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

doi:10.1073/pnas.0605832103

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

^aDepartment of Medical Oncology, Dana–Farber Cancer Institute, Boston, MA 02115;
^bProgram in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;
^dDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089;
Departments of ^eGenetics and
^mMedicine and
^gBiopolymers Facility, Harvard Medical School, Boston, MA 02115;
^fLaboratory of Molecular Immunology, Center for Neurologic Disease, Brigham and Women's Hospital, Boston, MA 02115;
^hGenomics Collaborative, Division of SeraCare Life Sciences, Inc., Cambridge, MA 02139;
ⁱNorthern California Cancer Center, Fremont, CA 94538;
^jDepartment of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305;
^kDepartments of Medicine and Urology and
^lComprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109; and
ⁿCenter for Human Genetic Research and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114

Communicated by Eric S. Lander, Broad Institute, Cambridge, MA, July 12, 2006
↵ ^cM.L.F., C.A.H., and N.P. contributed equally to this work. (received for review May 24, 2006)

Abstract

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 (P < 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 (P < 4.2 × 10⁻⁹) 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.

Footnotes

^oTo whom correspondence should be addressed at:
Department of Genetics, Harvard Medical School, New Research Building, 77 Avenue Louis Pasteur, Boston, MA 02115.
E-mail: reich{at}receptor.med.harvard.edu
Author contributions: M.L.F., N.P., D.A., B.E.H., and D.R. designed research; M.L.F., C.A.H., N.P., G.J.M., A.T., A.W., K.P., R.G.S., and D.R. performed research; C.A.H., N.P., A.T., R.G.S., K.A., E.M.J., I.O.-G., A.S.W., K.A.C., S.A.I., B.E.H., and D.R. contributed new reagents/analytic tools; C.A.H., N.P., A.T., and D.R. analyzed data; and M.L.F., C.A.H., N.P., A.S.W., D.A., and D.R. wrote the paper.
Conflict of interest statement: No conflicts declared.
Abbreviations:

LOD,

logarithm of odds;

OR,

odds ratio.