Genome-wide Association Studies of Cancer Predisposition

Stadler, Zsofia K.; Vijai, Joseph; Thom, Peter; Kirchhoff, Tomas; Hansen, Nichole; Kauff, Noah D.; Offit, Kenneth

doi:10.1016/j.hoc.2010.06.009

Cited by 40 publications

(23 citation statements)

References 155 publications

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“…Several studies examining the influence of all known breast cancer–associated SNPs on risk are now under way (85). Overall, it now appears likely that combinations of risk variants will improve stratification of the risk for breast cancer, leading to better identification of women who will benefit from enhanced screening and intervention (89). …”

Section: Polygenic Risk Modelingmentioning

confidence: 99%

Two Decades After BRCA: Setting Paradigms in Personalized Cancer Care and Prevention

Couch

Nathanson

Offit

2014

Science

Self Cite

319

251

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The cloning of the breast cancer susceptibility genes BRCA1 and BRCA2 nearly two decades ago helped set in motion an avalanche of research exploring how genomic information can be optimally applied to identify and clinically care for individuals with a high risk of developing cancer. Genetic testing for mutations in BRCA1, BRCA2, and other breast cancer susceptibility genes has since proved to be a valuable tool for determining eligibility for enhanced screening and prevention strategies, as well as for identifying patients most likely to benefit from a targeted therapy. Here, we discuss the landscape of inherited mutations and sequence variants in BRCA1 and BRCA2, the complexities of determining disease risk when the pathogenicity of sequence variants is uncertain, and current strategies for clinical management of women who carry BRCA1/2 mutations.

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Section: Polygenic Risk Modelingmentioning

confidence: 99%

Two Decades After BRCA: Setting Paradigms in Personalized Cancer Care and Prevention

Couch

Nathanson

Offit

2014

Science

Self Cite

319

251

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“…A polygenic risk score calculated as the sum of the ORs for each allele, correlated with risk of early onset breast cancer ( OR = 3.37, P = 0.03) [148] and other such studies are now under way [145], with the goal of leading to better identification of women who will benefit from enhanced screening and intervention [22]. …”

Section: Syndromes Of Breast Cancer Predispositionmentioning

confidence: 99%

“…As genomic testing continues to evolve, biomarkers of various strength and significance are being routinely detected and gene-gene and gene-environment interactions are beginning to emerge [17–22]. Understanding the functional significance of genomic alterations is conceptually critical in assessing the potential utility of genetic variants as biomarkers.…”

mentioning

confidence: 99%

Genomic Biomarkers for Breast Cancer Risk

Walsh

Nathanson

Couch

et al. 2016

Advances in Experimental Medicine and Biology

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Clinical risk assessment for cancer predisposition includes a three-generation pedigree and physical examination to identify inherited syndromes. Additionally genetic and genomic biomarkers may identify individuals with a constitutional basis for their disease that may not be evident clinically. Genomic biomarker testing may detect molecular variations in single genes, panels of genes, or entire genomes. The strength of evidence for the association of a genomic biomarker with disease risk may be weak or strong. The factors contributing to clinical validity and utility of genomic biomarkers include functional laboratory analyses and genetic epidemiologic evidence. Genomic biomarkers may be further classified as low, moderate or highly penetrant based on the likelihood of disease. Genomic biomarkers for breast cancer are comprised of rare highly penetrant mutations of genes such as BRCA1 or BRCA2, moderately penetrant mutations of genes such as CHEK2, as well as more common genomic variants, including single nucleotide polymorphisms, associated with modest effect sizes. When applied in the context of appropriate counseling and interpretation, identification of genomic biomarkers of inherited risk for breast cancer may decrease morbidity and mortality, allow for definitive prevention through assisted reproduction, and serve as a guide to targeted therapy.

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“…Although the genetic variants detected in GWAS have been of modest effect sizes (e.g., ORs of 1.01-1.5), understanding the risk particularly in men of African descent men and men with FPC/HPC may have clinical prediction utility in highrisk men (7). One area in need of accurate prostate cancer risk prediction is prostate cancer screening, particularly for high-risk men.…”

Section: Introductionmentioning

confidence: 99%

A Systematic Review of Replication Studies of Prostate Cancer Susceptibility Genetic Variants in High-Risk Men Originally Identified from Genome-Wide Association Studies

Ishak

Giri

2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Several prostate cancer genome-wide association studies (GWAS) have identified riskassociated genetic variants primarily in populations of European descent. Less is known about the association of these variants in high-risk populations, including men of African descent and men with a family history of prostate cancer. This article provides a detailed review of published studies of prostate cancer-associated genetic variants originally identified in GWAS and replicated in high-risk populations.Methods: Articles replicating GWAS findings (National Human Genome Research Institute GWAS database) were identified by searching PubMed and relevant data were extracted.Results: Eleven replication studies were eligible for inclusion in this review. Of more than 30 singlenucleotide polymorphisms (SNP) identified in prostate cancer GWAS, 19 SNPs (63%) were replicated in men of African descent and 10 SNPs (33%) were replicated in men with familial and/or hereditary prostate cancer (FPC/HPC). The majority of SNPs were located at the 8q24 region with modest effect sizes (OR 1.11-2.63 in African American men and OR 1.3-2.51 in men with FPC). All replicated SNPs at 8q24 among men of African descent were within or near regions 2 and 3.Conclusions: This systematic review revealed several GWAS markers with replicated associations with prostate cancer in men of African descent and men with FPC/HPC. The 8q24 region continues to be the most implicated in prostate cancer risk. These replication data support ongoing study of clinical utility and potential function of these prostate cancer-associated variants in high-risk men.Impact: The replicated SNPs presented in this review hold promise for personalizing risk assessment for prostate cancer for high-risk men upon further study. Cancer Epidemiol Biomarkers Prev; 20(8); 1599-610. Ó2011 AACR.

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Genome-wide Association Studies of Cancer Predisposition

Cited by 40 publications

References 155 publications

Two Decades After BRCA: Setting Paradigms in Personalized Cancer Care and Prevention

Two Decades After BRCA: Setting Paradigms in Personalized Cancer Care and Prevention

Genomic Biomarkers for Breast Cancer Risk

A Systematic Review of Replication Studies of Prostate Cancer Susceptibility Genetic Variants in High-Risk Men Originally Identified from Genome-Wide Association Studies

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