Identification of Genetic Modifiers of Breast Cancer Risk
Abstract
The purpose of this study is to identify genetic modifiers of cancer risk in women with BRCA1 and BRCA2 mutations. We are using two complementary strategies: 1) association studies in candidate genes from the immune surveillance and DNA damage response pathways and 2) a genome-wide scan using relative pairs with BRCA1 mutations to identify novel regions containing modifier genes. To date we have assembled a case-control sample set of 448 mutation carriers and a relative pairs set of 534 mutation carriers. We have completed a sequencing survey of a panel of immune surveillance genes and determined the population frequency of the variants we identified. We have examined a number of candidate genes and have data suggesting variants in TNF-alpha, IL-6, XPD and p53 may have a role in altering cancer risk in these high risk women. This work is important not only in leading to more refined cancer risk estimates for women with BRCA1 and BRCA2 mutations, but also will yield candidates for risk alleles in the general population and generate hypotheses for mechanisms that explain these effects. Once these mechanisms have been elucidated, these points in key pathways become excellent targets for preventative and therapeutic intervention.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396698
Entities
People
- Barbara L. Weber
- Katherine L Nathanson
Organizations
- University of Pennsylvania