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  Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 5  |  Page : 26-28
 

Methylene tetrahydrofolate reductasel reductase C677T polymorphisms and esophageal cancer susceptibility: A meta-analysis based on Chinese Han population


Department of Emergency, Huaihe Hospital of Henan University, Kaifeng, Henan, China

Date of Web Publication3-Nov-2015

Correspondence Address:
S Li
Department of Emergency, Huaihe Hospital of Henan University, Kaifeng, Henan
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.168952

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 » Abstract 

Objective: The aim of this meta-analysis was to assess the methylene tetrahydrofolate reductase (MTHFR) gene C677T polymorphisms and esophageal cancer susceptibility in Chinese Han population. Materials and Methods: The databases of PubMed, MEDLINE, Wanfang, and CNIK was electronic searched to find the case–control or cohort study about the relationship between MTHFR gene C677T polymorphisms and esophageal cancer susceptibility in Chinese Han population. The odds ratio (OR) was used to assess the relationship between CC, CT, and TT genotype and esophageal cancer risk. The data were pooled using Stata 11.0 software. Results: Eight articles included 1752 esophageal cancer and 2363 controls were found and included in this meta-analysis. The pooled OR was 1.86 with its 95% confidence interval of 1.21–2.86 and 1.62 with its 95% confidence interval of 1.15–2.27 for TT versus CC and CT versus CC model which indicated that people with TT OR CT genotype significant increase the risk of developing esophageal cancer. Conclusion: Esophageal cancer risk was significantly increased in people with TT/CT genotype of MTHFR gene.


Keywords: Esophageal cancer, meta-analysis, methylene tetrahydrofolate reductase, polymorphisms, risk


How to cite this article:
Yang Z, Wang X, Li S. Methylene tetrahydrofolate reductasel reductase C677T polymorphisms and esophageal cancer susceptibility: A meta-analysis based on Chinese Han population. Indian J Cancer 2015;52, Suppl S1:26-8

How to cite this URL:
Yang Z, Wang X, Li S. Methylene tetrahydrofolate reductasel reductase C677T polymorphisms and esophageal cancer susceptibility: A meta-analysis based on Chinese Han population. Indian J Cancer [serial online] 2015 [cited 2021 Jul 31];52, Suppl S1:26-8. Available from: https://www.indianjcancer.com/text.asp?2015/52/5/26/168952

FNx01Yang Z and Wang X contribute equally to this work



 » Introduction Top


Esophageal cancer is the eighth most common cancer globally with 456,000 new cases during the year of 2012.[1] Moreover, almost 400,000 deaths were caused by esophageal cancer that year. The incidence rate of esophageal cancer vary widely among countries, with about half of all cases occurring in China.[2] It is around 3 times more common in men than in women. The main caused esophageal cancer is tobacco (smoking or chewing) and alcohol consumption.[3],[4] Moreover, a recent study showed that mononucleotide polymorphisms of some genes were associated with the susceptibility of esophageal cancer. Methylenetetrahydrofolate reductase (MTHFR) was a gene that was confirmed to be related to esophageal cancer susceptibility.[5] However, the patients number of single individual study about MTHFR gene C677T polymorphisms and esophageal cancer susceptibility is small with weak statistical power. Hence, we evaluated the MTHFR gene C677T polymorphisms and esophageal cancer susceptibility in Chinese Han population by meta-analysis.


 » Materials and Methods Top


The databases of PubMed, MEDLINE, Wanfang, and CNIK was electronic searched to find the case–control or cohort study about the relationship between MTHFR gene C677T polymorphisms and esophageal cancer susceptibility in Chinese Han population. The searching words were (esophageal cancer odds ratio [OR] esophageal carcinoma) AND (MTHFR or methylenetetrahydrofolate reductase) AND (polymorphisms OR variant). The papers were screened and included according to the inclusion and exclusion criteria. The inclusion criteria were (1) patients were limited to Chinese Han people; (2) the esophageal cancer was confirmed by pathology or cytology; (3) the genotype was showed in each of the included papers; (4) the papers were published in English or Chinese. For the included articles, the following data were extracted by two reviewers independently. (1) Name of the first and corresponding authors; (2) paper publication year; (3) region; (4) genotype of CC, CT and TT distribution.

Statistical analysis

All the data were analyzed using Stata 11.0 software (Stata Corp., LP, http://www.stata.com; Stata Corporation, College Station, TX). Statistical heterogeneity among studies was evaluated by Chi-square (χ2) test.[6] The Begger's funnel plot and Egger's tests were used to evaluate possible publication bias.[7]


 » Results Top


Study characteristics

The databases of PubMed, MEDLINE, Wanfang and CNKI were searched by electronic methods. And, finally eight articles included 1752 esophageal cancer and 2363 controls were found and included in this meta-analysis. The publication year ranges from 2001 to 2008. All of the included eight studies were come from the Chinese mainland. The detailed information of the included eight papers was demonstrated in [Table 1].
Table 1: General characteristics of included studies

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TT versus CC

The median TT genotype rate was 17.64% with the rate range from 8.47% to 50.00% in the esophageal cancer group. Moreover, median TT genotype rate was 23.88% with the rate range from 16.33% to 70.83% in the control group. Statistical heterogeneity analysis indicated significant heterogeneity was found in pooling the OR for TT versus CC model (P < 0.05). The data were pooled by random effect model. The pooled OR was 1.86 with its 95% confidence interval of 1.21–2.86 which indicated that people with TT genotype significant increase the risk of developing esophageal cancer [Figure 1].
Figure 1: Forest plot of (methylene tetrahydrofolate reductase) C677>T polymorphisms and esophageal cancer risk

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CT versus CC

The median CT genotype rate was 45.00% with the rate range from 38.18% to 50.54% in the esophageal cancer group. And median TT genotype rate was 24.58–52.51% in the control group. Statistical heterogeneity analysis indicated significant heterogeneity was found in pooling the OR for CT versus CC model (P < 0.05). The data were pooled by random effect model. The pooled OR was 1.62 with its 95% confidence interval of 1.15–2.27 which indicated that people with CT genotype significant increase the risk of developing esophageal cancer [Figure 2].
Figure 2: Forest plot of (methylene tetrahydrofolate reductase) C677>T polymorphisms and esophageal cancer risk

Click here to view


Publication bias

The publication bias was evaluated by begg's funnel plot and Egger's line regression analysis. The Begger's funnel plot showed the plot was generally symmetrical for TT versus CC and CT versus CC model [Figure 3]. And Egger's line regression test indicated no significant publication bias (P > 0.05).
Figure 3: Begg's funnel plot for evaluation of publication bias

Click here to view



 » Discussion Top


According to the global cancer statistical data, esophageal cancer is the eight most common cancer worldwide. An estimated 17,460 new esophageal cancer cases and 15,070 deaths were occurred in the year of 2012 in the United States.[16] Tobacco and alcohol abuse were deemed as the major cause of esophageal cancer. And other risk factors were confirmed as high body mass, Barrett's esophagus, and gastroesophageal reflux disease. And recently, some articles demonstrated that the mononucleotide polymorphisms of MTHFR were associated with the susceptibility of esophageal cancer. MTHFR is the rate-limiting enzyme in the methyl cycle, and it is encoded by the MTHFR gene. Methylenetetrahydrofolate reductase catalyzes the conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine.[17] Song et al. evaluated the methylenetetrahydrofolate reductase polymorphisms and esophageal cancer susceptibility by case–control study and demonstrated that genetic polymorphisms in the MTHFR gene may contribute to susceptibility to carcinogenesis of the esophagus in the at-risk Chinese population.[8] In this meta-analysis, we finally included eight studies with 1752 esophageal cancer and 2363 controls. The pooled data indicated that esophageal cancer risk was significant increase in people with TT/CT genotype of MTHFR gene. However, several limitations were existed in this meta-analysis. First, significant statistical heterogeneity was found among the studies when pooling the data; Second, the patients and control number in each individual study was relatively small; third, the language was confided to Chinese and English.

 
 » References Top

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Chen W, Zheng R, Zhang S, Zeng H, Fan Y, Qiao Y, et al. Esophageal cancer incidence and mortality in China, 2010. Thorac Cancer 2014;5:343-8.  Back to cited text no. 2
    
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Oze I, Matsuo K, Ito H, Wakai K, Nagata C, Mizoue T, et al. Cigarette smoking and esophageal cancer risk: An evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol 2012;42:63-73.  Back to cited text no. 3
    
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Wu M, Zhao JK, Zhang ZF, Han RQ, Yang J, Zhou JY, et al. Smoking and alcohol drinking increased the risk of esophageal cancer among Chinese men but not women in a high-risk population. Cancer Causes Control 2011;22:649-57.  Back to cited text no. 4
    
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Yang CX, Matsuo K, Ito H, Shinoda M, Hatooka S, Hirose K, et al. Gene-environment interactions between alcohol drinking and the MTHFR C677T polymorphism impact on esophageal cancer risk: Results of a case-control study in Japan. Carcinogenesis 2005;26:1285-90.  Back to cited text no. 5
    
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DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88.  Back to cited text no. 6
    
7.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34.  Back to cited text no. 7
    
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Song C, Xing D, Tan W, Wei Q, Lin D. Methylenetetrahydrofolate reductase polymorphisms increase risk of esophageal squamous cell carcinoma in a Chinese population. Cancer Res 2001;61:3272-5.  Back to cited text no. 8
    
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Jianzhong W, Changming G, Jianhua D, Yanting L, Yu Z, Suping L, et al. Polymorphisms of methylenetetrahydrofolate reductase C677T and the risk of esophageal cancer. Tumor 2002;22:268-70.  Back to cited text no. 9
    
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Stolzenberg-Solomon RZ, Qiao YL, Abnet CC, Ratnasinghe DL, Dawsey SM, Dong ZW, et al. Esophageal and gastric cardia cancer risk and folate- and Vitamin B (12)-related polymorphisms in Linxian, China. Cancer Epidemiol Biomarkers Prev 2003;12 (11 Pt 1):1222-6.  Back to cited text no. 10
    
11.
Zhang J, Zotz RB, Li Y, Wang R, Kiel S, Schulz WA, et al. Methylenetetrahydrofolate reductase C677T polymorphism and predisposition towards esophageal squamous cell carcinoma in a German Caucasian and a northern Chinese population. J Cancer Res Clin Oncol 2004;130:574-80.  Back to cited text no. 11
    
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Wang LD, Guo RF, Fan ZM, He X, Gao SS, Guo HQ, et al. Association of methylenetetrahydrofolate reductase and thymidylate synthase promoter polymorphisms with genetic susceptibility to esophageal and cardia cancer in a Chinese high-risk population. Dis Esophagus 2005;18:177-84.  Back to cited text no. 12
    
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Yutong H, Yimin W, Jiahui Z, Yan L, Wei G, Na W. Correlation between a polymorphism in the methylene tetrahydrofolate reductase gene and susceptibility to carcinoma of the esophagus and gastric cardia. Chin J Clin Oncol 2007;34:194-7.  Back to cited text no. 13
    
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Qin JM, Yang L, Chen B, Wang XM, Li F, Liao PH, et al. Interaction of methylenetetrahydrofolate reductase C677T, cytochrome P4502E1 polymorphism and environment factors in esophageal cancer in Kazakh population. World J Gastroenterol 2008;14:6986-92.  Back to cited text no. 14
    
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Li H, Li DQ, Li HQ, Diao YT. Contraception and induced abortions for women of reproductive age married in recent years in rural areas of Shandong, China. Gynecol Obstet Invest 2009;68:174-80.  Back to cited text no. 15
    
16.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.  Back to cited text no. 16
    
17.
Verdy E, Berkane N, Magdelaine A, Soubrier F, Uzan S. Prevalence of factor V Leiden, hyperhomocysteinemia, prothrombin G20210A, and methylene tetrahydrofolate reductase C677T mutations in obstetrical complications. Ann Biol Clin (Paris) 1999;57:539-44.  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]

This article has been cited by
1 MTHFR C677T polymorphism and risk of esophageal cancer: An updated meta-analysis
Pradeep Kumar,Vandana Rai
Egyptian Journal of Medical Human Genetics. 2018; 19(4): 273
[Pubmed] | [DOI]



 

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