Characterizing genetic risk at known prostate cancer susceptibility loci in African Americans.
Haiman CA, Chen GK, Blot WJ, Strom SS, Berndt SI, Kittles RA, Rybicki BA, Isaacs WB, Ingles SA, Stanford JL, Diver WR, Witte JS, Chanock SJ, Kolb S, Signorello LB, Yamamura Y, Neslund-Dudas C, Thun MJ, Murphy A, Casey G, Sheng X, Wan P, Pooler LC, Monroe KR, Waters KM, Le Marchand L, Kolonel LN, Stram DO, Henderson BE
GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls), we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p≤0.05) with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in African Americans. At 8q24, we found 9 variants (p≤6×10(-4)) that best capture risk of prostate cancer in African Americans, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in African Americans (per allele OR = 1.17) over the alleles reported in the original GWAS (OR = 1.08). In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in African Americans. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry.