Study of the effect of Sep15 and GPx4 gene polymorphisms on prostate cancer risk

Abstract

Recent studies have reported functional polymorphisms in several selenoprotein genes and association of these allelic variants with cancer risk. The model for chemoprevention by selenium suggests that reduced levels of one or more selenoproteins increase cancer risk, with these levels affected by reduced dietary intake and genetic polymorphisms that result in an increased Se requirement. In this study, we investigated the effect of single nucleotide polymorphisms (SNPs) in the selenocysteine insertion sequence (SECIS) element which is vital for efficient selenoprotein translation, in selenoprotein 15 [Sep15 811C/T] and glutathione peroxidase [GPx4 718T/C]. Our study was carried out in men from a low Se status population and powered to detect a low odds ratio of 1.5 to 1.9, as often found for this type of association. Using the TaqMan allelic discrimination assay, we genotyped DNA from 1400 prostate cancer cases and 800 cancer-free controls matched for age and location who took part in the CAncer Prostate Sweden (CAPS) study. The combined genotypic, clinical and demographic data were analysed statistically (SPSS 12.0). Overall, control allele frequencies were consistent with previous reports (Sep15 811T allele, 0.21 and GPx4 718C allele, 0.58) and observed genotype frequencies were in Hardy-Weinberg equilibrium. Although no direct association between prostate cancer risk and genotype was found in the case-control analyses, we are examining the relationship between genotype and clinical markers of disease severity. The outcome may be useful in identifying men who are genetically susceptible to advanced disease and could benefit from Se supplementation.