Plasma antioxidants, genetic variation in SOD2, CAT, GPX1, GPX4, and prostate cancer survival
Blarigan, Erin Van
Kenfield, Stacey A.
Sesso, Howard D.
Giovannucci, Edward L.
Witte, John S.
Erdman, John W. Jr.
Chan, June M.
Penney, Kathryn L.
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CitationVan Blarigan, E. L., J. Ma, S. A. Kenfield, M. J. Stampfer, H. D. Sesso, E. L. Giovannucci, J. S. Witte, J. W. Erdman, J. M. Chan, and K. L. Penney. 2014. “Plasma Antioxidants, Genetic Variation in SOD2, CAT, GPX1, GPX4, and Prostate Cancer Survival.” Cancer Epidemiology Biomarkers & Prevention 23 (6): 1037–46. https://doi.org/10.1158/1055-9965.epi-13-0670.
AbstractBackground: Antioxidants may reduce risk of aggressive prostate cancer, and single-nucleotide polymorphisms (SNP) in antioxidant genes may modify this association. Methods: We used Cox proportional hazards regression to examine circulating prediagnostic a-tocopherol, g-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 a-tocopherol levels were associated with lower risk of lethal prostate cancer [ HR 3rd versus 1st quartile (Q): 0.51; 95% confidence interval (CI), 0.30-0.89; HR 4th versus 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 with 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 g-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 a-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 g-tocopherol and prostate cancer survival.Impact: Circulating tocopherol levels and variants in GPX4 may affect prostate cancer progression.
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