CYP1A1/2 Haplotypes and Lung Cancer and Assessment of Confounding by Population Stratification
CYP1A1/2 Haplotypes and Lung Cancer and Assessment of Confounding by Population Stratification
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DOI：
10.1158/0008-5472.can-08-2576
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发表时间：
2009-03-15
期刊：
影响因子：
11.2
通讯作者：
Wiencke, John K.
中科院分区：
文献类型：
--
作者：
Aldrich, Melinda C.;Selvin, Steve;Wiencke, John K.
对非裔美国人和拉丁裔种群中肺癌和CYP1A1/2的先前研究表明结果不一致，尚未研究CYP1A1/2的单倍型阻滞结构或解决潜在的人口分层。为了研究CYP1A1/2地区的单倍型和非裔美国人和拉丁美洲人的肺癌，我们进行了一项病例对照研究（1998-2003）。非洲裔美国人（n = 535）和拉丁裔（n = 412）在年龄，性别和自我报告的种族/种族上匹配。我们使用了一个定制的基因分型面板，该面板在CYP1A1/2区域中包含50个单核苷酸多态性，并选择了184个祖先信息标记物，这些标记被选为非洲人，欧洲人和美洲印第安人之间具有较大的等位基因频率差异。拉丁美洲人在调整混合物后即使在两个区块中也表现出显着的单倍型主要影响[赔率（OR），2.02； 95％置信区间（95％CI），1.28-3.19和OR，0.55； 95％CI，0.36-0.83]，但在非裔美国人中未发现主要影响。对混合物的调整表明，拉丁美洲人的人口分层是严重的混淆，而不是非裔美国人。在拉美裔和非裔美国人中，吸烟水平与单倍型之间的相互作用在统计学上没有意义。拉丁美洲人之间人口分层的证据强调了调整肺癌协会研究中混合物的重要性，尤其是在拉丁裔人群中。这些结果表明，在CYP1A2区域内发生的一种变异可能正在赋予拉丁美洲裔肺癌的风险增加。 [Cancer Res 2009; 69（6）：2340-8]
Prior studies of lung cancer and CYP1A1/2 in African-American and Latino populations have shown inconsistent results and have not yet investigated the haplotype block structure of CYP1A1/2 or addressed potential population stratification. To investigate haplotypes in the CYP1A1/2 region and lung cancer in African-Americans and Latinos, we conducted a case-control study (1998-2003). African-Americans (n = 535) and Latinos (n = 412) were frequency matched on age, sex, and self-reported race/ethnicity. We used a custom genotyping panel containing 50 single nucleotide polymorphisms in the CYP1A1/2 region and 184 ancestry informative markers selected to have large allele frequency differences between Africans, Europeans, and Amerindians. Latinos exhibited significant haplotype main effects in two blocks even after adjusting for admixture [odds ratio (OR), 2.02; 95% confidence interval (95% CI), 1.28-3.19 and OR, 0.55; 95% CI, 0.36-0.83], but no main effects were found among African-Americans. Adjustment for admixture revealed substantial confounding by population stratification among Latinos but not African-Americans. Among Latinos and African-Americans, interactions between smoking level and haplotypes were not statistically significant. Evidence of population stratification among Latinos underscores the importance of adjusting for admixture in lung cancer association studies, particularly in Latino populations. These results suggest that a variant occurring within the CYP1A2 region may be conferring an increased risk of lung cancer in Latinos. [Cancer Res 2009;69(6):2340-8]