Shanghai Lung Tumour Clinical Medical Centre, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200030, China.
Mutagenesis. 2011 May;26(3):437-46. doi: 10.1093/mutage/ger002. Epub 2011 Mar 14.
The cytochrome P450 1A1 (CYP1A1) is a phase I enzyme involved in many oxidative reactions that has attracted considerable attention as a candidate gene for lung cancer susceptibility based on its function as a key factor required for bioactivation of carcinogenic polycyclic aromatic hydrocarbons and catechol oestrogen formation. In the past decade, the relationship between CYP1A1 and lung cancer has been reported in various ethnic groups; however, these studies have yielded contradictory results. To investigate this inconsistency, we performed a meta-analysis of 71 studies involving a total of 30 368 subjects for the MspI and Ile-Val polymorphism of the CYP1A1 gene to evaluate the effect of CYP1A1 on genetic susceptibility for lung cancer. In a combined analysis, the summary per-allele odds ratios for lung cancer of the MspI and Ile-Val polymorphism were 1.19 [95% confidence interval (CI): 1.11-1.28] and 1.20 (95% CI: 1.08-1.33), respectively. Significant results were also observed using dominant or recessive genetic model. In the subgroup analysis by ethnicity, significantly increased risks were found for the MspI and Ile-Val polymorphism among East Asians in almost all genetic models. However, only marginal significant associations were detected for the MspI polymorphism among Caucasians and other population, while no significant associations were observed for the Ile-Val polymorphism in Caucasians and other population. This meta-analysis demonstrated that the MspI and Ile-Val polymorphism of CYP1A1 is a risk factor associated with increased lung cancer susceptibility, but these associations vary in different ethnic populations.
细胞色素 P450 1A1（CYP1A1）是一种参与许多氧化反应的 I 相酶，因其作为多环芳烃和儿茶酚雌激素生物活化所需的关键因素，作为肺癌易感性的候选基因而受到极大关注。在过去的十年中，CYP1A1 与肺癌之间的关系在不同种族中都有报道；然而，这些研究的结果却相互矛盾。为了研究这种不一致性，我们对 71 项研究进行了荟萃分析，这些研究共涉及 30368 名受试者，研究 CYP1A1 基因的 MspI 和 Ile-Val 多态性与肺癌的关系，以评估 CYP1A1 对肺癌遗传易感性的影响。在综合分析中，MspI 和 Ile-Val 多态性与肺癌的每一个等位基因的比值比（OR）分别为 1.19（95%可信区间[CI]：1.11-1.28）和 1.20（95%CI：1.08-1.33）。显性或隐性遗传模型也得到了显著的结果。按种族进行亚组分析，在几乎所有遗传模型中，东亚人群的 MspI 和 Ile-Val 多态性与肺癌风险显著增加。然而，在白种人群和其他人群中，MspI 多态性只检测到边缘显著的相关性，而在白种人群和其他人群中，Ile-Val 多态性与肺癌没有显著相关性。这项荟萃分析表明，CYP1A1 的 MspI 和 Ile-Val 多态性是与肺癌易感性增加相关的风险因素，但这些关联在不同的种族群体中存在差异。
