Association between genetic variants in glutathione peroxidase 1 (GPx1) gene, GPx activity and the risk of prostate cancer

Aim. The aim of this study was to investigate the association between GPx1 Pro198Leu polymorphism with the development and progression of prostate cancer (PCa) and evaluate whether smoking status and advanced age could modify this association. Methods. A total of 134 PCa patients and 159 healthy control subjects with serum prostate specific antigen (PSA) levels <4 ng/mL and normal digital rectal examination (DRE) findings were enrolled in this prospectively designed study. PCA patients were classified as low (T ₁ or T ₂ and N0M0 stages) and high stage disease (T ₃ or T ₄ and N0M0 or N1 or M1 stages). GPx1 Pro198Leu polymorphism was determined using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (95%CI). Results. Compared to the carriers of Pro/Pro genotype, subjects with the variant genotypes (Pro/Leu or Leu/Leu) had significantly higher risk of PCa. The Leu/Leu genotype was correlated with lower GPx activity among both controls and PCa patients. With respect to tumor stage, Leu/Leu genotype was more frequent in patients with high stage disease than those of low stage disease. In stratified analyses, although the variant Leu/Leu genotype was significantly associated with increased risk of PCa in older age, smoking did not alter this association. Conclusion. The present data provide evidence that GPx1 Pro198Leu polymorphism may be associated with the development and progression of PCa and older ages may influence the association.between GPx1 Pro198Leu polymorphism and PCa.