title: Polymorphic variants in PTGS2 and prostate cancer risk: results from two large nested case-control studies.
abstract: Chronic inflammation has been hypothesized to increase prostate cancer risk. Prostaglandin-endoperoxide synthase 2 (PTGS2) encodes the proinflammatory 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 2321 prostate cancer cases and 2560 controls in two large case-control studies nested within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Cancer Prevention Study II Nutrition Cohort. Five single nucleotide polymorphisms (SNPs) (rs5277, rs20432, rs4648276, rs5275 and rs689470) were examined in SNP and haplotype analyses (five SNPs in PLCO and four 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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20852, USA. danfortk@mail.nih.gov
authors.forename: Kim N
authors.initials: KN
authors.lastname: Danforth
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodriguez
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Lori C
authors.initials: LC
authors.lastname: Sakoda
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Huang
authors.forename: Bingshu E
authors.initials: BE
authors.lastname: Chen
authors.forename: Jinbo
authors.initials: J
authors.lastname: Chen
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Andriole
authors.forename: Eugenia E
authors.initials: EE
authors.lastname: Calle
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jacobs
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Chu
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.forename: Dominique S
authors.initials: DS
authors.lastname: Michaud
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thun
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human