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Antioxidant and vitamin E transport genes and risk of high‐grade prostate cancer and prostate cancer recurrence
Author(s) -
Bauer Scott R.,
Richman Erin L.,
Sosa Eduardo,
Weinberg Vivian,
Song Xiaoling,
Witte John S.,
Carroll Peter R.,
Chan June M.
Publication year - 2013
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22717
Subject(s) - prostate cancer , medicine , hazard ratio , oncology , odds ratio , prostatectomy , cancer , prostate , proportional hazards model , confidence interval , gynecology , gastroenterology
Abstract BACKGROUND Observational 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. METHODS We measured circulating α‐ and γ‐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 grade ≥ 8 or 7 with primary score ≥ 4; n = 117) using logistic regression, and risk of recurrence (56 events; 3.7 years median follow‐up) using Cox proportional hazards regression. RESULTS Circulating γ‐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). CONCLUSIONS Among 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 γ‐tocopherol levels may also be associated with an increased risk of high‐grade disease at diagnosis. Prostate 73:1786–1795, 2013 . © 2013 Wiley Periodicals, Inc.