|Grant Number:||5R01CA077571-05 Interpret this number|
|Primary Investigator:||Henderson, Brian|
|Organization:||University Of Southern California|
|Project Title:||BRCA1 and Brca2 in African-American and Latino Families|
DESCRIPTION: (Adapted from Investigator's Abstract) While our knowledge about the penetrance and attributable risks associated with BRCA1 and BRCA2 mutations is continuing to be refined, the potential impact of these genes in minority populations remains largely unknown. As examples from the Ashkenazi Jewish and Icelandic subpopulations have demonstrated, different ethnic groups are likely to have different spectrums of mutations and polymorphisms occurring in BRCA1 and BRCA2. The identification of germline mutations in cancer susceptibility genes such as BRCA1 and BRCA2 has opened up the possibility of identifying and characterizing high risk families and individuals. However, at the present time, the broad spectrum of mutations, limited knowledge of the functional role of these genes, and incomplete information on gene penetrance and factors that affect expression of these genes (i.e., gene-gene and gene-environment interactions) severely limit the practical application of such knowledge in cancer prevention and counseling. The investigators state that this application proposes to utilize a large multi-ethnic population-based cohort that will provide greater heterogeneity of gene mutations, allele frequencies, and environmental exposures than would be available within any single ethnic group. To fully exploit this multi-ethnic resource, they state they are studying families affected with at least two cases of breast or ovarian cancer and comparing affected and unaffected siblings within and across ethnic groups. Specifically, this application will investigate the role of BRCA1, BRCA2, the cytochrome P450cl7alpha gene (CYP17), and the 17beta-hydroxysteroid dehydrogenase 1 gene (HSD17B1) among African-American and Latino families with a history of breast and ovarian cancer and evaluate possible gene-gene and gene-environment interactions in the etiology of breast cancer. The primary rationale for studying families is to increase substantially the efficiency with which the specific aims can be achieved. Focusing on sibships with a family history of breast cancer will increase the proportion of subjects who carry a mutation in BRCA1 or BRCA2. Consequently, this will substantially increase the power of the study to estimate main effects and interactions. Further, the investigators state that a family-based design offers the advantage of being able to determine the role of polymorphisms in metabolic genes involved in estrogen biosynthesis without underlying confounding that can be introduced from genetic heterogeneity.