeldgaard, Anette Hvenegaard; Olesen, Frede;
recently diagnosed with cancer and among previous cancer patients. Materials and methods: In a nationwide database in Denmark (population 5.5 million) all contacts to the health care system are registered. We describe the pattern of contact with all parts of the health care system for a) the total...... who have recently undergone treatment and patients in the survivorship phase of cancer use different parts of the health care system, and how much they use FP. Information about this will enable us to discuss the need for shared care, integrated care and information exchange and create a platform for......Aims: We know that in Denmark some 90% of citizens have contact with family practice (FP) during a year and around 40% has contact with secondary care. This demands efforts to create integrated and shared care. The aim of this study is to document the pattern of contacts with FP among patients...
Breast cancer is one of the most frequent causes of death in developed countries and it is the second cause of female mortality for malignant tumor in Cuba. We conducted an observational, analytic, transversal study of cases and controls for the purpose of evaluating the clinical, epidemiologic and genealogical behavior of breast cancer in Cienfuegos province, in a period of 6 years. The universe of the study was made up of 304 women distributed in 152 cases and 152 controls; they were surveyed after they gave their informed consent. Collected data were processed by means of methods of inferential statistics. It was observed that most of the cases were diagnosed in patients aged 50 to 59 years, with 24.34%, the most frequent type was infiltrating duct carcinoma, with 43.42%. We found statistical association with the personal history of benign breast pathology and the family history of cancer of any type. Presence of familial aggregation was observed for breast cancer in the first-degree relatives and the non-genetic risk factors; they did not show significant association with the occurrence of the disease in the studied population
Anderson, E.; Berg, J; Black, R; Bradshaw, N.; Campbell, J.; Carnaghan, H; Cetnarkyj, R; Drummond, S; Davidson, R; Dunlop, J.; Fordyce, A.; Gibbons, B; Goudie, D; Gregory, H; Holloway, S
To evaluate current guidelines criteria for inclusion of women in special ‘breast cancer family history' surveillance programmes, records were reviewed of women referred to Scottish breast cancer family clinics between January 1994 and December 2003 but discharged as at ‘less than ‘moderate' familial risk'. The Scottish Cancer Registry was then interrogated to determine subsequent age-specific incidence of breast cancer in this cohort and corresponding Scottish population figures. Among 2074 ...
Myrhøj, T; Andersen, M-B; Bernstein, I
AIM: The aim of this study was to evaluate if Urine Cytology (UC) is an appropriate screening procedure for detecting urinary tract neoplasia at an early stage in persons at risk in Hereditary Non-Polyposis Colorectal Cancer families. METHOD: In the National Danish HNPCC-register persons at risk...... were identified in three categories of HNPCC-families (1) families harbouring a disease causing mutation in a Mismatch repair gene (MMR), (2) families fulfilling the Amsterdam I or II criteria and (3) families suspected of HNPCC. In total 3,411 persons were identified and traced in Patobank......) UC lead to a false positive screening diagnosis. During the study period fourteen persons (1.4%) developed a UTC and five of these were interval tumours. The sensitivity of UC in diagnosing asymptomatic UTC in HNPCC patients was 29%. Twelve of the tumours were found in persons from families with a...
Albright, Frederick; Stephenson, Robert A; Agarwal, Neeraj; Teerlink, Craig C.; Lowrance, William T.; Farnham, James M.; Albright, Lisa A Cannon
Background Prostate cancer (PC) relative risks (RRs) are typically estimated based on status of close relatives or presence of any affected relatives. This study provides RR estimates using extensive and specific PC family history. Methods A retrospective population-based study was undertaken to estimate RRs for PC based on complete family history of PC. A total of 635,443 males, all with ancestral genealogy data, were analyzed. RRs for PC were determined based upon PC rates estimated from ma...
Full Text Available Abstract Background Breast Cancer is the most commonly diagnosed cancer among Sri Lankan women. Germline mutations in the susceptibility genes BRCA1 and BRCA2 in hereditary breast/ovarian cancer, though low in prevalence, are highly penetrant and show geographical variations. There have been only a few reports from Asia on mutations in BRCA1/2 genes and none from Sri Lanka. Methods A total of 130 patients with (N = 66 and without (N = 64 a family history of breast cancer, 70 unaffected individuals with a family history of breast cancer and 40 control subjects were analysed for BRCA1 mutations. All but exon 11 were screened by single strand conformation analysis (SSCP and heteroduplex analysis. PCR products which showed abnormal patterns in SSCP were sequenced. Exon 11 was directly sequenced. Results Nineteen sequence variants were found in BRCA1 gene. Two novel deleterious frame-shift mutations; c.3086delT/exon11 (in one patient and c.5404delG/exon21 (in one patient and two of her family members were identified. A possibly pathogenic novel missense mutation (c.856T>G/exon 11 and three novel intronic variants (IVS7+36C>T, IVS7+41C>T, IVS7+49del15 were characterised. Ten previously reported common polymorphisms and three previously reported intronic variants were also observed. Conclusion After screening of 66 patients with family history and 64 sporadic breast cancer patients, 2 deleterious mutations (c.3086delT and c.5404delG in two families were identified and two more possibly pathogenic mutations (c.856T>G and IVS17-2A>T in two families were identified. Data base BRCA1 - Gene Bank: Accession # U14680 Version # 14680.1
Unic, Ivana; Stalmeier, Peep F. M.; Peer, Petronella G. M.; van Daal, Willem A. J.
Studies of variables predicting familial breast cancer (N=59) were analyzed to develop screening recommendations for women with nonhereditary familial breast cancer present. The pooled relative risk (RR) and cumulative probability were used to estimate risk. Data and conclusions are presented. Recommendations for screening and counseling are…
Roberts, Nicholas J.; Norris, Alexis L.; Petersen, Gloria M.; Bondy, Melissa L.; Brand, Randall; Gallinger, Steven; Kurtz, Robert C.; Olson, Sara H.; Rustgi, Anil K.; Schwartz, Ann G.; Stoffel, Elena; Syngal, Sapna; Zogopoulos, George; Ali, Syed Z.; Axilbund, Jennifer; Chaffee, Kari G.; Chen, Yun-Ching; Cote, Michele L.; Childs, Erica J.; Douville, Christopher; Goes, Fernando S.; Herman, Joseph M.; Iacobuzio-Donahue, Christine; Kramer, Melissa; Makohon-Moore, Alvin; McCombie, Richard W.; McMahon, K. Wyatt; Niknafs, Noushin; Parla, Jennifer; Pirooznia, Mehdi; Potash, James B.; Rhim, Andrew D.; Smith, Alyssa L.; Wang, Yuxuan; Wolfgang, Christopher L.; Wood, Laura D.; Zandi, Peter P.; Goggins, Michael; Karchin, Rachel; Eshleman, James R.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Hruban, Ralph H.; Klein, Alison P.
Pancreatic cancer is projected to become the second leading cause of cancer-related death in the United States by 2020. A familial aggregation of pancreatic cancer has been established, but the cause of this aggregation in most families is unknown. To determine the genetic basis of susceptibility in these families, we sequenced the germline genome of 638 familial pancreatic cancer patients. We also sequenced the exomes of 39 familial pancreatic adenocarcinomas. Our analyses support the role of previously identified familial pancreatic cancer susceptibility genes such as BRCA2, CDKN2A and ATM, and identify novel candidate genes harboring rare, deleterious germline variants for further characterization. We also show how somatic point mutations that occur during hematopoiesis can affect the interpretation of genome-wide studies of hereditary traits. Our observations have important implications for the etiology of pancreatic cancer and for the identification of susceptibility genes in other common cancer types. PMID:26658419
Objective: To examine family history (FH) as a prognostic factor following radiotherapy (RT). Materials and methods: Between 1989 and 2007, 1711 men with clinically localized prostate cancer and complete family history who had received RT (median RT dose = 74 Gy) without androgen deprivation therapy were analyzed. FH was defined as any prostate cancer in a first degree relative. For the biochemical failure (BF) outcome, this sample size has 85% power to detect a hazard ratio of 1.56 for positive versus negative FH. Results: With a median follow-up of 71 months, there was no significant difference in the distribution of Gleason score (GS) or prostate specific antigen (PSA) based on FH. A positive FH was not an independent predictor of BF, distant metastasis (DM), prostate cancer specific mortality (PCSM), or overall mortality (OM) in Cox proportional multivariable analysis. On further analysis in a Cox proportional multivariable analysis, men with two or more first degree relatives with prostate cancer had a significantly higher likelihood of BF and DM than those with no FH, although there was no difference in PCSM or OM. Men with a positive FH (23%) were more likely to be younger, have a lower PSA, and non-palpable disease. There was no interaction between a positive FH and neither race nor treatment era (pre-PSA vs. PSA era). Conclusions: A positive FH is not a prognostic factor following RT and should not alter standard treatment recommendations. Patients with two or more first degree relatives with prostate cancer had a higher likelihood of BF and DM, but there was no effect on survival. There was no interaction between a positive FH and African American race or treatment era. A positive FH was however, associated with more favorable PSA values and T-stage that may be the result of earlier screening
Full Text Available ... Affect Risk Breast Density on a Mammogram Family History of Breast, Ovarian or Prostate Cancer Inherited Gene ... Us About Us View About Us Our Mission & History Our People & Teams View Our People & Teams Scientific ...
Linton, Linda; Martin, Lisa J.; Li, Qing; Huszti, Ella; Minkin, Salomon; John, Esther M.; Rommens, Johanna; Paterson, Andrew D.; Boyd, Norman F
Introduction Percent mammographic density (PMD) is a strong and highly heritable risk factor for breast cancer. Studies of the role of PMD in familial breast cancer may require controls, such as the sisters of cases, selected from the same 'risk set' as the cases. The use of sister controls would allow control for factors that have been shown to influence risk of breast cancer such as race/ethnicity, socioeconomic status and a family history of breast cancer, but may introduce 'overmatching' ...
Danis, Marion; Abernethy, Amy P; Zafar, S Yousuf; Samsa, Gregory P.; Wolf, Steven P; Howie, Lynn; Taylor, Donald H.
Background Concerns about unsustainable costs in the US Medicare program loom as the number of retirees increase and experiences serious and costly illnesses like cancer. Engagement of stakeholders, particularly cancer patients and their families, in prioritizing insured services offers a valuable strategy for informing Medicare coverage policy. We designed and evaluated a decision exercise that allowed cancer patients and family members to choose Medicare benefits for advanced cancer patient...
Amuta, Ann O.; Barry, Adam E.
Background: Approximately 1580 people die from cancer each day. Family history is highlighted as an especially important indicator of cancer risk. Purpose: To determine whether having a family member with cancer influences preventive behaviors (e.g., smoking, physical activity, and screenings). Methods: We conducted a secondary data analysis…
Prouty, Anne M; Fischer, Judith; Purdom, Ann; Cobos, Everardo; Helmeke, Karen B
The researchers examined the spiritual coping, family communication, and family functioning of 95 participants in 34 families by an online survey. Multilevel linear regression was used to test whether individuals' and families' higher endorsement of more use of spiritual coping strategies to deal with a member's cancer would be associated with higher scores on family communication and family functioning, and whether better communication would also be associated with higher family functioning scores. Results revealed that spiritual coping was positively associated with family communication, and family communication was positively associated with healthier family functioning. The researchers provide suggestions for further research. PMID:26311053
Ashida, Sato; Hadley, Donald W.; Goergen, Andrea F.; Skapinsky, Kaley F.; Devlin, Hillary C.; Koehly, Laura M.
Purpose: This study evaluates the role of older family members as providers of social resources within familial network systems affected by an inherited cancer susceptibility syndrome. Design and Methods: Respondents who previously participated in a study that involved genetic counseling and testing for Lynch syndrome and their family network…
Full Text Available Introduction. A family of a child with cancer needs continuous help and support from medical and other professionals, relatives, friends and community at the moment of making diagnosis and during the treatment. The goal of this study was to find out the most frequent sources of individual or community based psychological support, reported by parents of children suffering from malignant diseases. We focused on the help received at the moment of making diagnosis and within the first and second year of treatment. Material and Methods. We analyzed data obtained by a questionnaire specially designed for parents of children suffering from different malignancies. The poll was conducted from April 2007 till October 2009 at the Hematology/ Oncology Department of Children’s Hospital of Novi Sad and it included 72 parents of both sexes, whose children were treated at our Department in the period from 2007 to 2009. The children were of different age. Results. The parents selected the following forms of support as the most important: support given by the emotional partner and other family members (together with sick and healthy child, communication with and accessibility of hospital stuff (physicians at the first place, but also psychologists, nurses, other parents, support groups…. They also expressed their need for contacting friends, relatives and other close people. The selected forms of support are extremely important for the patients (regardless of age and for their family. All forms of organized and professionally conducted psycho-social support of patients and their family result in higher quality of psychological survival during the treatment and further rehabilitation of patients after rejoining their primary social environment. Conclusion. Family is the primary and the most important social surrounding within which disease both happens and is resolved. Adequate support can help family to overcome such crises, thus leading to the positive
Sundquist Jan; Thomsen Hauke; Weires Marianne; Bevier Melanie; Hemminki Kari
Abstract Background Family size and birth order are known to influence the risk of some cancers. However, it is still unknown whether these effects change from early to later adulthood. We used the data of the Swedish Family-Cancer Database to further analyze these effects. Methods We selected over 5.7 million offspring with identified parents but no parental cancer. We estimated the effect of birth order and family size by Poisson regression adjusted for age, sex, period, region and socioeco...
Full Text Available Studies on survival between familial and sporadic cancers have been inconclusive and only recent data on a limited number of cancers are available on the concordance of survival between family members. In this review, we address these questions by evaluating the published and unpublished data from the nation-wide Swedish Family-Cancer Database and a total of 13 cancer sites were assessed. Using sporadic cancer as reference, HRs were close to 1.0 for most of the familial cancers in both the offspring and parental generations, which suggested that survival in patients with familial and sporadic cancers was equal, with an exception for ovarian cancer with a worse prognosis. Compared to offspring whose parents had a poor survival, those with a good parental survival had a decreased risk of death for most cancers and HR was significantly decreased for cancers in the breast, prostate, bladder, and kidney. For colorectal and nervous system cancers, favorable survival between the generations showed a borderline significance. These data are consistent in showing that both good and poor survival in certain cancers aggregate in families. Genetic factors are likely to contribute to the results. These observations call for intensified efforts to consider heritability in survival as one mechanism regulating prognosis in cancer patients.
Jacobs, Eric J.; Chanock, Stephen J.; Fuchs, Charles S.; LaCroix, Andrea; McWilliams, Robert R.; Steplowski, Emily; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gross, Myron; Helzlsouer, Kathy; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Allen, Naomi E.; Amundadottir, Laufey; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Canzian, Federico; Clipp, Sandra; Dorronsoro, Miren; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Jacobs, Kevin B.; Jenab, Mazda; Kraft, Peter; Kooperberg, Charles; Lynch, Shannon M.; Sund, Malin; Mendelsohn, Julie B.; Mouw, Tracy; Newton, Christina C.; Overvad, Kim; Palli, Domenico; Peeters, Petra H. M.; Rajkovic, Aleksandar; Shu, Xiao-Ou; Thomas, Gilles; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wactawski-Wende, Jean; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne
A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could
Andriana Barisic; Gord Glendon; Nayana Weerasooriya; Andrulis, Irene L.; Knight, Julia A.
Obtaining complete medical record information can be challenging and expensive in breast cancer studies. The current literature is limited with respect to the accuracy of self-report and factors that may influence this. We assessed the agreement between self-reported and medical record breast cancer information among women from the Ontario site of the Breast Cancer Family Registry. Women aged 20–69 years diagnosed with incident breast cancer 1996–1998 were identified from the Ontario Cancer R...
Tarleton, Heather P; Chang, Shen-Chih; Park, Sungshim Lani; Cai, Lin; Ding, Baoguo; He, Na; Hussain, Shehnaz K; Jiang, Qingwu; Mu, Li-Na; Rao, Jianyu; Wang, Hua; You, Nai-Chieh Y; Yu, Shun-Zhang; Zhao, Jin-Kou; Zhang, Zuo-Feng
Genetic variation at 8q24 is associated with prostate, bladder, breast, colorectal, thyroid, lung, ovarian, UADT, liver and stomach cancers. However, a role for variation at 8q24 in familial clustering of upper gastrointestinal cancers has not been studied. In order to explore potential inherited susceptibility, we analyzed epidemiologic data from a population-based case-control study of upper gastrointestinal cancers from Taixing, China. The study population includes 204 liver, 206 stomach, and 218 esophageal cancer cases and 415 controls. Associations between 8q24 rs1447295, rs16901979, rs6983267 and these cancers were stratified by family history of cancer. Odds ratios and 95% confidence intervals were adjusted for potential confounders: age, sex, education, tobacco smoking, alcohol consumption, and BMI at interview. We also adjusted for hepatitis B and aflatoxin (liver cancer) and Helicobacter pylori (stomach cancer). In a dominant model, among those with a family history of cancer, rs1447295 was positively associated with liver cancer (OR(adj) 2.80; 95% CI 1.15-6.80). Heterogeneity was observed (P(heterogeneity) = 0.029) with rs6983267 and liver cancer, with positive association in the dominant model among those with a family history of cancer and positive association in the recessive model among those without a family history of cancer. When considered in a genetic risk score model, each additional 8q24 risk genotype increased the odds of liver cancer by two-fold among those with a family history of cancer (OR(adj) 2.00; 95% CI 1.15-3.47). These findings suggest that inherited susceptibility to liver cancer may exist in the Taixing population and that variation at 8q24 might be a genetic component of that inherited susceptibility. PMID:24030569
Lindström, Linda Sofie
Cancer affects essentially everyone, directly or indirectly. The aim of this thesis was to study the genetic and environmental factors in cancer development and survival. Our studies were based on a record linkage between several Swedish population-based registries, principally the Multi-Generation Register, which records familial relationships, the Swedish Cancer Registry, and the Cause of Death Registry. In summary, the Swedish Family-Cancer database comprised over 11 mill...
Dimitra Lekka; Argiro Pachi; Athanasios Tselebis; Georgios Zafeiropoulos; Dionisios Bratis; Argiri Evmolpidi; Ioannis Ilias; Athanasios Karkanias; Georgios Moussas; Nikolaos Tzanakis; Konstantinos N. Syrigos
Lung cancer is a stressful condition for both patient and family. The anxiety and pain accompanying cancer and its treatment have a significant negative influence on the patient's quality of life. The aim of this study was to investigate the correlation between anxiety, pain, and perceived family support in a sample of lung cancer patients. The sample consisted of a total of 101 lung cancer outpatients receiving treatment at the oncology department of a general hospital. Anxiety, pain (severi...
Lindblom, A; Rotstein, S; Nordenskjöld, M; Larsson, C.
Recently, a putative breast cancer gene was localized to the long arm of chromosome 17. A collaboration study was undertaken to confirm linkage, to further map the gene, and to determine to what extent breast cancer families are linked to this locus. The Swedish material consisted of 29 breast cancer families in which 68 affected members were studied. Linkage analysis of breast cancer susceptibility was performed with a number of markers on 17q. In this material a weakly positive LOD score in...
Henderson, Beric R.
Inherited mutations in the BRCA1 gene predispose to a higher risk of breast/ovarian cancer. The BRCA1 tumor suppressor is a 1863 amino acid protein with multiple protein interaction domains that facilitate its roles in regulating DNA repair and maintenance, cell cycle progression, transcription, and cell survival/apoptosis. BRCA1 was first identified as a nuclear phosphoprotein, but has since been shown to contain different transport sequences including nuclear export and nuclear localization...
Lee, Jihyoun; Cho, Hyung Jung; Yoo, Han-Wook; Park, Sue K.; Yang, Jae Jeong; Kim, Sung-Won; Kang, Eunyoung; Ahn, Sei-Hyun; Lee, Soo-Jung; Suh, Young Jin; Kim, Sung Yong; Kim, Eun-Kyu; Moon, Nan Mo; Lee, Min Hyuk; ,
Purpose Systematic educational programs and genetic counseling certification courses for hereditary breast/ovarian cancer (HBOC) have not yet been introduced in Korea. We provided and evaluated the effects of genetic counseling education on Korean healthcare providers' knowledge, awareness, and counseling skills for patients at high risk of HBOC. Methods A 3-day educational program was conducted for healthcare providers who were interested in genetic counseling for patients at high risk of HB...
Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D1. Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations
Shuji Haraguchi, Kiyoshi Koizumi, Iwao Mikami, Okamoto Junichi, Yoshihito Iijima, Takayuki Ibi, Kazuo Shimizu
Introduction: Clinicopathological characteristics and prognosis of non-small cell lung cancer (NSCLC) patients with a family history of lung cancer (FHLC) have not been well established.Methods: Clinical records of patients with NSCLC treated at our institute from 1982 to 2010 were reviewed with special reference to family history of lung cancer and clinicopathological factors including patient's outcome. Univariate analyses of the factors between the groups of FHLC and non-FHLC were performe...
Haraguchi, Shuji; Koizumi, Kiyoshi; Mikami, Iwao; Junichi, Okamoto; Iijima, Yoshihito; Ibi, Takayuki; Shimizu, Kazuo
Introduction: Clinicopathological characteristics and prognosis of non-small cell lung cancer (NSCLC) patients with a family history of lung cancer (FHLC) have not been well established. Methods: Clinical records of patients with NSCLC treated at our institute from 1982 to 2010 were reviewed with special reference to family history of lung cancer and clinicopathological factors including patient's outcome. Univariate analyses of the factors between the groups of FHLC and non-FHLC were perform...
Full Text Available Abstract Background A truncating variant, 1100delC, in check point-kinase CHEK2, has been identified as a risk factor for familial and sporadic breast cancer. The prevalence in healthy non-breast cancer cases is low and varies between populations. Methods We analyzed the prevalence of CHEK2 1100delC in 763 breast cancer patients with a defined family history and 760 controls from the Stockholm region. The breast cancer patients originated from; a population-based cohort (n = 452 and from a familial cancer clinic (n = 311, the detailed family history was known in both groups. Results The variant was found in 2.9% of the familial cases from the population-based cohort and in 1.9% from the familial cancer clinic. In total 2.2% of the patients with a family history of breast cancer carried the variant compared to 0.7% of the controls (p = 0.03. There was no increased prevalence in sporadic patients (0.3%. The variant was most frequent in young familial patients (5.1% of cases ≤45 years, p = 0.003. The mean age at diagnosis of variant carriers was 12 years lower than in non-carriers (p = 0.001. Conclusion In conclusion, CHEK2 1100delC exists in the Swedish population. The prevalence is increased in familial breast cancer and the variant seems to influence age at onset.
Hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) are characterized by a high risk and early onset of colorectal cancer (CRC). HNPCC is due to a germline mutation in one of the following MMR genes: MLH1, MSH2, MSH6 and PMS2. A majority of FAP and attenuated FAP (AFAP) cases are due to germline mutations of APC, causing the development of multiple colorectal polyps. To date, over 450 MMR gene mutations and over 800 APC mutations have been identified. Mo...
Palmero Edenir I
Full Text Available Abstract Background Breast cancer is a significant public health problem worldwide and the development of tools to identify individuals at-risk for hereditary breast cancer syndromes, where specific interventions can be proposed to reduce risk, has become increasingly relevant. A previous study in Southern Brazil has shown that a family history suggestive of these syndromes may be prevalent at the primary care level. Development of a simple and sensitive instrument, easily applicable in primary care units, would be particularly helpful in underserved communities in which identification and referral of high-risk individuals is difficult. Methods A simple 7-question instrument about family history of breast, ovarian and colorectal cancer, FHS-7, was developed to screen for individuals with an increased risk for hereditary breast cancer syndromes. FHS-7 was applied to 9218 women during routine visits to primary care units in Southern Brazil. Two consecutive samples of 885 women and 910 women who answered positively to at least one question and negatively to all questions were included, respectively. The sensitivity, specificity and positive and negative predictive values were determined. Results Of the 885 women reporting a positive family history, 211 (23.8%; CI95%: 21.5–26.2 had a pedigree suggestive of a hereditary breast and/or breast and colorectal cancer syndrome. Using as cut point one positive answer, the sensitivity and specificity of the instrument were 87.6% and 56.4%, respectively. Concordance between answers in two different applications was given by a intra-class correlation (ICC of 0.84 for at least one positive answer. Temporal stability of the instrument was adequate (ICC = 0.65. Conclusion A simple instrument for the identification of the most common hereditary breast cancer syndrome phenotypes, showing good specificity and temporal stability was developed and could be used as a screening tool in primary care to refer at
Feng Wei; Xiubao Ren; Xishan Hao
CD40L-CD40 interaction is central to the control of thymusdependent humoral .immunity and cell mediated immune responses.CD40, a member of the tumor necrosis factor receptor (TNF- R) family,has been found on the surface of B lymphocytes, monocytes, hematopoietic progenitors, dendritic cells (DCs), endothelial cells, epithelial cells and so on. Its natural ligand (CD40 ligand, CD40L), CD154, a member of the tumor necrosis factor (TNF) family, is mainly expressed on activated CD4+ T lymphocytes. A direct growth-inhibitory effect can be found when ligated CD40 is on human breast, ovarian, cervical, bladder, non-small cell lung, and squamous epithelial carcinoma cells. This effect is related to the induction of cell cycle blockage and/or apoptosis. CD40L induces phenotypic and functional maturation of DCs, and can increase tumor immunogenicity through up-regulation of costimulatory molecular expression and cytokine production by epithelial cancer cells. As a result,CD40L can enhance tumor rejection immune responses. Furthermore, by means of a "bystander effect", even CD40-negative tumor subsets can be eliminated by activated tumor-reactive cytotoxic T lymphocytes(CTL),This review summarizes recent findings on CD40L recombinant protein and gene therapy-based tumor treatment approaches.
Shaw, Eric K; Scott, John G; Ferrante, Jeanne M
Extensive research has focused on understanding family dynamics of men with prostate cancer. However, little qualitative work has examined the role of family ties on men's prostate cancer decisions across the spectrum of screening, diagnosis, and treatment. Using data from a larger study, we qualitatively explored the influence of family ties on men's prostate cancer decisions. Semistructured interviews were conducted with men ages ≥50 (N = 64), and data were analyzed using a grounded theory approach and a series of immersion/crystallization cycles. Three major themes of spousal/family member influence were identified: (a) spousal/family member alliance marked by open communication and shared decision making, (b) men who actively opposed spouse/family member pressure and made final decisions themselves, and (c) men who yielded to spouse/family member pressure. Our findings provide insights into men's relational dynamics that are important to consider for the shared decision-making process across the prostate cancer spectrum. PMID:23459024
Most currently known breast cancer predisposition genes play a role in DNA repair by homologous recombination. Recent studies conducted on RAD51 paralogs, involved in the same DNA repair pathway, have identified rare germline mutations conferring breast and/or ovarian cancer predisposition in the RAD51C, RAD51D and XRCC2 genes. The present study analysed the five RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3) to estimate their contribution to breast and ovarian cancer predisposition. The study was conducted on 142 unrelated patients with breast and/or ovarian cancer either with early onset or with a breast/ovarian cancer family history. Patients were referred to a French family cancer clinic and had been previously tested negative for a BRCA1/2 mutation. Coding sequences of the five genes were analysed by EMMA (Enhanced Mismatch Mutation Analysis). Detected variants were characterized by Sanger sequencing analysis. Three splicing mutations and two likely deleterious missense variants were identified: RAD51B c.452 + 3A > G, RAD51C c.706-2A > G, RAD51C c.1026 + 5-1026 + 7del, RAD51B c.475C > T/p.Arg159Cys and XRCC3 c.448C > T/p.Arg150Cys. No RAD51D and XRCC2 gene mutations were detected. These mutations and variants were detected in families with both breast and ovarian cancers, except for the RAD51B c.475C > T/p.Arg159Cys variant that occurred in a family with 3 breast cancer cases. This study identified the first RAD51B mutation in a breast and ovarian cancer family and is the first report of XRCC3 mutation analysis in breast and ovarian cancer. It confirms that RAD51 paralog mutations confer breast and ovarian cancer predisposition and are rare events. In view of the low frequency of RAD51 paralog mutations, international collaboration of family cancer clinics will be required to more accurately estimate their penetrance and establish clinical guidelines in carrier individuals
袁瑛; 叶俊; 郑树
Background Hereditary nonpolyposis colorectal cancer (HNPPC) is one of the most common genetic syndrome related with mutation of human mismatch repair genes. This study was to evaluate the clinical significance of suspected hereditary nonpolyposis colorectal cancer (sHNPCC) criteria I and the clinical and genetic features of International Collaborative Group-HNPCC (ICG-HNPCC) and sHNPCC families.Methods Twenty-nine ICG-HNPCC families fulfilling the Amsterdam criteria and 34 sHNPCC families fulfilling the sHNPCC criteria I were collected. PCR-SSCP and DNA sequencing analysis were employed to screen the germline mutations of the hMLH1 and hMSH2 genes in these families.Results The ICG group had more colorectal cancer (CRC) patients per family than did the suspected group (P0.05), mutation type, and mutation distribution. Comparison of the families with and without mutation showed no significant difference in CRC patients per family, Lynch classification, and tumor spectrum.Conclusions ICG-HNPCC and sHNPCC families that have similar clinical manifestations and genetic basis indicate a similar nature for cancer development. The application of sHNPCC criteria I will facilitate clinical diagnosis and treatment of small families.
Larsen, Martin J; Thomassen, Mads; Tan, Qihua;
BACKGROUND: In more than 70% of families with a strong history of breast and ovarian cancers, pathogenic mutation in BRCA1 or BRCA2 cannot be identified, even though hereditary factors are expected to be involved. It has been proposed that tumors with similar molecular phenotypes also share similar...... and provide evidence for epigenetic inactivation of BRCA1 in three of the tumors. In addition, 7 BRCA2-like tumors were found. CONCLUSIONS: Our finding indicates involvement of hereditary factors in non-BRCA1/2 breast cancer families in which family members may carry genetic susceptibility not just to...... underlying pathophysiological mechanisms. In the current study, the aim was to investigate if global RNA profiling can be used to identify functional subgroups within breast tumors from families tested negative for BRCA1/2 germline mutations and how these subgroupings relate to different breast cancer...
Full Text Available Growth factors mediate their diverse biologic responses (regulation of cellular proliferation, differentiation, migration and survival by binding to and activating cell-surface receptors with intrinsic protein kinase activity named Receptor Tyrosine Kinases (RTKs. About 60 RTKs have been identified and can be classified into more than 16 different receptor families. Their activity is normally tightly controlled and regulated. Overexpression of RTK proteins or functional alterations caused by mutations in the corresponding genes or abnormal stimulation by autocrine growth factor loops contribute to constitutive RTK signaling, resulting in alterations in the physiological activities of cells. The ErbB receptor family of RTKs comprises four distinct receptors: the EGFR (also known as ErbB1/HER1, ErbB2 (neu, HER2, ErbB3 (HER3 and ErbB4 (HER4. ErbB family members are often overexpressed, amplified, or mutated in many forms of cancer, making them important therapeutic targets. EGFR has been found to be amplified in gliomas and non-small-cell lung carcinoma while ErbB2 amplifications are seen in breast, ovarian, bladder, non-small-cell lung carcinoma, as well as several other tumor types. Several data have shown that ErbB receptor family and its downstream pathway regulate epithelial-mesenchymal transition, migration, and tumor invasion by modulating extracellular matrix components. Recent findings indicate that extracellular matrix components such as matrikines bind specifically to EGF receptor and promote cell invasion. In this review, we will present an in-depth overview of the structure, mechanisms, cell signaling, and functions of ErbB family receptors in cell adhesion and migration. Furthermore, we will describe in a last part the new strategies developed in anti-cancer therapy to inhibit ErbB family receptor activation.
Keller, M; Jost, R; Haunstetter, C M; Sattel, H; Schroeter, C; Bertsch, U; Cremer, F; Kienle, P; Tariverdian, M; Kloor, M; Gebert, J; Brechtel, A
Few studies have reported prospective data on psychosocial outcomes after genetic counselling in families with suspected hereditary non-polyposis colorectal cancer (HNPCC). This prospective study examines the impact of multidisciplinary risk counselling on the psychosocial outcome of 139 affected cancer patients and 233 family members without cancer at risk for HNPCC. Participants completed questionnaires specific to HNPCC before and 8 weeks after attending the familial cancer clinic. Affected patients' levels of distress were closely related to their health status and exceeded that of unaffected individuals, as did worry regarding their relatives' risk. A significant reduction in general anxiety (Hospital Anxiety and Depression Scale), distress specific to familial CRC (Impact of Events Scale) and general cancer worry (Distress Hereditary Disorder) was demonstrated after counselling in both affected patients and unaffected individuals. Reduction in distress was more pronounced in affected patients given a high risk of HNPCC compared with those at intermediate risk. Among unaffected individuals, distress declined regardless of what clinical risk they were assigned. Their perceptions of risk and cancer-related threat declined, while confidence in effective surveillance increased. These results suggest the beneficial effects of multidisciplinary counselling even when high-risk information is conveyed. A patient's previous cancer experience is likely to contribute to clinically relevant distress (15% of those patients), indicating the need for appropriate counselling. PMID:18954412
Lim, Jennifer N W; Hewison, Jenny; Chu, Carol E; Al-Habsi, Hamdan
Patient self-initiated consultations to discuss family history of cancer in primary care and the factors leading to these consultations have not been investigated. Seventy-one out of 150 asymptomatic patients with a family history of cancer at the Yorkshire Cancer Genetics Service participated in this study. A semi-structured questionnaire was administered. The results show that (1) family cancer events, doctors' advice and reaching the age of cancer-affected relatives were more salient in raising awareness of the added cancer risk due to family history than media and publicity, and knowledge of the genetics services; (2) knowledge of family medical history and its clinical value is not easy to ascertain; (3) the inter-relationships with other causal beliefs are of interest and could provide insights to understand the factors motivating patients to discuss family history or cancer risk; (4) the belief that 'cancer runs in the family' or is 'a family thing' may not be sufficient to heighten perceived cancer risk and motivate patients to seek medical advice; and (5) understanding of the medical concept and clinical value of family history is poor even in this group of patients who initiated the GP consultations. In conclusion, because most primary care practitioners are likely to rely on patient initiated discussion to identify individuals at an increased risk of cancer because of their family history, these findings are therefore important to help doctors and health providers understand the reasons influencing asymptomatic patients to self-refer themselves in primary care and discuss cancer risk in order to provide appropriate care. PMID:22109720
Murphy, Gwen; Shu, Xiao Ou; Gao, Yu-Tang; Ji, Bu-Tian; Cook, Michael Blaise; YANG, Gong; Li, Hong-Lan; Rothman, Nathaniel; Zheng, Wei; Chow, Wong-Ho
An elevated risk of colorectal cancer has been associated with sporadic colorectal cancer in first degree relatives, mostly in Western populations. Limited data exists from traditionally low-risk areas, such as Asia, where the prevalence of risk factors may differ. We examined the association of family history of cancer and subsequent colorectal cancer risk in a cohort of traditionally low-risk Chinese women.
Full Text Available Recent genome-wide studies identified a risk locus for colorectal cancer at 18q21, which maps to the SMAD7 gene. Our objective was to confirm the association between SMAD7 SNPs and colorectal cancer risk in the multi-center Colon Cancer Family Registry.23 tagging SNPs in the SMAD7 gene were genotyped among 1,592 population-based and 253 clinic-based families. The SNP-colorectal cancer associations were assessed in multivariable conditional logistic regression.Among the population-based families, both SNPs rs12953717 (odds ratio, 1.29; 95% confidence interval, 1.12-1.49, and rs11874392 (odds ratio, 0.80; 95% confidence interval, 0.70-0.92 were associated with risk of colorectal cancer. These associations were similar among the population- and the clinic-based families, though they were significant only among the former. Marginally significant differences in the SNP-colorectal cancer associations were observed by use of nonsteroidal anti-inflammatory drugs, cigarette smoking, body mass index, and history of polyps.SMAD7 SNPs were associated with colorectal cancer risk in the Colon Cancer Family Registry. There was evidence suggesting that the association between rs12953717 and colorectal cancer risk may be modified by factors such as smoking and use of nonsteroidal anti-inflammatory drugs.
Laing, Catherine M; Moules, Nancy J
The purpose of this philosophical hermeneutic inquiry was to understand the meaning of children's cancer camps for the child with cancer and the family. Six childhood cancer families and 5 cancer camp counselors were interviewed, in order to bring understanding to this topic. Findings from this research revealed that camp means different things for different families, and that much is at play in the cancer camp experience: the healing and developmental power of play, finding acceptance and fit, grief as something to live with versus "get over," storytelling as a means of reshaping and understanding traumatic experiences, and the solidarity of the community as one that creates intense, healing bonds. Children's cancer camps, we conclude, should be considered a necessity, versus a luxury, and could even be thought of as a psychosocial intervention for some children and families. Barriers such as structure of funding and access to resources are present and likely due to the separateness of camps from hospital programs. PMID:25643975
Chavand, Aurélie; Grandjean, Hélène; Vignes, Michel
Adolescent medicine is expanding in Europe with particular attention being given to cancer of adolescents and its treatment. At a time where specialised units for adolescents are being born, it is essential to collect the current knowledge on the pathological impact of the illness in this age period whose limits themselves are often blurred (13-21 years or 15-25 years). Adolescence is a transition between childhood and adulthood, during which one seeks psychological and emotional development. Cancer, by its direct repercussion on the adolescent and also by the disorganisation of the family, can involve risks impending the process of maturation and can also be a purveyor of psychological after-affects. The occurrence of the illness can isolate the adolescent and leak to a restriction of the psychological investment. The reality of possible death can hinder the ill adolescent from developing his natural opposition to the adults who represent authority such as parents or nurses, thereby hindering access to autonomy, independence and identity construction. One can find oneself locked in a state of trouble, confusion, becoming a stranger to oneself, with an impression of distance waxing between the young patient and others. The parents find themselves weakening and must make calls on their supporters. The siblings see their daily life becoming more unsettled and find themselves confronted by parents less available and reassuring. The impact on the brothers and sisters vary depending on their age and the capacity of the parent's adaptation. From the onset, adolescents struck by cancer necessitate an adaptation of the medical staff. The medical information, the treatment and the aid-care contracts must be approved by the adolescent himself but the parent's involvement remains essential. It is necessary to create an alliance of three. Conflicts and rivalry occur frequently between parents and the medical staff. One must study the possibility of creating a place adapted to
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
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...
Mosher, Catherine E.; Given, Barbara A.; Ostroff, Jamie S.
Although family caregivers of patients with lung and other cancers show high rates of psychological distress, they underuse mental health services. This qualitative study aimed to identify barriers to mental health service use among 21 distressed family caregivers of lung cancer patients. Caregivers had not received mental health services during the patient’s initial months of care at a comprehensive cancer centre in New York City. Thematic analysis of interview data was framed by Andersen’s ...
Liu, Yu; Cao, Chunmei
Objective: To investigate the relationship between family history of cancer, coping style and psychological distress. Methods: Total 80 patients with family history of cancer and 72 normal controls were analyzed using self-reporting inventory (SCL-90), coping style scale and impact of event scale-revised (IES-R). Results: 1. Between the two groups of patients, there were significant differences in anxiety, depression, cancer-specific distress and coping style. 2. Psychological distress (anxie...
Jin, Y. T.; Xu, Y C; Yang, R D; Huang, C. F.; Xu, C W; He, X Z
To investigate whether lung cancer clusters in families in a high incidence county of China, an analysis was conducted using data on domestic fuel history and tobacco use for family members of 740 deceased lung cancer probands and 740 controls (probands' spouses). Lung cancer prevalence was compared among first-degree relatives of probands and of controls, taking into account various factors using logistic regression and generalised estimating equations. First-degree relatives of probands, co...
Cimete, Guler; Kuguoglu, Sema
The aim of this qualitative study was to determine what the emotional reactions, experiences, and coping and support systems of families would be after the death of their children from cancer. The sample comprised 19 family members from five families. At the time of the interviews, it had been 8-14 months since the death of their children. The…
Teixeira, Natalia; Azevedo Koike Folgueira, Maria Aparecida; Maistro, Simone; Encinas, Giselly; de Bock, Geertruida Hendrika; Estevez Diz, Maria Del Pilar
Objectives: to analyze factors that might indicate familial predisposition for ovarian cancer in patients diagnosed with this disease. Methods: in a prospective single center cohort study at the Institute of Cancer of the State of Sao Paulo (ICESP), 51 women diagnosed with ovarian cancer were includ
Full Text Available Abstract Background Family size and birth order are known to influence the risk of some cancers. However, it is still unknown whether these effects change from early to later adulthood. We used the data of the Swedish Family-Cancer Database to further analyze these effects. Methods We selected over 5.7 million offspring with identified parents but no parental cancer. We estimated the effect of birth order and family size by Poisson regression adjusted for age, sex, period, region and socioeconomic status. We divided the age at diagnosis in two groups, below and over 50 years, to identify the effect of family size and birth order for different age periods. Results Negative associations for increasing birth order were found for endometrial, testicular, skin, thyroid and connective tissue cancers and melanoma. In contrast, we observed positive association between birth order and lung, male and female genital cancers. Family size was associated with decreasing risk for endometrial and testicular cancers, melanoma and squamous cell carcinoma; risk was increased for leukemia and nervous system cancer. The effect of birth order decreased for lung and endometrial cancer from age at diagnosis below to over 50 years. Combined effects for birth order and family size were marginally significant for thyroid gland tumors. Especially, the relative risk for follicular thyroid gland tumors was significantly decreased for increasing birth order. Conclusion Our findings suggest that the effect of birth order decreases from early to late adulthood for lung and endometrial cancer.
Family size and birth order are known to influence the risk of some cancers. However, it is still unknown whether these effects change from early to later adulthood. We used the data of the Swedish Family-Cancer Database to further analyze these effects. We selected over 5.7 million offspring with identified parents but no parental cancer. We estimated the effect of birth order and family size by Poisson regression adjusted for age, sex, period, region and socioeconomic status. We divided the age at diagnosis in two groups, below and over 50 years, to identify the effect of family size and birth order for different age periods. Negative associations for increasing birth order were found for endometrial, testicular, skin, thyroid and connective tissue cancers and melanoma. In contrast, we observed positive association between birth order and lung, male and female genital cancers. Family size was associated with decreasing risk for endometrial and testicular cancers, melanoma and squamous cell carcinoma; risk was increased for leukemia and nervous system cancer. The effect of birth order decreased for lung and endometrial cancer from age at diagnosis below to over 50 years. Combined effects for birth order and family size were marginally significant for thyroid gland tumors. Especially, the relative risk for follicular thyroid gland tumors was significantly decreased for increasing birth order. Our findings suggest that the effect of birth order decreases from early to late adulthood for lung and endometrial cancer
Purpose: In thyroid cancer patients, radioiodine treatment has been shown to be associated with an increased risk of colon carcinoma. The aim of this study in thyroid cancer patients was to evaluate the role of familial factors in the risk of colorectal cancer and their potential interaction with radioiodine exposure. Methods and Materials: We performed a case-control study on 15 colorectal cancer patients and 76 matched control subjects, nested in a cohort of 3708 thyroid cancer patients treated between 1933 and 1998. For each patient, the radiation dose delivered to the colon by radioiodine was estimated by use of standard tables. In those who received external radiation therapy, the average radiation doses delivered to the colon and rectum were estimated by use of DOSEg software. A complete familial history was obtained by face-to-face interviews, and a familial index was defined to evaluate the degree of familial aggregation. Results: The risk of colorectal cancer increased with familial aggregation of colorectal cancer (p = 0.02). After adjustment for the radiation dose delivered to the colon and rectum, the risk of colorectal cancer was 2.8-fold higher (95% CI, 1.0-8.0) for patients with at least one relative affected by colorectal cancer than for patients without such a family history (p = 0.05). The radiation dose delivered to the colon and rectum by 131I and external radiation therapy was associated with an increase of risk near the significance threshold (p = 0.1). No significant interaction was found between radiation dose and having an affected relative (p = 0.9). Conclusions: The role of familial background in the risk of colorectal cancer following a differentiated thyroid carcinoma appears to increase with the radiation dose delivered to the colon and rectum. However, the study population was small and no interaction was found between these two factors
M F Atoum
Full Text Available Purpose : Staging of breast tumor has important implications for treatment and prognosis. This study aims at pinpointing the frequency of each stage among familial and nonfamilial breast cancers. Materials and Methods : Ninety-nine Jordanian females diagnosed with familial and nonfamilial breast cancer between 2000 and 2002 were enrolled in this study All breast cancer cases were staged according to the TNM classification into in situ, early invasive, advanced invasive and metastatic. Results : Forty-three cases were familial breast cancer and 56 were nonfamilial. One female breast cancer was diagnosed with ductal carcinoma in situ (DCIS cancer. Fifty cases were diagnosed in early stages of invasive breast cancer, of which 31 cases were familial, 29 cases were classified as advanced invasive, where 21 cases were nonfamilial and 19 cases were metastatic stage of breast cancer, with 16 nonfamilial cases. Stage 2b was the most common stage of early invasive cases and represented 48% of the early stage of breast cancer. On the other hand, among cases diagnosed with advanced invasive breast cancer, stage 3a was the most common stage and represented 89.6% of the advanced stage. Interestingly, all cases of stage 3a belonged to TNM stages of T2N2M0 and T3N1M0. The tumor size in all cases of Jordanian females diagnosed with advanced invasive breast cancer exceeded 2 cm in size due to selection bias from symptomatic women in our study. Conclusion : The incidence of nonfamilial breast cancer was slightly higher than that of the familial type amongst studied the Jordanian females studied. The early invasive stage of breast cancer was more common in the familial while the advanced invasive and metastatic breast cancer cases were encountered more often in the nonfamilial type. Our study was based on a small sample and symptomatic women. Therefore, more research with larger population samples is needed to confirm this conclusion.
Full Text Available Abstract Background Germ-line mutations in the BRCA1 and BRCA2 genes are major contributors to hereditary breast/ovarian cancer. Large rearrangements are less frequent in the BRCA2 gene than in BRCA1. We report, here, the first total deletion of exon 3 in the BRCA2 gene that was detected during screening of 2058 index cases from breast/ovarian cancer families for BRCA2 large rearrangements. Deletion of exon 3, which is in phase, does not alter the reading frame. Low levels of alternative transcripts lacking exon 3 (Δ3 delta3 transcript have been reported in normal tissues, which raises the question whether deletion of exon 3 is pathogenic. Methods Large BRCA2 rearrangements were analysed by QMPSF (Quantitative Multiplex PCR of Short Fluorescent Fragments or MLPA (Multiplex Ligation-Dependent Probe Amplification. The exon 3 deletion was characterized with a "zoom-in" dedicated CGH array to the BRCA2 gene and sequencing. To determine the effect of exon 3 deletion and assess its pathogenic effect, three methods of transcript quantification were used: fragment analysis of FAM-labelled PCR products, specific allelic expression using an intron 2 polymorphism and competitive quantitative RT-PCR. Results Large rearrangements of BRCA2 were detected in six index cases out of 2058 tested (3% of all deleterious BRCA2 mutations. This study reports the first large rearrangement of the BRCA2 gene that includes all of exon 3 and leads to an in frame deletion of exon 3 at the transcriptional level. Thirty five variants in exon 3 and junction regions of BRCA2 are also reported, that contribute to the interpretation of the pathogenicity of the deletion. The quantitative approaches showed that there are three classes of delta3 BRCA2 transcripts (low, moderate and exclusive. Exclusive expression of the delta3 transcript by the mutant allele and segregation data provide evidence for a causal effect of the exon 3 deletion. Conclusion This paper highlights that large
... in one breast only) diagnosed after age 50 Grandmother with breast cancer diagnosed at age 75 Get ... breast cancer diagnosed at age 45 and paternal grandmother (fatherâ€™s mother) with breast cancer diagnosed at age ...
Margolin, Sara; Eiberg, Hans; Lindblom, Annika;
763 breast cancer patients with a defined family history and 760 controls from the Stockholm region. The breast cancer patients originated from; a population-based cohort (n = 452) and from a familial cancer clinic (n = 311), the detailed family history was known in both groups. RESULTS: The variant......BACKGROUND: A truncating variant, 1100delC, in check point-kinase CHEK2, has been identified as a risk factor for familial and sporadic breast cancer. The prevalence in healthy non-breast cancer cases is low and varies between populations. METHODS: We analyzed the prevalence of CHEK2 1100delC in...... was found in 2.9% of the familial cases from the population-based cohort and in 1.9% from the familial cancer clinic. In total 2.2% of the patients with a family history of breast cancer carried the variant compared to 0.7% of the controls (p = 0.03). There was no increased prevalence in sporadic...
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
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 ...
Vivar, Cristina G
AIMS The aims of this thesis are to provide understanding of the psychosocial impact of recurrent cancer on patients and family members and to develop a substantive theory that explains the phenomenon of recurrence from a psychosocial perspective. BACKGROUND Cancer survival is increasing, and as people live longer, cancer recurrence is a real possibility. Recurrence has been described as one of the most stressful phases of cancer. Despite this reality, recurrence is poorly unde...
Full Text Available Research question : What are the various areas and burden a family experiences due to presence of oral and oropharyngeal cancer patient. Objectives: 1. To identify the family burden like financial burden, disruption of routine activities and family leisure etc. 2. To study the severity of family burden experienced by the families of oral and oropharyngeal cancer patients. Study design: Case- control. Setting: Gujarat Cancer and Research Institute (G.C.R.I, Ahmedabad. Participants: 100 cases belonging to the diagnostic categories no. 140-46 of ICD â€"9 and 100 controls belonging to the diagnostic categories other than no. 140-46 of ICD-9 Statistical analysis: Proportions, Chi-square test and Z test. Results: Financial burden was observed in 36% of cases and 43% of controls had burden on the family. Out of 43% respondents reporting any burden, 36(83.72% were identified with severe burden.
Il-Jin Kim; Hio Chung Kang; Yong Shin; Byong Chul Yoo; Han-Kwang Yang; Jae-Gahb Park
@@ TO THE EDITOR Although the incidence of gastric cancer has declined somewhat in recent years, it remains one of the most common cancers worldwide, and is the most common cancer in East Asian countries such as Korea and Japan.In terms of the genetics of gastric cancer, mutations in CDH1 (E-cadberin) have been associated with hereditary diffuse gastric cancer (HDGC). The first germline mutation in CDH1 was reported in a large Maori HDGC family,with subsequent corroborations in Western and Asian HDGC families[3-5], CDH1 mutations are believed to be associated with up to 50% of HDGC families, but have not been linked with sporadic or intestinal types of gastric cancer.
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
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
I.I.H. van Oostrom (Iris)
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
McWhinney, Ian R.; Hoddinott, Susan N.; Bass, Martin J.; Gay, Keith; Shearer, Robin
To assess the involvement of family physicians in the continuing care of cancer patients, 499 patients attending the London Regional Cancer Centre for follow-up appointments were questioned. Of the 493 patients with a family doctor, 282 (57.2%) reported that their family doctor had been involved in the diagnosis, 132 (26.8%) in the treatment, and 214 (43.4%) in the follow up. Only 60% thought that their family doctor was aware of their current problems, and only 31.4% had an appointment to se...
Madersbacher, Stephan; Alcaraz, Antonio; Emberton, Mark; Hammerer, Peter; Ponholzer, Anton; Schröder, Fritz H; Tubaro, Andrea
• The most recent evidence for the link between a family history of prostate cancer and individual risk for future disease was examined, with the aim of understanding what the existence and nature of a family history of prostate cancer does to a man's risk of developing the disease. • Our findings highlighted the clear association between a family history of prostate cancer and increased risk of developing the disease; with a greater proximity of relatedness, greater number of family members affected and/or earlier age at diagnosis of the family member elevating risk further. • These findings have important clinical implications for the identification and subsequent management of men deemed to be at increased risk of developing prostate cancer. The evidence for prostate cancer risk reduction with the mono 5α-reductase inhibitor (5ARI) finasteride in a low-risk population and, more recently, with the dual 5ARI dutasteride in a population at increased risk of developing the disease, has potential to expand management options for men at risk of developing prostate cancer beyond more frequent and/or earlier surveillance. • Given that family history can be easily assessed in routine clinical practice, it should be regarded as an important parameter to consider alongside PSA level for prostate cancer risk assessment. PMID:21166744
Anderson, E; Berg, J; Black, R; Bradshaw, N; Campbell, J; Carnaghan, H; Cetnarkyj, R; Drummond, S; Davidson, R; Dunlop, J; Fordyce, A; Gibbons, B; Goudie, D; Gregory, H; Holloway, S; Longmuir, M; McLeish, L; Murday, V; Miedzybrodska, Z; Nicholson, D; Pearson, P; Porteous, M; Reis, M; Slater, S; Smith, K; Smyth, E; Snadden, L; Steel, M; Stirling, D; Watt, C; Whyte, C; Young, D
To evaluate current guidelines criteria for inclusion of women in special ‘breast cancer family history' surveillance programmes, records were reviewed of women referred to Scottish breast cancer family clinics between January 1994 and December 2003 but discharged as at ‘less than ‘moderate' familial risk'. The Scottish Cancer Registry was then interrogated to determine subsequent age-specific incidence of breast cancer in this cohort and corresponding Scottish population figures. Among 2074 women, with an average follow-up of 4.0 years, 28 invasive breast cancers were recorded up to December 2003, where 14.4 were expected, a relative risk (RR) of 1.94. Eleven further breast cancers were recorded between January 2004 and February 2006 (ascertainment incomplete for this period). The overall RR for women in the study cohort exceeded the accepted ‘cutoff' level (RR=1.7) for provision of special counselling and surveillance. The highest RR was found for the age group 45–59 years and this group also generated the majority of breast cancers. The National Institute for Clinical Excellence (‘NICE') guidelines appear to be more accurate than those of the Scottish Intercollegiate Guidelines Network (‘SIGN') in defining ‘moderate' familial risk, and longer follow-up of this cohort could generate an evidence base for further modification of familial breast cancer services. PMID:18283300
WUZhengyan; ZHENLinlin; FANPing
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.
Heiniger, Louise; Price, Melanie A; Charles, Margaret; Butow, Phyllis N
Little is known about the process of psychosocial adaptation to familial risk in tested and untested individuals at increased familial risk of cancer. This paper presents findings from a qualitative study of 36 women participating in the Kathleen Cuningham Consortium for Research into Familial Breast cancer (kConFab) Psychosocial study. Facilitators and challenges in psychosocial adaptation were identified through semi-structured interviews. The women, who were either tested (carriers or non-carriers of breast cancer susceptibility mutations) or untested (ineligible for testing or eligible but delayed or declined testing), described personal, support network and healthcare characteristics that impacted on the adaptation process. Challenges in one domain could be overcome by facilitators in other domains and key differences relating to whether women had undergone testing, or not, were identified. Tested and untested women with an increased familial risk of breast cancer may benefit from support tailored to their mutation testing status in order to enhance adaptation. PMID:25735441
Expert-reviewed information summary about the challenges faced by family caregivers of cancer patients. This summary focuses on typical caregiver roles and concerns, and helpful interventions for caregivers.
Zipprich, Jennifer; Terry, Mary Beth; Liao, Yuyan; Agrawal, Meenakshi; Gurvich, Irina; Senie, Ruby; Santella, Regina M.
Reactive Oxygen Species (ROS) are important in the pathogenesis of many diseases, including breast cancer. Several population-based case-control studies have demonstrated that various biomarkers of oxidative stress are associated with an increase in breast cancer risk. We selected sisters discordant for breast cancer (n=645) from the New York site of the Breast Cancer Family Registry to explore factors that contribute to variation in plasma protein carbonyls, and to determine whether this bio...
Zhang, Amy Y; Siminoff, Laura A
This study examined the phenomenon of avoidance of family communication about cancer. Thirty-seven Stage III or IV lung cancer patients and 40 caregivers, including 24 primary and 16 secondary caregivers, were interviewed; a total of 26 families were studied. The interviews were audiotaped and transcribed. Analysis of the interviews indicated that two thirds of the families (65%) experienced communication problems. The avoidance of family communication was associated with several underlying thought processes: avoidance of psychological distress; desire for "mutual protection;" and belief in positive thinking. Family communication was further hindered by the increasing difficulty of issues inherent to late-stage cancer. The adverse impact of communication avoidance and the implications of our findings are discussed. PMID:14527866
Begum, Parvin; Richardson, Caroline E; Carmichael, Amtul R.
Background: Obesity and physical activity are modifiable risk factors in the development of postmenopausal breast cancer. The aim of this study was to assess the level of awareness and prevalence of these factors in women attending family history clinics. Methods: Women attending the breast cancer family history clinic from 2004 to 2006 completed a questionnaire (SP15 format) about their knowledge of and exposure to various diet and lifestyle factors. All women had been counselled by a Co...
Fernandez, E.; La Vecchia, C.; D'Avanzo, B; De Negri, E.; Franceschi, S
The relationship between lifestyle factors, past medical conditions, daily meal frequency, diet and the risk of 'familial' colorectal cancer has been analysed using data from a case-control study conducted in northern Italy. A total of 1584 colorectal cancer patients and 2879 control subjects were admitted to a network of hospitals in the Greater Milan area and the Pordenone province. The subjects included for analysis were the 112 cases and the 108 control subjects who reported a family hist...
Stockdale Alan; Ashikaga Takamaru; Wood Marie E; Flynn Brian S; Dana Greg S; Naud Shelly
Abstract Background Family history (FH) assessment is useful in identifying and managing patients at increased risk for cancer. This study assessed reported FH quality and associations with physician perceptions. Methods Primary care physicians practicing in two northeastern U.S. states were surveyed (n = 880; 70% response rate). Outcome measures of FH quality were extent of FH taken and ascertaining age at cancer diagnosis for affected family members. Predictors of quality measured in this s...
Elanur Yιlmaz Karabulutlu
Objective: Cancer is a disease that not only affects the individual′s mental and physical integrity but also affects the functionality of the family system. Caregivers experience stress when patients cannot cope with the symptoms they are experiencing. The stress experienced by caregivers gives rise to psychological and physical symptoms. The purpose of this study is to determine the attitude of coping with stress of family caregivers of cancer patients. Methods: This study was conducted as a...
Laitman, Yael; Simeonov, Monica; Herskovitz, Liron; Kushnir, Anya; Shimon-Paluch, Shani; Kaufman, Bella; Zidan, Jamal; Friedman, Eitan
The spectrum of germline mutations among Jewish non Ashkenazi high risk breast/ovarian cancer families includes a few predominant mutations in BRCA1 (185delAG and Tyr978X) and BRCA2 (8765delAG). A few additional recurring mutations [A1708E, 981delAT, C61G (BRCA1) R2336P, and IVS2 + 1G > A (BRCA2)] have been reported in Jewish non Ashkenazi families. The 4153delA*BRCA1 C61G*BRCA1 and the 4075delGT*BRCA2 has been reported to recur in Russian/Polish non Jews and Ashkenazim, respectively. The rate of these recurring mutations has not been reported in Israeli high risk families. Genotyping for these recurring mutations by restriction enzyme digest and sequencing method was applied to high risk, predominantly cancer affected, unrelated Israeli individuals of Ashkenazi (n = 827), non Ashkenazi (n = 2,777), non Jewish Caucasians (n = 193), and 395 of mixed ethnicity. Jewish participants included 827 Ashkenazi, 804 Balkans, 847 North Africans, 234 Yemenites, and 892 Asians (Iraq and Iran). Age at diagnosis of breast cancer (median ± SD) (n = 2,484) was 47.2 ± 9.6 for all women participants. Males (n = 236) were also included, of whom 24 had breast cancer and 35 had pancreatic cancer. Overall, 8/282 (2.8%) of the Balkan cases carried the BRCA1*A1708E mutation, 4/180 (2.2%) the R2336P mutation, and 0/270 the IVS2 + 1G > A BRCA2 mutations, respectively. Of North Africans, 7/264 (2.65%) carried the BRCA1*981delAT mutation. The BRCA1*C61G mutation was detected in 3/269 Ashkenazi, non Ashkenazi, and non Jewish Russians; the BRCA1*Tyr978X mutation was detected in 23/3220 individuals of non Ashkenazi origin, exclusively of Asian ethnicity (23/892, 2.6% of the Asians tested). The BRCA1*4153delA mutation was noted in 2/285 non Jewish Caucasians, and none of the Ashkenazim (n = 500) carried the BRCA2*4075delGT mutation. Jewish high risk families of North African, Asian, and Balkan descent should be screened for the 981delAT, Tyr978X, A1708E BRCA1, and the R2336P BRCA2 mutations
Gabriella De Benedetta
Full Text Available Objective. Anorexia nervosa is difficult to diagnose in cancer patients since weight loss, aversion for food, and eating disturbances are frequent in patients undergoing chemotherapy and radiotherapy. Nevertheless, efforts are mandatory to recognize and manage this condition which may occur also in cancer patients with a special regard to adolescents. Methods. Through the clinical history of Anna, a 15-year-old adolescent with advanced cancer, we describe the effectiveness of a family-based systemic intervention to manage anorexia nervosa occurring in concomitance to osteosarcoma. Results. Through a two-year psychotherapy period involving different techniques applied to the whole family such as family genogram, family collage, and sculpture of family time, Anna was relieved from her condition. Conclusions. Upon early diagnosis and appropriate treatment, anorexia nervosa can be effectively approached in adolescent cancer patients. The presence of a life-threatening medical condition such as cancer may provide motivation for a patient to control disordered eating behavior in the context of an appropriate family-based systemic intervention. The general frame of anorexia occurring in cancer-bearing adolescents is reviewed and discussed.
Zhang, J.X.; Fu, L.; Voer, R.M. de; Hahn, M.M.; Jin, P.; Lv, C.X.; Verwiel, E.T.; Ligtenberg, M.J.L.; Hoogerbrugge, N.; Kuiper, R.P.; Sheng, J.Q.; Geurts van Kessel, A.H.M.
AIM: To investigate whether whole-exome sequencing may serve as an efficient method to identify known or novel colorectal cancer (CRC) predisposing genes in early-onset or familial CRC cases. METHODS: We performed whole-exome sequencing in 23 Chinese patients from 21 families with non-polyposis CRC
Wu, Kitty K. Y.
Explored emotional states of dying patients, age, and family support. Findings from 26 terminally ill female cancer patients revealed that younger patients expressed more bargaining and complaints than older patients who revealed more depression and acceptance. Patients with immediate family support expressed less depression and more fears than…
Gazendam-Donofrio, S.M.; Hoekstra, H.J.; van der Graaf, W.T.A.; van de Wiel, H.B.; Visser, A.; Huizinga, G.A.; Hoekstra-Weebers, J.E.
Background: This article focuses on possible relationships between functioning of adolescents with a parent diagnosed with cancer 1-5 years earlier and family environment. Patients and methods: In all, 138 patients, 114 spouses and 221 adolescents completed the Family Environment Scale. Additionally
Valdespino-Gómez, Víctor M; Valdespino-Castillo, Víctor E
More than 200 cancer susceptibility syndromes (CSS) have been recognized through performing classic epidemiologic studies and genetic linkage analysis. In most CSSs clinical conditions of the patients have been identified as well as their hereditary patterns and the predisponent genes to cancer development. Cancer hereditary identification is a useful condition, since cancer family integrants may benefit of efficient strategies in early screening and in tumor prevention strategies; this consultation is performed by oncogenetic molecular medical consultants who must be scientifically competent for Human Genetics and Cancer molecular biology domains. The oncogenetic molecular consult of patients and family relatives of cancer predisposition families is a medical service in health programs of developed and developing countries; in our country this type of medical service needs to be organized and settled to be part of the integral oncology medical service. The oncogenetic molecular consultation is a structural process of assessment and communication of the associated integral problems of the cancer inherited susceptibility in familial cancer. PMID:27100983
Visser, A; Huizinga, GA; van der Graaf, WTA; Hoekstra, HJ; Hoekstra-Weebers, JEHM
Objective. Children of cancer patients may go through a distressing time. The aim of this review was to survey present knowledge on the impact of parental cancer on children and the family. Design. Studies published between January 1980 and March 2004 addressing emotional, social, behavioural, cogni
Madersbacher, Stephan; Alcaraz, Antonio; Emberton, Mark; Hammerer, Peter; Ponholzer, Anton; Schroeder, Fritz H.; Tubaro, Andrea
A family history of prostate cancer has long been identified as an important risk factor for developing the disease. This risk factor can be easily assessed in clinical practice and current guidelines recommend to initiate prostate cancer early detection 5 years earlier (i.e. around the age of 40 ye
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.
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
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
Jakovljević, Gordana; Čulić, Srđana; Benko, Marta; Kalebić Jakupčević, Katja; Stepan, Jasminka; Šprajc, Mirjana
Objective: Psychological interactions between parents,children and social environment are very important for childhood health. The type of personality and stressful events are probably also cancer risk factors. We investigated personality types A/B and D (negative affectivity and social inhibition) in parents of children with cancer (PCC), as well as social environmental factors, and family / children’s stressful events before the appearance of cancer. Subjects and methods: Bortne...
Otis-Green, Shirley; Sidhu, Rupinder K; Del Ferraro, Catherine; Ferrell, Betty
Lung cancer patients and their family caregivers face a wide range of potentially distressing symptoms across the four domains of quality of life. A multidimensional approach to addressing these complex concerns with early integration of palliative care has proven beneficial. This article highlights opportunities to integrate social work using a comprehensive quality of life model and a composite patient scenario from a large lung cancer educational intervention National Cancer Institute-funded program project grant. PMID:24797998
Gabriella De Benedetta; Ida Bolognini; Silvia D'Ovidio; Antonello Pinto
Objective. Anorexia nervosa is difficult to diagnose in cancer patients since weight loss, aversion for food, and eating disturbances are frequent in patients undergoing chemotherapy and radiotherapy. Nevertheless, efforts are mandatory to recognize and manage this condition which may occur also in cancer patients with a special regard to adolescents. Methods. Through the clinical history of Anna, a 15-year-old adolescent with advanced cancer, we describe the effectiveness of a family-based s...
Dempster, Martin; McCorry, Noleen; Brennan, Emma; Donnelly, Michael; Murray, Liam,; Johnston, Brian T.
Objective: The research aimed to determine the extent to which illness cognitions and coping explain psychological distress (fear of cancer recurrence, anxiety and depression symptoms) among family carers of survivors of oesophageal cancer.Methods: Carers of patients registered with the Oesophageal Patients' Association in the UK were mailed a questionnaire booklet containing questions about medical and demographic variables, the Illness Perception Questionnaire-Revised, the Cancer Coping Que...
Full Text Available In human cancer, expression of the let-7 family is significantly reduced, and this is associated with shorter survival times in patients. However, the mechanisms leading to let-7 downregulation in cancer are still largely unclear. Since an alteration in copy-number is one of the causes of gene deregulation in cancer, we examined copy number alterations of the let-7 family in 2,969 cancer specimens from a high-resolution SNP array dataset. We found that there was a reduction in the copy number of let-7 genes in a cancer-type specific manner. Importantly, focal deletion of four let-7 family members was found in three cancer types: medulloblastoma (let-7a-2 and let-7e, breast cancer (let-7a-2, and ovarian cancer (let-7a-3/let-7b. For example, the genomic locus harboring let-7a-3/let-7b was deleted in 44% of the specimens from ovarian cancer patients. We also found a positive correlation between the copy number of let-7b and mature let-7b expression in ovarian cancer. Finally, we showed that restoration of let-7b expression dramatically reduced ovarian tumor growth in vitro and in vivo. Our results indicate that copy number deletion is an important mechanism leading to the downregulation of expression of specific let-7 family members in medulloblastoma, breast, and ovarian cancers. Restoration of let-7 expression in tumor cells could provide a novel therapeutic strategy for the treatment of cancer.
Full text: The aim of this study is to contribute to the characterization of familial breast cancer in our country. Patients and methods. We analyzed 152 families referred to the Hospital Unit Onco genetics Clinic, who had 3 or more cases of breast cancer (C M)(at least one diagnosed before age 50 years) (n = 92)or 2 cases with some sub-criterion (paternal transmission, C M bilateral C M male, ovarian cancer (O C), Ashkenazi Jewish ancestry, a case diagnosed before 40 years) (n = 47)or 4 or more cases without regard to age at diagnosis (n = 4)or an single case diagnosed before age 35 (n = 9). The clinical data collection was conducted onco genetics the query was entered in which, among others, the presence or absence of nongenetic risk factors, personal and family history of breast, ovarian and other tumors and age of diagnosis. Results. 152 cases were selected indices, carrying 148 C M (bilateral n = 29)and 4 CO. The median age at diagnosis of C M developed in these patients was 48 years (range: 25-54). Twenty-three of the 151 patients had a second tumor extra mammary (ovary n = 7; melanoma n = 2, n = 3 cervix, colon n = 4, n = 1 sarcoma, ENT = 1, = 1 pancreas, kidney = 2, CBP = 1, esophagus = 1). Among the relatives of the relevant parent branch were 329 C M (25 bilateral, 2 male)diagnosed before 50 years in more than 60 % of cases and 22 ovarian cancers. Comparing the frequency of different tumor locations both branches parents. In the relevant parent branch, and the prevalence of C M and CO documented a higher frequency of prostate, stomach, pancreas and melanoma. It was possible to obtain information He r2 tumor expression, estrogen receptor (E R) and progesterone receptor (P R) in 25 patients, finding that 10 patients (0.40)had He r2 overexpression, 11 (0.46 R E and / / or P R positive, HER2 negative and 4 E R, P R and He r2 negative (0.16). Conclusions. The characteristics of the families studied, including the frequency of tumors extramamarios agrees with
Song, Honglin; Ramus, Susan J; Kjaer, Susanne Krüger;
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...
K. Hemminki; Mutanen, P
We used the Swedish Family-Cancer Database to analyse the effects of birth order and family size on the risk of common cancers among offspring born over the period 1958–96. Some 1.38 million offspring up to age 55 years with 50.6 million person-years were included. Poisson regression analysis included age at diagnosis, birth cohort, socio-economic status and region of residence as other explanatory variables. The only significant associations were an increasing risk for breast cancer by birth...
Full Text Available Abstract Background The growing possibilities of cancer prevention and treatment as well as the increasing knowledge about hereditary cancers require proper identification of the persons at risk. The aim of this study was to test the outcome of population screening in the scientific and practical evaluation of hereditary cancer. Methods Population screening for hereditary cancer was carried out retrospectively in a geographic area of Latvia. Family cancer histories were collected from 18642 adults representing 76.6% of the population of this area. Hereditary cancer syndromes were diagnosed clinically. Molecular testing for BRCA1 founder mutations 300 T/G, 4153delA and 5382insC was conducted in 588 persons who reported at least one case of breast or ovary cancer among blood relatives. Results Clinically, 74 (0.40%; 95% confidence interval (CI: 0.32 - 0.50% high-risk and 548 (2.94%, 95% CI: 2.71 - 3.19 moderate-risk hereditary cancer syndromes were detected covering wide cancer spectrum. All syndromes were characterised by high cancer frequency among blood relatives ranging 8.6 - 46.2% in contrast to spouse correlation of 2.5 - 3.6%. The mean age of cancer onset ranged 38.0 - 72.0 years in different syndromes. The BRCA1 gene mutations were identified in 10 (1.7%; 95% CI: 0.9 - 3.1% probands. Families with established BRCA1 gene founder mutations were identified with the frequency 1:2663 clinically screened persons. Conclusions Population screening is a useful practical tool for the identification of persons belonging to families with high frequency of malignant tumours. The whole hereditary and familial cancer spectrum along with the age structure was identified adjusting follow-up guidelines. Another benefit of the population screening is the possibility to identify oncologically healthy persons belonging to hereditary and familial cancer families so that appropriate surveillance can be offered. Clinical diagnostics is appropriate for population
Full Text Available Purpose: Family history is associated with gliomas, but this association has not ben established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study (OBTS. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%, 78 meningioma (65%, 49 pituitary adenoma (73.1% and 152 glioma patients (58.2%. The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs and 95% confidence intervals (95% CI. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusions: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.
Martin J Blaser; Abraham Nomura; James Lee; Stemmerman, Grant N; Perez-Perez, Guillermo I
Editors' Summary Background. Although the theory that certain cancers might be caused by infectious agents (such as bacteria and viruses) has been around for some time, concrete evidence linking specific cancers and infections is only recently beginning to emerge. There is now very good evidence that stomach cancer, once one of the frequent types worldwide but now less common, is strongly associated with a particular infection of the stomach lining. This specific bacterium colonizing the stom...
Mesher, David; Dove-Edwin, Isis; Sasieni, Peter;
centers. DNA mismatch repair deficiency was excluded by genetic testing. Families were classified as FCC type X if they fulfilled the original Amsterdam criteria (AC) and late onset (LOFCC) if they fulfilled the AC apart from not having a cancer aged under 50. The most advanced findings on colonoscopy......Surveillance guidelines for the management of familial colorectal cancer (FCC), a dominant family history of colorectal cancer in which the polyposis syndromes and Lynch syndrome have been excluded, are not firmly established. The outcome of colonoscopic surveillance is studied using data from six...... were analyzed. One thousand five hundred eighty-five individuals (median age 47.3, 44% male) from 530 FCC families (349 FCC type X) underwent a total of 4,992 colonoscopies with 7,904 patient-years of follow-up. Results for FCC type X and LOFCC were very similar. At baseline, 22 prevalent asymptomatic...
It has been known for decades that nulliparity is associated with an increased risk for certain reproductive malignancies, including breast, ovarian and uterine cancers. A recent commentary in The Lancet summarized the available evidence based on data in nulliparous women and concluded that the risk of nulliparity was related to the increased number of ovulatory cycles, and so might be preventable by utilization of oral contraceptives. That communication described significant differences in age-dependent cancer mortality in nulliparous nuns, as well as in parous controls, between breast, ovarian and uterine cancers. Moreover, the steep inclines in cancer mortality in nuns are only observed decades after the menopause. Taken together, these observations make it appear unlikely that the number of ovulations is associated aetiologically with increased cancer risks in nulliparous nuns. Here are postulated other possible primary mechanisms that could be responsible for the reported age-related increase in cancer risks in nulliparous women, such as nuns, and conclude that a better understanding of such mechanisms may offer important new insights into tumour initiation in general. PMID:23518034
S. Saadatmand (Sepideh)
markdownabstract__Abstract__ We estimated influence of tumor size and number of positive lymph nodes at breast cancer detection on survival in the current era of new system (neo) adjuvant therapies. We showed that early breast cancer detection remains of great influence. Relative 5-year survival wa
S.L. Knijnenburg; L.C. Kremer; C. Bos; K.I. Braam; M.W.M. Jaspers
Background. Knowledge about past disease, treatment, and possible late effects has previously been shown to be low in survivors of childhood cancer and their relatives. This study investigated the information needs of childhood cancer survivors and their parents and explored possible determinants fo
Zadnik, Vesna; Krajc, Mateja
The incidence of hormone-related cancers tends to be higher in the developed world than in other countries. In Slovenia, six hormone-related cancers (breast, ovarian, endometrial, prostate, testicular, and thyroid) account for a quarter of all cancers. Their incidence goes up each year, breast and prostate cancer in particular. The age at diagnosis is not decreasing for any of the analysed cancer types. The risk of breast cancer is higher in the western part of the country, but no differences in geographical distribution have been observed for other hormone-related cancers. Furthermore, areas polluted with endocrine-disrupting chemicals that affect hormone balance such as PCBs, dioxins, heavy metals, and pesticides, do not seem to involve a greater cancer risk. We know little about how many cancers can be associated with endocrine disruptors, as there are too few reliable exposure studies to support an association. PMID:27331295
Mucci, Lorelei A.; Hjelmborg, Jacob B.; Harris, Jennifer R.;
and 123,382 same-sex dizygotic twin individuals (N = 203,691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50,990 individuals who died of any cause, and 3804 who emigrated and were lost to...... (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death. RESULTS: A total of 27,156 incident cancers were diagnosed in 23......-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling....
Li Rita Zhang; Chiarelli, Anna M; Gord Glendon; Lucia Mirea; Knight, Julia A.; Andrulis, Irene L.; Paul Ritvo
Background. Few prospective studies have examined associations between breast cancer worry and screening behaviours in women with elevated breast cancer risks based on family history. Methods. This study included 901 high familial risk women, aged 23–71 years, from the Ontario site of the Breast Cancer Family Registry. Self-reported breast screening behaviours at year-one followup were compared between women at low (N = 305), medium (N = 433), and high (N = 163) levels of baseline breast canc...
Catucci, Irene; Milgrom, Roni; Kushnir, Anya; Laitman, Yael; Paluch-Shimon, Shani; Volorio, Sara; Ficarazzi, Filomena; Bernard, Loris; Radice, Paolo; Friedman, Eitan; Peterlongo, Paolo
Germline mutations in BRCA1 and BRCA2 account for ~30 % of inherited breast cancer. BRIP1 and PALB2 are likely genes for breast cancer susceptibility, based on their roles in maintaining cellular integrity. Indeed, few pathogenic germline mutations in both genes are reported in ethnically diverse breast cancer families. There is a paucity of data on the putative contribution of both genes to inherited breast cancer in Jewish high risk families. High risk Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1/BRCA2, were screened for BRIP1 germline mutations by combined denaturing gradient gel electrophoresis, high resolution melting and sequencing. Direct sequencing of exons and flanking intronic sequences was used for PALB2 mutational analysis. Overall, 149 women, all of high risk, cancer prone families of Ashkenazi origin, were genotyped for BRIP1 mutations: 127 with breast cancer, 22 with ovarian cancer. No truncating mutations were noted and one novel (p.Ala745Thr) and two previously described missense mutations were detected. For PALB2, 93 women were genotyped (87 with breast cancer) of Ashkenazi (n = 32) and non Ashkenazi Jewish origin. Fifteen sequence variants were detected, of these, none was truncating, four were not previously reported, and two (p.Asp871Gly and p.Leu1119Pro) were seemingly pathogenic based on the PolyPhen2 protein prediction algorithm. These missense mutations were not detected in any of 113 healthy Ashkenazi and 109 Moroccan, cancer free controls. In conclusion, germline mutations in BRIP1 and PALB2 contribute marginally to breast cancer susceptibility in ethnically diverse, Jewish high risk families. PMID:22692731
Igci, Mehri; Kalender, Mehmet Emin; Borazan, Ersin; Bozgeyik, Ibrahim; Bayraktar, Recep; Bozgeyik, Esra; Camci, Celaletdin; Arslan, Ahmet
Mammalian Sirtuins have been shown to perform distinct cellular functions and deregulated expression of these genes was reported to be involved in the development of various malignancies including breast cancer. An increasing number of evidence indicates that Sirtuins have both tumor promoter and tumor suppressor functions. However, the roles of Sirtuins have not been well-reported in breast cancer. In the present study, quantitative expression levels of Sirtuins (SIRT1-7) in breast cancer patients and breast cancer cell lines (MCF-7 and SKBR3) and control cell line (CRL-4010) were assessed by using a high-throughput real-time PCR method. As a result, Sirtuins were found to be differentially expressed in breast cancer tissues and cancer cell lines. Particularly, expressions of SIRT1 and SIRT4 were found to be significantly down-regulated in breast cancer tissues and SKBR3 breast cancer cells. In contrast, SIRT2, SIRT3, and SIRT5 genes were shown to be up-regulated in our study. Although SIRT6 and SIRT7 were also up-regulated in breast cancer tissues, these expression changes were statistically insignificant. Additionally, SIRT2, SIRT3, SIRT5, SIRT6 and SIRT7 were found to be differentially expressed in breast cancer cell lines. Yet, these changes were not well-correlated with tissue expression levels. In conclusion, Sirtuin family of genes shows differential expressions in breast cancer tissues and cells and SIRT1 and SIRT4 seem to play key tumor suppressor roles in breast cancer development. Herein, we report expression levels of Sirtuin family of genes in both breast cancer tissues and cancer cell lines simultaneously. PMID:27080717
Hashishe Mervat M
Full Text Available Abstract Background Breast cancer is one of the most common diseases affecting women. Inherited susceptibility genes, BRCA1 and BRCA2, are considered in breast, ovarian and other common cancers etiology. BRCA1 and BRCA2 genes have been identified that confer a high degree of breast cancer risk. Objective Our study was performed to identify germline mutations in some exons of BRCA1 and BRCA2 genes for the early detection of presymptomatic breast cancer in females. Methods This study was applied on Egyptian healthy females who first degree relatives to those, with or without a family history, infected with breast cancer. Sixty breast cancer patients, derived from 60 families, were selected for molecular genetic testing of BRCA1 and BRCA2 genes. The study also included 120 healthy first degree female relatives of the patients, either sisters and/or daughters, for early detection of presymptomatic breast cancer mutation carriers. Genomic DNA was extracted from peripheral blood lymphocytes of all the studied subjects. Universal primers were used to amplify four regions of the BRCA1 gene (exons 2,8,13 and 22 and one region (exon 9 of BRCA2 gene using specific PCR. The polymerase chain reaction was carried out. Single strand conformation polymorphism assay and heteroduplex analysis were used to screen for mutations in the studied exons. In addition, DNA sequencing of the normal and mutated exons were performed. Results Mutations in both BRCA1 and BRCA2 genes were detected in 86.7% of the families. Current study indicates that 60% of these families were attributable to BRCA1 mutations, while 26.7% of them were attributable to BRCA2 mutations. Results showed that four mutations were detected in the BRCA1 gene, while one mutation was detected in the BRCA2 gene. Asymptomatic relatives, 80(67% out of total 120, were mutation carriers. Conclusions BRCA1 and BRCA2 genes mutations are responsible for a significant proportion of breast cancer. BRCA mutations
Gage-Bouchard, Elizabeth A; Devine, Katie A; Heckler, Charles E
The factors that influence caregiver coping mechanism preferences after a child's diagnosis with cancer are not fully understood. This study examines the relationship between caregivers' socio-demographic characteristics and the coping strategies they use to adapt to childhood cancer. Sixty caregivers of pediatric cancer patients completed a socio-demographic questionnaire, the Family Environment Scale, and the COPE inventory. There were no significant differences in family environment by income or education. Caregiver educational attainment was positively associated with use of planning and active coping styles, while income was not associated with caregiver coping style. Mothers were more likely than fathers to use active coping, instrumental support, religious coping, and emotional support. Men with lower education engaged in greater substance use coping and lower planning. The findings show that educational attainment and caregiver gender influence caregiver coping styles following a pediatric cancer diagnosis and suggest that educational attainment rather than financial resources drive the association between SES and coping. Programs that address educational gaps and teach caregivers planning and active coping skills may be beneficial for parents with lower educational attainment, particularly men. PMID:23670676
Akabayashi, A.; Fetters, M. D.; Elwyn, T S
The dilemma of whether and how to disclose a diagnosis of cancer or of any other terminal illness continues to be a subject of worldwide interest. We present the case of a 62-year-old Japanese woman afflicted with advanced gall bladder cancer who had previously expressed a preference not to be told a diagnosis of cancer. The treating physician revealed the diagnosis to the family first, and then told the patient: "You don't have any cancer yet, but if we don't treat you, it will progress to a...
Full Text Available Background: Germ-line mutations of BRCA1 and BRCA2 genes are responsible for approximately 25-30% of dominantly inherited familial breast cancers; still a big part of genetic component is unknown. The aim of this study was to investigate genetic causes of familial breast cancer in a pedigree with recessive pattern of inheritance.Methods: We applied exome sequencing as a useful approach in heterogeneous diseases gene identification in present study for familial breast cancer. Sanger sequencing was applied for validation and segregation analysis of mutations.Results: Here, we describe a family with three affected sisters of early-onset invasive ductal carcinoma due to heterozygous frame shift mutation rs80359352 in BRCA2 gene as the first report in Iranian patients in association with a novel missense SNP of STK11 (p.S422G. These mutations are inherited from their normal father.Conclusion: Despite apparent recessive pattern of inheritance a dominant gene (here BRCA2 can be involved in pathogenesis of hereditary breast cancer which can be explained by incomplete penetrance of BRCA2 mutations. Keywords: BRCA2, Familial breast cancer, rs80359352, STK11, Iran
Vieira, Daniela Koeller Rodrigues; Attianezi, Margareth; Esposito, Ana Carolina; Barth, Anneliese; Sequeira, Cecília; Krause, Nathália; Oliveira, Vivian; Lucidi, Alexandre; Serao, Cassio; Llerena, Juan C
Identification of families with history of cancer in the municipality of Angra dos Reis, Rio de Janeiro (Brazil), through the Brazilian Unified Primary Health Care System was explored based in the Community Health Agents (CHA) program. This study was divided into two phases: a descriptive one with a cross-sectional epidemiological data of families with history of cancer based on CHA-collected data from home visits in four primary health care units. The second phase consisted in identifying familial clustering of three or more individuals with cancer through construction of a three-generation pedigree and revisited by an itinerant group of medical geneticists. Genetic counseling was carried out with the intent of selecting potential families at risk for hereditary familial cancers. In the first phase of the study, 1,581 families were interviewed by the CHA at their homes. A positive history for cancer was present in 42.3 % of families, comprising 22.3 % with only one case per family, 11.2 % with two cases, and 8.6 % with three or more cases in the family. The informant reported that 15 % of the cases were from the father lineage, 12 % from the mother lineage, and 12.1 % within siblings. In the remaining 60.9 % families, cancer was present in both sides of the family. The types of cancer reported were uterus 8.7 % (n = 137), stomach 7.7 % (n = 122), breast 6.9 % (n = 109), throat 6.8 % (n = 99), prostate 5.4 % (n = 85), lung 5.6 % (n = 88), bowel 3.7 % (n = 59), and unspecified sites in 6.8 % (n = 108) of families. No statistical differences were noted between the data collected on each primary care unit. In the second phase of the study, 136 families (2.9 %) from the total of families interviewed in phase 1 were selected due to the presence of three or more individuals with cancer in the family. Among those, only 73 families attended genetic counseling. Comparison between the data obtained by the CHA and the medical
Mlacki, Michal; Kikulska, Agnieszka; Krzywinska, Ewa; Pawlak, Magdalena; Wilanowski, Tomasz
The Grainyhead-like (GRHL) family of transcription factors has three mammalian members, which are currently termed Grainyhead-like 1 (GRHL1), Grainyhead-like 2 (GRHL2), and Grainyhead-like 3 (GRHL3). These factors adopt a DNA-binding immunoglobulin fold homologous to the DNA-binding domain of key tumor suppressor p53. Their patterns of expression are tissue and developmentally specific. Earlier studies of the GRHL proteins focused on their functions in mammalian development. In recent years, these factors have been linked to many different types of cancer: squamous cell carcinoma of the skin, breast cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer, clear cell renal cell carcinoma, neuroblastoma, prostate cancer, and cervical cancer. The roles of GRHL proteins in these various types of cancer are complex, and in some cases appear to be contradictory: they can serve to promote cancer development, or they may act as tumor suppressors, depending on the particular GRHL protein involved and on the cancer type. The reasons for obvious discrepancies in results from different studies remain unclear. At the molecular level, the GRHL transcription factors regulate the expression of genes whose products are involved in cellular proliferation, differentiation, adhesion, and polarity. We herein review the roles of GRHL proteins in cancer development, and we critically examine relevant molecular mechanisms, which were proposed by different authors. We also discuss the significance of recent discoveries implicating the involvement of GRHL transcription factors in cancer and highlight potential future applications of this knowledge in cancer treatment. PMID:26069269
Dettenborn, Lucia; James, Gary D; Britton, Julie A; Bovbjerg, Dana H
Research strongly suggests that lower overall adiposity and higher central adiposity are independent risk factors for premenopausal breast cancer in the general population. We aimed to test the possibility that these factors may contribute to familial risk of premenopausal breast cancer. A convenience sample of healthy women, ages 25-49, was recruited to yield three study groups: (1) Women with first-degree family histories of premenopausal breast cancer, operationally defined as being diagnosed prior to age 50 (Group FH or = 50, n = 33); and (3) Women without a history of breast cancer in first-degree relatives (Group FH-, n = 132). Multinomial logistic regression analyses, including possible confounders, waist circumference, and BMI, revealed a lower BMI among FH or = 50 women (OR = 0.75; 95% CI = 0.60-0.95), and higher waist circumferences in FH or = 50 women (OR = 1.16; 95% CI = 1.05-1.28). No group differences were seen for waist skinfold measures. These results support the possibility that differences in patterns of adiposity may contribute to familial risk of premenopausal breast cancer, and suggest the importance of conducting large scale, population-based studies of the link between body size characteristics and familial breast cancer risk. PMID:18161037
Huang, Jiamiao; Yang, Ya; Yang, Jian; LI, XIAN
Regenerating gene family member 4 (REG4), a secreted protein, is overexpressed in several cancers, including gastric cancer. The present study was undertaken to determine the roles of REG4 in the growth of gastric cancer in the nude mice and in the proliferation and migration in human gastric cancer cell line and its downstream signaling pathway. Gastric cancer models were elicited by intraperitoneally injecting MKN45 human gastric cancer cells and the tumor size was measured every other day....
Half of the familial aggregation of ovarian cancer can't be explained by any known risk genes, suggesting the existence of other genetic risk factors. Some of these unknown factors may not be traditional protein encoding genes. MicroRNA (miRNA) plays a critical role in tumorigenesis, but it is still unknown if variants in miRNA genes lead to predisposition to cancer. Considering the fact that miRNA regulates a number of tumor suppressor genes (TSGs) and oncogenes, genetic variations in miRNA genes could affect the levels of expression of TSGs or oncogenes and, thereby, cancer risk. To test this hypothesis in familial ovarian cancer, we screened for genetic variants in thirty selected miRNA genes, which are predicted to regulate key ovarian cancer genes and are reported to be misexpressed in ovarian tumor tissues, in eighty-three patients with familial ovarian cancer. All of the patients are non-carriers of any known BRCA1/2 or mismatch repair (MMR) gene mutations. Seven novel genetic variants were observed in four primary or precursor miRNA genes. Among them, three rare variants were found in the precursor or primary precursor of the miR-191 gene. In functional assays, the one variant located in the precursor of miR-191 resulted in conformational changes in the predicted secondary structures, and consequently altered the expression of mature miR-191. In further analysis, we found that this particular variant exists in five family members who had ovarian cancer. Our findings suggest that there are novel genetic variants in miRNA genes, and those certain genetic variants in miRNA genes can affect the expression of mature miRNAs and, consequently, might alter the regulation of TSGs or oncogenes. Additionally, the variant might be potentially associated with the development of familial ovarian cancer
Lokeshwar, Vinata B.; Mirza, Summan; Jordan, Andre
Hyaluronic acid or hyaluronan (HA) is perhaps one of the most uncomplicated large polymers that regulates several normal physiological processes and, at the same time, contributes to the manifestation of a variety of chronic and acute diseases, including cancer. Members of the HA signaling pathway (HA synthases, HA receptors, and HYAL-1 hyaluronidase) have been experimentally shown to promote tumor growth, metastasis, and angiogenesis, and hence each of them is a potential target for cancer t...
Ayşe Selda Tekiner; Gülseren Lale; A. Gülsen Ceyhun Peker2
Aim: Family physicians, as role models for their patients, self health behaviors are important. We aimed to investigate the rate of undergoing cancer screening among family physicians. Methods: This is a descriptive and questionnaire-based study. Although we aimed to interview 1100 family physicians aged 40 or older working at family health centers of Ankara, the study was performed with 453 physicians. The questionnaire form comprised of the doctors’ opinions about cancer s...
Peters June A
Full Text Available Abstract Background Testicular cancer, while rare compared with other adult solid tumors, is the most common cancer in young men in northern Europe and North America. Risk factors include white race, positive family history, contralateral testicular cancer, cryptorchidism, infertility and testicular microlithiasis. As the genetic causes of familial clusters (Familial Testicular Cancer or FTC are being sought, it is also important to understand the psycho-social experiences of members of FTC families. Methods This is a cross-sectional examination via the Colored Eco-Genetic Relationship Map (CEGRM of social connections reported by 49 men in FTC families participating in NCI research study 02-C-178. Results The CEGRM was acceptable and feasible for use with men in FTC families, and valuable in understanding their social connections. These men have largely adjusted to the TC history in themselves and/or their relatives. They have considerable social and emotional support from family and friends, although there is wide variability in sources and types. Conclusions The CEGRM focuses on men's social connections and close emotional bonds in FTC families. This action-oriented process of placing colored symbols on significant relationships uncovered previously under-appreciated emotions accompanying men's social exchanges. Most men in FTC families succeed in re-establishing a sense of normalcy in their lives and social connections, in the aftermath of a testicular cancer diagnosis.
Full Text Available Abstract Background Pancreatic cancer (PC is considered the most lethal cancer and approximately 10% of PC is hereditary. The purpose of the study was to assess attitudes of at-risk family members with two or more relatives affected with pancreas cancer (PC toward PC risk and future screening options. Methods At-risk family members and primary care controls were surveyed regarding perceived PC risk, PC worry/concern, attitude toward cancer screening, screening test accuracy, and intentions regarding PC screening via blood testing or more invasive endoscopic ultrasound (EUS. Results PC family members reported greater perceived risk of PC than controls (54% vs. 6%, respectively, p 89% receptivity to the potential PC screening options presented, though receptivity was greater among PC family members as compared to controls (p Conclusions Receptivity to screening options for PC appears high. Clinicians should address behavioral and genetic risk factors for PC and foster appropriate concern regarding PC risk among at-risk individuals.
Jobsen, Jan J.; Palen, van der Job; Brinkhuis, Mariël; Ong, Francisca; Struikmans, Henk
Background. The aim of this study is to analyze the impact of first degree relative (FDR) of young breast cancer patients. Methods. Data were used from our prospective population-based cohort study which started in 1983. The family history (FH) was registered with regard to FDR: the presence or abs
Full Text Available Studies on familial aggregation of cancer may suggest an overall contribution of inherited genes or a shared environment in the development of malignant disease. We performed a meta-analysis on familial clustering of prostate cancer. Out of 74 studies reporting data on familial aggregation of prostate cancer in unselected populations retrieved by a Pubmed search and browsing references, 33 independent studies meeting the inclusion criteria were used in the analysis performed with the random effects model. The pooled rate ratio (RR for first-degree family history, i.e. affected father or brother, is 2.48 (95% confidence interval: 2.25-2.74. The incidence rate for men who have a brother who got prostate cancer increases 3.14 times (CI:2.37-4.15, and for those with affected father 2.35 times (CI:2.02-2.72. The pooled estimate of RR for two or more affected first-degree family members relative to no history in father and in brother is 4.39 (CI:2.61-7.39. First-degree family history appears to increase the incidence rate of prostate cancer more in men under 65 (RR:2.87, CI:2.21-3.74, than in men aged 65 and older (RR:1.92, CI:1.49-2.47, p for interaction = 0.002. The attributable fraction among those having an affected first-degree relative equals to 59.7% (CI:55.6-63.5% for men at all ages, 65.2% (CI:57.7-71.4% for men younger than 65 and 47.9% (CI:37.1-56.8% for men aged 65 or older. For those with a family history in 2 or more first-degree family members 77.2% (CI:65.4-85.0% of prostate cancer incidence can be attributed to the familial clustering. Our combined estimates show strong familial clustering and a significant effect-modification by age meaning that familial aggregation was associated with earlier disease onset (before age 65.
da Silva, Marcelle Miranda; Lima, Lorhanna da Silva
The objective was to understand the perspective of nurses about the participation of the family in palliative cancer care and to analyze the nursing care strategies to meet their needs. Descriptive and qualitative research, conducted at the National Cancer Institute between January and March 2013, with 17 nurses. Elements of the Roy Adaptation Model were used for the interpretation of the data. Two categoriesemergedfrom the thematic analysis: perspective of nurses about the presence and valuation of family in the hospital; and appointing strategies to encourage family participation in care and meet their needs. This participation is essentialand represents a training opportunity for the purpose of homecare. Nurses create strategies to encourage it and seek to meet the needs. The results contribute to promote the family adaptation and integrity, in order to balance the dependent and independent behaviors, aimingfor quality of life and comfort. Further studies are neededdue to the challenges of the specialty. PMID:25842775
Ruth M Pfeiffer
Full Text Available BACKGROUND: Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer. METHODS AND FINDINGS: Using data on white, non-Hispanic women aged 50+ y from two large population-based cohorts (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [PLCO] and the National Institutes of Health-AARP Diet and Health Study [NIH-AARP], we estimated relative and attributable risks and combined them with age-specific US-population incidence and competing mortality rates. All models included parity. The breast cancer model additionally included estrogen and progestin menopausal hormone therapy (MHT use, other MHT use, age at first live birth, menopausal status, age at menopause, family history of breast or ovarian cancer, benign breast disease/biopsies, alcohol consumption, and body mass index (BMI; the endometrial model included menopausal status, age at menopause, BMI, smoking, oral contraceptive use, MHT use, and an interaction term between BMI and MHT use; the ovarian model included oral contraceptive use, MHT use, and family history or breast or ovarian cancer. In independent validation data (Nurses' Health Study cohort the breast and ovarian cancer models were well calibrated; expected to observed cancer ratios were 1.00 (95% confidence interval [CI]: 0.96-1.04 for breast cancer and 1.08 (95% CI: 0.97-1.19 for ovarian cancer. The number of endometrial cancers was significantly overestimated, expected/observed = 1.20 (95% CI: 1.11-1.29. The areas under the receiver operating characteristic curves (AUCs; discriminatory power were 0.58 (95% CI: 0.57-0.59, 0.59 (95% CI: 0.56-0.63, and 0.68 (95% CI: 0.66-0.70 for the breast, ovarian, and endometrial models, respectively. CONCLUSIONS: These models predict absolute risks for breast, endometrial, and ovarian