Candidate genetic modifiers for breast and ovarian cancer risk inBRCA1andBRCA2 mutation carriers

On Behalf Of Gemo Study Collaborators

Research output: Contribution to journalArticlepeer-review


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 inmany 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 analysiswas 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.

Original languageEnglish
Pages (from-to)308-316
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Issue number1
StatePublished - 1 Jan 2015
Externally publishedYes


FundersFunder number
Breast Cancer Research Foundation
Canadian Institutes of Health Research
Cancer Association of South Africa
Cancer Research UKC5047/A10692, C5047/ A15007, C5047/A8384, C1287/A 10710, C1287/A16563, C12292/A11174, C1287/A10118, C1281/A12014
National Cancer InstituteUM1 CA164920
National Institutes of HealthCA128978
Ovarian Cancer Research Fund
Suomen Akatemia266528
National Cancer InstituteU10CA180822
National Cancer Institute


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