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Paraoxonase 1 (PON1) polymorphisms and prostate cancer in the CPS‐II Nutrition Cohort
Author(s) -
Stevens Victoria L.,
Rodriguez Carmen,
Talbot Jeffrey T.,
Pavluck Alexandre L.,
Thun Michael J.,
Calle Eugenia E.
Publication year - 2008
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20796
Subject(s) - prostate cancer , paraoxonase , single nucleotide polymorphism , pon1 , medicine , oncology , case control study , snp , genotype , cancer , cohort , prostate , nonsynonymous substitution , allele , endocrinology , genetics , biology , oxidative stress , gene , genome
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 L55M SNP may be associated with increased risk of aggressive prostate, perhaps through attenuation of paraoxonase l activity. Prostate 68:1336–1340, 2008. © 2008 Wiley‐Liss, Inc.