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Polymorphic variants in PTGS2 and prostate cancer risk: results from two large nested case-control studies

  1. Author:
    Danforth, K. N.
    Hayes, R. B.
    Rodriguez, C.
    Yu, K.
    Sakoda, L. C.
    Huang, W. Y.
    Chen, B. E.
    Chen, J. B.
    Andriole, G. L.
    Calle, E. E.
    Jacobs, E. J.
    Chu, L. W.
    Figueroa, J. D.
    Yeager, M.
    Platz, E. A.
    Michaud, D. S.
    Chanock, S. J.
    Thun, M.

  2. Author Address

    Danforth, Kim N.; Hayes, Richard B.; Yu, Kai, Huang, Wen-Yi, Figueroa, Jonine D.; Chanock, Stephen J.; Hsing, Ann W.] NCI, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Rodriguez, Carmen, Calle, Eugenia E.; Jacobs, Eric J.; Thun, Michael J.] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30303 USA. [Sakoda, Lori C.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Chen, Bingshu E.] Concordia Univ, Dept Mat & Stat, Montreal, PQ H3G 1M8, Canada. [Chen, Jinbo] Hosp Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Chu, Lisa W.; Figueroa, Jonine D.] NCI, NIH, Dept Hlth & Human Serv, Div Canc Prevent,Off Prevent Oncol,Canc Prevent F, Rockville, MD 20852 USA. [Chanock, Stephen J.] NCI Frederick, SAIC Frederick Inc, Adv Technol Program, Div Canc Epidemiol & Genet,Core Genotyping Facil, Frederick, MD 20877 USA. [Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Michaud, Dominique S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chanock, Stephen J.] NCI, NIH, Dept Hlth & Human Serv, Ctr Canc Res, Bethesda, MD 20892 USA.
    1. Year: 2008
  2. Journal: Carcinogenesis
    1. 29
    2. 3
    3. Pages: 568-572
  4. Type of Article: Article
  1. 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.

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