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Multiple loci identified in a genome-wide association study of prostate cancer

  1. Author:
    Thomas, G.
    Jacobs, K. B.
    Yeager, M.
    Kraft, P.
    Wacholder, S.
    Orr, N.
    Yu, K.
    Chatterjee, N.
    Welch, R.
    Hutchinson, A.
    Crenshaw, A.
    Cancel-Tassin, G.
    Staats, B. J.
    Wang, Z.
    Gonzalez-Bosquet, J.
    Fang, J.
    Deng, X.
    Berndt, S. I.
    Calle, E.

  2. Author Address

    Thomas, Gilles, Yeager, Meredith, Wacholder, Sholom, Orr, Nick, Yu, Kai, Chatterjee, Nilanjan, Welch, Robert, Hutchinson, Amy, Crenshaw, Andrew, Staats, Brian J.; Wang, Zhaoming, Gonzalez-Bosquet, Jesus, Fang, Jun, Deng, Xiang, Berndt, Sonja I.; Albanes, Demetrius, Weinstein, Stephanie, Tucker, Margaret, Fraumeni, Joseph F., Jr.; Hoover, Robert, Hayes, Richard B.; Hunter, David J.; Chanock, Stephen J.] NCI, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Jacobs, Kevin B.] Bioinformed Consulting Serv, Gaithersburg, MD 20877 USA. [Yeager, Meredith, Welch, Robert, Hutchinson, Amy, Crenshaw, Andrew, Staats, Brian J.; Wang, Zhaoming, Deng, Xiang] NCI Frederick, SAIC Frederick Inc, Adv Technol Program, Core Genotyping Facil, Frederick, MD 21702 USA. [Kraft, Peter, Schumacher, Fredrick R.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Calle, Eugenia E.; Feigelson, Heather Spencer, Thun, Michael J.; Rodriguez, Carmen] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, FIN-0030 Helsinki, Finland. [Thomas, Gilles, Giovannucci, Edward, Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63108 USA. [Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Dept Surg, Denver, CO 80014 USA. [Gerhard, Daniela S.] NCI, NIH, Dept Hlth & Human Serv, Ctr Canc Res,Off Canc Genom, Bethesda, MD 20892 USA. [Chanock, Stephen J.] NCI, NIH, Dept Hlth & Human Serv, Ctr Canc Res,Pediat Oncol Branch, Bethesda, MD 20892 USA. [Cancel-Tassin, Geraldine, Cussenot, Olivier, Valeri, Antoine] CeRePP Hop Tenon, AP HP, F-75970 Paris, France.
    1. Year: 2008
    2. Date: Mar
  2. Journal: Nature Genetics
    1. 40
    2. 3
    3. Pages: 310-315
  4. Type of Article: Article
  5. ISSN: 1061-4036
  1. Abstract:

    We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin-nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial prospective study-by testing 26,958 SNPs in four independent studies (total of 3,941 cases and 3,964 controls). In the combined joint analysis, we confirmed three previously reported loci (two independent SNPs at 8q24 and one in HNF1B (formerly known as TCF2 on 17q); P < 10(-10)). In addition, loci on chromosomes 7, 10 (two loci) and 11 were highly significant (between P < 7.31 x 10(-13) and P < 2.14 x 10(-6)). Loci on chromosome 10 include MSMB, which encodes beta-microseminoprotein, a primary constituent of semen and a proposed prostate cancer biomarker, and CTBP2, a gene with antiapoptotic activity, the locus on chromosome 7 is at JAZF1, a transcriptional repressor that is fused by chromosome translocation to SUZ12 in endometrial cancer. Of the nine loci that showed highly suggestive associations (P < 2.5 x 10(-5)), four best fit a recessive model and included candidate susceptibility genes: CPNE3, IL16 and CDH13. Our findings point to multiple loci with moderate effects associated with susceptibility to prostate cancer that, taken together, in the future may predict high risk in select individuals.

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  2. DOI: 10.1038/ng.91
  3. PMID: 18264096

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