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Plasma antioxidants, genetic variation in SOD2, CAT, GPX1, GPX4, and prostate cancer survival.

ABSTRACT: Antioxidants may reduce risk of aggressive prostate cancer, and single-nucleotide polymorphisms (SNP) in antioxidant genes may modify this association.We used Cox proportional hazards regression to examine circulating prediagnostic ?-tocopherol, ?-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.We observed 223 events over a median follow-up of 10 years. Higher ?-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 ?-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).Among men with nonmetastatic prostate cancer, higher circulating prediagnostic ?-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 ?-tocopherol and prostate cancer survival.Circulating tocopherol levels and variants in GPX4 may affect prostate cancer progression. Cancer Epidemiol Biomarkers Prev; 23(6); 1037-46. ©2014 AACR.

SUBMITTER: Van Blarigan EL

PROVIDER: S-EPMC4047147 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Plasma antioxidants, genetic variation in SOD2, CAT, GPX1, GPX4, and prostate cancer survival.

Van Blarigan Erin L EL Ma Jing J Kenfield Stacey A SA Stampfer Meir J MJ Sesso Howard D HD Giovannucci Edward L EL Witte John S JS Erdman John W JW Chan June M JM Penney Kathryn L KL

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20140407 6

<h4>Background</h4>Antioxidants may reduce risk of aggressive prostate cancer, and single-nucleotide polymorphisms (SNP) in antioxidant genes may modify this association.<h4>Methods</h4>We used Cox proportional hazards regression to examine circulating prediagnostic α-tocopherol, γ-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 Prof ...[more]

PMID: 24711484

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Project description:Background: Oxidative stress plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). Glutathione peroxidase 1 (GPx1) and catalase (CAT) are the major intracellular antioxidant enzymes that can detoxify hydrogen peroxide into water, preventing cellular injury from reactive oxygen species. The aim of the present study was to investigate the association of GPx1 P198L (Pro198Leu, C559T, rs1050450) and CAT C-262T (rs1001179) genetic polymorphisms with the risk of PCOS and evaluate the effects of the genotypes on clinical, hormonal, metabolic and oxidative stress parameters in Chinese women. Methods: This is a case-control study of 654 patients with PCOS and 535 controls. The GPx1 P198L, CAT C-262T, and superoxide dismutase 2 (SOD2) A16V genotypes were determined by polymerase chain reaction amplification and restriction analysis. Clinical, hormonal, metabolic and oxidative stress parameters were also analyzed. Results: The frequencies of the PL + LL genotype (14.1 vs. 8.4%) and L allele (7.3 vs. 4.4%) of GPx1 P198L polymorphism were significantly higher in patients with PCOS than in control subjects. Genotype (PL + LL) remained a significant predictor for PCOS in prognostic models including age, body mass index (BMI), insulin resistance index, total cholesterol, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol as covariates (OR = 2.105, 95%CI: 1.330-3.331, P = 0.001). Patients carrying the L allele had relatively high average ovarian volume, waist circumference, and malondialdehyde levels (P < 0.07) compared with patients with the PP genotype. We also demonstrated that the subjects with both GPx1 L and SOD2 A alleles further increase the risk of PCOS compared with the individuals carrying the PP/VV genotype after adjusting for age and BMI (OR = 5.774, 95%CI: 2.243-14.863, P < 0.001). However, no significant differences were observed in the frequencies of the CAT C-262T genotypes and alleles between PCOS and control groups. Conclusions: The GPx1 P198L, but not CAT C-262T, genetic polymorphism is associated with the risk of PCOS in Chinese women.

Dataset Information

Plasma antioxidants, genetic variation in SOD2, CAT, GPX1, GPX4, and prostate cancer survival.

Publications

Plasma antioxidants, genetic variation in SOD2, CAT, GPX1, GPX4, and prostate cancer survival.

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