Background
Antioxidants may reduce risk of aggressive prostate cancer, and single nucleotide polymorphisms (SNPs) in antioxidant genes may modify this association.
Methods
We used Cox proportional hazards regression to examine circulating prediagnostic alpha-tocopherol, gamma-tocopherol, and lycopene; SNPs in SOD2 (n=5), CAT (n=6), GPX1 (n=2), GPX4 (n=3); and their interactions and risk of lethal prostate cancer among 2,439 men with nonmetastatic prostate cancer in the Health Professionals Follow-up Study and Physicians’ Health Study.
Results
We observed 223 events over a median follow-up of 10 years. Higher alpha-tocopherol levels were associated with lower risk of lethal prostate cancer (hazard ratio (HR) 3rd v. 1st quartile (Q): 0.51; 95% confidence interval (CI): 0.30, 0.89; HR 4th v. 1st Q: 0.68; 95% CI: 0.41, 1.13; p-trend: 0.02). Men homozygous for the less common allele (G) at rs3746165 in GPX4 had a 35% lower risk of lethal prostate cancer compared to men homozygous for the more common allele (A) (HR: 0.65; 95% CI: 0.43, 0.99). Among men homozygous for the less common allele in rs3746165, high gamma-tocopherol levels were associated with a 3.5-fold increased risk of lethal prostate cancer (95% CI: 1.27, 9.72; p-value: 0.02; interaction p-value 0.01).
Conclusions
Among men with nonmetastatic prostate cancer, higher circulating prediagnostic alpha-tocopherol may be associated with lower risk of developing lethal disease. Variants in GPX4 may be associated with risk of lethal prostate cancer, and may modify the relation between gamma-tocopherol and prostate cancer survival.
Impact
Circulating tocopherol levels and variants in GPX4 may affect prostate cancer progression.