Common Variants in 8q24 Are Associated With Risk for Prostate Cancer and Tumor Aggressiveness in Men of European Ancestry

BACKGROUND. Recent whole genome association studies have independently identified multiple prostate cancer (PC) risk variants on 8q24. We have evaluated association of common variants in this region with PC susceptibility and tumor aggressiveness in a sample of European American men. METHODS. Forty-nine tagging SNPs including three previously reported significant variants (rs1447295, rs6983267, rs16901979) and seven variants in the 5' upstream region of the MYC proto-oncogene were tested for association with susceptibility to PC and tumor aggressiveness in 596 histologically verified PC cases and 567 ethnically matched controls. RESULTS. Significant associations with susceptibility to PC were found at 17 SNPs, four of which (rs1016342, rs1378897, rs871135, and rs6470517) remained significant after adjusting for multiple corrections. One of the associated SNPs, rs871135, is located in the putative gene POU5F1P1 within the 8q24 region. An in slico analysis showed that the associated variant of this SNP alters a transcription factor implicating a plausible regulatory role. Additionally, one of the significantly associated SNPs, rs6470517, with PC susceptibility showed a significant over-representation of the G allele in cases with aggressive tumor. CONCLUSIONS. Although this study does not directly confirm associations of the three specific SNPs (cited above), it corroborates reported signals of association in 8q24 reaffirming that genetic variation on 8q24 influences susceptibility to PC in men of European ancestry. Although our study did not confirm the allelic association of rs1447295, meta-analysis of this SNP provided support to previous reported associations. Further, this study implicates the 8q24 region with aggressive forms of PC. Prostate 69: 1548-1556, 2009. (C) 2009 Wiley-Liss, Inc.