Polymorphisms in oxidative stress pathway genes and prostate cancer risk

Age-related factors including oxidative stress play an important role in prostate carcinogenesis. We hypothesize that germline single-nucleotide polymorphisms (SNPs) in oxidative stress pathway are associated with prostate cancer (PCa) risk. In this study, we aim to examine which of these SNPs is associated with PCa.

Participants included in this analyses came from the "Genetic Susceptibility, Environment and Prostate Cancer Risk Study" conducted at the Veterans Affairs Portland Health Care System. After applying exclusion criteria, 231 PCa cases and 382 prostate biopsy-negative controls who had genotyping data on twenty-two single-nucleotide polymorphisms (SNPs) in six genes (MAPK14, NRF2, CAT, GPX1, GSTP1, SOD2, and XDH) associated with oxidative stress pathway were included in the analyses. The genotyping of SNPs was conducted by the Illumina BeadXpress VeraCode platform. We investigated these SNPs in relation to overall and aggressive PCa risk using logistic regression models controlling for relevant covariates.

One SNP in the MAPK14 (rs851023) was significantly associated with incident PCa risk. Compared to men carrying two copies of allele A, the presence of one or two copies of the G allele was associated with decreased risk of PCa [OR (95% CI) 0.19 (0.06-0.51)]. There was no statistically significant association between other SNPs in the NRF2, CAT, GPX1, GSTP1, SOD2, and XDH genes and PCa risk.

The MAPK14 gene SNP rs851023 was associated with PCa and aggressive PCa risk after multiple comparison adjustment. Further studies in other populations or functional studies are needed to validate the finding.