Minority Health and Health Equity Archive

Permanent URI for this collectionhttp://hdl.handle.net/1903/21769

Welcome to the Minority Health and Health Equity Archive (MHHEA), an electronic archive for digital resource materials in the fields of minority health and health disparities research and policy. It is offered as a no-charge resource to the public, academic scholars and health science researchers interested in the elimination of racial and ethnic health disparities.

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    Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men
    (2006) Freedman, Matthew L.; Haiman, Christopher A.; Patterson, Nick; McDonald, Gavin J.; Tandon, Arti; Waliszewska, Alicja; Penney, Kathryn; Steen, Robert G.; Kristin Ardlie, Kristin; John, Esther M.; Oakley-Girvan, Ingrid; Whittemore, Alice S.; Cooney, Kathleen A.; Ingles, Sue A.; Altshuler, David; Henderson, Brian E.; Reich, David
    A whole-genome admixture scan in 1,597 African Americans identified a 3.8Mbinterval 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<4.2109) 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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    Systematic Evaluation of Genetic Variation at the Androgen Receptor Locus and Risk of Prostate Cancer in a Multiethnic Cohort Study
    (2005) Freedman, Matthew L.; Pearce, Celeste L.; Penney, Kathryn L.; Hirschhorn, Joel N.; Kolonel, Laurence N.; Henderson, Brian E.; Altshuler, David
    Repeat length of the CAG microsatellite polymorphism in exon 1 of the androgen receptor (AR) gene has been associated with risk of prostate cancer in humans. This association has been the focus of >20 primary epidemiological publications and multiple review articles, but a consistent and reproducible association has yet to be confirmed. We systematically addressed possible causes of false-negative and false-positive association in >4,000 individuals from a multiethnic, prospective cohort study of prostate cancer, comprehensively studying genetic variation by microsatellite genotyping, direct resequencing of exons in advanced cancer cases, and haplotype analysis across the 180-kb AR genomic locus. These data failed to confirm that common genetic variation in the AR gene locus influences risk of prostate cancer. A systematic approach that assesses both coding and noncoding genetic variation in large and diverse patient samples can help clarify hypotheses about association between genetic variants and disease.