CYP1A1 T3801C polymorphism and lung cancer:: A pooled analysis of 2,451 cases and 3,358 controls
CYP1A1 T3801C polymorphism and lung cancer:: A pooled analysis of 2,451 cases and 3,358 controls
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DOI：
10.1002/ijc.10995
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发表时间：
2003-05-01
影响因子：
6.4
通讯作者：
Taioli, E
中科院分区：
文献类型：
--
作者：
Vineis, P;Veglia, F;Taioli, E
CYP1A1 参与苯并芘（一种疑似肺癌致癌物）的代谢；因此可以想象，基因决定的其活性变化会改变个体对肺癌的易感性。 CYP I A I Msp1 多态性在肺癌中的作用已被广泛研究，但尚未完全阐明。我们对 22 项有关 CYP1A1 和肺癌风险的病例对照研究进行了汇总分析，纳入了 2,451 例病例和 3,358 名对照。我们发现白种人的 CYP I A I 纯合 Msp1 限制性片段长度多态性 (RFLP) 与肺癌风险之间存在明显关联（年龄和性别调整优势比 = 2.36；95% 置信区间 1.16-4.81）；其他相关性较弱或不具有统计显着性。在白种人中，鳞状细胞癌和腺癌与纯合变异的相关性同样强烈。我们按吸烟时间分析了风险：对于具有 Msp1 RFLP 组合变异体（纯合子加杂合子）的白种人受试者，肺癌风险的增加比具有纯合参考等位基因的个体更陡峭。我们的分析表明，具有纯合变异 CYP1A1 多态性的白种人患肺癌的风险较高。白种人中的数据更加一致，鳞状细胞癌和腺癌中的纯合变异之间存在很强的相关性，并且男性中的相关性强于女性。亚洲人的分析更加不一致，未能达到统计显着性。这一观察结果可能是由于亚洲研究中的设计特殊性或未知的效果调节剂所致。 (C) 2003 Wiley-Liss, Inc.
CYP1A1 is involved in the metabolism of benzopyrene, a suspected lung carcinogen; it is therefore conceivable that genetically determined variations in its activity modify individual susceptibility to lung cancer. The role of the CYP I A I Msp1 polymorphism in lung cancer has been widely studied but has not been fully clarified. We have included 2,451 cases and 3,358 controls in a pooled analysis of 22 case-control studies on CYP1A1 and lung cancer risk. We found a clear association between the CYP I A I homozygous Msp1 restriction fragment length polymorphism (RFLP) and lung cancer risk in Caucasians (age- and gender-adjusted odds ratio = 2.36; 95% confidence interval 1.16-4.81); other associations were weaker or not statistically significant. The association with the homozygous variant was equally strong for squamous cell carcinomas and adenocarcinomas among Caucasians. We analyzed the risk by duration of smoking: for Caucasian subjects with the Msp1 RFLP combined variants (homozygotes plus heterozygotes), the increase in the risk of lung cancer was steeper than among the individuals with the homozygous reference allele. Our analysis suggests that Caucasians with homozygous variant CYP1A1 polymorphism have a higher risk of lung cancer. The data were more consistent among Caucasians, with a strong association between the homozygous variant in both squamous cell carcinomas and adenocarcinomas, and a stronger association in men than in women. The analyses were more inconsistent and failed to reach statistical significance in Asians. This observation might be due to design specificities or unknown effect modifiers in the Asian studies. (C) 2003 Wiley-Liss, Inc.