Carcinogenesis Advance Access originally published online on November 13, 2007
Carcinogenesis 2008 29(3):568-572; doi:10.1093/carcin/bgm253
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Polymorphic variants in PTGS2 and prostate cancer risk: results from two large nested case–control studies
1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20852
2 Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, GA 30303
3 Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195
4 Department of Mathematics and Statistics, Concordia University, Montreal, Quebec H3G 1M8, Canada
5 Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
6 Division of Urologic Surgery, Washington University School of Medicine, St Louis, MO 63110
7 Cancer Prevention Fellowship Program, Office of Preventive Oncology, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20852
8 Core Genotyping Facility, Division of Cancer Epidemiology and Genetics, Advanced Technology Program, SAIC Frederick, Inc., NCI-Frederick, Frederick, MD 20877
9 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205
10 Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115
11 Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892
* To whom correspondence should be addressed. Tel: +1 301 594 5631; Fax: +1 301 402 0916; Email: danfortk{at}mail.nih.gov
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.
Abbreviations: CGEMS, Cancer Genetic Markers of Susceptibility; CPS-II, Cancer Prevention Study II; CI, confidence interval; NCI, National Cancer Institute; NSAID, non-steroidal anti-inflammatory drug; OR, odds ratio; PTGS2, prostaglandin-endoperoxide synthase 2; PLCO, Prostate, Lung, Colorectal and Ovarian; SNP, single nucleotide polymorphism
Received September 7, 2007; revised November 2, 2007; accepted November 4, 2007.