Inherited predisposition and breast cancer: Modifiers of BRCA1/2-associated breast cancer risk


  • Timothy R. Rebbeck

    Corresponding author
    1. Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine and Cancer Center, Philadelphia, Pennsylvania
    • Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, 904 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021
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Germline mutations in the BRCA1 and BRCA2 (BRCA1/2) genes explain a substantial proportion of hereditary breast and ovarian cancer. Women who have inherited a mutation in one of these genes are at increased risk to develop breast and/or ovarian cancer, although there is variability in the manifestation of tumors by age and site. This variability may be explained, in part, by the BRCA1/2 mutation type or location. However, it is also possible that risk-modifying factors exist that explain interindividual variability in cancer risk. These factors include genes at other loci and endogenous or exogenous exposures. A more complete understanding of factors that modify cancer risk in BRCA1 and BRCA2 mutation carriers may help to refine estimates of cancer risk. A number of exposures, including reproductive history and exogenous hormone use, have been implicated as BRCA1/2-associated cancer risk modifiers. Similarly, genes involved in hormone metabolism, including the AIB1 and AR genes, have been linked with altered breast cancer risk. Therefore, although germline BRCA1/2 mutations raise a woman's breast and ovarian cancer risk, other factors may interact with BRCA1/2 mutations to modulate this risk. Environ. Mol. Mutagen. 39:228–234, 2002. © 2002 Wiley-Liss, Inc.