BACKGROUND BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. METHODS Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. RESULTS The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. CONCLUSION There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. IMPACT Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.
DOI: 10.1158/1055-9965.EPI-14-0532
Projects: GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer
Publication type: Journal article
Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Human Diseases: Hereditary breast ovarian cancer syndrome
Citation: Cancer Epidemiology Biomarkers & Prevention 24(1):308-316
Date Published: 13th Jan 2015
Registered Mode: imported from a bibtex file
Views: 1891
Created: 15th Jul 2020 at 12:51
Last updated: 7th Dec 2021 at 17:58
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