Confirmation study of prostate cancer risk variants at 8q24 in african american men identifies a novel risk locus Free

B102

Prostate cancer still remains the most common male specific malignancy diagnosed in the U.S. and disproportionately affects African American Men (AA) compared to European Americans (EA). Recent published findings have identified several common variants on chromosome 8q24 to be associated with increased risk for prostate cancer. These findings were found not only in multiple studies but also in different ethnic groups specifically in AA men further making these findings very interesting. Our objective was to confirm these common variants associated with prostate cancer in our hospital-based-case-control sample set of 1,057 AA men (490 prostate cancer cases and 567 healthy male matched controls). 24 markers along 8q24 were genotyped using the Sequenom platform. Association analyses of the 8q24 markers with prostate cancer risk were adjusted for both global and local 8q24 admixture stratification using estimates from the ancestry informative markers that had been previously genotyped in this sample set. We replicated the association of rs16901979 with prostate cancer (P=0.002) yet found that other published risk variants in the region such as rs1447295 and DG8S737 did not replicate in our data set. Interestingly though we identified rs7008482, which maps to the 8q24.13 region, as an additional independent prostate cancer risk variant (P= 5 x 10-4). Both rs7008482 and rs16901979 independently predicted risk and remained significant (P<0.001) after controlling for each other. Our data combined with additional replications of 8q24 markers provide compelling support for multiple regions of risk for prostate cancer on 8q24. Further additional genotyping within this region and functional analyses are underway to facilitate the identification of causal alleles. As prostate cancer disproportionately affects AA, the discovery of the true risk allele could have important implications for early detection of prostate cancer in this high-risk population.