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

作者：Matthew L. Freedman, Christopher A. Haiman, Nick Patterson, Gavin J. McDonald, Arti Tandon, Alicja Waliszewska, Kathryn L. Penney, Robert Steen, Kristin Ardlie, Esther M. John, Ingrid Oakley‐Girvan, Alice S. Whittemore, Kathleen A. Cooney, Sue A. Ingles, David Altshuler, Brian E. Henderson, David Reich · 发表于：Proceedings of the National Academy of Sciences · 年份：2006 · DOI：10.1073/pnas.0605832103 · 被引用次数：617 · 研究领域：Genetic Associations and Epidemiology、Prostate Cancer Treatment and Research、Molecular Biology Techniques and Applications

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 x 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.