Skip to main content
PMC home page
Oncotarget logoLink to Oncotarget
. 2018 Feb 20;9(19):15111–15121. doi: 10.18632/oncotarget.24534

Association between the Glutathione-S-transferase T1 null genotype and esophageal cancer susceptibility: a meta-analysis involving 11,163 subjects

Feng He 1, Changyu Liu 1, Ruijie Zhang 1, Zhipeng Hao 1, Yangkai Li 1, Ni Zhang 1, Liang Zheng 2
PMCID: PMC5871102  PMID: 29599931

Abstract

Background

Glutathione-S-Transferase T1 (GSTT1) null genotype has been shown to be associated with the risk of esophageal cancer. However, the results remain inconsistent. Thus a comprehensive meta-analysis was conducted to assess the strength of association between GSTT1 null genotype and the risk of esophageal cancer.

Materials and Methods

A literature search of PubMed, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases up to March 31, 2017 was conducted and 30 eligible articles with 4482 cases and 6681 controls were finally recruited. The strength of correlation between GSTT1 polymorphism and the susceptibility of esophageal cancer was assessed by the crude odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses and sensitivity analyses were performed to further identify the association.

Results

GSTT1 null genotype significantly increased the risk of esophageal cancer (OR = 1.20; 95% CI 1.04–1.40; P < 0.05). In a subgroup analysis by ethnicity, GSTT1 null genotype was correlated with a significantly increased risk of esophageal cancer among Asians (OR = 1.33; 95% CI 1.12–1.58; P < 0.05), instead of Caucasians or Africans (OR = 0.91; 95% CI 0.65–1.26; P > 0.05 for Caucasians and OR = 1.32; 95% CI 0.98–1.77; P > 0.05 for Africans). In the analysis by histological type, GSTT1 null genotype was correlated with a significantly increased risk of esophageal squamous cell carcinoma (OR = 1.34; 95% CI 1.12–1.61; P < 0.05), particularly among Asians (OR = 1.54; 95% CI 1.30–1.82; P < 0.05), but not among Caucasians or Africans (OR = 0.87; 95% CI 0.48–1.57; P > 0.05 for Caucasians and OR = 1.32; 95% CI 0.98–1.77; P > 0.05 for Africans). In addition, there is no significant correlation between GSTT1 null genotype and the risk of esophageal adenocarcinoma (OR = 0.98; 95% CI 0.71–1.35; P > 0.05).

Conclusions

Our findings demonstrate that GSTT1 null genotype significantly increases esophageal cancer risk, particularly in Asians.

Keywords: Glutathione-S-transferase T1, esophageal cancer, gene polymorphism, meta-analysis

INTRODUCTION

Esophageal cancer is the sixth leading cause of cancer-related mortality and the eighth most common cancer worldwide [1]. An estimated 455,800 new esophageal cancer cases and 400,200 deaths occurred in 2012 worldwide [2]. The two major types are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EADC). Smoking and drinking are well-known environmental risk factors for ESCC, whereas obesity and chronic gastroesophageal refluxing are main EADC risk factors. However, only a subset of individuals exposed to those environmental risk factors develop EC, suggesting a role of host susceptibility factors. Some studies have suggested that genetic polymorphisms might explain individual differences in susceptibility to esophageal cancer [3, 4].

Glutathione-S-transferases (GSTs) are important phase II biotransformation enzymes that catalyzing the nucleophilic addition of glutathione to several hazardous xenobiotics, including phase I electrophilic and carcinogenic metabolites [5]. However, these enzymes can also activate certain chemicals that target cellular proteins and DNA to elicit detrimental carcinogenic effects through genotoxic and non-genotoxic mechanisms. One of important enzymes in GSTs family is GSTT1. GSTT1 is genetically polymorphic, and deletion polymorphism of the GSTT1 loci (null genotype) results in the loss of functional activity. Several studies have found that GSTT1 null genotype is strongly associated with susceptibility to a number of cancers, such as colorectal, renal and oral cancers et al. [6–8]. Previous studies have been published to estimate the association between GSTT1 null genotype and the risk of esophageal cancer, but the results are inconsistent [9–11].

To date, several meta-analysis studies have reported the association between null GSTT1 genotype and the risk of esophageal cancer. However, the results of these studies remain outdated and incomprehensive [12–14]. In the last 4 years, many case-control studies were published to estimate this association. Thus, to obtain a conclusive result about this association, we performed current meta-analysis that includes all recent publications to review and summarize the association between the GSTT1 polymorphism and the risk of esophageal cancer.

RESULTS

Characteristics

In total, 100 articles were retrieved. Figure 1 summarized the selecting process. Finally, a total of 30 studies with 4482 cases and 6681 controls met the inclusion criteria [9–11, 15–41]. Among them, 18 were from Asians, 10 were from Caucasians, and 2 were from Africans. There were 21 studies focused on the risk of ESCC with 3272 cases and 5535 controls, and 8 studies focused on the risk of EADC with 646 cases and 1908 controls. Characteristics of included studies and the distribution of GSTT1 polymorphism are summarized in Table 1 and Table 2, respectively.

Figure 1. Flow chart shows studies included procedure for meta-analysis.

Figure 1

Open in a new tab

Table 1. Characteristics of the individual studies included in the meta-analysis.

Study Year Country Ethnicity Sample size Genotype method
Makhdoomi MA 2014 India Asian 492/492 multiplex PCR
Sharma A 2013 India Asian 315/436 multiplex PCR
Dura P 2013 Netherlands Caucasian 432/591 PCR
Talukdar FR 2013 India Asian 112/130 PCR
Zhang L 2013 China Asian 138/170 PCR
Djansugurova LB 2013 Kazakhstan Caucasian 107/96 PCR
Gao P 2012 China Asian 40/80 PCR
Matejcic M 2011 South Africa African 528/876 PCR
Malik MA 2010 India Asian 135/195 multiplex PCR
Li D 2010 South Africa African 238/280 PCR
Moaven O 2010 Iran Asian 148/136 PCR
Liu R 2010 China Asian 97/97 multiplex PCR
Ji R 2010 China Asian 189/216 multiplex PCR
Zendehdel K 2009 Sweden Caucasian 172/470 multiplex PCR
Zhang WL 2009 China Asian 88/72 PCR
Deng J 2008 China Asian 87/162 PCR
Rossini A 2007 Brazil Caucasian 125/252 multiplex PCR
Wideroff L 2007 USA Caucasian 67/208 PCR
Casson AG 2006 Canada Caucasian 56/95 multiplex PCR
Jain M 2006 India Asian 100/137 multiplex PCR
Yin LH 2005 China Asian 106/106 PCR
Roth MJ 2004 China Asian 131/454 PCR
Abbas A 2004 French Caucasian 70/115 multiplex PCR
Wang LD 2003 China Asian 62/38 multiplex PCR
Casson AG 2003 Canada Caucasian 45/45 multiplex PCR
Ribeiro Pinto LF 2003 Brazil Caucasian 32/67 PCR
Gao CM 2002 China Asian 141/223 multiplex PCR
Tan W 2000 China Asian 150/150 multiplex PCR
van Lieshout EM 1999 Netherlands Caucasian 34/247 PCR
Lin DX 1998 China Asian 45/45 multiplex PCR
Open in a new tab

Table 2. Distribution of GSTT1 null genotype among cases and controls.

Study Year Control EC ESCC EADC
Present Null Present Null Present Null Present Null
Makhdoomi MA 2014 367 125 306 186 306 186 / /
Sharma A 2013 373 63 233 82 233 82 / /
Dura P 2013 463 128 335 97 87 18 248 79
Talukdar FR 2013 92 38 66 46 66 46 / /
Zhang L 2013 90 80 62 76 62 76 / /
Djansugurova LB 2013 35 61 19 88 19 88 / /
Gao P 2012 55 25 18 22 18 22 / /
Matejcic M 2011 648 228 375 153 375 153 / /
Malik MA 2010 146 49 110 25 / / / /
Li D 2010 178 102 125 113 125 113 / /
Moaven O 2010 105 31 112 36 112 36 / /
Liu R 2010 57 40 34 63 34 63 / /
Ji R 2010 122 94 91 98 91 98 / /
Zendehdel K 2009 394 76 150 22 70 7 80 15
Zhang LW 2009 39 33 31 57 31 57 / /
Deng J 2008 75 87 36 51 / / / /
Rossini A 2007 192 60 110 15 110 15 / /
Wideroff L 2007 173 35 59 8 / / 59 8
Casson AG 2006 80 15 42 14 / / 42 14
Jain M 2006 100 37 72 28 56 20 6 3
Yin LH 2005 55 51 60 46 / / / /
Roth MJ 2004 211 243 54 77 54 77 / /
Abbas A 2004 85 30 56 14 31 13 25 1
Wang LD 2003 18 20 28 34 25 34 / /
Casson AG 2003 33 12 37 8 / / 37 8
Rebeiro 2003 52 15 26 6 / / / /
Gao CM 2002 104 119 67 74 / / / /
Tan W 2000 91 59 90 60 90 60 / /
van Lieshout EM 1999 198 49 28 6 11 2 17 4
Lin DX 1998 22 23 26 19 / / / /
Open in a new tab

Abbreviations: EC: esophageal cancer; ESCC: esophageal squamous cell carcinoma; EADC: esophageal adenocarcinoma.

Quantitative synthesis

Table 3 showed the main result of the association between GSTT1 null genotype and the risk of esophageal cancer. Overall, there was a significant correlation of GSTT1 null genotype with esophageal cancer risk (OR = 1.20; 95% CI 1.04–1.40; P < 0.05; Table 3 and Figure 2). In a subgroup analysis by ethnicity, GSTT1 null genotype was correlated with a significantly increased risk of esophageal cancer among Asians (OR = 1.33; 95% CI 1.12–1.58; P < 0.05; Table 3 and Figure 2), but not among Caucasians and Africans (OR = 0.91; 95% CI 0.65–1.26; P > 0.05 for Caucasians and OR = 1.32; 95% CI 0.98–1.77; P > 0.05 for Africans; Table 3 and Figure 2).

Table 3. Meta-analysis of the GSTT1 null genotype and esophageal cancer risk.

Number of Study OR (95%CI) P P (Q-test) I-squared
Total 30 1.20 (1.04–1.40) 0.014 0.000 60.2
Ethnicity
 Asians 18 1.33 (1.12–1.58) 0.001 0.003 54.9
 Caucasians 10 0.91 (0.65–1.26) 0.569 0.01 58.3
 Africans 2 1.32 (0.98–1.77) 0.070 0.157 50.0
ESCC 21 1.34 (1.12–1.61) 0.001 0.000 62.6
Ethnicity
 Asians 13 1.54 (1.30–1.82) 0.000 0.097 35.7
 Caucasians 6 0.87 (0.48–1.57) 0.640 0.002 73.5
 Africans 2 1.32 (0.98–1.77) 0.070 0.157 50.0
EADC 8 0.98 (0.71–1.35) 0.911 0.240 23.7
Open in a new tab

Figure 2. Forest plot of the association of GSTT1 null genotype with esophageal cancer risk.

Figure 2

Open in a new tab

In the analysis by histological type, GSTT1 null genotype were correlated with a significantly increased risk of ESCC (OR = 1.34; 95% CI 1.12–1.61; P < 0.05; Table 3 and Figure 3). Moreover, in a subgroup analysis by ethnicity, GSTT1 null genotype was correlated with a significantly increased risk of ESCC among Asians (OR = 1.54; 95% CI 1.30–1.82; P < 0.05; Table 3 and Figure 3), but not among Caucasians and Africans (OR = 0.87; 95% CI 0.48–1.57; P > 0.05 for Caucasians and OR = 1.32; 95% CI 0.98–1.77; P > 0.05 for Africans; Table 3 and Figure 3). In addition, there is no significant correlation of GSTT1 null genotype with the risk of EADC (OR = 0.98; 95% CI 0.71–1.35; P > 0.05; Table 3 and Figure 4).

Figure 3. Forest plot of the association of GSTT1 null genotype with esophageal squamous cell carcinoma risk.

Figure 3

Open in a new tab

Figure 4. Forest plot of the association of GSTT1 null genotype with esophageal adenocarcinoma risk.

Figure 4

Open in a new tab

Test for publication bias, sensitivity analyses, and heterogeneity

Publication bias was assessed by both the Begg’s funnel plot and the Egger’s test. The shape of the Begg’s funnel plot did not reveal any evidence of obvious asymmetry (Figure 5). Egger’s test further suggested no evidence of publication bias (P = 0.210). Thus, there was no obvious publication bias in this meta-analysis.

Figure 5. Begg's funnel plot analysis of GSTT1 polymorphism with esophageal cancer risk.

Figure 5

Open in a new tab

The sensitivity analysis was conducted to test the influence of an individual data on the pooled ORs and CIs by eliding a study in turn. Our findings suggested that the present meta-analysis results were relatively robust and stable (Figure 6).

Figure 6. One-way sensitivity analysis of GSTT1 polymorphism with esophageal cancer risk.

Figure 6

Open in a new tab

As showed in Figure 2 and Figure 3, heterogeneity was significant in overall and in some subgroups. Thus, we measured the sources of heterogeneity by subgroup analysis. The results showed that Caucasians may lead to the major source of heterogeneity.

DISCUSSION

Many studies suggest genetic variants play important roles in individual susceptibility to esophageal cancer [3, 42]. In decades, epidemiological studies have been performed to assess the association of GSTT1 null genotype with the risk of esophageal cancer. However, the results were inconsistent [34, 36]. Previous meta-analyses also investigated the association [12–14], the findings should be interpreted with very cautions. In Weng et al. study, 11 studies included in the meta-analysis were in Chinese Han population. Although the results showed a significant association between GSTT1 null genotype and esophageal cancer risk, the single Chinese Han population limited the power of the statistical analysis [12]. Also In Yi et al. study, 15 studies included in the meta-analysis were in Asian population. Although the results showed a significant association between GSTT1 null genotype and esophageal cancer risk, the single Asian population limited the power of the statistical analysis [13]. In Cai et al. study, a total of 24 studies were used. Adjusted ORs with corresponding 95% CIs were reported in 9 studies. In the overall analysis there was no significant association between GSTT1 null genotype and esophageal cancer risk. However, meta-analysis of adjusted ORs showed a significant association between GSTT1 null genotype and esophageal cancer risk [14]. Because of the lack of available data, subgroup analysis by histological type was not performed in these studies [12–14]. Thus we conducted a comprehensive meta-analysis, to investigate not only the strength of association between GSTT1 null genotype and the risk of esophageal cancer, but also the association of GSTT1 null genotype with the risk of different histological types.

This meta-analysis, including 30 case-control studies with 4482 cases and 6681 controls, identified the association between GSTT1 null genotype and esophageal cancer risk. GSTT1 null genotype significantly increased overall esophageal cancer risk. In a subgroup analysis by ethnicity, GSTT1 null genotype was correlated with a significantly increased risk of esophageal cancer among Asians. In the analysis by histological type, GSTT1 null genotype was correlated with a significantly increased risk of ESCC, particularly in Asians. However, there was no significant correlation of GSTT1 null genotype with the risk of EADC. To date, this is the first meta-analysis concerning the association of GSTT1 null genotype with the risk of different histological types.

GSTT1, encodes an enzyme that plays a crucial role in the detoxification of a variety of endogenous or exogenous carcinogens. It is located on 22q11.23 with 8146 base pairs, 5 exons and 4 introns in all [5]. GSTT1 is genetically polymorphic, and GSTT1 null genotype results in the loss of functional activity [12]. Our results demonstrated that GSTT1 null genotype significantly increased overall esophageal cancer risk.

Since the results from meta-analysis can be affected by histological types, a subgroup analysis was carried out regarding different histological type for the GSTT1 null genotype. GSTT1 null genotype was correlated with a significantly increased risk of ESCC among Asians, but not among Caucasians and Africans. However, there was no significant correlation of GSTT1 null genotype with the risk of EADC. All results should be interpreted with caution. Only two African studies were recruited in the current meta-analysis, which may restrict statistical power to detect a real assessment in Africans. More large scale studies are needed to verify the results. Subgroup analyses were also performed regarding ethnicity for the GSTT1 null genotype. GSTT1 null genotype was correlated with a significantly increased risk of esophageal cancer among Asians, but not among Caucasians and Africans. The results were more robust on histological type of ESCC. This meta-analysis confirmed the mutual effect of GSTT1 null genotype in different populations to the risk of esophageal cancer. Possible explanations include: (1) significance of these enzymes may vary with the ethnicity genetic backgrounds, environmental exposures and histological types. The regional difference in the frequency of esophageal cancer is probably due to genetic polymorphism and variable exposure to environmental factors; (2) GSTs metabolize a variety of overlapping substrates and individuals lacking GSTT1 can also metabolize the carcinogens by other alternative GST enzymes. Furthermore, there was only one study concerning the association between GSTT1 null genotype and EADC on Asians. Thus, we failed to evaluate the potential role of GSTT1 null genotype in EADC risk in Asians due to the lack of available data to date. More case-control studies on the GSTT1 null genotype are encouraged, especially in Asians, for a better understanding the role of GSTT1 null genotype in the EADC development.

Some limitations must be acknowledged in the current meta-analysis. First, significant heterogeneity was observed between publications for GSTT1 null genotype. Potential sources of heterogeneity include the study design, publication year, ethnicity, country, histological type, sample size, and so on. When subgroup analyses were carried out according to ethnicity and histological type, this heterogeneity was reduced or removed in some subgroups, implying different effects on histological types and ethnic populations. These findings should be interpreted with very cautions. Second, our findings were based on unadjusted ORs and CIs, whereas a more precisely investigation could be performed if the sufficient individual data were available. Third, only two African studies were recruited in the current meta-analysis, the results in African population should be interpreted with caution. More large scale studies are needed to verify the results in Africans. Finally, due to lack of uniform individual-level data, further stratified analysis to measure any interactions between gene–gene variation and gene-metabolic traits was not performed.

In conclusion, our meta-analysis findings demonstrated that GSTT1 null genotype significantly increased esophageal cancer risk, particularly in Asians. In addition, GSTT1 null genotype was correlated with a significantly increased risk of ESCC, particularly among Asians. However, more studies are warranted to confirm or refute these correlations, particularly with respect to gene-gene and gene-environment interactions.

MATERIALS AND METHODS

Study selection

Pubmed, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases (the search was updated in March 31, 2017) were searched using the following terms: ‘glutathione S-transferase T1’ or ‘GSTT1’, ‘polymorphism’ or ‘variant’, and ‘esophageal’ or ‘esophagus’, and ‘cancer’ or ‘carcinoma’ or ‘tumor’ or ‘malignancy’. The literature search was limited to English or Chinese articles. Additional publications were identified by a manual search based on references of retrieved studied or reviews.

Inclusion and exclusion criteria

The selection criteria were: (1) in a case-control study design, (2) studies that evaluated the relationship between the GSTT1 null genotype polymorphism and esophageal cancer, (3) usable data on genotype frequency. Thus, reports without usable data, reviews, comments and duplicated publications were excluded.

Data extraction

The data were collected by two independent reviewers. The extracted information contained: first author, year of publication, country of origin, ethnicity, number of cases and controls, genotyping method and characteristics of cases and controls. When come to conflicting assessment, disagreements were settled through a discussion among all authors.

Statistical analysis

The strength of correlation between GSTT1 null genotype and the susceptibility of esophageal cancer was assessed by the crude odds ratios (ORs) with 95% confidence intervals (CIs). A P < 0.05 (two-tailed) was considered as statistical significance. A Chi-square-based I2 test was used to detect heterogeneity [43] and an I2 < 25% indicates low heterogeneity, 25% ≤ I2 ≤ 50% indicates moderate heterogeneity, and I2 > 50% indicates large heterogeneity [44]. When I2 > 50% or P < 0.10 (two-sided), the random-effects model (the DerSimonian-Laird method) was utilized to pool the data [45], otherwise the fixed-effects model (the Mantel-Haenszel method) was used [46]. Subgourp analyses were conducted according to different ethnicity to identify the specific effects of heterogeneity. Publication bias was assessed by Begg’s funnel plot and Egger’s test [47]. Sensitivity analyses were conducted by one-way method. All statistical analyses were performed using STATA version 12.0 software (Stata Corporation, College Station, TX, USA).

Acknowledgments

We thank Dr. Haiyong Gu for his invaluable help. This study is supported in part by Changzhou High-Level Medical Talents Training Project (No: 2016CZBJ043) and The Applied Basic Research Programs of ChangZhou (No: CJ20159030).

Abbreviations

Glutathione-S-Transferase T1

GSTT1

China National Knowledge Infrastructure

CNKI

odds ratios

ORs

confidence intervals

CIs

esophageal squamous cell carcinoma

ESCC

esophageal adenocarcinoma

EADC

Author contributions

FH, NZ and LZ designed the study. All authors were involved in article search, extraction, analysis and interpretation of data. FH drafted the manuscript, which was critically revised by NZ and LZ. All authors read and approved the final manuscript.

CONFLICTS OF INTEREST

The authors report no conflicts of interest.

FUNDING

Changzhou High-Level Medical Talents Training Project (No: 2016CZBJ043). The Applied Basic Research Programs of ChangZhou (No: CJ20159030).

REFERENCES

  • 1.Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. doi: 10.3322/caac.20107. https://doi.org/10.3322/caac.20107. [DOI] [PubMed] [Google Scholar]
  • 2.Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108. doi: 10.3322/caac.21262. https://doi.org/10.3322/caac.21262. [DOI] [PubMed] [Google Scholar]
  • 3.Wang LD, Zhou FY, Li XM, Sun LD, Song X, Jin Y, Li JM, Kong GQ, Qi H, Cui J, Zhang LQ, Yang JZ, Li JL, et al. Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54. Nat Genet. 2010;42:759–63. doi: 10.1038/ng.648. https://doi.org/10.1038/ng.648. [DOI] [PubMed] [Google Scholar]
  • 4.Wu C, Kraft P, Zhai K, Chang J, Wang Z, Li Y, Hu Z, He Z, Jia W, Abnet CC, Liang L, Hu N, Miao X, et al. Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions. Nat Genet. 2012;44:1090–7. doi: 10.1038/ng.2411. https://doi.org/10.1038/ng.2411. [DOI] [PubMed] [Google Scholar]
  • 5.Hayes JD, Strange RC. Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology. 2000;61:154–66. doi: 10.1159/000028396. [DOI] [PubMed] [Google Scholar]
  • 6.Xu D, Yan S, Yin J, Zhang P. Null genotype of GSTT1 contributes to colorectal cancer risk in Asian populations: evidence from a meta-analysis. Asian Pac J Cancer Prev. 2011;12:2279–84. [PubMed] [Google Scholar]
  • 7.Zhang ZJ, Hao K, Shi R, Zhao G, Jiang GX, Song Y, Xu X, Ma J. Glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms, smoking, and their interaction in oral cancer: a HuGE review and meta-analysis. Am J Epidemiol. 2011;173:847–57. doi: 10.1093/aje/kwq480. https://doi.org/10.1093/aje/kwq480. [DOI] [PubMed] [Google Scholar]
  • 8.Cheng HY, You HY, Zhou TB. Relationship between GSTM1/GSTT1 null genotypes and renal cell carcinoma risk: a meta-analysis. Ren Fail. 2012;34:1052–7. doi: 10.3109/0886022X.2012.708380. https://doi.org/10.3109/0886022X.2012.708380. [DOI] [PubMed] [Google Scholar]
  • 9.Sharma A, Das BC, Sehgal A, Mehrotra R, Kar P, Sardana S, Phukan R, Mahanta J, Purkayastha J, Saxena S, Kapur S, Chatterjee I, Sharma JK. GSTM1 and GSTT1 polymorphism and susceptibility to esophageal cancer in high- and low-risk regions of India. Tumour Biol. 2013;34:3249–57. doi: 10.1007/s13277-013-0897-6. https://doi.org/10.1007/s13277-013-0897-6. [DOI] [PubMed] [Google Scholar]
  • 10.Talukdar FR, Ghosh SK, Laskar RS, Mondal R. Epigenetic, genetic and environmental interactions in esophageal squamous cell carcinoma from northeast India. PLoS One. 2013;8:e60996. doi: 10.1371/journal.pone.0060996. https://doi.org/10.1371/journal.pone.0060996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Makhdoomi MA, Shah IA, Bhat GA, Amin S, Lone MM, Islami F, Dar NA. Association between GSTM1 and GSTT1 polymorphisms and esophageal squamous cell carcinoma: results from a case-control study in Kashmir, India. Tumour Biol. 2015;36:2613–9. doi: 10.1007/s13277-014-2882-0. https://doi.org/10.1007/s13277-014-2882-0. [DOI] [PubMed] [Google Scholar]
  • 12.Weng Y, Fei B, He P, Cai M. Glutathione-S-transferase T1 polymorphism is associated with esophageal cancer risk in Chinese Han population. Asian Pac J Cancer Prev. 2012;13:4403–7. doi: 10.7314/apjcp.2012.13.9.4403. [DOI] [PubMed] [Google Scholar]
  • 13.Yi SM, Li GY. Null genotype of GSTT1 contributes to esophageal cancer risk in Asian populations: evidence from a meta-analysis. Asian Pac J Cancer Prev. 2012;13:4967–71. doi: 10.7314/apjcp.2012.13.10.4967. [DOI] [PubMed] [Google Scholar]
  • 14.Cai Y, Wang J. Significant association of glutathione S-transferase T1 null genotype with esophageal cancer risk: a meta-analysis. Mol Biol Rep. 2013;40:2397–403. doi: 10.1007/s11033-012-2320-6. https://doi.org/10.1007/s11033-012-2320-6. [DOI] [PubMed] [Google Scholar]
  • 15.Lin DX, Tang YM, Peng Q, Lu SX, Ambrosone CB, Kadlubar FF. Susceptibility to esophageal cancer and genetic polymorphisms in glutathione S-transferases T1, P1, and M1 and cytochrome P450 2E1. Cancer Epidemiol Biomarkers Prev. 1998;7:1013–8. [PubMed] [Google Scholar]
  • 16.van Lieshout EM, Roelofs HM, Dekker S, Mulder CJ, Wobbes T, Jansen JB, Peters WH. Polymorphic expression of the glutathione S-transferase P1 gene and its susceptibility to Barrett’s esophagus and esophageal carcinoma. Cancer Res. 1999;59:586–9. [PubMed] [Google Scholar]
  • 17.Tan W, Song N, Wang GQ, Liu Q, Tang HJ, Kadlubar FF, Lin DX. Impact of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferases M1, T1, and P1 on susceptibility to esophageal cancer among high-risk individuals in China. Cancer Epidemiol Biomarkers Prev. 2000;9:551–6. [PubMed] [Google Scholar]
  • 18.Gao CM, Takezaki T, Wu JZ, Li ZY, Liu YT, Li SP, Ding JH, Su P, Hu X, Xu TL, Sugimura H, Tajima K. Glutathione-S-transferases M1 (GSTM1) and GSTT1 genotype, smoking, consumption of alcohol and tea and risk of esophageal and stomach cancers: a case-control study of a high-incidence area in Jiangsu Province, China. Cancer Lett. 2002;188:95–102. doi: 10.1016/s0304-3835(02)00115-5. [DOI] [PubMed] [Google Scholar]
  • 19.Casson AG, Zheng Z, Chiasson D, MacDonald K, Riddell DC, Guernsey JR, Guernsey DL, McLaughlin J. Associations between genetic polymorphisms of Phase I and II metabolizing enzymes, p53 and susceptibility to esophageal adenocarcinoma. Cancer Detect Prev. 2003;27:139–46. doi: 10.1016/s0361-090x(03)00033-3. [DOI] [PubMed] [Google Scholar]
  • 20.Ribeiro Pinto LF, Teixeira Rossini AM, Albano RM, Felzenszwalb I, de Moura Gallo CV, Nunes RA, Andreollo NA. Mechanisms of esophageal cancer development in Brazilians. Mutat Res. 2003;544:365–73. doi: 10.1016/j.mrrev.2003.06.021. [DOI] [PubMed] [Google Scholar]
  • 21.Wang LD, Zheng S, Liu B, Zhou JX, Li YJ, Li JX. CYP1A1, GSTs and mEH polymorphisms and susceptibility to esophageal carcinoma: study of population from a high- incidence area in north China. World J Gastroenterol. 2003;9:1394–7. doi: 10.3748/wjg.v9.i7.1394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Abbas A, Delvinquiere K, Lechevrel M, Lebailly P, Gauduchon P, Launoy G, Sichel F. GSTM1, GSTT1, GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population: different pattern of squamous cell carcinoma and adenocarcinoma. World J Gastroenterol. 2004;10:3389–93. doi: 10.3748/wjg.v10.i23.3389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Roth MJ, Abnet CC, Johnson LL, Mark SD, Dong ZW, Taylor PR, Dawsey SM, Qiao YL. Polymorphic variation of Cyp1A1 is associated with the risk of gastric cardia cancer: a prospective case-cohort study of cytochrome P-450 1A1 and GST enzymes. Cancer Causes Control. 2004;15:1077–83. doi: 10.1007/s10552-004-2233-3. [DOI] [PubMed] [Google Scholar]
  • 24.Yin LH, Pu YP, Song YH, Hu X, Liu YZ, Kai HT. Polymorphisms of susceptible genes for esophageal cancer risk in Huaian population in Jiangsu province. Tumor. 2005:04. [Google Scholar]
  • 25.Casson AG, Zheng Z, Porter GA, Guernsey DL. Genetic polymorphisms of microsomal epoxide hydroxylase and glutathione S-transferases M1, T1 and P1, interactions with smoking, and risk for esophageal (Barrett) adenocarcinoma. Cancer Detect Prev. 2006;30:423–31. doi: 10.1016/j.cdp.2006.09.005. https://doi.org/10.1016/j.cdp.2006.09.005. [DOI] [PubMed] [Google Scholar]
  • 26.Jain M, Kumar S, Rastogi N, Lal P, Ghoshal UC, Tiwari A, Pant MC, Baiq MQ, Mittal B. GSTT1, GSTM1 and GSTP1 genetic polymorphisms and interaction with tobacco, alcohol and occupational exposure in esophageal cancer patients from North India. Cancer Lett. 2006;242:60–7. doi: 10.1016/j.canlet.2005.10.034. https://doi.org/10.1016/j.canlet.2005.10.034. [DOI] [PubMed] [Google Scholar]
  • 27.Rossini A, Rapozo DC, Soares Lima SC, Guimaraes DP, Ferreira MA, Teixeira R, Kruel CD, Barros SG, Andreollo NA, Acatauassu R, Matos HJ, Albano RM, Pinto LF. Polymorphisms of GSTP1 and GSTT1, but not of CYP2A6, CYP2E1 or GSTM1, modify the risk for esophageal cancer in a western population. Carcinogenesis. 2007;28:2537–42. doi: 10.1093/carcin/bgm222. https://doi.org/10.1093/carcin/bgm222. [DOI] [PubMed] [Google Scholar]
  • 28.Wideroff L, Vaughan TL, Farin FM, Gammon MD, Risch H, Stanford JL, Chow WH. GST, NAT1, CYP1A1 polymorphisms and risk of esophageal and gastric adenocarcinomas. Cancer Detect Prev. 2007;31:233–6. doi: 10.1016/j.cdp.2007.03.004. https://doi.org/10.1016/j.cdp.2007.03.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Deng J, Guo RL, Yue HW, Huang ZG, Ma YX. A Case-control Study of the Polymorphisms of Phase I and Phase II Metabolic Genes and Esophageal Carcinoma Susceptibility. PJCCPVD. 2008:07. [Google Scholar]
  • 30.Zendehdel K, Bahmanyar S, McCarthy S, Nyren O, Andersson B, Ye W. Genetic polymorphisms of glutathione S-transferase genes GSTP1, GSTM1, and GSTT1 and risk of esophageal and gastric cardia cancers. Cancer Causes Control. 2009;20:2031–8. doi: 10.1007/s10552-009-9399-7. https://doi.org/10.1007/s10552-009-9399-7. [DOI] [PubMed] [Google Scholar]
  • 31.Zhang LW, Sheyhidin I, Wu MB, Zhang Z, Li DS, Liu Z. Study on relations between genetic polymorphisms in CYP2C19, GSTT1 and risk of Kazakh’s esophageal cancer in Xinjiang. Journal of Practical Oncology. 2009:03. [Google Scholar]
  • 32.Ji R, Wu J, Zhou YN, Zhang B, Zhang ZY, Yang Z. Relationship between CYP1A1, GSTM1 and GSTT1 genetic polymorphisms and susceptibility of esophageal cancer in Wuwei, Gansu province. Journal of Lanzhou University (Medical Sciences) 2010:02. [Google Scholar]
  • 33.Li D, Dandara C, Parker MI. The 341C/T polymorphism in the GSTP1 gene is associated with increased risk of oesophageal cancer. BMC Genet. 2010;11:47. doi: 10.1186/1471-2156-11-47. https://doi.org/10.1186/1471-2156-11-47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Liu R, Yin L, Pu Y, Li Y, Liang G, Zhang J, Li X. Functional alterations in the glutathione S-transferase family associated with enhanced occurrence of esophageal carcinoma in China. J Toxicol Environ Health A. 2010;73:471–82. doi: 10.1080/15287390903523394. https://doi.org/10.1080/15287390903523394. [DOI] [PubMed] [Google Scholar]
  • 35.Malik MA, Upadhyay R, Mittal RD, Zargar SA, Mittal B. Association of xenobiotic metabolizing enzymes genetic polymorphisms with esophageal cancer in Kashmir Valley and influence of environmental factors. Nutr Cancer. 2010;62:734–42. doi: 10.1080/01635581003605904. https://doi.org/10.1080/01635581003605904. [DOI] [PubMed] [Google Scholar]
  • 36.Moaven O, Raziee HR, Sima HR, Ganji A, Malekzadeh R, A’Rabi A, Abdollahi A, Memar B, Sotoudeh M, Naseh H, Nekoui N, Razavipour A, Gholamin M, et al. Interactions between Glutathione-S-Transferase M1, T1 and P1 polymorphisms and smoking, and increased susceptibility to esophageal squamous cell carcinoma. Cancer Epidemiol. 2010;34:285–90. doi: 10.1016/j.canep.2010.03.009. https://doi.org/10.1016/j.canep.2010.03.009. [DOI] [PubMed] [Google Scholar]
  • 37.Matejcic M, Li D, Prescott NJ, Lewis CM, Mathew CG, Parker MI. Association of a deletion of GSTT2B with an altered risk of oesophageal squamous cell carcinoma in a South African population: a case-control study. PLoS One. 2011;6:e29366. doi: 10.1371/journal.pone.0029366. https://doi.org/10.1371/journal.pone.0029366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Gao P, Tian Y, Ye XF, Ge J, Zhang D, Xu WD. Study of CTPIA1, GSTT1, GSTM1 polymorphisms and susceptibility on esophageal carcinoma in Ningxia Hui nationality. Ningxia Med J. 2012:03. [Google Scholar]
  • 39.Djansugurova LB, Perfilyeva AV, Zhunusova GS, Djantaeva KB, Iksan OA, Khussainova EM. The determination of genetic markers of age-related cancer pathologies in populations from Kazakhstan. Front Genet. 2013;4:70. doi: 10.3389/fgene.2013.00070. https://doi.org/10.3389/fgene.2013.00070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Dura P, Salomon J, Te Morsche RH, Roelofs HM, Kristinsson JO, Wobbes T, Witteman BJ, Tan AC, Drenth JP, Peters WH. No role for glutathione S-transferase genotypes in Caucasian esophageal squamous cell or adenocarcinoma etiology: an European case-control study. BMC Gastroenterol. 2013;13:97. doi: 10.1186/1471-230X-13-97. https://doi.org/10.1186/1471-230X-13-97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Zhang L, Ma W, Li Y, Jiang YZ, Ma GY. Genetic polymorphisms of cytochrome P450 and glutathione S-transferase in relation to human esophageal carcinoma. Chin J Publ Health. 2013;10:3. [Google Scholar]
  • 42.Wu C, Li D, Jia W, Hu Z, Zhou Y, Yu D, Tong T, Wang M, Lin D, Qiao Y, Zhou Y, Chang J, Zhai K, et al. Genome-wide association study identifies common variants in SLC39A6 associated with length of survival in esophageal squamous-cell carcinoma. Nat Genet. 2013;45:632–8. doi: 10.1038/ng.2638. https://doi.org/10.1038/ng.2638. [DOI] [PubMed] [Google Scholar]
  • 43.Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58. doi: 10.1002/sim.1186. https://doi.org/10.1002/sim.1186. [DOI] [PubMed] [Google Scholar]
  • 44.Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60. doi: 10.1136/bmj.327.7414.557. https://doi.org/10.1136/bmj.327.7414.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88. doi: 10.1016/0197-2456(86)90046-2. [DOI] [PubMed] [Google Scholar]
  • 46.Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48. [PubMed] [Google Scholar]
  • 47.Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34. doi: 10.1136/bmj.315.7109.629. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Oncotarget are provided here courtesy of Impact Journals, LLC

RESOURCES