quantitative assessment of the influence of cytochrome P450 1A2 gene polymorphism and colorectal cancer risk.
quantitative assessment of the influence of cytochrome P450 1A2 gene polymorphism and colorectal cancer risk.
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DOI：
10.1371/journal.pone.0071481
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Han YS
中科院分区：
文献类型：
--
作者：
Zhao Y;Chen ZX;Rewuti A;Ma YS;Wang XF;Xia Q;Fu D;Han YS
细胞色素P450 1A2(CYP1A2)是细胞色素P450超家族中的一员，在激活和解毒许多与结直肠癌发生有关的致癌物和内源性化合物中起着核心作用。CYP1A2*C(Rs2069514)和CYP1A2*F(Rs762551)是该基因最常研究的两个与结直肠癌风险相关的多态，但结果相互矛盾。为了更准确地估计CYP1A2与结直肠癌遗传风险的关系，我们进行了一项全面的荟萃分析，包括来自12个已发表的病例对照研究的7088个病例和7568个对照。在联合分析中，CYP1A2*F和*C等位基因对结直肠癌的累积每等位基因优势比分别为0.91(95%CI：0.83~1.00，P = 0.04)和0.91(95%CI：0.68~1.22，P = 0.53)。在按种族进行的亚组分析中，在亚洲人中发现了与CYP1A2*F和CYP1A2*C显著相关的基因，而在高加索人群中没有发现显著的相关性。用显性遗传模型也观察到了类似的结果。通过亚组分析和Meta回归分析，寻找可能的异质性来源。在大多数比较中没有检测到显著的异质性。这一荟萃分析表明，在亚洲人中，CYP1A2*F和*C多态是预防结直肠癌的保护因素。
Cytochrome P450 1A2 (CYP1A2) encodes a member of the cytochrome P450 superfamily of enzymes, which play a central role in activating and detoxifying many carcinogens and endogenous compounds thought to be involved in the development of colorectal cancer (CRC). The CYP1A2*C (rs2069514) and CYP1A2*F (rs762551) polymorphism are two of the most commonly studied polymorphisms of the gene for their association with risk of CRC, but the results are conflicting. To derive a more precise estimation of the relationship between CYP1A2 and genetic risk of CRC, we performed a comprehensive meta-analysis which included 7088 cases and 7568 controls from 12 published case-control studies. In a combined analysis, the summary per-allele odds ratio for CRC was 0.91 (95% CI: 0.83–1.00, P = 0.04), and 0.91 (95% CI: 0.68–1.22, P = 0.53), for CYP1A2 *F and *C allele, respectively. In the subgroup analysis by ethnicity, significant associations were found in Asians for CYP1A2*F and CYP1A2*C, while no significant associations were detected among Caucasian populations. Similar results were also observed using dominant genetic model. Potential sources of heterogeneity were explored by subgroup analysis and meta-regression. No significant heterogeneity was detected in most of comparisons. This meta-analysis suggests that the CYP1A2 *F and *C polymorphism is a protective factor against CRC among Asians.