Meng Fan-dong, Ma Ping, Sui Cheng-guang, Tian Xin, Jiang You-hong
Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Shenyang 110001, China.
Sci Rep. 2015 Jan 29;5:8108. doi: 10.1038/srep08108.
Cytochrome P450 1A1 (CYP1A1) usually metabolizes carcinogens to their inactive derivatives but occasionally converts the chemicals to more potent carcinogens. To date, many studies have evaluated the association between the CYP1A1 MspI and Ile462Val polymorphisms and renal cell carcinoma (RCC) risk, but the results have been conflicting. To more precisely evaluate the potential association, we carried out a meta-analysis of seven published case-control studies. The meta-analysis indicated that the MspI polymorphism was associated with an increased RCC risk (allele model: OR = 1.49, 95%CI 1.03-2.16; homozygous model: OR = 1.64, 95%CI 1.13-2.40; dominant model: OR = 1.72, 95%CI 1.07-2.76). No significant associations were found for the Ile462Val polymorphism for all genetic models. When stratified by smoking status, smokers carrying the variant Vt and Val allele were more susceptible to RCC (Vt allele: OR = 3.37, 95%CI = 2.24-5.06; Val allele: OR = 2.07, 95%CI = 1.34-3.19). These data indicate that the CYP1A1 MspI polymorphism significantly increased RCC risk, while the Ile462Val polymorphism was not associated with RCC. Among smokers, individuals with the CYP1A1 Vt allele and Val allele showed a significantly increased risk of RCC. More well-designed studies with larger samples are warranted to show the underlying mechanisms of CYP1A1 in the development of RCC.
细胞色素P450 1A1(CYP1A1)通常将致癌物代谢为无活性的衍生物,但偶尔也会将这些化学物质转化为更强效的致癌物。迄今为止,许多研究评估了CYP1A1 MspI和Ile462Val多态性与肾细胞癌(RCC)风险之间的关联,但结果相互矛盾。为了更精确地评估潜在关联,我们对七项已发表的病例对照研究进行了荟萃分析。荟萃分析表明,MspI多态性与RCC风险增加相关(等位基因模型:OR = 1.49,95%CI 1.03 - 2.16;纯合子模型:OR = 1.64,95%CI 1.13 - 2.40;显性模型:OR = 1.72,95%CI 1.07 - 2.76)。对于所有遗传模型,Ile462Val多态性均未发现显著关联。按吸烟状态分层时,携带变异Vt和Val等位基因的吸烟者更易患RCC(Vt等位基因:OR = 3.37,95%CI = 2.24 - 5.06;Val等位基因:OR = 2.07,95%CI = 1.34 - 3.19)。这些数据表明,CYP1A1 MspI多态性显著增加RCC风险,而Ile462Val多态性与RCC无关。在吸烟者中,携带CYP1A1 Vt等位基因和Val等位基因的个体患RCC的风险显著增加。需要更多设计良好、样本量更大的研究来揭示CYP1A1在RCC发生发展中的潜在机制。