Evaluation of established breast cancer risk factors as modifiers of BRCA1 or BRCA2: a multi-center case-only analysis.

Journal Article

The incomplete penetrance of mutations in BRCA1 and BRCA2 suggests that some combination of environmental and genetic factors modifies the risk of breast cancer in mutation carriers. This study sought to identify possible interactions between established breast cancer risk factors and BRCA1 or BRCA2 mutations using a case-only study design. Breast cancer cases that had been tested for BRCA1 and BRCA2 mutations were identified from 11 collaborating centers. Comparisons of reproductive and lifestyle risk factors were made between women with breast cancer who were positive for BRCA1 mutations (n = 283), BRCA2 mutations (n = 204), or negative for both BRCA1 and BRCA2 mutations (n = 894). Interaction risk ratios (IRRs) were calculated using multinominal logistic regression models. Compared with non-carriers, statistically significant IRRs were observed for later age at menarche among BRCA2 mutation carriers, for a greater number of pregnancies among both BRCA1 and BRCA2 mutation carriers, and for alcohol use among BRCA1 mutation carriers. Our data suggest that the risk for breast cancer among BRCA1 or BRCA2 carriers may be modified by reproductive characteristics and alcohol use. However, our results should be interpreted cautiously given the overall inconsistency in the epidemiologic literature on modifiers of BRCA1 and BRCA2.

Full Text

Duke Authors

Cited Authors

  • Moorman, PG; Iversen, ES; Marcom, PK; Marks, JR; Wang, F; Kathleen Cuningham Consortium for Research into Familial Breast Cancer, ; Lee, E; Ursin, G; Rebbeck, TR; Domchek, SM; Arun, B; Susswein, L; Isaacs, C; Garber, JE; Visvanathan, K; Griffin, CA; Sutphen, R; Brzosowicz, J; Gruber, S; Finkelstein, DM; Schildkraut, JM

Published Date

  • November 2010

Published In

Volume / Issue

  • 124 / 2

Start / End Page

  • 441 - 451

PubMed ID

  • 20309627

Electronic International Standard Serial Number (EISSN)

  • 1573-7217

Digital Object Identifier (DOI)

  • 10.1007/s10549-010-0842-y

Language

  • eng

Conference Location

  • Netherlands