Division of Liver Transplantation, Department of Liver and Vascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
PLoS One. 2012;7(8):e43821. doi: 10.1371/journal.pone.0043821. Epub 2012 Aug 23.
Microsomal epoxide hydrolase (EPHX1) plays an important role in both the activation and detoxification of PAHs, which are carcinogens found in cooked meat and tobacco smoking. Polymorphisms at exons 3 and 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. The aim of this study is to quantitatively summarize the relationship between EPHX1 polymorphisms and colorectal cancer (CRC) risk.
Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before June 2012. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for EPHX1 Tyr113His (rs1051740) and His139Arg (rs2234922) polymorphisms and CRC were calculated in a fixed-effects model and a random-effects model when appropriate.
This meta-analysis yielded 14 case-control studies, which included 13 studies for Tyr113His (6395 cases and 7893 controls) and 13 studies for His139Arg polymorphisms (5375 cases and 6962 controls). Overall, the pooled results indicated that EPHX1 Tyr113His polymorphism was not associated with CRC risk; while the His139Arg polymorphism was significantly associated with decreased CRC risk (Arg/His vs. His/His, OR = 0.90, 95%CI = 0.83-0.98; dominant model, OR = 0.92, 95%CI = 0.85-0.99). The statistically significant association between EPHX1 His139Arg polymorphism and CRC was observed among Caucasians and population-based case-control studies. This association showed little heterogeneity and remained consistently strong when analyses were limited to studies in which genotype frequencies were in Hardy-Weinberg equilibrium, or limited to studies with matched controls. When cumulative meta-analyses of the two associations were conducted by studies' publication time, the results were persistent and robust.
This meta-analysis suggests that EPHX1 Tyr113His polymorphism may be not associated with CRC development; while the EPHX1 His139Arg polymorphism may have a potential protective effect on CRC.
微粒体环氧化物水解酶（EPHX1）在多环芳烃（PAHs）的激活和解毒中起着重要作用，而多环芳烃存在于熟肉和吸烟的烟草中，属于致癌物质。EPHX1 基因的exon3 和 exon4 上的多态性与 EPHX1 活性的变化有关。本研究的目的是定量总结 EPHX1 多态性与结直肠癌（CRC）风险之间的关系。
两名研究员独立检索了 Medline、Embase、CNKI 和中国生物医学数据库，以获取截至 2012 年 6 月发表的研究。使用固定效应模型和随机效应模型计算 EPHX1 Tyr113His（rs1051740）和 His139Arg（rs2234922）多态性与 CRC 的汇总比值比（OR）和 95%置信区间（CI）。
本荟萃分析纳入了 14 项病例对照研究，其中 13 项研究针对 Tyr113His（6395 例病例和 7893 例对照），13 项研究针对 His139Arg 多态性（5375 例病例和 6962 例对照）。总体而言，汇总结果表明 EPHX1 Tyr113His 多态性与 CRC 风险无关；而 His139Arg 多态性与 CRC 风险降低显著相关（Arg/His 与 His/His 相比，OR=0.90，95%CI=0.83-0.98；显性模型，OR=0.92，95%CI=0.85-0.99）。EPHX1 His139Arg 多态性与 CRC 之间的显著关联仅在高加索人群和基于人群的病例对照研究中观察到。这种关联的异质性较小，当分析仅限于基因型频率符合 Hardy-Weinberg 平衡的研究，或仅限于匹配对照的研究时，关联仍然保持一致。当通过研究的发表时间对这两种关联进行累积荟萃分析时，结果仍然是持续且稳健的。
本荟萃分析表明，EPHX1 Tyr113His 多态性可能与 CRC 发生无关；而 EPHX1 His139Arg 多态性可能对 CRC 具有潜在的保护作用。
