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Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2

  1. Author:
    Prokunina-Olsson, L.
    Fu, Y. P.
    Tang, W.
    Jacobs, K. B.
    Hayes, R. B.
    Kraft, P.
    Berndt, S. I.
    Wacholder, S.
    Yu, K.
    Hutchinson, A.
    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. A.
    Henderson, B. E.
    Kolonel, L.
    Le Marchand, L.
    Siddiq, A.
    Riboli, E.
    Travis, R.
    Kaaks, R.
    Isaacs, W. B.
    Isaacs, S. D.
    Gronberg, H.
    Wiklund, F.
    Xu, J. F.
    Vatten, L. J.
    Hveem, K.
    Kumle, M.
    Tucker, M.
    Hoover, R. N.
    Fraumeni, J. F.
    Hunter, D. J.
    Thomas, G.
    Chatterjee, N.
    Chanock, S. J.
    Yeager, M.
  2. Author Address

    [Prokunina-Olsson, Ludmila; Fu, Yi-Ping; Tang, Wei; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Jacobs, Kevin B.; Hutchinson, Amy; Chanock, Stephen J.; Yeager, Meredith] NCI, Core Genotyping Facil, Adv Technol Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. [Jacobs, Kevin B.] Bioinformed Consulting Serv, Gaithersburg, MD USA. [Hayes, Richard B.] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. [Kraft, Peter; Schumacher, Fredrick R.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Cambridge, MA 02138 USA. [Schumacher, Fredrick R.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. [Hunter, David J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. [Feigelson, Heather Spencer; Thun, Michael J.; Diver, W. Ryan] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine] Hop Tenon, AP HP, Ctr Rech Pathol Prostat, F-75970 Paris, France. [Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Crawford, E. David] Univ Colorado, Dept Surg, Denver, CO 80202 USA. [Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Kolonel, Laurence; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [Siddiq, Afshan; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. [Travis, Ruth] Univ Oxford, Canc Epidemiol Unit, Oxford, England. [Kaaks, Rudolf] German Canc Res Ctr, Div Clin Epidemiol, Heidelberg, Germany. [Isaacs, William B.; Isaacs, Sarah D.] Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. [Gronberg, Henrik; Wiklund, Fredrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Xu, Jianfeng] Wake Forest Univ, Sch Med, Ctr Canc Genom, Winston Salem, NC 27109 USA. [Vatten, Lars J.; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth, N-7034 Trondheim, Norway. [Kumle, Merethe] Univ Tromso, Inst Community Med, Tromso, Norway.;Prokunina-Olsson, L, NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 8717 Grovemont Circle, Bethesda, MD 20892 USA.;prokuninal@mail.nih.gov
    1. Year: 2010
    2. Date: May
  1. Journal: Cancer Epidemiology Biomarkers & Prevention
    1. 19
    2. 5
    3. Pages: 1349-1355
  2. Type of Article: Article
  3. ISSN: 1055-9965
  1. Abstract:

    Background: Genome-wide association studies have identified multiple genetic variants associated with susceptibility to prostate cancer (PrCa). In the two-stage Cancer Genetic Markers of Susceptibility prostate cancer scan, a single-nucleotide polymorphism (SNP), rs10486567, located within intron 2 of JAZF1 gene on chromosome 7p15.2, showed a promising association with PrCa overall (P = 2.14 x 10(-6)), with a suggestion of stronger association with aggressive disease (P = 1.2 x 10(-7)). Methods: In the third stage of genome-wide association studies, we genotyped 106 JAZF1 SNPs in 10,286 PrCa cases and 9,135 controls of European ancestry. Results: The strongest association was observed with the initial marker rs10486567, which now achieves genome-wide significance [P = 7.79 x 10(-11); ORHET, 1.19 (95% confidence interval, 1.12-1.27); ORHOM, 1.37 (95% confidence interval, 1.20-1.56)]. We did not confirm a previous suggestion of a stronger association of rs10486567 with aggressive disease (P = 1.60 x 10(-4) for aggressive cancer, n = 4,597; P = 3.25 x 10(-8) for non-aggressive cancer, n = 4,514). Based on a multilocus model with adjustment for rs10486567, no additional independent signals were observed at chromosome 7p15.2. There was no association between PrCa risk and SNPs in JAZF1 previously associated with height (rs849140; P = 0.587), body stature (rs849141, tagged by rs849136; P = 0.171), and risk of type 2 diabetes and systemic lupus erythematosus (rs864745, tagged by rs849142; P = 0.657). Conclusion: rs10486567 remains the most significant marker for PrCa risk within JAZF1 in individuals of European ancestry. Impact: Future studies should identify all variants in high linkage disequilibrium with rs10486567 and evaluate their functional significance for PrCa. Cancer Epidemiol Biomarkers Prev; 19(5); 1349-55. (C)2010 AACR.

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External Sources

  1. DOI: 10.1158/1055-9965.epi-09-1181
  2. WOS: 000278489800023

Library Notes

  1. Fiscal Year: FY2009-2010
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