Breast cancer is the most common malignancy in women. Its incidence is lower among Hispanic women than among Caucasian women of non-Hispanic origin, but Hispanic women are more likely to die from the disease because of diagnosis at a later stage. Targeting high risk women for screening may be an effective means of improving health care in this group. Genetic factors, mainly mutations in BRCA1 and BRCA2, are believed to account for at least 5 percent of breast cancer and have received very little attention in Hispanics. In this proposal we will define the mutational spectrum of BRCA1 and 2 in a North American Hispanic population. The study will focus on Mexican Mestizos (mixed Spanish and Native American) because most U.S. Hispanics are of Mexican Mestizo origin. In preliminary studies we cataloged a large number of BRCA mutations from a Spanish population, and we will determine if any of these mutations are present as high frequency, founder mutations in North American Hispanics. We will test high risk Mexican families without mutations of Spanish origin for other mutations. If the mutational spectrum is limited in high risk families, the frequency of BRCA mutations in an unselected breast cancer population will be estimated by screening for specific mutations. The project will also result in ascertainment of a cohort of Hispanic BRCA mutation carriers for studies of modifying genes and environmental factors.