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A Large Study of Androgen Receptor Germline Variants and Their Relation to Sex Hormone Levels and Prostate Cancer Risk. Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

  1. Author:
    Lindstrom, S.
    Ma, J.
    Altshuler, D.
    Giovannucci, E.
    Riboli, E.
    Albanes, D.
    Allen, N. E.
    Berndt, S. I.
    Boeing, H.
    Bueno-de-Mesquita, H. B.
    Chanock, S. J.
    Dunning, A. M.
    Feigelson, H. S.
    Gaziano, J. M.
    Haiman, C. A.
    Hayes, R. B.
    Henderson, B. E.
    Hunter, D. J.
    Kaaks, R.
    Kolonel, L. N.
    Le Marchand, L.
    Martinez, C.
    Overvad, K.
    Siddiq, A.
    Stampfer, M.
    Stattin, P.
    Stram, D. O.
    Thun, M. J.
    Trichopoulos, D.
    Tumino, R.
    Virtamo, J.
    Weinstein, S. J.
    Yeager, M.
    Kraft, P.
    Freedman, M. L.

  2. Author Address

    [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lindstroem, Sara; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Lindstroem, Sara; Stampfer, Meir; Trichopoulos, Dimitrios; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward; Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ma, Jing; Hunter, David J.; Stampfer, Meir] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. [Altshuler, David] Broad Inst Massachusetts Inst Technol MIT & Harva, Program Med & Populat Genet, Cambridge, MA USA. [Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Riboli, Elio; Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Epidemiol & Publ Hlth, London, England. [Albanes, Demetrius; Berndt, Sonja I.; Chanock, Stephen J.; Hayes, Richard B.; Weinstein, Stephanie J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Allen, Naomi E.] Univ Oxford, Canc Epidemiol Unit, Oxford, England. [Boeing, Heiner] German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. [Dunning, Alison M.] Univ Cambridge, Dept Oncol, Cambridge, England. [Feigelson, Heather Spencer; Thun, Michael J.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [Feigelson, Heather Spencer] Kaiser Permanente, Denver, CO USA. [Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr, Boston, MA USA. [Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Haiman, Christopher A.; Henderson, Brian E.; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Hayes, Richard B.] NYU, Div Epidemiol, Langone Med Ctr, New York, NY USA. [Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Martinez, Carmen] Ctr Invest Biomed Red Epidemiol & Salud Publ, Granada, Spain. [Martinez, Carmen] Andalusian Sch Publ Hlth, Granada, Spain. [Overvad, Kim] Aarhus Univ Hosp, Aalborg Hosp, Aalborg, Denmark. [Stattin, Paer] Umea Univ, Umea, Sweden. [Tumino, Rosario] Canc Registry Azienda Osped Civile MP Arezzo, Ragusa, Italy. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Yeager, Meredith] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Freedman, Matthew L.] Broad Inst Harvard & MIT, Cambridge, MA USA.;Freedman, ML, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.;mfreedman@partners.org
    1. Year: 2010
    2. Date: Sep
  2. Journal: Journal of Clinical Endocrinology & Metabolism
    1. 95
    2. 9
    3. Pages: E121-E127
  4. Type of Article: Article
  5. ISSN: 0021-972X
  1. Abstract:

    Background: Androgens are key regulators of prostate gland maintenance and prostate cancer growth, and androgen deprivation therapy has been the mainstay of treatment for advanced prostate cancer for many years. Along-standing hypothesis has been that inherited variation in the androgen receptor (AR) gene plays a role in prostate cancer initiation. However, studies to date have been inconclusive and often suffered from small sample sizes. Objective and Methods: We investigated the association of AR sequence variants with circulating sex hormone levels and prostate cancer risk in 6058 prostate cancer cases and 6725 controls of Caucasian origin within the Breast and Prostate Cancer Cohort Consortium. We genotyped a highly polymorphic CAG microsatellite in exon 1 and six haplotype tagging single nucleotide polymorphisms and tested each genetic variant for association with prostate cancer risk and with sex steroid levels. Results: We observed no association between AR genetic variants and prostate cancer risk. However, there was a strong association between longer CAG repeats and higher levels of testosterone (P = 4.73 x 10(-5)) and estradiol (P = 0.0002), although the amount of variance explained was small (0.4 and 0.7%, respectively). Conclusions: This study is the largest to date investigating AR sequence variants, sex steroid levels, and prostate cancer risk. Although we observed no association between AR sequence variants and prostate cancer risk, our results support earlier findings of a relation between the number of CAG repeats and circulating levels of testosterone and estradiol. (J Clin Endocrinol Metab 95: E121-E127, 2010)

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External Sources

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  2. DOI: 10.1210/jc.2009-1911
  3. View record in Web of Science®
  4. WOS: 000281640300020

Library Notes

  1. Fiscal Year: FY2009-2010
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