Epidemiology Program

CAREGEN: Genetic susceptibility and the risk of breast cancer

PI: Kathi Malone PhD

This is an ancillary study of the NICHD Women’s CARE Study, a large population-based multi-center case-control study among Caucasian and African-American women that is designed primarily to evaluate the risk of breast cancer in women ages 35-64 in relation to oral contraceptive (OC) use and hormone replacement therapy (HRT). Altogether, 4575 women with invasive breast cancer (cases) selected via population-based cancer registries and 4682 women without breast cancer selected via centralized random digit dialing from the general population (controls) in five field centers were interviewed as part of this study. Standardized in-person interviews elicited information similarly from cases and controls on factors potentially related to the risk of breast cancer, including: reproductive, menstrual, OC and HRT use histories; lifestyle factors such as smoking, alcohol use, body weight, and physical activity; selected medical conditions and procedures; and a detailed family history of cancer.

Blood samples collected from 1628 cases and 1435 controls (all subjects with a first-degree family history of breast cancer plus a random sample of women without a first-degree family history) are being used for molecular genetic analyses. Genes under study include: BRCA1 and BRCA2 (n=1628 cases and 674 controls) plus a battery  of genes selected for their role in estrogen metabolism or mediation (n=1628 cases and 1435 controls.  The primary goals of these analyses are: (1) to determine the “main” effects of putative alterations in specific genes on the risk of breast cancer, and (2) to evaluate the effects of OCs, HRT, and other risk factors (i.e. alcohol, tobacco, body size) on the risk of breast cancer according to categories of genetic susceptibility as defined by mutations/ rare variants/ polymorphisms in each of the above breast cancer susceptibility genes. 

This study will increase our understanding of breast cancer etiology by: (1) establishing the population prevalence of mutations, rare variants, and polymorphisms for BRCA1, BRCA2, and the allele frequencies for the specific polymorphisms examined in the other genes, among cases and controls overall and according to racial group, age, and geographic area, (2) assessing gene-environment interactions and even gene-gene interactions within a well-defined study population, and (3) assessing the contributions of breast cancer risk factors in women who may be most and least likely to be genetically vulnerable to the effects of such risk factors through identification of the carriers and non-carriers of rare but highly penetrant autosomal dominant mutations and common but low risk polymorphisms.