Genome-wide Association Study Identifies a Genetic Variant Associated with Risk for More Aggressive Prostate Cancer

Background: Of the 200,000 U. S. men annually diagnosed with prostate cancer, approximately 20% to 30% will have clinically aggressive disease. Although factors such as Gleason score and tumor stage are used to assess prognosis, there are no biomarkers to identify men at greater risk for developing aggressive prostate cancer. We therefore undertook a search for genetic variants associated with risk of more aggressive disease. Methods: A genome-wide scan was conducted in 202 prostate cancer cases with a more aggressive phenotype and 100 randomly sampled, age-matched prostate-specific antigen screened negative controls. Analysis of 387,384 autosomal single nucleotide polymorphisms (SNPs) was followed by validation testing in an independent set of 527 cases with more aggressive and 595 cases with less aggressive prostate cancer, and 1,167 age-matched controls. Results: A variant on 15q13, rs6497287, was confirmed to be most strongly associated with more aggressive (P-discovery = 5.20 x 10(-5), P-validation = 0.004) than less aggressive disease (P = 0.14). Another SNP on 3q26, rs3774315, was found to be associated with prostate cancer risk; however, the association was not stronger for more aggressive disease. Conclusions: This study provides suggestive evidence for a genetic predisposition to more aggressive prostate cancer and highlights the fact that larger studies are warranted to confirm this supposition and identify further risk variants. Impact: These findings raise the possibility that assessment of genetic variation may one day be useful to discern men at higher risk for developing clinically significant prostate cancer. Cancer Epidemiol Biomarkers Prev; 20(6); 1196-203. (C)2011 AACR.