Publications Search

Abstract

Title: Polymorphic variants in PTGS2 and prostate cancer risk: results from two large nested case-control studies.
Author: Danforth KN, Hayes RB, Rodriguez C, Yu K, Sakoda LC, Huang WY, Chen BE, Chen J, Andriole GL, Calle EE, Jacobs EJ, Chu LW, Figueroa JD, Yeager M, Platz EA, Michaud DS, Chanock SJ, Thun MJ, Hsing AW
Journal: Carcinogenesis 29(3):568-572
Year: 2008
Month: March

Abstract: Chronic inflammation has been hypothesized to increase prostate cancer risk. Prostaglandin-endoperoxide synthase 2 (PTGS2) encodes the pro-inflammatory cyclooxygenase 2 enzyme believed to be the rate-limiting step in the synthesis of prostaglandins, important mediators of inflammation. We investigated associations between PTGS2 polymorphisms and prostate cancer risk among 2,321 prostate cancer cases and 2,560 controls in two large case-control studies nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and the Cancer Prevention Study II Nutrition Cohort. Five single nucleotide polymorphisms (SNPs) (rs5277, rs20432, rs4648276, rs5275, rs689470) were examined in single-SNP and haplotype analyses (5 SNPs in PLCO, 4 SNPs in the Nutrition Cohort). In PLCO, the Ex10 +837 T>C marker (rs5275) was initially associated with prostate cancer risk (p-trend=0.02) but became non-significant after adjustment for multiple comparisons (p=0.08); this SNP showed no association with prostate cancer risk in the Nutrition Cohort (p-trend=0.54) or in an analysis pooling the two cohorts (p-trend=0.20). No other SNP was associated with prostate cancer risk in PLCO or the Nutrition Cohort individually or combined. Haplotype analyses suggested an association between PTGS2 variants in PLCO alone (global p=0.007), but not in the Nutrition Cohort (global p=0.78) or pooled analysis (global p=0.18). In conclusion, despite the potential importance of inflammation in prostate carcinogenesis, results from our large study of five PTGS2 SNPs does not support a strong association between PTGS2 variants and prostate cancer risk in non-Hispanic white men.