Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, United States of America.
PLoS Genet. 2011 May;7(5):e1001387. doi: 10.1371/journal.pgen.1001387. Epub 2011 May 26.
GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls), we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p≤0.05) with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in African Americans. At 8q24, we found 9 variants (p≤6×10(-4)) that best capture risk of prostate cancer in African Americans, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in African Americans (per allele OR = 1.17) over the alleles reported in the original GWAS (OR = 1.08). In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in African Americans. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry.
GWAS 已成功揭示了与前列腺癌病因相关的常见遗传变异和新的生物学途径。通过继续进行此类发现工作，并在不同的种族和族裔群体中测试已知的风险等位基因，将更全面地了解普通人群中对前列腺癌的遗传易感性。在这项针对非裔美国男性前列腺癌的大型研究中（3425 例前列腺癌病例和 3290 例对照），我们测试了 49 个位于欧洲和亚洲男性 GWAS 确定的 28 个基因组区域的风险变异，并且复制了与这些标记物大约一半的关联（p≤0.05）。通过精细映射，我们在许多区域确定了附近的标记，这些标记更好地定义了非洲裔美国人的关联。在 8q24 上，我们发现了 9 个变体（p≤6×10(-4))，这些变体可以最好地捕捉非洲裔美国人患前列腺癌的风险，其中许多变体在非洲裔男性中比欧洲裔男性更为常见。在每个基因座发现与风险相关的标记物提高了非洲裔美国人的风险建模（每个等位基因 OR=1.17），超过了原始 GWAS 中报告的等位基因（OR=1.08）。总的来说，在对 GWAS 报告的前列腺癌风险位点的详细分析中，我们验证并改进了一些区域的风险标记物，这些标记物可以更好地定义与非洲裔美国人前列腺癌的关联。我们在 8q24 上发现的变体也强化了该区域作为非洲裔男性前列腺癌主要风险位点的重要性。
