Paraoxonase 1 (PON1) polymorphisms and prostate cancer in the CPS-II nutrition cohort

BACKGROUND. The HDL-associated enzyme paraoxonase 1 acts to decrease oxidative stress, which is thought to contribute to cancer development. PON1, which encodes paraoxonase 1, has two common, nonsynonymous SNPs that alter the activity of this enzyme and may influence cancer risk. METHODS. We investigated the association the nonsynonymous SNPs, Q192R and L55M, with prostate cancer risk in a nested case-control analysis of 1,268 cases and 1,268 matched controls from the American Cancer Society CPS-II Nutrition Cohort. RESULTS. For both the Q192R and L55MSNPs, the presence of the variant allele was associated with an increased risk of aggressive prostate cancer that approached statistical significance. The genotype combination that included one variant allele from both SNPs (QR/LM) was associated with an increased risk of more than twofold (OR = 2.18, 95% CI: 1.31, 3.64). CONCLUSIONS. These findings suggest that the Q129R and the L55MSNP may be associated with increased risk of aggressive prostate, perhaps through attenuation of paraoxonase 1 activity.