Emerging technologies to create inducible and genetically defined porcine cancer models

Directory of Open Access Journals (Sweden)

Lawrence B Schook

2016-02-01

Full Text Available There is an emerging need for new animal models that address unmet translational cancer research requirements. Transgenic porcine models provide an exceptional opportunity due to their genetic, anatomic and physiological similarities with humans. Due to recent advances in the sequencing of domestic animal genomes and the development of new organism cloning technologies, it is now very feasible to utilize pigs as a malleable species, with similar anatomic and physiological features with humans, in which to develop cancer models. In this review, we discuss genetic modification technologies successfully used to produce porcine biomedical models, in particular the Cre-loxP System as well as major advances and perspectives the CRISPR/Cas9 System. Recent advancements in porcine tumor modeling and genome editing will bring porcine models to the forefront of translational cancer research.

Emerging Technologies to Create Inducible and Genetically Defined Porcine Cancer Models.

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Schook, Lawrence B; Rund, Laurie; Begnini, Karine R; Remião, Mariana H; Seixas, Fabiana K; Collares, Tiago

2016-01-01

There is an emerging need for new animal models that address unmet translational cancer research requirements. Transgenic porcine models provide an exceptional opportunity due to their genetic, anatomic, and physiological similarities with humans. Due to recent advances in the sequencing of domestic animal genomes and the development of new organism cloning technologies, it is now very feasible to utilize pigs as a malleable species, with similar anatomic and physiological features with humans, in which to develop cancer models. In this review, we discuss genetic modification technologies successfully used to produce porcine biomedical models, in particular the Cre-loxP System as well as major advances and perspectives the CRISPR/Cas9 System. Recent advancements in porcine tumor modeling and genome editing will bring porcine models to the forefront of translational cancer research.

[Genetic diagnostics of cancer diseases].

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Cobilanschi, Joana

2013-11-27

Cancer is caused by genetic alterations, but only 10% of the cancer diseases are inherited. The probability for an individual or a family of having inherited cancer, individual consequences of the respective results of genetic testing, as well as its costs and reimbursement by the health insurance must be addressed by expert genetic counseling which at-risk requires special expertise. Identification of a germline mutation which may predispose to a variety of different cancer types allows determination of an individual's specific life time risk in symptomatic as well as in a-symptomatic family members. Identification of the underlying defective gene in heritable cancer disorders also enables optimized preventive and novel therapeutic approaches specifically targeting the underlying molecular pathomechanisms.

A deficiency in chromatin repair, genetic instability, and predisposition to cancer

International Nuclear Information System (INIS)

Sanford, K.K.; Parshad, R.; Gantt, R.R.; Tarone, R.E.

1989-01-01

This review traces steps leading to malignant neoplastic transformation of rodent and human cells in culture and in vivo. Emphasis is placed on an abnormal response characterized by persistent chromatid damage following irradiation of cells in culture with X-rays or fluorescent light during G2 phase of the cell cycle. Evidence is presented that deficient or unbalanced DNA repair during G2 accounts for the abnormal response. This G2 repair deficiency can be inherited or acquired by normal tissue cells during the process of or following attainment of infinite lifespan. It appears as an early, possibly initiating step in neoplastic transformation. It characterizes all human tumor cells examined irrespective of histopathology or tissue of origin. It has a genetic basis. In an animal model, the BALB/c mouse, this phenotype is associated with genes on chromosomes 1 and 4. It characterizes skin fibroblasts and blood lymphocytes from individuals with genetic or familial conditions predisposing to cancer and can be used to identify clinically normal family members carrying a gene(s) for any one of the three cancer-prone genetic disorders studied to date. Furthermore, it can provide the basis of a test for carriers of genes predisposing to a high risk of cancer. We conclude that the G2 repair deficiency, whether inherited or acquired, is a prerequisite for cancer development and that it accounts for the genetic instability of the cancer cell. 167 refs

Molecular concept in human oral cancer.

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Krishna, Akhilesh; Singh, Shraddha; Kumar, Vijay; Pal, U S

2015-01-01

The incidence of oral cancer remains high in both Asian and Western countries. Several risk factors associated with development of oral cancer are now well-known, including tobacco chewing, smoking, and alcohol consumption. Cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. Oral squamous carcinogenesis is a multistep process in which multiple genetic events occur that alter the normal functions of proto-oncogenes/oncogenes and tumor suppressor genes. Furthermore, these gene alterations can deregulate the normal activity such as increase in the production of growth factors (transforming growth factor-α [TGF-α], TGF-β, platelet-derived growth factor, etc.) or numbers of cell surface receptors (epidermal growth factor receptor, G-protein-coupled receptor, etc.), enhanced intracellular messenger signaling and mutated production of transcription factors (ras gene family, c-myc gene) which results disturb to tightly regulated signaling pathways of normal cell. Several oncogenes and tumor suppressor genes have been implicated in oral cancer especially cyclin family, ras, PRAD-1, cyclin-dependent kinase inhibitors, p53 and RB1. Viral infections, particularly with oncogenic human papilloma virus subtype (16 and 18) and Epstein-Barr virus have tumorigenic effect on oral epithelia. Worldwide, this is an urgent need to initiate oral cancer research programs at molecular and genetic level which investigates the causes of genetic and molecular defect, responsible for malignancy. This approach may lead to development of target dependent tumor-specific drugs and appropriate gene therapy.

Application Form for NCI Cancer Genetics Services Directory

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Professionals who provide services related to cancer genetics (cancer risk assessment, genetic counseling, genetic susceptibility testing, and others) may fill out this application form to be listed in the National Cancer Institute's Cancer Genetics Services Directory.

Inclusion Criteria for NCI Cancer Genetics Services Directory

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Professionals who provide services related to cancer genetics (cancer risk assessment, genetic counseling, genetic susceptibility testing, and others) must meet these criteria before applying to be listed in the National Cancer Institute's Cancer Genetics Services Directory.

Spontaneous chromosome aberrations in cancer cells. Evidence of existence of hidden genetic lesions in genetic structures

International Nuclear Information System (INIS)

Poryadkova-Luchnik, N.A.; Kuz'mina, E.G.

1996-01-01

Chromosome aberrations spontaneously observed in cancer cells were quantitively studied under the effect of non-mutagenic (suboptimal temperature, low content of propilgallate and caffeine) and mutagenic (ionizing radiation) factors. Human larynx cancer cells during several years or gamma-irradiation were used to carry out experiments. The experiments linked with cloning of the initial population and investigation into chromosome aberrations in 22 clones demonstrated persuasively the occurrence of latent genetic lesions in cancer cells

Update on Sporadic Colorectal Cancer Genetics.

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Hardiman, Karin M

2018-05-01

Our understanding of the genetics of colorectal cancer has changed dramatically over recent years. Colorectal cancer can be classified in multiple different ways. Along with the advent of whole-exome sequencing, we have gained an understanding of the scale of the genetic changes found in sporadic colorectal cancer. We now know that there are multiple pathways that are commonly involved in the evolution of colorectal cancer including Wnt/β-catenin, RAS, EGFR, and PIK3 kinase. Another recent leap in our understanding of colorectal cancer genetics is the recognition that many, if not all tumors, are actually genetically heterogeneous within individual tumors and also between tumors. Recent research has revealed the prognostic and possibly therapeutic implications of various specific mutations, including specific mutations in BRAF and KRAS . There is increasing interest in the use of mutation testing for screening and surveillance through stool and circulating DNA testing. Recent advances in translational research in colorectal cancer genetics are dramatically changing our understanding of colorectal cancer and will likely change therapy and surveillance in the near future.

Human genetics and genomics a decade after the release of the draft sequence of the human genome

Science.gov (United States)

2011-01-01

Substantial progress has been made in human genetics and genomics research over the past ten years since the publication of the draft sequence of the human genome in 2001. Findings emanating directly from the Human Genome Project, together with those from follow-on studies, have had an enormous impact on our understanding of the architecture and function of the human genome. Major developments have been made in cataloguing genetic variation, the International HapMap Project, and with respect to advances in genotyping technologies. These developments are vital for the emergence of genome-wide association studies in the investigation of complex diseases and traits. In parallel, the advent of high-throughput sequencing technologies has ushered in the 'personal genome sequencing' era for both normal and cancer genomes, and made possible large-scale genome sequencing studies such as the 1000 Genomes Project and the International Cancer Genome Consortium. The high-throughput sequencing and sequence-capture technologies are also providing new opportunities to study Mendelian disorders through exome sequencing and whole-genome sequencing. This paper reviews these major developments in human genetics and genomics over the past decade. PMID:22155605

Cancer Genetics and Signaling | Center for Cancer Research

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The Cancer, Genetics, and Signaling (CGS) Group at the National Cancer Institute at Frederick  offers a competitive postdoctoral training and mentoring program focusing on molecular and genetic aspects of cancer. The CGS Fellows Program is designed to attract and train exceptional postdoctoral fellows interested in pursuing independent research career tracks. CGS Fellows participate in a structured mentoring program designed for scientific and career development and transition to independent positions.

Genetic Differences Between Humans and Great Apes -- Implications for the Evolution of Humans

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Varki, Ajit

2004-06-01

At the level of individual protein sequences, humans are 97-100% identical to the great apes, our closest evolutionary relatives. The evolution of humans (and of human intelligence) from a common ancestor with the chimpanzee and bonobo involved many steps, influenced by interactions amongst factors of genetic, developmental, ecological, microbial, climatic, behavioral, cultural and social origin. The genetic factors can be approached by direct comparisons of human and great ape genomes, genes and gene products, and by elucidating biochemical and biological consequences of any differences found. We have discovered multiple genetic and biochemical differences between humans and great apes, particularly with respect to a family of cell surface molecules called sialic acids, as well as in the metabolism of thyroid hormones. The hormone differences have potential consequences for human brain development. The differences in sialic acid biology have multiple implications for the human condition, ranging from susceptibility or resistance to microbial pathogens, effects on endogenous receptors in the immune system, and potential effects on placental signaling, expression of oncofetal antigens in cancers, consequences of dietary intake of animal foods, and development of the mammalian brain.

Genetic mutation analysis of human gastric adenocarcinomas using ion torrent sequencing platform.

Directory of Open Access Journals (Sweden)

Zhi Xu

Full Text Available Gastric cancer is the one of the major causes of cancer-related death, especially in Asia. Gastric adenocarcinoma, the most common type of gastric cancer, is heterogeneous and its incidence and cause varies widely with geographical regions, gender, ethnicity, and diet. Since unique mutations have been observed in individual human cancer samples, identification and characterization of the molecular alterations underlying individual gastric adenocarcinomas is a critical step for developing more effective, personalized therapies. Until recently, identifying genetic mutations on an individual basis by DNA sequencing remained a daunting task. Recent advances in new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent sequencing platform, makes DNA sequencing cheaper, faster, and more reliable. In this study, we aim to identify genetic mutations in the genes which are targeted by drugs in clinical use or are under development in individual human gastric adenocarcinoma samples using Ion Torrent sequencing. We sequenced 737 loci from 45 cancer-related genes in 238 human gastric adenocarcinoma samples using the Ion Torrent Ampliseq Cancer Panel. The sequencing analysis revealed a high occurrence of mutations along the TP53 locus (9.7% in our sample set. Thus, this study indicates the utility of a cost and time efficient tool such as Ion Torrent sequencing to screen cancer mutations for the development of personalized cancer therapy.

Emerging Cancer Vaccines: The Promise of Genetic Vectors

International Nuclear Information System (INIS)

Aurisicchio, Luigi; Ciliberto, Gennaro

2011-01-01

Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost

MMP9 polymorphisms and breast cancer risk: a report from the Shanghai Breast Cancer Genetics Study.

Science.gov (United States)

Beeghly-Fadiel, Alicia; Lu, Wei; Shu, Xiao-Ou; Long, Jirong; Cai, Qiuyin; Xiang, Yongbin; Gao, Yu-Tang; Zheng, Wei

2011-04-01

In addition to tumor invasion and angiogenesis, matrix metalloproteinase (MMP)9 also contributes to carcinogenesis and tumor growth. Genetic variation that may influence MMP9 expression was evaluated among participants of the Shanghai Breast Cancer Genetics Study (SBCGS) for associations with breast cancer susceptibility. In stage 1, 11 MMP9 single nucleotide polymorphisms (SNPs) were genotyped by the Affymetrix Targeted Genotyping System and/or the Affymetrix Genome-Wide Human SNP Array 6.0 among 4,227 SBCGS participants. One SNP was further genotyped using the Sequenom iPLEX MassARRAY platform among an additional 6,270 SBCGS participants. Associations with breast cancer risk were evaluated by odds ratios (OR) and 95% confidence intervals (CI) from logistic regression models that included adjustment for age, education, and genotyping stage when appropriate. In Stage 1, rare allele homozygotes for a promoter SNP (rs3918241) or a non-synonymous SNP (rs2274756, R668Q) tended to occur more frequently among breast cancer cases (P value = 0.116 and 0.056, respectively). Given their high linkage disequilibrium (D' = 1.0, r (2) = 0.97), one (rs3918241) was selected for additional analysis. An association with breast cancer risk was not supported by additional Stage 2 genotyping. In combined analysis, no elevated risk of breast cancer among homozygotes was found (OR: 1.2, 95% CI: 0.8-1.8). Common genetic variation in MMP9 was not found to be significantly associated with breast cancer susceptibility among participants of the Shanghai Breast Cancer Genetics Study.

Genetic counseling about cancer in Peru

OpenAIRE

Manrique, Javier E.; Dirección de Promoción de la Salud, Prevención y Control Nacional del Cáncer, Instituto Nacional de Enfermedades Neoplásicas. Lima, Perú. Cirujano oncólogo.; Sullcahuamán-Allende, Yasser; Unidad de Genética y Biología Molecular, Instituto Nacional de Enfermedades Neoplásicas. Lima, Perú. médico genetista.; Limache-García, Abel; Dirección de Promoción de la Salud, Prevención y Control Nacional del Cáncer, Instituto Nacional de Enfermedades Neoplásicas. Lima, Perú. enfermero.

2014-01-01

Cancer is a genetic disease caused by changes in the DNA sequence or expression. Based on the origin of these changes, cancer can be classified as sporadic, and hereditary or familial. Based on the cancer records in Peru, it is expected that 5 to 30% of all patients with cancer, i.e. about 2,000 to 12,000 people, have hereditary cancer, meaning that a similar number of families have a higher risk of developing cancer compared to the general population. Therefore, the purpose of genetic co...

Genetic Mutations in Cancer

Science.gov (United States)

Many different types of genetic mutations are found in cancer cells. This infographic outlines certain types of alterations that are present in cancer, such as missense, nonsense, frameshift, and chromosome rearrangements.

Distinct Mechanisms of Nuclease-Directed DNA-Structure-Induced Genetic Instability in Cancer Genomes.

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Zhao, Junhua; Wang, Guliang; Del Mundo, Imee M; McKinney, Jennifer A; Lu, Xiuli; Bacolla, Albino; Boulware, Stephen B; Zhang, Changsheng; Zhang, Haihua; Ren, Pengyu; Freudenreich, Catherine H; Vasquez, Karen M

2018-01-30

Sequences with the capacity to adopt alternative DNA structures have been implicated in cancer etiology; however, the mechanisms are unclear. For example, H-DNA-forming sequences within oncogenes have been shown to stimulate genetic instability in mammals. Here, we report that H-DNA-forming sequences are enriched at translocation breakpoints in human cancer genomes, further implicating them in cancer etiology. H-DNA-induced mutations were suppressed in human cells deficient in the nucleotide excision repair nucleases, ERCC1-XPF and XPG, but were stimulated in cells deficient in FEN1, a replication-related endonuclease. Further, we found that these nucleases cleaved H-DNA conformations, and the interactions of modeled H-DNA with ERCC1-XPF, XPG, and FEN1 proteins were explored at the sub-molecular level. The results suggest mechanisms of genetic instability triggered by H-DNA through distinct structure-specific, cleavage-based replication-independent and replication-dependent pathways, providing critical evidence for a role of the DNA structure itself in the etiology of cancer and other human diseases. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Comparative oncology: what dogs and other species can teach us about humans with cancer

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Schiffman, Joshua D.; Breen, Matthew

2015-01-01

Over 1.66 million humans (approx. 500/100 000 population rate) and over 4.2 million dogs (approx. 5300/100 000 population rate) are diagnosed with cancer annually in the USA. The interdisciplinary field of comparative oncology offers a unique and strong opportunity to learn more about universal cancer risk and development through epidemiology, genetic and genomic investigations. Working across species, researchers from human and veterinary medicine can combine scientific findings to understand more quickly the origins of cancer and translate these findings to novel therapies to benefit both human and animals. This review begins with the genetic origins of canines and their advantage in cancer research. We next focus on recent findings in comparative oncology related to inherited, or genetic, risk for tumour development. We then detail the somatic, or genomic, changes within tumours and the similarities between species. The shared cancers between humans and dogs that we discuss include sarcoma (osteosarcoma, soft tissue sarcoma, histiocytic sarcoma, hemangiosarcoma), haematological malignancies (lymphoma, leukaemia), bladder cancer, intracranial neoplasms (meningioma, glioma) and melanoma. Tumour risk in other animal species is also briefly discussed. As the field of genomics advances, we predict that comparative oncology will continue to benefit both humans and the animals that live among us. PMID:26056372

Cancer Genetics Overview (PDQ®)—Health Professional Version

Science.gov (United States)

Cancer Genetics Overview discusses hereditary cancers and the role of genetic variants (mutations). Get information about genetic counseling, familial cancer syndromes, genomic sequencing, germline and somatic testing, ethical and legal issues and more in this summary for clinicians.

Long interspersed element-1 protein expression is a hallmark of many human cancers.

Science.gov (United States)

Rodić, Nemanja; Sharma, Reema; Sharma, Rajni; Zampella, John; Dai, Lixin; Taylor, Martin S; Hruban, Ralph H; Iacobuzio-Donahue, Christine A; Maitra, Anirban; Torbenson, Michael S; Goggins, Michael; Shih, Ie-Ming; Duffield, Amy S; Montgomery, Elizabeth A; Gabrielson, Edward; Netto, George J; Lotan, Tamara L; De Marzo, Angelo M; Westra, William; Binder, Zev A; Orr, Brent A; Gallia, Gary L; Eberhart, Charles G; Boeke, Jef D; Harris, Chris R; Burns, Kathleen H

2014-05-01

Cancers comprise a heterogeneous group of human diseases. Unifying characteristics include unchecked abilities of tumor cells to proliferate and spread anatomically, and the presence of clonal advantageous genetic changes. However, universal and highly specific tumor markers are unknown. Herein, we report widespread long interspersed element-1 (LINE-1) repeat expression in human cancers. We show that nearly half of all human cancers are immunoreactive for a LINE-1-encoded protein. LINE-1 protein expression is a common feature of many types of high-grade malignant cancers, is rarely detected in early stages of tumorigenesis, and is absent from normal somatic tissues. Studies have shown that LINE-1 contributes to genetic changes in cancers, with somatic LINE-1 insertions seen in selected types of human cancers, particularly colon cancer. We sought to correlate this observation with expression of the LINE-1-encoded protein, open reading frame 1 protein, and found that LINE-1 open reading frame 1 protein is a surprisingly broad, yet highly tumor-specific, antigen. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Molecular and genetic epidemiology of cancer in low- and medium-income countries.

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Malhotra, Jyoti

2014-01-01

Genetic and molecular factors can play an important role in an individual's cancer susceptibility and response to carcinogen exposure. Cancer susceptibility and response to carcinogen exposure can be either through inheritance of high penetrance but rare germline mutations that constitute heritable cancer syndromes, or it can be inherited as common genetic variations or polymorphisms that are associated with low to moderate risk for development of cancer. These polymorphisms can interact with environmental exposures and can influence an individual's cancer risk through multiple pathways, including affecting the rate of metabolism of carcinogens or the immune response to these toxins. Thus, these genetic polymorphisms can account for some of the geographical differences seen in cancer prevalence between different populations. This review explores the role of molecular epidemiology in the field of cancer prevention and control in low- and medium-income countries. Using data from Human Genome Project and HapMap Project, genome-wide association studies have been able to identify multiple susceptibility loci for different cancers. The field of genetic and molecular epidemiology has been further revolutionized by the discovery of newer, faster, and more efficient DNA-sequencing technologies including next-generation sequencing. The new DNA-sequencing technologies can play an important role in planning and implementation of cancer prevention and screening strategies. More research is needed in this area, especially in investigating new biomarkers and measuring gene-environment interactions. Copyright © 2014 Icahn School of Medicine at Mount Sinai. Published by Elsevier Inc. All rights reserved.

Comparing the DNA hypermethylome with gene mutations in human colorectal cancer.

Directory of Open Access Journals (Sweden)

Kornel E Schuebel

2007-09-01

Full Text Available We have developed a transcriptome-wide approach to identify genes affected by promoter CpG island DNA hypermethylation and transcriptional silencing in colorectal cancer. By screening cell lines and validating tumor-specific hypermethylation in a panel of primary human colorectal cancer samples, we estimate that nearly 5% or more of all known genes may be promoter methylated in an individual tumor. When directly compared to gene mutations, we find larger numbers of genes hypermethylated in individual tumors, and a higher frequency of hypermethylation within individual genes harboring either genetic or epigenetic changes. Thus, to enumerate the full spectrum of alterations in the human cancer genome, and to facilitate the most efficacious grouping of tumors to identify cancer biomarkers and tailor therapeutic approaches, both genetic and epigenetic screens should be undertaken.

Progress in cancer genetics: lessons from pancreatic cancer

NARCIS (Netherlands)

Goggins, M.; Kern, S. E.; Offerhaus, J. A.; Hruban, R. H.

1999-01-01

In the near future advances in the molecular basis of cancer are expected to facilitate cancer diagnosis, to rationalize treatment, to facilitate screening, and to identify individuals requiring cancer prevention strategies. The literature was reviewed concerning the genetic alterations that

The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer.

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Krupke, Debra M; Begley, Dale A; Sundberg, John P; Richardson, Joel E; Neuhauser, Steven B; Bult, Carol J

2017-11-01

Research using laboratory mice has led to fundamental insights into the molecular genetic processes that govern cancer initiation, progression, and treatment response. Although thousands of scientific articles have been published about mouse models of human cancer, collating information and data for a specific model is hampered by the fact that many authors do not adhere to existing annotation standards when describing models. The interpretation of experimental results in mouse models can also be confounded when researchers do not factor in the effect of genetic background on tumor biology. The Mouse Tumor Biology (MTB) database is an expertly curated, comprehensive compendium of mouse models of human cancer. Through the enforcement of nomenclature and related annotation standards, MTB supports aggregation of data about a cancer model from diverse sources and assessment of how genetic background of a mouse strain influences the biological properties of a specific tumor type and model utility. Cancer Res; 77(21); e67-70. ©2017 AACR . ©2017 American Association for Cancer Research.

Strategies for Integrated Analysis of Genetic, Epigenetic, and Gene Expression Variation in Cancer

DEFF Research Database (Denmark)

Thingholm, Louise B; Andersen, Lars; Makalic, Enes

2016-01-01

The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis...... to integration strategies used for analyzing genetic risk factors for cancer. We critically examine the ability of these strategies to handle the complexity of the human genome and also accommodate information about the biological and functional interactions between the elements that have been measured...

Human cancers converge at the HIF-2alpha oncogenic axis.

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Franovic, Aleksandra; Holterman, Chet E; Payette, Josianne; Lee, Stephen

2009-12-15

Cancer development is a multistep process, driven by a series of genetic and environmental alterations, that endows cells with a set of hallmark traits required for tumorigenesis. It is broadly accepted that growth signal autonomy, the first hallmark of malignancies, can be acquired through multiple genetic mutations that activate an array of complex, cancer-specific growth circuits [Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57-70; Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10:789-799]. The superfluous nature of these pathways is thought to severely limit therapeutic approaches targeting tumor proliferation, and it has been suggested that this strategy be abandoned in favor of inhibiting more systemic hallmarks, including angiogenesis (Ellis LM, Hicklin DJ (2008) VEGF-targeted therapy: Mechanisms of anti-tumor activity. Nat Rev Cancer 8:579-591; Stommel JM, et al. (2007) Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318:287-290; Kerbel R, Folkman J (2002) Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2:727-739; Kaiser J (2008) Cancer genetics: A detailed genetic portrait of the deadliest human cancers. Science 321:1280-1281]. Here, we report the unexpected observation that genetically diverse cancers converge at a common and obligatory growth axis instigated by HIF-2alpha, an element of the oxygen-sensing machinery. Inhibition of HIF-2alpha prevents the in vivo growth and tumorigenesis of highly aggressive glioblastoma, colorectal, and non-small-cell lung carcinomas and the in vitro autonomous proliferation of several others, regardless of their mutational status and tissue of origin. The concomitant deactivation of select receptor tyrosine kinases, including the EGFR and IGF1R, as well as downstream ERK/Akt signaling, suggests that HIF-2alpha exerts its proliferative effects by endorsing these major pathways. Consistently

Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers.

Science.gov (United States)

Nath, Aritro; Chan, Christina

2016-01-04

Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets. Our association analysis revealed a uniform pattern of Warburg effect mutations influencing prognosis across all tumor types, while copy number alterations in the electron transport chain gene SCO2, fatty acid uptake (CAV1, CD36) and lipogenesis (PPARA, PPARD, MLXIPL) genes were enriched in metastatic tumors. Using gene expression profiles, we established a gene-signature (CAV1, CD36, MLXIPL, CPT1C, CYP2E1) that strongly associated with epithelial-mesenchymal program across multiple cancers. Moreover, stratification of samples based on the copy number or expression profiles of the genes identified in our analysis revealed a significant effect on patient survival rates, thus confirming prominent roles of fatty acid uptake and metabolism in metastatic progression and poor prognosis of human cancers.

Risk perception after genetic counseling in patients with increased risk of cancer

Directory of Open Access Journals (Sweden)

Rantala Johanna

2009-08-01

population. Difference in risk perception for children/siblings as for the general population was significant between the first and second measurement time points. Anxiety about developing cancer again among affected participants continued to be high throughout this investigation. Conclusion The participant's accuracy in risk perception was poor, especially in low risk individuals before genetic counseling. There was a general trend towards more accurate estimation in all risk groups after genetic counseling. The importance of preventive programs was well understood. Cancer anxiety was prevalent and associated with risk perception, but decreased after genetic counseling. 1 National Society of Genetic Counselors (2005, Genetic Counseling as a Profession. Available at http://www.nsgc.org/about/definition.cfm (accessed November 25th 2007 2 Julian-Reynier C., Welkenhuysen M-, Hagoel L., Decruyenaere M., Hopwood P. (2003 Risk communication strategies: state of the art and effectiveness in the context of cancer genetic services. Eur J of Human Genetics 11, 725–736.

Genetic prognostic markers in colorectal cancer.

OpenAIRE

Houlston, R S; Tomlinson, I P

1997-01-01

The contribution of molecular genetics to colorectal cancer has been restricted largely to relatively rare inherited tumours and to the detection of germline mutations predisposing to these cancers. However, much is now also known about somatic events leading to colorectal cancer. A number of studies has been undertaken examining possible relations between genetic features and prognostic indices. While many of these studies are small and inconclusive, it is clear that a number of different pa...

Genetics and Genomics: Discovery, Validation, and Utility of Novel Tools for management of Prostate Cancer

Directory of Open Access Journals (Sweden)

Alan W. Shindel

2017-01-01

Full Text Available Genomics is the science of how genes influence human health and disease states. It differs from traditional genetic screening in that the transcriptional activity (or other markers in full panels of related genes are studied. Compared to simple genetic testing, assessment of expression levels in a panel of genes provides a more nuanced and holistic understanding of genetic modulation of human disease. Genomic testing may be used to great effect in resolving controversial questions on detection and treatment of prostate cancer. Genomic tests are currently in use for numerous facets of prostate cancer care, including screening, biopsy, and treatment planning. The clinical validity (predictive capacity of these assays has been well established; studies on clinical utility (i.e. usefulness of these tests in guiding patient/provider decisions have shown promising results. Men’s health specialists should be familiar with the role genomic testing will play in contemporary management of prostate cancer.

Competences, education and support for new roles in cancer genetics services: outcomes from the cancer genetics pilot projects.

Science.gov (United States)

Bennett, Catherine; Burton, Hilary; Farndon, Peter

2007-01-01

In 2004 the Department of Health in collaboration with Macmillan Cancer Support set up service development projects to pilot the integration of genetics in mainstream medicine in the area of cancer genetics.In developing these services, new roles and responsibilities were devised that required supporting programmes of education and training. The NHS National Genetics Education and Development Centre has worked with the projects to draw together their experience in these aspects. New roles include the Cancer Family Nurse Specialist, in which a nurse working in a cancer setting was trained to identify and manage genetic or family history concerns, and the Genetic Risk Assessment Practitioner--a small team of practitioners working within a secondary care setting to deliver a standardised risk assessment pathway. Existing roles were also adapted for a different setting, in particular the use of genetic counsellors working in a community ethnic minority setting. These practitioners undertook a range of clinical activities that can be mapped directly to the 'UK National Workforce Competences for Genetics in Clinical Practice for Non-genetics Healthcare Staff' framework developed by Skills for Health and the NHS National Genetics Education and Development Centre (2007; draft competence framework). The main differences between the various roles were in the ordering of genetic tests and the provision of advice on invasive preventive options such as mastectomy. Those involved in service development also needed to develop competences in project management, business skills, audit and evaluation, working with users, general management (personnel, multi-agency work and marketing), educational supervision, IT, public and professional outreach, and research. Important resources to support the development of new roles and competences included pathways and guidelines, a formal statement of competences, a recognised syllabus, appropriate and timely courses, the availability of a

Inflammatory Genetic Markers of Prostate Cancer Risk

International Nuclear Information System (INIS)

Tindall, Elizabeth A.; Hayes, Vanessa M.; Petersen, Desiree C.

2010-01-01

Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk

Inflammatory Genetic Markers of Prostate Cancer Risk

Energy Technology Data Exchange (ETDEWEB)

Tindall, Elizabeth A.; Hayes, Vanessa M. [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia); University of New South Wales, Kensington Campus, Sydney, NSW 2052 (Australia); Petersen, Desiree C., E-mail: dpetersen@ccia.unsw.edu.au [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia)

2010-06-08

Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk.

Intention to seek information on cancer genetics

Directory of Open Access Journals (Sweden)

J.E. Andrews

2005-01-01

Full Text Available Objective. The public has a high interest in seeking personal genetic information, which holds implications for health information seeking research and health care policy. Rapid advances in cancer genetics research promise early detection, prevention and treatment, yet consumers may have greater difficulty finding and using the information they may need to make informed decisions regarding their personal health and the future of their families. Design. A statewide telephone survey was conducted of non-institutionalized Kentucky residents 18 years of age or older to investigate factors associated with the intention to seek cancer genetics information, including the need for such information seeking help. Results. The results show that intention to seek cancer genetics information, if testing were readily available, is moderately high (62.5% of those responding; n=835, and that status as a racial minority, the perception that cancer runs in one's family, and frequent worrying about cancer risk are statistically significant predictors of intent to seek genetics information. Conclusion. . We argue that an already complex health information environment will be even more difficult for individuals to navigate as genetic research becomes more ubiquitous in health care. An increase in demand for genetics information in various forms, as suggested by these results and those of other studies, implies that enduring intervention strategies are needed to help individuals acquire necessary health information literacy skills, with special attention given to racial minorities.

Evaluating human genetic diversity

National Research Council Canada - National Science Library

This book assesses the scientific value and merit of research on human genetic differences--including a collection of DNA samples that represents the whole of human genetic diversity--and the ethical...

[The genetics of thrombosis in cancer].

Science.gov (United States)

Soria, José Manuel; López, Sonia

2015-01-01

Venous thromboembolism (VTE) is a multifactorial and complex disease in which the interaction of genetic factors (estimated at 60%) and environmental factors (e.g., the use of oral contraceptives, pregnancy, immobility and cancer) determine the risk of thrombosis for each individual. In particular, the association between thrombosis and cancer is well established. Approximately 20% of patients with cancer develop a thromboembolic event over the course of the natural history of the tumor process, with thrombosis being the second leading cause of death for these patients. One of the greatest challenges currently facing the field of oncology is the identification of patients at high risk of VTE who can benefit from thromboprophylaxis. Currently, there is a VTE risk prediction model for patients with cancer (the Khorana risk score); however, its ability to identify patients at high risk is very low. It is important to note that this score, which is based on five clinical parameters, ignores the genetic variability associated with VTE risk. In this article, we present the preliminary results of the Oncothromb study, whose objective is to develop an individual VTE risk prediction model for patients with cancer who are treated with outpatient chemotherapy. Our model includes the clinical and genetic data on each patient (Thrombo inCode(®) genetic profile). Only by integrating multiple layers of biological information (clinical, plasmatic and genetic) we could obtain models that provide accurate information as to which patients are at high risk of developing a thromboembolic event associated with cancer so as to take appropriate prophylactic measures. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Genetic predisposition to kidney cancer.

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Schmidt, Laura S; Linehan, W Marston

2016-10-01

Kidney cancer is not a single disease but is made up of a number of different types of cancer classified by histology that are disparate in presentation, clinical course, and genetic basis. Studies of families with inherited renal cell carcinoma (RCC) have provided the basis for our understanding of the causative genes and altered metabolic pathways in renal cancer with different histologies. Von Hippel-Lindau disease was the first renal cancer disorder with a defined genetic basis. Over the next two decades, the genes responsible for a number of other inherited renal cancer syndromes including hereditary papillary renal carcinoma, Birt-Hogg-Dube´syndrome, hereditary leiomyomatosis and renal cell carcinoma, and succinate dehydrogenase-associated renal cancer were identified. Recently, renal cell carcinoma has been confirmed as part of the clinical phenotype in individuals from families with BAP1-associated tumor predisposition syndrome and MiTF-associated cancer syndrome. Here we summarize the clinical characteristics of and causative genes for these and other inherited RCC syndromes, the pathways that are dysregulated when the inherited genes are mutated, and recommended clinical management of patients with these inherited renal cancer syndromes. Published by Elsevier Inc.

Influence of genetic discrimination perceptions and knowledge on cancer genetics referral practice among clinicians.

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Lowstuter, Katrina J; Sand, Sharon; Blazer, Kathleen R; MacDonald, Deborah J; Banks, Kimberly C; Lee, Carol A; Schwerin, Barbara U; Juarez, Margaret; Uman, Gwen C; Weitzel, Jeffrey N

2008-09-01

To describe nongenetics clinicians' perceptions and knowledge of cancer genetics and laws prohibiting genetic discrimination, attitudes toward the use of cancer genetic testing, and referral practices. Invitations to participate were sent to a random stratified sample of California Medical Association members and to all members of California Association of Nurse Practitioners and California Latino Medical Association. Responders in active practice were eligible and completed a 47-item survey. There were 1181 qualified participants (62% physicians). Although 96% viewed genetic testing as beneficial for their patients, 75% believed fear of genetic discrimination would cause patients to decline testing. More than 60% were not aware of federal or California laws prohibiting health insurance discrimination--concern about genetic discrimination was selected as a reason for nonreferral by 11%. A positive attitude toward genetic testing was the strongest predictor of referral (odds ratio: 3.55 [95% confidence interval: 2.24-5.63], P genetic discrimination, the less likely a participant was to refer (odds ratio: 0.72 [95% confidence interval: 0.518-0.991], P genetic discrimination law was associated with comfort recommending (odds ratio: 1.18 [95% confidence interval: 1.11-1.25], P genetic discrimination and knowledge deficits may be barriers to cancer genetics referrals. Clinician education may help promote access to cancer screening and prevention.

Transcriptional profiling of human breast cancer cells cultured under microgravity conditions revealed the key role of genetic gravity sensors previously detected in Drosophila melanogaster

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Valdivia-Silva, Julio E.; Lavan, David; Diego Orihuela-Tacuri, M.; Sanabria, Gabriela

2016-07-01

Currently, studies in Drosophila melanogaster has shown emerging evidence that microgravity stimuli can be detected at the genetic level. Analysis of the transcriptome in the pupal stage of the fruit flies under microgravity conditions versus ground controls has suggested the presence of a few candidate genes as "gravity sensors" which are experimentally validated. Additionally, several studies have shown that microgravity causes inhibitory effects in different types of cancer cells, although the genes involved and responsible for these effects are still unknown. Here, we demonstrate that the genes suggested as the sensors of gravitational waves in Drosophila melanogaster and their human counterpart (orthologous genes) are highly involved in carcinogenesis, proliferation, anti-apoptotic signals, invasiveness, and metastatic potential of breast cancer cell tumors. The transcriptome analyses suggested that the observed inhibitory effect in cancer cells could be due to changes in the genetic expression of these candidates. These results encourage the possibility of new therapeutic targets managed together and not in isolation.

Genetics of human hydrocephalus

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Williams, Michael A.; Rigamonti, Daniele

2006-01-01

Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders. A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human

Genetic & epigenetic approach to human obesity

Directory of Open Access Journals (Sweden)

K Rajender Rao

2014-01-01

Full Text Available Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D, cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12 th u0 pdate of Human Obesity Gene Map there are 253 quantity trait loci (QTL for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.

[Quality assurance in human genetic testing].

Science.gov (United States)

Stuhrmann-Spangenberg, Manfred

2015-02-01

Advances in technical developments of genetic diagnostics for more than 50 years, as well as the fact that human genetic testing is usually performed only once in a lifetime, with additional impact for blood relatives, are determining the extraordinary importance of quality assurance in human genetic testing. Abidance of laws, directives, and guidelines plays a major role. This article aims to present the major laws, directives, and guidelines with respect to quality assurance of human genetic testing, paying careful attention to internal and external quality assurance. The information on quality assurance of human genetic testing was obtained through a web-based search of the web pages that are referred to in this article. Further information was retrieved from publications in the German Society of Human Genetics and through a PubMed-search using term quality + assurance + genetic + diagnostics. The most important laws, directives, and guidelines for quality assurance of human genetic testing are the gene diagnostics law (GenDG), the directive of the Federal Medical Council for quality control of clinical laboratory analysis (RiliBÄK), and the S2K guideline for human genetic diagnostics and counselling. In addition, voluntary accreditation under DIN EN ISO 15189:2013 offers a most recommended contribution towards quality assurance of human genetic testing. Legal restraints on quality assurance of human genetic testing as mentioned in § 5 GenDG are fulfilled once RiliBÄK requirements are followed.

Genetic profiles distinguish different types of hereditary ovarian cancer

DEFF Research Database (Denmark)

Domanska, Katarina; Malander, Susanne; Staaf, Johan

2010-01-01

(HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers......Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer...... that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer....

Genetic etiology of oral cancer.

Science.gov (United States)

Ali, Johar; Sabiha, Bibi; Jan, Hanif Ullah; Haider, Syed Adnan; Khan, Abid Ali; Ali, Saima S

2017-07-01

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. It accounts for 2.5% of all new cancer cases and 1.9% of all cancer deaths annually. More than 90% of oral cancers (occurring in the mouth, lip, and tongue) are oral squamous cell carcinoma. The incidence rate of oral cancer varies widely throughout the world, with an evident prevalence in South Asian countries. This high incidence occurs in correlation with oral cancer-associated behaviors such as alcohol, tobacco use. Researchers have reported that these behaviors lead to genetic variations in tumor suppressor genes (APC, p53), proto-oncogenes (Myc), oncogene (Ras) and genes controlling normal cellular processes (EIF3E, GSTM1). Processes such as segregation of chromosomes, genomic copy number, loss of heterozygosity, telomere stabilities, regulations of cell-cycle checkpoints, DNA damage repairs and defects in notch signaling pathways are involved in causing oral cancer. In order to develop preventive and therapeutic options, it is necessary to comprehend the basic molecular mechanisms forcing oral tumorigenesis. This review examines, in detail, the mechanisms of genetic alteration which are considered to be responsible for the initiation of oral cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Awareness of Cancer Susceptibility Genetic Testing

Science.gov (United States)

Mai, Phuong L.; Vadaparampil, Susan Thomas; Breen, Nancy; McNeel, Timothy S.; Wideroff, Louise; Graubard, Barry I.

2014-01-01

Background Genetic testing for several cancer susceptibility syndromes is clinically available; however, existing data suggest limited population awareness of such tests. Purpose To examine awareness regarding cancer genetic testing in the U.S. population aged ≥25 years in the 2000, 2005, and 2010 National Health Interview Surveys. Methods The weighted percentages of respondents aware of cancer genetic tests, and percent changes from 2000–2005 and 2005–2010, overall and by demographic, family history, and healthcare factors were calculated. Interactions were used to evaluate the patterns of change in awareness between 2005 and 2010 among subgroups within each factor. To evaluate associations with awareness in 2005 and 2010, percentages were adjusted for covariates using multiple logistic regression. The analysis was performed in 2012. Results Awareness decreased from 44.4% to 41.5% (pAwareness increased between 2005 and 2010 in most subgroups, particularly among individuals in the South (p-interaction=0.03) or with a usual place of care (p-interaction=0.01). In 2005 and 2010, awareness was positively associated with personal or family cancer history and high perceived cancer risk, and inversely associated with racial/ethnic minorities, age 25–39 or ≥60 years, male gender, lower education and income levels, public or no health insurance, and no provider contact in 12 months. Conclusions Despite improvement from 2005 to 2010, ≤50% of the U.S. adult population was aware of cancer genetic testing in 2010. Notably, disparities persist for racial/ethnic minorities and individuals with limited health care access or income. PMID:24745633

Genetics of Skin Cancer (PDQ®)—Health Professional Version

Science.gov (United States)

Genetics of Skin Cancer includes information about genes and hereditary syndromes associated with basal cell, squamous cell, and melanoma skin cancer. Get comprehensive information about the genetics of skin cancer and interventions in this summary for clinicians.

Pathway-based Analysis of the Hidden Genetic Heterogeneities in Cancers

Directory of Open Access Journals (Sweden)

Xiaolei Zhao

2014-02-01

Full Text Available Many cancers apparently showing similar phenotypes are actually distinct at the molecular level, leading to very different responses to the same treatment. It has been recently demonstrated that pathway-based approaches are robust and reliable for genetic analysis of cancers. Nevertheless, it remains unclear whether such function-based approaches are useful in deciphering molecular heterogeneities in cancers. Therefore, we aimed to test this possibility in the present study. First, we used a NCI60 dataset to validate the ability of pathways to correctly partition samples. Next, we applied the proposed method to identify the hidden subtypes in diffuse large B-cell lymphoma (DLBCL. Finally, the clinical significance of the identified subtypes was verified using survival analysis. For the NCI60 dataset, we achieved highly accurate partitions that best fit the clinical cancer phenotypes. Subsequently, for a DLBCL dataset, we identified three hidden subtypes that showed very different 10-year overall survival rates (90%, 46% and 20% and were highly significantly (P = 0.008 correlated with the clinical survival rate. This study demonstrated that the pathway-based approach is promising for unveiling genetic heterogeneities in complex human diseases.

WHO HAS TO UNDERGO CANCER GENETIC TESTING? A PERSPECTIVE.

Directory of Open Access Journals (Sweden)

Carmen Rinaldi

2017-10-01

Full Text Available Genetic testing is a medical tool employed to screen changes in genes linked to cancer and other genetic diseases. Genetic tests are available for breast, ovarian, colon, thyroid, and some other cancers and they represent the main tool for early identification of the “risk” subjects. The choice to undergo genetic testing by a healthy or affected cancer patient with family history of the cancer has to be the fruit of a careful and prudent assessment of the advantages and disadvantages discussed during oncogenetic counselling. The latter, in turn, in the case of a patient's positive and informed choice, must constantly affiliate the genetic testing, in order to preserve the prediction and information role of the test as much as possible.

Genetic and Non-genetic Factors Associated WithConstipation in Cancer Patients Receiving Opioids

OpenAIRE

Laugsand, Eivor Alette; Skorpen, Frank; Kaasa, Stein; Sabatowski, Rainer; Strasser, Florian; Fayers, Peter; Klepstad, Pål

2015-01-01

Objectives: To examine whether the inter-individual variation in constipation among patients receiving opioids for cancer pain is associated with genetic or non-genetic factors. Methods: Cancer patients receiving opioids were included from 17 centers in 11 European countries. Intensity of constipation was reported by 1,568 patients on a four-point categorical scale. Non-genetic factors were included as covariates in stratified regression analyses on the association between constipation a...

The genetic alteration of p53 in esophageal cancer

Energy Technology Data Exchange (ETDEWEB)

Cho, Jae Il; Baik, Hee Jong; Kim, Chang Min; Kim, Mi Hee [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

1996-01-01

Genetic alterations in the p53 gene have been detected in various human malignancies, and its alterations inactive the function of p53 as a tumor suppressor. Point mutation and gene deletion are the main mechanisms of p53 inactivation. To determine the incidence of genetic alteration of p53 and their clinical implications in Korean patients of esophageal cancer, we investigated p53 alterations in 26 esophageal cancer tissues paired with its normal tissue by Southern blot analysis, PCR-SSCP, and direct sequencing. Allelic loss of chromosome 17p occurred in 12 out of 21 informative cases(57%) by Southern blot analysis, and 16 cases showed mobility shift in PCR-SSCP, so overall incidence of p53 gene alterations was 77%(20/26). The mutations detected was randomly dispersed over exon4-8 and was frequently G-T transversion and C:T transitions. Three identical mutations were clustered at codon 213 suggested the same etiologic agents in this cases. The p53 gene alterations play a significant role in the development of esophageal cancers, however, no relationship between p53 mutation and clinical data was detected so far. 9 refs. (Author).

Cancer genetics meets biomolecular mechanism-bridging an age-old gulf.

Science.gov (United States)

González-Sánchez, Juan Carlos; Raimondi, Francesco; Russell, Robert B

2018-02-01

Increasingly available genomic sequencing data are exploited to identify genes and variants contributing to diseases, particularly cancer. Traditionally, methods to find such variants have relied heavily on allele frequency and/or familial history, often neglecting to consider any mechanistic understanding of their functional consequences. Thus, while the set of known cancer-related genes has increased, for many, their mechanistic role in the disease is not completely understood. This issue highlights a wide gap between the disciplines of genetics, which largely aims to correlate genetic events with phenotype, and molecular biology, which ultimately aims at a mechanistic understanding of biological processes. Fortunately, new methods and several systematic studies have proved illuminating for many disease genes and variants by integrating sequencing with mechanistic data, including biomolecular structures and interactions. These have provided new interpretations for known mutations and suggested new disease-relevant variants and genes. Here, we review these approaches and discuss particular examples where these have had a profound impact on the understanding of human cancers. © 2018 Federation of European Biochemical Societies.

Novel innate cancer killing activity in humans

Directory of Open Access Journals (Sweden)

Lovato James

2011-08-01

Full Text Available Abstract Background In this study, we pilot tested an in vitro assay of cancer killing activity (CKA in circulating leukocytes of 22 cancer cases and 25 healthy controls. Methods Using a human cervical cancer cell line, HeLa, as target cells, we compared the CKA in circulating leukocytes, as effector cells, of cancer cases and controls. The CKA was normalized as percentages of total target cells during selected periods of incubation time and at selected effector/target cell ratios in comparison to no-effector-cell controls. Results Our results showed that CKA similar to that of our previous study of SR/CR mice was present in human circulating leukocytes but at profoundly different levels in individuals. Overall, males have a significantly higher CKA than females. The CKA levels in cancer cases were lower than that in healthy controls (mean ± SD: 36.97 ± 21.39 vs. 46.28 ± 27.22. Below-median CKA was significantly associated with case status (odds ratio = 4.36; 95% Confidence Interval = 1.06, 17.88 after adjustment of gender and race. Conclusions In freshly isolated human leukocytes, we were able to detect an apparent CKA in a similar manner to that of cancer-resistant SR/CR mice. The finding of CKA at lower levels in cancer patients suggests the possibility that it may be of a consequence of genetic, physiological, or pathological conditions, pending future studies with larger sample size.

Outcome of genetic evaluation of patients with kidney cancer referred for suspected hereditary cancer syndromes.

Science.gov (United States)

Stratton, Kelly L; Alanee, Shaheen; Glogowski, Emily A; Schrader, Kasmintan A; Rau-Murthy, Rohini; Klein, Robert; Russo, Paul; Coleman, Jonathan; Offit, Kenneth

2016-05-01

To analyze patients with kidney cancer referred for evaluation at a high-volume genetics service at a comprehensive cancer center and identify factors associated with positive tests for hereditary cancer syndromes. A retrospective review of patients referred to the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center was performed, and patients with a personal history of kidney cancer were identified. Patient and disease characteristics were reviewed. In all, 4 variables including age at diagnosis of kidney tumor, presence of syndromic manifestations, family history of kidney cancer, and number of primary malignancies were evaluated for association with positive test results in 2 groups: patients tested for renal cell carcinoma syndromes and Lynch syndrome. Guidance for genetic testing strategy in patients with kidney cancer is provided. Between 1999 and 2012, 120 patients with a history of kidney cancer were evaluated by the Clinical Genetics Service. The mean age at kidney cancer diagnosis was 52 years (interquartile range: 42-63), with 57% being women. A family history of kidney cancer was reported by 39 patients (33%). Time between diagnosis of first cancer and genetic consultation was 5 years in the remaining 23%. Overall, 95 patients were tested for genetic abnormalities with 27 (28%) testing positive. Testing for renal cell carcinoma (RCC)-related syndromes was performed on 43 patients, with 13 testing positive (30%). Lynch syndrome testing was positive in 9 patients (32%) after 28 were tested. In RCC-associated syndromes, young age of diagnosis was associated with positive test results. Conversely, syndromic manifestations and increasing number of primary malignancies were associated with positive Lynch testing. The discovery of inherited kidney cancer syndromes has provided a unique opportunity to identify patients at increased risk for cancer. Factors associated with positive genetic testing are unique to different syndromes. These data

A monograph proposing the use of canine mammary tumours as a model for the study of hereditary breast cancer susceptibility genes in humans.

Science.gov (United States)

Goebel, Katie; Merner, Nancy D

2017-05-01

Canines are excellent models for cancer studies due to their similar physiology and genomic sequence to humans, companion status and limited intra-breed heterogeneity. Due to their affliction to mammary cancers, canines can serve as powerful genetic models of hereditary breast cancers. Variants within known human breast cancer susceptibility genes only explain a fraction of familial cases. Thus, further discovery is necessary but such efforts have been thwarted by genetic heterogeneity. Reducing heterogeneity is key, and studying isolated human populations have helped in the endeavour. An alternative is to study dog pedigrees, since artificial selection has resulted in extreme homogeneity. Identifying the genetic predisposition to canine mammary tumours can translate to human discoveries - a strategy currently underutilized. To explore this potential, we reviewed published canine mammary tumour genetic studies and proposed benefits of next generation sequencing canine cohorts to facilitate moving beyond incremental advances.

Understanding participation by African Americans in cancer genetics research.

Science.gov (United States)

McDonald, Jasmine A; Barg, Frances K; Weathers, Benita; Guerra, Carmen E; Troxel, Andrea B; Domchek, Susan; Bowen, Deborah; Shea, Judy A; Halbert, Chanita Hughes

2012-01-01

Understanding genetic factors that contribute to racial differences in cancer outcomes may reduce racial disparities in cancer morbidity and mortality. Achieving this goal will be limited by low rates of African American participation in cancer genetics research. We conducted a qualitative study with African American adults (n = 91) to understand attitudes about participating in cancer genetics research and to identify factors that are considered when making a decision about participating in this type of research. Participants would consider the potential benefits to themselves, family members, and their community when making a decision to participate in cancer genetics research. However, concerns about exploitation, distrust of researchers, and investigators' motives were also important to participation decisions. Individuals would also consider who has access to their personal information and what would happen to these data. Side effects, logistical issues, and the potential to gain knowledge about health issues were also described as important factors in decision making. African Americans may consider a number of ethical, legal, and social issues when making a decision to participate in cancer genetics research. These issues should be addressed as part of recruitment efforts.

Strategies for Integrated Analysis of Genetic, Epigenetic, and Gene Expression Variation in Cancer: Addressing the Challenges

DEFF Research Database (Denmark)

Thingholm, Louise Bruun; Andersen, Lars; Makalic, Enes

2016-01-01

to integration strategies used for analyzing genetic risk factors for cancer. We critically examine the ability of these strategies to handle the complexity of the human genome and also accommodate information about the biological and functional interactions between the elements that have been measured......The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis...

What factors impact upon a woman’s decision to undertake genetic cancer testing?

Directory of Open Access Journals (Sweden)

Julie Anne Quinlivan

2014-01-01

Full Text Available Introduction: The advent of human genome project has lead to genetic tests that identify high-risk states for certain cancers. Many are privately marketed on the Internet. Despite the availability of tests, limited data has evaluated factors that lead to test uptake. The aim of the present study was to explore the attitudes of a cohort of new mothers towards uptake of a genetic cancer test with a 50% predictive value of cancer.Methods: A cross-sectional survey was undertaken. The project targeted women who had recently given birth at an Australian tertiary referral hospital. Women were asked about a theoretical blood test that detected an increased risk for the development of cancer. Attitudes and knowledge questionnaires were completed. Results: Of 232 consecutive women approached, 32 declined, giving a response rate of 86.2%. Only 63 (31.5% women stated they would have the test. Absence of religious belief, higher level of education, better knowledge of terms used in genetics, an absence of concern over emotional, employment and insurance discrimination and previous acceptance of Down syndrome screening in pregnancy were each associated with significantly higher rate of test uptake in univariate analysis (all pConclusion: Concern over discrimination and having made a prior decision to have genetic testing were the principal factors associated with decision-making.

Genetically Engineered Immunotherapy for Advanced Cancer

Science.gov (United States)

In this trial, doctors will collect T lymphocytes from patients with advanced mesothelin-expressing cancer and genetically engineer them to recognize mesothelin. The gene-engineered cells will be multiplied and infused into the patient to fight the cancer

Genetics and tumor genomics in familial colorectal cancer

NARCIS (Netherlands)

Middeldorp, Janneke Willemijn

2010-01-01

Colorectal cancer (CRC) is one of the most common cancers in the Western world and in about 30% hereditary factors play a role. Although several genetic factors that predispose families to CRC are known, in many families affected with CRC the underlying genetics remain elusive. The work described in

Colorectal cancer and detoxification enzymes, with emphasis on enzyme modulation and genetic polymorphisms.

NARCIS (Netherlands)

Logt, E.M.J. van der

2005-01-01

The aetiology of sporadic colorectal cancer (CRC) is complex and involves genetic and lifestyle factors. To deal with the daily load of carcinogens, present in food, tobacco smoke etc., humans possess an efficient system of defence against such compounds and an important role is reserved for the

Exploring Asian Indian and Pakistani views about cancer and participation in cancer genetics research: toward the development of a community genetics intervention.

Science.gov (United States)

Leader, Amy E; Mohanty, Salini; Selvan, Preethi; Lum, Ray; Giri, Veda N

2018-01-01

Cancer is a leading cause of mortality among the three million Asian Indian/Pakistanis (AIPs) in the USA. AIPs have traditionally been underrepresented in cancer-related research, although reasons remain largely unexplored. We sought to understand AIP's awareness and perceptions of cancer to improve their participation in risk assessment and cancer genetics research. Four focus groups, stratified by gender and birthplace (US-born vs. foreign-born), were held at an AIP cultural center. Discussions focused on knowledge and awareness of cancer risk; how AIP culture influences cancer perceptions; access to health care services for cancer screening, diagnosis, or treatment; and willingness to or experiences with participating in cancer genetics research. Sessions were audio-recorded, transcribed verbatim, and content analyzed using NVivo ® 11 for dominant themes. Thirty-two AIP adults participated in a focus group. Information on family cancer history is challenging to obtain due to the desire for privacy, cancer stigma, and loss of medical records. Interest in genetic testing for cancer risk was mixed: some were in favor of knowing their personal risk, yet many noted that future generations in their family would benefit more by knowing their risk. Participants felt that the AIP community has largely been overlooked in recruitment efforts for research studies. Recommendations for improving recruitment efforts included partnering with community events and festivities, posting culturally and linguistically relevant recruitment materials, and focusing on population-wide health improvement. Understanding the culture and perceptions of AIPs, separate from Asian Americans at large, will allow for more tailored approaches for including this population in cancer genetics research.

Personalized medicine and human genetic diversity.

Science.gov (United States)

Lu, Yi-Fan; Goldstein, David B; Angrist, Misha; Cavalleri, Gianpiero

2014-07-24

Human genetic diversity has long been studied both to understand how genetic variation influences risk of disease and infer aspects of human evolutionary history. In this article, we review historical and contemporary views of human genetic diversity, the rare and common mutations implicated in human disease susceptibility, and the relevance of genetic diversity to personalized medicine. First, we describe the development of thought about diversity through the 20th century and through more modern studies including genome-wide association studies (GWAS) and next-generation sequencing. We introduce several examples, such as sickle cell anemia and Tay-Sachs disease that are caused by rare mutations and are more frequent in certain geographical populations, and common treatment responses that are caused by common variants, such as hepatitis C infection. We conclude with comments about the continued relevance of human genetic diversity in medical genetics and personalized medicine more generally. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics.

Science.gov (United States)

Simpson, Siobhan; Dunning, Mark David; de Brot, Simone; Grau-Roma, Llorenç; Mongan, Nigel Patrick; Rutland, Catrin Sian

2017-10-24

Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is relatively poor, with 5 year OSA survival rates in people not having improved in decades. For dogs, 1 year survival rates are only around ~ 45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human OSA. Finally, the current position of canine OSA genetic research is discussed and areas for additional work within the canine population are identified.

Awareness and uptake of direct-to-consumer genetic testing among cancer cases, their relatives, and controls: the Northwest Cancer Genetics Network.

Science.gov (United States)

Hall, Taryn O; Renz, Anne D; Snapinn, Katherine W; Bowen, Deborah J; Edwards, Karen L

2012-07-01

To determine if awareness of, interest in, and use of direct-to-consumer (DTC) genetic testing is greater in a sample of high-risk individuals (cancer cases and their relatives), compared to controls. Participants were recruited from the Northwest Cancer Genetics Network. A follow-up survey was mailed to participants to assess DTC genetic testing awareness, interest, and use. One thousand two hundred sixty-seven participants responded to the survey. Forty-nine percent of respondents were aware of DTC genetic testing. Of those aware, 19% indicated interest in obtaining and testing. Additional information supplied by respondents who reported use of DTC genetic tests indicated that 55% of these respondents likely engaged in clinical genetic testing, rather than DTC genetic testing. Awareness of DTC genetic testing was greater in our sample of high-risk individuals than in controls and population-based studies. Although interest in and use of these tests among cases in our sample were equivalent to other population-based studies, interest in testing was higher among relatives and people who self-referred for a registry focused on cancer than among cases and controls. Additionally, our results suggest that there may be some confusion about what constitutes DTC genetic testing.

Protocols in human molecular genetics

National Research Council Canada - National Science Library

Mathew, Christopher G

1991-01-01

... sequences has led to the development of DNA fingerprinting. The application of these techniques to the study of the human genome has culminated in major advances such as the cloning of the cystic fibrosis gene, the construction of genetic linkage maps of each human chromosome, the mapping of many genes responsible for human inherited disorders, genet...

Lung cancer, genetic predisposition and smoking

DEFF Research Database (Denmark)

Hjelmborg, Jacob; Korhonen, Tellervo; Holst, Klaus

2017-01-01

Background: We aimed to disentangle genetic and environmental causes in lung cancer while considering smoking status. Methods: Four Nordic twin cohorts (43 512 monozygotic (MZ) and 71 895 same sex dizygotic (DZ) twin individuals) had smoking data before cancer diagnosis. We used time...

Molecular concept in human oral cancer

OpenAIRE

Krishna, Akhilesh; Singh, Shraddha; Kumar, Vijay; Pal, U. S.

2015-01-01

The incidence of oral cancer remains high in both Asian and Western countries. Several risk factors associated with development of oral cancer are now well-known, including tobacco chewing, smoking, and alcohol consumption. Cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. Oral squamous carcinogenesis is a multistep process in...

Linkage of DNA Methylation Quantitative Trait Loci to Human Cancer Risk

Directory of Open Access Journals (Sweden)

Holger Heyn

2014-04-01

Full Text Available Epigenetic regulation and, in particular, DNA methylation have been linked to the underlying genetic sequence. DNA methylation quantitative trait loci (meQTL have been identified through significant associations between the genetic and epigenetic codes in physiological and pathological contexts. We propose that interrogating the interplay between polymorphic alleles and DNA methylation is a powerful method for improving our interpretation of risk alleles identified in genome-wide association studies that otherwise lack mechanistic explanation. We integrated patient cancer risk genotype data and genome-scale DNA methylation profiles of 3,649 primary human tumors, representing 13 solid cancer types. We provide a comprehensive meQTL catalog containing DNA methylation associations for 21% of interrogated cancer risk polymorphisms. Differentially methylated loci harbor previously reported and as-yet-unidentified cancer genes. We suggest that such regulation at the DNA level can provide a considerable amount of new information about the biology of cancer-risk alleles.

Human genetics and sleep behavior.

Science.gov (United States)

Shi, Guangsen; Wu, David; Ptáček, Louis J; Fu, Ying-Hui

2017-06-01

Why we sleep remains one of the greatest mysteries in science. In the past few years, great advances have been made to better understand this phenomenon. Human genetics has contributed significantly to this movement, as many features of sleep have been found to be heritable. Discoveries about these genetic variations that affect human sleep will aid us in understanding the underlying mechanism of sleep. Here we summarize recent discoveries about the genetic variations affecting the timing of sleep, duration of sleep and EEG patterns. To conclude, we also discuss some of the sleep-related neurological disorders such as Autism Spectrum Disorder (ASD) and Alzheimer's Disease (AD) and the potential challenges and future directions of human genetics in sleep research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability.

Science.gov (United States)

Colotta, Francesco; Allavena, Paola; Sica, Antonio; Garlanda, Cecilia; Mantovani, Alberto

2009-07-01

Inflammatory conditions in selected organs increase the risk of cancer. An inflammatory component is present also in the microenvironment of tumors that are not epidemiologically related to inflammation. Recent studies have begun to unravel molecular pathways linking inflammation and cancer. In the tumor microenvironment, smoldering inflammation contributes to proliferation and survival of malignant cells, angiogenesis, metastasis, subversion of adaptive immunity, reduced response to hormones and chemotherapeutic agents. Recent data suggest that an additional mechanism involved in cancer-related inflammation (CRI) is induction of genetic instability by inflammatory mediators, leading to accumulation of random genetic alterations in cancer cells. In a seminal contribution, Hanahan and Weinberg [(2000) Cell, 100, 57-70] identified the six hallmarks of cancer. We surmise that CRI represents the seventh hallmark.

Genetics and molecular biology of breast cancer

Energy Technology Data Exchange (ETDEWEB)

King, M.C. [California Univ., Berkeley, CA (United States); Lippman, M. [Georgetown Univ. Medical Center, Washington, DC (United States)] [comps.

1992-12-31

This volume contains the abstracts of oral presentations and poster sessions presented at the Cold Springs Harbor Meeting on Cancer Cells, this meeting entitled Genetics and Molecular Biology of Breast Cancer.

Integrated screening concept in women with genetic predisposition for breast cancer

International Nuclear Information System (INIS)

Bick, U.

1997-01-01

Breast cancer is in 5% of cases due to a genetic disposition. BRCA1 and BRCA2 are by far the most common breast cancer susceptibility genes. For a woman with a genetic predisposition, the individual risk of developing breast cancer sometime in her life is between 70 and 90%. Compared to the spontaneous forms of breast cancer, woman with a genetic predisposition often develop breast cancer at a much younger age. This is why conventional screening programs on the basis of mammography alone cannot be applied without modification to this high-risk group. In this article, an integrated screening concept for women with genetic prodisposition for breast cancer using breast self-examination, clinical examination, ultrasound, mammography and magnetic resonance imaging is introduced. (orig.) [de

Identification of novel genetic markers of breast cancer survival

NARCIS (Netherlands)

Q. Guo (Qi); M.K. Schmidt (Marjanka); P. Kraft (Peter); S. Canisius (Sander); C. Chen (Constance); S. Khan (Sofia); J.P. Tyrer (Jonathan); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); K. Michailidou (Kyriaki); M. Lush (Michael); S. Kar (Siddhartha); J. Beesley (Jonathan); A.M. Dunning (Alison); M. Shah (Mitul); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); D. Lambrechts (Diether); C. Weltens (Caroline); K. Leunen; S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); C. Blomqvist (Carl); K. Aittomäki (Kristiina); R. Fagerholm (Rainer); T.A. Muranen (Taru); F.J. Couch (Fergus); J.E. Olson (Janet); C. Vachon (Celine); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.-M. Mulligan (Anna-Marie); A. Broeks (Annegien); F.B.L. Hogervorst (Frans); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Hopper (John); H. Tsimiklis (Helen); C. Apicella (Carmel); M.C. Southey (Melissa); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); G.G. Giles (Graham G.); R.L. Milne (Roger L.); C.A. McLean (Catriona Ann); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); J.W.M. Martens (John W. M.); A.M.W. van den Ouweland (Ans); F. Marme (Federick); A. Schneeweiss (Andreas); R. Yang (Rongxi); B. Burwinkel (Barbara); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); J. Lissowska (Jolanta); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); B. Holleczek (B.); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); J. Li (Jingmei); J.S. Brand (Judith S.); M.K. Humphreys (Manjeet); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); P. Radice (Paolo); P. Peterlongo (Paolo); B. Bonnani (Bernardo); P. Mariani (Paolo); P.A. Fasching (Peter); M.W. Beckmann (Matthias); R. Hein (Rebecca); A.B. Ekici (Arif); G. Chenevix-Trench (Georgia); R. Balleine (Rosemary); K.-A. Phillips (Kelly-Anne); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); P. Menéndez (Primitiva); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); U. Hamann (Ute); M. Kabisch (Maria); H.U. Ulmer (Hans); T. Rud̈iger (Thomas); S. Margolin (Sara); V. Kristensen (Vessela); S. Nord (Silje); D.G. Evans (Gareth); J. Abraham (Jean); H. Earl (Helena); L. Hiller (Louise); J.A. Dunn (J.); S. Bowden (Sarah); C.D. Berg (Christine); D. Campa (Daniele); W.R. Diver (Ryan); S.M. Gapstur (Susan M.); M.M. Gaudet (Mia); S.E. Hankinson (Susan); R.N. Hoover (Robert); A. Hüsing (Anika); R. Kaaks (Rudolf); M.J. Machiela (Mitchell J.); W.C. Willett (Walter C.); M. Barrdahl (Myrto); F. Canzian (Federico); S.-F. Chin (Suet-Feung); C. Caldas (Carlos); D. Hunter (David); S. Lindstrom (Stephen); M. García-Closas (Montserrat); P. Hall (Per); D.F. Easton (Douglas); D. Eccles (Diana); N. Rahman (Nazneen); H. Nevanlinna (Heli); P.D.P. Pharoah (Paul)

2015-01-01

textabstractBackground: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. Methods: We conducted a large

Frequent mutations in EGFR, KRAS and TP53 genes in human lung cancer tumors detected by ion torrent DNA sequencing.

Directory of Open Access Journals (Sweden)

Xin Cai

Full Text Available Lung cancer is the most common malignancy and the leading cause of cancer deaths worldwide. While smoking is by far the leading cause of lung cancer, other environmental and genetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive lung cancer molecular profile is essential for developing more effective, tailored therapies. Until recently, personalized DNA sequencing to identify genetic mutations in cancer was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 76 human lung cancer samples. The sequencing analysis revealed missense mutations in KRAS, EGFR, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.

Courting the future: cancer and genetics in Cuba.

Science.gov (United States)

2014-01-01

Describing this double issue of MEDICC Review could be an exercise for a first-year philosophy course in logic. It's not about "cancer and genetics" in Cuba. It's about cancer in Cuba and about genetics in Cuba, not about exploring relationships between them. Nevertheless, while the marriage of the two themes was fortuitous, in that the two had long been scheduled for the journal in 2014, there is a certain felicity to their sharing an issue. To date, the outstanding accomplishments of genetics have been most helpful for conditions occurring at the beginning of life and cancer is largely (though not exclusively) a disease related to aging. But the two are intrinsically connected: Although only a few of the more than 100 different diseases grouped under the term cancer are known to be hereditary, every cancer begins with a mutation in one or more genes, whether the mutation is inherited, due to an exposure, or is simply a random error in the millions of cell divisions that are part and parcel of cellular reproduction. Our cover image, a stained-glass window by Cuban artist Rosa María de la Terga at Cuba's National Medical Genetics Center, illustrates the elegance of the DNA molecule, the intricate key to life.

Insights into genetic and epigenetic determinants with impact on vitamin D signaling and cancer association studies: The case of thyroid cancer

Directory of Open Access Journals (Sweden)

Gregoire B Morand

2014-11-01

Full Text Available Vitamin D is a key regulator of calcium metabolism and has been implicated as a cancer preventive agent. However, clinical studies have revealed conflicting results on its cancer preventive properties, attributed in part to multiple metabolic and regulatory factors susceptible to affect individual responses to exogenous vitamin D. Vitamin D is obtained from dietary sources and sun exposure, which depends on numerous parameters such as skin type, latitude, and lifestyle factors. Focusing on thyroid cancer, we document that genetic and epigenetic determinants can greatly impact individual response to vitamin D and may outweigh the classical clinical correlative studies that focus on sun exposure/dietary intake factors. In particular, genetic determinants innate to host intrinsic metabolic pathways such as highly polymorphic cytochromes P450s responsible for the metabolic activation of vitamin D are expressed in many organs, including the thyroid gland and can impact vitamin D interaction with its nuclear receptor (VDR in thyroid tissue. Moreover, downstream regulatory pathways in vitamin D signalling as well as VDR are also subject to wide genetic variability among human populations as shown by genome-wide studies. These genetic variations in multiple components of vitamin D pathways are critical determinants for the re-valuation of the potential preventive and anticancer properties of vitamin D in thyroid cancer.

Identification of novel genetic markers of breast cancer survival

DEFF Research Database (Denmark)

Guo, Qi; Schmidt, Marjanka K; Kraft, Peter

2015-01-01

BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. METHODS: We conducted a large meta-analysis ......BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. METHODS: We conducted a large meta......-analysis of studies in populations of European ancestry, including 37954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200000 and 900000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference...... panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)-negative patients (920 events) and 23059 ER-positive patients (1333 events). All statistical tests were two-sided. RESULTS: We identified one new locus (rs2059614 at 11q24...

Rexin-G, a targeted genetic medicine for cancer.

Science.gov (United States)

Gordon, Erlinda M; Hall, Frederick L

2010-05-01

Rexin-G, a tumor-targeted retrovector bearing a cytocidal cyclin G1 construct, is the first targeted gene therapy vector to gain fast track designation and orphan drug priorities for multiple cancer indications in the US. This review describes the major milestones in the clinical development of Rexin-G: from the molecular cloning and characterization of the human cyclin G1 proto-oncogene in 1994, to the design of the first knockout constructs and genetic engineering of the targeted delivery system from 1995 to 1997, through the initial proofs-of-concept, molecular pharmacology and toxicology studies of Rexin-G in preclinical cancer models from 1997 to 2001, to the pioneering clinical studies in humans from 2002 to 2004, which--together with the advancements in bioprocess development of high-potency clinical grade vectors circa 2005 - 2006--led to the accelerated approval of Rexin-G for all solid tumors by the Philippine FDA in 2007 and the rapid progression of clinical studies from 2007 to 2009 to the cusp of pivotal Phase III trials in the US. In recording the development of Rexin-G as a novel form of targeted biological therapy, this review also highlights important aspects of vector design engineering which served to overcome the physiological barriers to gene delivery as it addresses the key regulatory issues involved in the development of a targeted gene therapy product. Progressive clinical development of Rexin-G demonstrates the potential safety and efficacy of targeted genetic medicine, while validating the design engineering of the molecular biotechnology platform.

Genetics of Kidney Cancer (Renal Cell Cancer) (PDQ®)—Health Professional Version

Science.gov (United States)

Genetics of Kidney Cancer (Renal Cell) includes the hereditary cancer syndromes von Hippel-Lindau disease, hereditary leiomyomatosis and renal cell cancer, Birt-Hogg-Dubé syndrome, and hereditary papillary renal carcinoma. Get comprehensive information on these syndromes in this clinician summary.

Understanding the development of human bladder cancer by using a whole-organ genomic mapping strategy.

Science.gov (United States)

Majewski, Tadeusz; Lee, Sangkyou; Jeong, Joon; Yoon, Dong-Sup; Kram, Andrzej; Kim, Mi-Sook; Tuziak, Tomasz; Bondaruk, Jolanta; Lee, Sooyong; Park, Weon-Seo; Tang, Kuang S; Chung, Woonbok; Shen, Lanlan; Ahmed, Saira S; Johnston, Dennis A; Grossman, H Barton; Dinney, Colin P; Zhou, Jain-Hua; Harris, R Alan; Snyder, Carrie; Filipek, Slawomir; Narod, Steven A; Watson, Patrice; Lynch, Henry T; Gazdar, Adi; Bar-Eli, Menashe; Wu, Xifeng F; McConkey, David J; Baggerly, Keith; Issa, Jean-Pierre; Benedict, William F; Scherer, Steven E; Czerniak, Bogdan

2008-07-01

The search for the genomic sequences involved in human cancers can be greatly facilitated by maps of genomic imbalances identifying the involved chromosomal regions, particularly those that participate in the development of occult preneoplastic conditions that progress to clinically aggressive invasive cancer. The integration of such regions with human genome sequence variation may provide valuable clues about their overall structure and gene content. By extension, such knowledge may help us understand the underlying genetic components involved in the initiation and progression of these cancers. We describe the development of a genome-wide map of human bladder cancer that tracks its progression from in situ precursor conditions to invasive disease. Testing for allelic losses using a genome-wide panel of 787 microsatellite markers was performed on multiple DNA samples, extracted from the entire mucosal surface of the bladder and corresponding to normal urothelium, in situ preneoplastic lesions, and invasive carcinoma. Using this approach, we matched the clonal allelic losses in distinct chromosomal regions to specific phases of bladder neoplasia and produced a detailed genetic map of bladder cancer development. These analyses revealed three major waves of genetic changes associated with growth advantages of successive clones and reflecting a stepwise conversion of normal urothelial cells into cancer cells. The genetic changes map to six regions at 3q22-q24, 5q22-q31, 9q21-q22, 10q26, 13q14, and 17p13, which may represent critical hits driving the development of bladder cancer. Finally, we performed high-resolution mapping using single nucleotide polymorphism markers within one region on chromosome 13q14, containing the model tumor suppressor gene RB1, and defined a minimal deleted region associated with clonal expansion of in situ neoplasia. These analyses provided new insights on the involvement of several non-coding sequences mapping to the region and identified

Genetics of Human and Canine Dilated Cardiomyopathy.

Science.gov (United States)

Simpson, Siobhan; Edwards, Jennifer; Ferguson-Mignan, Thomas F N; Cobb, Malcolm; Mongan, Nigel P; Rutland, Catrin S

2015-01-01

Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed.

Genetic Mechanisms of Immune Evasion in Colorectal Cancer.

Science.gov (United States)

Grasso, Catherine S; Giannakis, Marios; Wells, Daniel K; Hamada, Tsuyoshi; Mu, Xinmeng Jasmine; Quist, Michael; Nowak, Jonathan A; Nishihara, Reiko; Qian, Zhi Rong; Inamura, Kentaro; Morikawa, Teppei; Nosho, Katsuhiko; Abril-Rodriguez, Gabriel; Connolly, Charles; Escuin-Ordinas, Helena; Geybels, Milan S; Grady, William M; Hsu, Li; Hu-Lieskovan, Siwen; Huyghe, Jeroen R; Kim, Yeon Joo; Krystofinski, Paige; Leiserson, Mark D M; Montoya, Dennis J; Nadel, Brian B; Pellegrini, Matteo; Pritchard, Colin C; Puig-Saus, Cristina; Quist, Elleanor H; Raphael, Ben J; Salipante, Stephen J; Shin, Daniel Sanghoon; Shinbrot, Eve; Shirts, Brian; Shukla, Sachet; Stanford, Janet L; Sun, Wei; Tsoi, Jennifer; Upfill-Brown, Alexander; Wheeler, David A; Wu, Catherine J; Yu, Ming; Zaidi, Syed H; Zaretsky, Jesse M; Gabriel, Stacey B; Lander, Eric S; Garraway, Levi A; Hudson, Thomas J; Fuchs, Charles S; Ribas, Antoni; Ogino, Shuji; Peters, Ulrike

2018-06-01

To understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 colorectal cancer primary tumor samples, including 179 classified as microsatellite instability-high (MSI-high). This set includes The Cancer Genome Atlas colorectal cancer cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of colorectal cancer, had a high rate of significantly mutated genes in important immune-modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy-number alterations and copy-neutral loss of heterozygosity. WNT/β-catenin signaling genes were significantly mutated in all colorectal cancer subtypes, and activated WNT/β-catenin signaling was correlated with the absence of T-cell infiltration. This large-scale genomic analysis of colorectal cancer demonstrates that MSI-high cases frequently undergo an immunoediting process that provides them with genetic events allowing immune escape despite high mutational load and frequent lymphocytic infiltration and, furthermore, that colorectal cancer tumors have genetic and methylation events associated with activated WNT signaling and T-cell exclusion. Significance: This multi-omic analysis of 1,211 colorectal cancer primary tumors reveals that it should be possible to better monitor resistance in the 15% of cases that respond to immune blockade therapy and also to use WNT signaling inhibitors to reverse immune exclusion in the 85% of cases that currently do not. Cancer Discov; 8(6); 730-49. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 663 . ©2018 American Association for Cancer Research.

Genetic variants in FGFR2 and FGFR4 genes and skin cancer risk in the Nurses' Health Study

International Nuclear Information System (INIS)

Nan, Hongmei; Qureshi, Abrar A; Hunter, David J; Han, Jiali

2009-01-01

The human fibroblast growth factor (FGF) and its receptor (FGFR) play an important role in tumorigenesis. Deregulation of the FGFR2 gene has been identified in a number of cancer sites. Overexpression of the FGFR4 protein has been linked to cutaneous melanoma progression. Previous studies reported associations between genetic variants in the FGFR2 and FGFR4 genes and development of various cancers. We evaluated the associations of four genetic variants in the FGFR2 gene highly related to breast cancer risk and the three common tag-SNPs in the FGFR4 gene with skin cancer risk in a nested case-control study of Caucasians within the Nurses' Health Study (NHS) among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases, and 870 controls. We found no evidence for associations between these seven genetic variants and the risks of melanoma and nonmelanocytic skin cancer. Given the power of this study, we did not detect any contribution of genetic variants in the FGFR2 or FGFR4 genes to inherited predisposition to skin cancer among Caucasian women

Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence.

Science.gov (United States)

Alsbeih, Ghazi A; Al-Harbi, Najla M; Bin Judia, Sara S; Khoja, Hatim A; Shoukri, Mohamed M; Tulbah, Asma M

2017-07-01

Cervical cancer is a predominantly human papillomavirus (HPV)-driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence. Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples. The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV-positive and 16 HPV genotypes were detected-mostly genotypes 16 (75%) and 18 (9%)-with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P Cervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. Cancer 2017;123:2459-66. © 2017 American Cancer Society. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Cancer Genetics Risk Assessment and Counseling (PDQ®)—Health Professional Version

Science.gov (United States)

Cancer genetics risk assessment and genetic counseling includes family history, psychosocial assessments, and education on hereditary cancer syndromes, testing, and risk. Get more information including the ethical, legal, and social implications of genetic testing in this summary for clinicians.

Population genetic testing for cancer susceptibility: founder mutations to genomes.

Science.gov (United States)

Foulkes, William D; Knoppers, Bartha Maria; Turnbull, Clare

2016-01-01

The current standard model for identifying carriers of high-risk mutations in cancer-susceptibility genes (CSGs) generally involves a process that is not amenable to population-based testing: access to genetic tests is typically regulated by health-care providers on the basis of a labour-intensive assessment of an individual's personal and family history of cancer, with face-to-face genetic counselling performed before mutation testing. Several studies have shown that application of these selection criteria results in a substantial proportion of mutation carriers being missed. Population-based genetic testing has been proposed as an alternative approach to determining cancer susceptibility, and aims for a more-comprehensive detection of mutation carriers. Herein, we review the existing data on population-based genetic testing, and consider some of the barriers, pitfalls, and challenges related to the possible expansion of this approach. We consider mechanisms by which population-based genetic testing for cancer susceptibility could be delivered, and suggest how such genetic testing might be integrated into existing and emerging health-care structures. The existing models of genetic testing (including issues relating to informed consent) will very likely require considerable alteration if the potential benefits of population-based genetic testing are to be fully realized.

Applications of genetic programming in cancer research.

Science.gov (United States)

Worzel, William P; Yu, Jianjun; Almal, Arpit A; Chinnaiyan, Arul M

2009-02-01

The theory of Darwinian evolution is the fundamental keystones of modern biology. Late in the last century, computer scientists began adapting its principles, in particular natural selection, to complex computational challenges, leading to the emergence of evolutionary algorithms. The conceptual model of selective pressure and recombination in evolutionary algorithms allow scientists to efficiently search high dimensional space for solutions to complex problems. In the last decade, genetic programming has been developed and extensively applied for analysis of molecular data to classify cancer subtypes and characterize the mechanisms of cancer pathogenesis and development. This article reviews current successes using genetic programming and discusses its potential impact in cancer research and treatment in the near future.

Prevalence and detection of psychosocial problems in cancer genetic counseling.

Science.gov (United States)

Eijzenga, W; Bleiker, E M A; Hahn, D E E; Van der Kolk, L E; Sidharta, G N; Aaronson, N K

2015-12-01

Only a minority of individuals who undergo cancer genetic counseling experience heightened levels of psychological distress, but many more experience a range of cancer genetic-specific psychosocial problems. The aim of this study was to estimate the prevalence of such psychosocial problems, and to identify possible demographic and clinical variables associated significantly with them. Consenting individuals scheduled to undergo cancer genetic counseling completed the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire, the Hospital Anxiety and Depression Scale (HADS) and the Distress Thermometer (DT) prior to or immediately following their counseling session. More than half of the 137 participants reported problems on three or more domains of the PAHC, most often in the domains 'living with cancer' (84%), 'family issues' (46%), 'hereditary predisposition' (45%), and 'child-related issues' (42%). Correlations between the PAHC, the HADS and the DT were low. Previous contact with a psychosocial worker, and having a personal history of cancer were associated significantly with HADS scores, but explained little variance (9%). No background variables were associated significantly with the DT. Previous contact with a psychosocial worker, and having children were significantly associated with several PAHC domains, again explaining only a small percentage of the variance (2-14%). The majority of counselees experience specific cancer genetic counseling-related psychosocial problems. Only a few background variables are associated significantly with distress or psychosocial problems. Thus we recommend using the PAHC or a similar problem-oriented questionnaire routinely in cancer genetic counseling to identify individuals with such problems.

Genetics of Human and Canine Dilated Cardiomyopathy

Directory of Open Access Journals (Sweden)

Siobhan Simpson

2015-01-01

Full Text Available Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed.

CGMIM: Automated text-mining of Online Mendelian Inheritance in Man (OMIM to identify genetically-associated cancers and candidate genes

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Jones Steven

2005-03-01

Full Text Available Abstract Background Online Mendelian Inheritance in Man (OMIM is a computerized database of information about genes and heritable traits in human populations, based on information reported in the scientific literature. Our objective was to establish an automated text-mining system for OMIM that will identify genetically-related cancers and cancer-related genes. We developed the computer program CGMIM to search for entries in OMIM that are related to one or more cancer types. We performed manual searches of OMIM to verify the program results. Results In the OMIM database on September 30, 2004, CGMIM identified 1943 genes related to cancer. BRCA2 (OMIM *164757, BRAF (OMIM *164757 and CDKN2A (OMIM *600160 were each related to 14 types of cancer. There were 45 genes related to cancer of the esophagus, 121 genes related to cancer of the stomach, and 21 genes related to both. Analysis of CGMIM results indicate that fewer than three gene entries in OMIM should mention both, and the more than seven-fold discrepancy suggests cancers of the esophagus and stomach are more genetically related than current literature suggests. Conclusion CGMIM identifies genetically-related cancers and cancer-related genes. In several ways, cancers with shared genetic etiology are anticipated to lead to further etiologic hypotheses and advances regarding environmental agents. CGMIM results are posted monthly and the source code can be obtained free of charge from the BC Cancer Research Centre website http://www.bccrc.ca/ccr/CGMIM.

Targeted Cancer Therapy: Vital Oncogenes and a New Molecular Genetic Paradigm for Cancer Initiation Progression and Treatment

Science.gov (United States)

Willis, Rudolph E.

2016-01-01

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis. PMID:27649156

Identification of differentially expressed microRNAs in human male breast cancer

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Schipper Elisa

2010-03-01

Full Text Available Abstract Background The discovery of small non-coding RNAs and the subsequent analysis of microRNA expression patterns in human cancer specimens have provided completely new insights into cancer biology. Genetic and epigenetic data indicate oncogenic or tumor suppressor function of these pleiotropic regulators. Therefore, many studies analyzed the expression and function of microRNA in human breast cancer, the most frequent malignancy in females. However, nothing is known so far about microRNA expression in male breast cancer, accounting for approximately 1% of all breast cancer cases. Methods The expression of 319 microRNAs was analyzed in 9 primary human male breast tumors and in epithelial cells from 15 male gynecomastia specimens using fluorescence-labeled bead technology. For identification of differentially expressed microRNAs data were analyzed by cluster analysis and selected statistical methods. Expression levels were validated for the most up- or down-regulated microRNAs in this training cohort using real-time PCR methodology as well as in an independent test cohort comprising 12 cases of human male breast cancer. Results Unsupervised cluster analysis separated very well male breast cancer samples and control specimens according to their microRNA expression pattern indicating cancer-specific alterations of microRNA expression in human male breast cancer. miR-21, miR519d, miR-183, miR-197, and miR-493-5p were identified as most prominently up-regulated, miR-145 and miR-497 as most prominently down-regulated in male breast cancer. Conclusions Male breast cancer displays several differentially expressed microRNAs. Not all of them are shared with breast cancer biopsies from female patients indicating male breast cancer specific alterations of microRNA expression.

Breast Cancer Genetic Counseling: A Surgeon’s Perspective

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Doreen Marie Agnese

2016-01-01

Full Text Available As surgeons who care for patients with breast cancer, the possibility of a cancer diagnosis being related to a hereditary predisposition is always a consideration. Not only are we as surgeons always trying to identify these patients and families, but also we are often asked about a potential hereditary component by the patients and their family members. It is therefore critical that we accurately assess patients to determine who may benefit from genetic testing. Importantly, the potential benefit for identifying a hereditary breast cancer extends beyond the patient to other family members and the risk may not be only for the development of breast cancers, but for other cancers as well. As a surgeon with additional training in clinical cancer genetics, I have perhaps a unique perspective on the issue and feel that a review of some of the more practical considerations is important.

Building capacity for human genetics and genomics research in Trinidad and Tobago

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Allana Roach

Full Text Available Advances in human genetics and genomic sciences and the corresponding explosion of biomedical technologies have deepened current understanding of human health and revolutionized medicine. In developed nations, this has led to marked improvements in disease risk stratification and diagnosis. These advances have also led to targeted intervention strategies aimed at promoting disease prevention, prolonging disease onset, and mitigating symptoms, as in the well-known case of breast cancer and the BRCA1 gene. In contrast, in the developing nation of Trinidad and Tobago, this scientific revolution has not translated into the development and application of effective genomics-based interventions for improving public health. While the reasons for this are multifactorial, the underlying basis may be rooted in the lack of pertinence of internationally driven genomics research to the local public health needs in the country, as well as a lack of relevance of internationally conducted genetics research to the genetic and environmental contexts of the population. Indeed, if Trinidad and Tobago is able to harness substantial public health benefit from genetics/genomics research, then there is a dire need, in the near future, to build local capacity for the conduct and translation of such research. Specifically, it is essential to establish a national human genetics/genomics research agenda in order to build sustainable human capacity through education and knowledge transfer and to generate public policies that will provide the basis for the creation of a mutually beneficial framework (including partnerships with more developed nations that is informed by public health needs and contextual realities of the nation.

Human genetic factors in tuberculosis: an update.

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van Tong, Hoang; Velavan, Thirumalaisamy P; Thye, Thorsten; Meyer, Christian G

2017-09-01

Tuberculosis (TB) is a major threat to human health, especially in many developing countries. Human genetic variability has been recognised to be of great relevance in host responses to Mycobacterium tuberculosis infection and in regulating both the establishment and the progression of the disease. An increasing number of candidate gene and genome-wide association studies (GWAS) have focused on human genetic factors contributing to susceptibility or resistance to TB. To update previous reviews on human genetic factors in TB we searched the MEDLINE database and PubMed for articles from 1 January 2014 through 31 March 2017 and reviewed the role of human genetic variability in TB. Search terms applied in various combinations were 'tuberculosis', 'human genetics', 'candidate gene studies', 'genome-wide association studies' and 'Mycobacterium tuberculosis'. Articles in English retrieved and relevant references cited in these articles were reviewed. Abstracts and reports from meetings were also included. This review provides a recent summary of associations of polymorphisms of human genes with susceptibility/resistance to TB. © 2017 John Wiley & Sons Ltd.

Molecular genetics of cancer and tumorigenesis: Drosophila models

Institute of Scientific and Technical Information of China (English)

Wu-Min Deng

2011-01-01

Why do some cells not respond to normal control of cell division and become tumorous? Which signals trigger some tumor cells to migrate and colonize other tissues? What genetic factors are responsible for tumorigenesis and cancer development? What environmental factors play a role in cancer formation and progression? In how many ways can our bodies prevent and restrict the growth of cancerous cells?How can we identify and deliver effective drugs to fight cancer? In the fight against cancer,which kills more people than any other disease,these and other questions have long interested researchers from a diverse range of fields.To answer these questions and to fight cancer more effectively,we must increase our understanding of basic cancer biology.Model organisms,including the fruit fly Drosophila melanogaster,have played instrumental roles in our understanding of this devastating disease and the search for effective cures.Drosophila and its highly effective,easy-touse,and ever-expanding genetic tools have contributed toand enriched our knowledge of cancer and tumor formation tremendously.

Endometrial cancer : from a molecular genetic perspective

NARCIS (Netherlands)

E. Smid-Koopman (Ellen)

2002-01-01

textabstractThe first observations indicative of a role of genetic factors in carcinogenesis were made as early as 1912, when Rous demonstrated that a filterable agent (i.e. virus) could induce cancer in chicken (Rous 1965). In 1914, Boveri postulated a "genetic" theory on carcinogenesis by

Prevalence and detection of psychosocial problems in cancer genetic counseling

NARCIS (Netherlands)

Eijzenga, W.; Bleiker, E.M.A.; Hahn, D.E.E.; van der Kolk, L.E.; Sidharta, G.N.; Aaronson, N.K.

2015-01-01

Only a minority of individuals who undergo cancer genetic counseling experience heightened levels of psychological distress, but many more experience a range of cancer genetic-specific psychosocial problems. The aim of this study was to estimate the prevalence of such psychosocial problems, and to

Genetic basis of interindividual susceptibility to cancer cachexia

Indian Academy of Sciences (India)

Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of biological processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications and biological ...

Asymmetry in family history implicates nonstandard genetic mechanisms: application to the genetics of breast cancer.

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Clarice R Weinberg

2014-03-01

Full Text Available Genome-wide association studies typically target inherited autosomal variants, but less studied genetic mechanisms can play a role in complex disease. Sex-linked variants aside, three genetic phenomena can induce differential risk in maternal versus paternal lineages of affected individuals: 1. maternal effects, reflecting the maternal genome's influence on prenatal development; 2. mitochondrial variants, which are inherited maternally; 3. autosomal genes, whose effects depend on parent of origin. We algebraically show that small asymmetries in family histories of affected individuals may reflect much larger genetic risks acting via those mechanisms. We apply these ideas to a study of sisters of women with breast cancer. Among 5,091 distinct families of women reporting that exactly one grandmother had breast cancer, risk was skewed toward maternal grandmothers (p<0.0001, especially if the granddaughter was diagnosed between age 45 and 54. Maternal genetic effects, mitochondrial variants, or variant genes with parent-of-origin effects may influence risk of perimenopausal breast cancer.

Genetic variation in DNA repair gene XRCC7 (G6721T) and susceptibility to breast cancer.

Science.gov (United States)

Nasiri, Meysam; Saadat, Iraj; Omidvari, Shahpour; Saadat, Mostafa

2012-08-15

The human XRCC7 is a DNA double-strand break (DSBs) repair gene, involved in non-homologous end joining (NHEJ). It is speculated that DNA DSBs repair have an important role during development of breast cancer. The human XRCC7 is a NHEJ DSBs repair gene. Genetic variation G6721T of XRCC7 (rs7003908) is located in the intron 8 of the gene. This polymorphism may regulate splicing and cause mRNA instability. In the present study, we specifically investigated whether common G6721T genetic variant of XRCC7 was associated with an altered risk of breast cancer. The present study included 362 females with breast cancer. Age frequency-matched controls (362 persons) were randomly selected from the healthy female blood donors, according to the age distribution of the cases. Using RFLP-PCR based method, the polymorphism of XRCC7 was determined. The TG (OR=1.20, 95% CI: 0.83-1.74, P=0.320) and TT (OR=1.01, 95% CI: 0.67-1.53, P=0.933) genotypes had no significant effect on risk of breast cancer, in comparison with the GG genotype. Our present findings indicate that the TT and TG genotypes were not associated with an altered breast cancer risk. Copyright © 2012 Elsevier B.V. All rights reserved.

Molecular genetics of breast cancer

International Nuclear Information System (INIS)

Radice, P.; Pierotti, M. A.

1997-01-01

In the last two decades, molecular studies have enlightened the complexity of the genetic alterations that occur in breast cancer cells. To date, more than 40 different genes or loci have been found to be altered in breast carcinomas. Although some of these genes, as for example ERBB2, appear to be mutated in a high proportion of cases, their mechanism of action and their role in the different stages of cancer development are still poorly understood. More recently, two major determinants of the inherited predisposition to breast cancer, BRCA1 and BRCA2, have been isolated. As a consequence, it is now possible to screen families with a positive history of breast carcinomas for the identification of mutations carriers, in order to address these individuals into adequate programs of cancer surveillance and prevention

Genetic variants in hormone-related genes and risk of breast cancer.

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Tess Clendenen

Full Text Available Sex hormones play a key role in the development of breast cancer. Certain polymorphic variants (SNPs and repeat polymorphisms in hormone-related genes are associated with sex hormone levels. However, the relationship observed between these genetic variants and breast cancer risk has been inconsistent. We conducted a case-control study nested within two prospective cohorts to assess the relationship between specific genetic variants in hormone-related genes and breast cancer risk. In total, 1164 cases and 2111 individually-matched controls were included in the study. We did not observe an association between potential functional genetic polymorphisms in the estrogen pathway, SHBG rs6259, ESR1 rs2234693, CYP19 rs10046 and rs4775936, and UGT1A1 rs8175347, or the progesterone pathway, PGR rs1042838, with the risk of breast cancer. Our results suggest that these genetic variants do not have a strong effect on breast cancer risk.

Genetic evidence linking lung cancer and COPD: a new perspective

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Crapo JD

2011-07-01

Full Text Available Robert P Young1,4, Raewyn J Hopkins1, Gregory D Gamble1, Carol Etzel2, Randa El-Zein2, James D Crapo31Department of Medicine and School of Biological Sciences, University of Auckland, Auckland, New Zealand; 2Department of Epidemiology, UT MD Anderson Cancer Center, Houston, TX, USA; 3National Jewish Health, Denver, CO, USA; 4Synergenz Biosciences Ltd, Auckland, New ZealandAbstract: Epidemiological studies indicate that tobacco smoke exposure accounts for nearly 90% of cases of chronic obstructive pulmonary disease (COPD and lung cancer. However, genetic factors may explain why 10%–30% of smokers develop these complications. This perspective reviews the evidence suggesting that COPD is closely linked to susceptibility to lung cancer and outlines the potential relevance of this observation. Epidemiological studies show that COPD is the single most important risk factor for lung cancer among smokers and predates lung cancer in up to 80% of cases. Genome-wide association studies of lung cancer, lung function, and COPD have identified a number of overlapping “susceptibility” loci. With stringent phenotyping, it has recently been shown that several of these overlapping loci are independently associated with both COPD and lung cancer. These loci implicate genes underlying pulmonary inflammation and apoptotic processes mediated by the bronchial epithelium, and link COPD with lung cancer at a molecular genetic level. It is currently possible to derive risk models for lung cancer that incorporate lung cancer-specific genetic variants, recently identified “COPD-related” genetic variants, and clinical variables. Early studies suggest that single nucleotide polymorphism-based risk stratification of smokers might help better target novel prevention and early diagnostic strategies in lung cancer.Keywords: lung cancer, chronic obstructive pulmonary disease, association study, single nucleotide polymorphism, risk model

The Impact of Mental Illness on Uptake of Genetic Counseling for Hereditary Breast Cancer and Ovarian Cancer in a Multiethnic Cohort of Breast Cancer Patients.

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Ackerman, Marra G; Shapiro, Peter A; Coe, Austin; Trivedi, Meghna S; Crew, Katherine D

2017-09-01

We evaluated whether mental illness is a barrier to genetic counseling for hereditary breast and ovarian cancer (HBOC) in multiethnic breast cancer patients. We conducted a retrospective analysis of 308 women with newly diagnosed breast cancer and eligible for HBOC genetic testing seen in the breast clinic of an academic, urban medical center from 2007 to 2015. Uptake of genetic services and history of mental health disorder (MHD), defined as a psychiatric diagnosis or treatment with an antidepressant, mood stabilizer, anxiolytic, or antipsychotic medication, were ascertained by medical chart review. The mean age at breast cancer diagnosis was 56 years, with 44% non-Hispanic whites, 37% Hispanics, and 15% non-Hispanic blacks. Ninety-nine (32%) women met study criteria for MHD, 73% had a genetics referral, 57% had genetic counseling, and 54% completed BRCA testing. Uptake of genetic counseling services did not differ by race/ethnicity or presence of MHD. In multivariable analysis, younger age at diagnosis, Ashkenazi Jewish heritage, and family history of breast cancer were associated with HBOC genetic counseling. A relatively high proportion of breast cancer patients eligible for HBOC genetic testing were referred to a genetic counselor and referral status did not vary by MHD or race/ethnicity. © 2017 Wiley Periodicals, Inc.

HSP90 Shapes the Consequences of Human Genetic Variation.

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Karras, Georgios I; Yi, Song; Sahni, Nidhi; Fischer, Máté; Xie, Jenny; Vidal, Marc; D'Andrea, Alan D; Whitesell, Luke; Lindquist, Susan

2017-02-23

HSP90 acts as a protein-folding buffer that shapes the manifestations of genetic variation in model organisms. Whether HSP90 influences the consequences of mutations in humans, potentially modifying the clinical course of genetic diseases, remains unknown. By mining data for >1,500 disease-causing mutants, we found a strong correlation between reduced phenotypic severity and a dominant (HSP90 ≥ HSP70) increase in mutant engagement by HSP90. Examining the cancer predisposition syndrome Fanconi anemia in depth revealed that mutant FANCA proteins engaged predominantly by HSP70 had severely compromised function. In contrast, the function of less severe mutants was preserved by a dominant increase in HSP90 binding. Reducing HSP90's buffering capacity with inhibitors or febrile temperatures destabilized HSP90-buffered mutants, exacerbating FA-related chemosensitivities. Strikingly, a compensatory FANCA somatic mutation from an "experiment of nature" in monozygotic twins both prevented anemia and reduced HSP90 binding. These findings provide one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Levels of Evidence: Cancer Genetics Studies (PDQ®)—Health Professional Version

Science.gov (United States)

Levels of Evidence for Cancer Genetics Studies addresses the process and challenges of developing evidence-based summaries. Get information about how to weigh the strength of the evidence from cancer genetics studies in this summary for clinicians.

Biology of lung cancer: genetic mutation, epithelial-mesenchymal transition, and cancer stem cells.

Science.gov (United States)

Aoi, Takashi

2016-09-01

At present, most cases of unresectable cancer cannot be cured. Genetic mutations, EMT, and cancer stem cells are three major issues linked to poor prognosis in such cases, all connected by inter- and intra-tumor heterogeneity. Issues on inter-/intra-tumor heterogeneity of genetic mutation could be resolved with recent and future technologies of deep sequencers, whereas, regarding such issues as the "same genome, different epigenome/phenotype", we expect to solve many of these problems in the future through further research in stem cell biology. We herein review and discuss the three major issues in the biology of cancers, especially from the standpoint of stem cell biology.

Establishing a Cancer Genetics Programme in Asia - the Singapore Experience

Directory of Open Access Journals (Sweden)

Chieng Wei-Shieng

2006-06-01

Full Text Available Abstract Cancer genetics is now an established oncology subspecialty with the primary prevention role of identifying high-risk individuals through genetic information for enrolment into screening and preventive programmes. Integrated into major Western centres since the late 1990s, such a programme has been established in Singapore since 2001. Our programme has evaluated 367 index patients comprising mainly breast and colorectal cancer cases. Cancer patients were receptive to genetic counselling, but cost posed a major barrier to genetic testing. However, when the cost barrier was removed through government subsidy plans, more than half of high-risk patients still declined testing. The major barriers were reluctance to involve family members, perception that the information would not change management, and fears of negative feelings. Confirmed mutation carriers were compliant to screening and receptive to prophylactic surgery. Uptake of predictive testing among cancer-free family members has been low, possibly arising from the stigma associated with cancer in our Asian culture. These potential barriers are being addressed through government subsidy plans, continuing education to increase awareness, and being culturally sensitive when dealing with the Asian family.

Breast Cancer in Men: Treatments and Genetic Counseling

Science.gov (United States)

... Products For Consumers Home For Consumers Consumer Updates Breast Cancer in Men: Treatments and Genetic Counseling Share Tweet ... knowledge for others with this disease,” Prowell says. Breast Cancer Symptoms for Men Each year, about 2,000 ...

Psychological impact of genetic counseling for hereditary nonpolyposis colorectal cancer: the role of cancer history, gender, age, and psychological distress.

Science.gov (United States)

Hasenbring, Monika I; Kreddig, Nina; Deges, Gabriele; Epplen, Joerg T; Kunstmann, Erdmute; Stemmler, Susanne; Schulmann, Karsten; Willert, Joerg; Schmiegel, Wolf

2011-04-01

We prospectively examined the impact of an initial interdisciplinary genetic counseling (human geneticist, oncologist, and psycho-oncologist) on feelings of anxiety with a special focus on subgroups related to personal cancer history, gender, age, and education. At baseline, cancer-affected men revealed a significantly higher level of anxiety than unaffected men (pDepression Scale-A cases can be predicted by general distress (Brief Symptom Inventory) as well as by hereditary nonpolyposis colorectal cancer-related cognitions of intrusion and avoidance (impact of event scale) with a correct classification of 86%. Although initial hereditary nonpolyposis colorectal cancer counseling leads to an overall reduction of anxiety, differential effects of cancer history, gender, and age focus on subgroups of cancer-affected men, who may display unexpectedly high anxiety scores at baseline. Especially younger men do not seem to reduce this high anxiety level. Baseline anxiety was mainly determined by maladaptive situation-specific cognitions. Therefore, consulters should be more aware of anxiety-related cognitions in cancer-affected younger men.

Frequency of human papillomavirus infection in patients with gastrointestinal cancer.

Science.gov (United States)

Roesch-Dietlen, F; Cano-Contreras, A D; Sánchez-Maza, Y J; Espinosa-González, J M; Vázquez-Prieto, M Á; Valdés-de la O, E J; Díaz-Roesch, F; Carrasco-Arroniz, M Á; Cruz-Palacios, A; Grube-Pagola, P; Sumoza-Toledo, A; Vivanco-Cid, H; Mellado-Sánchez, G; Meixueiro-Daza, A; Silva-Cañetas, C S; Carrillo-Toledo, M G; Lagunes-Torres, R; Amieva-Balmori, M; Gómez-Castaño, P C; Reyes-Huerta, J U; Remes-Troche, J M

2018-02-15

Cancer is the result of the interaction of genetic and environmental factors. It has recently been related to viral infections, one of which is human papillomavirus. The aim of the present study was to describe the frequency of human papillomavirus infection in patients with digestive system cancers. A prospective, multicenter, observational study was conducted on patients with gastrointestinal cancer at 2public healthcare institutes in Veracruz. Two tumor samples were taken, one for histologic study and the other for DNA determination of human papillomavirus and its genotypes. Anthropometric variables, risk factors, sexual habits, tumor location, and histologic type of the cancer were analyzed. Absolute and relative frequencies were determined using the SPSS version 24.0 program. Fifty-three patients were studied. They had gastrointestinal cancer located in: the colon (62.26%), stomach (18.87%), esophagus (7.55%), rectum (7.55%), and small bowel (3.77%). Human papillomavirus was identified in 11.32% of the patients, 66.7% of which corresponded to squamous cell carcinoma and 33.3% to adenocarcinoma. Only genotype 18 was identified. Mean patient age was 61.8±15.2 years, 56.60% of the patients were men, and 43.40% were women. A total of 15.8% of the patients had a family history of cancer and 31.6% had a personal history of the disease, 38.6% were tobacco smokers, and 61.4% consumed alcohol. Regarding sex, 5.3% of the patients said they were homosexual, 3.5% were bisexual, 29.8% engaged in oral sex, and 24.6% in anal sex. Our study showed that human papillomavirus infection was a risk factor for the development of gastrointestinal cancer, especially of squamous cell origin. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Human BLCAP transcript: new editing events in normal and cancerous tissues.

Science.gov (United States)

Galeano, Federica; Leroy, Anne; Rossetti, Claudia; Gromova, Irina; Gautier, Philippe; Keegan, Liam P; Massimi, Luca; Di Rocco, Concezio; O'Connell, Mary A; Gallo, Angela

2010-07-01

Bladder cancer-associated protein (BLCAP) is a highly conserved protein among species, and it is considered a novel candidate tumor suppressor gene originally identified from human bladder carcinoma. However, little is known about the regulation or the function of this protein. Here, we show that the human BLCAP transcript undergoes multiple A-to-I editing events. Some of the new editing events alter the highly conserved amino terminus of the protein creating alternative protein isoforms by changing the genetically coded amino acids. We found that both ADAR1 and ADAR2-editing enzymes cooperate to edit this transcript and that different tissues displayed distinctive ratios of edited and unedited BLCAP transcripts. Moreover, we observed a general decrease in BLCAP-editing level in astrocytomas, bladder cancer and colorectal cancer when compared with the related normal tissues. The newly identified editing events, found to be downregulated in cancers, could be useful for future studies as a diagnostic tool to distinguish malignancies or epigenetic changes in different tumors.

Archives: Egyptian Journal of Medical Human Genetics

African Journals Online (AJOL)

Items 1 - 34 of 34 ... Archives: Egyptian Journal of Medical Human Genetics. Journal Home > Archives: Egyptian Journal of Medical Human Genetics. Log in or Register to get access to full text downloads.

An overview of human genetic privacy.

Science.gov (United States)

Shi, Xinghua; Wu, Xintao

2017-01-01

The study of human genomics is becoming a Big Data science, owing to recent biotechnological advances leading to availability of millions of personal genome sequences, which can be combined with biometric measurements from mobile apps and fitness trackers, and of human behavior data monitored from mobile devices and social media. With increasing research opportunities for integrative genomic studies through data sharing, genetic privacy emerges as a legitimate yet challenging concern that needs to be carefully addressed, not only for individuals but also for their families. In this paper, we present potential genetic privacy risks and relevant ethics and regulations for sharing and protecting human genomics data. We also describe the techniques for protecting human genetic privacy from three broad perspectives: controlled access, differential privacy, and cryptographic solutions. © 2016 New York Academy of Sciences.

An overview of human genetic privacy

Science.gov (United States)

Shi, Xinghua; Wu, Xintao

2016-01-01

The study of human genomics is becoming a Big Data science, owing to recent biotechnological advances leading to availability of millions of personal genome sequences, which can be combined with biometric measurements from mobile apps and fitness trackers, and of human behavior data monitored from mobile devices and social media. With increasing research opportunities for integrative genomic studies through data sharing, genetic privacy emerges as a legitimate yet challenging concern that needs to be carefully addressed, not only for individuals but also for their families. In this paper, we present potential genetic privacy risks and relevant ethics and regulations for sharing and protecting human genomics data. We also describe the techniques for protecting human genetic privacy from three broad perspectives: controlled access, differential privacy, and cryptographic solutions. PMID:27626905

Genetic testing and your cancer risk

Science.gov (United States)

... patientinstructions/000842.htm Genetic testing and your cancer risk To use the sharing features on this page, ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Genetic and cellular studies highlight that A Disintegrin and Metalloproteinase 19 is a protective biomarker in human prostate cancer

International Nuclear Information System (INIS)

Hoyne, Gerard; Rudnicka, Caroline; Sang, Qing-Xiang; Roycik, Mark; Howarth, Sarah; Leedman, Peter; Schlaich, Markus; Candy, Patrick; Matthews, Vance

2016-01-01

Prostate cancer is the second most frequently diagnosed cancer in men worldwide. Current treatments include surgery, androgen ablation and radiation. Introduction of more targeted therapies in prostate cancer, based on a detailed knowledge of the signalling pathways, aims to reduce side effects, leading to better clinical outcomes for the patient. ADAM19 (A Disintegrin And Metalloproteinase 19) is a transmembrane and soluble protein which can regulate cell phenotype through cell adhesion and proteolysis. ADAM19 has been positively associated with numerous diseases, but has not been shown to be a tumor suppressor in the pathogenesis of any human cancers. Our group sought to investigate the role of ADAM19 in human prostate cancer. ADAM19 mRNA and protein levels were assessed in well characterised human prostate cancer cohorts. ADAM19 expression was assessed in normal prostate epithelial cells (RWPE-1) and prostate cancer cells (LNCaP, PC3) using western blotting and immunocytochemistry. Proliferation assays were conducted in LNCaP cells in which ADAM19 was over-expressed. In vitro scratch assays were performed in PC3 cells over-expressing ADAM19. Immunohistochemical studies highlighted that ADAM19 protein levels were elevated in normal prostate tissue compared to prostate cancer biopsies. Results from the clinical cohorts demonstrated that high levels of ADAM19 in microarrays are positively associated with lower stage (p = 0.02591) and reduced relapse (p = 0.00277) of human prostate cancer. In vitro, ADAM19 expression was higher in RWPE-1 cells compared to LNCaP cells. In addition, human ADAM19 over-expression reduced LNCaP cell proliferation and PC3 cell migration. Taken together, our immunohistochemical and microarray results and cellular studies have shown for the first time that ADAM19 is a protective factor for human prostate cancer. Further, this study suggests that upregulation of ADAM19 expression could be of therapeutic potential in human prostate cancer

CRISPR-Cas9: a promising genetic engineering approach in cancer research

Science.gov (United States)

Ratan, Zubair Ahmed; Son, Young-Jin; Uddin, Bhuiyan Mohammad Mahtab; Yusuf, Md. Abdullah; Zaman, Sojib Bin; Kim, Jong-Hoon; Banu, Laila Anjuman

2018-01-01

Bacteria and archaea possess adaptive immunity against foreign genetic materials through clustered regularly interspaced short palindromic repeat (CRISPR) systems. The discovery of this intriguing bacterial system heralded a revolutionary change in the field of medical science. The CRISPR and CRISPR-associated protein 9 (Cas9) based molecular mechanism has been applied to genome editing. This CRISPR-Cas9 technique is now able to mediate precise genetic corrections or disruptions in in vitro and in vivo environments. The accuracy and versatility of CRISPR-Cas have been capitalized upon in biological and medical research and bring new hope to cancer research. Cancer involves complex alterations and multiple mutations, translocations and chromosomal losses and gains. The ability to identify and correct such mutations is an important goal in cancer treatment. In the context of this complex cancer genomic landscape, there is a need for a simple and flexible genetic tool that can easily identify functional cancer driver genes within a comparatively short time. The CRISPR-Cas system shows promising potential for modeling, repairing and correcting genetic events in different types of cancer. This article reviews the concept of CRISPR-Cas, its application and related advantages in oncology. PMID:29434679

Molecular genetic approach for screening of hereditary non-polyposis colorectal cancer

Directory of Open Access Journals (Sweden)

Metka Ravnik-Glavač

2005-07-01

Full Text Available Background: The main goal of knowledge concerning human diseases is to transfer as much as possible useful information into clinical applications. Hereditary non-polyposis colorectal cancer (HNPCC is the most common autosomal dominant inherited predisposition for colorectal cancer, accounting for 1–2% of all bowel cancer. The only way to diagnose HNPCC is by a family history consistent with the disease defined by International Collaborative Group on HNPCC (Amsterdam criteria I and II. The main molecular cause of HNPCC is a constitutional mutation in one of the mismatch repair (MMR genes. Since HNPCC mutations have been detected also in families that did not fulfil the Amsterdam criteria, molecular genetic characteristics of HNPCC cancers have been proposed as valuable first step in HNPCC identification. Microsatellite instability is present in about 90% of cancers of HNPCC patients. However, of all MSI colorectal cancers 80– 90% are sporadic. Several molecular mechanisms have been uncovered that enable distinguishing to some extent between sporadic and HNPCC cancers with MSI including hypermethylation of hMLH1 promoter and frequent mutations in BAX and TGFBR2 in sporadic CRC with MSI-H.Conclusions: The determination of MSI status and careful separation of MSI positive colorectal cancer into sporadic MSIL, sporadic MSI-H, and HNPCC MSI-H followed by mutation detection in MMR genes is important for prevention, screening and management of colorectal cancer. In some studies we and others have already shown that large-scale molecular genetic analysis for HNPCC can be done and is sensitive enough to approve population screening. Population screening includes also colonoscopy which is restricted only to the obligate carriers of the mutation. This enables that the disease is detected in earlier stages which would greatly decrease medical treatment costs and most importantly decrease mortality. In Slovenia we have started population screening based

Endogenous retroviral promoter exaptation in human cancer

Directory of Open Access Journals (Sweden)

Artem Babaian

2016-12-01

Full Text Available Abstract Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes. Aberrant expression of coding genes or long non-coding RNAs (lncRNAs with oncogenic properties can be caused by translocations, gene amplifications, point mutations or other less characterized mechanisms. One such mechanism is the inappropriate usage of normally dormant, tissue-restricted or cryptic enhancers or promoters that serve to drive oncogenic gene expression. Dispersed across the human genome, endogenous retroviruses (ERVs provide an enormous reservoir of autonomous gene regulatory modules, some of which have been co-opted by the host during evolution to play important roles in normal regulation of genes and gene networks. This review focuses on the “dark side” of such ERV regulatory capacity. Specifically, we discuss a growing number of examples of normally dormant or epigenetically repressed ERVs that have been harnessed to drive oncogenes in human cancer, a process we term onco-exaptation, and we propose potential mechanisms that may underlie this phenomenon.

Genetics of Prostate Cancer (PDQ®)—Health Professional Version

Science.gov (United States)

Familial prostate cancer is associated with certain inherited gene mutations (variants). Learn about the hereditary prostate cancer genes, genetic testing, clinical management, and psychosocial issues in this expert-reviewed summary.

Non-codingRNA sequence variations in human chronic lymphocytic leukemia and colorectal cancer.

Science.gov (United States)

Wojcik, Sylwia E; Rossi, Simona; Shimizu, Masayoshi; Nicoloso, Milena S; Cimmino, Amelia; Alder, Hansjuerg; Herlea, Vlad; Rassenti, Laura Z; Rai, Kanti R; Kipps, Thomas J; Keating, Michael J; Croce, Carlo M; Calin, George A

2010-02-01

Cancer is a genetic disease in which the interplay between alterations in protein-coding genes and non-coding RNAs (ncRNAs) plays a fundamental role. In recent years, the full coding component of the human genome was sequenced in various cancers, whereas such attempts related to ncRNAs are still fragmentary. We screened genomic DNAs for sequence variations in 148 microRNAs (miRNAs) and ultraconserved regions (UCRs) loci in patients with chronic lymphocytic leukemia (CLL) or colorectal cancer (CRC) by Sanger technique and further tried to elucidate the functional consequences of some of these variations. We found sequence variations in miRNAs in both sporadic and familial CLL cases, mutations of UCRs in CLLs and CRCs and, in certain instances, detected functional effects of these variations. Furthermore, by integrating our data with previously published data on miRNA sequence variations, we have created a catalog of DNA sequence variations in miRNAs/ultraconserved genes in human cancers. These findings argue that ncRNAs are targeted by both germ line and somatic mutations as well as by single-nucleotide polymorphisms with functional significance for human tumorigenesis. Sequence variations in ncRNA loci are frequent and some have functional and biological significance. Such information can be exploited to further investigate on a genome-wide scale the frequency of genetic variations in ncRNAs and their functional meaning, as well as for the development of new diagnostic and prognostic markers for leukemias and carcinomas.

Ethical, legal and social implications of prenatal and preimplantation genetic testing for cancer susceptibility.

Science.gov (United States)

Wang, C-W; Hui, E C

2009-01-01

With the progress in cancer genetics and assisted reproductive technologies, it is now possible for cancer gene mutation carriers not only to reduce cancer mortality through the targeting of surveillance and preventive therapies, but also to avoid the birth of at-risk babies through the choice of different means of reproduction. Thus, the incidence of hereditary cancer syndromes may be decreased in the future. The integration of cancer genetic testing and assisted reproductive technologies raises certain ethical, legal and social issues beyond either genetic testing or assisted reproductive technology itself. In this paper, the reproductive decisions/choices of at-risk young couples and the ethical, legal and social concerns of prenatal genetic testing and preimplantation genetic diagnosis for susceptibility to hereditary cancer syndromes are discussed. Specifically, three ethical principles related to the integration of cancer genetic testing and assisted reproductive technologies, i.e. informed choice, beneficence to children and social justice, and their implications for the responsible translation of these medical techniques into common practice of preventive medicine are highlighted.

Mutation and Expression of the DCC Gene in Human Lung Cancer

Directory of Open Access Journals (Sweden)

Takashi Kohno

2000-07-01

Full Text Available Chromosome 18q is frequently deleted in lung cancers, a common region of 18q deletions was mapped to chromosome 18g21. Since the DCC candidate tumor suppressor gene has been mapped in this region, mutation and expression of the DCC gene were examined in 46 lung cancer cell lines, consisting of 14 small cell lung carcinomas (SCLCs and 32 non-small cell lung carcinomas (NSCLCs, to elucidate the pathogenetic significance of DCC alterations in human lung carcinogenesis. A heterozygous missense mutation was detected in a NSCLC cell line, Ma26, while homozygous deletion was not detected in any of the cell lines. The DCC gene was expressed in 11 (24% of the 46 cell lines, the incidence of DCC expression was significantly higher in SCLCs (7/14, 50% than in NSCLCs (4/32, 13% (P = .01, Fisher's exact test. Therefore, genetic alterations of DCC are infrequent; however, the levels of DCC expression vary among lung cancer cells, in particular, between SCLCs and NSCLCs. The present result does not implicate DCC as a specific mutational target of 18q deletions in human lung cancer; however, it suggests that DCC is a potential target of inactivation by genetic defects including intron or promoter mutations and/or epigenetic alterations. The present result also suggests that DCC expression is associated with some properties of SCLCs, such as a neuroendocrine (NE feature.

Synthetic Genetic Targeting of Genome Instability in Cancer

International Nuclear Information System (INIS)

Sajesh, Babu V.; Guppy, Brent J.; McManus, Kirk J.

2013-01-01

Cancer is a leading cause of death throughout the World. A limitation of many current chemotherapeutic approaches is that their cytotoxic effects are not restricted to cancer cells, and adverse side effects can occur within normal tissues. Consequently, novel strategies are urgently needed to better target cancer cells. As we approach the era of personalized medicine, targeting the specific molecular defect(s) within a given patient’s tumor will become a more effective treatment strategy than traditional approaches that often target a given cancer type or sub-type. Synthetic genetic interactions are now being examined for their therapeutic potential and are designed to target the specific genetic and epigenetic phenomena associated with tumor formation, and thus are predicted to be highly selective. In general, two complementary approaches have been employed, including synthetic lethality and synthetic dosage lethality, to target aberrant expression and/or function associated with tumor suppressor genes and oncogenes, respectively. Here we discuss the concepts of synthetic lethality and synthetic dosage lethality, and explain three general experimental approaches designed to identify novel genetic interactors. We present examples and discuss the merits and caveats of each approach. Finally, we provide insight into the subsequent pre-clinical work required to validate novel candidate drug targets

Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017

NARCIS (Netherlands)

V.N. Giri (Veda); Knudsen, K.E. (Karen E.); Kelly, W.K. (William K.); Abida, W. (Wassim); G.L. Andriole (Gerald); C.H. Bangma (Chris); Bekelman, J.E. (Justin E.); Benson, M.C. (Mitchell C.); A. Blanco (Amie); Burnett, A. (Arthur); Catalona, W.J. (William J.); Cooney, K.A. (Kathleen A.); M.R. Cooperberg (Matthew); D. Crawford (David); Den, R.B. (Robert B.); Dicker, A.P. (Adam P.); S. Eggener (Scott); N.E. Fleshner (Neil); Freedman, M.L. (Matthew L.); F. Hamdy (Freddie); Hoffman-Censits, J. (Jean); Hurwitz, M.D. (Mark D.); Hyatt, C. (Colette); Isaacs, W.B. (William B.); Kane, C.J. (Christopher J.); Kantoff, P. (Philip); R.J. Karnes (Jeffrey); Karsh, L.I. (Lawrence I.); Klein, E.A. (Eric A.); Lin, D.W. (Daniel W.); Loughlin, K.R. (Kevin R.); Lu-Yao, G. (Grace); Malkowicz, S.B. (S. Bruce); Mann, M.J. (Mark J.); Mark, J.R. (James R.); McCue, P.A. (Peter A.); Miner, M.M. (Martin M.); Morgan, T. (Todd); Moul, J.W. (Judd W.); Myers, R.E. (Ronald E.); Nielsen, S.M. (Sarah M.); Obeid, E. (Elias); Pavlovich, C.P. (Christian P.); Peiper, S.C. (Stephen C.); D.F. Penson (David F.); D.P. Petrylak (Daniel P); Pettaway, C.A. (Curtis A.); R. Pilarski (Robert); P. Pinto (Peter); Poage, W. (Wendy); Raj, G.V. (Ganesh V.); R. Rebbeck (Timothy); M. Robson (Mark); Rosenberg, M.T. (Matt T.); Sandler, H. (Howard); A.O. Sartor (Oliver); Schaeffer, E. (Edward); Schwartz, G.F. (Gordon F.); Shahin, M.S. (Mark S.); N.D. Shore (Neal); Shuch, B. (Brian); Soule, H.R. (Howard R.); S.A. Tomlins (Scott A); Trabulsi, E.J. (Edouard J.); Uzzo, R. (Robert); Griend, D.J.V. (Donald J. Vander); P.C. Walsh (Patrick); Weil, C.J. (Carol J.); Wender, R. (Richard); Gomella, L.G. (Leonard G.)

2018-01-01

textabstractPurpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling,

A transcriptome anatomy of human colorectal cancers

International Nuclear Information System (INIS)

Lü, Bingjian; Xu, Jing; Lai, Maode; Zhang, Hao; Chen, Jian

2006-01-01

Accumulating databases in human genome research have enabled integrated genome-wide study on complicated diseases such as cancers. A practical approach is to mine a global transcriptome profile of disease from public database. New concepts of these diseases might emerge by landscaping this profile. In this study, we clustered human colorectal normal mucosa (N), inflammatory bowel disease (IBD), adenoma (A) and cancer (T) related expression sequence tags (EST) into UniGenes via an in-house GetUni software package and analyzed the transcriptome overview of these libraries by GOTree Machine (GOTM). Additionally, we downloaded UniGene based cDNA libraries of colon and analyzed them by Xprofiler to cross validate the efficiency of GetUni. Semi-quantitative RT-PCR was used to validate the expression of β-catenin and. 7 novel genes in colorectal cancers. The efficiency of GetUni was successfully validated by Xprofiler and RT-PCR. Genes in library N, IBD and A were all found in library T. A total of 14,879 genes were identified with 2,355 of them having at least 2 transcripts. Differences in gene enrichment among these libraries were statistically significant in 50 signal transduction pathways and Pfam protein domains by GOTM analysis P < 0.01 Hypergeometric Test). Genes in two metabolic pathways, ribosome and glycolysis, were more enriched in the expression profiles of A and IBD than in N and T. Seven transmembrane receptor superfamily genes were typically abundant in cancers. Colorectal cancers are genetically heterogeneous. Transcription variants are common in them. Aberrations of ribosome and glycolysis pathway might be early indicators of precursor lesions in colon cancers. The electronic gene expression profile could be used to highlight the integral molecular events in colorectal cancers

[Assisted Reproduction and Preimplantation Genetic Diagnosis in Patients Susceptible to Breast Cancer].

Science.gov (United States)

Veselá, K; Kocur, T; Horák, J; Horňák, M; Oráčová, E; Hromadová, L; Veselý, J; Trávník, P

2016-01-01

Assisted reproduction, as well as pregnancy itself, in patients with breast cancer or other hereditary type of cancer, is a widely discussed topic. In the past, patients treated for breast cancer were rarely involved in the discussion about reproductive possibilities or infertility treatment. However, current knowledge suggests, that breast cancer is neither a contraindication to pregnancy, nor to assisted reproduction techniques. On the contrary, assisted reproduction and preimplantation genetic diagnosis methods might prevent the transmission of genetic risks to the fetus. In this review we summarize data concerning pregnancy risks in patients with increased risk of breast cancer. In addition, we introduce current possibilities and approaches to fertility preservation prior to assisted reproduction treatment as well as novel methods improving the safety of fertility treatment. In the second part of this review, we focus on karyomapping--an advanced molecular genetic tool for elimination of germinal mutations in patients with predisposition to cancer. Moreover, the rapid development of preimplantation genetic diagnosis methods contributes to detection of both chromosomal aneuploidy and causal mutations in a relatively short time-span.

HCSD: the human cancer secretome database

DEFF Research Database (Denmark)

Feizi, Amir; Banaei-Esfahani, Amir; Nielsen, Jens

2015-01-01

The human cancer secretome database (HCSD) is a comprehensive database for human cancer secretome data. The cancer secretome describes proteins secreted by cancer cells and structuring information about the cancer secretome will enable further analysis of how this is related with tumor biology...... database is limiting the ability to query the increasing community knowledge. We therefore developed the Human Cancer Secretome Database (HCSD) to fulfil this gap. HCSD contains >80 000 measurements for about 7000 nonredundant human proteins collected from up to 35 high-throughput studies on 17 cancer...

Modeling Human Cancers in Drosophila.

Science.gov (United States)

Sonoshita, M; Cagan, R L

2017-01-01

Cancer is a complex disease that affects multiple organs. Whole-body animal models provide important insights into oncology that can lead to clinical impact. Here, we review novel concepts that Drosophila studies have established for cancer biology, drug discovery, and patient therapy. Genetic studies using Drosophila have explored the roles of oncogenes and tumor-suppressor genes that when dysregulated promote cancer formation, making Drosophila a useful model to study multiple aspects of transformation. Not limited to mechanism analyses, Drosophila has recently been showing its value in facilitating drug development. Flies offer rapid, efficient platforms by which novel classes of drugs can be identified as candidate anticancer leads. Further, we discuss the use of Drosophila as a platform to develop therapies for individual patients by modeling the tumor's genetic complexity. Drosophila provides both a classical and a novel tool to identify new therapeutics, complementing other more traditional cancer tools. © 2017 Elsevier Inc. All rights reserved.

Lobular breast cancer: incidence and genetic and non-genetic risk factors.

Science.gov (United States)

Dossus, Laure; Benusiglio, Patrick R

2015-03-13

While most invasive breast cancers consist of carcinomas of the ductal type, about 10% are invasive lobular carcinomas. Invasive lobular and ductal carcinomas differ with respect to risk factors. Invasive lobular carcinoma is more strongly associated with exposure to female hormones, and therefore its incidence is more subject to variation. This is illustrated by US figures during the 1987 to 2004 period: after 12 years of increases, breast cancer incidence declined steadily from 1999 to 2004, reflecting among other causes the decreasing use of menopausal hormone therapy, and these variations were stronger for invasive lobular than for invasive ductal carcinoma. Similarly, invasive lobular carcinoma is more strongly associated with early menarche, late menopause and late age at first birth. As for genetic risk factors, four high-penetrance genes are tested in clinical practice when genetic susceptibility to breast cancer is suspected, BRCA1, BRCA2, TP53 and CDH1. Germline mutations in BRCA1 and TP53 are predominantly associated with invasive ductal carcinoma, while BRCA2 mutations are associated with both ductal and lobular cancers. CDH1, the gene coding for the E-cadherin adhesion protein, is of special interest as mutations are associated with invasive lobular carcinoma, but never with ductal carcinoma. It was initially known as the main susceptibility gene for gastric cancer of the diffuse type, but the excess of breast cancers of the lobular type in CDH1 families led researchers to identify it also as a susceptibility gene for invasive lobular carcinoma. The risk of invasive lobular carcinoma is high in female mutation carriers, as about 50% are expected to develop the disease. Carriers must therefore undergo intensive breast cancer screening, with, for example, yearly magnetic resonance imaging and mammogram starting at age 30 years.

Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

Directory of Open Access Journals (Sweden)

Christopher M. Fulkerson

2017-01-01

Full Text Available Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs.

Science.gov (United States)

Fulkerson, Christopher M; Dhawan, Deepika; Ratliff, Timothy L; Hahn, Noah M; Knapp, Deborah W

2017-01-01

Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

Genetics of Human and Canine Dilated Cardiomyopathy

OpenAIRE

Siobhan Simpson; Jennifer Edwards; Thomas F. N. Ferguson-Mignan; Malcolm Cobb; Nigel P. Mongan; Catrin S. Rutland

2015-01-01

Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In th...

Genetic and Non-genetic Factors Associated With Constipation in Cancer Patients Receiving Opioids.

Science.gov (United States)

Laugsand, Eivor A; Skorpen, Frank; Kaasa, Stein; Sabatowski, Rainer; Strasser, Florian; Fayers, Peter; Klepstad, Pål

2015-06-18

To examine whether the inter-individual variation in constipation among patients receiving opioids for cancer pain is associated with genetic or non-genetic factors. Cancer patients receiving opioids were included from 17 centers in 11 European countries. Intensity of constipation was reported by 1,568 patients on a four-point categorical scale. Non-genetic factors were included as covariates in stratified regression analyses on the association between constipation and 75 single-nucleotide polymorphisms (SNPs) within 15 candidate genes related to opioid- or constipation-signaling pathways (HTR3E, HTR4, HTR2A, TPH1, ADRA2A, CHRM3, TACR1, CCKAR, KIT, ARRB2, GHRL, ABCB1, COMT, OPRM1, and OPRD1). The non-genetic factors significantly associated with constipation were type of laxative, mobility and place of care among patients receiving laxatives (N=806), in addition to Karnofsky performance status and presence of metastases among patients not receiving laxatives (N=762) (Pconstipation. Five SNPs, rs1800532 in TPH1, rs1799971 in OPRM1, rs4437575 in ABCB1, rs10802789 in CHRM3, and rs2020917 in COMT were associated with constipation (Phospitalization, Karnofsky performance status, presence of metastases, and five SNPs within TPH1, OPRM1, ABCB1, CHRM3, and COMT may contribute to the variability in constipation among cancer patients treated with opioids. Knowledge of these factors may help to develop new therapies and to identify patients needing a more individualized approach to treatment.

African American women's limited knowledge and experiences with genetic counseling for hereditary breast cancer.

Science.gov (United States)

Sheppard, Vanessa B; Graves, Kristi D; Christopher, Juleen; Hurtado-de-Mendoza, Alejandra; Talley, Costellia; Williams, Karen Patricia

2014-06-01

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 employed to analyze interview data. Breast cancer survivors had more knowledge about genetic counseling and testing than participants who were unaffected with cancer. However, knowledge about genetic counseling was limited in both groups. Barriers to pursuing genetic counseling and testing included poor understanding of the genetic counseling and testing process, fear of carrying the mutation, concerns about discrimination, and cost. Motivators to participate in genetic counseling and testing included desire to help family members, insurance coverage, and potential of benefiting the larger African American community. Education efforts are needed to increase genetic counseling and testing awareness in the African American community.

Evaluating human genetic diversity

National Research Council Canada - National Science Library

... into human evolution and origins and serving as a springboard for important medical research. It also addresses issues of confidentiality and individual privacy for participants in genetic diversity research studies.

Genetic Alterations in Hungarian Patients with Papillary Thyroid Cancer.

Science.gov (United States)

Tobiás, Bálint; Halászlaki, Csaba; Balla, Bernadett; Kósa, János P; Árvai, Kristóf; Horváth, Péter; Takács, István; Nagy, Zsolt; Horváth, Evelin; Horányi, János; Járay, Balázs; Székely, Eszter; Székely, Tamás; Győri, Gabriella; Putz, Zsuzsanna; Dank, Magdolna; Valkusz, Zsuzsanna; Vasas, Béla; Iványi, Béla; Lakatos, Péter

2016-01-01

The incidence of thyroid cancers is increasing worldwide. Some somatic oncogene mutations (BRAF, NRAS, HRAS, KRAS) as well as gene translocations (RET/PTC, PAX8/PPAR-gamma) have been associated with the development of thyroid cancer. In our study, we analyzed these genetic alterations in 394 thyroid tissue samples (197 papillary carcinomas and 197 healthy). The somatic mutations and translocations were detected by Light Cycler melting method and Real-Time Polymerase Chain Reaction techniques, respectively. In tumorous samples, 86 BRAF (44.2%), 5 NRAS (3.1%), 2 HRAS (1.0%) and 1 KRAS (0.5%) mutations were found, as well as 9 RET/PTC1 (4.6%) and 1 RET/PTC3 (0.5%) translocations. No genetic alteration was seen in the non tumorous control thyroid tissues. No correlation was detected between the genetic variants and the pathological subtypes of papillary cancer as well as the severity of the disease. Our results are only partly concordant with the data found in the literature.

[A survey of willingness about genetic counseling and tests in patients of epithelial ovarian cancer].

Science.gov (United States)

Li, L; Qiu, L; Wu, M

2017-11-21

Objective: To analyze patients' tendency towards genetics counseling and tests based on a prospective cohort study on hereditary ovarian cancer. Methods: From February 2017 to June 2017, among 220 cases of epithelial ovarian cancer in Peking Union Medical College Hospital, we collected epidemiological, pathological and tendency towards genetics counseling and tests via medical records and questionnaire.All patients would get education about hereditary ovarian cancer by pamphlets and WeChat.If they would receive further counseling, a face to face interview and tests will be given. Results: Among all 220 patients, 10 (4.5%) denied further counseling.For 210 patients receiving genetic counseling, 170 (81%) accepted genetic tests.In multivariate analysis, risk factors relevant to acceptance of genetic tests included: being charged by physicians of gynecologic oncology for diagnosis and treatment, receiving counseling in genetic counseling clinics, and having family history of breast cancer.For patients denying genetic tests, there were many subjective reasons, among which, "still not understanding genetic tests" (25%) and "unable bear following expensive targeting medicine" . Conclusions: High proportion patients of epithelial ovarian cancer would accept genetic counseling and tests.Genetic counseling clinics for gynecologic oncology would further improve genetic tests for patients.

76 FR 28439 - Submission for OMB Review; Comment Request; NCI Cancer Genetics Services Directory Web-Based...

Science.gov (United States)

2011-05-17

...; Comment Request; NCI Cancer Genetics Services Directory Web-Based Application Form and Update Mailer... currently valid OMB control number. Proposed Collection: Title: NCI Cancer Genetics Services Directory Web... included in the NCI Cancer Genetics Services Directory on NCI's Cancer.gov Web site. The information...

Genetic and Non-genetic Factors Associated With Constipation in Cancer Patients Receiving Opioids

Science.gov (United States)

Laugsand, Eivor A; Skorpen, Frank; Kaasa, Stein; Sabatowski, Rainer; Strasser, Florian; Fayers, Peter; Klepstad, Pål

2015-01-01

Objectives: To examine whether the inter-individual variation in constipation among patients receiving opioids for cancer pain is associated with genetic or non-genetic factors. Methods: Cancer patients receiving opioids were included from 17 centers in 11 European countries. Intensity of constipation was reported by 1,568 patients on a four-point categorical scale. Non-genetic factors were included as covariates in stratified regression analyses on the association between constipation and 75 single-nucleotide polymorphisms (SNPs) within 15 candidate genes related to opioid- or constipation-signaling pathways (HTR3E, HTR4, HTR2A, TPH1, ADRA2A, CHRM3, TACR1, CCKAR, KIT, ARRB2, GHRL, ABCB1, COMT, OPRM1, and OPRD1). Results: The non-genetic factors significantly associated with constipation were type of laxative, mobility and place of care among patients receiving laxatives (N=806), in addition to Karnofsky performance status and presence of metastases among patients not receiving laxatives (N=762) (P<0.01). Age, gender, body mass index, cancer diagnosis, time on opioids, opioid dose, and type of opioid did not contribute to the inter-individual differences in constipation. Five SNPs, rs1800532 in TPH1, rs1799971 in OPRM1, rs4437575 in ABCB1, rs10802789 in CHRM3, and rs2020917 in COMT were associated with constipation (P<0.01). Only rs2020917 in COMT passed the Benjamini–Hochberg criterion for a 10% false discovery rate. Conclusions: Type of laxative, mobility, hospitalization, Karnofsky performance status, presence of metastases, and five SNPs within TPH1, OPRM1, ABCB1, CHRM3, and COMT may contribute to the variability in constipation among cancer patients treated with opioids. Knowledge of these factors may help to develop new therapies and to identify patients needing a more individualized approach to treatment. PMID:26087058

Novel genetic variants in miR-191 gene and familial ovarian cancer

International Nuclear Information System (INIS)

Shen, Jie; DiCioccio, Richard; Odunsi, Kunle; Lele, Shashikant B; Zhao, Hua

2010-01-01

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

Strategies for integrated analysis of genetic, epigenetic and gene expression variation in cancer: addressing the challenges

Directory of Open Access Journals (Sweden)

Louise Bruun Thingholm

2016-02-01

Full Text Available The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis. However, integration of heterogeneous measurements of biological variation is a non-trivial exercise due to the diversity of the human genome and the variety of output data formats and genome coverage obtained from the commonly used molecular platforms. This review article will provide an introduction to integration strategies used for analyzing genetic risk factors for cancer. We critically examine the ability of these strategies to handle the complexity of the human genome and also accommodate information about the biological and functional interactions between the elements that have been measured – making the assessment of disease risk against a composite genomic factor possible. The focus of this review is to provide an overview and introduction to the main strategies and to discuss where there is a need for further development.

Risk Perception and Psychological Distress in Genetic Counselling for Hereditary Breast and/or Ovarian Cancer.

Science.gov (United States)

Cicero, G; De Luca, R; Dorangricchia, P; Lo Coco, G; Guarnaccia, C; Fanale, D; Calò, V; Russo, A

2017-10-01

Oncological Genetic Counselling (CGO) allows the identification of a genetic component that increases the risk of developing a cancer. Individuals' psychological reactions are influenced by both the content of the received information and the subjective perception of their own risk of becoming ill or being a carrier of a genetic mutation. This study included 120 participants who underwent genetic counselling for breast and/or ovarian cancer. The aim of the study was to examine the relation between their cancer risk perception and the genetic risk during CGO before receiving genetic test results, considering the influence of some psychological variables, in particular distress, anxiety and depression. Participants completed the following tools during a psychological interview: a socio-demographic form, Cancer Risk Perception (CRP) and Genetic Risk Perception (GRP), Hospital Anxiety and Depression Scale (HADS) and Distress Thermometer (DT). The data seem to confirm our hypothesis. Positive and significant correlations were found between the observed variables. Moreover, genetic risk perception determined an increase in depressive symptomatology and cancer risk perception led to an increase in anxious symptomatology, specifically in participants during cancer treatment. The present results suggest the importance of assessing genetic and cancer risk perception in individuals who undergo CGO, to identify those who are at risk of a decrease in psychological well-being and of developing greater psychological distress.

Organoid Models of Human and Mouse Ductal Pancreatic Cancer

Science.gov (United States)

Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H.M.; Molenaar, I. Quintus; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G.J.; Clevers, Hans; Tuveson, David A.

2015-01-01

SUMMARY Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation and exhibit ductal- and disease stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy. PMID:25557080

Does the diagnosis of breast or ovarian cancer trigger referral to genetic counseling?

Science.gov (United States)

Powell, C Bethan; Littell, Ramey; Hoodfar, Elizabeth; Sinclair, Fiona; Pressman, Alice

2013-03-01

Kaiser Permanente Northern California is a large integrated health care delivery system in the United States that has guidelines for referring women with newly diagnosed BRCA1-and BRCA2-associated cancers for genetic counseling. This study assesses adherence to genetic counseling referral guidelines within this health system. Chart review was performed to identify patients with cancer who met the following pathology-based Kaiser Permanente Northern California guidelines for referral for genetic counseling: invasive breast cancer, younger than age 40; nonmucinous epithelial ovarian, fallopian tube, or peritoneal cancer, younger than age 60; women with synchronous or metachronous primary cancers of the breast and ovaries; and male breast cancer. We assessed compliance with referral guidelines. An electronic notice was sent to the managing physician of patients with newly diagnosed cancer to assess the feasibility of this intervention. A total of 340 patients were identified with breast cancer at younger than age 40 or with ovarian, peritoneal, or tubal cancer between January and June, 2008. Upon chart review, 105 of these patients met pathology-based criteria for referral to genetic counseling, of whom 47 (45%) were referred within the 2-year study period. Of the 67 subjects with breast cancer, 40 subjects (60%) were referred. In contrast, only 7 (21%) of 33 patients with ovarian cancer were referred (P < 0.001). A pilot study was performed to test the feasibility of notifying managing oncologists with an electronic letter alerting them of eligibility for genetic referral of patients with new diagnosis (n = 21). In the 3 to 6 months after this notification, 12 of these 21 patients were referred for counseling including 5 of 7 patients with a diagnosis of ovarian cancer. There is a missed opportunity for referring patients to genetic counseling, especially among patients with ovarian cancer. A pilot study suggests that alerting treating physicians is a feasible

Genetic Testing and Its Implications: Human Genetics Researchers Grapple with Ethical Issues.

Science.gov (United States)

Rabino, Isaac

2003-01-01

Contributes systematic data on the attitudes of scientific experts who engage in human genetics research about the pros, cons, and ethical implications of genetic testing. Finds that they are highly supportive of voluntary testing and the right to know one's genetic heritage. Calls for greater genetic literacy. (Contains 87 references.) (Author/NB)

Genetics of Breast and Gynecologic Cancers (PDQ®)—Health Professional Version

Science.gov (United States)

Genetics of Breast and Gynecologic Cancers includes information on BRCA1 and BRCA2 variants (breast and ovarian cancer) and Lynch syndrome (endometrial cancer). Get more information about hereditary breast and gynecologic cancer syndromes in this clinician summary.

Glycerol restores the p53 function in human lingual cancer cells bearing mutant p53

International Nuclear Information System (INIS)

Ota, Ichiro; Yane, Katsunari; Yuki, Kazue; Kanata, Hirokazu; Hosoi, Hiroshi; Miyahara, Hiroshi

2001-01-01

Mutations in p53, tumor suppressor gene, have recently been shown to have an impact on the clinical course of several human tumors, including head and neck cancers. The genetic status of the p53 gene has been focused on as the most important candidate among various cancer-related genes for prognosis-predictive assays of cancer therapy. We examined the restoration of radiation- or cisplatin (CDDP)-induced p53-dependent apoptosis in human lingual cancer cells. The results suggest that glycerol is effective in inducing a conformational change of p53 and restoring normal function of mutant p53, leading to enhanced radiosensitivity or chemosensitivity through the induction of apoptosis. We have also represented the same results in vivo as in vitro. Thus, this novel tool for enhancement of radiosensitivity or chemosensitivity in cancer cells bearing m p53 may be applicable for p53-targeted cancer therapy. (author)

CGPD: Cancer Genetics and Proteomics Database - A Dataset for Computational Analysis and Online Cancer Diagnostic Centre

Directory of Open Access Journals (Sweden)

Muhammad Rizwan Riaz

2014-06-01

Full Text Available Cancer Genetics and Proteomics Database (CGPD is a repository for genetics and proteomics data of those Homo sapiens genes which are involved in Cancer. These genes are categorized in the database on the basis of cancer type. 72 genes of 13 types of cancers are considered in this database yet. Primers, promoters and peptides of these genes are also made available. Primers provided for each gene, with their features and conditions given to facilitate the researchers, are useful in PCR amplification, especially in cloning experiments. CGPD also contains Online Cancer Diagnostic Center (OCDC. It also contains transcription and translation tools to assist research work in progressive manner. The database is publicly available at http://www.cgpd.comyr.com.

Basic Genetics: A Human Approach.

Science.gov (United States)

Biological Sciences Curriculum Study, Colorado Springs, CO. Center for Education in Human and Medical Genetics.

This document (which has the form of a magazine) provides a variety of articles, stories, editorials, letters, interviews, and other types of magazine features (such as book reviews) which focus on human genetics. In addition to providing information about the principles of genetics, nearly all of the sections in the "magazine" address moral,…

Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein-Barr Virus (EBV).

Science.gov (United States)

Lawson, James S; Salmons, Brian; Glenn, Wendy K

2018-01-01

Although the risk factors for breast cancer are well established, namely female gender, early menarche and late menopause plus the protective influence of early pregnancy, the underlying causes of breast cancer remain unknown. The development of substantial recent evidence indicates that a handful of viruses may have a role in breast cancer. These viruses are mouse mammary tumor virus (MMTV), bovine leukemia virus (BLV), human papilloma viruses (HPVs), and Epstein-Barr virus (EBV-also known as human herpes virus type 4). Each of these viruses has documented oncogenic potential. The aim of this review is to inform the scientific and general community about this recent evidence. MMTV and human breast cancer-the evidence is detailed and comprehensive but cannot be regarded as conclusive. BLV and human breast cancer-the evidence is limited. However, in view of the emerging information about BLV in human breast cancer, it is prudent to encourage the elimination of BLV in cattle, particularly in the dairy industry. HPVs and breast cancer-the evidence is substantial but not conclusive. The availability of effective preventive vaccines is a major advantage and their use should be encouraged. EBV and breast cancer-the evidence is also substantial but not conclusive. Currently, there are no practical means of either prevention or treatment. Although there is evidence of genetic predisposition, and cancer in general is a culmination of events, there is no evidence that inherited genetic traits are causal. The influence of oncogenic viruses is currently the major plausible hypothesis for a direct cause of human breast cancer.

Attitude towards pre-implantation genetic diagnosis for hereditary cancer

NARCIS (Netherlands)

Lammens, Chantal; Bleiker, Eveline; Aaronson, Neil; Vriends, Annette; Ausems, Margreet; Jansweijer, Maaike; Wagner, Anja; Sijmons, Rolf; van den Ouweland, Ans; van der Luijt, Rob; Spruijt, Liesbeth; Gómez García, Encarna; Ruijs, Mariëlle; Verhoef, Senno

2009-01-01

The use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer predisposition.

[Genetics and susceptibility to human papillomaviruses: epidermodysplasia verruciformis, a disease model].

Science.gov (United States)

Orth, Gérard

2010-06-01

The outcomes of infection by human papillomaviruses (HPV), both oncogenic and non oncogenic, show major interindividual variability The underlying genetic factors and mechanisms are poorly known, but their complexity is illustrated by epidermodysplasia verruciformis (EV), a rare autosomal recessive genodermatosis associated with a high risk of non melanoma skin cancer. This model disease is characterized by abnormal susceptibility to widespread betapapillomaviruses, including HPV-5, a virus associated with EV cancers. Most cases of EV are caused by a mutation that inactivates either of two related genes, EVER1 and EVER2. This inactivation likely compensates for the absence of a viral gene (E5 or E8) essential for HPV pathogenicity. Proteins E5 and E8 interfere with the interaction between EVER proteins and ZnT1, a zinc transporter EV is thus likely to represent a primary defect of intrinsic (constitutive) immunity or innate immunity to betapapillomaviruses, involving modulation of zinc homeostasis upon keratinocyte infection. It remains to be established which cellular genes are involved in intrinsic, innate or acquired immune responses to other human papillomaviruses, including oncogenic genital types.

Signature of genetic associations in oral cancer.

Science.gov (United States)

Sharma, Vishwas; Nandan, Amrita; Sharma, Amitesh Kumar; Singh, Harpreet; Bharadwaj, Mausumi; Sinha, Dhirendra Narain; Mehrotra, Ravi

2017-10-01

Oral cancer etiology is complex and controlled by multi-factorial events including genetic events. Candidate gene studies, genome-wide association studies, and next-generation sequencing identified various chromosomal loci to be associated with oral cancer. There is no available review that could give us the comprehensive picture of genetic loci identified to be associated with oral cancer by candidate gene studies-based, genome-wide association studies-based, and next-generation sequencing-based approaches. A systematic literature search was performed in the PubMed database to identify the loci associated with oral cancer by exclusive candidate gene studies-based, genome-wide association studies-based, and next-generation sequencing-based study approaches. The information of loci associated with oral cancer is made online through the resource "ORNATE." Next, screening of the loci validated by candidate gene studies and next-generation sequencing approach or by two independent studies within candidate gene studies or next-generation sequencing approaches were performed. A total of 264 loci were identified to be associated with oral cancer by candidate gene studies, genome-wide association studies, and next-generation sequencing approaches. In total, 28 loci, that is, 14q32.33 (AKT1), 5q22.2 (APC), 11q22.3 (ATM), 2q33.1 (CASP8), 11q13.3 (CCND1), 16q22.1 (CDH1), 9p21.3 (CDKN2A), 1q31.1 (COX-2), 7p11.2 (EGFR), 22q13.2 (EP300), 4q35.2 (FAT1), 4q31.3 (FBXW7), 4p16.3 (FGFR3), 1p13.3 (GSTM1-GSTT1), 11q13.2 (GSTP1), 11p15.5 (H-RAS), 3p25.3 (hOGG1), 1q32.1 (IL-10), 4q13.3 (IL-8), 12p12.1 (KRAS), 12q15 (MDM2), 12q13.12 (MLL2), 9q34.3 (NOTCH1), 17p13.1 (p53), 3q26.32 (PIK3CA), 10q23.31 (PTEN), 13q14.2 (RB1), and 5q14.2 (XRCC4), were validated to be associated with oral cancer. "ORNATE" gives a snapshot of genetic loci associated with oral cancer. All 28 loci were validated to be linked to oral cancer for which further fine-mapping followed by gene-by-gene and gene

Alternate service delivery models in cancer genetic counseling: a mini-review

Directory of Open Access Journals (Sweden)

Adam Hudson Buchanan

2016-05-01

Full Text Available Demand for cancer genetic counseling has grown rapidly in recent years as germline genomic information has become increasingly incorporated into cancer care and the field has entered the public consciousness through high-profile celebrity publications. Increased demand and existing variability in the availability of trained cancer genetics clinicians place a priority on developing and evaluating alternate service delivery models for genetic counseling. This mini-review summarizes the state of science regarding service delivery models such as telephone counseling, telegenetics and group counseling. Research on comparative effectiveness of these models in traditional individual, in-person genetic counseling has been promising for improving access to care in a manner acceptable to patients. Yet, it has not fully evaluated the short- and long-term patient- and system-level outcomes that will help answer the question of whether these models achieve the same beneficial psychosocial and behavioral outcomes as traditional cancer genetic counseling. We propose a research agenda focused on comparative effectiveness of available service delivery models and how to match models to patients and practice settings. Only through this rigorous research can clinicians and systems find the optimal balance of clinical quality, ready and secure access to care, and financial sustainability. Such research will be integral to achieving the promise of genomic medicine in oncology.

Genetic testing and its implications: human genetics researchers grapple with ethical issues.

Science.gov (United States)

Rabino, Isaac

2003-01-01

To better understand ethical issues involved in the field of human genetics and promote debate within the scientific community, the author surveyed scientists who engage in human genetics research about the pros, cons, and ethical implications of genetic testing. This study contributes systematic data on attitudes of scientific experts. The survey finds respondents are highly supportive of voluntary testing and the right to know one's genetic heritage. The majority consider in utero testing and consequent pregnancy termination acceptable for cases involving likelihood of serious disease but disapprove for genetic reasons they consider arbitrary, leaving a gray area of distinguishing between treatment of disorders and enhancement still to be resolved. While safeguarding patient confidentiality versus protecting at-risk third parties (kin, reproductive partners) presents a dilemma, preserving privacy from misuse by institutional third parties (employers, insurers) garners strong consensus for legislation against discrimination. Finally, a call is made for greater genetic literacy.

A genetic atlas of human admixture history.

Science.gov (United States)

Hellenthal, Garrett; Busby, George B J; Band, Gavin; Wilson, James F; Capelli, Cristian; Falush, Daniel; Myers, Simon

2014-02-14

Modern genetic data combined with appropriate statistical methods have the potential to contribute substantially to our understanding of human history. We have developed an approach that exploits the genomic structure of admixed populations to date and characterize historical mixture events at fine scales. We used this to produce an atlas of worldwide human admixture history, constructed by using genetic data alone and encompassing over 100 events occurring over the past 4000 years. We identified events whose dates and participants suggest they describe genetic impacts of the Mongol empire, Arab slave trade, Bantu expansion, first millennium CE migrations in Eastern Europe, and European colonialism, as well as unrecorded events, revealing admixture to be an almost universal force shaping human populations.

Host genetic variation impacts microbiome composition across human body sites.

Science.gov (United States)

Blekhman, Ran; Goodrich, Julia K; Huang, Katherine; Sun, Qi; Bukowski, Robert; Bell, Jordana T; Spector, Timothy D; Keinan, Alon; Ley, Ruth E; Gevers, Dirk; Clark, Andrew G

2015-09-15

The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale. Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes. Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.

Genetically modified dendritic cell-based cancer vaccines

Czech Academy of Sciences Publication Activity Database

Bubeník, Jan

2001-01-01

Roč. 47, č. 5 (2001), s. 153-155 ISSN 0015-5500 R&D Projects: GA MZd NC5526 Keywords : dendritic cell s * cancer vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.519, year: 2001

Epidemiology, major risk factors and genetic predisposition for breast cancer in the Pakistani population.

Science.gov (United States)

Shaukat, Uzma; Ismail, Muhammad; Mehmood, Nasir

2013-01-01

Occurrence of breast cancer is related to genetic as well as cultural, environmental and life-style factors. Variations in diversity of these factors among different ethnic groups and geographical areas emphasize the immense need for studies in all racial-ethnic populations. The incidence of breast cancer in Pakistan is highest in Asians after Jews in Israel and 2.5 times higher than that in neighboring countries like Iran and India, accounting for 34.6% of female cancers. The Pakistani population is deficient in information regarding breast cancer etiology and epidemiology, but efforts done so far had suggested consanguinity as a major risk factor for frequent mutations leading to breast cancer and has also shed light on genetic origins in different ethnic groups within Pakistan. World-wide research efforts on different ethnicities have enhanced our understanding of genetic predisposition to breast cancer but despite these discoveries, 75% of the familial risk of breast cancer remains unexplained, highlighting the fact that the majority of breast cancer susceptibility genes remain unidentified. For this purpose Pakistani population provides a strong genetic pool to elucidate the genetic etiology of breast cancer because of cousin marriages. In this review, we describe the known breast cancer predisposition factors found in the local Pakistani population and the epidemiological research work done to emphasize the importance of exploring factors/variants contributing to breast cance, in order to prevent, cure and decrease its incidence in our country.

[Genetic variants in miRNAs and its association with breast cancer].

Science.gov (United States)

Méndez-Gómez, Susana; Ruiz Esparza-Garrido, Ruth; Velázquez-Flores, Miguel; Dolores-Vergara, Maria; Salamanca-Gómez, Fabio; Arenas-Aranda, Diego Julio

2014-01-01

In Mexico, breast cancer represents the first cause of cancer death in females. At the molecular level, non-coding RNAs and especially microRNAs have played an important role in the origin and development of this neoplasm In the Anglo-Saxon population, diverse genetic variants in microRNA genes and in their targets are associated with the development of this disease. In the Mexican population it is not known if these or other variants exist. Identification of these or new variants in our population is fundamental in order to have a better understanding of cancer development and to help establish a better diagnostic strategy. DNA was isolated from mammary tumors, adjacent tissue and peripheral blood of Mexican females with or without cancer. From DNA, five microRNA genes and three of their targets were amplified and sequenced. Genetic variants associated with breast cancer in an Anglo- Saxon population have been previously identified in these sequences. In the samples studied we identified seven single nucleotide polymorphisms (SNPs). Two had not been previously described and were identified only in women with cancer. The new variants may be genetic predisposition factors for the development of breast cancer in our population. Further experiments are needed to determine the involvement of these variants in the development, establishment and progression of breast cancer.

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

Directory of Open Access Journals (Sweden)

Nunes Virginia

2008-01-01

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

African American Women’s Limited Knowledge and Experiences with Genetic Counseling for Hereditary Breast Cancer

Science.gov (United States)

Sheppard, Vanessa B.; Graves, Kristi D.; Christopher, Juleen; Hurtado-de-Mendoza, Alejandra; Talley, Costellia; Williams, Karen Patricia

2014-01-01

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 employed to analyze interview data. Breast cancer survivors had more knowledge about genetic counseling and testing than participants who were unaffected with cancer. However, knowledge about genetic counseling was limited in both groups. Barriers to pursuing genetic counseling and testing included poor understanding of the genetic counseling and testing process, fear of carrying the mutation, concerns about discrimination, and cost. Motivators to participate in genetic counseling and testing included desire to help family members, insurance coverage, and potential of benefiting the larger African American community. Education efforts are needed to increase genetic counseling and testing awareness in the African American community. PMID:24186304

A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0529 TITLE: A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk PRINCIPAL INVESTIGATOR...AND SUBTITLE A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1...STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer is the most commonly diagnosed cancer in

Influence of race/ethnicity on genetic counseling and testing for hereditary breast and ovarian cancer.

Science.gov (United States)

Forman, Andrea D; Hall, Michael J

2009-01-01

Risk assessment coupled with genetic counseling and testing for the cancer predisposition genes BRCA1 and BRCA2 (BRCA1/2) has become an integral element of comprehensive patient evaluation and cancer risk management in the United States for individuals meeting high-risk criteria for hereditary breast and ovarian cancer (HBOC). For mutation carriers, several options for risk modification have achieved substantial reductions in future cancer risk. However, several recent studies have shown lower rates of BRCA1/2 counseling and testing among minority populations. Here, we explore the role of race/ethnicity in cancer risk assessment, genetic counseling and genetic testing for HBOC and the BRCA1/2 cancer predisposition genes. Barriers to genetic services related to race/ethnicity and underserved populations, including socioeconomic barriers (e.g., time, access, geographic, language/cultural, awareness, cost) and psychosocial barriers (e.g., medical mistrust, perceived disadvantages to genetic services), as well as additional barriers to care once mutation carriers are identified, will be reviewed.

Human Cancer Models Initiative | Office of Cancer Genomics

Science.gov (United States)

The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer research.

Human genetic issues from scientific and Islamic perspectives | Alwi ...

African Journals Online (AJOL)

This paper aims at revealing the Human Genome Project (HGP) and human genetic issues arising from science and Islamic perspectives such as Darwin's evolutionary theory, human cloning and eugenics. Finally, issues arising from the applications of human genetic technology need to be addressed to the best possible ...

Ethnic Background and Genetic Variation in the Evaluation of Cancer Risk: A Systematic Review

OpenAIRE

Jing, Lijun; Su, Li; Ring, Brian Z.

2014-01-01

The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in ...

Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

DEFF Research Database (Denmark)

Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N

2015-01-01

Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address...... this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested...... that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We...

Study of human genetic diversity : inferences on population origin and history

OpenAIRE

Haber, Marc, 1980-

2013-01-01

Patterns of human genetic diversity suggest that all modern humans originated from a small population in Africa that expanded rapidly 50,000 years ago to occupy the whole world. While moving into new environments, genetic drift and natural selection affected populations differently, creating genetic structure. By understanding the genetic structure of human populations, we can reconstruct human history and understand the genetic basis of diseases. The work presented here contributes to the on...

A genetic atlas of human admixture history

Science.gov (United States)

Hellenthal, Garrett; Busby, George B.J.; Band, Gavin; Wilson, James F.; Capelli, Cristian

2014-01-01

Modern genetic data combined with appropriate statistical methods have the potential to contribute substantially to our understanding of human history. We have developed an approach that exploits the genomic structure of admixed populations to date and characterize historical mixture events at fine scales. We used this to produce an atlas of worldwide human admixture history, constructed using genetic data alone and encompassing over 100 events occurring over the past 4,000 years. We identify events whose dates and participants suggest they describe genetic impacts of the Mongol Empire, Arab slave trade, Bantu expansion, first millennium CE migrations in eastern Europe, and European colonialism, as well as unrecorded events, revealing admixture to be an almost universal force shaping human populations. PMID:24531965

Genetic Modification of the Lung Directed Toward Treatment of Human Disease.

Science.gov (United States)

Sondhi, Dolan; Stiles, Katie M; De, Bishnu P; Crystal, Ronald G

2017-01-01

Genetic modification therapy is a promising therapeutic strategy for many diseases of the lung intractable to other treatments. Lung gene therapy has been the subject of numerous preclinical animal experiments and human clinical trials, for targets including genetic diseases such as cystic fibrosis and α1-antitrypsin deficiency, complex disorders such as asthma, allergy, and lung cancer, infections such as respiratory syncytial virus (RSV) and Pseudomonas, as well as pulmonary arterial hypertension, transplant rejection, and lung injury. A variety of viral and non-viral vectors have been employed to overcome the many physical barriers to gene transfer imposed by lung anatomy and natural defenses. Beyond the treatment of lung diseases, the lung has the potential to be used as a metabolic factory for generating proteins for delivery to the circulation for treatment of systemic diseases. Although much has been learned through a myriad of experiments about the development of genetic modification of the lung, more work is still needed to improve the delivery vehicles and to overcome challenges such as entry barriers, persistent expression, specific cell targeting, and circumventing host anti-vector responses.

Human genetics of diabetic vascular complications

Indian Academy of Sciences (India)

Diabetic vascular complications (DVC) affecting several important organ systems of human body such as the cardiovascular system constitute a major public health problem. There is evidence demonstrating that genetic factors contribute to the risk of DVC genetic variants, structural variants, and epigenetic changes play ...

A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition

DEFF Research Database (Denmark)

Ropero, S; Fraga, MF; Ballestar, E

2006-01-01

Disruption of histone acetylation patterns is a common feature of cancer cells, but very little is known about its genetic basis. We have identified truncating mutations in one of the primary human histone deacetylases, HDAC2, in sporadic carcinomas with microsatellite instability and in tumors a...... deacetylase inhibitors. As such drugs may serve as therapeutic agents for cancer, our findings support the use of HDAC2 mutational status in future pharmacogenetic treatment of these individuals....

Cost sharing and hereditary cancer risk: predictors of willingness-to-pay for genetic testing.

Science.gov (United States)

Matro, Jennifer M; Ruth, Karen J; Wong, Yu-Ning; McCully, Katen C; Rybak, Christina M; Meropol, Neal J; Hall, Michael J

2014-12-01

Increasing use of predictive genetic testing to gauge hereditary cancer risk has been paralleled by rising cost-sharing practices. Little is known about how demographic and psychosocial factors may influence individuals' willingness-to-pay for genetic testing. The Gastrointestinal Tumor Risk Assessment Program Registry includes individuals presenting for genetic risk assessment based on personal/family cancer history. Participants complete a baseline survey assessing cancer history and psychosocial items. Willingness-to-pay items include intention for: genetic testing only if paid by insurance; testing with self-pay; and amount willing-to-pay ($25-$2,000). Multivariable models examined predictors of willingness-to-pay out-of-pocket (versus only if paid by insurance) and willingness-to-pay a smaller versus larger sum (≤$200 vs. ≥$500). All statistical tests are two-sided (α = 0.05). Of 385 evaluable participants, a minority (42%) had a personal cancer history, while 56% had ≥1 first-degree relative with colorectal cancer. Overall, 21.3% were willing to have testing only if paid by insurance, and 78.7% were willing-to-pay. Predictors of willingness-to-pay were: 1) concern for positive result; 2) confidence to control cancer risk; 3) fewer perceived barriers to colorectal cancer screening; 4) benefit of testing to guide screening (all p testing (all p testing, and anticipate benefits to reducing cancer risk. Identifying factors associated with willingness-to-pay for genetic services is increasingly important as testing is integrated into routine cancer care.

Genetic recombination between human and animal parasites creates novel strains of human pathogen.

Science.gov (United States)

Gibson, Wendy; Peacock, Lori; Ferris, Vanessa; Fischer, Katrin; Livingstone, Jennifer; Thomas, James; Bailey, Mick

2015-03-01

Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr) responsible for sleeping sickness (Human African Trypanosomiasis, HAT) in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT.

Genetic recombination between human and animal parasites creates novel strains of human pathogen.

Directory of Open Access Journals (Sweden)

Wendy Gibson

2015-03-01

Full Text Available Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr responsible for sleeping sickness (Human African Trypanosomiasis, HAT in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT.

Evaluating the Genetic, Hormonal, and Exogenous Factors Affecting Somatic Copy Number Variation in Breast Cancer

Science.gov (United States)

2016-10-01

assess genomic instability in different mammary epithelial populations in vivo and in vitro, 2) determine how mutations in heritable breast cancer genes...respectively, located on chromosome 6. When loci harboring the shRNAs are deleted by a spontaneous mutation event, affected cells become GFP and/or RFP...assay adapted from the yeast genetics literature, we will determine whether baseline deletion rates in normal human mammary epithelial cells (HMECs

Behavior genetic modeling of human fertility

DEFF Research Database (Denmark)

Rodgers, J L; Kohler, H P; Kyvik, K O

2001-01-01

Behavior genetic designs and analysis can be used to address issues of central importance to demography. We use this methodology to document genetic influence on human fertility. Our data come from Danish twin pairs born from 1953 to 1959, measured on age at first attempt to get pregnant (First......Try) and number of children (NumCh). Behavior genetic models were fitted using structural equation modeling and DF analysis. A consistent medium-level additive genetic influence was found for NumCh, equal across genders; a stronger genetic influence was identified for FirstTry, greater for females than for males....... A bivariate analysis indicated significant shared genetic variance between NumCh and FirstTry....

Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

OpenAIRE

Simpson, Siobhan; Dunning, Mark D.; de Brot, Simone; Grau-Roma, Llorenc; Mongan, Nigel P.; Rutland, Catrin S.

2017-01-01

Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is poor, with five year osteosarcoma survival rates in people not having improved in decades. For dogs, one year survival rates are only around ~45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with th...

Genetics of Endometrial Cancers

Directory of Open Access Journals (Sweden)

Tsuyoshi Okuda

2010-01-01

Full Text Available Endometrial cancers exhibit a different mechanism of tumorigenesis and progression depending on histopathological and clinical types. The most frequently altered gene in estrogen-dependent endometrioid endometrial carcinoma tumors is PTEN. Microsatellite instability is another important genetic event in this type of tumor. In contrast, p53 mutations or Her2/neu overexpression are more frequent in non-endometrioid tumors. On the other hand, it is possible that the clear cell type may arise from a unique pathway which appears similar to the ovarian clear cell carcinoma. K-ras mutations are detected in approximately 15%–30% of endometrioid carcinomas, are unrelated to the existence of endometrial hyperplasia. A β-catenin mutation was detected in about 20% of endometrioid carcinomas, but is rare in serous carcinoma. Telomere shortening is another important type of genomic instability observed in endometrial cancer. Only non-endometrioid endometrial carcinoma tumors were significantly associated with critical telomere shortening in the adjacent morphologically normal epithelium. Lynch syndrome, which is an autosomal dominantly inherited disorder of cancer susceptibility and is characterized by a MSH2/MSH6 protein complex deficiency, is associated with the development of non-endometrioid carcinomas.

Genetics of Colorectal Cancer (PDQ®)—Health Professional Version

Science.gov (United States)

Hereditary colorectal cancer syndromes include Lynch syndrome and several polyposis syndromes (familial adenomatous polyposis, MUTYH-associated polyposis, juvenile polyposis syndrome, Peutz-Jeghers syndrome, and serrated polyposis syndrome). Learn about the genetics, clinical manifestations, management, and psychosocial aspects of these and other hereditary colon cancer syndromes in this expert-reviewed summary.

INHIBITION OF SPONTANEOUS APOPTOSIS IN HUMAN BREAST CANCER

Institute of Scientific and Technical Information of China (English)

邵志敏; 江明; 吴炅; 余黎民; 韩企夏; 张延璆; 沈镇宙

1996-01-01

Breast tumorigenesis proceeds through an accumulation of specific genetic alteration. Breast malignant transformation is dependent on not only the rate of cell production but also on apoptcsis,a genetically prograined process of autonomous ceil death. We investigated whether breast tumorigenesis involved an altered susceptibility to apoptosis and proliferation by examining normal breast epithelium and breast cancer sampies. We found there is a great inhibition of spontaneous apoptosis in breast cancer ceils compared with normal breast epithelium. The inhibition of apoptosis in breast cancer may contribute to neoplastic transformation.

Genetic variation in bone morphogenetic protein (BMP) and colon and rectal cancer

Science.gov (United States)

Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Kadlubar, Susan; Caan, Bette J.; Potter, John D.; Wolff, Roger K.

2011-01-01

Bone morphogenetic proteins (BMP) are part of the TGF-β-signaling pathway; genetic variation in these genes may be involved in colorectal cancer. In this study we evaluated the association between genetic variation in BMP1 (11 tagSNPs), BMP2 (5 tagSNPs), BMP4 (3 tagSNPs), BMPR1A (9 tagSNPs), BMPR1B (21 tagSNPs), BMPR2 (11 tagSNPs), and GDF10 (7 tagSNPs) with risk of colon and rectal cancer and tumor molecular phenotype. We used data from population-based case-control studies (colon cancer n=1574 cases, 1970 controls; rectal cancer n=791 cases, 999 controls). We observed that genetic variation in BMPR1A, BMPR1B, BMPR2, BMP2, and BMP4 was associated with risk of developing colon cancer, with 20 to 30% increased risk for most high-risk genotypes. A summary of high-risk genotypes showed over a twofold increase in colon cancer risk at the upper risk category (OR 2.49 95% CI 1.95, 3.18). BMPR2, BMPR1B, BMP2, and GDF10 were associated with rectal cancer. BMPR2 rs2228545 was associated with an almost twofold increased risk of rectal cancer. The risk associated with the highest category of the summary score for rectal cancer was 2.97 (95% CI 1.87, 4.72). Genes in the BMP-signaling pathway were consistently associated with CIMP+ status in combination with both KRAS-mutated and MSI tumors. BMP genes interacted statistically significantly with other genes in the TGF-β-signaling pathway, including TGFβ1, TGFβR1, Smad 3, Smad 4, and Smad 7. Our data support a role for genetic variation in BMP-related genes in the etiology of colon and rectal cancer. One possible mechanism is via the TGF-β-signaling pathway. PMID:21387313

The influence of acculturation and breast cancer-specific distress on perceived barriers to genetic testing for breast cancer among women of African descent.

Science.gov (United States)

Sussner, Katarina M; Thompson, Hayley S; Jandorf, Lina; Edwards, Tiffany A; Forman, Andrea; Brown, Karen; Kapil-Pair, Nidhi; Bovbjerg, Dana H; Schwartz, Marc D; Valdimarsdottir, Heiddis B

2009-09-01

Rising health disparities are increasingly evident in relation to use of genetic services (including genetic counseling and testing) for breast cancer risk, with women of African descent less likely to use genetic services compared with Whites. Meanwhile, little is known regarding potential within-group acculturation and psychological differences underlying perceived barriers to genetic testing among women of African descent. Hypothesized contributions of acculturation factors and breast cancer-specific distress to perceived barriers to genetic testing were examined with a statistical analysis of baseline data from 146 women of African descent (56% US born and 44% foreign born) meeting genetic breast cancer risk criteria and participating in a larger longitudinal study that included the opportunity for free genetic counseling and testing. Perceived barriers assessed included: (1) anticipation of negative emotional reactions, (2) stigma, (3) confidentiality concerns, (4) family-related worry, and (5) family-related guilt associated with genetic testing. In multivariate analyses, being foreign born was a significant predictor of anticipated negative emotional reactions about genetic testing (beta=0.26; SE=0.11; p=0.01). Breast cancer-specific distress scores (avoidance symptoms) were positively related to anticipated negative emotional reactions (beta=0.02; SE=0.005; p=barriers to genetic testing among women of African descent. The potential utility of culturally tailored genetic counseling services taking into account such influences and addressing emotional and psychological concerns of women considering genetic testing for breast cancer should be investigated.

New genetic variants of LATS1 detected in urinary bladder and colon cancer.

Science.gov (United States)

Saadeldin, Mona K; Shawer, Heba; Mostafa, Ahmed; Kassem, Neemat M; Amleh, Asma; Siam, Rania

2014-01-01

LATS1, the large tumor suppressor 1 gene, encodes for a serine/threonine kinase protein and is implicated in cell cycle progression. LATS1 is down-regulated in various human cancers, such as breast cancer, and astrocytoma. Point mutations in LATS1 were reported in human sarcomas. Additionally, loss of heterozygosity of LATS1 chromosomal region predisposes to breast, ovarian, and cervical tumors. In the current study, we investigated LATS1 genetic variations including single nucleotide polymorphisms (SNPs), in 28 Egyptian patients with either urinary bladder or colon cancers. The LATS1 gene was amplified and sequenced and the expression of LATS1 at the RNA level was assessed in 12 urinary bladder cancer samples. We report, the identification of a total of 29 variants including previously identified SNPs within LATS1 coding and non-coding sequences. A total of 18 variants were novel. Majority of the novel variants, 13, were mapped to intronic sequences and un-translated regions of the gene. Four of the five novel variants located in the coding region of the gene, represented missense mutations within the serine/threonine kinase catalytic domain. Interestingly, LATS1 RNA steady state levels was lost in urinary bladder cancerous tissue harboring four specific SNPs (16045 + 41736 + 34614 + 56177) positioned in the 5'UTR, intron 6, and two silent mutations within exon 4 and exon 8, respectively. This study identifies novel single-base-sequence alterations in the LATS1 gene. These newly identified variants could potentially be used as novel diagnostic or prognostic tools in cancer.

Insights into the genetic foundations of human communication.

Science.gov (United States)

Graham, Sarah A; Deriziotis, Pelagia; Fisher, Simon E

2015-03-01

The human capacity to acquire sophisticated language is unmatched in the animal kingdom. Despite the discontinuity in communicative abilities between humans and other primates, language is built on ancient genetic foundations, which are being illuminated by comparative genomics. The genetic architecture of the language faculty is also being uncovered by research into neurodevelopmental disorders that disrupt the normally effortless process of language acquisition. In this article, we discuss the strategies that researchers are using to reveal genetic factors contributing to communicative abilities, and review progress in identifying the relevant genes and genetic variants. The first gene directly implicated in a speech and language disorder was FOXP2. Using this gene as a case study, we illustrate how evidence from genetics, molecular cell biology, animal models and human neuroimaging has converged to build a picture of the role of FOXP2 in neurodevelopment, providing a framework for future endeavors to bridge the gaps between genes, brains and behavior.

Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis.

Science.gov (United States)

Higdon, Jane V; Delage, Barbara; Williams, David E; Dashwood, Roderick H

2007-03-01

Cruciferous vegetables are a rich source of glucosinolates and their hydrolysis products, including indoles and isothiocyanates, and high intake of cruciferous vegetables has been associated with lower risk of lung and colorectal cancer in some epidemiological studies. Glucosinolate hydrolysis products alter the metabolism or activity of sex hormones in ways that could inhibit the development of hormone-sensitive cancers, but evidence of an inverse association between cruciferous vegetable intake and breast or prostate cancer in humans is limited and inconsistent. Organizations such as the National Cancer Institute recommend the consumption of five to nine servings of fruits and vegetables daily, but separate recommendations for cruciferous vegetables have not been established. Isothiocyanates and indoles derived from the hydrolysis of glucosinolates, such as sulforaphane and indole-3-carbinol (I3C), have been implicated in a variety of anticarcinogenic mechanisms, but deleterious effects also have been reported in some experimental protocols, including tumor promotion over prolonged periods of exposure. Epidemiological studies indicate that human exposure to isothiocyanates and indoles through cruciferous vegetable consumption may decrease cancer risk, but the protective effects may be influenced by individual genetic variation (polymorphisms) in the metabolism and elimination of isothiocyanates from the body. Cooking procedures also affect the bioavailability and intake of glucosinolates and their derivatives. Supplementation with I3C or the related dimer 3,3'-diindolylmethane (DIM) alters urinary estrogen metabolite profiles in women, but the effects of I3C and DIM on breast cancer risk are not known. Small preliminary trials in humans suggest that I3C supplementation may be beneficial in treating conditions related to human papilloma virus infection, such as cervical intraepithelial neoplasia and recurrent respiratory papillomatosis, but larger randomized

CRISPR/Cas9-mediated noncoding RNA editing in human cancers.

Science.gov (United States)

Yang, Jie; Meng, Xiaodan; Pan, Jinchang; Jiang, Nan; Zhou, Chengwei; Wu, Zhenhua; Gong, Zhaohui

2018-01-02

Cancer is characterized by multiple genetic and epigenetic alterations, including a higher prevalence of mutations of oncogenes and/or tumor suppressors. Mounting evidences have shown that noncoding RNAs (ncRNAs) are involved in the epigenetic regulation of cancer genes and their associated pathways. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) system, a revolutionary genome-editing technology, has shed light on ncRNA-based cancer therapy. Here, we briefly introduce the classifications and mechanisms of CRISPR/Cas9 system. Importantly, we mainly focused on the applications of CRISPR/Cas9 system as a molecular tool for ncRNA (microRNA, long noncoding RNA and circular RNA, etc.) editing in human cancers, and the novel techniques that are based on CRISPR/Cas9 system. Additionally, the off-target effects and the corresponding solutions as well as the challenges toward CRISPR/Cas9 were also evaluated and discussed. Long- and short-ncRNAs have been employed as targets in precision oncology, and CRISPR/Cas9-mediated ncRNA editing may provide an excellent way to cure cancer.

Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

International Nuclear Information System (INIS)

Raufman, Jean-Pierre; Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng

2011-01-01

Highlights: ► Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. ► Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. ► Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers – this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre-treatment with anti-MMP1 antibody. This study contributes to understanding

Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

Energy Technology Data Exchange (ETDEWEB)

Raufman, Jean-Pierre, E-mail: jraufman@medicine.umaryland.edu [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States); Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States)

2011-11-18

Highlights: Black-Right-Pointing-Pointer Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. Black-Right-Pointing-Pointer Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. Black-Right-Pointing-Pointer Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers - this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre

Human Genetic Engineering: A Survey of Student Value Stances

Science.gov (United States)

Wilson, Sara McCormack; And Others

1975-01-01

Assesses the values of high school and college students relative to human genetic engineering and recommends that biology educators explore instructional strategies merging human genetic information with value clarification techniques. (LS)

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

NARCIS (Netherlands)

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

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

Nature, Nurture, and Cancer Risks: Genetic and Nutritional Contributions to Cancer.

Science.gov (United States)

Theodoratou, Evropi; Timofeeva, Maria; Li, Xue; Meng, Xiangrui; Ioannidis, John P A

2017-08-21

It is speculated that genetic variants are associated with differential responses to nutrients (known as gene-diet interactions) and that these variations may be linked to different cancer risks. In this review, we critically evaluate the evidence across 314 meta-analyses of observational studies and randomized controlled trials of dietary risk factors and the five most common cancers (breast, lung, prostate, colorectal, and stomach). We also critically evaluate the evidence across 13 meta-analyses of observational studies of gene-diet interactions for the same cancers. Convincing evidence for association was found only for the intake of alcohol and whole grains in relation to colorectal cancer risk. Three nutrient associations had highly suggestive evidence and another 15 associations had suggestive evidence. Among the examined gene-diet interactions, only one had moderately strong evidence.

Non-genetic health professionals' attitude towards, knowledge of and skills in discussing and ordering genetic testing for hereditary cancer

NARCIS (Netherlands)

Douma, Kirsten F. L.; Smets, Ellen M. A.; Allain, Dawn C.

2016-01-01

Non-genetic health professionals (NGHPs) have insufficient knowledge of cancer genetics, express educational needs and are unprepared to counsel their patients regarding their genetic test results. So far, it is unclear how NGHPs perceive their own communication skills. This study was undertaken to

Advancement of Phenotype Transformation of Cancer-associated Fibroblasts: 
from Genetic Alterations to Epigenetic Modification

Directory of Open Access Journals (Sweden)

Dali CHEN

2015-02-01

Full Text Available In the field of human cancer research, even though the vast majority attentions were paid to tumor cells as “the seeds”, the roles of tumor microenvironments as “the soil” are gradually explored in recent years. As a dominant compartment of tumor microenvironments, cancer-associated fibroblasts (CAFs were discovered to correlated with tumorigenesis, tumor progression and prognosis. And the exploration of the mechanisms of CAF phenotype transformation would conducive to the further understand of the CAFs function in human cancers. As we known that CAFs have four main origins, including epithelial cells, endothelial cells, mesenchymal stem cells (MSCs and local mesenchymal cells. However, researchers found that all these origins finally conduct similiar phenotypes from intrinsic to extrinsic ones. Thus, what and how a mechanism can conduct the phenotype transformation of CAFs with different origins? Two viewpoints are proposed to try to answer the quetsion, involving genetic alterations and epigenetic modifications. This review will systematically summarize the advancement of mechanisms of CAF phenotype transformations in the aspect of genentic and epigenetic modifications.

Association of genetic ancestry with breast cancer in ethnically diverse women from Chicago.

Directory of Open Access Journals (Sweden)

Umaima Al-Alem

Full Text Available Non-Hispanic (nH Black and Hispanic women are disproportionately affected by early onset disease, later stage, and with more aggressive, higher grade and ER/PR negative breast cancers. The purpose of this analysis was to examine whether genetic ancestry could account for these variation in breast cancer characteristics, once data were stratified by self-reported race/ethnicity and adjusted for potential confounding by social and behavioral factors.We used a panel of 100 ancestry informative markers (AIMs to estimate individual genetic ancestry in 656 women from the "Breast Cancer Care in Chicago" study, a multi-ethnic cohort of breast cancer patients to examine the association between individual genetic ancestry and breast cancer characteristics. In addition we examined the association of individual AIMs and breast cancer to identify genes/regions that may potentially play a role in breast cancer disease disparities.As expected, nH Black and Hispanic patients were more likely than nH White patients to be diagnosed at later stages, with higher grade, and with ER/PR negative tumors. Higher European genetic ancestry was protective against later stage at diagnosis (OR 0.7 95%CI: 0.54-0.92 among Hispanic patients, and higher grade (OR 0.73, 95%CI: 0.56-0.95 among nH Black patients. After adjustment for multiple social and behavioral risk factors, the association with later stage remained, while the association with grade was not significant. We also found that the AIM SNP rs10954631 on chromosome 7 was associated with later stage (p = 0.02 and higher grade (p = 0.012 in nH Whites and later stage (p = 0.03 in nH Blacks.Non-European genetic ancestry was associated with later stage at diagnosis in ethnic minorities. The relation between genetic ancestry and stage at diagnosis may be due to genetic factors and/or unmeasured environmental factors that are overrepresented within certain racial/ethnic groups.

The concept of human dignity in the ethics of genetic research.

Science.gov (United States)

Chan, David K

2015-05-01

Despite criticism that dignity is a vague and slippery concept, a number of international guidelines on bioethics have cautioned against research that is contrary to human dignity, with reference specifically to genetic technology. What is the connection between genetic research and human dignity? In this article, I investigate the concept of human dignity in its various historical forms, and examine its status as a moral concept. Unlike Kant's ideal concept of human dignity, the empirical or relational concept takes human dignity as something that is affected by one's circumstances and what others do. I argue that the dignity objection to some forms of genetic research rests on a view of human nature that gives humans a special status in nature - one that is threatened by the potential of genetic research to reduce individuals to their genetic endowment. I distinguish two main philosophical accounts of human nature. One of these, the Aristotelian view, is compatible with the use of genetic technology to help humans realize their inherent potential to a fuller extent. © 2014 John Wiley & Sons Ltd.

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

NARCIS (Netherlands)

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

2006-01-01

This study explores the effect of age at the time of parental cancer diagnosis or death on psychological distress and cancer risk perception in individuals undergoing genetic testing for a specific cancer susceptibility. Cancer-related distress, worry and risk perception were assessed in 271

Inauguration of the cameroonian society of human genetics.

Science.gov (United States)

Wonkam, Ambroise; Kenfack, Marcel Azabji; Bigoga, Jude; Nkegoum, Blaise; Muna, Wali

2009-10-20

The conjunction of "hard genetics" research centers, with well established biomedical and bioethics research groups, and the exceptional possibility to hold the 6th annual meeting of the African Society of Human Genetics (AfSHG, 13th-15th March 2009) was an excellent opportunity to get together in synergy the entire Cameroonian "DNA/RNA scientists" . This laid to the foundation of the Cameroonian Society of Human Genetics (CSHG) that was privilege to hold its inaugural meeting in conjunction to the 6th annual meeting of the AfSHG. The theme was "Human Origin, Genetic Diversity and Health". The AfSHG and CSHG invited leading African and international scientists in genomics and population genetics to review recent data and provide an understanding of the state-of-knowledge of Human Origin and Genetic Diversity. Overall one opening ceremony eight session, five keynote and guest speakers, 18 invited oral communications, 13 free oral communications, 43 posters and two social events could summarize the meeting. This year's conference was graced by the presence of one Nobel Prize winner Dr Richard Roberts (Physiology and Medicine 1993). The meeting registered up to ten contributions of Cameroonian scientists from the Diaspora (currently in USA, Belgium, Gambia, Sudan and Zimbabwe). Such Diaspora participation is an opportunity to generate collaborations with home country scientists and ultimately turn the "brain drain" to "brain circulation" that could reduce the impact of the migration of health professional from Africa. Interestingly, the personal implication of the Cameroonian Ministry of Public Heath who opened the meeting in the presence of the Secretary General of the Ministry of Higher Education and a representative of the Ministry of Scientific Research and Innovation was a wonderful opportunity for advocacy of genetic issues at the decision-makers level. Beyond our expectation, a major promise of the Cameroonian government was the creation of the National Human

DBGC: A Database of Human Gastric Cancer

Science.gov (United States)

Wang, Chao; Zhang, Jun; Cai, Mingdeng; Zhu, Zhenggang; Gu, Wenjie; Yu, Yingyan; Zhang, Xiaoyan

2015-01-01

The Database of Human Gastric Cancer (DBGC) is a comprehensive database that integrates various human gastric cancer-related data resources. Human gastric cancer-related transcriptomics projects, proteomics projects, mutations, biomarkers and drug-sensitive genes from different sources were collected and unified in this database. Moreover, epidemiological statistics of gastric cancer patients in China and clinicopathological information annotated with gastric cancer cases were also integrated into the DBGC. We believe that this database will greatly facilitate research regarding human gastric cancer in many fields. DBGC is freely available at http://bminfor.tongji.edu.cn/dbgc/index.do PMID:26566288

Genetic and Epigenetic Tumor Suppressor Gene Silencing Are Distinct Molecular Phenotypes Driven by Growth Promoting Mutations in Nonsmall Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Carmen J. Marsit

2008-01-01

Full Text Available Both genetic and epigenetic alterations characterize human nonsmall cell lung cancer (NSCLC, but the biological processes that create or select these alterations remain incompletely investigated. Our hypothesis posits that a roughly reciprocal relationship between the propensity for promoter hypermethylation and a propensity for genetic deletion leads to distinct molecular phenotypes of lung cancer. To test this hypothesis, we examined promoter hypermethylation of 17 tumor suppressor genes, as a marker of epigenetic alteration propensity, and deletion events at the 3p21 region, as a marker of genetic alteration. To model the complex biology between these somatic alterations, we utilized an item response theory model. We demonstrated that tumors exhibiting LOH at greater than 30% of informative alleles in the 3p21 region have a significantly reduced propensity for hypermethylation. At the same time, tumors with activating KRAS mutations showed a significantly increased propensity for hypermethylation of the loci examined, a result similar to what has been observed in colon cancer. These data suggest that NSCLCs have distinct epigenetic or genetic alteration phenotypes acting upon tumor suppressor genes and that mutation of oncogenic growth promoting genes, such as KRAS, is associated with the epigenetic phenotype.

Combinations of genetic data in a study of oral cancer

DEFF Research Database (Denmark)

Mellerup, Erling Thyge; Møller, Gert Lykke; Mondal, Pinaki

2015-01-01

In the single locus strategy a number of genetic variants are analyzed, in order to find variants that are distributed significantly different between controls and patients. A supplementary strategy is to analyze combinations of genetic variants. A combination that is the genetic basis...... for a polygenic disorder will not occur in in control persons genetically unrelated to patients, so the strategy is to analyze combinations of genetic variants present exclusively in patients. In a previous study of oral cancer and leukoplakia 325 SNPs were analyzed. This study has been supplemented...

Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

DEFF Research Database (Denmark)

Pearce, C L; Near, A M; Van Den Berg, D J

2009-01-01

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had...... been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P... and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted....

Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women

Science.gov (United States)

... their family history of cancer. Depending on a woman’s family history, the doctor or nurse may then use a ... against routine genetic counseling or BRCA testing of women whose family history is not associated with an increased risk for ...

Rare endocrine cancers have novel genetic alterations

Science.gov (United States)

A molecular characterization of adrenocortical carcinoma, a rare cancer of the adrenal cortex, analyzed 91 cases for alterations in the tumor genomes and identified several novel genetic mutations as likely mechanisms driving the disease as well as whole genome doubling as a probable driver of the disease.

Views of female breast cancer patients who donated biologic samples regarding storage and use of samples for genetic research.

Science.gov (United States)

Kaphingst, K A; Janoff, J M; Harris, L N; Emmons, K M

2006-05-01

Although social and ethical issues related to the storage and use of biologic specimens for genetic research have been discussed extensively in the medical literature, few empiric data exist describing patients' views. This qualitative study explored the views of 26 female breast cancer patients who had consented to donate blood or tissue samples for breast cancer research. Participants generally did not expect personal benefits from research and had few unprompted concerns. Few participants had concerns about use of samples for studies not planned at the time of consent. Some participants did express concerns about insurance or employment discrimination, while others believed that current privacy protections might actually slow breast cancer research. Participants were generally more interested in receiving individual genetic test results from research studies than aggregate results. Most participants did not want individual results of uncertain clinical significance, although others believed that they should be able to receive such information. These data examined the range of participants' views regarding the storage and use of biologic samples. Further research with different and diverse patient populations is critical to establishing an appropriate balance between protecting the rights of human subjects in genetic research and allowing research to progress.

Human genetics in troubled times and places.

Science.gov (United States)

Harper, Peter S

2018-01-01

The development of human genetics world-wide during the twentieth century, especially across Europe, has occurred against a background of repeated catastrophes, including two world wars and the ideological problems and repression posed by Nazism and Communism. The published scientific literature gives few hints of these problems and there is a danger that they will be forgotten. The First World War was largely indiscriminate in its carnage, but World War 2 and the preceding years of fascism were associated with widespread migration, especially of Jewish workers expelled from Germany, and of their children, a number of whom would become major contributors to the post-war generation of human and medical geneticists in Britain and America. In Germany itself, eminent geneticists were also involved in the abuses carried out in the name of 'eugenics' and 'race biology'. However, geneticists in America, Britain and the rest of Europe were largely responsible for the ideological foundations of these abuses. In the Soviet Union, geneticists and genetics itself became the object of persecution from the 1930s till as late as the mid 1960s, with an almost complete destruction of the field during this time; this extended also to Eastern Europe and China as part of the influence of Russian communism. Most recently, at the end of the twentieth century, China saw a renewal of government sponsored eugenics programmes, now mostly discarded. During the post-world war 2 decades, human genetics research benefited greatly from recognition of the genetic dangers posed by exposure to radiation, following the atomic bomb explosions in Japan, atmospheric testing and successive accidental nuclear disasters in Russia. Documenting and remembering these traumatic events, now largely forgotten among younger workers, is essential if we are to fully understand the history of human genetics and avoid the repetition of similar disasters in the future. The power of modern human genetic and genomic

Genetic bases of the radiosensitivity of breast cancer

International Nuclear Information System (INIS)

Delaloge, S.; Marsiglia, H.

2005-01-01

Local-regional radiation therapy is one of the major therapeutic means in the management of breast cancer. Three questions however arise from the important advances, achieved in this domain in the past years. The first question concerns the possibilities to identify and overcome the radioresistance of a subset of tumours. The second question is how to recognize women likely to benefit from adjuvant radiation therapy, and therefore to diminish treatment indications in other groups. Finally, the third question is how to identify subjects at high risk for long term injury following breast irradiation, in order to adapt techniques and indications in such populations. The major advances of breast cancer molecular genetics in the past years should provide clinicians with tools to answer these important questions. In this paper, we review the molecular germ line (BRCA1, BRCA2, ATM,...) and somatic (p53, tyrosine kinase receptors, as well as actors of cell cycle, signal transduction, apoptosis, DNA repair...) main bases of breast cancer radiosensitivity. Recent methods of exploration of the genetic background of both the host and the tumours (gene and protein expression profiles) are also reviewed as major tools of breast cancer management in the next few years. (author)

Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes.

Science.gov (United States)

Macdonald, Lynn E; Karow, Margaret; Stevens, Sean; Auerbach, Wojtek; Poueymirou, William T; Yasenchak, Jason; Frendewey, David; Valenzuela, David M; Giallourakis, Cosmas C; Alt, Frederick W; Yancopoulos, George D; Murphy, Andrew J

2014-04-08

Genetic humanization, which involves replacing mouse genes with their human counterparts, can create powerful animal models for the study of human genes and diseases. One important example of genetic humanization involves mice humanized for their Ig genes, allowing for human antibody responses within a mouse background (HumAb mice) and also providing a valuable platform for the generation of fully human antibodies as therapeutics. However, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which they were genetically humanized. Heretofore, most genetic humanizations have involved disruption of the endogenous mouse gene with simultaneous introduction of a human transgene at a new and random location (so-called KO-plus-transgenic humanization). More recent efforts have attempted to replace mouse genes with their human counterparts at the same genetic location (in situ humanization), but such efforts involved laborious procedures and were limited in size and precision. We describe a general and efficient method for very large, in situ, and precise genetic humanization using large compound bacterial artificial chromosome-based targeting vectors introduced into mouse ES cells. We applied this method to genetically humanize 3-Mb segments of both the mouse heavy and κ light chain Ig loci, by far the largest genetic humanizations ever described. This paper provides a detailed description of our genetic humanization approach, and the companion paper reports that the humoral immune systems of mice bearing these genetically humanized loci function as efficiently as those of WT mice.

The genetic alteration of retinoblastoma gene in esophageal cancer

International Nuclear Information System (INIS)

Cho, Jae Il; Shim, Yung Mok; Kim, Chang Min

1994-12-01

Retinoblastoma(RB) gene is the prototype of tumor suppressor gene and it's alteration have been frequently observed in a large number of human tumors. To investigate the role of RB in esophageal cancer, we studied 36 esophageal cancer tissues with Southern blot analysis to detect gross LOH and PCR-SSCP method to find minute LOH and mutation, if any. In the cases with abnormalities, the nucleotide sequence analysis was performed. Allelic loss of chromosome 13q14 occurred in 20 out of 32 informative cases (62.5%) by Southern analysis. Furthermore, PCR-LOH added three positive cases. Mobility shift by PCR-SSCP was observed in one case at exon 22, which showed 1 bp deletion in codon 771 of RB gene resulting in frame shift mutation. Besides, nine PCR-band alteration in tumor tissue compared with normal tissue were observed in exon 14 and 22, but mutation was not found on sequencing analysis suggesting the epigenetic alteration in tumor tissue. Analysis of the clinical data did not show any difference depending upon RB alteration. However, the total incidence of RB gene may play an important role in the development of esophageal cancer. The main genetic alteration of RB gene was deletion detected by Southern blot and one bp deletion leading to frame shift was also observed. 8 figs, 5 tabs. (Author)

The genetic alteration of retinoblastoma gene in esophageal cancer

Energy Technology Data Exchange (ETDEWEB)

Cho, Jae Il; Shim, Yung Mok; Kim, Chang Min [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1994-12-01

Retinoblastoma(RB) gene is the prototype of tumor suppressor gene and it`s alteration have been frequently observed in a large number of human tumors. To investigate the role of RB in esophageal cancer, we studied 36 esophageal cancer tissues with Southern blot analysis to detect gross LOH and PCR-SSCP method to find minute LOH and mutation, if any. In the cases with abnormalities, the nucleotide sequence analysis was performed. Allelic loss of chromosome 13q14 occurred in 20 out of 32 informative cases (62.5%) by Southern analysis. Furthermore, PCR-LOH added three positive cases. Mobility shift by PCR-SSCP was observed in one case at exon 22, which showed 1 bp deletion in codon 771 of RB gene resulting in frame shift mutation. Besides, nine PCR-band alteration in tumor tissue compared with normal tissue were observed in exon 14 and 22, but mutation was not found on sequencing analysis suggesting the epigenetic alteration in tumor tissue. Analysis of the clinical data did not show any difference depending upon RB alteration. However, the total incidence of RB gene may play an important role in the development of esophageal cancer. The main genetic alteration of RB gene was deletion detected by Southern blot and one bp deletion leading to frame shift was also observed. 8 figs, 5 tabs. (Author).

Human population genetics and “ancestrality” business

OpenAIRE

André Langaney

2009-01-01

Following the foundation of theoretical population genetics by Wright, Fischer, Haldane and Malécot, in the first half of the 20th century, applied human population genetics developed with great success with the improvement and accumulation of new technologies to measure genetic polymorphism, first through protein polymorphisms since the 1960’s, then through DNA typing and sequencing since the 1980’s. The field of population genetics and biological anthropology was developed by a handful of d...

History, genetics, and strategies for cancer prevention in Lynch syndrome.

Science.gov (United States)

Kastrinos, Fay; Stoffel, Elena M

2014-05-01

Colorectal cancer (CRC) is the most common gastrointestinal malignancy and the third cause of cancer death in men and women in the United States. The majority of CRC cases diagnosed annually are due to sporadic events, but up to 6% are attributed to known monogenic disorders that confer a markedly increased risk for the development of CRC and multiple extracolonic malignancies. Lynch syndrome is the most common inherited CRC syndrome and is associated with mutations in DNA mismatch repair genes, mainly MLH1 and MSH2 but also MSH6, PMS2, and EPCAM. Although the risk of CRC and endometrial cancer may approach near 75% and 50%, respectively, in gene mutation carriers, the identification of these individuals and at-risk family members through predictive genetic testing provides opportunities for cancer prevention including specialized cancer screening, intensified surveillance, and/or prophylactic surgeries. This article will provide a review of the major advances in risk assessment, molecular genetics, DNA mutational analyses, and cancer prevention and management made since Lynch syndrome was first described 100 years ago. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Multi-disciplinary summit on genetics services for women with gynecologic cancers: A Society of Gynecologic Oncology White Paper.

Science.gov (United States)

Randall, Leslie M; Pothuri, Bhavana; Swisher, Elizabeth M; Diaz, John P; Buchanan, Adam; Witkop, Catherine T; Bethan Powell, C; Smith, Ellen Blair; Robson, Mark E; Boyd, Jeff; Coleman, Robert L; Lu, Karen

2017-08-01

To assess current practice, advise minimum standards, and identify educational gaps relevant to genetic screening, counseling, and testing of women affected by gynecologic cancers. The Society of Gynecologic Oncology (SGO) organized a multidisciplinary summit that included representatives from the American College of Obstetricians and Gynecologists (ACOG), the American Society Clinical Oncology (ASCO), the National Society of Genetic Counselors (NSGC), and patient advocacy groups, BrightPink and Facing our Risk of Cancer Empowered (FORCE). Three subject areas were discussed: care delivery models for genetic testing, barriers to genetic testing, and educational opportunities for providers of genetic testing. The group endorsed current SGO, National Comprehensive Cancer Network (NCCN), and NSGC genetic testing guidelines for women affected with ovarian, tubal, peritoneal cancers, or DNA mismatch repair deficient endometrial cancer. Three main areas of unmet need were identified: timely and universal genetic testing for women with ovarian, fallopian tube, and peritoneal cancers; education regarding minimum standards for genetic counseling and testing; and barriers to implementation of testing of both affected individuals as well as cascade testing of family members. Consensus building among all stakeholders resulted in an action plan to address gaps in education of gynecologic oncology providers and delivery of cancer genetics care. Copyright © 2017. Published by Elsevier Inc.

Inauguration of the Cameroonian Society of Human Genetics

Directory of Open Access Journals (Sweden)

Jude Bigoga

2009-10-01

Full Text Available The conjunction of “hard genetics” research centers, with well established biomedical and bioethics research groups, and the exceptional possibility to hold the 6th annual meeting of the African Society of Human Genetics (AfSHG, 13th-15th March 2009 was an excellent opportunity to get together in synergy the entire Cameroonian “DNA/RNA scientists” . This laid to the foundation of the Cameroonian Society of Human Genetics (CSHG that was privilege to hold its inaugural meeting in conjunction to the 6th annual meeting of the AfSHG. The theme was "Human Origin, Genetic Diversity and Health”. The AfSHG and CSHG invited leading African and international scientists in genomics and population genetics to review recent data and provide an understanding of the state-of-knowledge of Human Origin and Genetic Diversity. Overall one opening ceremony eight session, five keynote and guest speakers, 18 invited oral communications, 13 free oral communications, 43 posters and two social events could summarize the meeting. This year’s conference was graced by the presence of one Nobel Prize winner Dr Richard Roberts (Physiology and Medicine 1993. The meeting registered up to ten contributions of Cameroonian scientists from the Diaspora (currently in USA, Belgium, Gambia, Sudan and Zimbabwe. Such Diaspora participation is an opportunity to generate collaborations with home country scientists and ultimately turn the “brain drain” to “brain circulation” that could reduce the impact of the migration of health professional from Africa. Interestingly, the personal implication of the Cameroonian Ministry of Public Heath who opened the meeting in the presence of the Secretary General of the Ministry of Higher Education and a representative of the Ministry of Scientific Research and Innovation was a wonderful opportunity for advocacy of genetic issues at the decision-makers level. Beyond our expectation, a major promise of the Cameroonian government was

Oral mucosa and lung cancer: Are genetic changes in the oral ...

African Journals Online (AJOL)

2016-02-03

Feb 3, 2016 ... to lung cancer, although other risk factors (such as genetic tendency) ... analysis of oral mucosa identifying individuals predisposed to lung cancer. ... of the study is that oral epithelial cells of smokers who have lung cancer are ... Stratec Molecular, Berlin, Germany). p53 codon 72 ..... Validity and reliability of.

Barriers and Facilitators for Utilization of Genetic Counseling and Risk Assessment Services in Young Female Breast Cancer Survivors

Directory of Open Access Journals (Sweden)

Beth Anderson

2012-01-01

Full Text Available Introduction. Women diagnosed with breast cancer at a young age are more likely to carry a cancer predisposing genetic mutation. Per the current NCCN recommendations, women diagnosed under age 50 should be referred to cancer genetic counseling for further risk evaluation. This study seeks to assess patient-reported barriers and facilitators to receiving genetic counseling and risk assessment among a community-based population of young breast cancer survivors (YBCS. Methods. Through the Michigan Cancer Surveillance Program, a state-based cancer registry, 488 women diagnosed with breast cancer before age 50 in 2006-2007 were identified. They received a mail survey regarding family history and facilitators and barriers to receiving genetic counseling and risk assessment. Results. Responses were received from 289 women (59.2%. One hundred twenty-two (42.2% reported having received cancer genetic counseling. The most frequent reason identified for receiving services was to benefit their family's future. The top reasons for not attending were “no one recommended it” and “medical insurance coverage issues.” Discussion. This study is the first published report using a state cancer registry to determine facilitators and barriers to receiving genetic counseling and risk assessment among YBCS. These findings demonstrate the need for additional awareness and education about appropriate indications for genetic services.

Barriers and Facilitators for Utilization of Genetic Counseling and Risk Assessment Services in Young Female Breast Cancer Survivors

International Nuclear Information System (INIS)

Anderson, B.; McLosky, J.; Wasilevich, E.; Callo, S. L.; Duquette, D.; Copeland, G.

2012-01-01

Introduction. Women diagnosed with breast cancer at a young age are more likely to carry a cancer predisposing genetic mutation. Per the current NCCN recommendations, women diagnosed under age 50 should be referred to cancer genetic counseling for further risk evaluation. This study seeks to assess patient-reported barriers and facilitators to receiving genetic counseling and risk assessment among a community-based population of young breast cancer survivors (YBCS). Methods. Through the Michigan Cancer Surveillance Program, a state-based cancer registry, 488 women diagnosed with breast cancer before age 50 in 2006-2007 were identified. They received a mail survey regarding family history and facilitators and barriers to receiving genetic counseling and risk assessment. Results. Responses were received from 289 women (59.2%). One hundred twenty-two (42.2%) reported having received cancer genetic counseling. The most frequent reason identified for receiving services was to benefit their family's future. The top reasons for not attending were “no one recommended it” and “medical insurance coverage issues.” Discussion. This study is the first published report using a state cancer registry to determine facilitators and barriers to receiving genetic counseling and risk assessment among YBCS. These findings demonstrate the need for additional awareness and education about appropriate indications for genetic services.

Evaluating human cancer cell metastasis in zebrafish

International Nuclear Information System (INIS)

Teng, Yong; Xie, Xiayang; Walker, Steven; White, David T; Mumm, Jeff S; Cowell, John K

2013-01-01

invasion potential. We also demonstrate, using lung cancers, that the zebrafish model can evaluate the metastatic ability of cancer cells isolated from primary tumors. The zebrafish model described here offers a rapid, robust, and inexpensive means of evaluating the metastatic potential of human cancer cells. Using this model it is possible to critically evaluate whether genetic manipulation of signaling pathways affects metastasis and whether primary tumors contain metastatic cells

Hopefulness predicts resilience after hereditary colorectal cancer genetic testing: a prospective outcome trajectories study

OpenAIRE

Chu Annie TW; Bonanno George A; Ho Judy WC; Ho Samuel MY; Chan Emily MS

2010-01-01

Abstract Background - Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC. Methods - A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer R...

International Szent-Györgyi Prize for Progress in Cancer Research: basic and translational research recognition : Mary-Claire King received the 2016 Prize for her pioneering research that demonstrated the first evidence of genetic predisposition to breast cancer.

Science.gov (United States)

Hartmann, Hali; Zhao, Jie; Ba, Sujuan

2017-11-21

The Szent-Györgyi Prize for Progress in Cancer Research is a prestigious scientific award sponsored by the National Foundation for Cancer Research (NFCR)-a leading cancer research charitable organization in the United States that supports innovative cancer research globally with the ultimate goal to cure cancer. The coveted Szent-Györgyi Prize annually honors a scientist whose seminal discovery or body of work has resulted in, or led toward, notable contributions to cancer prevention, diagnosis, or treatment; and the discovery has had a high direct impact of saving people's lives. In addition, the prize promotes public awareness of the importance of basic cancer research and encourages the sustained investment needed to accelerate the translation of these research discoveries into new cancer treatments. In 2016, NFCR's Szent-Györgyi Prize Selection Committee was unanimous in its decision to recognize an icon in human disease genetics, Dr. Mary-Claire King, for her pioneering research that demonstrated the first evidence of genetic predisposition to breast cancer. Her proof of existence of BRCA1 gene and its location has made genetic screening for breast and ovarian cancers possible, saving lives of many people who are at high risk with inherited BRCA1 mutations.

Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV, Bovine Leukemia Virus (BLV, Human Papilloma Virus (HPV, and Epstein–Barr Virus (EBV

Directory of Open Access Journals (Sweden)

James S. Lawson

2018-01-01

Full Text Available BackgroundAlthough the risk factors for breast cancer are well established, namely female gender, early menarche and late menopause plus the protective influence of early pregnancy, the underlying causes of breast cancer remain unknown. The development of substantial recent evidence indicates that a handful of viruses may have a role in breast cancer. These viruses are mouse mammary tumor virus (MMTV, bovine leukemia virus (BLV, human papilloma viruses (HPVs, and Epstein–Barr virus (EBV-also known as human herpes virus type 4. Each of these viruses has documented oncogenic potential. The aim of this review is to inform the scientific and general community about this recent evidence.The evidenceMMTV and human breast cancer—the evidence is detailed and comprehensive but cannot be regarded as conclusive. BLV and human breast cancer—the evidence is limited. However, in view of the emerging information about BLV in human breast cancer, it is prudent to encourage the elimination of BLV in cattle, particularly in the dairy industry. HPVs and breast cancer—the evidence is substantial but not conclusive. The availability of effective preventive vaccines is a major advantage and their use should be encouraged. EBV and breast cancer—the evidence is also substantial but not conclusive. Currently, there are no practical means of either prevention or treatment. Although there is evidence of genetic predisposition, and cancer in general is a culmination of events, there is no evidence that inherited genetic traits are causal.ConclusionThe influence of oncogenic viruses is currently the major plausible hypothesis for a direct cause of human breast cancer.

Exosomal microRNA Biomarkers: Emerging Frontiers in Colorectal and Other Human Cancers

Science.gov (United States)

Goel, Ajay; Tovar-Camargo, Oscar A; Toden, Shusuke

2016-01-01

Diagnostic strategies, particularly non-invasive blood-based screening approaches, are gaining increased attention for the early detection and attenuation of mortality associated with colorectal cancer (CRC). However, the majority of current screening approaches are inadequate at replacing the conventional CRC diagnostic procedures. Yet, due to technological advances and a better understanding of molecular events underlying human cancer, a new category of biomarkers are on the horizon. Recent evidence indicates that cells release a distinct class of small vesicles called ‘exosomes’, which contain nucleic acids and proteins that reflect and typify host-cell molecular architecture. Intriguingly, exosomes released from cancer cells have a distinct genetic and epigenetic makeup, which allows them to undertake their tumorigenic function. From a clinical standpoint, these unique cancer-specific fingerprints present in exosomes appear to be detectable in a small amount of blood, making them very attractive substrates for developing cancer biomarkers, particularly noninvasive diagnostic approaches. PMID:26892862

Psychosocial aspects of hereditary cancer (PAHC) questionnaire: development and testing of a screening questionnaire for use in clinical cancer genetics.

Science.gov (United States)

Eijzenga, W; Bleiker, E M A; Hahn, D E E; Kluijt, I; Sidharta, G N; Gundy, C; Aaronson, N K

2014-08-01

Up to three-quarters of individuals who undergo cancer genetic counseling and testing report psychosocial problems specifically related to that setting. The objectives of this study were to develop and evaluate the screening properties of a questionnaire designed to assess specific psychosocial problems related to cancer genetic counseling. We adopted the European Organisation for Research and Treatment of Cancer Quality of Life Group guidelines to develop the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire, a 26-item questionnaire organized into six problem domains: genetics, practical issues, family, living with cancer, emotions, and children. The Distress Thermometer and a question per domain on the perceived need for extra psychosocial services were included as well. We administered the questionnaire and the Hospital Anxiety and Depression Scale to 127 counselees at the time of genetic counseling and 3 weeks after DNA test disclosure. As a gold standard to evaluate the screening properties of the questionnaire, participants underwent a semi-structured interview with an experienced social worker who assessed the presence and severity of problems per domain. A cutoff score representing responses of 'quite a bit' or 'very much' to one or more items within a given problem domain yielded moderate to high sensitivity across domains. A cutoff of 4 on the Distress Thermometer yielded high sensitivity. The questions regarding the perceived need for extra psychosocial services yielded high specificity and negative predictive values. The Psychosocial Aspects of Hereditary Cancer questionnaire in combination with the Distress Thermometer can be used as a first-line screener for psychosocial problems within the cancer genetic counseling setting. Copyright © 2014 John Wiley & Sons, Ltd.

Seeking perfection: a Kantian look at human genetic engineering.

Science.gov (United States)

Gunderson, Martin

2007-01-01

It is tempting to argue that Kantian moral philosophy justifies prohibiting both human germ-line genetic engineering and non-therapeutic genetic engineering because they fail to respect human dignity. There are, however, good reasons for resisting this temptation. In fact, Kant's moral philosophy provides reasons that support genetic engineering-even germ-line and non-therapeutic. This is true of Kant's imperfect duties to seek one's own perfection and the happiness of others. It is also true of the categorical imperative. Kant's moral philosophy does, however, provide limits to justifiable genetic engineering.

The history and development of the Human Genetics Society of Australasia.

Science.gov (United States)

Sutherland, Grant R

2008-08-01

The Human Genetics Society of Australasia is a vibrant professional society with more than 900 members that promotes and regulates the practice of human and medical genetics in Australia and New Zealand. The growth of human genetics was stimulated by the development of diagnostic clinical cytogenetics laboratories in the early to mid 1960s. This coincided with the recognition by medical specialists, mainly pediatricians, that genetic disorders, especially inborn errors of metabolism and birth defects, were of clinical interest and potentially challenging areas for their skills. The organization of professionals in human genetics was slow to evolve. There was an early Western Australian Human Genetics Society, and the cytogenetics community had begun to meet annually from about 1966 but was coordinated by a mailing list rather than as a formal organization. In 1976, as part of the celebrations of the Centenary Year of the Adelaide Children's Hospital, a clinical genetics meeting involving several high profile international speakers and most of the senior medical geneticists in Australia and New Zealand along with the annual meeting of the loose-knit cytogeneticists group agreed that a small working group be charged with setting up a Human Genetics Society. The society was formally incorporated in South Australia in 1977.

Genetically modified vaccines augment the efficacy of cancer surgery and chemotherapy

Czech Academy of Sciences Publication Activity Database

Bubeník, Jan

2009-01-01

Roč. 55, č. 6 (2009), s. 199-200 ISSN 0015-5500 Institutional research plan: CEZ:AV0Z50520514 Keywords : genetically modified vaccines * cancer surgery and chemotherapy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.924, year: 2009

An existential analysis of genetic engineering and human rights ...

African Journals Online (AJOL)

Genetic engineering for purposes of human enhancement poses risks that justify regulation. However, this paper argues philosophically that it is inappropriate to use human rights treaties to prohibit germ-line genetic engineering whether therapeutic or for purposes of enhancement. When also looked at existentially, the ...

Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence

Science.gov (United States)

Yano, Shuya; Takehara, Kiyoto; Miwa, Shinji; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Urata, Yasuo; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

2016-01-01

We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model. PMID:27689331

A Follow-Up Community Survey of Knowledge and Beliefs About Cancer and Genetics.

Science.gov (United States)

Sweeney, Shannon M; Hastrup, Janice L; Hyland, Andrew; Rivard, Cheryl

2016-06-01

The purpose of this study is to assess changes since the launch of the US Surgeon General's campaign in the public's beliefs about the role of genetics in the etiology of cancer, as well as changes in recording family health history. We conducted a survey of 480 Western New York adults, assessing: (1) experiences with cancer, (2) beliefs about cancer and genetics, and (3) practices of recording family health history. Most respondents were aware of the importance of family history. The sample also showed increased knowledge about cancer and genetics compared with a previous survey. However, only 7 % kept written records that included medical conditions, which was not different from a previous survey. Time constraints, apathy, and reluctance to find out negative health information were the most reported barriers. Results suggest a need for continued education of the public, with increased emphasis on written family health records.

Migrant breast cancer patients and their participation in genetic counseling : results from a registry-based study

NARCIS (Netherlands)

Baars, J E; van Dulmen, A M; Velthuizen, M E; Theunissen, E B M; Vrouenraets, B C; Kimmings, A N; van Dalen, T; van Ooijen, B; Witkamp, A J; van der Aa, M A; Ausems, M G E M

Certain ethnic groups seem to have less access to cancer genetic counseling. Our study was to investigate the participation in cancer genetic counseling among migrant breast cancer patients of Turkish and Moroccan origin. Hospital medical records of Turkish and Moroccan and of a comparative group of

Migrant breast cancer patients and their participation in genetic counseling: results from a registry-based study.

NARCIS (Netherlands)

Baars, J.E.; Dulmen, A.M. van; Velthuizen, M.E.; Theunissen, E.B.M.; Vrouenraets, B.C.; Kimmings, A.N.; Dalen, T. van; Ooijen, B. van; Witkamp, A.J.; Aa, M.A. van der; Ausems, M.G.E.M.

2016-01-01

Certain ethnic groups seem to have less access to cancer genetic counseling. Our study was to investigate the participation in cancer genetic counseling among migrant breast cancer patients of Turkish and Moroccan origin. Hospital medical records of Turkish and Moroccan and of a comparative group of

Migrant breast cancer patients and their participation in genetic counseling: results from a registry-based study

NARCIS (Netherlands)

Baars, J.E.; Dulmen, A.M. van; Velthuizen, M.E.; Theunissen, E.B.; Vrouenraets, B.C.; Kimmings, A.N.; Dalen, T. van; Ooijen, B. van; Witkamp, A.J.; Aa, M.A. van der; Ausems, M.G.

2016-01-01

Certain ethnic groups seem to have less access to cancer genetic counseling. Our study was to investigate the participation in cancer genetic counseling among migrant breast cancer patients of Turkish and Moroccan origin. Hospital medical records of Turkish and Moroccan and of a comparative group of

Genetic Modeling of Radiation Injury in Prostate Cancer Patients Treated with Radiotherapy

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0681 TITLE: Genetic Modeling of Radiation Injury in Prostate Cancer Patients Treated with Radiotherapy PRINCIPAL...TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0681Genetic Modeling of Radiation Injury in Prostate Cancer Patients Treated...effects, urinary morbidity, rectal injury, sexual dysfunction 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF

Patterns of Cancer Genetic Testing: A Randomized Survey of Oregon Clinicians

International Nuclear Information System (INIS)

Cox, S. L.; Zlot, A. I.; Silvey, S. K.; Silvey, S. K.

2012-01-01

Introduction. Appropriate use of genetic tests for population-based cancer screening, diagnosis of inherited cancers, and guidance of cancer treatment can improve health outcomes. We investigated clinicians’ use and knowledge of eight breast, ovarian, and colorectal cancer genetic tests. Methods. We conducted a randomized survey of 2,191 Oregon providers, asking about their experience with fecal DNA, OncoVue, BRCA, MMR, CYP2D6, tumor gene expression profiling, UGT1A1, and KRAS. Results. Clinicians reported low confidence in their knowledge of medical genetics; most confident were OB-GYNs and specialists. Clinicians were more likely to have ordered/recommended BRCA and MMR than the other tests, and OB-GYNs were twice as likely to have ordered/recommended BRCA testing than primary care providers. Less than 10% of providers ordered/recommended OncoVue, fecal DNA, CYP2D6, or UGT1A1; less than 30% ordered/recommended tumor gene expression profiles or KRAS. The most common reason for not ordering/recommending these tests was lack of familiarity. Conclusions. Use of appropriate, evidence-based testing can help reduce incidence and mortality of certain cancers, but these tests need to be better integrated into clinical practice. Continued evaluation of emerging technologies, dissemination of findings, and an increase in provider confidence and knowledge are necessary to achieve this end.

Pathogenesis of Gastric Cancer: Genetics and Molecular Classification.

Science.gov (United States)

Figueiredo, Ceu; Camargo, M C; Leite, Marina; Fuentes-Pananá, Ezequiel M; Rabkin, Charles S; Machado, José C

Gastric cancer is the fifth most incident and the third most common cause of cancer-related death in the world. Infection with Helicobacter pylori is the major risk factor for this disease. Gastric cancer is the final outcome of a cascade of events that takes decades to occur and results from the accumulation of multiple genetic and epigenetic alterations. These changes are crucial for tumor cells to expedite and sustain the array of pathways involved in the cancer development, such as cell cycle, DNA repair, metabolism, cell-to-cell and cell-to-matrix interactions, apoptosis, angiogenesis, and immune surveillance. Comprehensive molecular analyses of gastric cancer have disclosed the complex heterogeneity of this disease. In particular, these analyses have confirmed that Epstein-Barr virus (EBV)-positive gastric cancer is a distinct entity. The identification of gastric cancer subtypes characterized by recognizable molecular profiles may pave the way for a more personalized clinical management and to the identification of novel therapeutic targets and biomarkers for screening, prognosis, prediction of response to treatment, and monitoring of gastric cancer progression.

Cytokine Genetic Variations and Fatigue Among Patients With Breast Cancer

Science.gov (United States)

Bower, Julienne E.; Ganz, Patricia A.; Irwin, Michael R.; Castellon, Steven; Arevalo, Jesusa; Cole, Steven W.

2013-01-01

Purpose Fatigue is a common adverse effect of cancer treatment and may persist for years after treatment completion. However, risk factors for post-treatment fatigue have not been determined. On the basis of studies suggesting an inflammatory basis for fatigue, this study tested the hypothesis that expression-regulating polymorphisms in proinflammatory cytokine genes would predict post-treatment fatigue in breast cancer survivors. Patients and Methods Women diagnosed with early-stage breast cancer (n = 171) completed questionnaires to assess fatigue and other behavioral symptoms (ie, depressive symptoms, memory complaints, sleep disturbance) and provided blood for genotyping within 3 months after primary treatment. Genomic DNA was extracted from peripheral-blood leukocytes and assayed for single nucleotide polymorphisms (SNPs) in the promoter regions of three cytokine genes: ILB −511 C>T (rs16944), IL6 −174 G>C (rs1800795), and TNF −308 G>A (rs1800629). An additive genetic risk score was computed by summing the number of high-expression alleles (zero, one, or two) across all three polymorphisms. Results The genetic risk index was significantly associated with fatigue; as the number of high-expression alleles increased, so did self-reported fatigue severity (P = .002). Analyses of individual SNPs showed that TNF −308 and IL6 −174 were independently associated with fatigue (P = .032). The genetic risk index was also associated with depressive symptoms (P = .007) and memory complaints (P = .016). Conclusion These findings further implicate inflammatory processes as contributors to cancer-related fatigue and suggest a new strategy for identifying and treating patients at risk for this symptom based on genetic variants in proinflammatory cytokine genes. PMID:23530106

Colorectal Cancer in the Family: Psychosocial Distress and Social Issues in the Years Following Genetic Counselling

Directory of Open Access Journals (Sweden)

Bleiker Eveline MA

2007-06-01

Full Text Available Abstract Background This study examined: (1 levels of cancer-specific distress more than one year after genetic counselling for hereditary nonpolyposis colorectal cancer (HNPCC; (2 associations between sociodemographic, clinical and psychosocial factors and levels of distress; (3 the impact of genetic counselling on family relationships, and (4 social consequences of genetic counselling. Methods In this cross-sectional study, individuals who had received genetic counselling for HNPCC during 1986–1998 completed a self-report questionnaire by mail. Results 116 individuals (81% response rate completed the questionnaire, on average 4 years after the last counselling session. Of all respondents, 6% had clinically significant levels of cancer-specific distress (Impact of Event Scale, IES. Having had contact with a professional psychosocial worker for cancer risk in the past 10 years was significantly associated with higher levels of current cancer specific distress. Only a minority of the counselees reported any adverse effects of genetic counselling on: communication about genetic counselling with their children (9%, family relationships (5%, obtaining life insurance (8%, choice or change of jobs (2%, and obtaining a mortgage (2%. Conclusion On average, four years after genetic counselling for HNPCC, only a small minority of counselled individuals reports clinically significant levels of distress, or significant family or social problems.

Human genome and genetic sequencing research and informed consent

International Nuclear Information System (INIS)

Iwakawa, Mayumi

2003-01-01

On March 29, 2001, the Ethical Guidelines for Human Genome and Genetic Sequencing Research were established. They have intended to serve as ethical guidelines for all human genome and genetic sequencing research practice, for the purpose of upholding respect for human dignity and rights and enforcing use of proper methods in the pursuit of human genome and genetic sequencing research, with the understanding and cooperation of the public. The RadGenomics Project has prepared a research protocol and informed consent document that follow these ethical guidelines. We have endeavored to protect the privacy of individual information, and have established a procedure for examination of research practices by an ethics committee. Here we report our procedure in order to offer this concept to the patients. (authors)

Intra-tumor genetic heterogeneity and mortality in head and neck cancer: analysis of data from the Cancer Genome Atlas.

Science.gov (United States)

Mroz, Edmund A; Tward, Aaron D; Tward, Aaron M; Hammon, Rebecca J; Ren, Yin; Rocco, James W

2015-02-01

Although the involvement of intra-tumor genetic heterogeneity in tumor progression, treatment resistance, and metastasis is established, genetic heterogeneity is seldom examined in clinical trials or practice. Many studies of heterogeneity have had prespecified markers for tumor subpopulations, limiting their generalizability, or have involved massive efforts such as separate analysis of hundreds of individual cells, limiting their clinical use. We recently developed a general measure of intra-tumor genetic heterogeneity based on whole-exome sequencing (WES) of bulk tumor DNA, called mutant-allele tumor heterogeneity (MATH). Here, we examine data collected as part of a large, multi-institutional study to validate this measure and determine whether intra-tumor heterogeneity is itself related to mortality. Clinical and WES data were obtained from The Cancer Genome Atlas in October 2013 for 305 patients with head and neck squamous cell carcinoma (HNSCC), from 14 institutions. Initial pathologic diagnoses were between 1992 and 2011 (median, 2008). Median time to death for 131 deceased patients was 14 mo; median follow-up of living patients was 22 mo. Tumor MATH values were calculated from WES results. Despite the multiple head and neck tumor subsites and the variety of treatments, we found in this retrospective analysis a substantial relation of high MATH values to decreased overall survival (Cox proportional hazards analysis: hazard ratio for high/low heterogeneity, 2.2; 95% CI 1.4 to 3.3). This relation of intra-tumor heterogeneity to survival was not due to intra-tumor heterogeneity's associations with other clinical or molecular characteristics, including age, human papillomavirus status, tumor grade and TP53 mutation, and N classification. MATH improved prognostication over that provided by traditional clinical and molecular characteristics, maintained a significant relation to survival in multivariate analyses, and distinguished outcomes among patients having

Inter-chromosomal variation in the pattern of human population genetic structure

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Baye Tesfaye M

2011-05-01

Full Text Available Abstract Emerging technologies now make it possible to genotype hundreds of thousands of genetic variations in individuals, across the genome. The study of loci at finer scales will facilitate the understanding of genetic variation at genomic and geographic levels. We examined global and chromosomal variations across HapMap populations using 3.7 million single nucleotide polymorphisms to search for the most stratified genomic regions of human populations and linked these regions to ontological annotation and functional network analysis. To achieve this, we used five complementary statistical and genetic network procedures: principal component (PC, cluster, discriminant, fixation index (FST and network/pathway analyses. At the global level, the first two PC scores were sufficient to account for major population structure; however, chromosomal level analysis detected subtle forms of population structure within continental populations, and as many as 31 PCs were required to classify individuals into homogeneous groups. Using recommended population ancestry differentiation measures, a total of 126 regions of the genome were catalogued. Gene ontology and networks analyses revealed that these regions included the genes encoding oculocutaneous albinism II (OCA2, hect domain and RLD 2 (HERC2, ectodysplasin A receptor (EDAR and solute carrier family 45, member 2 (SLC45A2. These genes are associated with melanin production, which is involved in the development of skin and hair colour, skin cancer and eye pigmentation. We also identified the genes encoding interferon-γ (IFNG and death-associated protein kinase 1 (DAPK1, which are associated with cell death, inflammatory and immunological diseases. An in-depth understanding of these genomic regions may help to explain variations in adaptation to different environments. Our approach offers a comprehensive strategy for analysing chromosome-based population structure and differentiation, and demonstrates the

miR-134: A Human Cancer Suppressor?

Directory of Open Access Journals (Sweden)

Jing-Yu Pan

2017-03-01

Full Text Available MicroRNAs (miRNAs are small noncoding RNAs approximately 20–25 nt in length, which play crucial roles through directly binding to corresponding 3′ UTR of targeted mRNAs. It has been reported that miRNAs are involved in numerous of diseases, including cancers. Recently, miR-134 has been identified to dysregulate in handles of human cancers, such as lung cancer, glioma, breast cancer, colorectal cancer, and so on. Increasing evidence indicates that miR-134 is essential for human carcinoma and participates in tumor cell proliferation, apoptosis, invasion and metastasis, drug resistance, as well as cancer diagnosis, treatment, and prognosis. Nevertheless, its roles in human cancer are still ambiguous, and its mechanisms are sophisticated as well, referring to a variety of targets and signal pathways, such as STAT5B, KRAS, MAPK/ERK signal pathway, Notch pathway, etc. Herein, we review the crucial roles of miR-134 in scores of human cancers via analyzing latest investigations, which might provide evidence for cancer diagnose, treatment, prognosis, or further investigations.

Association of education & lifestyle factors with the perception of genetic knowledge on the development of lung cancer

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Liang Wang

2016-01-01

Full Text Available Background & objectives: The perception of genetic knowledge is useful for improving the heath behaviour change against developing cancers. However, no studies have investigated the perception of genetic knowledge on the development of lung cancer. The aim of this study was to examine demographic and lifestyle factors of the perception of genetic knowledge on the development of lung cancer. Methods: Data on 2,295 US adults (739 had the perception of genetic knowledge were taken from the 2003 Health Information National Trends Survey. Multiple logistic regression models were used to evaluate potential factors of the perception of genetic knowledge of lung cancer. Results: Participants aged ≥65 yr were more likely to have the perception of genetic knowledge than those aged 18-44 yr (OR=1.77, 95% CI=1.27-2.46. Higher education was associated with a greater perception of genetic knowledge (OR=1.47, 95% CI=1.16-1.87. Subjects with correct smoking attitude were more than three times more likely to have the perception of genetic knowledge (OR=3.15, 95% CI=2.10-4.72. Subjects with exercise were at an increased likelihood of having the perception of genetic knowledge than those without exercise (OR=1.63, 95% CI=1.24-2.13. Interpretation & conclusions: Positive associations were observed between education and lifestyle factors and the perception of genetic knowledge on the development of lung cancer among US adults. Strategies developed to improve the perception of genetic knowledge of lung cancer may target on individuals who are young, less educated, and lack correct smoking attitude or exercise.

Open reading frames associated with cancer in the dark matter of the human genome.

Science.gov (United States)

Delgado, Ana Paula; Brandao, Pamela; Chapado, Maria Julia; Hamid, Sheilin; Narayanan, Ramaswamy

2014-01-01

The uncharacterized proteins (open reading frames, ORFs) in the human genome offer an opportunity to discover novel targets for cancer. A systematic analysis of the dark matter of the human proteome for druggability and biomarker discovery is crucial to mining the genome. Numerous data mining tools are available to mine these ORFs to develop a comprehensive knowledge base for future target discovery and validation. Using the Genetic Association Database, the ORFs of the human dark matter proteome were screened for evidence of association with neoplasms. The Phenome-Genome Integrator tool was used to establish phenotypic association with disease traits including cancer. Batch analysis of the tools for protein expression analysis, gene ontology and motifs and domains was used to characterize the ORFs. Sixty-two ORFs were identified for neoplasm association. The expression Quantitative Trait Loci (eQTL) analysis identified thirteen ORFs related to cancer traits. Protein expression, motifs and domain analysis and genome-wide association studies verified the relevance of these OncoORFs in diverse tumors. The OncoORFs are also associated with a wide variety of human diseases and disorders. Our results link the OncoORFs to diverse diseases and disorders. This suggests a complex landscape of the uncharacterized proteome in human diseases. These results open the dark matter of the proteome to novel cancer target research. Copyright© 2014, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

Telomere Length and the Cancer-Atherosclerosis Trade-Off.

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Rivka C Stone

2016-07-01

Full Text Available Modern humans, the longest-living terrestrial mammals, display short telomeres and repressed telomerase activity in somatic tissues compared with most short-living small mammals. The dual trait of short telomeres and repressed telomerase might render humans relatively resistant to cancer compared with short-living small mammals. However, the trade-off for cancer resistance is ostensibly increased age-related degenerative diseases, principally in the form of atherosclerosis. In this communication, we discuss (a the genetics of human telomere length, a highly heritable complex trait that is influenced by genetic ancestry, sex, and paternal age at conception, (b how cancer might have played a role in the evolution of telomere biology across mammals, (c evidence that in modern humans telomere length is a determinant (rather than only a biomarker of cancer and atherosclerosis, and (d the potential influence of relatively recent evolutionary forces in fashioning the variation in telomere length across and within populations, and their likely lasting impact on major diseases in humans. Finally, we propose venues for future research on human telomere genetics in the context of its potential role in shaping the modern human lifespan.

Genetic susceptibility loci, pesticide exposure and prostate cancer risk.

Directory of Open Access Journals (Sweden)

Stella Koutros

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

The need for interaction between assisted reproduction technology and genetics: recommendations of the European Societies of Human Genetics and Human Reproduction and Embryology.

Science.gov (United States)

2006-08-01

Infertility and reproductive genetic risk are both increasing in our societies because of lifestyle changes and possibly environmental factors. Owing to the magnitude of the problem, they have implications not only at the individual and family levels but also at the community level. This leads to an increasing demand for access to assisted reproduction technology (ART) and genetic services, especially when the cause of infertility may be genetic in origin. The increasing application of genetics in reproductive medicine and vice versa requires closer collaboration between the two disciplines. ART and genetics are rapidly evolving fields where new technologies are currently introduced without sufficient knowledge of their potential long-term effects. As for any medical procedures, there are possible unexpected effects which need to be envisaged to make sure that the balance between benefits and risks is clearly on the benefit side. The development of ART and genetics as scientific activities is creating an opportunity to understand the early stages of human development, which is leading to new and challenging findings/knowledge. However, there are opinions against investigating the early stages of development in humans who deserve respect and attention. For all these reasons, these two societies, European Society of Human Genetics (ESHG) and European Society of Human Reproduction and Embryology (ESHRE), have joined efforts to explore the issues at stake and to set up recommendations to maximize the benefit for the couples in need and for the community.

Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk

DEFF Research Database (Denmark)

Blackburn, Anneke C; Hill, Linda Z; Roberts, Amy L

2007-01-01

Low-penetrance breast cancer susceptibility alleles seem to play a significant role in breast cancer risk but are difficult to identify in human cohorts. A genetic screen of 176 N2 backcross progeny of two Trp53(+/-) strains, BALB/c and C57BL/6, which differ in their susceptibility to mammary...... tumors, identified a modifier of mammary tumor susceptibility in an approximately 25-Mb interval on mouse chromosome 7 (designated SuprMam1). Relative to heterozygotes, homozygosity for BALB/c alleles of SuprMam1 significantly decreased mammary tumor latency from 70.7 to 61.1 weeks and increased risk...

A genome editing approach to study cancer stem cells in human tumors.

Science.gov (United States)

Cortina, Carme; Turon, Gemma; Stork, Diana; Hernando-Momblona, Xavier; Sevillano, Marta; Aguilera, Mònica; Tosi, Sébastien; Merlos-Suárez, Anna; Stephan-Otto Attolini, Camille; Sancho, Elena; Batlle, Eduard

2017-07-01

The analysis of stem cell hierarchies in human cancers has been hampered by the impossibility of identifying or tracking tumor cell populations in an intact environment. To overcome this limitation, we devised a strategy based on editing the genomes of patient-derived tumor organoids using CRISPR/Cas9 technology to integrate reporter cassettes at desired marker genes. As proof of concept, we engineered human colorectal cancer (CRC) organoids that carry EGFP and lineage-tracing cassettes knocked in the LGR5 locus. Analysis of LGR5-EGFP + cells isolated from organoid-derived xenografts demonstrated that these cells express a gene program similar to that of normal intestinal stem cells and that they propagate the disease to recipient mice very efficiently. Lineage-tracing experiments showed that LGR5 + CRC cells self-renew and generate progeny over long time periods that undergo differentiation toward mucosecreting- and absorptive-like phenotypes. These genetic experiments confirm that human CRCs adopt a hierarchical organization reminiscent of that of the normal colonic epithelium. The strategy described herein may have broad applications to study cell heterogeneity in human tumors. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

The impact of direct-to-consumer marketing of cancer genetic testing on women according to their genetic risk.

Science.gov (United States)

Lowery, Jan T; Byers, Tim; Axell, Lisen; Ku, Lisa; Jacobellis, Jillian

2008-12-01

To assess the impact of direct-to-consumer marketing for genetic testing among women of varying genetic risk for breast and ovarian cancer. Telephone surveys were conducted with 315 women in Denver, Colorado, one target audience for the Myriad BRACAnalysis ad campaign. Genetic risk was determined from personal and family history and grouped by probability of having a BRCA1/2 mutation (low or =10%). High-risk women were more knowledgeable about BRACAnalysis and more likely to recall the media ads than were low-risk women (60 vs. 39%, P audience. Concern about breast cancer was not appreciably increased. A large percentage of low-risk women (not candidates for testing) expressed interest in testing, suggesting the campaign was too broad. A campaign targeted at high-risk women, who may benefit from testing might be preferred.

Animal models for human genetic diseases | Sharif | African Journal ...

African Journals Online (AJOL)

The study of human genetic diseases can be greatly aided by animal models because of their similarity to humans in terms of genetics. In addition to understand diverse aspects of basic biology, model organisms are extensively used in applied research in agriculture, industry, and also in medicine, where they are used to ...

Genetic toxicology and cancer risk assessment

National Research Council Canada - National Science Library

Choy, Wai Nang

2001-01-01

... their risks to humans are obvious goals for the protection of public health. When exposure is unavoidable, an accurate estimation of human risk as a result of exposure is essential for making regulatory decisions. Quantitative cancer risk assessment is an intricate process that utilizes knowledge from many different scien...

Pre-test genetic counseling services for hereditary breast and ovarian cancer delivered by non-genetics professionals in the state of Florida.

Science.gov (United States)

Vadaparampil, S T; Scherr, C L; Cragun, D; Malo, T L; Pal, T

2015-05-01

Genetic counseling and testing for hereditary breast and ovarian cancer now includes practitioners from multiple healthcare professions, specialties, and settings. This study examined whether non-genetics professionals (NGPs) perform guideline-based patient intake and informed consent before genetic testing. NGPs offering BRCA testing services in Florida (n = 386) were surveyed about clinical practices. Among 81 respondents (response rate = 22%), approximately half reported: sometimes scheduling a separate session for pre-test counseling lasting 11-30 min prior to testing, discussing familial implications of testing, benefits and limitations of risk management options, and discussing the potential psychological impact and insurance-related issues. Few constructed a three-generation pedigree, discussed alternative hereditary cancer syndromes, or the meaning of a variant result. This lack of adherence to guideline-based practice may result in direct harm to patients and their family members. NGPs who are unable to deliver guideline adherent cancer genetics services should focus on identification and referral of at-risk patients to in person or telephone services provided by genetics professionals. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

International Nuclear Information System (INIS)

Chistiakov, Dimitry A.; Voronova, Natalia V.; Chistiakov, Pavel A.

2008-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2008-06-15

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

Expression and new exon mutations of the human Beta defensins and their association on colon cancer development.

Directory of Open Access Journals (Sweden)

Abdelhabib Semlali

Full Text Available The development of cancer involves genetic predisposition and a variety of environmental exposures. Genome-wide linkage analyses provide evidence for the significant linkage of many diseases to susceptibility loci on chromosome 8p23, the location of the human defensin gene cluster. Human β-defensins (hBDs are important molecules of innate immunity. This study was designed to analyze the expression and genetic variations in hBDs (hBD-1, hBD-2, hBD-3 and hBD-4 and their putative association with colon cancer. hBD gene expression and relative protein expression were evaluated by Real-Time polymerase chain reaction (qPCR and immunohistochemistry, respectively, from 40 normal patients and 40 age-matched patients with colon cancer in Saudi Arabia. In addition, hBD polymorphisms were genotyped by exon sequencing and by promoter methylation. hBD-1, hBD-2, hBD-3 and hBD-4 basal messenger RNA expression was significantly lower in tumor tissues compared with normal tissues. Several insertion mutations were detected in different exons of the analyzed hBDs. However, no methylation in any hBDs promoters was detected because of the limited number of CpG islands in these regions. We demonstrated for the first time a link between hBD expression and colon cancer. This suggests that there is a significant link between innate immunity deregulation through disruption of cationic peptides (hBDs and the potential development of colon cancer.

Randomized trial of proactive rapid genetic counseling versus usual care for newly diagnosed breast cancer patients.

Science.gov (United States)

Schwartz, Marc D; Peshkin, Beth N; Isaacs, Claudine; Willey, Shawna; Valdimarsdottir, Heiddis B; Nusbaum, Rachel; Hooker, Gillian; O'Neill, Suzanne; Jandorf, Lina; Kelly, Scott P; Heinzmann, Jessica; Zidell, Aliza; Khoury, Katia

2018-04-02

Breast cancer patients who carry BRCA1/BRCA2 gene mutations may consider bilateral mastectomy. Having bilateral mastectomy at the time of diagnosis not only reduces risk of a contralateral breast cancer, but can eliminate the need for radiation therapy and yield improved reconstruction options. However, most patients do not receive genetic counseling or testing at the time of their diagnosis. In this trial, we tested proactive rapid genetic counseling and testing (RGCT) in newly diagnosed breast cancer patients in order to facilitate pre-surgical genetic counseling and testing. We recruited newly diagnosed breast cancer patients at increased risk for carrying a BRCA1/2 mutation. Of 379 eligible patients who completed a baseline survey, 330 agreed to randomization in a 2:1 ratio to RGCT (n = 220) versus UC (n = 108). Primary outcomes were genetic counseling and testing uptake and breast cancer surgical decisions. RGCT led to higher overall (83.8% vs. 54.6%; p genetic counseling uptake compared to UC. Despite higher rates of genetic counseling, RGCT did not differ from UC in overall (54.1% vs. 49.1%, p > 0.10) or pre-surgical (30.6% vs. 27.4%, p > 0.10) receipt of genetic test results nor did they differ in uptake of bilateral mastectomy (26.6% vs. 21.8%, p > 0.10). Although RGCT yielded increased genetic counseling participation, this did not result in increased rates of pre-surgical genetic testing or impact surgical decisions. These data suggest that those patients most likely to opt for genetic testing at the time of diagnosis are being effectively identified by their surgeons.

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

Directory of Open Access Journals (Sweden)

Kendra A Williams

2014-11-01

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

The knowledge value-chain of genetic counseling for breast cancer: an empirical assessment of prediction and communication processes.

Science.gov (United States)

Amara, Nabil; Blouin-Bougie, Jolyane; Jbilou, Jalila; Halilem, Norrin; Simard, Jacques; Landry, Réjean

2016-01-01

The aim of this paper is twofold: to analyze the genetic counseling process for breast cancer with a theoretical knowledge transfer lens and to compare generalists, medical specialists, and genetic counselors with regards to their genetic counseling practices. This paper presents the genetic counseling process occurring within a chain of value-adding activities of four main stages describing health professionals' clinical practices: (1) evaluation, (2) investigation, (3) information, and (4) decision. It also presents the results of a cross-sectional study based on a Canadian medical doctors and genetic counselors survey (n = 176) realized between July 2012 and March 2013. The statistical exercise included descriptive statistics, one-way ANOVA and post-hoc tests. The results indicate that even though all types of health professionals are involved in the entire process of genetic counseling for breast cancer, genetic counselors are more involved in the evaluation of breast cancer risk, while medical doctors are more active in the decision toward breast cancer risk management strategies. The results secondly demonstrate the relevance and the key role of genetic counselors in the care provided to women at-risk of familial breast cancer. This paper presents an integrative framework to understand the current process of genetic counseling for breast cancer in Canada, and to shed light on how and where health professionals contribute to the process. It also offers a starting point for assessing clinical practices in genetic counseling in order to establish more clearly where and to what extent efforts should be undertaken to implement future genetic services.

Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic

Directory of Open Access Journals (Sweden)

Samantha B. Foley

2015-01-01

Full Text Available Despite the potential of whole-genome sequencing (WGS to improve patient diagnosis and care, the empirical value of WGS in the cancer genetics clinic is unknown. We performed WGS on members of two cohorts of cancer genetics patients: those with BRCA1/2 mutations (n = 176 and those without (n = 82. Initial analysis of potentially pathogenic variants (PPVs, defined as nonsynonymous variants with allele frequency < 1% in ESP6500 in 163 clinically-relevant genes suggested that WGS will provide useful clinical results. This is despite the fact that a majority of PPVs were novel missense variants likely to be classified as variants of unknown significance (VUS. Furthermore, previously reported pathogenic missense variants did not always associate with their predicted diseases in our patients. This suggests that the clinical use of WGS will require large-scale efforts to consolidate WGS and patient data to improve accuracy of interpretation of rare variants. While loss-of-function (LoF variants represented only a small fraction of PPVs, WGS identified additional cancer risk LoF PPVs in patients with known BRCA1/2 mutations and led to cancer risk diagnoses in 21% of non-BRCA cancer genetics patients after expanding our analysis to 3209 ClinVar genes. These data illustrate how WGS can be used to improve our ability to discover patients' cancer genetic risks.

Potential role of genetic markers in the management of kidney cancer

NARCIS (Netherlands)

Junker, K.; Ficarra, V.; Kwon, E.D.; Leibovich, B.C.; Thompson, R.H.; Oosterwijk, E.

2013-01-01

CONTEXT: Kidney cancer is not a single entity but comprises a number of different types of cancer that occur in the kidney including renal cell tumours as the most common type. Four major renal cell tumour subtypes can be distinguished based on morphologic and genetic characteristics. To

Hereditary breast/ovarian cancer--pitfalls in genetic counseling.

Science.gov (United States)

Dagan, E; Gershoni-Baruch, R

2001-10-01

Genetic counseling and risk assessment, given to women with a family history of breast/ovarian cancer, are regularly based on pedigree analysis. In the Ashkenazi Jewish population, hereditary breast/ovarian cancer is mainly attributed to three founder mutations, namely, 185delAG, 5382insC, and 6174delT, in BRCA1/2 genes. The overall frequency of these mutations, in the Jewish Ashkenazi population, is as high as 2.5%. Based on clinical and family history data, the results of BRCA molecular testing, in Ashkenazi individuals at risk, are appropriately anticipated in most cases. Here we report on five families, in which the segregation of BRCA1/2 mutations, in affected and unaffected family members, was unexpected, emphasizing the need to test, for founder mutations, every Ashkenazi individual at risk, irrespective of the genotype of affected family members. Ultimately, risk assessments and recommendations, in Ashkenazi women, should be invariably based on the results of genetic testing.

Women’s Satisfaction with Genetic Counseling for Hereditary Breast-Ovarian Cancer: Psychological Aspects

OpenAIRE

Tercyak, Kenneth P.; DeMarco, Tiffani A.; Mars, Bryn D.; Peshkin, Beth N.

2004-01-01

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...

Discretization of Gene Expression Data Unmasks Molecular Subgroups Recurring in Different Human Cancer Types.

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Manfred Beleut

Full Text Available Despite the individually different molecular alterations in tumors, the malignancy associated biological traits are strikingly similar. Results of a previous study using renal cell carcinoma (RCC as a model pointed towards cancer-related features, which could be visualized as three groups by microarray based gene expression analysis. In this study, we used a mathematic model to verify the presence of these groups in RCC as well as in other cancer types. We developed an algorithm for gene-expression deviation profiling for analyzing gene expression data of a total of 8397 patients with 13 different cancer types and normal tissues. We revealed three common Cancer Transcriptomic Profiles (CTPs which recurred in all investigated tumors. Additionally, CTPs remained robust regardless of the functions or numbers of genes analyzed. CTPs may represent common genetic fingerprints, which potentially reflect the closely related biological traits of human cancers.

Genetic and Epigenetic Tumor Suppressor Gene Silencing are Distinct Molecular Phenotypes Driven by Growth Promoting Mutations in Non small Cell Lung Cancer

International Nuclear Information System (INIS)

Marsit, C. J.; Kelsey, K. T.; Houseman, E. A.; Kelsey, K. T.; Houseman, E. A.; Nelson, H. H.

2008-01-01

Both genetic and epigenetic alterations characterize human non small cell lung cancer (NSCLC), but the biological processes that create or select these alterations remain incompletely investigated. Our hypothesis posits that a roughly reciprocal relationship between the propensity for promoter hyper methylation and a propensity for genetic deletion leads to distinct molecular phenotypes of lung cancer. To test this hypothesis, we examined promoter hyper methylation of 17 tumor suppressor genes, as a marker of epigenetic alteration propensity, and deletion events at the 3p21 region, as a marker of genetic alteration. To model the complex biology between these somatic alterations, we utilized an item response theory model. We demonstrated that tumors exhibiting LOH at greater than 30% of informative alleles in the 3p21 region have a significantly reduced propensity for hyper methylation. At the same time, tumors with activating KRAS mutations showed a significantly increased propensity for hyper methylation of the loci examined, a result similar to what has been observed in colon cancer. These data suggest that NSCLCs have distinct epigenetic or genetic alteration phenotypes acting upon tumor suppressor genes and that mutation of oncogenic growth promoting genes, such as KRAS, is associated with the epigenetic phenotype.

Human genetics of infectious diseases: a unified theory

Science.gov (United States)

Casanova, Jean-Laurent; Abel, Laurent

2007-01-01

Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predisposing the individual to a principal or single type of infection is emerging. In parallel, several common infections have been shown to reflect the inheritance of one major susceptibility gene, at least in some populations. This novel causal relationship (one gene, one infection) blurs the distinction between patient-based Mendelian genetics and population-based complex genetics, and provides a unified conceptual frame for exploring the molecular genetic basis of infectious diseases in humans. PMID:17255931

Genetic contributions to human brain morphology and intelligence

DEFF Research Database (Denmark)

Hulshoff Pol, HE; Schnack, HG; Posthuma, D

2006-01-01

Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology...... of specific GM areas in the brain have been studied, the heritability of focal WM is unknown. Similarly, it is unresolved whether there is a common genetic origin of focal GM and WM structures with intelligence. We explored the genetic influence on focal GM and WM densities in magnetic resonance brain images...

Co-carcinogenesis: Human Papillomaviruses, Coal Tar Derivatives, and Squamous Cell Cervical Cancer

Directory of Open Access Journals (Sweden)

Harry W. Haverkos

2017-11-01

Full Text Available Cervical cancer (CC is the fourth most common cancers among women worldwide. Human papillomaviruses (HPVs play a major role in the etiology of CC, with several lines of epidemiologic and experimental evidence supporting a role for non-viral (co-carcinogens and host genetic factors in controlling the risk for progression to neoplasia among HPV-infected individuals. The role of co-carcinogens in the development of CC is significant in the developing world where poor sanitation and other socio-economic conditions increase the infectious cancer burden. Here, we discuss how exposure to environmental factors such as coal tar derivatives from cigarette smoking, tar-based sanitary products, and inhaled smoke from biomass-burning stoves, could activate host pathways involved in development of HPV-associated squamous cell cancers in resource-limited settings. Understanding interactions between these pathways with certain oncogenic HPV genotypes may guide implementation of strategies for control and treatment of HPV-associated cancers that develop in populations at high risk of exposure to various co-carcinogens.

Genetic factors and breast cancer laterality

International Nuclear Information System (INIS)

Amer, Magid H

2014-01-01

between patients and their first-degree relatives in regards to cancer laterality and possibly age at initial diagnosis of cancer may suggest an underlying inherited genetic predisposition

Cancer Screening and Genetics: A Tale of Two Paradigms

OpenAIRE

Hamilton, Jada G.; Edwards, Heather M.; Khoury, Muin J.; Taplin, Stephen H.

2014-01-01

The long-standing medical tradition to “first do no harm” is reflected in population-wide evidence-based recommendations for cancer screening tests that focus primarily on reducing morbidity and mortality. The conventional cancer screening process is predicated on finding early-stage disease that can be treated effectively; yet emerging genetic and genomic testing technologies have moved the target earlier in the disease development process to identify a probabilistic predisposition to diseas...

Fetal Microchimerism in Cancer Protection and Promotion: Current Understanding in Dogs and the Implications for Human Health.

Science.gov (United States)

Bryan, Jeffrey N

2015-05-01

Fetal microchimerism is the co-existence of small numbers of cells from genetically distinct individuals living within a mother's body following pregnancy. During pregnancy, bi-directional exchange of cells occurs resulting in maternal microchimerism and even sibling microchimerism in offspring. The presence of fetal microchimerism has been identified with lower frequency in patients with cancers such as breast and lymphoma and with higher frequency in patients with colon cancer and autoimmune diseases. Microchimeric cells have been identified in healing and healed tissues as well as normal and tumor tissues. This has led to the hypothesis that fetal microchimerism may play a protective role in some cancers and may provoke other cancers or autoimmune disease. The long periods of risk for these diseases make it a challenge to prospectively study this phenomenon in human populations. Dogs get similar cancers as humans, share our homes and environmental exposures, and live compressed life-spans, allowing easier prospective study of disease development. This review describes the current state of understanding of fetal microchimerism in humans and dogs and highlights the similarities of the common cancers mammary carcinoma, lymphoma, and colon cancer between the two species. Study of fetal microchimerism in dogs might hold the key to characterization of the type and function of microchimeric cells and their role in health and disease. Such an understanding could then be applied to preventing and treating disease in humans.

[Human papilloma virus and cervical cancer. An historical review on the development of research on cancer of the cervix uteri in Venezuela].

Science.gov (United States)

García-Tamayo, Jorge; Molina, Julia; Blasco-Olaetxea, Eduardo

2010-06-01

The history on the relationship of VPH infection and cervical cancer was examined. Findings were initially reported in Maracaibo(1971), later in Mexico(1973) and thereafter several studies on the ultrastructure and immunohistochemistry of VPH infection and its role on cervical cancer were described. The ultrastructural findings of viral particles of HPV and their proteins, as well as their role in the incorporation of the viral genome to the human cervical cells were also described. Glycoproteins on the surface of cervical cells were reviewed and their importance on HPV infection was related to p16, blood group antigens and early genetic changes in the cell cycle with loss of heterozigocity, all of which, stimulated by the high risk HPV infection lead to cervical cancer.

Carcinogenesis. Genetics and circumstances

International Nuclear Information System (INIS)

Hino, Okio

2005-01-01

Described are the author's study and aspect concerning carcinogenesis and radiation carcinogenesis, where he thinks cancer is not automatic, has a process and takes time. For radiation carcinogenic studies, he has used a model of the rat with genetically determined kidney cancer which is highly radiosensitive. That is, mutation by the so-called 2nd-hit of the causal gene (tumor suppressing gene Tsc2) is studied in the animal where the 1st-hit has been done by retrotransposon insertion, with and without exposure to radiations (X-ray, heavy particle beam and cosmic ray) for elucidating the mutation spectrum of the causal gene, the carcinogenic target, for the ultimate aim to prevent human cancer. He discusses the drama-type molecular mechanisms leading to cancer, gene abnormality and disease crisis, discontinuity in continuity in cancer formation, and importance of the timely diagnosis and appropriate therapy, and concludes the present age is becoming such one as that the nature of cancer even if genetic can be controlled by circumstances like timely and appropriate intervention. (S.I.)

Tumor-Associated Neutrophils in Human Lung Cancer

Science.gov (United States)

2017-10-01

markers in humans. The logistical, ethical , and regulatory difficulties in obtaining human tumor tissue for research also act to discourage such...Mouse models of cancer. Annu. Rev. Pathol 6, 95–119 52. Merlo, L.M. et al. (2006) Cancer as an evolutionary and ecological process. Nat. Rev. Cancer...some effect on the phenotype and function of TANs. The logistical, ethical , and regulatory difficulties in obtaining human tumor tissue for research

Tutorial dialogues and gist explanations of genetic breast cancer risk.

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Widmer, Colin L; Wolfe, Christopher R; Reyna, Valerie F; Cedillos-Whynott, Elizabeth M; Brust-Renck, Priscila G; Weil, Audrey M

2015-09-01

The intelligent tutoring system (ITS) BRCA Gist is a Web-based tutor developed using the Shareable Knowledge Objects (SKO) platform that uses latent semantic analysis to engage women in natural-language dialogues to teach about breast cancer risk. BRCA Gist appears to be the first ITS designed to assist patients' health decision making. Two studies provide fine-grained analyses of the verbal interactions between BRCA Gist and women responding to five questions pertaining to breast cancer and genetic risk. We examined how "gist explanations" generated by participants during natural-language dialogues related to outcomes. Using reliable rubrics, scripts of the participants' verbal interactions with BRCA Gist were rated for content and for the appropriateness of the tutor's responses. Human researchers' scores for the content covered by the participants were strongly correlated with the coverage scores generated by BRCA Gist, indicating that BRCA Gist accurately assesses the extent to which people respond appropriately. In Study 1, participants' performance during the dialogues was consistently associated with learning outcomes about breast cancer risk. Study 2 was a field study with a more diverse population. Participants with an undergraduate degree or less education who were randomly assigned to BRCA Gist scored higher on tests of knowledge than those assigned to the National Cancer Institute website or than a control group. We replicated findings that the more expected content that participants included in their gist explanations, the better they performed on outcome measures. As fuzzy-trace theory suggests, encouraging people to develop and elaborate upon gist explanations appears to improve learning, comprehension, and decision making.

Cancer in Drosophila

DEFF Research Database (Denmark)

Herranz, Héctor; Eichenlaub, Teresa; Cohen, Stephen M

2016-01-01

Cancer genomics has greatly increased our understanding of the complexity of the genetic and epigenetic changes found in human tumors. Understanding the functional relationships among these elements calls for the use of flexible genetic models. We discuss the use of Drosophila models to study...

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

Science.gov (United States)

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

2015-11-01

The American Society of Clinical Oncology (ASCO) has long affirmed that the recognition and management of individuals with an inherited susceptibility to cancer are core elements of oncology care. ASCO released its first statement on genetic testing in 1996 and updated that statement in 2003 and 2010 in response to developments in the field. In 2014, the Cancer Prevention and Ethics Committees of ASCO commissioned another update to reflect the impact of advances in this area on oncology practice. In particular, there was an interest in addressing the opportunities and challenges arising from the application of massively parallel sequencing-also known as next-generation sequencing-to cancer susceptibility testing. This technology introduces a new level of complexity into the practice of cancer risk assessment and management, requiring renewed effort on the part of ASCO to ensure that those providing care to patients with cancer receive the necessary education to use this new technology in the most effective, beneficial manner. The purpose of this statement is to explore the challenges of new and emerging technologies in cancer genetics and provide recommendations to ensure their optimal deployment in oncology practice. Specifically, the statement makes recommendations in the following areas: germline implications of somatic mutation profiling, multigene panel testing for cancer susceptibility, quality assurance in genetic testing, education of oncology professionals, and access to cancer genetic services. © 2015 by American Society of Clinical Oncology.

Translating genomics: cancer genetics, public health and the making of the (de)molecularised body in Cuba and Brazil.

Science.gov (United States)

Gibbon, Sahra

2016-01-01

This article examines how cancer genetics has emerged as a focus for research and healthcare in Cuba and Brazil. Drawing on ethnographic research undertaken in community genetics clinics and cancer genetics services, the article examines how the knowledge and technologies associated with this novel area of healthcare are translated and put to work by researchers, health professionals, patients and their families in these two contexts. It illuminates the comparative similarities and differences in how cancer genetics is emerging in relation to transnational research priorities, the history and contemporary politics of public health and embodied vulnerability to cancer that reconfigures the scope and meaning of genomics as "personalised" medicine.

The impact of genetic counselling on risk perception and mental health in women with a family history of breast cancer.

Science.gov (United States)

Watson, M; Lloyd, S; Davidson, J; Meyer, L; Eeles, R; Ebbs, S; Murday, V

1999-02-01

The present study investigated: (1) perception of genetic risk and, (2) the psychological effects of genetic counselling in women with a family history of breast cancer. Using a prospective design, with assessment pre- and post-genetic counselling at clinics and by postal follow-up at 1, 6 and 12 months, attenders at four South London genetic clinics were assessed. Participants included 282 women with a family history of breast cancer. Outcome was measured in terms of mental health, cancer-specific distress and risk perception. High levels of cancer-specific distress were found pre-genetic counselling, with 28% of participants reporting that they worried about breast cancer 'frequently or constantly' and 18% that worry about breast cancer was 'a severe or definite problem'. Following genetic counselling, levels of cancer-specific distress were unchanged. General mental health remained unchanged over time (33% psychiatric cases detected pre-genetic counselling, 27% at 12 months after genetic counselling). Prior to their genetics consultation, participants showed poor knowledge of their lifetime risk of breast cancer since there was no association between their perceived lifetime risk (when they were asked to express this as a 1 in x odds ratio) and their actual risk, when the latter was calculated by the geneticist at the clinic using the CASH model. In contrast, women were more accurate about their risk of breast cancer pre-genetic counselling when this was assessed in broad categorical terms (i.e. very much lower/very much higher than the average woman) with a significant association between this rating and the subsequently calculated CASH risk figure (P = 0.001). Genetic counselling produced a modest shift in the accuracy of perceived lifetime risk, expressed as an odds ratio, which was maintained at 12 months' follow-up. A significant minority failed to benefit from genetic counselling; 77 women continued to over-estimate their risk and maintain high levels of

Ethnic background and genetic variation in the evaluation of cancer risk: a systematic review.

Science.gov (United States)

Jing, Lijun; Su, Li; Ring, Brian Z

2014-01-01

The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort's ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be studied and employed.

Ethnic Background and Genetic Variation in the Evaluation of Cancer Risk: A Systematic Review

Science.gov (United States)

Jing, Lijun; Su, Li; Ring, Brian Z.

2014-01-01

The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort’s ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be studied and

Factors influencing and modifying the decision to pursue genetic testing for skin cancer risk.

Science.gov (United States)

Fogel, Alexander L; Jaju, Prajakta D; Li, Shufeng; Halpern-Felsher, Bonnie; Tang, Jean Y; Sarin, Kavita Y

2017-05-01

Across cancers, the decision to pursue genetic testing is influenced more by subjective than objective factors. However, skin cancer, which is more prevalent, visual, and multifactorial than many other malignancies, may offer different motivations for pursuing such testing. The primary objective was to determine factors influencing the decision to receive genetic testing for skin cancer risk. A secondary objective was to assess the impact of priming with health questions on the decision to receive testing. We distributed anonymous online surveys through ResearchMatch.org to assess participant health, demographics, motivations, and interest in pursuing genetic testing for skin cancer risk. Two surveys with identical questions but different question ordering were used to assess the secondary objective. We received 3783 responses (64% response rate), and 85.8% desired testing. Subjective factors, including curiosity, perceptions of skin cancer, and anxiety, were the most statistically significant determinants of the decision to pursue testing (P < .001), followed by history of sun exposure (odds ratio 1.85, P < .01) and history of skin cancer (odds ratio 0.5, P = .01). Age and family history of skin cancer did not influence this decision. Participants increasingly chose testing if first queried about health behaviors (P < .0001). The decision to pursue hypothetical testing may differ from in-clinic decision-making. Self-selected, online participants may differ from the general population. Surveys may be subject to response bias. The decision to pursue genetic testing for skin cancer is primarily determined by subjective factors, such as anxiety and curiosity. Health factors, including skin cancer history, also influenced decision-making. Priming with consideration of objective health factors can increase the desire to pursue testing. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Ethnic background and genetic variation in the evaluation of cancer risk: a systematic review.

Directory of Open Access Journals (Sweden)

Lijun Jing

Full Text Available The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort's ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be

Beliefs about Cancer and Diet among Those Considering Genetic Testing for Colon Cancer

Science.gov (United States)

Palmquist, Aunchalee E. L.; Upton, Rachel; Lee, Seungjin; Panter, Abby T.; Hadley, Don W.; Koehly, Laura M.

2011-01-01

Objective: To assess beliefs about the role of diet in cancer prevention among individuals considering genetic testing for Lynch Syndrome. Design: Family-centered, cascade recruitment; baseline assessment of a longitudinal study. Setting: Clinical research setting. Participants: Participants were 390 persons, ages 18 and older, including persons…

L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice.

Directory of Open Access Journals (Sweden)

Hao Hong

Full Text Available New therapeutic modalities are needed for ovarian cancer, the most lethal gynecologic malignancy. Recent clinical trials have demonstrated the impressive therapeutic potential of adoptive therapy using chimeric antigen receptor (CAR-redirected T cells to target hematological cancers, and emerging studies suggest a similar impact may be achieved for solid cancers. We sought determine whether genetically-modified T cells targeting the CE7-epitope of L1-CAM, a cell adhesion molecule aberrantly expressed in several cancers, have promise as an immunotherapy for ovarian cancer, first demonstrating that L1-CAM was highly over-expressed on a panel of ovarian cancer cell lines, primary ovarian tumor tissue specimens, and ascites-derived primary cancer cells. Human central memory derived T cells (TCM were then genetically modified to express an anti-L1-CAM CAR (CE7R, which directed effector function upon tumor antigen stimulation as assessed by in vitro cytokine secretion and cytotoxicity assays. We also found that CE7R+ T cells were able to target primary ovarian cancer cells. Intraperitoneal (i.p. administration of CE7R+ TCM induced a significant regression of i.p. established SK-OV-3 xenograft tumors in mice, inhibited ascites formation, and conferred a significant survival advantage compared with control-treated animals. Taken together, these studies indicate that adoptive transfer of L1-CAM-specific CE7R+ T cells may offer a novel and effective immunotherapy strategy for advanced ovarian cancer.

Trends in human papillomavirus-related oropharyngeal cancer in Israel.

Science.gov (United States)

Amit, Moran; Ilana, Kaplan; Avraham, Sharon Pelles; Binenbaum, Yoav; Bachar, Gideon; Billan, Salem; Zaarura, Suliman; Czerninski, Rakefet; Bar-Tov, Matan; Maly, Alexander; Akrish, Sharon; Gil, Ziv

2016-04-01

The role of human papillomavirus (HPV) infection in oropharyngeal cancer (SCC) is well established. The annual incidence of oropharyngeal SCC in Israel is considerably lower than that in the United States. The purpose of this study was to assess the rate of HPV-related oropharyngeal SCC in Israel. The cohort included patients with oropharyngeal SCC who were treated during 1999 to 2011 in Israel. HPV typing was carried out using reverse hybridization and immunohistochemistry. Of the 74 patients analyzed, 25 (33.7%) had detectable HPV DNA. Patients in the HPV-positive group tended to be younger, with a higher rate of nodal metastases, and no history of smoking (p Israel as approximately 3-fold lower than in Western countries. Low exposure to HPV-16, a lower rate of transformation, to cancer or protective genetic factors may contribute to the lower rate of oropharyngeal SCC in Israel. © 2015 Wiley Periodicals, Inc. Head Neck 38: E274-E278, 2016. © 2015 Wiley Periodicals, Inc.

Genetic variant as a marker for bladder cancer therapy

Science.gov (United States)

Patients who have inherited a specific common genetic variant develop bladder cancer tumors that strongly express a protein known as prostate stem cell antigen (PSCA), which is also expressed in many pancreatic and prostate tumors, according to research a

DNA fingerprinting techniques for the analysis of genetic and epigenetic alterations in colorectal cancer.

Science.gov (United States)

Samuelsson, Johanna K; Alonso, Sergio; Yamamoto, Fumiichiro; Perucho, Manuel

2010-11-10

Genetic somatic alterations are fundamental hallmarks of cancer. In addition to point and other small mutations targeting cancer genes, solid tumors often exhibit aneuploidy as well as multiple chromosomal rearrangements of large fragments of the genome. Whether somatic chromosomal alterations and aneuploidy are a driving force or a mere consequence of tumorigenesis remains controversial. Recently it became apparent that not only genetic but also epigenetic alterations play a major role in carcinogenesis. Epigenetic regulation mechanisms underlie the maintenance of cell identity crucial for development and differentiation. These epigenetic regulatory mechanisms have been found substantially altered during cancer development and progression. In this review, we discuss approaches designed to analyze genetic and epigenetic alterations in colorectal cancer, especially DNA fingerprinting approaches to detect changes in DNA copy number and methylation. DNA fingerprinting techniques, despite their modest throughput, played a pivotal role in significant discoveries in the molecular basis of colorectal cancer. The aim of this review is to revisit the fingerprinting technologies employed and the oncogenic processes that they unveiled. 2010 Elsevier B.V. All rights reserved.

Inferences of Recent and Ancient Human Population History Using Genetic and Non-Genetic Data

Science.gov (United States)

Kitchen, Andrew

2008-01-01

I have adopted complementary approaches to inferring human demographic history utilizing human and non-human genetic data as well as cultural data. These complementary approaches form an interdisciplinary perspective that allows one to make inferences of human history at varying timescales, from the events that occurred tens of thousands of years…

Prediction of breast cancer risk based on profiling with common genetic variants

DEFF Research Database (Denmark)

Mavaddat, Nasim; Pharoah, Paul D P; Michailidou, Kyriaki

2015-01-01

BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. M...

Prediction of breast cancer risk based on profiling with common genetic variants

NARCIS (Netherlands)

N. Mavaddat (Nasim); P.D.P. Pharoah (Paul); K. Michailidou (Kyriaki); J.P. Tyrer (Jonathan); M.N. Brook (Mark N.); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); A.M. Dunning (Alison); M. Shah (Mitul); R.N. Luben (Robert); J. Brown (Judith); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune F.); H. Flyger (Henrik); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); J. Peto (Julian); I. dos Santos Silva (Isabel); F. Dudbridge (Frank); N. Johnson (Nichola); M.K. Schmidt (Marjanka); A. Broeks (Annegien); S. Verhoef; E.J. Rutgers (Emiel J.); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); L.A. Brinton (Louise); J. Lissowska (Jolanta); F.J. Couch (Fergus); J.E. Olson (Janet); C. Vachon (Celine); V.S. Pankratz (Shane); D. Lambrechts (Diether); H. Wildiers (Hans); C. van Ongeval (Chantal); E. van Limbergen (Erik); V. Kristensen (Vessela); G. Grenaker Alnæs (Grethe); S. Nord (Silje); A.-L. Borresen-Dale (Anne-Lise); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P.A. Fasching (Peter); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias); B. Burwinkel (Barbara); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); A. Trentham-Dietz (Amy); P. Newcomb (Polly); L. Titus (Linda); K.M. Egan (Kathleen M.); D. Hunter (David); S. Lindstrom (Stephen); R. Tamimi (Rulla); P. Kraft (Peter); N. Rahman (Nazneen); C. Turnbull (Clare); A. Renwick (Anthony); S. Seal (Sheila); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); P. Menéndez (Primitiva); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); T. Dörk (Thilo); H. Anton-Culver (Hoda); S.L. Neuhausen (Susan); A. Ziogas (Argyrios); L. Bernstein (Leslie); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); E.K. Khusnutdinova (Elza); M. Bermisheva (Marina); D. Prokofyeva (Darya); Z. Takhirova (Zalina); A. Meindl (Alfons); R.K. Schmutzler (Rita); C. Sutter (Christian); R. Yang (Rongxi); P. Schürmann (Peter); M. Bremer (Michael); H. Christiansen (Hans); T.-W. Park-Simon; P. Hillemanns (Peter); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); M. Sanchez (Marie); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); V. Pensotti (Valeria); J. Hopper (John); H. Tsimiklis (Helen); C. Apicella (Carmel); M.C. Southey (Melissa); H. Brauch (Hiltrud); T. Brüning (Thomas); Y.-D. Ko (Yon-Dschun); A.J. Sigurdson (Alice); M.M. Doody (Michele M.); U. Hamann (Ute); D. Torres (Diana); H.U. Ulmer (Hans); A. Försti (Asta); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A. Marie Mulligan (Anna); G. Chenevix-Trench (Georgia); R. Balleine (Rosemary); G.G. Giles (Graham); R.L. Milne (Roger); C.A. McLean (Catriona Ann); A. Lindblom (Annika); S. Margolin (Sara); C.A. Haiman (Christopher); B.E. Henderson (Brian); F. Schumacher (Fredrick); L. Le Marchand (Loic); U. Eilber (Ursula); S. Wang-Gohrke (Shan); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A.M.W. van den Ouweland (Ans); L.B. Koppert (Lisa); J. Carpenter (Jane); C. Clarke (Christine); R.J. Scott (Rodney J.); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); H. Brenner (Hermann); V. Arndt (Volker); C. Stegmaier (Christa); A. Karina Dieffenbach (Aida); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); K. Offit (Kenneth); J. Vijai (Joseph); M. Robson (Mark); R. Rau-Murthy (Rohini); M. Dwek (Miriam); R. Swann (Ruth); K. Annie Perkins (Katherine); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); D. Eccles (Diana); W. Tapper (William); M. Rafiq (Meena); E.M. John (Esther M.); A.S. Whittemore (Alice); S. Slager (Susan); D. Yannoukakos (Drakoulis); A.E. Toland (Amanda); S. Yao (Song); W. Zheng (Wei); S.L. Halverson (Sandra L.); A. González-Neira (Anna); G. Pita (Guillermo); M. Rosario Alonso; N. Álvarez (Nuria); D. Herrero (Daniel); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); M. Maranian (Melanie); S. Healey (Sue); J. Simard (Jacques); P. Hall (Per); D.F. Easton (Douglas); M. García-Closas (Montserrat)

2015-01-01

textabstractBackground: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is

The genetic component of human longevity

DEFF Research Database (Denmark)

Dato, Serena; Thinggaard, Mette Sørensen; De Rango, Francesco

2018-01-01

In human longevity studies, single nucleotide polymorphism (SNP) analysis identified a large number of genetic variants with small effects, yet not easily replicable in different populations. New insights may come from the combined analysis of different SNPs, especially when grouped by metabolic...... pathway. We applied this approach to study the joint effect on longevity of SNPs belonging to three candidate pathways, the insulin/insulin-like growth factor signalling (IIS), DNA repair and pro/antioxidant. We analysed data from 1,058 tagging SNPs in 140 genes, collected in 1825 subjects (1......, was further found influencing longitudinal survival in nonagenarian females (p = .026). Results here presented highlight the validity of SNP-SNP interactions analyses for investigating the genetics of human longevity, confirming previously identified markers but also pointing to novel genes as central nodes...

Noise genetics: inferring protein function by correlating phenotype with protein levels and localization in individual human cells.

Directory of Open Access Journals (Sweden)

Shlomit Farkash-Amar

2014-03-01

Full Text Available To understand gene function, genetic analysis uses large perturbations such as gene deletion, knockdown or over-expression. Large perturbations have drawbacks: they move the cell far from its normal working point, and can thus be masked by off-target effects or compensation by other genes. Here, we offer a complementary approach, called noise genetics. We use natural cell-cell variations in protein level and localization, and correlate them to the natural variations of the phenotype of the same cells. Observing these variations is made possible by recent advances in dynamic proteomics that allow measuring proteins over time in individual living cells. Using motility of human cancer cells as a model system, and time-lapse microscopy on 566 fluorescently tagged proteins, we found 74 candidate motility genes whose level or localization strongly correlate with motility in individual cells. We recovered 30 known motility genes, and validated several novel ones by mild knockdown experiments. Noise genetics can complement standard genetics for a variety of phenotypes.

Generation of Genetically Modified Organotypic Skin Cultures Using Devitalized Human Dermis.

Science.gov (United States)

Li, Jingting; Sen, George L

2015-12-14

Organotypic cultures allow the reconstitution of a 3D environment critical for cell-cell contact and cell-matrix interactions which mimics the function and physiology of their in vivo tissue counterparts. This is exemplified by organotypic skin cultures which faithfully recapitulates the epidermal differentiation and stratification program. Primary human epidermal keratinocytes are genetically manipulable through retroviruses where genes can be easily overexpressed or knocked down. These genetically modified keratinocytes can then be used to regenerate human epidermis in organotypic skin cultures providing a powerful model to study genetic pathways impacting epidermal growth, differentiation, and disease progression. The protocols presented here describe methods to prepare devitalized human dermis as well as to genetically manipulate primary human keratinocytes in order to generate organotypic skin cultures. Regenerated human skin can be used in downstream applications such as gene expression profiling, immunostaining, and chromatin immunoprecipitations followed by high throughput sequencing. Thus, generation of these genetically modified organotypic skin cultures will allow the determination of genes that are critical for maintaining skin homeostasis.

Characteristics of human amniotic fluid mesenchymal stem cells and their tropism to human ovarian cancer.

Directory of Open Access Journals (Sweden)

Liru Li

Full Text Available The mesenchymal stem cells (MSCs derived from amniotic fluid (AF have become an attractive stem cells source for cell-based therapy because they can be harvested at low cost and avoid ethical disputes. In human research, stem cells derived from AF gradually became a hot research direction for disease treatment, specifically for their plasticity, their reduced immunogenicity and their tumor tropism regardless of the tumor size, location and source. Our work aimed to obtain and characterize human amniotic fluid mesenchymal stem cells (AFMSCs and detect their ovarian cancer tropsim in nude mice model. Ten milliliters of twenty independent amniotic fluid samples were collected from 16-20 week pregnant women who underwent amniocentesis for fetal genetic determination in routine prenatal diagnosis in the first affiliated hospital of Harbin medical university. We successfully isolated the AFMSCs from thirteen of twenty amniotic fluid samples. AFMSCs presented a fibroblastic-like morphology during the culture. Flow cytometry analyses showed that the cells were positive for specific stem cell markers CD73,CD90, CD105, CD166 and HLA-ABC (MHC class I, but negative for CD 45,CD40, CD34, CD14 and HLA-DR (MHC class II. RT-PCR results showed that the AFMSCs expressed stem cell marker OCT4. AFMSCs could differentiate into bone cells, fat cells and chondrocytes under certain conditions. AFMSCs had the high motility to migrate to ovarian cancer site but didn't have the tumorigenicity. This study enhances the possibility of AFMSCs as drug carrier in human cell-based therapy. Meanwhile, the research emphasis in the future can also put in targeting therapy of ovarian cancer.

A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.

Science.gov (United States)

Hampel, Heather; Bennett, Robin L; Buchanan, Adam; Pearlman, Rachel; Wiesner, Georgia L

2015-01-01

The practice guidelines of the American College of Medical Genetics and Genomics (ACMG) and the National Society of Genetic Counselors (NSGC) are developed by members of the ACMG and NSGC to assist medical geneticists, genetic counselors, and other health-care providers in making decisions about appropriate management of genetic concerns, including access to and/or delivery of services. Each practice guideline focuses on a clinical or practice-based issue and is the result of a review and analysis of current professional literature believed to be reliable. As such, information and recommendations within the ACMG and NSGC joint practice guidelines reflect the current scientific and clinical knowledge at the time of publication, are current only as of their publication date, and are subject to change without notice as advances emerge. In addition, variations in practice, which take into account the needs of the individual patient and the resources and limitations unique to the institution or type of practice, may warrant approaches, treatments, and/or procedures that differ from the recommendations outlined in this guideline. Therefore, these recommendations should not be construed as dictating an exclusive course of management, nor does the use of such recommendations guarantee a particular outcome. Genetic counseling practice guidelines are never intended to displace a health-care provider's best medical judgment based on the clinical circumstances of a particular patient or patient population. Practice guidelines are published by the ACMG or the NSGC for educational and informational purposes only, and neither the ACMG nor the NSGC "approve" or "endorse" any specific methods, practices, or sources of information.Cancer genetic consultation is an important aspect of the care of individuals at increased risk of a hereditary cancer syndrome. Yet several patient, clinician, and system-level barriers hinder identification of individuals appropriate for cancer genetics

The comparative radiation genetics of humans and mice

International Nuclear Information System (INIS)

Neel, J.V.

1990-01-01

The attempt by geneticists to predict the genetic consequences for humans of exposure to ionizing radiation has arguably been one of the most serious social responsibilities they have faced in the past half century. Important for its own sake, this issue also serves as a prototype for the effort to evaluate the ultimate genetic impact on ourselves of other human perturbations of the environment in which our species functions. Recently the authors have been developing the thesis that according to the results of studies on the children of survivors of the atomic bombings, humans may not be as sensitive to the genetic effects of radiation as has been projected by various committees on the basis of data from the most commonly employed paradigm, the laboratory mouse. In this paper, the authors attempt as detailed a comparison as space permits of the findings on humans and mice, presenting the data in a fashion that will enable those who at certain critical points in the argument wish to make other assumptions, to do so. The authors argue that a reconsideration that includes all the data now available on mice brings the estimate of the doubling dose for mice into satisfactory agreement with the higher estimate based on humans

Apoptotic Cell Death Induced by Resveratrol Is Partially Mediated by the Autophagy Pathway in Human Ovarian Cancer Cells.

Directory of Open Access Journals (Sweden)

Fangfang Lang

Full Text Available Resveratrol (trans-3,4,5'-trihydroxystilbene is an active compound in food, such as red grapes, peanuts, and berries. Resveratrol exhibits an anticancer effect on various human cancer cells. However, the mechanism of resveratrol-induced anti-cancer effect at the molecular level remains to be elucidated. In this study, the mechanism underlying the anti-cancer effect of resveratrol in human ovarian cancer cells (OVCAR-3 and Caov-3 was investigated using various molecular biology techniques, such as flow cytometry, western blotting, and RNA interference, with a major focus on the potential role of autophagy in resveratrol-induced apoptotic cell death. We demonstrated that resveratrol induced reactive oxygen species (ROS generation, which triggers autophagy and subsequent apoptotic cell death. Resveratrol induced ATG5 expression and promoted LC3 cleavage. The apoptotic cell death induced by resveratrol was attenuated by both pharmacological and genetic inhibition of autophagy. The autophagy inhibitor chloroquine, which functions at the late stage of autophagy, significantly reduced resveratrol-induced cell death and caspase 3 activity in human ovarian cancer cells. We also demonstrated that targeting ATG5 by siRNA also suppressed resveratrol-induced apoptotic cell death. Thus, we concluded that a common pathway between autophagy and apoptosis exists in resveratrol-induced cell death in OVCAR-3 human ovarian cancer cells.

Awareness, knowledge, perceptions, and attitudes towards genetic testing for cancer risk among ethnic minority groups: a systematic review.

Science.gov (United States)

Hann, Katie E J; Freeman, Madeleine; Fraser, Lindsay; Waller, Jo; Sanderson, Saskia C; Rahman, Belinda; Side, Lucy; Gessler, Sue; Lanceley, Anne

2017-05-25

Genetic testing for risk of hereditary cancer can help patients to make important decisions about prevention or early detection. US and UK studies show that people from ethnic minority groups are less likely to receive genetic testing. It is important to understand various groups' awareness of genetic testing and its acceptability to avoid further disparities in health care. This review aims to identify and detail awareness, knowledge, perceptions, and attitudes towards genetic counselling/testing for cancer risk prediction in ethnic minority groups. A search was carried out in PsycInfo, CINAHL, Embase and MEDLINE. Search terms referred to ethnicity, genetic testing/counselling, cancer, awareness, knowledge, attitudes, and perceptions. Quantitative and qualitative studies, written in English, and published between 2000 and 2015, were included. Forty-one studies were selected for review: 39 from the US, and two from Australia. Results revealed low awareness and knowledge of genetic counselling/testing for cancer susceptibility amongst ethnic minority groups including African Americans, Asian Americans, and Hispanics. Attitudes towards genetic testing were generally positive; perceived benefits included positive implications for personal health and being able to inform family. However, negative attitudes were also evident, particularly the anticipated emotional impact of test results, and concerns about confidentiality, stigma, and discrimination. Chinese Australian groups were less studied, but of interest was a finding from qualitative research indicating that different views of who close family members are could impact on reported family history of cancer, which could in turn impact a risk assessment. Interventions are needed to increase awareness and knowledge of genetic testing for cancer risk and to reduce the perceived stigma and taboo surrounding the topic of cancer in ethnic minority groups. More detailed research is needed in countries other than the US and

Prediction of individual genetic risk to prostate cancer using a polygenic score

DEFF Research Database (Denmark)

Szulkin, Robert; Whitington, Thomas; Eklund, Martin

2015-01-01

BACKGROUND: Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate ca...

Association between N142D genetic polymorphism of GSTO2 and susceptibility to colorectal cancer.

Science.gov (United States)

Masoudi, Mohammad; Saadat, Iraj; Omidvari, Shahpour; Saadat, Mostafa

2011-10-01

Expression pattern analysis has been revealed that glutathione S-transferase omega 2 (GSTO2, a member of class omega) is ubiquitously expressed. Over expression of GSTO2 induced apoptosis. The gene encoding GSTO2 was localized to human chromosome 10q24.3, a region that may harbor gene(s) involved in the developing of colorectal cancer. To investigate the association between GSTO2 N142D genetic polymorphism and susceptibility to colorectal cancer the present study was done. We studied 63 (26 females, 37 males) colorectal cancer patients and 126 (52 females, 74 males) healthy individuals. The control subjects were frequency matched for age and gender with the colorectal cancer group. The genotypes were performed using RFLP-PCR method. The ND and DD genotypes were not associated with risk of colorectal cancer, in comparison with the NN genotype. Family history for cancer in the first degree of relatives significantly differed between cases and controls (P = 0.012). The profiles of GSTO2 genotypes and family history in control and cancerous groups were compared to each other. Subjects with NN genotype and positive family history significantly were at high risk to develop colorectal cancer in comparison with subjects with DD or ND genotypes and negative family history (P = 0.003). Present findings indicating that GSTO2 NN genotype increase the risk of colorectal cancer in persons with positive family history for cancer in the first degree relatives.

Gaps in Incorporating Germline Genetic Testing Into Treatment Decision-Making for Early-Stage Breast Cancer.

Science.gov (United States)

Kurian, Allison W; Li, Yun; Hamilton, Ann S; Ward, Kevin C; Hawley, Sarah T; Morrow, Monica; McLeod, M Chandler; Jagsi, Reshma; Katz, Steven J

2017-07-10

Purpose Genetic testing for breast cancer risk is evolving rapidly, with growing use of multiple-gene panels that can yield uncertain results. However, little is known about the context of such testing or its impact on treatment. Methods A population-based sample of patients with breast cancer diagnosed in 2014 to 2015 and identified by two SEER registries (Georgia and Los Angeles) were surveyed about genetic testing experiences (N = 3,672; response rate, 68%). Responses were merged with SEER data. A patient subgroup at higher pretest risk of pathogenic mutation carriage was defined according to genetic testing guidelines. Patients' attending surgeons were surveyed about genetic testing and results management. We examined patterns and correlates of genetic counseling and testing and the impact of results on bilateral mastectomy (BLM) use. Results Six hundred sixty-six patients reported genetic testing. Although two thirds of patients were tested before surgical treatment, patients without private insurance more often experienced delays. Approximately half of patients (57% at higher pretest risk, 42% at average risk) discussed results with a genetic counselor. Patients with pathogenic mutations in BRCA1/2 or another gene had the highest rates of BLM (higher risk, 80%; average risk, 85%); however, BLM was also common among patients with genetic variants of uncertain significance (VUS; higher risk, 43%; average risk, 51%). Surgeons' confidence in discussing testing increased with volume of patients with breast cancer, but many surgeons (higher volume, 24%; lower volume, 50%) managed patients with BRCA1/2 VUS the same as patients with BRCA1/2 pathogenic mutations. Conclusion Many patients with breast cancer are tested without ever seeing a genetic counselor. Half of average-risk patients with VUS undergo BLM, suggesting a limited understanding of results that some surgeons share. These findings emphasize the need to address challenges in personalized communication

Systematic meta-analysis on association of human papilloma virus and oral cancer.

Science.gov (United States)

Chaitanya, Nallan C S K; Allam, Neeharika Satya Jyothi; Gandhi Babu, D B; Waghray, Shefali; Badam, R K; Lavanya, Reddy

2016-01-01

Oral cancer is a disease with complex etiology. There is a strong evidence for the role of smoking, alcohol, genetic susceptibility, and indications that DNA viruses could also be involved in oral cancer. Recognized initially as sexually transmitted agent, human papilloma virus (HPV) is now considered a human carcinogen. Papilloma viruses are epitheliotropic viruses. A strong association of cervical cancer has been implicated with high-risk HPV16 and HPV18 infections, establishing the viral pathogenesis of the carcinoma. The etiopathogenesis is still unclear referring mainly to conflicting evidences in the detection of such viruses in oral carcinoma in spite of few studies suggesting their positive correlation. This systematic meta-analysis aimed to provide evidence-based analysis of literature relating oral cancer and HPV, along with identification of reliable diagnostic methodology for identifying HPV in oral and oropharyngeal cancer. A systematic review was performed using PubMed (from the year 1995 to 2015), Medline, Cochrane, ScienceDirect, and the Internet search. Reviewed literature included randomized control trials, cross sectional and cohort studies. Pooled data were analyzed by calculating relative risk and odds ratios (ORs), using a binary random-effects model. Out of 1497 cases, 588 patients were positive for HPV DNA, detected by various methods. About 39.27% of case samples were positive for HPV DNA. The calculated OR was 2.82 and 95% confidence interval, which showed significantly an increased risk of HPV among case group when compared to that of controls. The present meta-analysis suggests a potentially significant casual relation between HPV and oral and oropharyngeal cancers.

Phenotypic Characterization of Genetically Lowered Human Lipoprotein(a) Levels

Science.gov (United States)

Emdin, Connor A.; Khera, Amit V.; Natarajan, Pradeep; Klarin, Derek; Won, Hong-Hee; Peloso, Gina M.; Stitziel, Nathan O.; Nomura, Akihiro; Zekavat, Seyedeh M.; Bick, Alexander G.; Gupta, Namrata; Asselta, Rosanna; Duga, Stefano; Merlini, Piera Angelica; Correa, Adolfo; Kessler, Thorsten; Wilson, James G.; Bown, Matthew J.; Hall, Alistair S.; Braund, Peter S.; Samani, Nilesh J.; Schunkert, Heribert; Marrugat, Jaume; Elosua, Roberto; McPherson, Ruth; Farrall, Martin; Watkins, Hugh; Willer, Cristen; Abecasis, Gonçalo R.; Felix, Janine F.; Vasan, Ramachandran S.; Lander, Eric; Rader, Daniel J.; Danesh, John; Ardissino, Diego; Gabriel, Stacey; Saleheen, Danish; Kathiresan, Sekar

2017-01-01

BACKGROUND Genomic analyses have suggested that the LPA gene and its associated plasma biomarker, lipoprotein(a) (Lp[a]), represent a causal risk factor for coronary heart disease (CHD). As such, lowering Lp(a) has emerged as a therapeutic strategy. Beyond target identification, human genetics may contribute to the development of new therapies by defining the full spectrum of beneficial and adverse consequences and by developing a dose-response curve of target perturbation. OBJECTIVES We attempted to establish the full phenotypic impact of LPA gene variation and to estimate a dose-response curve between genetically altered plasma Lp(a) and risk for CHD. METHODS We leveraged genetic variants at the LPA gene from 3 data sources: individual-level data from 112,338 participants in the UK Biobank; summary association results from large-scale genome-wide association studies; and LPA gene sequencing results from cases with and controls free of CHD. RESULTS One standard deviation genetically lowered Lp(a) level was associated with 29% lower risk of CHD (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.69 to 0.73), 31% lower risk of peripheral vascular disease (OR: 0.69; 95% CI: 0.59 to 0.80), 13% lower risk of stroke (OR: 0.87; 95% CI: 0.79 to 0.96), 17% lower risk of heart failure (OR: 0.83; 95% CI: 0.73 to 0.94), and 37% lower risk of aortic stenosis (OR: 0.63; 95% CI: 0.47 to 0.83). We observed no association with 31 other disorders including type 2 diabetes and cancer. Variants that led to gain of LPA gene function increased risk for CHD whereas those that led to loss of gene function reduced CHD risk. CONCLUSIONS Beyond CHD, genetically lowered Lp(a) is associated with a lower risk of peripheral vascular disease, stroke, heart failure, and aortic stenosis. As such, pharmacological lowering of plasma Lp(a) may impact a range of atherosclerosis-related diseases. PMID:28007139

Colorectal Cancer Genetic Heterogeneity Delineated by Multi-Region Sequencing.

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You-Wang Lu

Full Text Available Intratumor heterogeneity (ITH leads to an underestimation of the mutational landscape portrayed by a single needle biopsy and consequently affects treatment precision. The extent of colorectal cancer (CRC genetic ITH is not well understood in Chinese patients. Thus, we conducted deep sequencing by using the OncoGxOne™ Plus panel, targeting 333 cancer-specific genes in multi-region biopsies of primary and liver metastatic tumors from three Chinese CRC patients. We determined that the extent of ITH varied among the three cases. On average, 65% of all the mutations detected were common within individual tumors. KMT2C aberrations and the NCOR1 mutation were the only ubiquitous events. Subsequent phylogenetic analysis showed that the tumors evolved in a branched manner. Comparison of the primary and metastatic tumors revealed that PPP2R1A (E370X, SETD2 (I1608V, SMAD4 (G382T, and AR splicing site mutations may be specific to liver metastatic cancer. These mutations might contribute to the initiation and progression of distant metastasis. Collectively, our analysis identified a substantial level of genetic ITH in CRC, which should be considered for personalized therapeutic strategies.

Genetic Mutation and Exosome Signature of Human Papilloma Virus Associated Oropharyngeal Cancer

Science.gov (United States)

Kannan, Anbarasu; Hertweck, Kate L.; Philley, Julie V.; Wells, Robert B.; Dasgupta, Santanu

2017-01-01

Human papilloma virus-16 (HPV-16) associated oropharyngeal cancer (HPVOPC) is increasing alarmingly in the United States. We performed whole genome sequencing of a 44 year old, male HPVOPC subject diagnosed with moderately differentiated tonsillar carcinoma. We identified new somatic mutation in MUC16 (A.k.a. CA-125), MUC12, MUC4, MUC6, MUC2, SIRPA, HLA-DRB1, HLA-A and HLA-B molecules. Increased protein expression of MUC16, SIRPA and decreased expression of HLA-DRB1 was further demonstrated in this HPVOPC subject and an additional set of 15 HPVOPC cases. Copy number gain (3 copies) was also observed for MUC2, MUC4, MUC6 and SIRPA. Enhanced expression of MUC16, SIRPA and HPV-16-E7 protein was detectable in the circulating exosomes of numerous HPVOPC subjects. Treatment of non-tumorigenic mammary epithelial cells with exosomes derived from aggressive HPVOPC cells harboring MUC16, SIRPA and HPV-16-E7 proteins augmented invasion and induced epithelial to mesenchymal transition (EMT) accompanied by an increased expression ratio of the EMT markers Vimentin/E-cadherin. Exosome based screening of key HPVOPC associated molecules could be beneficial for early cancer diagnosis, monitoring and surveillance. PMID:28383029

Journal of Genetics | Indian Academy of Sciences

Indian Academy of Sciences (India)

Here we report genetic variations and alterations of the TRs that have been described in the literature as well as their potential role in the development of some human diseases including cancers. The functional effects of some mutations and polymorphisms in TRs on disease susceptibility, especially on cancer risk, are now ...

Human Prostate Cancer Hallmarks Map

Science.gov (United States)

Datta, Dipamoy; Aftabuddin, Md.; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

2016-01-01

Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

College of Science Magazine explores genetic medicine, cancer therapies

OpenAIRE

Doss, Catherine

2010-01-01

The newest issue of the College of Science Magazine features a host of scientific research projects underway at Virginia Tech. New avenues in genetic medicine, environmental links to breast cancer, and resistance training for diabetics are just a few of the topics.

Accuracy of family history of cancer : clinical genetic implications

NARCIS (Netherlands)

Sijmons, RH; Boonstra, AE; Reefhuis, J; Hordijk-Hos, JM; de Walle, HEK; Oosterwijk, JC; Cornel, MC

Family medical history is the cornerstone of clinical genetic diagnosis and management in cases of familial cancer. The soundness of medical decisions can be compromised if reports by the family on affected relatives are inaccurate. Although very time consuming, family medical histories are

Colon cancer associated transcripts in human cancers.

Science.gov (United States)

Chen, Yincong; Xie, Haibiao; Gao, Qunjun; Zhan, Hengji; Xiao, Huizhong; Zou, Yifan; Zhang, Fuyou; Liu, Yuchen; Li, Jianfa

2017-10-01

Long non-coding RNAs serve as important regulators in complicated cellular activities, including cell differentiation, proliferation and death. Dysregulation of long non-coding RNAs occurs in the formation and progression of cancers. The family of colon cancer associated transcripts, long non-coding RNAs colon cancer associated transcript-1 and colon cancer associated transcript-2 are known as oncogenes involved in various cancers. Colon cancer associated transcript-1 is a novel lncRNA located in 8q24.2, and colon cancer associated transcript-2 maps to the 8q24.21 region encompassing rs6983267. Colon cancer associated transcripts have close associations with clinical characteristics, such as lymph node metastasis, high TNM stage and short overall survival. Knockdown of them can reverse the malignant phenotypes of cancer cells, including proliferation, migration, invasion and apoptosis. Moreover, they can increase the expression level of c-MYC and oncogenic microRNAs via activating a series of complex mechanisms. In brief, the family of colon cancer associated transcripts may serve as potential biomarkers or therapeutic targets for human cancers. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

DNA Amplification by Breakage/Fusion/Bridge Cycles Initiated by Spontaneous Telomere Loss in a Human Cancer Cell Line

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Anthony W.l. Lo

2002-01-01

Full Text Available The development of genomic instability is an important step in generatingthe multiple genetic changes required for cancer. One consequence of genomic instability is the overexpression of oncogenes due to gene amplification. One mechanism for gene amplification is the breakagelfusionlbridge (B/F/Bcyclethatinvolvesthe repeated fusion and breakage of chromosomes following the loss of a telomere. B/F/B cycles have been associated with low-copy gene amplification in human cancer cells, and have been proposed to be an initiating event in high-copy gene amplification. We have found that spontaneous telomere loss on a marker chromosome 16 in a human tumor cell line results in sister chromatid fusion and prolonged periods of chromosome instability. The high rate of anaphase bridges involving chromosome 16 demonstrates that this instability results from B/F/B cycles. The amplification of subtelomeric DNA on the marker chromosome provides conclusive evidence that B/F/B cycles initiated by spontaneous telomere loss are a mechanism for gene amplification in human cancer cells.

Telemedicine vs in-person cancer genetic counseling: measuring satisfaction and conducting economic analysis

Directory of Open Access Journals (Sweden)

Datta SK

2011-05-01

Full Text Available Santanu K Datta1,2, Adam H Buchanan3, Gail P Hollowell4, Henry F Beresford5, Paul K Marcom1,3, Martha B Adams1,61Department of Medicine, Duke University; 2Center for Health Services Research in Primary Care, Durham VA Medical Center; 3Duke Cancer Institute, Duke University; 4Department of Biology, North Carolina Central University; 5School of Nursing, Duke University; 6Department of Community and Family Medicine, Duke University, Durham, NC, USAAbstract: Cancer genetic counseling (CGC provides benefits and is the standard of care for individuals at increased risk of having a hereditary cancer syndrome. CGC services are typically centered in urban medical centers, leading to limited access to counseling in rural communities. Telemedicine has the potential to improve access to CGC, increase efficient use of genetic counselors, and improve patient care in rural communities. For telemedicine CGC to gain wide acceptance and implementation it needs to be shown that individuals who receive telemedicine CGC have high satisfaction levels and that CGC is cost-effective; however little research has been conducted to measure the impact of telemedicine CGC. This paper describes the design and methodology of a randomized controlled trial comparing telemedicine with in-person CGC. Measurement of patient satisfaction and effectiveness outcomes are described, as is measurement of costs that are included in an economic analysis. Study design and methodologies used are presented as a contribution to future comparative effectiveness investigations in the telemedicine genetic counseling field.Keywords: cancer genetics, genetic counseling, rural health services, telemedicine, satisfaction, cost

Population prevalence of hereditary breast cancer phenotypes and implementation of a genetic cancer risk assessment program in southern Brazil

Science.gov (United States)

2009-01-01

In 2004, a population-based cohort (the Núcleo Mama Porto Alegre - NMPOA Cohort) was started in Porto Alegre, southern Brazil and within that cohort, a hereditary breast cancer study was initiated, aiming to determine the prevalence of hereditary breast cancer phenotypes and evaluate acceptance of a genetic cancer risk assessment (GCRA) program. Women from that cohort who reported a positive family history of cancer were referred to GCRA. Of the 9218 women enrolled, 1286 (13.9%) reported a family history of cancer. Of the 902 women who attended GCRA, 55 (8%) had an estimated lifetime risk of breast cancer ≥ 20% and 214 (23.7%) had pedigrees suggestive of a breast cancer predisposition syndrome; an unexpectedly high number of these fulfilled criteria for Li-Fraumeni-like syndrome (122 families, 66.7%). The overall prevalence of a hereditary breast cancer phenotype was 6.2% (95%CI: 5.67-6.65). These findings identified a problem of significant magnitude in the region and indicate that genetic cancer risk evaluation should be undertaken in a considerable proportion of the women from this community. The large proportion of women who attended GCRA (72.3%) indicates that the program was well-accepted by the community, regardless of the potential cultural, economic and social barriers. PMID:21637504

Does genetic diversity predict health in humans?

Directory of Open Access Journals (Sweden)

Hanne C Lie

2009-07-01

Full Text Available Genetic diversity, especially at genes important for immune functioning within the Major Histocompatibility Complex (MHC, has been associated with fitness-related traits, including disease resistance, in many species. Recently, genetic diversity has been associated with mate preferences in humans. Here we asked whether these preferences are adaptive in terms of obtaining healthier mates. We investigated whether genetic diversity (heterozygosity and standardized mean d(2 at MHC and nonMHC microsatellite loci, predicted health in 153 individuals. Individuals with greater allelic diversity (d(2 at nonMHC loci and at one MHC locus, linked to HLA-DRB1, reported fewer symptoms over a four-month period than individuals with lower d(2. In contrast, there were no associations between MHC or nonMHC heterozygosity and health. NonMHC-d(2 has previously been found to predict male preferences for female faces. Thus, the current findings suggest that nonMHC diversity may play a role in both natural and sexual selection acting on human populations.

Animal models for human genetic diseases

African Journals Online (AJOL)

Sharif Sons

The study of human genetic diseases can be greatly aided by animal models because of their similarity .... and gene targeting in embryonic stem cells) has been a powerful tool in .... endonucleases that are designed to make a doublestrand.

Novel Stromal Biomarkers in Human Breast Cancer Tissues Provide Evidence for the More Malignant Phenotype of Estrogen Receptor-Negative Tumors

Directory of Open Access Journals (Sweden)

Zahraa I. Khamis

2011-01-01

Full Text Available Research efforts were focused on genetic alterations in epithelial cancer cells. Epithelial-stromal interactions play a crucial role in cancer initiation, progression, invasion, angiogenesis, and metastasis; however, the active role of stroma in human breast tumorigenesis in relation to estrogen receptor (ER status of epithelial cells has not been explored. Using proteomics and biochemical approaches, we identified two stromal proteins in ER-positive and ER-negative human breast cancer tissues that may affect malignant transformation in breast cancer. Two putative biomarkers, T-cell receptor alpha (TCR-α and zinc finger and BRCA1-interacting protein with a KRAB domain (ZBRK1, were detected in leukocytes of ER-positive and endothelial cells of ER-negative tissues, respectively. Our data suggest an immunosuppressive role of leukocytes in invasive breast tumors, propose a multifunctional nature of ZBRK1 in estrogen receptor regulation and angiogenesis, and demonstrate the aggressiveness of ER-negative human breast carcinomas. This research project may identify new stromal drug targets for the treatment of breast cancer patients.

Non-genetic health professionals' attitude towards, knowledge of and skills in discussing and ordering genetic testing for hereditary cancer.

Science.gov (United States)

Douma, Kirsten F L; Smets, Ellen M A; Allain, Dawn C

2016-04-01

Non-genetic health professionals (NGHPs) have insufficient knowledge of cancer genetics, express educational needs and are unprepared to counsel their patients regarding their genetic test results. So far, it is unclear how NGHPs perceive their own communication skills. This study was undertaken to gain insight in their perceptions, attitudes and knowledge. Two publically accessible databases were used to invite NGHPs providing cancer genetic services to complete a questionnaire. The survey assessed: sociodemographic attributes, experience in ordering hereditary cancer genetic testing, attitude, knowledge, perception of communication skills (e.g. information giving, decision-making) and educational needs. Of all respondents (N = 49, response rate 11%), most have a positive view of their own information giving (mean = 53.91, range 13-65) and decision making skills (64-77% depending on topic). NGHPs feel responsible for enabling disease and treatment related behavior (89-91%). However, 20-30% reported difficulties managing patients' emotions and did not see management of long-term emotions as their responsibility. Correct answers on knowledge questions ranged between 41 and 96%. Higher knowledge was associated with more confidence in NGHPs' own communication skills (r(s) = .33, p = 0.03). Although NGHPs have a positive view of their communication skills, they perceive more difficulties managing emotions. The association between less confidence in communication skills and lower knowledge level suggests awareness of knowledge gaps affects confidence. NGHPs might benefit from education about managing client emotions. Further research using observation of actual counselling consultations is needed to investigate the skills of this specific group of providers.

A systems biology approach to predict and characterize human gut microbial metabolites in colorectal cancer.

Science.gov (United States)

Wang, QuanQiu; Li, Li; Xu, Rong

2018-04-18

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths. It is estimated that about half the cases of CRC occurring today are preventable. Recent studies showed that human gut microbiota and their collective metabolic outputs play important roles in CRC. However, the mechanisms by which human gut microbial metabolites interact with host genetics in contributing CRC remain largely unknown. We hypothesize that computational approaches that integrate and analyze vast amounts of publicly available biomedical data have great potential in better understanding how human gut microbial metabolites are mechanistically involved in CRC. Leveraging vast amount of publicly available data, we developed a computational algorithm to predict human gut microbial metabolites for CRC. We validated the prediction algorithm by showing that previously known CRC-associated gut microbial metabolites ranked highly (mean ranking: top 10.52%; median ranking: 6.29%; p-value: 3.85E-16). Moreover, we identified new gut microbial metabolites likely associated with CRC. Through computational analysis, we propose potential roles for tartaric acid, the top one ranked metabolite, in CRC etiology. In summary, our data-driven computation-based study generated a large amount of associations that could serve as a starting point for further experiments to refute or validate these microbial metabolite associations in CRC cancer.

MicroRNAs Induce Epigenetic Reprogramming and Suppress Malignant Phenotypes of Human Colon Cancer Cells.

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Hisataka Ogawa

Full Text Available Although cancer is a genetic disease, epigenetic alterations are involved in its initiation and progression. Previous studies have shown that reprogramming of colon cancer cells using Oct3/4, Sox2, Klf4, and cMyc reduces cancer malignancy. Therefore, cancer reprogramming may be a useful treatment for chemo- or radiotherapy-resistant cancer cells. It was also reported that the introduction of endogenous small-sized, non-coding ribonucleotides such as microRNA (miR 302s and miR-369-3p or -5p resulted in the induction of cellular reprogramming. miRs are smaller than the genes of transcription factors, making them possibly suitable for use in clinical strategies. Therefore, we reprogrammed colon cancer cells using miR-302s and miR-369-3p or -5p. This resulted in inhibition of cell proliferation and invasion and the stimulation of the mesenchymal-to-epithelial transition phenotype in colon cancer cells. Importantly, the introduction of the ribonucleotides resulted in epigenetic reprogramming of DNA demethylation and histone modification events. Furthermore, in vivo administration of the ribonucleotides in mice elicited the induction of cancer cell apoptosis, which involves the mitochondrial Bcl2 protein family. The present study shows that the introduction of miR-302s and miR-369s could induce cellular reprogramming and modulate malignant phenotypes of human colorectal cancer, suggesting that the appropriate delivery of functional small-sized ribonucleotides may open a new avenue for therapy against human malignant tumors.

Genetically engineered rat gliomas: PDGF-driven tumor initiation and progression in tv-a transgenic rats recreate key features of human brain cancer.

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Nina P Connolly

Full Text Available Previously rodent preclinical research in gliomas frequently involved implantation of cell lines such as C6 and 9L into the rat brain. More recently, mouse models have taken over, the genetic manipulability of the mouse allowing the creation of genetically accurate models outweighed the disadvantage of its smaller brain size that limited time allowed for tumor progression. Here we illustrate a method that allows glioma formation in the rat using the replication competent avian-like sarcoma (RCAS virus / tumor virus receptor-A (tv-a transgenic system of post-natal cell type-specific gene transfer. The RCAS/tv-a model has emerged as a particularly versatile and accurate modeling technology by enabling spatial, temporal, and cell type-specific control of individual gene transformations and providing de novo formed glial tumors with distinct molecular subtypes mirroring human GBM. Nestin promoter-driven tv-a (Ntv-a transgenic Sprague-Dawley rat founder lines were created and RCAS PDGFA and p53 shRNA constructs were used to initiate intracranial brain tumor formation. Tumor formation and progression were confirmed and visualized by magnetic resonance imaging (MRI and spectroscopy. The tumors were analyzed using histopathological and immunofluorescent techniques. All experimental animals developed large, heterogeneous brain tumors that closely resembled human GBM. Median survival was 92 days from tumor initiation and 62 days from the first point of tumor visualization on MRI. Each tumor-bearing animal showed time dependent evidence of malignant progression to high-grade glioma by MRI and neurological examination. Post-mortem tumor analysis demonstrated the presence of several key characteristics of human GBM, including high levels of tumor cell proliferation, pseudopalisading necrosis, microvascular proliferation, invasion of tumor cells into surrounding tissues, peri-tumoral reactive astrogliosis, lymphocyte infiltration, presence of numerous tumor

Interaction between common breast cancer susceptibility variants, genetic ancestry, and nongenetic risk factors in Hispanic women.

Science.gov (United States)

Fejerman, Laura; Stern, Mariana C; John, Esther M; Torres-Mejía, Gabriela; Hines, Lisa M; Wolff, Roger K; Baumgartner, Kathy B; Giuliano, Anna R; Ziv, Elad; Pérez-Stable, Eliseo J; Slattery, Martha L

2015-11-01

Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population. We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions. We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74-1.20), 1.20 (0.94-1.53), and 1.49 (1.28-1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72-1.42), 1.19 (0.98-1.45), and 1.69 (1.26-2.26) for never, 12 months breastfeeding, respectively, Pinteraction 0.014]. The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women. These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk. ©2015 American Association for Cancer Research.

Genetic Counselors' Experiences Regarding Communication of Reproductive Risks with Autosomal Recessive Conditions found on Cancer Panels.

Science.gov (United States)

Mets, Sarah; Tryon, Rebecca; Veach, Patricia McCarthy; Zierhut, Heather A

2016-04-01

The development of hereditary cancer genetic testing panels has altered genetic counseling practice. Mutations within certain genes on cancer panels pose not only a cancer risk, but also a reproductive risk for autosomal recessive conditions such as Fanconi anemia, constitutional mismatch repair deficiency syndrome, and ataxia telangiectasia. This study aimed to determine if genetic counselors discuss reproductive risks for autosomal recessive conditions associated with genes included on cancer panels, and if so, under what circumstances these risks are discussed. An on-line survey was emailed through the NSGC list-serv. The survey assessed 189 cancer genetic counselors' experiences discussing reproductive risks with patients at risk to carry a mutation or variant of uncertain significance (VUS) in a gene associated with both an autosomal dominant cancer risk and an autosomal recessive syndrome. Over half (n = 82, 55 %) reported having discussed reproductive risks; the remainder (n = 66, 45 %) had not. Genetic counselors who reported discussing reproductive risks primarily did so when patients had a positive result and were of reproductive age. Reasons for not discussing these risks included when a patient had completed childbearing or when a VUS was identified. Most counselors discussed reproductive risk after obtaining results and not during the informed consent process. There is inconsistency as to if and when the discussion of reproductive risks is taking place. The wide variation in responses suggests a need to develop professional guidelines for when and how discussions of reproductive risk for autosomal recessive conditions identified through cancer panels should occur with patients.

Lung cancer exosomes as drivers of epithelial mesenchymal transition.

Science.gov (United States)

Rahman, Mohammad A; Barger, Jennifer F; Lovat, Francesca; Gao, Min; Otterson, Gregory A; Nana-Sinkam, Patrick

2016-08-23

Exosomes, a subgroup of extracellular vesicles (EVs), have been shown to serve as a conduit for the exchange of genetic information between cells. Exosomes are released from all types of cells but in abundance from cancer cells. The contents of exosomes consist of proteins and genetic material (mRNA, DNA and miRNA) from the cell of origin. In this study, we examined the effects of exosomes derived from human lung cancer serum and both highly metastatic and non-metastatic cells on recipient human bronchial epithelial cells (HBECs). We found that exosomes derived from highly metastatic lung cancer cells and human late stage lung cancer serum induced vimentin expression, and epithelial to mesenchymal transition (EMT) in HBECs. Exosomes derived from highly metastatic cancer cells as well as late stage lung cancer serum induce migration, invasion and proliferation in non-cancerous recipient cells. Our results suggest that cancer derived exosomes could be a potential mediator of EMT in the recipient cells.

Genetics for the ophthalmologist

Directory of Open Access Journals (Sweden)

Karthikeyan A Sadagopan

2012-01-01

Full Text Available The eye has played a major role in human genomics including gene therapy. It is the fourth most common organ system after integument (skin, hair and nails, nervous system, and musculoskeletal system to be involved in genetic disorders. The eye is involved in single gene disorders and those caused by multifactorial etiology. Retinoblastoma was the first human cancer gene to be cloned. Leber hereditary optic neuropathy was the first mitochondrial disorder described. X-Linked red-green color deficiency was the first X-linked disorder described. The eye, unlike any other body organ, allows directly visualization of genetic phenomena such as skewed X-inactivation in the fundus of a female carrier of ocular albinism. Basic concepts of genetics and their application to clinical ophthalmological practice are important not only in making a precise diagnosis and appropriate referral, but also in management and genetic counseling.

Using Quality Improvement Methods and Time-Driven Activity-Based Costing to Improve Value-Based Cancer Care Delivery at a Cancer Genetics Clinic.

Science.gov (United States)

Tan, Ryan Y C; Met-Domestici, Marie; Zhou, Ke; Guzman, Alexis B; Lim, Soon Thye; Soo, Khee Chee; Feeley, Thomas W; Ngeow, Joanne

2016-03-01

To meet increasing demand for cancer genetic testing and improve value-based cancer care delivery, National Cancer Centre Singapore restructured the Cancer Genetics Service in 2014. Care delivery processes were redesigned. We sought to improve access by increasing the clinic capacity of the Cancer Genetics Service by 100% within 1 year without increasing direct personnel costs. Process mapping and plan-do-study-act (PDSA) cycles were used in a quality improvement project for the Cancer Genetics Service clinic. The impact of interventions was evaluated by tracking the weekly number of patient consultations and access times for appointments between April 2014 and May 2015. The cost impact of implemented process changes was calculated using the time-driven activity-based costing method. Our study completed two PDSA cycles. An important outcome was achieved after the first cycle: The inclusion of a genetic counselor increased clinic capacity by 350%. The number of patients seen per week increased from two in April 2014 (range, zero to four patients) to seven in November 2014 (range, four to 10 patients). Our second PDSA cycle showed that manual preappointment reminder calls reduced the variation in the nonattendance rate and contributed to a further increase in patients seen per week to 10 in May 2015 (range, seven to 13 patients). There was a concomitant decrease in costs of the patient care cycle by 18% after both PDSA cycles. This study shows how quality improvement methods can be combined with time-driven activity-based costing to increase value. In this paper, we demonstrate how we improved access while reducing costs of care delivery. Copyright © 2016 by American Society of Clinical Oncology.

Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization.

Science.gov (United States)

Pauletti, G; Godolphin, W; Press, M F; Slamon, D J

1996-07-04

Amplification and overexpression of the HER-2/neu gene occurs in 25-30% of human breast cancers. This genetic alteration is associated with a poor clinical prognosis in women with either node negative or node positive breast cancers. The initial studies testing this association were somewhat controversial and this controversy was due in large part to significant heterogeneity in both the methods and/or reagents used in testing archival material for the presence of the alteration. These methods included a number of solid matrix blotting techniques for DNA, RNA and protein as well as immunohistochemistry. Fluorescence in situ hybridization (FISH) represents the newest methodologic approach for testing for this genetic alteration. In this study, FISH is compared to Southern, Northern and Western blot analyses as well as immunohistochemistry in a large cohort of archival human breast cancer specimens. FISH was found to be superior to all other methodologies tested in assessing formalin fixed, paraffin embedded material for HER-2/neu amplification. The results from this study also confirm that overexpression of HER-2/neu rarely occurs in the absence of gene amplification in breast cancer (approximately 3% of cases). This method of analysis is rapid, reproducible and extremely reliable in detecting presence of HER-2/neu gene amplification and should have clinical utility.

The risk for cancer and genetic abnormalities after radioiodine treatment of hyperthyroidism

International Nuclear Information System (INIS)

Reiners, C.

1997-01-01

According to recent studies, the risk for thyroid cancer is not increased after radioiodine treatment in patients with hyperthyroidism. Only the risk of cancer of the stomach seems to be increased slightly in patents treated with I-131 because of functional autonomy. However, the risk for gastric cancer is not increased after higher activities of I-131 because of thyroid cancer. There is no increased risk for genetic abnormalities after radioiodine treatment of hyperthyroidism. (orig.) [de

Genetically Predicted Body Mass Index and Breast Cancer Risk

DEFF Research Database (Denmark)

Guo, Yan; Warren Andersen, Shaneda; Shu, Xiao-Ou

2016-01-01

BACKGROUND: Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or enviro...

Assessment of genetic risk for human exposure to radiation. State of the art

International Nuclear Information System (INIS)

Shevchenko, V.A.

2000-01-01

Historical aspects of the conception of genetic risk of human irradiation for recent 40 years. Methodology of assessing the genetic risk of radiation exposure is based on the concept of hitting the target. To predict genetic risk of irradiation, the direct and indirect methods of assessment, extrapolation, integral and populational criteria of risk analysis is widely used. Combination of these methods permits to calculate the risk from human exposure on the basis of data obtained for mice. Method of doubling dose based on determination of the dose doubling the level of natural mutational process in humans is the main one used to predict the genetic risk. Till 1972 the main model for assessing the genetic risk was the human/mouse model (the use of data on the spontaneous human variability and data on the frequency of induced mutations in mice). In the period from 1972 till 1994 the mouse/mouse model was intensively elaborated in many laboratories. This model was also used in this period to analyse the genetic risk of human irradiation. Recent achievements associated with the study of molecular nature of many hereditary human diseases as well as the criticism of a fundamental principles of the mouse/mouse model for estimating the genetic risk on a new basis. Estimates of risk for the different classes of genetic diseases have been obtained using the doubling-dose method [ru

Different differences: The use of ‘genetic ancestry’ versus race in biomedical human genetic research

Science.gov (United States)

Fujimura, Joan H.; Rajagopalan, Ramya

2011-01-01

This article presents findings from our ethnographic research on biomedical scientists’ studies of human genetic variation and common complex disease. We examine the socio-material work involved in genome-wide association studies (GWAS) and discuss whether, how, and when notions of race and ethnicity are or are not used. We analyze how researchers produce simultaneously different kinds of populations and population differences. Although many geneticists use race in their analyses, we find some who have invented a statistical genetics method and associated software that they use specifically to avoid using categories of race in their genetics analysis. Their method allows them to operationalize their concept of ‘genetic ancestry’ without resorting to notions of race and ethnicity. We focus on the construction and implementation of the software’s algorithms, and discuss the consequences and implications of the software technology for debates and policies around the use of race in genetics research. We also demonstrate that the production and use of their method involves a dynamic and fluid assemblage of actors in various disciplines responding to disciplinary and sociopolitical contexts and concerns. This assemblage also includes particular discourses on human history and geography as they become entangled with research on genetic markers and disease. We introduce the concept of ‘genome geography’, to analyze how some researchers studying human genetic variation ‘locate’ stretches of DNA in different places and times. The concept of genetic ancestry and the practice of genome geography rely on old discourses, but they also incorporate new technologies, infrastructures, and political and scientific commitments. Some of these new technologies provide opportunities to change some of our institutional and cultural forms and frames around notions of difference and similarity. Neverthless, we also highlight the slipperiness of genome geography and the

Exploring the relationship between lifestyles, diets and genetic adaptations in humans.

Science.gov (United States)

Valente, Cristina; Alvarez, Luis; Marks, Sarah J; Lopez-Parra, Ana M; Parson, Walther; Oosthuizen, Ockie; Oosthuizen, Erica; Amorim, António; Capelli, Cristian; Arroyo-Pardo, Eduardo; Gusmão, Leonor; Prata, Maria J

2015-05-28

One of the most important dietary shifts underwent by human populations began to occur in the Neolithic, during which new modes of subsistence emerged and new nutrients were introduced in diets. This change might have worked as a selective pressure over the metabolic pathways involved in the breakdown of substances extracted from food. Here we applied a candidate gene approach to investigate whether in populations with different modes of subsistence, diet-related genetic adaptations could be identified in the genes AGXT, PLRP2, MTRR, NAT2 and CYP3A5. At CYP3A5, strong signatures of positive selection were detected, though not connected to any dietary variable, but instead to an environmental factor associated with the Tropic of Cancer. Suggestive signals of adaptions that could indeed be connected with differences in dietary habits of populations were only found for PLRP2 and NAT2. Contrarily, the demographic history of human populations seemed enough to explain patterns of diversity at AGXT and MTRR, once both conformed the evolutionary expectations under selective neutrality. Accumulated evidence indicates that CYP3A5 has been under adaptive evolution during the history of human populations. PLRP2 and NAT2 also appear to have been modelled by some selective constrains, although clear support for that did not resist to a genome wide perspective. It is still necessary to clarify which were the biological mechanisms and the environmental factors involved as well as their interactions, to understand the nature and strength of the selective pressures that contributed to shape current patterns of genetic diversity at those loci.

An overview of human genetic privacy

OpenAIRE

Shi, Xinghua; Wu, Xintao

2016-01-01

The study of human genomics is becoming a Big Data science, owing to recent biotechnological advances leading to availability of millions of personal genome sequences, which can be combined with biometric measurements from mobile apps and fitness trackers, and of human behavior data monitored from mobile devices and social media. With increasing research opportunities for integrative genomic studies through data sharing, genetic privacy emerges as a legitimate yet challenging concern that nee...

[Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease].

Science.gov (United States)

Maroto Rey, José Pablo; Cillán Narvaez, Elena

2013-06-01

There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

Genetic effects on gene expression across human tissues

NARCIS (Netherlands)

Battle, Alexis; Brown, Christopher D.; Engelhardt, Barbara E.; Montgomery, Stephen B.; Aguet, François; Ardlie, Kristin G.; Cummings, Beryl B.; Gelfand, Ellen T.; Getz, Gad; Hadley, Kane; Handsaker, Robert E.; Huang, Katherine H.; Kashin, Seva; Karczewski, Konrad J.; Lek, Monkol; Li, Xiao; MacArthur, Daniel G.; Nedzel, Jared L.; Nguyen, Duyen T.; Noble, Michael S.; Segrè, Ayellet V.; Trowbridge, Casandra A.; Tukiainen, Taru; Abell, Nathan S.; Balliu, Brunilda; Barshir, Ruth; Basha, Omer; Bogu, Gireesh K.; Brown, Andrew; Castel, Stephane E.; Chen, Lin S.; Chiang, Colby; Conrad, Donald F.; Cox, Nancy J.; Damani, Farhan N.; Davis, Joe R.; Delaneau, Olivier; Dermitzakis, Emmanouil T.; Eskin, Eleazar; Ferreira, Pedro G.; Frésard, Laure; Gamazon, Eric R.; Garrido-Martín, Diego; Gewirtz, Ariel D. H.; Gliner, Genna; Gloudemans, Michael J.; Guigo, Roderic; Hall, Ira M.; Han, Buhm; He, Yuan

2017-01-01

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression

Subjective versus objective risk in genetic counseling for hereditary breast and/or ovarian cancers

Directory of Open Access Journals (Sweden)

Sperduti Isabella

2009-12-01

Full Text Available Abstract Background Despite the fact that genetic counseling in oncology provides information regarding objective risks, it can be found a contrast between the subjective and objective risk. The aims of this study were to evaluate the accuracy of the perceived risk compared to the objective risk estimated by the BRCApro computer model and to evaluate any associations between medical, demographic and psychological variables and the accuracy of risk perception. Methods 130 subjects were given medical-demographic file, Cancer and Genetic Risk Perception, Hospital Anxiety-Depression Scale. It was also computed an objective evaluation of the risk by the BRCApro model. Results The subjective risk was significantly higher than objective risk. The risk of tumour was overestimated by 56%, and the genetic risk by 67%. The subjects with less cancer affected relatives significantly overestimated their risk of being mutation carriers and made a more innacurate estimation than high risk subjects. Conclusion The description of this sample shows: general overestimation of the risk, inaccurate perception compared to BRCApro calculation and a more accurate estimation in those subjects with more cancer affected relatives (high risk subjects. No correlation was found between the levels of perception of risk and anxiety and depression. Based on our findings, it is worth pursuing improved communication strategies about the actual cancer and genetic risk, especially for subjects at "intermediate and slightly increased risk" of developing an hereditary breast and/or ovarian cancer or of being mutation carrier.

The genetic component of human longevity

DEFF Research Database (Denmark)

Dato, Serena; Thinggaard, Mette Sørensen; De Rango, Francesco

2018-01-01

In human longevity studies, single nucleotide polymorphism (SNP) analysis identified a large number of genetic variants with small effects, yet not easily replicable in different populations. New insights may come from the combined analysis of different SNPs, especially when grouped by metabolic ...

Genetic Mutations and Epigenetic Modifications: Driving Cancer and Informing Precision Medicine

Science.gov (United States)

Coyle, Krysta Mila; Boudreau, Jeanette E.

2017-01-01

Cancer treatment is undergoing a significant revolution from “one-size-fits-all” cytotoxic therapies to tailored approaches that precisely target molecular alterations. Precision strategies for drug development and patient stratification, based on the molecular features of tumors, are the next logical step in a long history of approaches to cancer therapy. In this review, we discuss the history of cancer treatment from generic natural extracts and radical surgical procedures to site-specific and combinatorial treatment regimens, which have incrementally improved patient outcomes. We discuss the related contributions of genetics and epigenetics to cancer progression and the response to targeted therapies and identify challenges and opportunities for the success of precision medicine. The identification of patients who will benefit from targeted therapies is more complex than simply identifying patients whose tumors harbour the targeted aberration, and intratumoral heterogeneity makes it difficult to determine if a precision therapy is successful during treatment. This heterogeneity enables tumors to develop resistance to targeted approaches; therefore, the rational combination of therapeutic agents will limit the threat of acquired resistance to therapeutic success. By incorporating the view of malignant transformation modulated by networks of genetic and epigenetic interactions, molecular strategies will enable precision medicine for effective treatment across cancer subtypes. PMID:28685150

DNA Fingerprinting Techniques for the Analysis of Genetic and Epigenetic Alterations in Colorectal Cancer

OpenAIRE

Samuelsson, Johanna K.; Alonso, Sergio; Yamamoto, Fumiichiro; Perucho, Manuel

2010-01-01

Genetic somatic alterations are fundamental hallmarks of cancer. In addition to point and other small mutations targeting cancer genes, solid tumors often exhibit aneuploidy as well as multiple chromosomal rearrangements of large fragments of the genome. Whether somatic chromosomal alterations and aneuploidy are a driving force or a mere consequence of tumorigenesis remains controversial. Recently it became apparent that not only genetic but also epigenetic alterations play a major role in ca...

Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry.

Science.gov (United States)

Zhao, Zhiguo; Wen, Wanqing; Michailidou, Kyriaki; Bolla, Manjeet K; Wang, Qin; Zhang, Ben; Long, Jirong; Shu, Xiao-Ou; Schmidt, Marjanka K; Milne, Roger L; García-Closas, Montserrat; Chang-Claude, Jenny; Lindstrom, Sara; Bojesen, Stig E; Ahsan, Habibul; Aittomäki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Benitez, Javier; Blomqvist, Carl; Bogdanova, Natalia V; Børresen-Dale, Anne-Lise; Brand, Judith; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Cai, Qiuyin; Casey, Graham; Chenevix-Trench, Georgia; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Dörk, Thilo; Dumont, Martine; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fostira, Florentia; Gammon, Marilie; Giles, Graham G; Guénel, Pascal; Haiman, Christopher A; Hamann, Ute; Harrington, Patricia; Hartman, Mikael; Hooning, Maartje J; Hopper, John L; Jakubowska, Anna; Jasmine, Farzana; John, Esther M; Johnson, Nichola; Kabisch, Maria; Khan, Sofia; Kibriya, Muhammad; Knight, Julia A; Kosma, Veli-Matti; Kriege, Mieke; Kristensen, Vessela; Le Marchand, Loic; Lee, Eunjung; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Luben, Robert; Lubinski, Jan; Malone, Kathleen E; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Miao, Hui; Muir, Kenneth; Neuhausen, Susan L; Nevanlinna, Heli; Neven, Patrick; Olson, Janet E; Perkins, Barbara; Peterlongo, Paolo; Phillips, Kelly-Anne; Pylkäs, Katri; Rudolph, Anja; Santella, Regina; Sawyer, Elinor J; Schmutzler, Rita K; Schoemaker, Minouk; Shah, Mitul; Shrubsole, Martha; Southey, Melissa C; Swerdlow, Anthony J; Toland, Amanda E; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Ursin, Giske; Van Der Luijt, Rob B; Verhoef, Senno; Wang-Gohrke, Shan; Whittemore, Alice S; Winqvist, Robert; Pilar Zamora, M; Zhao, Hui; Dunning, Alison M; Simard, Jacques; Hall, Per; Kraft, Peter; Pharoah, Paul; Hunter, David; Easton, Douglas F; Zheng, Wei

2016-05-01

Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies. The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk.

Genetics of breast cancer: Applications to the Mexican population

Directory of Open Access Journals (Sweden)

Elad Ziv

2011-10-01

Full Text Available Breast cancer research has yielded several important results including the strong susceptibility genes,BRCA1 and BRCA2 and more recently 19 genes and genetic loci that confer a more moderate risk.The pace of discovery is accelerating as genetic technology and computational methods improve. These discoveries will change the way that breast cancer risk is understood in Mexico over the next few decades.La investigación en cáncer de mama ha dado varios resultados importantes incluyendo los genes fuertemente susceptibles, BRCA1 y BRCA2, y más recientemente 19 genes y loci genéticos que confieren un riesgo moderado. El ritmo de los descubrimientos se acelera conforme mejora la tecnología y métodos computacionales.Estosdescubrimientoscambiarán la forma en que la investigación del cáncer es comprendida en México en las próximas décadas.

Use of fluorescent proteins and color-coded imaging to visualize cancer cells with different genetic properties.

Science.gov (United States)

Hoffman, Robert M

2016-03-01

Fluorescent proteins are very bright and available in spectrally-distinct colors, enable the imaging of color-coded cancer cells growing in vivo and therefore the distinction of cancer cells with different genetic properties. Non-invasive and intravital imaging of cancer cells with fluorescent proteins allows the visualization of distinct genetic variants of cancer cells down to the cellular level in vivo. Cancer cells with increased or decreased ability to metastasize can be distinguished in vivo. Gene exchange in vivo which enables low metastatic cancer cells to convert to high metastatic can be color-coded imaged in vivo. Cancer stem-like and non-stem cells can be distinguished in vivo by color-coded imaging. These properties also demonstrate the vast superiority of imaging cancer cells in vivo with fluorescent proteins over photon counting of luciferase-labeled cancer cells.

Genetic Engineering and Human Mental Ecology: Interlocking Effects and Educational Considerations

OpenAIRE

Affifi, Ramsey

2017-01-01

This paper describes some likely semiotic consequences of genetic engineering on what Gregory Bateson has called ?the mental ecology? (1979) of future humans, consequences that are less often raised in discussions surrounding the safety of GMOs (genetically modified organisms). The effects are as follows: an increased 1) habituation to the presence of GMOs in the environment, 2) normalization of empirically false assumptions grounding genetic reductionism, 3) acceptance that humans are capabl...

Prevalence of Human Papillomavirus in endometrial cancer

DEFF Research Database (Denmark)

Olesen, Tina Bech; Svahn, Malene Frøsig; Faber, Mette Tuxen

2014-01-01

HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer.......HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer....