Carcinogenesis Advance Access published online on November 13, 2007
Carcinogenesis, 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, NIH, DHHS, Bethesda, MD
2 Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, GA
3 Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA
4 Department of Mathematics and Statistics, Concordia University, Montreal, Quebec, Canada
5 Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA
6 Division of Urologic Surgery, Washington University School of Medicine, St. Louis, MO
7 Cancer Prevention Fellowship Program, Office of Preventive Oncology, Division of Cancer Prevention, National Cancer Institute, NIH, DHHS, Bethesda, MD
8 Core Genotyping Facility, Division of Cancer Epidemiology and Genetics, Advanced Technology Program, SAIC Frederick, Inc., NCI-Frederick, Frederick, MD
9 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
10 Department of Epidemiology, Harvard School of Public Health, Boston, MA
11 Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD
* To whom correspondence should be addressed: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd, Suite 550, MSC 7234, Rockville, MD 20852, USA. Phone: (301) 594-5631 ; Fax: (301) 402-0916; E-mail: danfortk{at}mail.nih.gov
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.
Key Words: PTGS2, COX-2 • inflammation • genetic susceptibility • prostate cancer
Received September 7, 2007; revised November 2, 2007; accepted November 4, 2007.