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. 2015 Mar 23;5:9392. doi: 10.1038/srep09392

The Association of GSTM1 Deletion Polymorphism with Lung Cancer Risk in Chinese Population: Evidence from an Updated Meta-analysis

Haiyan Yang 1, Siyu Yang 1, Jing Liu 1, Fuye Shao 1, Haiyu Wang 2, Yadong Wang 2,a
PMCID: PMC4369748  PMID: 25797617

Abstract

Previous studies have reported the association of glutathione S-transferase M1 (GSTM1) deletion polymorphism with genetic susceptibility of lung cancer in Chinese population. However, the results remained controversial. The aim of this study was to clarify the association of GSTM1 deletion polymorphism with lung cancer risk in Chinese population. Systematic searches were performed through the search engines of Medline/Pubmed, Web of Science, EMBASE, CNKI and Wanfang Medical Online. The pooled effects were calculated by STATA 10.0 software package and Review Manager 5.0.24. Overall, we observed an association of GSTM1 deletion polymorphism with increased lung cancer risk in Chinese population (odds ratio (OR) = 1.46, 95% confidence interval (95%CI): 1.32–1.66 for null genotype vs. present genotype) based on 53 studies including 7,833 cases and 10,353 controls. We also observed an increased risk of GSTM1 null genotype for lung cancer in stratified analyses by source of control, smoking status and histological type. The findings suggest that GSTM1 deletion polymorphism may contribute to lung cancer risk in Chinese population. Further, well-designed studies with larger sample sizes are required to verify the results.

The global incidence of lung cancer is 1,608,800 per year, with an annual mortality rate of 1,378,400. It was the most commonly diagnosed cancer as well as the leading cause of cancer death in males globally, and among females, it was the fourth most commonly diagnosed cancer and the second leading cause of cancer death1. About 85% to 90% of lung cancers are non-small cell lung cancer including squamous cell carcinoma, adenocarcinoma, large cell carcinoma and other subtypes.

Epidemiological data have shown that environmental exposures such as tobacco smoking and asbestos are the main etiological factors in lung carcinogenesis2,3. However, only a small fraction of people, who are exposed to such risk factors, will develop lung cancer. This indicates that an individual's susceptibility might play a certain role in lung carcinogenesis. Recently, increasing evidence has been accumulated to support the hypothesis that common genetic variations of drug-metabolizing enzyme genes may be of importance in determining an individual's sensitivity to develop lung cancer4.

Glutathione S-transferases (GSTs) are a group of phase II detoxification enzymes which detoxify a broad range of compounds, including xenobiotics, pesticides, products of oxidative stress, chemotherapeutic drugs and carcinogens such as benzo(a)pyrene and other polycyclic aromatic hydrocarbons5. Glutathione S-transferase mu-1 (GSTM1) is a polymorphic member of the mu class gene family of the GSTs. GSTM1 deletion polymorphism has been shown to result in the elimination of the activity of GSTM1 enzymes and modulate lung cancer risk6. To date, results from epidemiological studies on the association between GSTM1 deletion polymorphism and lung cancer risk in Chinese population have been mixed7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59. Recently, two meta-analyses have reported the association of GSTM1 deletion polymorphism with increased lung cancer risk in Chinese population60,61. Unfortunately, some overlapping articles were not excluded and several published papers were missing in their papers. In order to obtain a more precise estimation of this relationship, a meta-analysis including a total of 53 studies was conducted, which may provide more comprehensive evidence for the association of GSTM1 deletion polymorphism with lung cancer risk in Chinese population.

Methods

Literature and methods

Systematic searches were performed in Medline/Pubmed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure (CNKI) and Wanfang Medical Online, with the following terms utilized: “lung cancer” or “lung tumor” or “lung carcinoma” or “non-small cell lung cancer” or “small cell lung cancer” and “polymorphism” and “GSTM1” and “Chinese” or “China”. All publications were updated to July 15, 2014. Additional relevant references quoted in the searched articles were also selected.

Criteria of literature inclusion were (a) the subjects of literature must be Chinese; (b) the papers should evaluate the association of GSTM1 deletion polymorphism with lung cancer risk; (c) case-control studies or cohort studies; (d) studies should have sufficient data for estimating odds ratio (OR) with 95% confidence intervals (CI). The exclusion criteria were (a) studies without the number of case and control or other essential information and (b) reviews and repeated or overlapping studies. For repeated studies or overlapping studies, the publication with more information was selected when more than one article was identified for the same study population.

In total, ninety eight published articles were identified with the association of GSTM1 deletion polymorphism with lung cancer risk in Chinese population. We reviewed all papers according to the criteria listed, above; forty one overlapping studies and four reviews were excluded. At last, fifty three original articles that focused on the association between GSTM1 deletion polymorphism and lung cancer risk in Chinese population were determined to be eligible to enter our study (Fig. 1 Flow diagram).

Figure 1. Flow diagram of selection process.

Figure 1

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Data extraction

Data were carefully extracted from all selected articles by two of the authors, independently. The following information was subtracted from selected studies: author's name, publishing date, area, source of control, number of case and control, and number of null and present genotypes. Data coming from similar stratum were combined to make full use of them if the study provided stratum information. Characteristics of selected studies were summarized in Table 1.

Table 1. Studies on the association between GSTM1 deletion polymorphism and lung cancer risk in Chinese population included in this study.

Author Year Area Source of control Number of case Number of control Stratified factors
Ai C7 2011 Sichuan Healthy subjects 50 50  
Chan EC8 2005 Taiwan Healthy subjects 75 162 Sex
Chan Y40 2002 Yunnan Healthy subjects 56 99  
Chan-Yeung M9 2004 Hong Kong Healthy subjects 229 197 Histological type
Chen CM10 2012 Zhejiang Healthy subjects 200 189 Smoking
Chen H11 2008 Anhui Healthy subjects 158 454 Smoking
Chen HC12 2006 Hunan Healthy subjects 97 197  
Chen LJ13 2003 Anhui Healthy subjects 38 99 Smoking
Chen SQ14 2001 Hubei Healthy subjects 106 106 Smoking and age
Cheng YW15 2000 Taiwan Hospitalized patients 73 33  
Dong CT16 2004 Sichuan Hospitalized patients 82 91  
Du GB17 2011 Sichuan Hospitalized patients 125 125 Histological type and smoking
Fowke JH18 2011 Shanghai Healthy subjects 208 785  
Gao Y19 1999 Guangdong Hospitalized patients and healthy subjects 59 132 Histological type and smoking
Ge H20 1996 Hongkong Hospitalized patients and healthy subjects 89 53  
Gu YF21 2007 Beijing Hospitalized patients and healthy subjects 279 684 Histological type and smoking
Huang XH22 2004 Guangdong Hospitalized patients and healthy subjects 85 138 Histological type and smoking
Jiang XY23 2014 Inner Mongolia Healthy subjects 180 266  
Lan Q24 2004 Yunnan Healthy subjects 122 122  
Lei FM25 2007 Sichuan Healthy subjects 42 103 Smoking and drinking
Li DR26 2005 Sichuan hospitalized patients 99 66 Smoking
Li WY27 2012 Beijing Healthy subjects 217 200 Smoking
Li Y28 2006 Henan Healthy subjects 98 138 Histological type and smoking
Liang GY29 2004 Jiangsu Hospitalized patients 152 152 Histological type
Liang KC30 2012 Guangxi Hospitalized patients 68 70  
Liu DZ31 2012 Heilongjiang Healthy subjects 360 360 Histological type and smoking
Liu Q32 2008 Shandong Healthy subjects 110 125  
London SJ33 2000 Shanghai Healthy subjects 232 710  
Lu QK34 2013 Guangdong Healthy subjects 91 138 Histological type and smoking
Luo CL35 2004 Guangdong Healthy subjects 63 47  
Lv W36 2002 Beijing Healthy subjects 314 314 Histological type and smoking
Pan CG37 2014 Jiangxi Healthy subjects 523 523 Histological type, smoking and sex
Persson I38 1999 Beijing Healthy subjects 75 119  
Qian BY39 2006 Tianjin Healthy subjects 108 108 Smoking
Qiao GB41 2005 Guangdong Hospitalized patients and healthy subjects 213 199 Smoking
Qu YH42 1998 Shanghai and Heilongjiang Healthy subjects 182 179  
Shi Y43 2002 Hubei Hospitalized patients 120 120  
Sun GF44 1997 Liaoning Healthy subjects 207 364 Smoking, age and sex
Wang JW45 2003 Beijing Healthy subjects 164 181 Smoking
Wang MJ46 2009 Inner Mongolia Healthy subjects 304 316  
Wang N47 2012 Henan Healthy subjects 209 256  
Wang QM48 2006 Hubei Healthy subjects 56 42 Smoking
Xia Y49 2008 Gansu Hospitalized patients 58 116 Smoking
Yang XH50 2004 Liaoning Healthy subjects 186 139  
Yao W51 2006 Henan Healthy subjects 77 107 Histological type
Yao ZG52 2012 Beijing Healthy subjects 150 150 Smoking
Zhang HY53 2014 Yunnan Healthy subjects 110 100  
Zhang JK54 2002 Guangdong Healthy subjects 161 165 Histological type and smoking
Zhang JQ55 2011 Yunnan Healthy subjects 50 50 Smoking
Zhang LZ56 2002 Jiangsu Healthy subjects 65 60 Histological type and smoking
Zhao B57 2001 Singapore Hospitalized patients 233 187  
Zheng DJ58 2010 Tianjin Healthy subjects 265 307 Histological type
Zhu XX59 2010 Hunan Healthy subjects 160 160  
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Quantitative data synthesis

The strength of the association between GSTM1 deletion polymorphism and lung cancer risk was measured by OR with 95%CI. The Cochrane Q statistics test was used to assess heterogeneity. The combined OR was estimated using both a fixed-effects model and a random-effects model62. The fixed-effects model was used when there was lack of heterogeneity. Otherwise, the random-effects model was used. The potential publication bias was firstly evaluated by visual inspection of the funnel plot. An asymmetric plot indicates that a possible publication bias exists. The funnel plot asymmetry was evaluated by the methods of Egger's test and Begg's test63,64.

Statistical analysis was done using Review Manager (Version 5.0.24, the Cochrane Collaboration) and STATA10.0 software package (Stata Corporation, College Station, Texas). All the tests were two-sided, a P value of less than 0.05 for any test or model was considered to be statistically significant.

Results

Meta-analysis databases

A database was built in the light of the extracted information from selected articles. Some essential information was listed in Table 1, which indicated the first author's name, year of publication, area, source of control, the number of case and control, and stratified factors. There were a total of 53 studies with 7,833 cases and 10,353 controls concerning the GSTM1 deletion polymorphism related to lung cancer risk. The frequency of GSTM1 null genotype was 57.7% and 50.1% in case and control, respectively.

Test of heterogeneity

The heterogeneity of GSTM1 null genotype vs. present genotype was analyzed for 53 selected studies. The results showed that GSTM1 null genotype vs. present genotype for squamous cell carcinoma, hospitalized patients-based control, smokers and nonsmokers had no heterogeneity with a P value ≥0.05. Therefore, a fixed-effects model was used to calculate the summary ORs for them. A random-effects model was used to calculate the summary ORs for the rest.

Quantitative data synthesis

Table 2 listed the summary ORs of GSTM1 deletion polymorphism related to lung cancer risk in Chinese population on the basis of 7,833 cases and 10,353 controls. We observed an association of GSTM1 deletion polymorphism with increased lung cancer risk in the total population (OR = 1.46, 95%CI: 1.32–1.61 for null vs. present) (Fig. 2). In subgroup analysis for source of control, we observed an increased risk of lung cancer with GSTM1 null genotype in healthy subjects-based control (OR = 1.48, 95%CI: 1.32–1.66) and hospitalized patients-based control (OR = 1.40, 95%CI: 1.22–1.60), respectively. We also observed an increased risk of GSTM1 null genotype for lung cancer stratified by smoking status (OR = 1.60, 95%CI: 1.41–1.81 for smokers and OR = 1.79, 95%CI: 1.54–2.08 for nonsmokers, respectively). We observed an association between GSTM1 null genotype and increased lung cancer risk in stratified analysis by histological type (OR = 1.50, 95%CI: 1.31–1.72 for squamous cell carcinoma and OR = 1.36, 95%CI: 1.08–1.70 for adenocarcinoma, respectively) (Table 2).

Table 2. Summery odds ratios on the relation of the GSTM1 deletion polymorphism to lung cancer risk in Chinese population.

Null vs. Present Case/Control Heterogeneity test Summery OR (95% CI) Hypothesis test   Begg's test Egger's test
Q P Z P df Z P t P
All studies 7833/10353 123.12 <0.00001 1.46 (1.32–1.61) 7.40 <0.00001 52 1.53 0.127 1.79 0.079
Stratification by source of control                      
Healthy subjects 6459/8420 108.7 <0.00001 1.48 (1.32–1.66) 6.56 <0.00001 41 1.82 0.069 1.94 0.059
Hospitalized patients 1735/1933 14.88 0.31 1.40 (1.22–1.60) 4.77 <0.00001 13 0.07 0.945 0.67 0.517
Stratification by smoking status                      
Yes 2284/2078 22.38 0.44 1.60 (1.41–1.81) 7.48 <0.00001 22 0.05 0.958 0.50 0.620
No 1468/2260 26.58 0.11 1.79 (1.54–2.08) 7.58 <0.00001 19 1.27 0.205 1.39 0.180
Stratification by histological Type                      
Squamous cell carcinoma 1218/3375 15.96 0.25 1.50 (1.31–1.72) 5.89 <0.00001 13 0.00 1.000 0.40 0.694
Adenocarcinoma 1150/3368 28.44 0.008 1.36 (1.08–1.70) 2.66 0.008 13 0.99 0.324 0.79 0.443
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Figure 2. Forest plot of odds ratio for GSTM1 deletion polymorphism associated with lung cancer risk in Chinese population.

Figure 2

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Bias diagnosis

Funnel plot was used to assess the publication bias, the shape of funnel plot seemed to be approximately symmetrical (Fig. 3). Results from Egger's test and Begg's test indicated that no obvious publication bias existed in this meta-analysis (Table 2).

Figure 3. Funnel plot analysis to detect publication bias for GSTM1 deletion polymorphism associated with lung cancer risk in Chinese population.

Figure 3

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Sensitivity analysis

The sensitivity analysis was performed to determine the influence of the individual dataset on the summary ORs by consecutively excluding individual studies. The overall effects were not changed significantly when the study was homogenous for GSTM1 null genotype vs. present genotype among total population by removing some eligible studies, indicating that our results were statistically robust (Fig. 4).

Figure 4. Sensitivity analysis for GSTM1 null genotype vs. present genotype in Chinese population.

Figure 4

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Discussion

GSTM1 gene is located on the short arm of chromosome 1 (1p13.3)65. It is 5,950 bp long consisting of seven introns and eight exons, which encodes a cytosolic protein of 218 amino acid residues with a molecular weight of 21/25 kDa. GSTM1 gene has a null variant allele, which results in an absence of enzyme activity. Individuals who carry homozygous deletions in this gene are thought to be increased risks for malignancies because of their reduced capacity to detoxify potential carcinogens66,67. In addition, GSTM1 null/present polymorphisms could predict the treatment response of the platinum-based chemotherapy in NSCLC patients, especially in East-Asian patients68. Some meta-analyses explored the association of GSTM1 null genotype with the development of several kinds of cancers in Chinese population69,70,71,72. In this paper, we performed a systematic literature review to comprehensively evaluate the association of GSTM1 deletion polymorphism with lung cancer risk in Chinese population. We also evaluated the possible effect modifications by source of control, smoking status and histological subtype. The frequency of GSTM1 null genotype was 57.7% (range: 34%~76.7%) and 50.1% (range: 14%~66.4%) in case and control, respectively. The highest frequency of GSTM1 null genotype (66.4%) in control was found in Beijing38 and the lowest frequency of GSTM1 null genotype (14%) in control was found in Yunnan55. In summary, we observed an increased lung cancer risk in subjects with GSTM1 null genotype. Two previous meta-analyses have reported the association of GSTM1 deletion polymorphism with increased lung cancer risk in Chinese population60,61. However, there are some key limitations in their studies. For example, three overlapping studies73,74,75 were not properly excluded from Shi et al' study and seven papers published before 200613,16,41,42,43,54,56 were missing. For Liu et al' paper, eighteen overlapping papers74,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92 were not properly excluded. Therefore, the findings from these two meta-analyses should be clarified urgently by using the updated data. The present meta-analysis of 53 published studies including 7,833 cases and 10,353 controls might present a precise estimation of the association of GSTM1 deletion polymorphism with lung cancer risk in Chinese population, owing to including the updated data.

Considering that cigarette smoking is an evident risk factor for lung cancer, and that GSTM1 is involved in the metabolism of various carcinogens present in cigarette smoking, a subgroup analysis regarding smoking status was conducted. After being stratified by smoking status, the GSTM1 null genotype was associated with an increased risk of lung cancer in both smokers and nonsmokers.

Lung cancer consists of at least three major histological subtypes: squamous cell carcinoma, adenocarcinoma and small cell carcinoma. It is well-known that the development of squamous cell carcinoma and small cell carcinoma is strongly correlated with cigarette smoking, whereas that of adenocarcinoma is less correlated compared with those two subtypes, which indicates that carcinogenic processes are different among the different subtypes of lung cancer93. Therefore, a stratified analysis was conducted by histological subtype. We observed significant associations of GSTM1 deletion polymorphism with the increased risk of both squamous cell carcinoma and adenocarcinoma. Further stratified analyses were not done in additional histological subtypes, since the sample size for them was relatively small.

This meta-analysis should be interpreted within the context of its potential limitations. First, the combined ORs were based on individual unadjusted estimates, while a more precise analysis depending on adjusted factors should be performed if detailed individual data were available. Secondly, only published papers were enrolled in this study, which may cause publication bias. To address this issue, Egger's test and Begg's test were conducted at the same time. Our findings demonstrated that the likelihood of key publication bias might not be present in this meta-analysis. Thirdly, each study had different eligibility criteria for subjects and different source of controls, which should be taken into account while expounding the combined effects. When subgroup analysis was performed by source of control, we observed an association between GSTM1 deletion polymorphism and increased lung cancer risk in both healthy subjects-based control and hospitalized patients-based control.

In conclusion, this comprehensive review demonstrates that GSTM1 null genotype might be a risk factor for lung cancer in the Chinese population. Large scale studies with the pooling of individual study data should be taken into consideration in the future studies to verify the results from this present meta-analysis.

Author Contributions

Conceived and designed the experiments: W.Y. and Y.H.; Performed the experiments: Y.S., S.F. and W.H.; Analyzed the data: Y.H. and L.J.; Contributed reagents/material/analysis tools: Y.S., S.F. and W.H.; Wrote the main manuscript text: W.Y. and Y.H.; Reference collection and data management: L.J. and Y.S.; Statistical analyses and paper writing: Y.H. and W.Y.; Study design: W.Y. and Y.H.; Prepared figures 1–4: W.H.; All authors reviewed the manuscript.

References

  1. Jemal A. et al. Global cancer statistics. CA Cancer J Clin 61, 69–90 (2011). [DOI] [PubMed] [Google Scholar]
  2. Nielsen L. S. et al. Occupational asbestos exposure and lung cancer--a systematic review of the literature. Arch Environ Occup Health 69, 191–206 (2014). [DOI] [PubMed] [Google Scholar]
  3. Luqman M. et al. Risk factors for lung cancer in the Pakistani population. Asian Pac J Cancer Prev 15, 3035–3039 (2014). [DOI] [PubMed] [Google Scholar]
  4. Wang Y. D., Yang H. Y., Liu J. & Wang H. Y. Updated Meta-analysis of the Association Between CYP2E1 RsaI/PstI Polymorphisms and Lung Cancer Risk in Chinese Population. Asian Pac J Cancer Prev 15, 5411–5416 (2014). [DOI] [PubMed] [Google Scholar]
  5. Hayes J. D. & Pulford D. J. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30, 445–600 (1995). [DOI] [PubMed] [Google Scholar]
  6. Phukan R. K. et al. Role of household exposure, dietary habits and glutathione S-Transferases M1, T1 polymorphisms in susceptibility to lung cancer among women in Mizoram India. Asian Pac J Cancer Prev 15, 3253–3260 (2014). [DOI] [PubMed] [Google Scholar]
  7. Ai C. Discuss the influence of GSTM1 gene polymorphism on lung cancer. Contemporary Medicine 17, 50 (2011). [Google Scholar]
  8. Chan E. C., Lam S. Y., Fu K. H. & Kwong Y. L. Polymorphisms of the GSTM1, GSTP1, MPO, XRCC1, and NQO1 genes in Chinese patients with non-small cell lung cancers: relationship with aberrant promoter methylation of the CDKN2A and RARB genes. Cancer Genet Cytogenet 162, 10–20 (2005). [DOI] [PubMed] [Google Scholar]
  9. Chan-Yeung M. et al. Lung cancer susceptibility and polymorphisms of glutathione-S-transferase genes in Hong Kong. Lung Cancer 45, 155–160 (2004). [DOI] [PubMed] [Google Scholar]
  10. Chen C. M. et al. Effects of CYP1A1 and GSTM1 gene polymorphisms and BPDE-DNA adducts on lung cancer. Chin J of Med Genet 29, 23–27 (2012). [DOI] [PubMed] [Google Scholar]
  11. Chen H. et al. Influence of genetic polymorphism of CYP1A1 gene and GSTM 1 gene on lung cancer. Shandong Medical Journal 48, 20–22 (2008). [Google Scholar]
  12. Chen H. C. et al. Genetic polymorphisms of phase II metabolic enzymes and lung cancer susceptibility in a population of Central South China. Dis Markers 22, 141–152 (2006). [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chen L. J., Sun H. L. & Xu Y. Q. Study on the allele frequency of GSTM1 gene in normal Han population in Wannan area and the relationship between GSTM1 genotype and the risk of lung cancer. Acta Academiae Medicinae Wannan 22, 13–16 (2003). [Google Scholar]
  14. Chen S., Xue K., Xu L., Ma G. & Wu J. Polymorphisms of the CYP1A1 and GSTM1 genes in relation to individual susceptibility to lung carcinoma in Chinese population. Mutat Res 458, 41–47 (2001). [DOI] [PubMed] [Google Scholar]
  15. Cheng Y. W. et al. DNA adduct level in lung tissue may act as a risk biomarker of lung cancer. Eur J Cancer 36, 1381–1388 (2000). [DOI] [PubMed] [Google Scholar]
  16. Dong C. T., Yang Q., Wang M. Z. & Dong Q. N. A Study on the Relationship between Polymorphism of CYP1A1, Lack of GSTM1 and Susceptibility to Lung Cancer. J Environ Occup Med 21, 440–442 (2004). [Google Scholar]
  17. Du G. B. et al. Relationship between genetic polymorphism of GSTM1 gene and susceptibility to lung cancer in the population of northern Sichuan of China. Chinese Clinical Oncology 16, 602–605 (2011). [Google Scholar]
  18. Fowke J. H. et al. Urinary isothiocyanate levels and lung cancer risk among non-smoking women: a prospective investigation. Lung Cancer 73, 18–24 (2011). [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gao Y. & Zhang Q. Polymorphisms of the GSTM1 and CYP2D6 genes associated with susceptibility to lung cancer in Chinese. Mutat Res 444, 441–449 (1999). [DOI] [PubMed] [Google Scholar]
  20. Ge H. et al. Analysis of L-myc and GSTM1 genotypes in Chinese non-small cell lung carcinoma patients. Lung Cancer 15, 355–366 (1996). [DOI] [PubMed] [Google Scholar]
  21. Gu Y. F. et al. Combined effects of genetic polymorphisms in cytochrome P450s and GSTM1 on lung cancer susceptibility. Natl Med J of China 87, 3064–3068 (2007). [PubMed] [Google Scholar]
  22. Huang X. H., Chen S. D., Wang B. G., Zhou W. P. & Cai X. L. Study on the Impact of GSTM1 Polymorphisms on the Risk of Histological Types of Lung Cancer: A Case-Control study. J of Pub Health and Prev Med 15, 24–26 (2004). [Google Scholar]
  23. Jiang X. Y., Chang F. H., Bai T. Y., Lv X. L. & Wang M. J. Susceptibility of Lung Cancer with Polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 Genotypes in the Population of Inner Mongolia Region. Asian Pac J Cancer Prev 15, 5207–5214 (2014). [DOI] [PubMed] [Google Scholar]
  24. Lan Q. & He X. Molecular epidemiological studies on the relationship between indoor coal burning and lung cancer in Xuan Wei, China. Toxicology 198, 301–305 (2004). [DOI] [PubMed] [Google Scholar]
  25. Lei M. F. et al. A case-control study of the impact of glutathione S-transferase M1 polymorphism on the risk of lung cancer. Modern Preventive Medicine 34, 724–726 (2007). [Google Scholar]
  26. Li D. R. et al. Study on the association between genetic polymorphism of CYP2E1, GSTM1 and susceptibility of lung cancer. Chin J of Lung Cancer 8, 14–19 (2005). [DOI] [PubMed] [Google Scholar]
  27. Li W. et al. Polymorphisms in GSTM1, CYP1A1, CYP2E1, and CYP2D6 are associated with susceptibility and chemotherapy response in non-small-cell lung cancer patients. Lung 190, 91–98 (2012). [DOI] [PubMed] [Google Scholar]
  28. Li Y. et al. CYP1A1 and GSTM1 polymorphisms and susceptibility to lung cancer. Journal of Zhengzhou University (Medical Sciences) 41, 1061–1064 (2006). [Google Scholar]
  29. Liang G. Y., Pu Y. P. & Yin L. H. Studies of the genes related to lung cancer susceptibility in Nanjing Han population, China. Hereditas 26, 584–588 (2004). [PubMed] [Google Scholar]
  30. Liang K. C. et al. Correlational research of the relationship between the genetic polymorphism of GSTM1 and GSTT1 in the Zhuang population and lung cancer. Acta Medicinae Sinica 25, 813–817 (2012). [Google Scholar]
  31. Liu D. et al. Association of glutathione S-transferase M1 polymorphisms and lung cancer risk in a Chinese population. Clin Chim Acta 414, 188–190 (2012). [DOI] [PubMed] [Google Scholar]
  32. Liu Q., Liu J., Song B. & Wang Z. H. Relationship between susceptibility to lung cancer and genetic polymorphism in CYP1A1 and GSTM1. Shandong Medical Journal 48, 32–34 (2008). [Google Scholar]
  33. London S. J. et al. Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms, and lung-cancer risk: a prospective study of men in Shanghai, China. Lancet 356, 724–729 (2000). [DOI] [PubMed] [Google Scholar]
  34. Lu Q. K. The correlation of GSTM1 polymorphism with lung cancer risk. Capital Medicine 24, 25–27 (2013). [Google Scholar]
  35. Luo C. L., Chen Q., Cao W. F. & Chen S. D. Combined Analysis of Polymorphisms of GSTM1 and Mutations of p53 Gene in the Patients with Lung Cancer. Chin J Clin Oncol 31, 22–24 (2004). [Google Scholar]
  36. Lv W. et al. Genetic polymorphism in myeloperoxidase but not GSTM1 is associated with risk of lung squamous cell carcinoma in a Chinese population. Int J Cancer 102, 275–279 (2002). [DOI] [PubMed] [Google Scholar]
  37. Pan C., Zhu G., Yan Z., Zhou Y. & Liu Z. Glutathione S-transferase T1 and M1 polymorphisms are associated with lung cancer risk in a gender-specific manner. Oncol Res Treat 37, 164–169 (2014). [DOI] [PubMed] [Google Scholar]
  38. Persson I. et al. Genetic polymorphism of xenobiotic metabolizing enzymes among Chinese lung cancer patients. Int J Cancer 81, 325–329 (1999). [DOI] [PubMed] [Google Scholar]
  39. Qian B. Y. et al. Case-Control Study Genetic Polymorphism in CYP1A1 and GSTM1 and Smoking and Susceptibility to Lung Cancer. Chin J Clin Oncol 33, 500–502 (2006). [Google Scholar]
  40. Chan Y., Wang X., Wang X. Y. & Liang Z. Q. A study of genetic polymorphism of GSTM1 gene in normal population and lung cancer population in Yunnan. Journal of Yunnan Normal University 22, 13–16 (2002). [Google Scholar]
  41. Qiao G. B., Sun C. S., Li L. S., Zeng W. S. & Jiang R. C. A case-control study on relationship between absence of GSTM1 gene, smoking and susceptibility to non-small cell lung cancer. J Fourth Mil Med Univ 26, 1008–1010 (2005). [Google Scholar]
  42. Qu Y. H. et al. The genotypes of cytochrome P450 1A1 and GSTM1 in non-smoking female cancer. Tumor 18, 20–22 (1998). [Google Scholar]
  43. Shi Y., Zhou X. W., Zhou Y. K. & Ren X. Analysis of CYP2E1, GSTM1 Genetic Polymorphisms in Relation to Human Lung Cancer and Esophageal Carcinoma. J Huazhong Univ Sci Tech [Health Sci] 31, 14–17 (2002). [Google Scholar]
  44. Sun G. F., Shimojo N., Pi J. B., Lee S. & Kumagai Y. Gene deficiency of glutathione S-transferase mu isoform associated with susceptibility to lung cancer in a Chinese population. Cancer Lett 113, 169–172 (1997). [DOI] [PubMed] [Google Scholar]
  45. Wang J. et al. Association of GSTM1, CYP1A1 and CYP2E1 genetic polymorphisms with susceptibility to lung adenocarcinoma: a case-control study in Chinese population. Cancer Sci 94, 448–452 (2003). [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wang M. J., Chang F. H., Yin Q., Qi J. & Wang G. Relationship of GSTM1 polymorphism and lung cancer susceptibility in Mongolian population. Chin J Public Health 25, 1447–1448 (2009). [Google Scholar]
  47. Wang N., Wu Y. & Zhou X. Association between genetic polymorphism of metabolizing enzymes and DNA repairing enzymes and the susceptibility of lung cancer in Henan population. Journal of Hygiene Research 41, 251–256 (2012). [PubMed] [Google Scholar]
  48. Wang Q. M., Lu Q. F., Zhen H. N., Bao M. & Zhang H. J. Relationship between CYP2C9 and GST M1 Genetic Polymorphism and Lung Cancer Susceptibility. Cancer Res Prev Treat 33, 8–10 (2006). [Google Scholar]
  49. Xia Y. et al. Polymorphisms of the cytochrome P450 and glutathione s-transferase genes associated with lung cancer susceptibility for the residents in high radon-exposed area. Chin J of Radio Med and Prot 28, 327–332 (2008). [Google Scholar]
  50. Yang X. R. et al. CYP1A1 and GSTM1 polymorphisms in relation to lung cancer risk in Chinese women. Cancer Lett 214, 197–204 (2004). [DOI] [PubMed] [Google Scholar]
  51. Yao W., Wang N., Wu Y. J. & Wu Y. M. Relationship between deletion of GSTM1, GSTT1 genes and susceptibility to lung cancer. Chin J Public Health 22, 1070–1072 (2006). [Google Scholar]
  52. Yao Z. G., E Y. & Wang H. Y. The Interacted Effects between Glutathione S-Transferase Gene Polymorphism and Smoking in Lung Cancer. Chinese Journal of Medicinal Guide 14, 185–186 (2012). [Google Scholar]
  53. Zhang H. Y. et al. Genetic Polymorphisms of Glutathione S-transferase M1 and T1 and Evaluation of Oxidative Stress in Patients with Non-small Cell Lung Cancer. Journal of China Medical University 43, 432–436 (2014). [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Zhang J. K., Hu Y. L., Hu C. F. & Wang S. Y. Relationship between genetic polymorphisms of GSTM1 as well as GSTT1 and lung cancer. Chinese Journal of Pathophysiology 18, 17–20 (2002). [Google Scholar]
  55. Zhang J. Q. et al. The Relationship between Glutathione S-transferase M1 and Susceptibility to Xuanwei's Lung Cancer. Journal of Kunming Medical University 32, 56–58 (2011). [Google Scholar]
  56. Zhang L. Z., Wang S., Hao X. Z., Shi Y. X. & Liu Z. H. Relationship between Susceptibility to Lung Cancer and Genetic Polymorphism in P4501A1, GSTM1. Chin J Clin Oncol 29, 8–12 (2002). [Google Scholar]
  57. Zhao B. et al. Dietary isothiocyanates, glutathione S-transferase -M1, -T1 polymorphisms and lung cancer risk among Chinese women in Singapore. Cancer Epidemiol Biomarkers Prev 10, 1063–1067 (2001). [PubMed] [Google Scholar]
  58. Zheng D., Hua F., Mei C., Wan H. & Zhou Q. Association between GSTM1 genetic polymorphism and lung cancer risk by SYBR green I real-time PCR assay. Chin J of Lung Cancer 13, 506–510 (2010). [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Zhu X. X., Hu C. P. & Gu Q. H. CYP1A1 polymorphisms, lack of glutathione S-transferase M1 (GSTM1), cooking oil fumes and lung cancer risk in non-smoking women. Chin J Tuberc Respir Dis 33, 817–822 (2011). [PubMed] [Google Scholar]
  60. Liu K. et al. The Associations between Two Vital GSTs Genetic Polymorphisms and Lung Cancer Risk in the Chinese Population: Evidence from 71 Studies. PLoS One 9, e102372 (2014). [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Shi X., Zhou S., Wang Z. & Zhou Z. CYP1A1 and GSTM1 polymorphisms and lung cancer risk in Chinese populations: a meta-analysis. Lung Cancer 59, 155–163 (2008). [DOI] [PubMed] [Google Scholar]
  62. DerSimonian R. & Laird N. Meta-analysis in clinical trials. Control Clin Trials 7, 177–188 (1986). [DOI] [PubMed] [Google Scholar]
  63. Egger M., Davey Smith G., Schneider M. & Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj 315, 629–634 (1997). [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Begg C. B. & Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 50, 1088–1101 (1994). [PubMed] [Google Scholar]
  65. Pearson W. R. et al. Identification of class-mu glutathione transferase genes GSTM1-GSTM5 on human chromosome 1p13. Am J Hum Genet 53, 220–233 (1993). [PMC free article] [PubMed] [Google Scholar]
  66. McIlwain C. C., Townsend D. M. & Tew K. D. Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene 25, 1639–1648 (2006). [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Hu Z. H. et al. Genetic polymorphisms of glutathione S-transferase M1 and prostate cancer risk in Asians: a meta-analysis of 18 studies. Asian Pac J Cancer Prev 14, 393–398 (2013). [DOI] [PubMed] [Google Scholar]
  68. Yang Y. & Xian L. The association between the GSTP1 A313G and GSTM1 null/present polymorphisms and the treatment response of the platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients: a meta-analysis. Tumour Biol 35, 6791–6799 (2014). [DOI] [PubMed] [Google Scholar]
  69. Wang D., Zhang L. M., Zhai J. X. & Liu D. W. GSTM1 and GSTT1 polymorphisms and colorectal cancer risk in Chinese population: a meta-analysis. Int J Colorectal Dis 27, 901–909 (2012). [DOI] [PubMed] [Google Scholar]
  70. Meng X., Liu Y. & Liu B. Glutathione S-transferase M1 null genotype meta-analysis on gastric cancer risk. Diagn Pathol 9, 122 (2014). [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Peng J., Liu H. Z. & Zhu Y. J. Null Glutathione S-transferase T1 and M1 genotypes and oral cancer susceptibility in China and India--a meta-analysis. Asian Pac J Cancer Prev 15, 287–290 (2014). [DOI] [PubMed] [Google Scholar]
  72. Teng Z., Wang L., Zhang J., Cai S. & Liu Y. Glutathione S-transferase M1 polymorphism and colorectal cancer risk in Chinese population. Tumour Biol 35, 2117–2121 (2014). [DOI] [PubMed] [Google Scholar]
  73. Gao J. R., Ren C. L. & Zhang Q. CYP2D6 and GSTM1 genetic polymorphism and lung cancer susceptibility. Chin J Oncol 20, 185–186 (1998). [PubMed] [Google Scholar]
  74. Ye W. Y., Chen S. D. & Chen Q. Interaction between serum selenium level and polymorphism of GSTM1 in lung cancer. Acta Nutrimenta Sinica 27, 17–20 (2005). [Google Scholar]
  75. Zeng M. et al. Case control study on relationship between lung cancer and its susceptibility marker. Chin J Public Health 21, 771–774 (2005). [Google Scholar]
  76. Cao Y. F. et al. Study on the relationship between the genetic polymorphisms of GSTM1 and GSTT1 genes and lung cancer susceptibility in the population of Hunan province of China. Life Science Research 8, 126–132 (2004). [Google Scholar]
  77. Chen S. D. et al. A case control study on the impact of CYP2E1 and GST-M1 polymorphisms on the risk of lung cancer. Tumour 24, 99–103 (2004). [PubMed] [Google Scholar]
  78. Li Y., Chen J., He X. & Gao Y. X. Influence of smoking and the polymorphisms of CYP1A1 and GSTM1 on the susceptibility of lung cancer. Journal of Chinese Practical Diagnosis and Therapy 25, 140–143 (2011). [Google Scholar]
  79. Zhang J. K., Hu Y. L., Hu C. F. & Wang S. Y. Study on Genetic Polymorphisms or GSTM 1 and GSTT1 Related with Inherenl Susceptibility to Lung Cancer in Women. China Public Health 18, 273–275 (2002). [Google Scholar]
  80. Chang F. H., Hu T. M. & Wang G. Relationship between CYP1A1 and GSTM1 genetic polymorphisms and lung cancer susceptibility in population of Inner Mongolia. Chin J of Lung Cancer 9, 413–417 (2006). [DOI] [PubMed] [Google Scholar]
  81. Cheng Y. W. et al. Gender difference in DNA adduct levels among nonsmoking lung cancer patients. Environ Mol Mutagen 37, 304–310 (2001). [DOI] [PubMed] [Google Scholar]
  82. Gao J. R. & Zhang Q. Study on the relationship between GSTM1 polymorphism and lung cancer susceptibility. Carcinogenesis, Teratogenesis and Mutagenesis 10, 149–151 (1998). [Google Scholar]
  83. Gu Y. F., Zhang S. C., Lai B. T., Wang H. & Zhan X. P. Relationship between genetic polymorphism of metabolizing enzymes and lung cancer susceptibility. Chin J of Lung Cancer 7, 112–117 (2004). [DOI] [PubMed] [Google Scholar]
  84. Han R. L. et al. GSTM1 gene polymorphism and lung cancer susceptibility in man population. Central South Pharmacy 10, 1–4 (2012). [Google Scholar]
  85. Jin Y. et al. Combined effects of cigarette smoking, gene polymorphisms and methylations of tumor suppressor genes on non small cell lung cancer: a hospital-based case-control study in China. BMC Cancer 10, 422 (2010). [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Lan Q., He X., Costa D. & Tian W. Glutathione S-transferase GSTM1 and GSTT1 genotypes and susceptibility to lung cancer. Journal of Hygiene Research 28, 9–11 (1999). [PubMed] [Google Scholar]
  87. Qi X. S. et al. A primary case-control study on the relationship between genetic polymorphisms of GSTT1 and lung cancer susceptibility to the people living in high radon-exposed area. Chin Occup Med 35, 361–363 (2008). [Google Scholar]
  88. Sun G. F., Pi J. B., Zheng Q. M. & Zheng M. Z. The study of GST μ gene deletion as the hereditary marker for susceptibility to lung cancer. Chin J Tuberc Respir Dis 18, 167–169 (1995). [PubMed] [Google Scholar]
  89. Wang J., Deng Y., Cheng J., Ding J. & Tokudome S. GST genetic polymorphisms and lung adenocarcinoma susceptibility in a Chinese population. Cancer Lett 201, 185–193 (2003). [DOI] [PubMed] [Google Scholar]
  90. Wang Y. S. et al. Study on the methylation of p16 gene and genetic polymorphism of GSTM1 gene related with susceptibility to non-small cell lung cancer. Modern Preventive Medicine 34, 1207–1209 (2007). [Google Scholar]
  91. Ye W. Y., Chen Q. & Chen S. D. Study on relationship between GSTM1 polymorphism, diet factors and lung cancer. Chin J Public Health 20, 1120–1121 (2004). [Google Scholar]
  92. Li W. Y., Lai B. T. & Zhan X. P. Polymorphism of metabolic enzyme genes associated with lung cancer susceptibility. Tuberculosis and Thoracic Tumor 4, 280–286 (2003). [Google Scholar]
  93. Sunaga N. et al. Contribution of the NQO1 and GSTT1 polymorphisms to lung adenocarcinoma susceptibility. Cancer Epidemiol Biomarkers Prev 11, 730–738 (2002). [PubMed] [Google Scholar]

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