Letter abstract


Nature Genetics 39, 638 - 644 (2007)
Published online: 1 April 2007 | doi:10.1038/ng2015

Multiple regions within 8q24 independently affect risk for prostate cancer

Christopher A Haiman1, Nick Patterson2, Matthew L Freedman2,3, Simon R Myers2, Malcolm C Pike1, Alicja Waliszewska2,4,5, Julie Neubauer2,4, Arti Tandon2,4, Christine Schirmer2,4, Gavin J McDonald2,4, Steven C Greenway4, Daniel O Stram1, Loic Le Marchand6, Laurence N Kolonel6, Melissa Frasco1, David Wong1, Loreall C Pooler1, Kristin Ardlie2,7, Ingrid Oakley-Girvan8,9, Alice S Whittemore9, Kathleen A Cooney10,11, Esther M John8,9, Sue A Ingles1, David Altshuler2,4,12,13, Brian E Henderson1 & David Reich2,4

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After the recent discovery that common genetic variation in 8q24 influences inherited risk of prostate cancer, we genotyped 2,973 SNPs in up to 7,518 men with and without prostate cancer from five populations. We identified seven risk variants, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 times 10-19 for the strongest association, and P < 1.5 times 10-4 for five of the variants, after controlling for each of the others). The variants define common genotypes that span a more than fivefold range of susceptibility to cancer in some populations. None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein.

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  1. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
  2. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
  3. Dana-Farber Cancer Institute, Department of Medical Oncology, Boston, Massachusetts 02115, USA.
  4. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  5. Laboratory of Molecular Immunology, Center for Neurologic Disease, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
  6. Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii 96813, USA.
  7. Genomics Collaborative, Division of SeraCare Life Sciences Inc, Cambridge, Massachusetts 02139, USA.
  8. Northern California Cancer Center, Fremont, California 94538, USA.
  9. Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California 94305, USA.
  10. Departments of Medicine and Urology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  11. University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109, USA.
  12. Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
  13. Center for Human Genetic Research and Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

Correspondence to: David Reich2,4 e-mail: reich@genetics.med.harvard.edu

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