title: Inherited predisposition and breast cancer: modifiers of BRCA1/2-associated breast cancer risk.
abstract: 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.
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine and Cancer Center, Philadelphia, Pennsylvania 19104-6021, USA. trebbeck@cceb.med.upenn.edu
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D015981:Epidemiologic Factors; D005260:Female; D005787:Gene Frequency; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D017584:Reproductive History; D012307:Risk Factors
chemical_list: D009363:Neoplasm Proteins