Antioxidant and Vitamin E Transport Genes and Risk of High-Grade Prostate Cancer and Prostate Cancer Recurrence

BACKGROUNDObservational studies suggest an inverse association between vitamin E and risk of prostate cancer, particularly aggressive tumors. However, three large randomized controlled trials have reported conflicting results. Thus, we examined circulating vitamin E and vitamin E-related genes in relation to risk of high-grade prostate cancer and prostate cancer recurrence among men initially diagnosed with clinically organ-confined disease. METHODSWe measured circulating - and -tocopherol and genotyped 30 SNPs in SOD1, SOD2, SOD3, TTPA, and SEC14L2 among 573 men with organ-confined prostate cancer who underwent radical prostatectomy. We examined associations between circulating vitamin E, genotypes, and risk of high-grade prostate cancer (Gleason grade8 or 7 with primary score4; n=117) using logistic regression, and risk of recurrence (56 events; 3.7 years median follow-up) using Cox proportional hazards regression. RESULTSCirculating -tocopherol was associated with an increased risk of high-grade prostate cancer (Q4 v. Q1 odds ratio [OR]=1.87; 95% confidence intervals [CI]: 0.97-3.58; P-trend=0.02). The less common allele in SOD3 rs699473 was associated with an increased risk of high-grade disease (T>C: OR=1.40, 95% CI: 1.04-1.89). Two independent SNPs in SOD1 were inversely associated with prostate cancer recurrence in additive models (rs17884057 hazard ratio [HR]=0.49, 95%CI: 0.25-0.96; rs9967983 HR=0.62, 95% CI: 0.40-0.95). CONCLUSIONSAmong men with clinically organ-confined prostate cancer, genetic variation in SOD may be associated with risk of high-grade disease at diagnosis and disease recurrence. Circulating -tocopherol levels may also be associated with an increased risk of high-grade disease at diagnosis. Prostate 73:1786-1795, 2013. (c) 2013 Wiley Periodicals, Inc.