Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men

  • Matthew L. Freedman
    Department of Medical Oncology, Dana–Farber Cancer Institute, Boston, MA 02115;
  • Christopher A. Haiman
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089;
  • Nick Patterson
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;
  • Gavin J. McDonald
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;
  • Arti Tandon
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;
  • Alicja Waliszewska
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;
  • Kathryn Penney
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;
  • Robert G. Steen
    Departments of eGenetics and
  • Kristin Ardlie
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;
  • Esther M. John
    Northern California Cancer Center, Fremont, CA 94538;
  • Ingrid Oakley-Girvan
    Northern California Cancer Center, Fremont, CA 94538;
  • Alice S. Whittemore
    Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305;
  • Kathleen A. Cooney
    Departments of Medicine and Urology and
  • Sue A. Ingles
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089;
  • David Altshuler
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;
  • Brian E. Henderson
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089;
  • David Reich
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;

書誌事項

公開日
2006-09-19
DOI
  • 10.1073/pnas.0605832103
公開者
Proceedings of the National Academy of Sciences

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説明

<jats:p> A whole-genome admixture scan in 1,597 African Americans identified a 3.8 Mb interval on chromosome 8q24 as significantly associated with susceptibility to prostate cancer [logarithm of odds (LOD) = 7.1]. The increased risk because of inheriting African ancestry is greater in men diagnosed before 72 years of age ( <jats:italic>P</jats:italic> < 0.00032) and may contribute to the epidemiological observation that the higher risk for prostate cancer in African Americans is greatest in younger men (and attenuates with older age). The same region was recently identified through linkage analysis of prostate cancer, followed by fine-mapping. We strongly replicated this association ( <jats:italic>P</jats:italic> < 4.2 × 10 <jats:sup>−9</jats:sup> ) but find that the previously described alleles do not explain more than a fraction of the admixture signal. Thus, admixture mapping indicates a major, still-unidentified risk gene for prostate cancer at 8q24, motivating intense work to find it. </jats:p>

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