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Large-scale fine mapping of the HNF1B locus and prostate cancer risk

  1. Author:
    Berndt, S. I.
    Sampson, J.
    Yeager, M.
    Jacobs, K. B.
    Wang, Z. M.
    Hutchinson, A.
    Chung, C.
    Orr, N.
    Wacholder, S.
    Chatterjee, N.
    Yu, K.
    Kraft, P.
    Feigelson, H. S.
    Thun, M. J.
    Diver, W. R.
    Albanes, D.
    Virtamo, J.
    Weinstein, S.
    Schumacher, F. R.
    Cancel-Tassin, G.
    Cussenot, O.
    Valeri, A.
    Andriole, G. L.
    Crawford, E. D.
    Haiman, C.
    Henderson, B.
    Kolonel, L.
    Le Marchand, L.
    Siddiq, A.
    Riboli, E.
    Travis, R. C.
    Kaaks, R.
    Isaacs, W.
    Isaacs, S.
    Wiley, K. E.
    Gronberg, H.
    Wiklund, F.
    Stattin, P.
    Xu, J. F.
    Zheng, S. L.
    Sun, J. L.
    Vatten, L. J.
    Hveem, K.
    Njolstad, I.
    Gerhard, D. S.
    Tucker, M.
    Hayes, R. B.
    Hoover, R. N.
    Fraumeni, J. F.
    Hunter, D. J.
    Thomas, G.
    Chanock, S. J.

  2. Author Address

    [Berndt, SI; Sampson, J; Yeager, M; Wang, ZM; Hutchinson, A; Chung, C; Orr, N; Wacholder, S; Chatterjee, N; Yu, K; Albanes, D; Weinstein, S; Tucker, M; Hoover, RN; Fraumeni, JF; Thomas, G; Chanock, SJ] NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA [Yeager, M; Wang, ZM; Hutchinson, A; Chung, C] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA [Jacobs, KB] Bioinformed Consulting Serv, Gaithersburg, MD USA [Kraft, P] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA [Feigelson, HS] Kaiser Permanente, Inst Hlth Res, Denver, CO USA [Thun, MJ; Diver, WR] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA [Virtamo, J] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland [Schumacher, FR; Haiman, C; Henderson, B] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA [Cancel-Tassin, G; Cussenot, O; Valeri, A] Hop Tenon, Assistance Publ Hop Paris, Ctr Rech Pathol Prostat, F-75970 Paris, France [Andriole, GL] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA [Crawford, ED] Univ Colorado, Hlth Sci Ctr, Denver, CO USA [Crawford, ED] Univ Colorado, Dept Surg, Denver, CO 80202 USA [Kolonel, L; Le Marchand, L] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA [Siddiq, A; Riboli, E] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England [Travis, RC] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England [Kaaks, R] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany [Isaacs, W; Isaacs, S; Wiley, KE] Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA [Gronberg, H; Wiklund, F] Karolinska Inst, CLINTEC, Dept Med Epidemiol & Biostat, Stockholm, Sweden [Stattin, P] Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden [Xu, JF; Zheng, SL; Sun, JL] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA [Vatten, LJ; Hveem, K] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, N-7034 Trondheim, Norway [Gerhard, DS] NCI, Off Canc Genom, US Dept HHS, NIH, Bethesda, MD 20892 USA [Njolstad, I] Univ Tromso, Inst Community Med, Tromso, Norway [Hayes, RB] NYU, Med Ctr, Dept Environm Med, New York, NY USA [Hunter, DJ] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA;Berndt, SI (reprint author), NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, 6120 Execut Blvd,EPS 8116,MSC 7240, Bethesda, MD 20892 USA;berndts@mail.nih.gov
    1. Year: 2011
    2. Date: Aug
  2. Journal: Human Molecular Genetics
    1. 20
    2. 16
    3. Pages: 3322-3329
  4. Type of Article: Article
  5. ISSN: 0964-6906
  1. Abstract:

    Previous genome-wide association studies have identified two independent variants in HNF1B as susceptibility loci for prostate cancer risk. To fine-map common genetic variation in this region, we genotyped 79 single nucleotide polymorphisms (SNPs) in the 17q12 region harboring HNF1B in 10 272 prostate cancer cases and 9123 controls of European ancestry from 10 case-control studies as part of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. Ten SNPs were significantly related to prostate cancer risk at a genome-wide significance level of P < 5 x 10(-8) with the most significant association with rs4430796 (P = 1.62 x 10(-24)). However, risk within this first locus was not entirely explained by rs4430796. Although modestly correlated (r(2) = 0.64), rs7405696 was also associated with risk (P = 9.35 x 10(-23)) even after adjustment for rs4430769 (P = 0.007). As expected, rs11649743 was related to prostate cancer risk (P = 3.54 x 10(-8)); however, the association within this second locus was stronger for rs4794758 (P = 4.95 x 10(-10)), which explained all of the risk observed with rs11649743 when both SNPs were included in the same model (P = 0.32 for rs11649743; P = 0.002 for rs4794758). Sequential conditional analyses indicated that five SNPs (rs4430796, rs7405696, rs4794758, rs1016990 and rs3094509) together comprise the best model for risk in this region. This study demonstrates a complex relationship between variants in the HNF1B region and prostate cancer risk. Further studies are needed to investigate the biological basis of the association of variants in 17q12 with prostate cancer.

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External Sources

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  2. DOI: 10.1093/hmg/ddr213
  3. View record in Web of Science®
  4. WOS: 000293027100018

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  1. Fiscal Year: FY2010-2011
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