Quantitative Assessment of the Effect of Cytochrome P450 2C9 Gene Polymorphism and Colorectal Cancer

CYP2C9 enzyme activity is involved in the metabolism of substances related to colorectal cancer (CRC), and it is functionally linked to a genetic polymorphism. Two allelic variants of the CYP2C9 gene, namely CYP2C9*2 and CYP2C9*3, differ from wild-type CYP2C9*1 by single amino acid substitutions. These mutated alleles encode enzymes with altered properties that are associated with impaired metabolism. In the past decade, a number of case-control studies have been carried out to investigate the relationship between the CYP2C9 polymorphism and CRC susceptibility, but the results were conflicting. To investigate this inconsistency, we performed a meta-analysis of 13 studies involving a total of 20,879 subjects for CYP2C9*2 and *3 polymorphisms to evaluate the effect of CYP2C9 on genetic susceptibility for CRC. Overall, the summary odds ratio of CRC was 0.94 (95%CI: 0.87–1.03, P = 0.18) and 1.00 (95%CI: 0.86–1.16, P = 0.99) for CYP2C9 *2 and *3 carriers, respectively. No significant results were observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. In the stratified analyses according to ethnicity, sample size, diagnostic criterion, HWE status and sex, no evidence of any gene-disease association was obtained. Our result suggest that the *2, *3 polymorphisms of CYP2C9 gene are not associated with CRC susceptibility.CYP2C9酶活性参与结直肠癌（colorectal cancer, CRC）相关物质的代谢，且其功能与遗传多态性存在关联。CYP2C9基因存在两种等位变异体，即CYP2C9*2与CYP2C9*3，二者与野生型CYP2C9*1的差异仅为单个氨基酸替换。上述突变等位基因所编码的酶其特性发生改变，且与代谢功能受损相关联。在过去十年间，已有多项病例对照研究探讨CYP2C9基因多态性与结直肠癌易感性之间的关联，但所得结果存在分歧。为厘清这一研究结论不一致的问题，本研究针对CYP2C9*2与CYP2C9*3基因多态性展开荟萃分析，共纳入13项相关研究、总计20,879名受试者，以评估CYP2C9对结直肠癌遗传易感性的影响。整体而言，携带CYP2C9*2与CYP2C9*3的受试者其结直肠癌的合并比值比分别为0.94（95%置信区间：0.87–1.03，P = 0.18）与1.00（95%置信区间：0.86–1.16，P = 0.99）。针对上述多态性，与野生基因型相比，杂合子与纯合子受试者均未观察到显著关联结果。根据种族、样本量、诊断标准、哈迪-温伯格平衡（Hardy-Weinberg equilibrium, HWE）状态以及性别进行分层分析后，未发现任何基因-疾病关联的证据。本研究结果显示，CYP2C9基因的*2、*3多态性与结直肠癌易感性无显著关联。