Evaluation of 8q24 and 17q Risk Loci and Prostate Cancer Mortality

Abstract

Purpose: Variants at chromosomal loci 8q24 and 17q are established risk factors for prostate cancer. Many studies have confirmed the findings for risk, but few have examined aggressiveness and other clinical variables in detail. Additionally, Gleason score is typically used as a surrogate for the primary end point of prostate cancer mortality. We investigated whether the 8q24 and 17q risk variants are associated with clinical variables as well as prostate cancer mortality.Experimental Design: In the Physicians' Health Study (1,347 cases and 1,462 controls), the Dana-Farber Harvard Cancer Center Specialized Program of Research Excellence (Gelb Center; 3,714 cases), and the Fred Hutchinson Cancer Research Center King County Case-Control Studies (1,308 cases and 1,266 controls), we examined eight previously identified 8q24 and 17q risk variants for association with prostate cancer mortality in men of European ancestry. We considered associations with other surrogate markers of prostate cancer aggressiveness, such as Gleason score, pathologic stage, prostate-specific antigen at diagnosis, and age at diagnosis. Results: Six of the eight variants were confirmed as prostate cancer risk factors. Several variants were nominally associated with age at diagnosis; when totaling all alleles for single nucleotide polymorphisms significantly associated with risk, each additional allele decreased age at diagnosis by an average of 6 months in the Physicians' Health Study (P = 0.0005) and 4 months in the Dana-Farber Harvard Cancer Center Specialized Program of Research Excellence (Gelb Center) cohort (P = 0.0016). However, there were no statistically significant associations with prostate cancer mortality. Conclusions: Our results suggest that the 8q24 and 17q prostate cancer risk variants may influence age at diagnosis but not disease aggressiveness.