Meta-Analysis
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World J Gastroenterol. Aug 28, 2014; 20(32): 11429-11438
Published online Aug 28, 2014. doi: 10.3748/wjg.v20.i32.11429
Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer susceptibility
Lei-Zhou Xia, Yi Liu, Xiao-Zhou Xu, Peng-Cheng Jiang, Gui Ma, Xue-Feng Bu, Yong-Jun Zhang, Feng Yu, Ke-Sen Xu, Hua Li
Lei-Zhou Xia, Peng-Cheng Jiang, Gui Ma, Xue-Feng Bu, Yong-Jun Zhang, Feng Yu, Hua Li, Department of General Surgery, Affiliated People’s Hospital, Jiangsu University, Zhenjiang 212002, Jiangsu Province, China
Yi Liu, Ke-Sen Xu, Department of Hepatobiliary Surgery, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
Xiao-Zhou Xu, Department of Surgery, Chang-Hai Hospital, The Second Military Medical University, Shanghai 200000, China
Author contributions: Xia LZ and Li H designed the research; Xia LZ, Liu Y, Xu XZ, Jiang PC, Ma G, Bu XF, Zhang YJ, Yu F and Xu KS performed the data search and meta-analysis; Xia LZ wrote the paper.
Correspondence to: Hua Li, MD, Department of General Surgery, Affiliated People’s Hospital, Jiangsu University, No. 8, Dianli Road, Zhenjiang 212002, Jiangsu Province, China. drlihua212@163.com
Telephone: +86-511-88915151 Fax: +86-511-88915151
Received: October 8, 2013
Revised: March 4, 2014
Accepted: May 12, 2014
Published online: August 28, 2014
Abstract

AIM: To identify the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and gastric cancer (GC) susceptibility.

METHODS: Systematic searches were performed on the electronic databases PubMed, ISI, Web of knowledge, CNKI and Wanfang, as well as manual searching of the references of the identified articles. A total of 26 papers were included in this meta-analysis. Overall and subgroup analyses were performed. Odds ratio (OR) and 95%CI were used to evaluate the associations between MTHFR polymorphisms and GC risk. The I2 statistics were used to evaluate between-study heterogeneity. Sensitivity analysis was also performed.

RESULTS: Increased risk was found for the MTHFR C677T polymorphism under four genetic models (TT + CT vs CC: OR = 1.23, P = 0.002; T vs C: OR = 1.15, P = 0.001; TT vs CC: OR = 1.37, P = 0.0005; TT vs CT + CC: OR = 1.17, P = 0.0008). Subgroup analysis by ethnicity suggested that C677T polymorphism conferred a risk of GC in eastern but not in western populations. Stratification by tumor site showed an association between the C677T polymorphism and gastric cardia cancer and non-cardia GC in the worldwide population and in eastern populations. Regardless of comparisons with controls or diffuse-type GC, a positive association was found for the C677T polymorphism and an increased risk of intestinal-type GC in the whole population and in western populations. With regard to the A1298C polymorphism, we found that genotype CC was significantly decreased and conferred protection against GC in eastern populations (CC vs AA: OR = 0.44, P = 0.03; CC vs AC + AA: OR = 0.46, P = 0.04).

CONCLUSION: MTHFR C677T polymorphism is a risk factor for GC, and the A1298C polymorphism may be a protective factor against GC in eastern populations.

Keywords: Methylenetetrahydrofolate reductase, Polymorphism, Gastric cancer, Meta-analysis

Core tip: Many studies have reported associations of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with susceptibility to gastric cancer (GC). There are several relevant published meta-analyses about this subject. Nevertheless, these articles failed to analysis MTHFR polymorphisms and GC risk per se in detail as follows. They failed to investigate the difference between gastric cardia cancer and non-cardia GC, and the distinction between diffuse and intestinal subtypes. Consequently, we performed a meta-analysis to clarify the roles of MTHFR C677T and A1298C polymorphisms in GC susceptibility among the eligible studies.