Zhou Li-Ping, Luan Hong, Dong Xi-Hua, Jin Guo-Jiang, Man Dong-Liang, Shang Hong
Department of Laboratory Medicine, the First Affiliated Hospital of China Medical University, Shenyang, China.
Asian Pac J Cancer Prev. 2012;13(7):3165-72. doi: 10.7314/apjcp.2012.13.7.3165.
Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A large number of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been reported to associate with cancer susceptibility. However, the results are controversial. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to summarize the evidence for associations.
Studies focusing on the relationship between CYP2D6 gene polymorphisms and susceptibility to cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated.
According to the inclusion criteria, forty-three studies with a total of 7,009 cancer cases and 9,646 healthy controls, were included in the meta-analysis. The results showed that there was a positive association between heterozygote (GC) of rs1135840 and cancer risk (OR=1.92, 95%CI: 1.14-3.21, P=0.01). In addition, we found that homozygote (CC) of rs1135840 might be a protective factor for cancer (OR=0.58, 95%CI: 0.34-0.97, P=0.04). Similarly, the G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 had negative associations with cancer risk (OR=0.69, 95%CI: 0.48-0.99, P=0.04; OR=0.60, 95%CI: 0.38-0.94, P=0.03; OR=0.50, 95%CI: 0.26-0.95, P=0.03; respectively).
This meta-analysis suggests that CYP2D6 gene polymorphisms are involved in the pathogenesis of various cancers. The heterozygote (GC) of rs1135840 in CYP2D6 gene might increase the risk while the homozygote (CC) of rs1135840, G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 might be protective factors.
代谢酶中的基因多态性与多种癌症相关。据报道，CYP2D6基因中的大量单核苷酸多态性（SNP）与癌症易感性相关。然而，结果存在争议。本人类基因组流行病学（HuGE）综述和荟萃分析的目的是总结相关关联的证据。
从PubMed、Cochrane图书馆、Embase、科学网、Springerlink、中国知网和中国生物医学文献数据库中筛选关注CYP2D6基因多态性与癌症易感性关系的研究。由两名独立评审员提取数据，并使用Review Manager 5.1.6版和STATA 12.0版软件进行荟萃分析。计算比值比（OR）及95%置信区间（95%CI）。
根据纳入标准，43项研究共7009例癌症病例和9646例健康对照被纳入荟萃分析。结果显示，rs1135840的杂合子（GC）与癌症风险呈正相关（OR = 1.92，95%CI：1.14 - 3.21，P = 0.01）。此外，我们发现rs1135840的纯合子（CC）可能是癌症的保护因素（OR = 0.58，95%CI：0.34 - 0.97，P = 0.04）。同样，rs16947的G等位基因和G携带者（AG + GG）以及rs35742686的杂合子（A/del）与癌症风险呈负相关（OR分别为0.69，95%CI：0.48 - 0.99，P = 0.04；OR = 0.60，95%CI：0.38 - 0.94，P = 0.03；OR = 0.50，95%CI：0.26 - 0.95，P = 0.03）。
本荟萃分析表明，CYP2D6基因多态性参与了多种癌症的发病机制。CYP2D6基因中rs1135840的杂合子（GC）可能增加风险，而rs1135840的纯合子（CC）、rs16947的G等位基因和G携带者（AG + GG）以及rs35742686的杂合子（A/del）可能是保护因素。
