Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Null Genotypes of GSTM1 and GSTT1 Contribute to Risk of Cervical Neoplasia: An Evidence-Based Meta-Analysis

  • Lin-Bo Gao ,

    Contributed equally to this work with: Lin-Bo Gao, Xin-Min Pan

    Affiliation Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China

  • Xin-Min Pan ,

    Contributed equally to this work with: Lin-Bo Gao, Xin-Min Pan

    Affiliations Department of Forensic Pathology, Henan University of Science and Technology, Luoyang, Henan, People's Republic of China, Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China

  • Li-Juan Li,

    Affiliation Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China

  • Wei-Bo Liang,

    Affiliation Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China

  • Peng Bai,

    Affiliation Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China

  • Li Rao,

    Affiliation Department of Cardiology, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China

  • Xiao-Wei Su,

    Affiliation Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China

  • Tao Wang,

    Affiliation Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China

  • Bin Zhou,

    Affiliation Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China

  • Yong-Gang Wei,

    Affiliation Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China

  • Lin Zhang

    zhanglin@scu.edu.cn

    Affiliation Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China

Null Genotypes of GSTM1 and GSTT1 Contribute to Risk of Cervical Neoplasia: An Evidence-Based Meta-Analysis

  • Lin-Bo Gao, 
  • Xin-Min Pan, 
  • Li-Juan Li, 
  • Wei-Bo Liang, 
  • Peng Bai, 
  • Li Rao, 
  • Xiao-Wei Su, 
  • Tao Wang, 
  • Bin Zhou, 
  • Yong-Gang Wei
PLOS
x

Abstract

Background and Objectives

Glutathione S-transferases (GSTs) are multifunctional enzymes that play a key role in the detoxification of varieties of both endogenous products of oxidative stress and exogenous carcinogens.

Methods

In this meta-analysis, twenty-five studies were identified by searching PubMed, EMBASE, ISI Web of Science and CBM databases: 23 evaluated GSTM1 and 19 evaluated GSTT1. Crude odds ratios with corresponding 95% confidence intervals were used to estimate the association between GSTM1 and GSTT1 polymorphisms and risk of cervical neoplasia. Subgroup analyses were conducted by pathological history, ethnicity, source of DNA for genotyping, quality score, and matching variable.

Results

The null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk of cervical neoplasia (for GSTM1: OR = 1.40; 95%CI, 1.19–1.65; for GSTT1: OR = 1.30; 95%CI, 1.05–1.62, respectively). Subgroup analyses showed that the null genotype of GSTM1 increased the risk of cervical neoplasia in Asians, studies with DNA isolation from white blood cells and tissue samples, both high and low quality studies, and matched studies. In GSTM1-GSTT1 interaction analysis, individuals with dual null genotype were associated with a significantly increased risk of cervical neoplasia (OR = 1.72; 95%CI, 1.18–2.51).

Conclusion

These findings indicate that GSTM1 and GSTT1 polymorphisms, particularly GSTM1-GSTT1 interaction, may play critical roles in the development of cervical neoplasia. A conservative manner should be adopted to interpret these results because of obvious heterogeneity between-study, unadjusted data, and relatively small sample size in this meta-analysis. Well designed studies with larger sample size are of great value to confirm these results.

Introduction

Cervical cancer is the second most frequent cancer among women worldwide, with approximately 493,000 new cases diagnosed and 274,000 deaths occurring each year (2002 estimates) [1]. Despite substantial declines in the incidence and mortality of cervical cancer in developed countries, more than 80% of all cervical cancer occurs in developing countries [1], [2]. The burden of cervical cancer is not only the high incidence rates in women in some developing countries, but also the societal impact because a fraction of patients who suffered from the disease in their 30's or 40's are still raising or supporting families.

It is well established that human papilloma virus (HPV) infection is a necessary but insufficient event for the development of cervical cancer [3][6], because not all HPV-infected patients do develop cervical cancer. Therefore, many research efforts were taken to identify cofactors for cervical cancer development. To date, the major risk cofactors have been confirmed by large meta-analysis, including smoking, multiple sexual partners, increasing parity, earlier age at first intercourse (≤20 years), and long duration of oral contraceptive use [7][9]. However, it is currently accepted that the development of cervical cancer is the result of complex interaction of both environmental and genetic factors [10]. Epidemiological evidence has shown that there is a significant familial clustering among biological relatives. The familial relative risk for individuals with biological full-sisters of cervical cancer cases is almost twice as high as those with biological full-sisters of controls [11][13]. Recently, several meta-analysis studies revealed that a polymorphic variant of the tumor suppressor P53 (Pro72Arg) may represent a genetic marker for cervical carcinogenesis [14][17].

Over the past decades, glutathione S-transferases (GSTs) genetic variants have been explored extensively as a predictive factor for cancer prognosis [18]. GSTs are a family of enzymes with a crucial function in the detoxification of a variety of both endogenous products of oxidative stress and exogenous carcinogens [19], [20]. In humans, GST super-family consists of many cytosolic, mitochondrial, and microsomal proteins. The cytosolic family has been assigned to eight distinct classes: alpha, kappa, mu, omega, pi, sigma, theta, and zeta [21]. The mu class of GSTs, encoded by the GSTM1 gene, is located on the short arm of chromosome 1 (1p13.3) [22]. The theta class of GSTs, encoded by the GSTT1 gene, is locate on the long arm of chromosome 22 (22q11.23) [23]. Both GSTM1 and GSTT1 gene exhibit an inherited homozygous deletion polymorphism (null genotype) that is associated with an absence of enzyme activity. Individuals with homozygous deletion polymorphism are considered to be at increased risk for malignancies due to reduced efficiency in protection against environmental carcinogens [18], [24].

In 1994, Warwick et al. explored for the first time the association between GSTM1 and GSTT1 polymorphisms and the risk of cervical neoplasia, and found that the combination of three factors (i.e., GSTM1 or GSTT1 null, CYP2D6 EM, and smoking) appeared significantly different frequency in cases and controls [25], [26]. Subsequently, a large number of epidemiological studies have been addressed to evaluate the association between GSTM1 and GSTT1 homozygous deletion polymorphisms and risk of cervical neoplasia in diverse ethnicities [25][49]. However, this issue remains controversial because of inconsistent results among different studies. The possibilities for this discrepancy may be that some positive results might occur by chance and some negative findings might be caused by insufficient statistical power with small sample size. Additionally, different experimental design and selection bias should also be considered.

In order to provide strong evidence of the effects of GSTM1 and GSTT1 polymorphisms on cervical neoplasia risk, we carried out a quantitative meta-analysis by combining data from all published case-control studies. Additionally, gene-gene and gene-environment interactions have also been examined in this meta-analysis.

Materials and Methods

Selection of Published Studies

We identified all publications by conducting computer-based searches of PubMed, EMBASE, ISI Web of Science, and CBM databases without language restrictions, using the following search algorithm: (“cervical cancer” or “cervical carcinoma” or “uterine cervix cancer” or “CC” or “cervical neoplasia”) and (“glutathione S-transferase” or “GST” or “GSTM” or “GSTM1” or “GSTT” or “GSTT1”) and (“polymorphism” or “polymorphisms” or “variant”). The literature search was performed up to Aug 2010. The inclusion criteria were: (a) case-control studies that investigated the association between GSTM1 and/or GSTT1 polymorphism and risk of cervical neoplasia; (b) presenting original data for the calculation of odds ratios (ORs) with corresponding 95% confidence intervals (95%CIs).

One hundred and fifty-four articles were identified by searching PubMed, EMBASE, ISI Web of Science and CBM databases. Eighty-four studies were excluded after screening the title or abstract (67 were not cervical cancer; eight were no polymorphism; six were not human studies; three were not case-control studies). Then full-text articles were retrieved for assessment in detail. Forty-three were excluded with reasons for not cervical cancer (n = 23), no GSTM1 and/or GSTT1 polymorphism (n = 13), no available data (n = 5) and review articles (n = 2). Additionally, we excluded two studies because the results were duplicated in subsequent publications [50], [51]. Finally, a total of 25 studies were included in this meta-analysis (Figure S1). Of the 25 studies, 23 studies investigated the association between GSTM1 polymorphism and risk of cervical neoplasia and 19 studies investigated the association between GSTT1 polymorphism and risk of cervical neoplasia.

The groups of pathologic type were set according to the report by Klug et al. [17]. Briefly, the selected studies in this analysis were composed of unclear type of cervical cancer, squamous cell carcinoma (SCC), adenocarcinoma (AC), adenosquamous carcinoma, high-grade lesions (HGL, containing high-grade squamous intraepithelial lesions and cervical intraepithelial lesions grades 2 and 3) and low-grade lesions (LGL, containing low-grade squamous intraepithelial lesions and cervical intraepithelial lesions grade 1).

This study was approved by the ethics committee of Sichuan University. The data included in this study was taken from literatures, and thus written consent given by the patients was not needed.

Data Extraction

Two independent researchers (Gao and Pan) extracted raw data according to the inclusion criteria. The following information was collected from each study using a data extraction form: the surname of the first author, date of publication, country of origin, year of sample collection, ethnicity, characteristics of cases and controls, DNA source for genotyping, matching variables, number of cases and controls, genotype distribution of cases and controls, and quality control for genotyping assay. Additionally, we extracted, if available, the genotype frequency of cases and controls based on age (>40 or ≤40 years), smoking status (smoking or non-smoking) and HPV infection status (HPV positive or HPV negative). Given that there was no distribution of null/present heterozygote in each single study selected, the Hardy-Weinberg equilibrium (HWE) test could not be conducted. To ensure the accuracy of data extraction, the original extraction information was checked by Li, and discordant results were settled through discussion among the three authors.

Quality Score Evaluation

Three investigators (Gao, Pan, and Li) independently assessed the quality of included studies based on a predetermined rating scale (Table S1) that was amended from previous studies [52][54]. Any discrepancies were resolved by consultation with the other authors in the team group, and an ultimate decision was made by the majority of the votes cast. A numerical score ranging from 0 to 12 was assigned as a quantitative measure of literature quality. Studies were categorized as “high quality” if the quality score was ≥7; otherwise, studies were categorized as “low quality”.

Statistical Analysis

We used crude ORs with corresponding 95% CIs as a measure of the association between GSTM1 and GSTT1 polymorphisms and risk of cervical neoplasia. Study-specific ORs comparing null genotype versus present genotype were combined using random-effects model (the DerSimonian and Laird) or fixed-effects model (the Mantel–Haenszel method), which was determined by the Q-test and I2 statistics [55], [56]. If the P value for heterogeneity was ≤0.10 or I2≥50%, indicating a high extent of heterogeneity between studies, we used the DerSimonian and Laird method to evaluate the summary ORs. In contrast, if the P value for heterogeneity was >0.10 and I2<50%, indicating an absence of heterogeneity between studies [57], [58], we used the Mantel–Haenszel method to evaluate the summary ORs.

Subgroup analyses were conducted by pathological history (squamous cell cervical carcinoma, adenocarcinoma and adenosquamous carcinoma, cervical cancer of unknown type, HGL, LGL, and mixed), ethnicity (Asian, Caucasian, and mixed), source of DNA for genotyping (white blood cells, exfoliated cervical cells, tissue sample, and mixed), quality score (high versus low), matching according to age (matched versus unmatched), smoking status (smoking versus non-smoking) and HPV infection status (HPV positive versus HPV negative). Additionally, we evaluated the effect of the GSTM1-GSTT1 interaction on cervical neoplasia compared with null/null versus present/present, null/null versus present/null, null/null versus null/present, null/present versus present/null, null/present versus present/present, and present/null versus present/present.

Logistic meta-regression was used to investigate possible sources of heterogeneity across studies. To determine the reliability of the outcomes in the meta-analysis, a sensitivity analysis was performed by exclusion an individual study each time. An evaluation of publication bias was carried out with funnel plot for visual inspection and Egger's regression asymmetry test [59]. All analyses were conducted in STATA software, version 10.0 (STATA Corp., College Station, TX).

Results

Characteristics of Studies

The baseline characteristics of the included studies are shown in Tables S2 and S3.

GSTM1 Polymorphism.

Totally, 23 studies met the inclusion criteria and were selected in this meta-analysis with 2,610 cases and 3,084 controls. Cases consisted of 32.5% patients with cervical cancer (histology not specified), 31.9% patients with SCC, 14.2% patients with HGL, 8.6% patients with LGL, 5.0% patients with SIL (unknown grade), 4.7% patients with both ICC and HGL and 3.0% patients with AC. Most of the controls (86.8%) were normal participants. There were sixteen studies of Asians, six studies of Caucasians, and two studies of mixed ethnicities that included more than one ethnicity. DNA used for GSTM1 genotyping was extracted from white blood cells in 15 studies (62.5%). 17 studies (70.8%) mentioned genotyping quality control methods, mainly using an internal control. However, only six studies (25.0%) reported smoking status and only four studies (16.7%) detected HPV infection status.

GSTT1 Polymorphism.

A total of 19 studies were included in the meta-analysis with 2,092 cases and 2,054 controls. Cases consisted of 27.1% patients with cervical cancer (histology not specified), 30.5% patients with SCC, 15.9% patients with HGL, 8.6% patients with LGL, 6.3% patients with SIL (unknown grade), 5.9% patients with both ICC and HGL and 5.8% patients with AC. Most of the controls (85.5%) were normal participants. Twelve studies were conducted in Asia; four in Europe; two in America and one in South America. Similar to GSTM1 polymorphism, most studies (68.4%) mentioned genotyping quality control methods, but only about 20% studies reported smoking status and HPV infection status.

Meta-analysis of GSTM1 Polymorphism and Cervical Neoplasia

The evaluations of the association between GSTM1 polymorphism and cervical neoplasia risk are summarized in Table S4.

The null genotype of GSTM1 polymorphism was associated with a significantly increased risk of cervical neoplasia when compared with present genotype (OR = 1.40; 95%CI, 1.19–1.65). When stratified by pathologic types, significantly elevated risks were observed in unknown type of cervical cancer (OR = 1.54; 95%CI, 1.16–2.04) and mixed group (OR = 1.98; 95%CI, 1.46–2.68) but not in groups of SCC, HGL, LGL and AC. In the subgroup analysis by ethnicity, significantly increased risks were observed in Asian population (OR = 1.60; 95%CI, 1.29–1.98) but not in Caucasian and mixed populations (Figure S2). Subgroup analysis on the basis of DNA source showed that the increased risks were found in studies that DNA was extracted from white blood cells (OR = 1.29; 95%CI, 1.08–1.55) or tissue sample (OR = 3.14; 95%CI, 1.90–5.19). No excess risk was found in studies that DNA was extracted from exfoliated cervical cells. Subgroup analysis was also performed according to quality criteria. The combined results showed that the null genotype was associated with an increased risk of cervical neoplasia in studies whether the quality score was high (OR = 1.31; 95%CI, 1.06–1.62) or low (OR = 1.49; 95%CI, 1.16–1.91). The increased risks were also found in studies in which controls were frequency matched to cases by age (OR = 1.54; 95%CI, 1.22–1.95), but not in studies in which controls were unmatched to cases by age. Additionally, subgroup analysis by age presented the results that the null genotype was associated with an increased risk of cervical neoplasia in studies with patients of age ≤40 years (OR = 2.02; 95%CI, 1.30–3.14).

Meta-analysis of GSTT1 Polymorphism and Cervical Neoplasia

The evaluations of the association of GSTT1 polymorphism and cervical neoplasia risk are listed in Table S5.

The null genotype of GSTT1 polymorphism was associated with a significantly increased risk of cervical neoplasia (OR = 1.30; 95%CI, 1.05–1.62) and unknown type of cervical cancer (OR = 1.49; 95%CI, 1.02–2.19), while the association was not observed in subgroup analyses according to ethnicity, DNA source, and quality criteria (Figure S3).

Meta-analysis of GSTM1-GSTT1 Interaction with Cervical Neoplasia

The evaluations of the association between GSTM1-GSTT1 interaction and cervical neoplasia risk are shown in Table S6.

The dual null genotype was associated with a significantly increased risk of cervical neoplasia when compared with the dual present genotype (OR = 1.72; 95%CI, 1.18–2.51) (Figure S4). No significantly increased risk was detected in any other comparison group.

Interaction between GSTM1 and GSTT1 and Environmental Exposure

There were six literatures which investigated the impact of interaction between GSTM1 polymorphism and smoking on cervical neoplasia, and there were four literatures which investigated the impact of interaction between GSTT1 polymorphism and smoking on cervical neoplasia. The effect of interaction between GSTM1 polymorphism and HPV infection status on cervical neoplasia was reported in four studies, and the effect of interaction between GSTT1 polymorphism and HPV infection status on cervical neoplasia was reported in five studies. No increased risks were found in the interaction between GSTM1 and GSTT1 polymorphisms and environmental exposure (i.e., smoking status and HPV infection status) (Tables S4 and S5).

Heterogeneity Analysis

The findings of Q-tests and I2 statistics were shown in Tables S4, S5, and S6. Significant heterogeneity across studies was present in overall analyses (for GSTM1, I2 = 53.3%; for GSTT1, I2 = 59.1%) and subgroup analyses. We explored several possible sources of the between-study heterogeneity, including cancer type, ethnicity, sample size, DNA source for genotyping and quality score. However, none of these variables could explain the heterogeneity.

Sensitivity Analysis and Publication Bias

To assess the effect of individual study on the overall meta-analysis estimate, we excluded one study at a time, and the exclusion of any single report did not alter the significance of the final decision, suggesting that the outcomes were robust. Funnel plot and Egger's test were used to assess publication bias of literatures on cervical neoplasia. No evidence of publication bias was observed in all comparison groups (P>0.05).

Discussion

The glutathiones S-transferases (GSTs) are the most important parts of phase II superfamily of metabolism enzymes. In humans, there are several GST classes that were encoded by distinct gene families [21]. Among them, GSTM1 and GSTT1 should be pointed out because a polymorphic deletion of these genes may influence the enzyme activity, and eventually increased vulnerability to genotoxic damage [60], [61]. Based on these backgrounds, the association has been intensively investigated between GSTM1 and GSTT1 polymorphisms and risk of cervical neoplasia [25][49]. Unfortunately, most of the studies have only a few hundred of participants, even less, which is too small to evaluate the overall effects precisely. Meta-analysis has been considered to be a powerful tool to overcome this problem by combining the results from independent studies together. In this meta-analysis, we found that the null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk of cervical neoplasia, suggesting that GSTM1 and GSTT1 polymorphisms may be involved in the development of cervical neoplasia. Notably, the between-study heterogeneity was observed in both overall analyses and some subgroup analyses, further studies therefore are warranted to confirm these findings.

After subgroup analysis according to ethnicity, significantly increased risks were observed in Asian population but not in Caucasian and mixed populations. The possibilities of the conflicting results among diverse ethnicities may be that the GSTM1 and GSTT1 polymorphisms have different effects on the risk of cervical neoplasia in different genetic backgrounds and environment which they exposed to. The major difference in the distribution of GSTM1 and GSTT1 polymorphisms has been reported among control groups in 2001. The frequency of GSTM1 null genotype was 53.1% (42.0–60.0%) in Caucasians, 52.9% (42.0–54.0%) in Asians, and 26.7% (16.0–36.0%) in Africans. The frequency of GSTT1 null genotype was 19.7% (13.0–26.0%) in Caucasians and 47.0% (35.0–52.0%) in Asians [62]. Additionally, the small sample size should also be taken into consideration because limited sample size may have not enough statistical power to detect a real effect or generate a fluctuated estimation. At present, limited studies investigated the association between GSTM1 and GSTT1 polymorphisms and the risk of cervical neoplasia in Caucasian and mixed populations. Therefore, well-designed studies with thousands of sample size are of great value to confirm this finding in Caucasians and other ethnic populations.

When stratified based on the source of DNA for GSTM1 and GSTT1 genotyping, the null genotype of GSTM1 significantly increased the cervical neoplasia risk in studies that the polymorphism was determined from white blood cells rather than from exfoliated cervical cells. The difference of studies with DNA isolation from exfoliated cervical cells tended to be significant (P = 0.057). It is likely that the potentially negative results were caused by small sample size with only 299 cases and 405 controls available in this meta-analysis. Another important issue is the source of cell used for DNA analysis. DNA isolation from different cell types may influence performance of genotyping, and eventually, lead to the conflicting results.

It is absolutely pivotal for a meta-analysis to assess the quality of literatures included. Currently, no standard quality score method was developed to evaluate observational case-control studies. We used a self-made rating scale for quality assessment, which was modified from previous studies [52][54]. Studies included in this meta-analysis were classified into high quality (≥7) or low quality (<7) according to the quality score. The combined results showed that the null genotype of GSTM1 polymorphism was associated with an increased risk of cervical neoplasia in both high quality studies and low quality studies. However, there was lack of association between GSTT1 polymorphism and cervical neoplasia risk either in high quality studies or in low quality studies. These findings denote that GSTM1 plays much more important roles than GSTT1 in the development of cervical neoplasia.

The hypothesis of cigarette smoking being a risk factor for cervical cancer was originally presented in 1977 [63]. Subsequently, amounts of epidemiological studies reported the support for this hypothesis [7], [64][69]. Despite the mechanism that tobacco smoking increase the risk of uterine cervical cancer remains unknown, it is believed that the occurrence of tobacco-initiated DNA damage in the cervical epithelium may be responsible for malignant transformation [70]. Tobacco smoke contains over fifty known carcinogens, such as polynuclear aromatic hydrocarbons, aromatic amines, nicotine, and nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl) -1-butanone (NNK) [70][73]. The concentrations of NNK in cervical mucous of cigarette smoking women were three times higher than those in non-smokers [70]. Such carcinogens may promote cancer through the stimulation of cell division or impairment of local immunosurveillance in the cervical epithelial tissue [67], [74]. In view of the crucial role that the smoking play in the etiology of cervical cancer, the effect of the interaction of GSTM1 and GSTT1 polymorphisms and smoking on the development of cervical neoplasia has been conducted in several studies [31][33], [37], [38], [46]. Therefore, it is necessary to analyze quantitatively the association between gene-environment interaction and the risk of cervical neoplasia using a meta-analysis. However, no evidence of correlation was observed between GSTM1 and GSTT1 polymorphisms and cervical neoplasia in combination with smoking habit. There may be a high risk of false negative results due to insufficient statistical power with very limited subjects eligible in this meta-analysis (for GSTM1 polymorphism: 737 cases and 704 controls; for GSTT1 polymorphism: 403 cases and 373 controls).

Persistent HPV infections are known to be the major cause of cervical cancer [5], [6]. Therefore, HPV infection status was also examined in subgroup analysis. Nevertheless, we failed to find any association between GSTM1 and GSTT1 polymorphisms and cervical neoplasia risk in either HPV positive women or HPV negative women. The null result may be owing to limited relevant studies included in this meta-analysis. Thus, large-scale prospective cohort studies are needed to provide the best evidence for the impact of interaction of gene-environment on the risk of cervical neoplasia.

Over the past decades, a large number of meta-analyses have been done to investigate the association between GSTM1 and GSTT1 polymorphisms and various cancers, including brain tumors [75], hepatocellular carcinoma [76], [77], colorectal cancer [78], [79], gastric cancer [80][84], breast cancer [85][90], bladder cancer [91][93], lung cancer [94][99], esophageal cancer [100], [101], prostate cancer [102], [103], nasopharyngeal carcinoma [104], head and neck cancer [105], oral and laryngeal cancer [106][108], and acute leukaemia [109], [110]. During revision of the manuscript, a similar report investigating the association between GSTM1 and GSTT1 polymorphisms and cervical cancer risk was published [111]. In the report, Economopoulos et al. identified publications by a search of Medline database (last search: August 3, 2009) and found that the GSTM1 polymorphism but not GSTT1 polymorphism was associated with the risk of cervical cancer [111]. In this meta-analysis, the eligible studies were identified by computer-based searches of three additional databases (i.e., EMBASE, ISI, and CBM) besides Medline, and the last search was performed up to August 2010. Moreover, studies examining the association between GSTM1 and GSTT1 polymorphisms and cervical intraepithelial neoplasia were also selected. Much more eligible studies, therefore, were included in this meta-analysis. Consistent with the results reported by Economopoulos et al., we found that the null genotype of GSTM1 polymorphism was associated with a significantly increased risk of cervical neoplasia. Inconsistent with the results reported by Economopoulos et al., we found an evidence of an association between GSTT1 polymorphism and the risk of cervical neoplasia with a borderline statistical significance. Larger sample size in this study may be responsible for the positive results. Our findings were in agreement with several previous reports. For example, Wang et al. reported that both GSTM1 and GSTT1 polymorphisms are associated with increased risk of hepatocellular carcinoma [77]. Economopoulos et al. reported that both GSTM1 and GSTT1 null genotype carriers exhibited higher colorectal cancer risk in Caucasian population [78]. In contrast, some researchers reported that GSTM1 and GSTT1 polymorphisms did not increase a substantial risk of breast cancer [88] and prostate cancer [102]. Taken together, these results indicate that GSTM1 and GSTT1 homozygous deletion polymorphisms may yield different effects on different types of cancers.

Our study has some limitations. Firstly, the between-study heterogeneity is a major problem in this meta-analysis because obvious heterogeneity was detected in overall analyses and also subgroup analyses. We explored several possible sources of heterogeneity, including cancer type, ethnicity, sample size, DNA source for genotyping and quality score. Unfortunately, we failed to find a bright reason for this variation, indicating that unknown confounding variables in single studies may have biased the findings. A conservative manner should, therefore, be adopted to interpret these results. Secondly, some potential confounding factors, such as age, sexual habits, and menopausal status can not be ruled out due to unadjusted data used. Finally, the sample size is relatively small in the meta-analysis, especially in some subgroup analyses.

In summary, this meta-analysis indicates that the null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk of cervical neoplasia. In GSTM1-GSTT1 interaction analysis, individuals with dual null genotype were associated with a significantly increased risk of cervical neoplasia. In gene-environment interaction analysis, neither smoking status nor HPV infection status was associated with GSTM1 and GSTT1 polymorphisms. To ensure a precise estimate of the effect of GSTM1 and GSTT1 polymorphisms on cervical neoplasia risk, additional unbiased studies with larger sample size are needed. Such studies will not only elucidate the pivotal roles GSTM1 and GSTT1 polymorphisms playing in the development of cervical neoplasia, but also increase our understanding the etiology of cervical neoplasia.

Supporting Information

Figure S1.

Flow diagram of the literature search.

https://doi.org/10.1371/journal.pone.0020157.s001

(TIF)

Figure S2.

Forest plot of cervical neoplasia risk of GSTM1 polymorphism in subgroup analysis according to ethnicity.

https://doi.org/10.1371/journal.pone.0020157.s002

(TIF)

Figure S3.

Forest plot of association between GSTT1 polymorphism and risk of cervical neoplasia.

https://doi.org/10.1371/journal.pone.0020157.s003

(TIF)

Figure S4.

Forest plot of GSTM1-GSTT1 interaction (null/null versus present/present).

https://doi.org/10.1371/journal.pone.0020157.s004

(TIF)

Table S1.

Quality assessment for the included studies.

https://doi.org/10.1371/journal.pone.0020157.s005

(DOC)

Table S2.

Overview of literatures included in the meta-analysis.

https://doi.org/10.1371/journal.pone.0020157.s006

(DOC)

Table S3.

Characteristics of the included studies.

https://doi.org/10.1371/journal.pone.0020157.s007

(DOC)

Table S4.

Summary odds ratios with confidence intervals between the GSTM1 polymorphism and cervical neoplasia risk.

https://doi.org/10.1371/journal.pone.0020157.s008

(DOC)

Table S5.

Summary odds ratios with confidence intervals between the GSTT1 polymorphism and cervical neoplasia risk.

https://doi.org/10.1371/journal.pone.0020157.s009

(DOC)

Table S6.

Summary odds ratios with confidence intervals between the GSTM1-GSTT1 interaction and cervical neoplasia risk.

https://doi.org/10.1371/journal.pone.0020157.s010

(DOC)

Author Contributions

Conceived and designed the experiments: L-BG X-MP LZ. Performed the experiments: X-MP L-JL W-BL PB. Analyzed the data: X-MP TW. Contributed reagents/materials/analysis tools: LR X-WS. Wrote the paper: L-BG LZ. Helped edit the manuscript: BZ Y-GW.

References

  1. 1. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55: 74–108.DM ParkinF. BrayJ. FerlayP. Pisani2005Global cancer statistics, 2002.CA Cancer J Clin5574108
  2. 2. Safaeian M, Solomon D, Castle PE (2007) Cervical cancer prevention–cervical screening: science in evolution. Obstet Gynecol Clin North Am 34: 739–760, ix.M. SafaeianD. SolomonPE Castle2007Cervical cancer prevention–cervical screening: science in evolution.Obstet Gynecol Clin North Am34739760, ix
  3. 3. Herrington CS (1999) Do HPV-negative cervical carcinomas exist?–revisited. J Pathol 189: 1–3.CS Herrington1999Do HPV-negative cervical carcinomas exist?–revisited.J Pathol18913
  4. 4. Walboomers JM, Meijer CJ (1997) Do HPV-negative cervical carcinomas exist? J Pathol 181: 253–254.JM WalboomersCJ Meijer1997Do HPV-negative cervical carcinomas exist?J Pathol181253254
  5. 5. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, et al. (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189: 12–19.JM WalboomersMV JacobsMM ManosFX BoschJA Kummer1999Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.J Pathol1891219
  6. 6. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S (2007) Human papillomavirus and cervical cancer. Lancet 370: 890–907.M. SchiffmanPE CastleJ. JeronimoAC RodriguezS. Wacholder2007Human papillomavirus and cervical cancer.Lancet370890907
  7. 7. Plummer M, Herrero R, Franceschi S, Meijer CJ, Snijders P, et al. (2003) Smoking and cervical cancer: pooled analysis of the IARC multi-centric case–control study. Cancer Causes Control 14: 805–814.M. PlummerR. HerreroS. FranceschiCJ MeijerP. Snijders2003Smoking and cervical cancer: pooled analysis of the IARC multi-centric case–control study.Cancer Causes Control14805814
  8. 8. Cancer. ICoESoC (2007) Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer 120: 885–891.Cancer. ICoESoC2007Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies.Int J Cancer120885891
  9. 9. Appleby P, Beral V, Berrington de Gonzalez A, Colin D, Franceschi S, et al. (2007) Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies. Lancet 370: 1609–1621.P. ApplebyV. BeralA. Berrington de GonzalezD. ColinS. Franceschi2007Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies.Lancet37016091621
  10. 10. Jee SH, Lee JE, Park JS (2003) Polymorphism of codon 72 of p53 and environmental factors in the development of cervical cancer. Int J Gynaecol Obstet 80: 69–70.SH JeeJE LeeJS Park2003Polymorphism of codon 72 of p53 and environmental factors in the development of cervical cancer.Int J Gynaecol Obstet806970
  11. 11. Magnusson PK, Sparen P, Gyllensten UB (1999) Genetic link to cervical tumours. Nature 400: 29–30.PK MagnussonP. SparenUB Gyllensten1999Genetic link to cervical tumours.Nature4002930
  12. 12. Hemminki K, Dong C, Vaittinen P (1999) Familial risks in cervical cancer: is there a hereditary component? Int J Cancer 82: 775–781.K. HemminkiC. DongP. Vaittinen1999Familial risks in cervical cancer: is there a hereditary component?Int J Cancer82775781
  13. 13. Magnusson PK, Gyllensten UB (2000) Cervical cancer risk: is there a genetic component? Mol Med Today 6: 145–148.PK MagnussonUB Gyllensten2000Cervical cancer risk: is there a genetic component?Mol Med Today6145148
  14. 14. Koushik A, Platt RW, Franco EL (2004) p53 codon 72 polymorphism and cervical neoplasia: a meta-analysis review. Cancer Epidemiol Biomarkers Prev 13: 11–22.A. KoushikRW PlattEL Franco2004p53 codon 72 polymorphism and cervical neoplasia: a meta-analysis review.Cancer Epidemiol Biomarkers Prev131122
  15. 15. Jee SH, Won SY, Yun JE, Lee JE, Park JS, et al. (2004) Polymorphism p53 codon-72 and invasive cervical cancer: a meta-analysis. Int J Gynaecol Obstet 85: 301–308.SH JeeSY WonJE YunJE LeeJS Park2004Polymorphism p53 codon-72 and invasive cervical cancer: a meta-analysis.Int J Gynaecol Obstet85301308
  16. 16. Sousa H, Santos AM, Pinto D, Medeiros R (2007) Is the p53 codon 72 polymorphism a key biomarker for cervical cancer development? A meta-analysis review within European populations. Int J Mol Med 20: 731–741.H. SousaAM SantosD. PintoR. Medeiros2007Is the p53 codon 72 polymorphism a key biomarker for cervical cancer development? A meta-analysis review within European populations.Int J Mol Med20731741
  17. 17. Klug SJ, Ressing M, Koenig J, Abba MC, Agorastos T, et al. (2009) TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies. Lancet Oncol 10: 772–784.SJ KlugM. RessingJ. KoenigMC AbbaT. Agorastos2009TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies.Lancet Oncol10772784
  18. 18. McIlwain CC, Townsend DM, Tew KD (2006) Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene 25: 1639–1648.CC McIlwainDM TownsendKD Tew2006Glutathione S-transferase polymorphisms: cancer incidence and therapy.Oncogene2516391648
  19. 19. Hayes JD, Pulford DJ (1995) 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.JD HayesDJ Pulford1995The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance.Crit Rev Biochem Mol Biol30445600
  20. 20. Ketterer B (1988) Protective role of glutathione and glutathione transferases in mutagenesis and carcinogenesis. Mutat Res 202: 343–361.B. Ketterer1988Protective role of glutathione and glutathione transferases in mutagenesis and carcinogenesis.Mutat Res202343361
  21. 21. Strange RC, Spiteri MA, Ramachandran S, Fryer AA (2001) Glutathione-S-transferase family of enzymes. Mutat Res 482: 21–26.RC StrangeMA SpiteriS. RamachandranAA Fryer2001Glutathione-S-transferase family of enzymes.Mutat Res4822126
  22. 22. Pearson WR, Vorachek WR, Xu SJ, Berger R, Hart I, et al. (1993) Identification of class-mu glutathione transferase genes GSTM1-GSTM5 on human chromosome 1p13. Am J Hum Genet 53: 220–233.WR PearsonWR VorachekSJ XuR. BergerI. Hart1993Identification of class-mu glutathione transferase genes GSTM1-GSTM5 on human chromosome 1p13.Am J Hum Genet53220233
  23. 23. Webb G, Vaska V, Coggan M, Board P (1996) Chromosomal localization of the gene for the human theta class glutathione transferase (GSTT1). Genomics 33: 121–123.G. WebbV. VaskaM. CogganP. Board1996Chromosomal localization of the gene for the human theta class glutathione transferase (GSTT1).Genomics33121123
  24. 24. Hayes JD, Flanagan JU, Jowsey IR (2005) Glutathione transferases. Annu Rev Pharmacol Toxicol 45: 51–88.JD HayesJU FlanaganIR Jowsey2005Glutathione transferases.Annu Rev Pharmacol Toxicol455188
  25. 25. Warwick A, Sarhanis P, Redman C, Pemble S, Taylor JB, et al. (1994) Theta class glutathione S-transferase GSTT1 genotypes and susceptibility to cervical neoplasia: interactions with GSTM1, CYP2D6 and smoking. Carcinogenesis 15: 2841–2845.A. WarwickP. SarhanisC. RedmanS. PembleJB Taylor1994Theta class glutathione S-transferase GSTT1 genotypes and susceptibility to cervical neoplasia: interactions with GSTM1, CYP2D6 and smoking.Carcinogenesis1528412845
  26. 26. Warwick AP, Redman CW, Jones PW, Fryer AA, Gilford J, et al. (1994) Progression of cervical intraepithelial neoplasia to cervical cancer: interactions of cytochrome P450 CYP2D6 EM and glutathione s-transferase GSTM1 null genotypes and cigarette smoking. Br J Cancer 70: 704–708.AP WarwickCW RedmanPW JonesAA FryerJ. Gilford1994Progression of cervical intraepithelial neoplasia to cervical cancer: interactions of cytochrome P450 CYP2D6 EM and glutathione s-transferase GSTM1 null genotypes and cigarette smoking.Br J Cancer70704708
  27. 27. de Carvalho CR, da Silva ID, Pereira JS, de Souza NC, Focchi GR, et al. (2008) Polymorphisms of p53, GSTM1 and GSTT1, and HPV in uterine cervix adenocarcinoma. Eur J Gynaecol Oncol 29: 590–593.CR de CarvalhoID da SilvaJS PereiraNC de SouzaGR Focchi2008Polymorphisms of p53, GSTM1 and GSTT1, and HPV in uterine cervix adenocarcinoma.Eur J Gynaecol Oncol29590593
  28. 28. Joseph T, Chacko P, Wesley R, Jayaprakash PG, James FV, et al. (2006) Germline genetic polymorphisms of CYP1A1, GSTM1 and GSTT1 genes in Indian cervical cancer: associations with tumor progression, age and human papillomavirus infection. Gynecol Oncol 101: 411–417.T. JosephP. ChackoR. WesleyPG JayaprakashFV James2006Germline genetic polymorphisms of CYP1A1, GSTM1 and GSTT1 genes in Indian cervical cancer: associations with tumor progression, age and human papillomavirus infection.Gynecol Oncol101411417
  29. 29. Sharma A, Sharma JK, Murthy NS, Mitra AB (2004) Polymorphisms at GSTM1 and GSTT1 gene loci and susceptibility to cervical cancer in Indian population. Neoplasma 51: 12–16.A. SharmaJK SharmaNS MurthyAB Mitra2004Polymorphisms at GSTM1 and GSTT1 gene loci and susceptibility to cervical cancer in Indian population.Neoplasma511216
  30. 30. Singh H, Sachan R, Devi S, Pandey SN, Mittal B (2008) Association of GSTM1, GSTT1, and GSTM3 gene polymorphisms and susceptibility to cervical cancer in a North Indian population. Am J Obstet Gynecol 198: 303 e301–306.H. SinghR. SachanS. DeviSN PandeyB. Mittal2008Association of GSTM1, GSTT1, and GSTM3 gene polymorphisms and susceptibility to cervical cancer in a North Indian population.Am J Obstet Gynecol198303 e301306
  31. 31. Sobti RC, Kaur S, Kaur P, Singh J, Gupta I, et al. (2006) Interaction of passive smoking with GST (GSTM1, GSTT1, and GSTP1) genotypes in the risk of cervical cancer in India. Cancer Genet Cytogenet 166: 117–123.RC SobtiS. KaurP. KaurJ. SinghI. Gupta2006Interaction of passive smoking with GST (GSTM1, GSTT1, and GSTP1) genotypes in the risk of cervical cancer in India.Cancer Genet Cytogenet166117123
  32. 32. Palma S, Novelli F, Padua L, Venuti A, Prignano G, et al. (2010) Interaction between glutathione-S-transferase polymorphisms, smoking habit, and HPV infection in cervical cancer risk. J Cancer Res Clin Oncol 136: 1101–1109.S. PalmaF. NovelliL. PaduaA. VenutiG. Prignano2010Interaction between glutathione-S-transferase polymorphisms, smoking habit, and HPV infection in cervical cancer risk.J Cancer Res Clin Oncol13611011109
  33. 33. Nishino K, Sekine M, Kodama S, Sudo N, Aoki Y, et al. (2008) Cigarette smoking and glutathione S-transferase M1 polymorphism associated with risk for uterine cervical cancer. J Obstet Gynaecol Res 34: 994–1001.K. NishinoM. SekineS. KodamaN. SudoY. Aoki2008Cigarette smoking and glutathione S-transferase M1 polymorphism associated with risk for uterine cervical cancer.J Obstet Gynaecol Res349941001
  34. 34. Niwa Y, Hirose K, Nakanishi T, Nawa A, Kuzuya K, et al. (2005) Association of the NAD(P)H: quinone oxidoreductase C609T polymorphism and the risk of cervical cancer in Japanese subjects. Gynecol Oncol 96: 423–429.Y. NiwaK. HiroseT. NakanishiA. NawaK. Kuzuya2005Association of the NAD(P)H: quinone oxidoreductase C609T polymorphism and the risk of cervical cancer in Japanese subjects.Gynecol Oncol96423429
  35. 35. Kim JW, Lee CG, Park YG, Kim KS, Kim IK, et al. (2000) Combined analysis of germline polymorphisms of p53, GSTM1, GSTT1, CYP1A1, and CYP2E1: relation to the incidence rate of cervical carcinoma. Cancer 88: 2082–2091.JW KimCG LeeYG ParkKS KimIK Kim2000Combined analysis of germline polymorphisms of p53, GSTM1, GSTT1, CYP1A1, and CYP2E1: relation to the incidence rate of cervical carcinoma.Cancer8820822091
  36. 36. Lee SA, Kim JW, Roh JW, Choi JY, Lee KM, et al. (2004) Genetic polymorphisms of GSTM1, p21, p53 and HPV infection with cervical cancer in Korean women. Gynecol Oncol 93: 14–18.SA LeeJW KimJW RohJY ChoiKM Lee2004Genetic polymorphisms of GSTM1, p21, p53 and HPV infection with cervical cancer in Korean women.Gynecol Oncol931418
  37. 37. Settheetham-Ishida W, Yuenyao P, Kularbkaew C, Settheetham D, Ishida T (2009) Glutathione S-transferase (GSTM1 and GSTT1) polymorphisms in cervical cancer in Northeastern Thailand. Asian Pac J Cancer Prev 10: 365–368.W. Settheetham-IshidaP. YuenyaoC. KularbkaewD. SettheethamT. Ishida2009Glutathione S-transferase (GSTM1 and GSTT1) polymorphisms in cervical cancer in Northeastern Thailand.Asian Pac J Cancer Prev10365368
  38. 38. Chen C, Madeleine MM, Weiss NS, Daling JR (1999) Glutathione S-transferase M1 genotypes and the risk of squamous carcinoma of the cervix: A population-based case-control study. American Journal of Epidemiology 150: 568–572.C. ChenMM MadeleineNS WeissJR Daling1999Glutathione S-transferase M1 genotypes and the risk of squamous carcinoma of the cervix: A population-based case-control study.American Journal of Epidemiology150568572
  39. 39. Sierra-Torres CH, Au WW, Arrastia CD, Cajas-Salazar N, Robazetti SC, et al. (2003) Polymorphisms for chemical metabolizing genes and risk for cervical neoplasia. Environmental and Molecular Mutagenesis 41: 69–76.CH Sierra-TorresWW AuCD ArrastiaN. Cajas-SalazarSC Robazetti2003Polymorphisms for chemical metabolizing genes and risk for cervical neoplasia.Environmental and Molecular Mutagenesis416976
  40. 40. Song GY, Shao SL, song ZY (2006) Association of single nucleotide polymorphism in glutathione S-transferase with susceptibility to cervical cancer. TumourJournal of the World 5: 192–194.GY SongSL ShaoZY song2006Association of single nucleotide polymorphism in glutathione S-transferase with susceptibility to cervical cancer.TumourJournal of the World5192194
  41. 41. Zhou Q, Wang J, Shao S, Ma X, Ding L (2006) The association between glutathione S-transferase M1, T1 polymorphisms and risk of cervical cancer. The study of the relationship between glutathione S-transferase M1, T1 genotypes and the risk of cervical cancer. Modem Preventive Medicine 33: 269–271.Q. ZhouJ. WangS. ShaoX. MaL. Ding2006The association between glutathione S-transferase M1, T1 polymorphisms and risk of cervical cancer. The study of the relationship between glutathione S-transferase M1, T1 genotypes and the risk of cervical cancer.Modem Preventive Medicine33269271
  42. 42. Ma C, Liu Y, Lu X, Ma Z (2009) Association between genetic polymorph ism of GSTM1 and susceptibility to cervical cancer in Uighur women in Xinjiang. Chin J Obstet Gynecol 44: 629–631.C. MaY. LiuX. LuZ. Ma2009Association between genetic polymorph ism of GSTM1 and susceptibility to cervical cancer in Uighur women in Xinjiang.Chin J Obstet Gynecol44629631
  43. 43. Huang YK, Hsieh HC, Sun JA, Chao CF, Huang RL, et al. (2006) Genetic polymorphisms of phase I and phase II xenobiotic enzymes in human papillomavirus related lesion and cancer of the uterine cervix. Tzu Chi Medical Journal 18: 267–274+328.YK HuangHC HsiehJA SunCF ChaoRL Huang2006Genetic polymorphisms of phase I and phase II xenobiotic enzymes in human papillomavirus related lesion and cancer of the uterine cervix.Tzu Chi Medical Journal18267274+328
  44. 44. Ueda M, Toji E, Nunobiki O, Izuma S, Okamoto Y, et al. (2008) Germline polymorphism of cancer susceptibility genes in gynecologic cancer. Human Cell 21: 95–104.M. UedaE. TojiO. NunobikiS. IzumaY. Okamoto2008Germline polymorphism of cancer susceptibility genes in gynecologic cancer.Human Cell2195104
  45. 45. Goodman MT, McDuffie K, Hernandez B, Bertram CC, Wilkens LR, et al. (2001) CYP1A1, GSTM1, and GSTT1 polymorphisms and the risk of cervical squamous intraepithelial lesions in a multiethnic population. Gynecol Oncol 81: 263–269.MT GoodmanK. McDuffieB. HernandezCC BertramLR Wilkens2001CYP1A1, GSTM1, and GSTT1 polymorphisms and the risk of cervical squamous intraepithelial lesions in a multiethnic population.Gynecol Oncol81263269
  46. 46. Agorastos T, Papadopoulos N, Lambropoulos AF, Chrisafi S, Mikos T, et al. (2007) Glutathione-S-transferase M1 and T1 and cytochrome P1A1 genetic polymorphisms and susceptibility to cervical intraepithelial neoplasia in Greek women. Eur J Cancer Prev 16: 498–504.T. AgorastosN. PapadopoulosAF LambropoulosS. ChrisafiT. Mikos2007Glutathione-S-transferase M1 and T1 and cytochrome P1A1 genetic polymorphisms and susceptibility to cervical intraepithelial neoplasia in Greek women.Eur J Cancer Prev16498504
  47. 47. Agodi A, Barchitta M, Cipresso R, Marzagalli R, La Rosa N, et al. (2010) Distribution of p53, GST, and MTHFR polymorphisms and risk of cervical intraepithelial lesions in sicily. International Journal of Gynecological Cancer 20: 141–146.A. AgodiM. BarchittaR. CipressoR. MarzagalliN. La Rosa2010Distribution of p53, GST, and MTHFR polymorphisms and risk of cervical intraepithelial lesions in sicily.International Journal of Gynecological Cancer20141146
  48. 48. Ueda M, Hung YC, Terai Y, Saito J, Nunobiki O, et al. (2005) Glutathione-S-transferase and p53 polymorphisms in cervical carcinogenesis. Gynecologic Oncology 96: 736–740.M. UedaYC HungY. TeraiJ. SaitoO. Nunobiki2005Glutathione-S-transferase and p53 polymorphisms in cervical carcinogenesis.Gynecologic Oncology96736740
  49. 49. Sierra-Torres CH, Arboleda-Moreno YY, Orejuela-Aristizabal L (2006) Exposure to wood smoke, HPV infection, and genetic susceptibility for cervical neoplasia among women in Colombia. Environ Mol Mutagen 47: 553–561.CH Sierra-TorresYY Arboleda-MorenoL. Orejuela-Aristizabal2006Exposure to wood smoke, HPV infection, and genetic susceptibility for cervical neoplasia among women in Colombia.Environ Mol Mutagen47553561
  50. 50. Liu Y, Ma W, Liu Q, Yang T, Xu X, et al. (2009) Association between genetic polymorph ism of GSTM1, CYP2E1 and susceptibility to cervical cancer and its precancerous lesions in Uighur women in Xinjiang. Prog Obstet Gynecol 18: 840–843.Y. LiuW. MaQ. LiuT. YangX. Xu2009Association between genetic polymorph ism of GSTM1, CYP2E1 and susceptibility to cervical cancer and its precancerous lesions in Uighur women in Xinjiang.Prog Obstet Gynecol18840843
  51. 51. Song GY, Song ZY, Xu JP, Shao SL (2008) Association of single nucleotide polymorphism in glutathione S-transferase-M1 with susceptibility to cervical cancer in Shanxi Province. Chinese Journal of Cancer Prevention and Treatment 15: 1054–1056.GY SongZY SongJP XuSL Shao2008Association of single nucleotide polymorphism in glutathione S-transferase-M1 with susceptibility to cervical cancer in Shanxi Province.Chinese Journal of Cancer Prevention and Treatment1510541056
  52. 52. Camargo MC, Mera R, Correa P, Peek RM Jr, Fontham ET, et al. (2006) Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms and gastric cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev 15: 1674–1687.MC CamargoR. MeraP. CorreaRM Peek JrET Fontham2006Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms and gastric cancer: a meta-analysis.Cancer Epidemiol Biomarkers Prev1516741687
  53. 53. Thakkinstian A, McEvoy M, Minelli C, Gibson P, Hancox B, et al. (2005) Systematic review and meta-analysis of the association between {beta}2-adrenoceptor polymorphisms and asthma: a HuGE review. Am J Epidemiol 162: 201–211.A. ThakkinstianM. McEvoyC. MinelliP. GibsonB. Hancox2005Systematic review and meta-analysis of the association between {beta}2-adrenoceptor polymorphisms and asthma: a HuGE review.Am J Epidemiol162201211
  54. 54. Gao LB, Pan XM, Li LJ, Liang WB, Zhu Y, et al. (2010) RAD51 135G/C polymorphism and breast cancer risk: a meta-analysis from 21 studies. Breast Cancer Res Treat [Epub ahead of print]. LB GaoXM PanLJ LiWB LiangY. Zhu2010RAD51 135G/C polymorphism and breast cancer risk: a meta-analysis from 21 studies.Breast Cancer Res Treat [Epub ahead of print]
  55. 55. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21: 1539–1558.JP HigginsSG Thompson2002Quantifying heterogeneity in a meta-analysis.Stat Med2115391558
  56. 56. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327: 557–560.JP HigginsSG ThompsonJJ DeeksDG Altman2003Measuring inconsistency in meta-analyses.BMJ327557560
  57. 57. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22: 719–748.N. MantelW. Haenszel1959Statistical aspects of the analysis of data from retrospective studies of disease.J Natl Cancer Inst22719748
  58. 58. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7: 177–188.R. DerSimonianN. Laird1986Meta-analysis in clinical trials.Control Clin Trials7177188
  59. 59. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315: 629–634.M. EggerG. Davey SmithM. SchneiderC. Minder1997Bias in meta-analysis detected by a simple, graphical test.BMJ315629634
  60. 60. Norppa H (2004) Cytogenetic biomarkers and genetic polymorphisms. Toxicol Lett 149: 309–334.H. Norppa2004Cytogenetic biomarkers and genetic polymorphisms.Toxicol Lett149309334
  61. 61. Hayes JD, Strange RC (2000) Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 61: 154–166.JD HayesRC Strange2000Glutathione S-transferase polymorphisms and their biological consequences.Pharmacology61154166
  62. 62. Garte S, Gaspari L, Alexandrie AK, Ambrosone C, Autrup H, et al. (2001) Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomarkers Prev 10: 1239–1248.S. GarteL. GaspariAK AlexandrieC. AmbrosoneH. Autrup2001Metabolic gene polymorphism frequencies in control populations.Cancer Epidemiol Biomarkers Prev1012391248
  63. 63. Winkelstein W Jr (1977) Smoking and cancer of the uterine cervix: hypothesis. Am J Epidemiol 106: 257–259.W. Winkelstein Jr1977Smoking and cancer of the uterine cervix: hypothesis.Am J Epidemiol106257259
  64. 64. Winkelstein W Jr, Shillitoe EJ, Brand R, Johnson KK (1984) Further comments on cancer of the uterine cervix, smoking, and herpesvirus infection. Am J Epidemiol 119: 1–8.W. Winkelstein JrEJ ShillitoeR. BrandKK Johnson1984Further comments on cancer of the uterine cervix, smoking, and herpesvirus infection.Am J Epidemiol11918
  65. 65. Winkelstein W Jr (1990) Smoking and cervical cancer–current status: a review. Am J Epidemiol 131: 945–957; discussion 958–960.W. Winkelstein Jr1990Smoking and cervical cancer–current status: a review.Am J Epidemiol131945957; discussion 958–960
  66. 66. Steckley SL, Pickworth WB, Haverkos HW (2003) Cigarette smoking and cervical cancer: Part II: a geographic variability study. Biomed Pharmacother 57: 78–83.SL SteckleyWB PickworthHW Haverkos2003Cigarette smoking and cervical cancer: Part II: a geographic variability study.Biomed Pharmacother577883
  67. 67. Haverkos HW, Soon G, Steckley SL, Pickworth W (2003) Cigarette smoking and cervical cancer: Part I: a meta-analysis. Biomed Pharmacother 57: 67–77.HW HaverkosG. SoonSL SteckleyW. Pickworth2003Cigarette smoking and cervical cancer: Part I: a meta-analysis.Biomed Pharmacother576777
  68. 68. Greenberg ER, Vessey M, McPherson K, Yeates D (1985) Cigarette smoking and cancer of the uterine cervix. Br J Cancer 51: 139–141.ER GreenbergM. VesseyK. McPhersonD. Yeates1985Cigarette smoking and cancer of the uterine cervix.Br J Cancer51139141
  69. 69. Sood AK (1991) Cigarette smoking and cervical cancer: meta-analysis and critical review of recent studies. Am J Prev Med 7: 208–213.AK Sood1991Cigarette smoking and cervical cancer: meta-analysis and critical review of recent studies.Am J Prev Med7208213
  70. 70. Prokopczyk B, Cox JE, Hoffmann D, Waggoner SE (1997) Identification of tobacco-specific carcinogen in the cervical mucus of smokers and nonsmokers. J Natl Cancer Inst 89: 868–873.B. ProkopczykJE CoxD. HoffmannSE Waggoner1997Identification of tobacco-specific carcinogen in the cervical mucus of smokers and nonsmokers.J Natl Cancer Inst89868873
  71. 71. Hoffmann D, Hoffmann I (1997) The changing cigarette, 1950–1995. J Toxicol Environ Health 50: 307–364.D. HoffmannI. Hoffmann1997The changing cigarette, 1950–1995.J Toxicol Environ Health50307364
  72. 72. Kjellberg L, Hallmans G, Ahren AM, Johansson R, Bergman F, et al. (2000) Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection. Br J Cancer 82: 1332–1338.L. KjellbergG. HallmansAM AhrenR. JohanssonF. Bergman2000Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection.Br J Cancer8213321338
  73. 73. Kuper H, Adami HO, Boffetta P (2002) Tobacco use, cancer causation and public health impact. J Intern Med 251: 455–466.H. KuperHO AdamiP. Boffetta2002Tobacco use, cancer causation and public health impact.J Intern Med251455466
  74. 74. Nadais Rda F, Campaner AB, Piato S, Longo Galvao MA, dos Santos RE, et al. (2006) Langerhans' cells and smoking in intraepithelial neoplasia of the cervix. Gynecol Oncol 102: 356–360.F. Nadais RdaAB CampanerS. PiatoMA Longo GalvaoRE dos Santos2006Langerhans' cells and smoking in intraepithelial neoplasia of the cervix.Gynecol Oncol102356360
  75. 75. Lai R, Crevier L, Thabane L (2005) Genetic polymorphisms of glutathione S-transferases and the risk of adult brain tumors: a meta-analysis. Cancer Epidemiol Biomarkers Prev 14: 1784–1790.R. LaiL. CrevierL. Thabane2005Genetic polymorphisms of glutathione S-transferases and the risk of adult brain tumors: a meta-analysis.Cancer Epidemiol Biomarkers Prev1417841790
  76. 76. White DL, Li D, Nurgalieva Z, El-Serag HB (2008) Genetic variants of glutathione S-transferase as possible risk factors for hepatocellular carcinoma: a HuGE systematic review and meta-analysis. Am J Epidemiol 167: 377–389.DL WhiteD. LiZ. NurgalievaHB El-Serag2008Genetic variants of glutathione S-transferase as possible risk factors for hepatocellular carcinoma: a HuGE systematic review and meta-analysis.Am J Epidemiol167377389
  77. 77. Wang B, Huang G, Wang D, Li A, Xu Z, et al. (2010) Null genotypes of GSTM1 and GSTT1 contribute to hepatocellular carcinoma risk: evidence from an updated meta-analysis. J Hepatol 53: 508–518.B. WangG. HuangD. WangA. LiZ. Xu2010Null genotypes of GSTM1 and GSTT1 contribute to hepatocellular carcinoma risk: evidence from an updated meta-analysis.J Hepatol53508518
  78. 78. Economopoulos KP, Sergentanis TN (2010) GSTM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: a comprehensive meta-analysis. Eur J Cancer 46: 1617–1631.KP EconomopoulosTN Sergentanis2010GSTM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: a comprehensive meta-analysis.Eur J Cancer4616171631
  79. 79. Raimondi S, Botteri E, Iodice S, Lowenfels AB, Maisonneuve P (2009) Gene-smoking interaction on colorectal adenoma and cancer risk: review and meta-analysis. Mutat Res 670: 6–14.S. RaimondiE. BotteriS. IodiceAB LowenfelsP. Maisonneuve2009Gene-smoking interaction on colorectal adenoma and cancer risk: review and meta-analysis.Mutat Res670614
  80. 80. Saadat M (2006) Genetic polymorphisms of glutathione S-transferase T1 (GSTT1) and susceptibility to gastric cancer: a meta-analysis. Cancer Sci 97: 505–509.M. Saadat2006Genetic polymorphisms of glutathione S-transferase T1 (GSTT1) and susceptibility to gastric cancer: a meta-analysis.Cancer Sci97505509
  81. 81. Chen B, Cao L, Zhou Y, Yang P, Wan HW, et al. (2010) Glutathione S-transferase T1 (GSTT1) gene polymorphism and gastric cancer susceptibility: a meta-analysis of epidemiologic studies. Dig Dis Sci 55: 1831–1838.B. ChenL. CaoY. ZhouP. YangHW Wan2010Glutathione S-transferase T1 (GSTT1) gene polymorphism and gastric cancer susceptibility: a meta-analysis of epidemiologic studies.Dig Dis Sci5518311838
  82. 82. Boccia S, La Torre G, Gianfagna F, Mannocci A, Ricciardi G (2006) Glutathione S-transferase T1 status and gastric cancer risk: a meta-analysis of the literature. Mutagenesis 21: 115–123.S. BocciaG. La TorreF. GianfagnaA. MannocciG. Ricciardi2006Glutathione S-transferase T1 status and gastric cancer risk: a meta-analysis of the literature.Mutagenesis21115123
  83. 83. La Torre G, Boccia S, Ricciardi G (2005) Glutathione S-transferase M1 status and gastric cancer risk: a meta-analysis. Cancer Lett 217: 53–60.G. La TorreS. BocciaG. Ricciardi2005Glutathione S-transferase M1 status and gastric cancer risk: a meta-analysis.Cancer Lett2175360
  84. 84. Wang H, Zhou Y, Zhuang W, Yin YQ, Liu GJ, et al. (2010) Glutathione S-transferase M1 null genotype associated with gastric cancer among Asians. Dig Dis Sci 55: 1824–1830.H. WangY. ZhouW. ZhuangYQ YinGJ Liu2010Glutathione S-transferase M1 null genotype associated with gastric cancer among Asians.Dig Dis Sci5518241830
  85. 85. Sergentanis TN, Economopoulos KP (2010) GSTT1 and GSTP1 polymorphisms and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 121: 195–202.TN SergentanisKP Economopoulos2010GSTT1 and GSTP1 polymorphisms and breast cancer risk: a meta-analysis.Breast Cancer Res Treat121195202
  86. 86. Sull JW, Ohrr H, Kang DR, Nam CM (2004) Glutathione S-transferase M1 status and breast cancer risk: a meta-analysis. Yonsei Med J 45: 683–689.JW SullH. OhrrDR KangCM Nam2004Glutathione S-transferase M1 status and breast cancer risk: a meta-analysis.Yonsei Med J45683689
  87. 87. Qiu LX, Yuan H, Yu KD, Mao C, Chen B, et al. (2010) Glutathione S-transferase M1 polymorphism and breast cancer susceptibility: a meta-analysis involving 46,281 subjects. Breast Cancer Res Treat 121: 703–708.LX QiuH. YuanKD YuC. MaoB. Chen2010Glutathione S-transferase M1 polymorphism and breast cancer susceptibility: a meta-analysis involving 46,281 subjects.Breast Cancer Res Treat121703708
  88. 88. Vogl FD, Taioli E, Maugard C, Zheng W, Pinto LF, et al. (2004) Glutathione S-transferases M1, T1, and P1 and breast cancer: a pooled analysis. Cancer Epidemiol Biomarkers Prev 13: 1473–1479.FD VoglE. TaioliC. MaugardW. ZhengLF Pinto2004Glutathione S-transferases M1, T1, and P1 and breast cancer: a pooled analysis.Cancer Epidemiol Biomarkers Prev1314731479
  89. 89. Egan KM, Cai Q, Shu XO, Jin F, Zhu TL, et al. (2004) Genetic polymorphisms in GSTM1, GSTP1, and GSTT1 and the risk for breast cancer: results from the Shanghai Breast Cancer Study and meta-analysis. Cancer Epidemiol Biomarkers Prev 13: 197–204.KM EganQ. CaiXO ShuF. JinTL Zhu2004Genetic polymorphisms in GSTM1, GSTP1, and GSTT1 and the risk for breast cancer: results from the Shanghai Breast Cancer Study and meta-analysis.Cancer Epidemiol Biomarkers Prev13197204
  90. 90. Gao Y, Cao Y, Tan A, Liao C, Mo Z, et al. (2010) Glutathione S-transferase M1 polymorphism and sporadic colorectal cancer risk: An updating meta-analysis and HuGE review of 36 case-control studies. Ann Epidemiol 20: 108–121.Y. GaoY. CaoA. TanC. LiaoZ. Mo2010Glutathione S-transferase M1 polymorphism and sporadic colorectal cancer risk: An updating meta-analysis and HuGE review of 36 case-control studies.Ann Epidemiol20108121
  91. 91. Johns LE, Houlston RS (2000) Glutathione S-transferase mu1 (GSTM1) status and bladder cancer risk: a meta-analysis. Mutagenesis 15: 399–404.LE JohnsRS Houlston2000Glutathione S-transferase mu1 (GSTM1) status and bladder cancer risk: a meta-analysis.Mutagenesis15399404
  92. 92. Garcia-Closas M, Malats N, Silverman D, Dosemeci M, Kogevinas M, et al. (2005) NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet 366: 649–659.M. Garcia-ClosasN. MalatsD. SilvermanM. DosemeciM. Kogevinas2005NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses.Lancet366649659
  93. 93. Engel LS, Taioli E, Pfeiffer R, Garcia-Closas M, Marcus PM, et al. (2002) Pooled analysis and meta-analysis of glutathione S-transferase M1 and bladder cancer: a HuGE review. Am J Epidemiol 156: 95–109.LS EngelE. TaioliR. PfeifferM. Garcia-ClosasPM Marcus2002Pooled analysis and meta-analysis of glutathione S-transferase M1 and bladder cancer: a HuGE review.Am J Epidemiol15695109
  94. 94. Benhamou S, Lee WJ, Alexandrie AK, Boffetta P, Bouchardy C, et al. (2002) Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk. Carcinogenesis 23: 1343–1350.S. BenhamouWJ LeeAK AlexandrieP. BoffettaC. Bouchardy2002Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk.Carcinogenesis2313431350
  95. 95. Shi X, Zhou S, Wang Z, Zhou Z (2008) CYP1A1 and GSTM1 polymorphisms and lung cancer risk in Chinese populations: a meta-analysis. Lung Cancer 59: 155–163.X. ShiS. ZhouZ. WangZ. Zhou2008CYP1A1 and GSTM1 polymorphisms and lung cancer risk in Chinese populations: a meta-analysis.Lung Cancer59155163
  96. 96. McWilliams JE, Sanderson BJ, Harris EL, Richert-Boe KE, Henner WD (1995) Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk. Cancer Epidemiol Biomarkers Prev 4: 589–594.JE McWilliamsBJ SandersonEL HarrisKE Richert-BoeWD Henner1995Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk.Cancer Epidemiol Biomarkers Prev4589594
  97. 97. Houlston RS (1999) Glutathione S-transferase M1 status and lung cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 8: 675–682.RS Houlston1999Glutathione S-transferase M1 status and lung cancer risk: a meta-analysis.Cancer Epidemiol Biomarkers Prev8675682
  98. 98. Carlsten C, Sagoo GS, Frodsham AJ, Burke W, Higgins JP (2008) Glutathione S-transferase M1 (GSTM1) polymorphisms and lung cancer: a literature-based systematic HuGE review and meta-analysis. Am J Epidemiol 167: 759–774.C. CarlstenGS SagooAJ FrodshamW. BurkeJP Higgins2008Glutathione S-transferase M1 (GSTM1) polymorphisms and lung cancer: a literature-based systematic HuGE review and meta-analysis.Am J Epidemiol167759774
  99. 99. Ye Z, Song H, Higgins JP, Pharoah P, Danesh J (2006) Five glutathione s-transferase gene variants in 23,452 cases of lung cancer and 30,397 controls: meta-analysis of 130 studies. PLoS Med 3: e91.Z. YeH. SongJP HigginsP. PharoahJ. Danesh2006Five glutathione s-transferase gene variants in 23,452 cases of lung cancer and 30,397 controls: meta-analysis of 130 studies.PLoS Med3e91
  100. 100. Zhuo WL, Zhang YS, Wang Y, Zhuo XL, Zhu B, et al. (2009) Association studies of CYP1A1 and GSTM1 polymorphisms with esophageal cancer risk: evidence-based meta-analyses. Arch Med Res 40: 169–179.WL ZhuoYS ZhangY. WangXL ZhuoB. Zhu2009Association studies of CYP1A1 and GSTM1 polymorphisms with esophageal cancer risk: evidence-based meta-analyses.Arch Med Res40169179
  101. 101. Yang CX, Matsuo K, Wang ZM, Tajima K (2005) Phase I/II enzyme gene polymorphisms and esophageal cancer risk: a meta-analysis of the literature. World J Gastroenterol 11: 2531–2538.CX YangK. MatsuoZM WangK. Tajima2005Phase I/II enzyme gene polymorphisms and esophageal cancer risk: a meta-analysis of the literature.World J Gastroenterol1125312538
  102. 102. Ntais C, Polycarpou A, Ioannidis JP (2005) Association of GSTM1, GSTT1, and GSTP1 gene polymorphisms with the risk of prostate cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev 14: 176–181.C. NtaisA. PolycarpouJP Ioannidis2005Association of GSTM1, GSTT1, and GSTP1 gene polymorphisms with the risk of prostate cancer: a meta-analysis.Cancer Epidemiol Biomarkers Prev14176181
  103. 103. Mo Z, Gao Y, Cao Y, Gao F, Jian L (2009) An updating meta-analysis of the GSTM1, GSTT1, and GSTP1 polymorphisms and prostate cancer: a HuGE review. Prostate 69: 662–688.Z. MoY. GaoY. CaoF. GaoL. Jian2009An updating meta-analysis of the GSTM1, GSTT1, and GSTP1 polymorphisms and prostate cancer: a HuGE review.Prostate69662688
  104. 104. Zhuo X, Cai L, Xiang Z, Li Q, Zhang X (2009) GSTM1 and GSTT1 polymorphisms and nasopharyngeal cancer risk: an evidence-based meta-analysis. J Exp Clin Cancer Res 28: 46.X. ZhuoL. CaiZ. XiangQ. LiX. Zhang2009GSTM1 and GSTT1 polymorphisms and nasopharyngeal cancer risk: an evidence-based meta-analysis.J Exp Clin Cancer Res2846
  105. 105. Hashibe M, Brennan P, Strange RC, Bhisey R, Cascorbi I, et al. (2003) Meta- and pooled analyses of GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes and risk of head and neck cancer. Cancer Epidemiol Biomarkers Prev 12: 1509–1517.M. HashibeP. BrennanRC StrangeR. BhiseyI. Cascorbi2003Meta- and pooled analyses of GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes and risk of head and neck cancer.Cancer Epidemiol Biomarkers Prev1215091517
  106. 106. Zhuo W, Wang Y, Zhuo X, Zhu Y, Wang W, et al. (2009) CYP1A1 and GSTM1 polymorphisms and oral cancer risk: association studies via evidence-based meta-analyses. Cancer Invest 27: 86–95.W. ZhuoY. WangX. ZhuoY. ZhuW. Wang2009CYP1A1 and GSTM1 polymorphisms and oral cancer risk: association studies via evidence-based meta-analyses.Cancer Invest278695
  107. 107. Varela-Lema L, Taioli E, Ruano-Ravina A, Barros-Dios JM, Anantharaman D, et al. (2008) Meta-analysis and pooled analysis of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers: a HuGE-GSEC review. Genet Med 10: 369–384.L. Varela-LemaE. TaioliA. Ruano-RavinaJM Barros-DiosD. Anantharaman2008Meta-analysis and pooled analysis of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers: a HuGE-GSEC review.Genet Med10369384
  108. 108. Zhuo WL, Wang Y, Zhuo XL, Zhu B, Zhu Y, et al. (2009) Polymorphisms of CYP1A1 and GSTM1 and laryngeal cancer risk: evidence-based meta-analyses. J Cancer Res Clin Oncol 135: 1081–1090.WL ZhuoY. WangXL ZhuoB. ZhuY. Zhu2009Polymorphisms of CYP1A1 and GSTM1 and laryngeal cancer risk: evidence-based meta-analyses.J Cancer Res Clin Oncol13510811090
  109. 109. Das P, Shaik AP, Bammidi VK (2009) Meta-analysis study of glutathione-S-transferases (GSTM1, GSTP1, and GSTT1) gene polymorphisms and risk of acute myeloid leukemia. Leuk Lymphoma 50: 1345–1351.P. DasAP ShaikVK Bammidi2009Meta-analysis study of glutathione-S-transferases (GSTM1, GSTP1, and GSTT1) gene polymorphisms and risk of acute myeloid leukemia.Leuk Lymphoma5013451351
  110. 110. Ye Z, Song H (2005) Glutathione s-transferase polymorphisms (GSTM1, GSTP1 and GSTT1) and the risk of acute leukaemia: a systematic review and meta-analysis. Eur J Cancer 41: 980–989.Z. YeH. Song2005Glutathione s-transferase polymorphisms (GSTM1, GSTP1 and GSTT1) and the risk of acute leukaemia: a systematic review and meta-analysis.Eur J Cancer41980989
  111. 111. Economopoulos KP, Choussein S, Vlahos NF, Sergentanis TN (2010) GSTM1 polymorphism, GSTT1 polymorphism, and cervical cancer risk: a meta-analysis. Int J Gynecol Cancer 20: 1576–1580.KP EconomopoulosS. ChousseinNF VlahosTN Sergentanis2010GSTM1 polymorphism, GSTT1 polymorphism, and cervical cancer risk: a meta-analysis.Int J Gynecol Cancer2015761580