Glutathione S‐transferase polymorphisms are associated with survival in anaplastic glioma patients

BACKGROUND:

Glutathione S‐transferases (GSTs) are polymorphic enzymes that are responsible for glutathione conjugation of alkylators and scavenging of free radicals created by radiation. GST polymorphisms may result in altered or absent enzyme activity and have been associated with survival in patients with cancer. The authors of this report hypothesized that patients with anaplastic glioma (AG) who have GST genotypes that encode for lower activity enzymes will have longer survival than similar patients who have higher activity genotypes. The current study was performed to investigate the role of GST enzyme polymorphisms in predicting the survival of patients with AG.

METHODS:

The medical records of 207 patients with AG from a single cancer center were reviewed retrospectively. Polymorphisms for the GST μ1 (GSTM1), GST θ1 (GSTT1), and GST π1 (GSTP1) enzymes were identified. Overall survival was compared using the Kaplan‐Meier method and Cox proportional hazards analyses adjusting for age, sex, histology, and therapy.

RESULTS:

Among the patients with oligodendroglial tumors (n = 94), patients who had the GSTT1 null genotype had a 2.9 times increased risk of death (95% confidence interval [CI], 1.3‐6.3) compared with patients who had the GSTT1 non‐null genotype. Adjustment for 1p/19q status did not change the finding. In the patients who had anaplastic astrocytoma (n = 113), the patients with all GSTP1 genotypes except GSTP1 *B/*B had a 3.8 times increased risk of death (95% CI, 0.5‐29.6) compared with patients who had the GSTP1 *B/*B genotype.

CONCLUSIONS:

In patients with anaplastic oligodendroglial tumors, the GSTT1 null genotype may be associated with poor survival, possibly because of modifications in therapy secondary to increased toxicity. This hypothesis is under investigation. In patients with anaplastic astrocytoma, the GSTP1 *B/*B genotype may confer a survival advantage. Cancer 2010. © 2010 American Cancer Society.     

Placental isoform glutathione S‐transferase and P‐glycoprotein expression in advanced nonsmall cell lung cancer

BACKGROUND.

Increased expression of the glutathione S‐transferase placental isoform (GST‐pi) and of P‐glycoprotein (P‐gp) in tissues from patients with nonsmall cell lung cancer (NSCLC) has been associated with poor antineoplastic drug sensitivity, response to treatment, and survival. However, the diagnosis of advanced NSCLC often is based on cytology. The objectives of the current study were to examine GST‐pi and P‐gp expression in cytologic specimens from patients with unresectable NSCLC and to determine the association of that expression with response to chemotherapy and survival.

METHODS.

Patients with unresectable, cytologically diagnosed NSCLC were eligible for the study. Diagnosis was made by fiberoptic bronchoscopy, and staging was done according to international standards. All patients received sequential chemoradiotherapy and were re‐evaluated for treatment response. GST‐pi and P‐gp expression levels were evaluated by immunocytochemistry and immunohistochemistry of bronchial brushing/washing and bronchial tissue biopsy, respectively. Survival was defined as the time between diagnosis and death or last follow‐up at 24 months.

RESULTS.

Thirty‐nine patients were included in the study. There were 35 men and 4 women, and the mean patient age (±standard deviation was 61.4 years (±9.1 years). There were 4 patients with stage IIIA NSCLC, 32 patients with stage IIIB NSCLC, and 3 patients with stage IV NSCLC. Cytologic evaluation of GST‐pi and P‐gp expression paralleled expression determined in pathology specimens. GST‐pi and P‐gp expression levels were associated inversely with response to chemotherapy and survival.

CONCLUSIONS.

Cytologic evaluation of GST‐pi and P‐gp expression may predictor the response to treatment and the survival of patients with advanced NSCLC. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.     

A meta‐analysis on the association of HER‐2 overexpression with prognosis in human osteosarcoma

LI Y.G. & GENG X. (2010) European Journal of Cancer Care 19, 313–316
A meta‐analysis on the association of HER‐2 overexpression with prognosis in human osteosarcoma Various studies examining the relationship between HER‐2 overexpression and clinical outcome in patients with osteosarcoma have yielded inconclusive results. The purpose of the current study was to evaluate the relation of HER‐2 status with clinical outcome in osteosarcoma. We conducted a meta‐analysis of five studies that evaluated the relation between HER‐2 status and 2‐year survival. DerSimonian‐Laird random effects analysis was used to estimate the effects of HER‐2 overexpression on 2‐year survival. The combined relative risk in patients with osteosarcoma for 2‐year survival was 1.26 (95% confidence interval, 0.50–3.14; P = 0.63). HER‐2‐positive status tended to be associated with a worse 2‐year survival, but the overall results were not formally statistically significant. An unfavourable prognostic effect of HER‐2 overexpression in osteosarcoma was evident from the meta‐analysis. However, because several studies were excluded by the current eligibility criteria, caution is needed in interpreting the results.     

Survival benefit from S‐1 as compared to Fluorouracil in Asian patients with advanced gastrointestinal cancer: A meta‐analysis

Whether S‐1 could replace 5‐Fluorouracil (5‐Fu) or not in the treatment of advanced gastrointestinal (GI) cancer (including advanced gastric cancer [AGS] and metastatic colorectal cancer [mCRC]) in Asian patients has been controversial. This meta‐analysis was performed to compare the activity, efficacy and toxicity of S‐1‐based versus 5‐Fu‐based chemotherapy in those Asian patients. Randomized controlled trials (RCTs) were identified by electronic search of Pubmed. Relevant abstracts were manually searched to identify relevant trials. A total of 2182 patients from eight RCTs were included, and our results demonstrated that S‐1‐based chemotherapy significantly improved overall survival (OS) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77–1.00) and overall response rate (ORR) (odds ratio [OR], 1.72; 95% CI, 1.09–2.70), but no significant progression‐free survival (PFS) benefit was found between arms (HR, 0.87; 95% CI, 0.72–1.06). Subgroup analyses revealed that S‐1‐based chemotherapy significantly improved OS and ORR in subgroups of patients with non‐platinum containing regimens (P = 0.041; P = 0.034) and patients with no prior chemotherapy history (P = 0.025; P = 0.016). Statistically significant improvements of PFS and ORR in the S‐1‐based chemotherapy were observed in the subgroup of patients with AGC (P < 0.001; P = 0.005). S‐1‐based chemotherapy was characterized by significantly higher incidences of diarrhea, fatigue and thrombocytopenia, and a lower incidence of nausea. This analysis provided strong evidence for survival benefits of S‐1, and S‐1‐based chemotherapy could be considered to replace 5‐Fu‐based therapy for the treatment of advanced GI cancer in Asian patients.     

Associations of Lys939Gln and Ala499Val polymorphisms of the XPC gene with cancer susceptibility: A meta‐analysis

XPC polymorphisms may alter DNA repair capacity, thus leading to genetic instability and carcinogenesis. Numerous studies have investigated the associations of XPC Lys939Gln (rs2228001) and Ala499Val (rs2228000) polymorphisms with cancer susceptibility; however, the findings are inconclusive. We searched literature from MEDLINE and EMBASE for eligible publications that assessed the associations between these two polymorphisms and cancer risk. We also assessed genotype‐mRNA expression correlation data from HapMap for rs2228001 and rs2228000 in normal cell lines derived from 270 subjects with different ethnicities. The final analysis included 62 published studies of 25,708 cases and 30,432 controls for the Lys939Gln and 34 studies with 14,877 cases and 17,888 controls for the Ala499Val. Overall, Lys939Gln was significantly associated with an increased overall cancer risk (Gln/Gln vs. Lys/Lys: OR = 1.16, 95% CI = 1.07 − 1.25, p < 0.001; recessive model: OR = 1.14, 95% CI = 1.06 − 1.22, p < 0.001; dominant model: OR = 1.06, 95% CI = 1.01 − 1.11, p = 0.015 and Gln vs. Lys: OR = 1.07, 95% CI = 1.03 − 1.10, p < 0.001) and further stratifications showed an increased risk for bladder, lung and colorectal cancer, Asian populations and population‐based studies. Likewise, Ala499Val was also significantly associated with an increased overall cancer risk (Val/Val vs. Ala/Ala: OR = 1.21, 95% CI = 1.07 − 1.36, p = 0.003 and recessive model: OR = 1.20, 95% CI = 1.08 − 1.34, p = 0.001) and further stratification showed an increased risk for breast and bladder cancer, particularly in Asian populations. Interestingly, significantly correlation between XPC genotypes and mRNA expression was found only for Asian populations as well. Despite some limitations, this meta‐analysis established some solid statistical evidence for an association between XPC polymorphisms and cancer risk, which warrants further validation in single large studies.     

GSTT1 and GSTM1 polymorphisms and myelodysplastic syndrome risk: a systematic review and meta‐analysis

Glutathione‐S‐transferace polymorphisms may make hematopoietic lineage cells susceptible to genotoxicity following exposure to heavy metals or benzene. We conducted a systematic review and meta‐analysis to define the effect of GSTM1 and GSTT1 null polymorphisms on MDS risk. We searched the PubMed and SCOPUS databases to identify peer‐reviewed published case‐control studies investigating the association between GSTT1 and/or GSTM1 null genotypes and development of MDS. Between‐study heterogeneity was assessed using Cochran's Q statistic and the I² statistic. Odds ratios from individual studies were pooled using fixed and random effects models. Thirteen studies were considered eligible for the GSTT1 meta‐analysis (1471 cases, 1907 controls) and 10 were considered eligible for the GSTM1 meta‐analysis (1161 cases, 1668 controls). For the GSTT1 polymorphism, there was moderate between study heterogeneity (p_Q = 0.01; I² = 52.3%) and the null genotype was significantly associated with increased risk of MDS development, random effects OR = 1.43 (95% CI, 1.09–1.89); p = 0.01. For the GSTM1 polymorphisms there was moderate between‐study heterogeneity (p = 0.07; I² = 43.1%) and the random effects OR = 1.02 (95% CI, 0.82–1.28) was non‐significant (p = 0.85). The GSTT1 null genotype is a significant risk factor for MDS development. Gene‐environment interactions need to be further explored.     

Candidate gene association studies and risk of Hodgkin lymphoma: a systematic review and meta‐analysis

To evaluate the contribution of association studies of candidate polymorphisms to inherited predisposition to Hodgkin lymphoma (HL), we conducted a systematic review and meta‐analysis of published case‐control studies. Of the variants examined more than once in candidate gene association studies, we identified 21 studies that reported on 12 polymorphic variants in 10 genes. Data were also extracted from a published genome wide association study to allow analysis of an additional 47 variants in a further 30 genes. Promising associations were seen in nine of the variants (p < 0.05). Given that the estimated false positive report probabilities (FPRPs) for all associations are high (i.e. FPRP > 0.2), these findings should be interpreted with caution. While studies of candidate polymorphisms may be an attractive means of identifying risk factors for HL, future studies should employ sample sizes adequately powered to identify variants having only modest effects on HL risk. Furthermore, because of aetiological heterogeneity within HL, stratification of genotyping according to age, tumour Epstein‐Barr virus status and histology is essential. Copyright © 2015 John Wiley & Sons, Ltd.     

Promoter methylation of glutathione S‐transferase π1 and multidrug resistance gene 1 in bronchioloalveolar carcinoma and its correlation with DNA methyltransferase 1 expression

BACKGROUND:

The presence of glutathione S‐transferase (GST) π1 (GSTP1) or multidrug resistance gene 1 (MDR1) promoter methylation in lung cancer was studied for the first time to the authors' knowledge; and, to date, the clinical significance of methylation is not clear. The objective of the current study was to determine the promoter methylation status of GSTP1 and MDR1, which encode GST‐π and P‐glycoprotein (Pgp), respectively, in patients with bronchioloalveolar carcinoma (BAC) and to investigate whether methyltransferase 1 (DNMT1)‐mediated GSTP1 or MDR1 methylation are responsible for disease progression and prognosis in patients with BAC.

METHODS:

Protein expression levels of DNTM1, GST‐π, and Pgp were determined by immunohistochemistry in samples from 36 patients with BAC. Promoter methylation status of the GSTP1 and MDR1 genes was determined by using methylation‐specific polymerase chain reaction analysis.

RESULTS:

The results demonstrated a significant correlation between the methylation of the GSTP1 or MDR1 promoters and negative expression of their respective proteins in BAC (P < .05). A significant correlation also was demonstrated between GSTP1 methylation and recurrence‐free and overall survival of patients with BAC. DNMT1 protein expression levels were correlated with GSTP1 promoter methylation and patient prognosis (P < .05). However, no correlation was observed between DNMT1 expression and MDR1 methylation.

CONCLUSIONS:

GSTP1 promoter methylation mediated by DNMT1 may promote BAC progression and could serve as a poor prognostic indicator for patients with this disease. DNMT1 protein expression also may be considered as a prognostic indicator. Methylation of the MDR1 promoter may be mediated through pathways other than DNMT1 in BAC and does not appear to be associated with disease progression or patient prognosis. Cancer 2009. © 2009 American Cancer Society.     

Genetic polymorphism of miR‐146a is associated with gastric cancer risk: a meta‐analysis

Several studies have investigated the associations between miR‐146a rs2910164 and gastric cancer (GC) risk, but results have been inconclusive. To derive a more precise estimation of the relationship, a meta‐analysis was performed. PubMed and China National Knowledge Infrastructure searches were carried out for relevant studies published before July 2014. Meta‐analysis was performed with the stata , version 11.0. A total of seven case–control studies, including 3283 cases and 4535 controls, were selected. A significant association was found between rs2910164 and GC risk under all genetic models (CC vs. GG, OR = 0.76, 95% CI = 0.66–0.87; CC vs. GC+GG, OR = 0.84, 95% CI = 0.71–0.99; CC+GC vs. GG, OR = 0.82, 95% CI = 0.73–0.91) for the total data. In the subgroup analysis by ethnicity, statistically significant association was found in Asian. This meta‐analysis suggested that the miR‐146a rs2910164 was a risk factor for developing GC.     

The PHLDB1 rs498872 (11q23.3) polymorphism and glioma risk: A meta‐analysis

The association between the rs498872 single nucleotide polymorphism (SNP) and glioma risk has been studied, but these studies have yielded conflicting results. In order to explore this association, we performed a meta‐analysis. A comprehensive literature search was performed using PubMed and EMBASE database, with the last search up to August 23, 2013. Six articles including 10 case‐control studies in English with 18 002 controls and 8434 cases were eligible for the meta‐analysis. Subgroup analyses were conducted by source of controls and ethnicity. The combined results showed that rs498872 polymorphism was significantly associated with glioma risks (TT vs CC: OR = 1.337, 95% CI = 1.222–1.462; TC vs CC: OR = 1.173, 95% CI = 1.081–1.272; dominant model: OR = 1.199, 95% CI = 1.101–1.306; recessive model: OR = 1.237, 95% CI = 1.135–1.347; additive model: OR = 1.156, 95% CI = 1.085–1.232). Moreover, there was increased cancer risk in all genetic models after stratification of the SNP data by the source of controls and ethnicity, and no evidence of publication bias was produced. Our meta‐analysis suggested that rs498872 polymorphism was associated with increased risk of glioma. However, additional studies exploring the combined effects of rs498872 polymorphisms in Asian population should be investigated.     

Clinicopathological and prognostic significance of circulating tumor cells in patients with gastric cancer: A meta‐analysis

The prognostic significance of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in patients with gastric cancer (GC) is controversial. The aims of our meta‐analysis are to assess its correlation with clinicopathological characteristics and prognostic significance in GC. PubMed, Embase, the Cochrane database, the Science citation index, the CNKI database and the references of relevant studies were systematically searched (up to November, 2013). Using the random‐effect model, the meta‐analysis was completed with odds ratio (OR), risk ratio, hazard ratio (HR) and 95% confidence intervals (CI) as effect values. Twenty‐six studies containing 2,566 patients with GC were analyzed. The overall analysis showed that the incidence difference of tumor cells (CTCs/DTCs) was significant when comparing the stage I/II group to the stage III/IV group (OR = 0.36, CI [0.23, 0.56]), the Lauren diffuse group to the intestinal group (OR = 2.06, CI [1.06, 4.00]), the poorly differentiated group to the well/moderate group (OR = 1.65, CI [1.10, 2.50]), the lymphatic involvement positive group to the positive group (OR = 2.92, CI [1.00, 8.55]). The detection of CTCs/DTCs was significantly related with the disease‐free survival of patients (HR = 3.42, CI [2.39, 4.91]) and the detection of CTCs in peripheral blood was significantly related with the overall survival of patients (HR = 2.13, CI [1.13, 4.03]). Our meta‐analysis indicates that detection of CTCs/DTCs is associated with prognosis for patients with GC and thus could act as a basis for GC staging.     

Prognostic role of neutrophil‐to‐lymphocyte ratio in colorectal cancer: A systematic review and meta‐analysis

The prognostic role of inflammation index like neutrophil‐to‐lymphocyte ratio (NLR) in colorectal cancer (CRC) remains controversial. We conduct a meta‐analysis to determine the predictable value of NLR in the clinical outcome of CRC patients. The analysis was carried out based on the data from 16 studies (19 cohorts) to evaluate the association between NLR and overall survival (OS) and progression‐free survival (PFS) in patients with CRC. In addition, the relationship between NLR and clinicopathological parameters was assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that elevated pretreatment NLR predicted poorer OS (HR: 1.813, 95% CI: 1.499–2.193) and PFS (HR: 2.102, 95% CI: 1.554–2.843) in patients with CRC. Increased NLR is also significantly associated with the poorer differentiation of the tumor (OR: 1.574, 95% CI: 1.226–2.022) and higher carcino‐embryonie antigen (CEA) level (OR: 1.493, 95% CI: 1.308–1.705). By these results, we conclude that NLR gains a prognostic value for patients with CRC. NLR should be monitored in CRC patients for rational stratification of the patients and adjusting the treatment strategy.     

XRCC1 gene polymorphisms and esophageal squamous cell carcinoma risk in Chinese population: A meta‐analysis of case–control studies

Two non‐synonymous polymorphisms Arg194Trp and Arg399Gln in the DNA‐base excision repair gene X‐ray repair cross‐complementing group 1 (XRCC1) have been implicated in risk for esophageal cancer. However, the results from different studies remain controversial. The present meta‐analysis of literatures was performed to clarify these associations in Chinese population. A comprehensive literature search was conducted to identify all case–control studies of XRCC1 polymorphisms Arg194Trp and Arg399Gln and risk for esophageal squamous cell carcinoma (ESCC). A total of 9 eligible studies, including 1,538 ESCC cases and 2,472 controls, were identified to the meta‐analysis. The odds ratio (OR) for the variant homozygous genotype Trp/Trp of the Arg194Trp polymorphism, compared with the wild‐type homozygote Arg/Arg, was 1.59 (p = 0.0007), with 95% confidence interval (95% CI) 1.22–2.09, for ESCC risk without between‐study heterogeneity. However, there was no statistically significant associations of ESCC risk in the dominant model Arg/Trp+Trp/Trp (OR 0.97; 95% CI 0.84–1.12; p = 0.69) and heterozygous genotype Arg/Trp (OR 0.90; 95% CI 0.77–1.04; p = 0.16) when comparing with wild‐type genotype Arg/Arg. For Arg399Gln, there was no effect in dominant modeling (Arg/Gln+Gln/Gln vs. Arg/Arg: OR 0.92; 95% CI 0.80–1.06; p = 0.25), and the variant Gln/Gln homozygote was not associated with ESCC risk (OR 1.29; 95% CI 0.79–2.10; p = 0.31), either. In conclusion, Arg194Trp genetic polymorphism may be associated with an increased risk for developing ESCC and a study with the larger sample size is needed to further evaluate gene–environment interaction on XRCC1 polymorphisms and ESCC risk. © 2009 UICC     

Prognostic role of platelet to lymphocyte ratio in non‐small cell lung cancers: A meta‐analysis including 3,720 patients

Platelet to lymphocyte ratio (PLR) was recently reported as a useful index in predicting the prognosis of lung cancer. However, the prognostic role of PLR in lung cancer remains controversial. The aim of this study was to evaluate the association between PLR and clinical outcome of lung cancer patients through a meta‐analysis. Relevant literatures were retrieved from PubMed, Ovid, the Cochrane Library and Web of Science databases. Meta‐analysis was performed using hazard ratio (HR) and 95% confidence intervals (CIs) as effect measures. A total of 5,314 patients from 13 studies were finally enrolled in the meta‐analysis. The summary results showed that elevated PLR predicted poorer overall survival (OS) (HR: 1.526, 95%CI: 1.268–1.836, p < 0.001) in patients with lung cancer and OS (HR: 1.631, 95%CI: 1.447–1.837, p < 0.001) in patients with nonsmall cell lung cancer (NSCLC). Subgroup analysis revealed that increased PLR was also associated with poor OS in NSCLC treated by surgical resection (HR: 1.884, 95%CI: 1.308‐2.714, P < 0.001) and non‐surgery (HR: 1.570, 95%CI: 1.323‐1.863, P < 0.001). In addition, PLR Cut‐off value ≤ 160 (HR: 1.506, 95%CI: 1.292‐1.756, P < 0.001) and PLR Cut‐off value>160 (HR: 1.842, 95%CI: 1.523‐2.228, P < 0.001). In contrast, elevated PLR was not associated with OS (HR: 1.117, 95%CI: 0.796‐1.569, P > 0.05) in patients with small cell lung cancer (SCLC).This meta‐analysis result suggested that elevated PLR might be a predicative factor of poor prognosis for NSCLC patients.     

Association between the MDR1 gene variant C3435T and risk of leukaemia: a meta‐analysis

Although a number of genetic studies have attempted to link the multidrug resistance (MDR1) C3435T polymorphism to risk of leukaemia, the results were often inconsistent. The present study aimed at investigating the pooled association using a meta‐analysis on the published studies. 1933 cases and 2215 controls of 11 published studies in English before June 2012 were involved in the updated meta‐analysis. Furthermore, subgroup analysis was performed in different ethnic and leukaemia subtype groups. This meta‐analysis suggests that the MDR1 C3435T polymorphism associate with risk of leukaemia. The effect of the variant on the expression levels and the possible functional role of the variant in leukaemia should be addressed in further studies.     

Adjuvant chemotherapy for patients with primary hepatocellular carcinoma: A meta‐analysis

Numerous studies have investigated the effects of adjuvant chemotherapy for primary hepatocellular carcinoma (HCC) patients. We conducted this analysis to evaluate the efficacy of adjuvant chemotherapy in HCC patients after hepatectomy. PubMed/MEDLINE, EMBASE, Cochrane, and other databases were searched for eligible studies. The major endpoints were overall survival (OS) and disease‐free survival (DFS). The pooled odds ratio (OR) was calculated using a random‐effects model to summarize the results. In the meta‐analysis of 13 randomized control trials (RCTs) and 35 observational studies with 4747 patients, hepatectomy plus adjuvant chemotherapy showed superiority over hepatectomy alone in 1‐year DFS (OR = 1.86, 1.38–2.51, p < 0.001), 3‐year DFS (OR = 2.37, 1.73–3.24, p < 0.001) and 5‐year DFS (OR = 1.99, 1.55–2.55, p < 0.001), as well as 1‐year OS (OR = 2.16, 95% confidence interval 1.75–2.68, p < 0.001), 3‐year OS (OR = 1.77, 1.48–2.13, p < 0.001) and 5‐year OS (OR = 1.92, 1.44–2.56, p < 0.001). Subgroup and sensitivity analysis revealed that only adjuvant TACE had significant survival benefits. The meta‐analysis of studies involving patients with portal vein tumor thrombus (PVTT), but not other factors related to recurrence risk, revealed favorable outcomes of the Treatment arm over the Control arm. The present study shows that adjuvant chemotherapy can improve outcomes for HCC patients. The benefits of adjuvant TACE have been confirmed whereas the effects of other adjuvant chemotherapy modalities remain uncertain. Adjuvant chemotherapy is likely to be more applicable to certain patient populations for instance those with PVTT, but further research in identifying these patient factors is of importance for tailoring adjuvant therapies to individual patients in the future.     

Association between polymorphisms in the GSTA4 gene and risk of lung cancer: a case-control study in a Southeastern Chinese population

GST Alpha 4 (GSTA4) has an important role in the protection against oxidative stress induced by carcinogens such as tobacco smoke. However, few studies investigated the association between GSTA4 polymorphisms and lung cancer risk. We genotyped three selected GSTA4 SNPs (rs182623 - 1718:T > A, rs3798804 + 5034:G > A and rs316141 + 13984:C > T) in a case-control study of 500 lung cancer patients and 517 cancer-free controls and evaluated the association between these SNPs and risk of lung cancer in this Han Chinese population. We found that there was a significant difference in genotype and allele frequency distributions of GSTA4 -1718 between the cases and the controls (P = 0.006 and P = 0.003, respectively). Compared with the GSTA4 -1718TT genotype, individuals with the TA + AA genotypes had a significantly decreased risk of lung cancer (adjusted OR, 0.63; 95% CI, 0.47-0.84; P = 0.006). Although there were no such statistical differences between the cases and controls at the loci +5034 and +13984, nor for histological types, individuals carrying the genotypes of -1718TA, +5034GG and +13984CT had a significantly decreased lung cancer risk (OR, 0.37; 95% CI, 0.23-0.61; P < 0.0001), especially for those smokers who smoked 相似文献