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

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Freedman, Matthew L., Haiman, Christopher A., Patterson, Nick, McDonald, Gavin J., Tandon, Arti, Waliszewska, Alicja, Penney, Kathryn, Steen, Robert G., Ardlie, Kristin, John, Esther M., Oakley-Girvan, Ingrid, Whittemore, Alice S., Cooney, Kathleen A., Ingles, Sue A., Altshuler, David, Henderson, Brian E., Reich, David·2006·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0605832103PMC PMC1599913

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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.

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Authors: Freedman, M. L., Haiman, C. A., Patterson, N., McDonald, G. J., Tandon, A., Waliszewska, A., Penney, K., Steen, R. G., Ardlie, K., John, E. M., Oakley-Girvan, I., Whittemore, A. S., Cooney, K. A., Ingles, S. A., Altshuler, D., Henderson, B. E., & Reich, D.
Affiliations: Broad Institute (US)
University of Southern California (US)
Harvard University (US)
Cancer Prevention Institute of California (US)
Stanford Medicine (US)
University of Michigan (US)
ORCID: Freedman, Matthew L.
Haiman, Christopher A.
Patterson, Nick
Penney, Kathryn
Steen, Robert G.
Ardlie, Kristin
John, Esther M.
Oakley-Girvan, Ingrid
Whittemore, Alice S.
Cooney, Kathleen A.
Ingles, Sue A.
Altshuler, David
Reich, David
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2006-09-19
Volume: 103
Issue: 38
Pages: 14068-14073
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0605832103
PMC: PMC1599913
OpenAlex: W1995404520
Cited by: 612
References: 26
Citations by year: 2026: 4 · 2025: 8 · 2024: 14 · 2023: 18 · 2022: 15 · 2021: 20 · 2020: 33 · 2019: 13 · 2018: 17 · 2017: 25 · 2016: 21 · 2015: 22 · 2014: 27 · 2013: 29 · 2012: 37
FWCI: 36.26
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
University Libraries (University of Maryland) (submittedVersion)
Digital Repository at the University of Maryland (University of Maryland College Park)
Funders: U.S. Department of Defense (CA63464)
University of Southern California (CA63464)
Rockefeller Brothers Fund
University of Michigan
Broad Institute
National Institutes of Health (CA63464, CA69568, CA79596)
University of Michigan Comprehensive Cancer Center
National Human Genome Research Institute (K01HG002758, HG02758)
National Cancer Institute (CA 69568, CA63464, U01CA063464, CA79596, CA67044, R01CA067044, R01CA079596, R01CA063464, P50CA069568, U01CA067044)
National Center for Research Resources
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
Keywords: prostate cancer, 8q24, African American men, admixture mapping, genetic susceptibility, African ancestry, age at diagnosis
MeSH terms: Aged, Alleles, Black or African American, Chromosome Mapping, Chromosomes, Human, Pair 8, Genetic Markers, Genotype, Humans, Male, Middle Aged, Neoplasm Staging, Phenotype, Prostatic Neoplasms, Risk Factors, Genetic Predisposition to Disease

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

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