Determination of cancer risk associated with germ line BRCA1 missense variants by functional analysis.

ABSTRACT: Germ line inactivating mutations in BRCA1 confer susceptibility for breast and ovarian cancer. However, the relevance of the many missense changes in the gene for which the effect on protein function is unknown remains unclear. Determination of which variants are causally associated with cancer is important for assessment of individual risk. We used a functional assay that measures the transactivation activity of BRCA1 in combination with analysis of protein modeling based on the structure of BRCA1 BRCT domains. In addition, the information generated was interpreted in light of genetic data. We determined the predicted cancer association of 22 BRCA1 variants and verified that the common polymorphism S1613G has no effect on BRCA1 function, even when combined with other rare variants. We est

SUBMITTER: Carvalho MA 

PROVIDER: S-EPMC2936786 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature