Aurora-A as a Modifier of Breast Cancer Risk in BRCA1/2 Mutation Carriers. Addendum

Abstract

Abstract : The AURORA-A/BTAK/STK15 gene encodes a centrosome-associated kinase that causes centrosome amplification, failure of cytokinesis, and aneuploidy when amplified and/or overexpressed in breast tumors. A number of gene association studies using matching breast cancer cases and controls have shown that the F31I polymorphism in STK15 increases risk of breast. We hypothesized that the F31I polymorphism is associated with increased risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Using over 7,000 carriers of BRCA1 and BRCA2 deleterious mutations we showed that F31I has no influence on breast cancer risk. In parallel, we completed an association study of 2400 polymorphisms in other cell division regulatory genes in 800 breast cancer cases and 800 controls collected at the Mayo Clinic. A total of 52 of these polymorphisms along with 332 other polymorphisms displaying associations with breast cancer risk were evaluated for associations with breast cancer risk in approximately 5,400 BRCA1 and BRCA2 mutation carriers. Several polymorphisms displaying significant associations (p<10-4) with risk of breast cancer in BRCA2 mutation carriers were observed.