Confirmation study of prostate cancer risk variants at 8q24 in African Americans identifies a novel risk locus
Confirmation study of prostate cancer risk variants at 8q24 in African Americans identifies a novel risk locus
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DOI：
10.1101/gr.6782707
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发表时间：
2007-12-01
期刊：
影响因子：
7
通讯作者：
Carpten, John
中科院分区：
文献类型：
--
作者：
Robbins, Christiane;Torres, Jada Benn;Carpten, John
前列腺癌是一种常见的复杂疾病，对非洲裔男性的影响尤为严重。最近，多项研究和种族群体显示，染色体 8q24 上的几种不同常见变异与前列腺癌相关。本研究的目的是确认 8q24 标记物与非裔美国人前列腺癌的关联。我们对 1057 名非裔美国男性（490 名前列腺癌病例和 567 名对照）的医院病例对照样本中沿 8q24 的 24 个标记和 80 个未连锁的祖先信息标记进行了基因分型。使用祖先信息标记的估计值，针对全局和局部 8q24 混合分层调整 8q24 标记与前列腺癌风险的关联分析。我们报告，映射到8q24.13区域的rs7008482是一个额外的独立前列腺癌风险变异（P = 5x10(-4)），并且我们还复制了rs16901979与前列腺癌的关联（P = 0.002）。该地区其他已发表的风险变异，例如 rs1447295 和 rs6983267，显示出类似的影响方向和程度，但在我们的人群中并不显着。 rs7008482和rs16901979均独立预测风险，并且在相互控制后仍然显着（P<0.001）。我们的数据与 8q24 标记的额外复制相结合，为 8q24 上多个前列腺癌风险区域提供了令人信服的支持。
Prostate cancer is a common complex disease that disproportionately affects men of African descent. Recently, several different common variants on chromosome 8q24 have been shown to be associated with prostate cancer in multiple studies and ethnic groups. The objective of this study was to confirm the association of 8q24 markers with prostate cancer in African Americans. We genotyped 24 markers along 8q24 and 80 unlinked ancestry informative markers in a hospital-based case-control sample of 1057 African American men ( 490 prostate cancer cases and 567 controls). Association analyses of 8q24 markers with prostate cancer risk were adjusted for both global and local 8q24 admixture stratification using estimates from ancestry informative markers. We report that rs7008482, which maps to the 8q24.13 region, is an additional independent prostate cancer risk variant ( P = 5x10(-4)), and we also replicate the association of rs16901979 with prostate cancer ( P = 0.002). Other published risk variants in the region such as rs1447295 and rs6983267 showed a similar direction and magnitude of effect, but were not significant in our population. Both rs7008482 and rs16901979 independently predicted risk and remained significant ( P < 0.001) after controlling for each other. Our data combined with additional replications of 8q24 markers provide compelling support for multiple regions of risk for prostate cancer on 8q24.