Association of GSTM1, GSTT1, and GSTP1 gene polymorphisms with the risk of prostate cancer: a meta-analysis.

The glutathione S-transferase (GST) gene superfamily encodes for enzymes involved in conjugation of electrophilic compounds to glutathione. Several polymorphisms in the GST genes have been implicated as risk factors for prostate cancer. We did a meta-analysis of 11 studies with GSTM1 genotyping (2,063 prostate cancer cases and 2,625 controls), 10 studies with GSTT1 genotyping (1,965 cases and 2,554 controls), and 12 studies with GSTP1 genotyping (2,528 cases and 3,076 controls). The random effects odds ratio was 1.08 [95% confidence interval (95% CI), 0.93-1.25, no significant between-study heterogeneity] for the GSTM1 null versus nondeleted genotype and 0.90 (95% CI, 0.73-1.12; P = 0.03 for heterogeneity) for the GSTT1 null versus nondeleted genotype. Overall, the random effects odds ratio was 1.05 (95% CI, 0.90-1.21; P < 0.01 for heterogeneity) for the GSTP1-Val versus GSTP1-Ile allele. For all three polymorphisms, there was a trend for the presence of an association in the earliest published studies, but this did not seem to be validated in subsequent research. For GSTT1, larger studies gave different results than smaller ones. The meta-analysis shows that these three polymorphisms are unlikely to be major determinants of susceptibility to prostate cancer on a wide population basis.     

GSTM1 and GSTT1 polymorphisms and postmenopausal breast cancer risk

Glutathione S-transferases (GSTs) are a family of important enzymes involved in the detoxification of a wide variety of known and suspected carcinogens, including potential mammary carcinogens identified in charred meats and tobacco smoke. A substantial proportion of the Caucasian population has a homozygous deletion (null) of the GSTM1 or GSTT1 gene, which results in lack of production of these isoenzymes. We conducted a case-control study in a cohort of postmenopausal Iowa women who in 1986 completed a mailed questionnaire on lifestyle factors including information on cigarette smoking and breast cancer risk factors. DNA samples and information related to charred meat intake were obtained, in the case-control study, from breast cancer cases diagnosed during 1992–1994, and a random sample of cancer-free cohort members. Included in this study were 202 cases and 481 controls who were genotyped for GSTM1 or GSTT1 gene polymorphisms. Compared to women who had both GSTM1 and GSTT1 genes, a 60% elevated risk (95% CI = 1.0–2.5) was observed among those whose GSTM1 or GSTT1 gene was deleted. When stratified by meat eating habits, the risk of breast cancer associated with null GSTM1 or GSTT1 genotype was observed primarily among women who ate meats consistently well- or very well-done. Women who carried either one of the null genotypes and consumed meat consistently well- or very well-done had a 3.4-fold elevated risk of developing breast cancer (95% CI = 1.6–7.1). Cigarette smoking was not a risk factor for breast cancer among women who had either the GSTM1 or GSTT1 genes. Among those with the null GSTT1 genotype, however, a significantly elevated risk of breast cancer was associated with cigarette smoking (OR = 2.5, 95% CI = 1.1–5.4) and the association was stronger among former (OR = 4.4, 95% CI = 1.5–12.8) than current smokers (OR = 1.3, 95% CI = 0.4–4.1). This study suggests that certain null GST genotypes may be associated with an elevated risk of breast cancer and the association may be modified by charred meat intake and cigarette smoking.     

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.     

The GSTT1 null genotype contributes to increased risk of prostate cancer in Asians: a meta-analysis

Background: Many studies have investigated the association between glutathione S-transferase T 1 (GSTT1)null genotype and risk of prostate cancer, but the impact of GSTT1 null genotype in Asians is still unclear owingto inconsistencies across results. Thie present meta-analysis aimed to quantify the strength of the associationbetween GSTT1 null genotype and risk of prostate cancer. Methods: We searched the PubMed, Embase andWangfang databases for studies of associations between the GSTT1 null genotype and risk of prostate cancer inAsians and estimated summary odds ratio (OR) with their 95% confidence interval (95% CI). Results: A totalof 11 case-control studies with 3,118 subjects were included in this meta-analysis, which showed the GSTT1null genotype to be significantly associated with increased risk of prostate cancer in Asians (random-effects OR= 1.49, 95% CI 1.15-1.92, P = 0.002), also after adjustment for heterogeneity (fixed-effects OR = 1.45, 95% CI1.23-1.70, P < 0.001). No evidence of publication bias was observed. Conclusions: This meta-analysis of availabledata suggested the GSTT1 null genotype does contribute to increased risk of prostate cancer in Asians.     

Glutathione s-transferase polymorphisms (GSTM1, GSTP1 and GSTT1) and the risk of acute leukaemia: a systematic review and meta-analysis

Glutathione s-transferase (GST) polymorphisms (GSTM1, GSTP1 and GSTT1) have been considered as risk factors for developing acute leukaemia in a number of studies; however the overall results of such studies are inconsistent. To investigate a putative association of GST polymorphisms with the risk of acute leukaemia, we performed a systematic review and meta-analysis of 30 published case-control studies. To take into account the possibility of heterogeneity across the studies, a statistical test was performed. The pooled odds ratios (ORs) were assessed using both a fixed-effects and a random-effects model. The pooled OR of acute leukaemia risks associated with GSTM1 null genotype, GSTP1 Val105 allele and GSTT1 null genotype were 1.22 (95% confidence interval (CI) 1.07-1.38), 1.07 (95% CI 1.00-1.13) and 1.19 (95% CI 1.00-1.41), respectively. Significantly increased risk of acute lymphoblastic leukaemia associated with GSTM1 and GSTT1 null genotypes was observed. Their pooled ORs were 1.24 (95% CI 1.17-1.31) and 1.30 (95% CI 1.06-1.60), respectively. We also found substantial evidence of heterogeneity between the studies. Our results suggest that GSTM1 and GSTT1, but not GSTP1 polymorphisms, appear to be associated with a modest increase in the risk of acute lymphoblastic leukaemia. It is conceivable that GSTM1 and GSTT1 null genotypes may thus play a role in leukemogenesis. A review of the 30 case-control studies indicates that greater attention should be paid to the design of future studies.     

GSTM1 null polymorphisms and oral cancer risk: a meta-analysis

Many studies have examined the association between the GSTM1 null gene polymorphism and oral cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and Embase databases were searched for case–control studies published up to May 2013. Data were extracted and pooled odds ratio (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 39 studies, comprising of 4,704 oral cancer cases and 7,090 controls, were included. Overall, for null versus present, the pooled OR was 1.29 (95 % CI?=?1.20–1.40), and the heterogeneity was found in all studies. In the stratified analysis by ethnicity, significant risks were found among Asians (OR?=?1.39, 95 % CI?=?1.27–1.53; P?=?0.000 for heterogeneity), but not in Caucasians (OR?=?0.99, 95 % CI?=?0.83–1.18; P?=?0.677 for heterogeneity). In conclusion, this meta-analysis demonstrates that the GSTM1 null gene polymorphism may be an increased risk of oral cancer in Asians but not in Caucasians.     

Associations of GSTM1 and GSTT1 polymorphisms with pancreatic cancer risk

Glutathione S-transferases (GSTs), including glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1), are multifunctional enzymes which play vital roles in the detoxification of a variety of carcinogens. The genetic polymorphisms of GSTM1 and GSTT1 have been implicated in pancreatic cancer risk, but the results of published studies remain conflicting. Thus, a meta-analysis was conducted to estimate the effect of GSTM1 and GSTT1 polymorphisms on the risk of developing pancreatic cancer. A comprehensive search was performed in the PubMed, Embase, Web of Science, and Wanfang databases to identify the available studies on the associations of GSTM1 and GSTT1 polymorphisms with pancreatic cancer risk. The pooled odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) was used to estimate the associations. Stratified analyses by ethnicity and sensitivity analyses were performed to further identify the relationships. Overall, the null genotype of GSTT1 was associated with an increased risk of pancreatic cancer (OR?=?1.61, 95 % CI 1.06–2.44, P _OR?=?0.025), but similar association was not found between the null genotype of GSTM1 and pancreatic cancer risk. Besides, a significant association of GSTT1 polymorphism with pancreatic cancer risk was identified in Asians (OR?=?2.58, 95 % CI 1.67–3.98, P _OR?<?0.001), but not in Caucasians (OR?=?1.16, 95 % CI 0.94–1.43, P _OR?=?0.170). Sensitivity analyses by sequential omission of individual study confirmed the stability of our results. Meta-analysis of available data thus far shows that the null genotype of GSTT1 is a risk factor for pancreatic cancer, particularly in the Asian population. The currently available data are not sufficient enough to identify the association between the GSTM1 polymorphism and pancreatic cancer risk.     

GSTT1 and GSTP1 polymorphisms and breast cancer risk: a meta-analysis

B and T lymphocyte attenuator (BTLA) is an immunoinhibitory receptor with the ability to deliver inhibitory signals for suppressing lymphocyte activation. To identify the influences of BTLA gene polymorphisms on the risk of sporadic breast cancer, a case–control study was conducted in women from northeast of China, Heilongjiang Province. We genotyped five SNPs (rs9288952, rs2931761, rs2633562, rs2705535 and rs1844089) in BTLA gene among exons and introns. Our research groups consist of 592 patients with breast cancer and 506 age/sex-matched healthy controls. Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction with confronting two-pair primer (PCR-CTPP) methods. Data were analyzed using the chi-square test by EXCEL, SPSS and Haploview softwares. The frequencies of BTLA rs1844089 CT and rs2705535 AG were higher in patients than in controls (P = 0.0164; P = 0.0031), and rs1844089 CC, rs2705535 GG and rs9288952 CC genotypes had lower incidences in patients than in controls (P = 0.0483; P = 0.0098; P = 0.0400). The frequency of haplotype CAAAT was significantly higher in patients (P = 0.0112). Strong association was shown between five SNPs of BTLA gene and tumor size, estrogen receptor (ER), progesterone receptor (PR), C-erbB-2 and P53 statuses. Strong association was observed between tumor size, ER, PR, P53 and the CAGAT(P = 0.012), TAAGT(P = 0.0378), CAGAT(P = 0.0013), CAAGT(P = 0.0373) and CAAAT(P = 0.0306) haplotypes. These results primarily suggested that BTLA gene polymorphisms may affect the sporadic breast cancer risk and prognosis in Chinese women in northeast of Heilongjiang Province.     

GSTM1, GSTT1 and GSTP1 polymorphisms and lung cancer risk

Previous studies have suggested that GST genotypes may play a role in determining susceptibility to lung cancer, though the data are often conflicting. In this study we investigated GSTM1, GSTT1 and GSTP1 status in relation to lung cancer risk in patients attending a Manchester bronchoscopy clinic. Cases were all patients (n=94) currently with, or with a history of, tumours of the lung, trachea or bronchus. The control group were all other patients (n=165) who were free of benign and malignant tumours both at the time of, or prior to, diagnosis. All patients were interviewed for information on lifestyle risk factors, and DNA extracted from bronchial lavage and blood samples was used for genotyping. GSTM1 null genotype was associated with decreased lung cancer risk (odds ratio (OR) 0.50, 95% confidence interval (CI) 0.29–0.87), particularly among men (OR 0.43, 95% CI 0.21–0.87) and those above the median age (OR 0.33, 95% CI 0.15–0.70). No difference in GSTT1 and GSTP1 genotype distribution was seen between cases and controls. The GSTM1 null genotype was associated with a decreased risk of squamous cell carcinoma: the OR, adjusted for age, sex and pack years was 0.32 (95% CI 0.12–0.82). As previous studies have reported that the GSTM1 null genotype is associated with an increased lung cancer risk, further work is required to determine whether the observed association is true, or whether it arises from bias or confounding factors.     

XRCC1 polymorphisms increase bladder cancer risk in Asians: a meta-analysis

X-ray cross complementing group 1 (XRCC1) polymorphisms and bladder cancer risk has been investigated for years, but the result in Asian population is till inconclusive. Thus, we performed this meta-analysis to determine the association of XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphisms with bladder cancer risk in the Asian population. PubMed, EMBASE, and China National Knowledge Infrastructure were searched up to January 2013 to identify eligible studies. The association strength was measured with odd ratios (ORs) and 95 % confidence intervals (95 % CIs). A total of nine eligible studies, including 1,931 bladder cancer patients and 2,192 controls, were identified. Significant increased risk of bladder cancer was observed for Arg194Trp polymorphism (allele comparison OR?=?1.20, 95 % CI: 1.06–1.36, P_{heterogeneity}?=?0.11; dominant model OR?=?1.20, 95 % CI: 1.02–1.41, P_{heterogeneity}?=?0.37) and Arg280His polymorphism (heterozygote comparison OR?=?1.87, 95 % CI: 1.21–2.90, P_{heterogeneity}?=?0.01; dominant model OR?=?1.75, 95 % CI: 1.05–2.90, P_{heterogeneity}?=?0.01); however, Arg399Gln was not associated with susceptibility to bladder cancer. No evidence of publication bias was detected. Our meta-analysis results suggest that XRCC1 Arg194Trp and Arg280His polymorphisms are associated with significantly increased risk of bladder cancer in Asians.     

Significant associations between GSTM1/GSTT1 polymorphisms and nasopharyngeal cancer risk

Glutathione S-transferases play a critical role in the detoxification and elimination of electrophilic carcinogens by conjugating them to glutathione. Homozygous deletions of GSTM1 and GSTT1 have been suggested as risk factors for some cancers, including colorectal, pancreatic, and esophageal cancers. Results of previous individual studies published to estimate the associations between GSTM1/GSTT1 polymorphisms and nasopharyngeal cancer (NPC) risk remained controversial. Thus, we carried out a meta-analysis by pooling the odds ratios (ORs) with corresponding 95 % confidence intervals (95 % CIs) of all currently available case–control studies to shed some light on the contradictory finding. A comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases up to October 20, 2012 was performed to identify eligible studies. A total of 15 separate publications involving 2,226 NPC cases and 3,339 controls were finally included into this meta-analysis. The meta-analysis of total studies showed that the null genotypes of GSTM1 and GSTT1 were both significantly associated with increased risk of NPC (for GSTM1: OR?=?1.54, 95 % CI 1.28–1.86, P _OR?<?0.001; for GSTT1: OR?=?2.25, 95 % CI 1.50–3.36, P _OR?<?0.001). Subgroup analysis by ethnicity suggested that carriers of both GSTM1 and GSTT1 null genotypes in Asians were more susceptible to NPC. Additionally, in the subgroup analysis based on the sample size, significant associations of the GSTM1 and GSTT1 polymorphisms with NPC susceptibility were identified among studies both with larger case sample size (number of cases ≥100) and smaller case sample size (number of cases <100). Sensitivity analysis confirmed the stability of our results. These results indicate that the GSTM1 and GSTT1 polymorphisms may play crucial roles in the development of NPC, especially in Asians.     

Association of GSTT1 gene polymorphisms with the risk of prostate cancer: an updating meta-analysis

It has been demonstrated that the glutathione S-transferase (GST) superfamily helps remove carcinogens from the body and thus might be associated with prostate cancer risk. In recent years, GSTT1 polymorphism has been extensively studied as a potential prostate cancer risk factor; however, the results are inconsistent. To investigate the association between GSTT1 and prostate cancer, we conducted a meta-analysis of 33 studies with 6,697 prostate patients and 7,643 controls. For GSTM1 null versus present genotype, the random effects odds ratio was 0.98 (95 % confidence interval (CI) 0.83–1.16) based on a wide population. Subgroup analyses in the different ethnic groups and different controls were performed. The OR was 1.01 (95 % CI 0.86–1.19) in Caucasians, 1.01 (95 % CI 0.70–1.47) in Asians, and 0.77 (95 % CI 0.42–1.42) in Africans. The OR was 0.98 (95 % CI 0.82–1.16) in non-benign prostate hyperplasia (BPH) controls and 1.09 (95 % CI 0.66–1.79) in BPH controls. In conclusion, our present meta-analysis demonstrates that there is no association between GSTT1 polymorphism and prostate cancer, even in the sub-analysis concerning different races and control sources. The direction of further research should focus not only on the simple relationship of GSTT1 and prostate cancer but also on gene–environment interaction and distinctions of different GSTs.     

The role of GSTM1 and GSTT1 polymorphisms in head and neck cancer risk

Head and neck cancer (HNC) is a serious health problem worldwide and tobacco smoke is a main causative factor for this malignancy. Interindividual genetic differences in enzymes involved in the metabolism of tobacco smoke carcinogens are one of the most important risk factors in the development of HNC. GSTM1 and GSTT1 enzymes participate in detoxifying of tobacco smoke carcinogens and have deletion polymorphisms. We performed a case control study to investigate a possible association between GSTM1 and GSTT1 variants and HNC risk. A total of 98 HNC cases, all of which were squamous cell carcinoma, and 120 healthy controls were investigated. GSTM1 and GSTT1 polymorphisms were genotyped using PCR. There was a significant association between HNC and GSTM1-null genotype (adjusted OR: 2.36, 95% CI: 1.303-4.26, p = 0.005). The frequency overall of GSTT1-null genotypes was not significant in HNC patients compared with that of GSTT1-positive genotypes (adjusted OR: 1.16, 95% CI: 0.563-2.397, p = 0.686). No combined effect was observed for GSTM1 and GSTT1 genotypes. When data were stratified by smoking status, cases having GSTM1-null genotype who were smokers conferred the highest risk (adjusted OR: 4.06, 95% CI: 1.3-12.63). Thus, our results suggest that GSTM1 polymorphism may significantly increase the risk of HNC and there is an additive interaction between GSTM1-null genotype and smoking on HNC risk.     

Association between glutathione S-transferases M1 and T1 gene polymorphisms and prostate cancer risk: a systematic review and meta-analysis

Genetic polymorphisms in glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) genes have been widely reported and considered to have a significant effect on prostate cancer (PCa) risk, but the results are inconsistent. To evaluate the impact of the GSTM1 and GSTT1 polymorphism on PCa risk, we conducted a comprehensive meta-analysis based on 18 eligible studies. A total of 18 studies, including 7,119 subjects for GSTM1 and 6,454 subjects for GSTT1 between 1999 and 2012 were identified through researching MEDLINE, PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure database, and Chinese Biomedical Literature database. A meta-analysis was performed to obtain summary-estimated odd ratios and 95 % confidence intervals of GSTM1 and GSTT1 polymorphisms for PCa, with attention to study quality and publication bias. Overall, there is a significant association between GSTM1 (odds ratio (OR)?=?1.407, 95 % confidence intervals (95 % CI)?=?1.147–1.727, I ²?=?73.2 %, P?= 0.001) genotypes and PCa susceptibility. Significant associations were also observed in subgroups of Caucasian populations (OR?=?1.262, 95 % CI?=?1.055–1.511, I ²?=?48.7 %, P?=?0.011) and Asian populations (OR?=?1.776, 95 % CI?=?1.134–2.781, I ²?=?83.4 %, P?=?0.012). However, no significant association was found (OR?=?1.776, 95 % CI?=?1.134–2.781, P?=?0.243) in African-American populations when stratified by ethnicity. While, there was no significant association seen between GSTT1 (OR?=?1.003, 95 % CI?=?0.823–1.298, I ²?=?68.8 %, P?=?0.778) genotypes and PCa risk. However, no significant associations were observed in subgroups of Caucasian populations (OR?=?1.086, 95 % CI?=?0.801–1.471, I ²?=?72.1 %, P?=?0.597) and Asian populations (OR?=?0.961, 95 % CI?=?0.644–1.434, I ²?=?73.0 %, P?=?0.846), and similar result was found among African-American populations (OR?=?0.802, 95 % CI?=?0.194–3.321, P?=?0.761) when stratified by ethnicity. Our results suggest that the GSTM1 gene polymorphism contributes to PCa susceptibility, while GSTT1 gene polymorphism is not associated with PCa in our study.     

CYP2E1 polymorphisms and colorectal cancer risk: a HuGE systematic review and meta-analysis

Studies investigating the associations between Cytochrome P4502E1 (CYP2E1) polymorphisms and colorectal cancer (CRC) risk report conflicting results. We conducted a meta-analysis to assess the association between CYP2E1 gene Rsa I/Pst I, Dral T/A and 96-bp insertion polymorphisms and CRC susceptibility. Two investigators independently searched the Medline, Embase, CNKI, Wanfang, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for CYP2E1 polymorphisms and CRC were calculated in a fixed-effect model (the Mantel–Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. Ultimately, 12, 5, and 4 studies were found to be eligible for meta-analyses of Rsa I/Pst I, Dral T/A, and 96-bp insertion polymorphisms, respectively. Our analysis suggested that the variant genotype of Rsa I/Pst I were associated with a significantly increased CRC risk (c2/c2 vs. c1/c1, OR?=?1.36, 95 % CI?=?1.04–1.77; recessive model, OR?=?1.35, 95 % CI?=?1.04–1.75). Moreover, similar results were observed between CYP2E1 96-bp insertion polymorphism and CRC risk (dominant model, OR?=?1.25, 95 % CI?=?1.07–1.45), while no association was observed between CYP2E1 Dral T/A polymorphism and CRC susceptibility in any genetic model. No publication bias was found in the present study. This meta-analysis shows that CYP2E1 Rsa I/Pst I and 96-bp insertion polymorphisms may be associated with CRC risk. The CYP2E1 Dral T/A polymorphism was not detected to be related to the risk for CRC.     

CYP1A1 and GSTM1 polymorphisms and lung cancer risk in Chinese populations: a meta-analysis

Genetic polymorphisms of cytochrome p450 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genes are thought to have significant effects on the metabolism of environmental carcinogens and thus on cancer risk, but the reported results are not always consistent. In this meta-analysis, we assessed reported studies of associations between polymorphisms of these two genes and risk of lung cancer in Chinese populations. Through a systematic literature search for publications between 1989 and 2006, we summarized the data from 46 studies on polymorphisms of MspI and exon7-Val of CYP1A1 and GSTM1 and lung cancer risk in Chinese populations, and found that compared with the wild-type homozygous genotype (type A), lung cancer risk for the combined variant genotypes (types B and C) was 1.34-fold (95% confidence interval [CI]=1.08-1.67) (Z=2.64, P=0.008); the risk for the combined variant genotypes (Ile/Val and Val/Val) of CYP1A1 exon7 was 1.61-fold (95% CI=1.24-2.08) (Z=3.62, P<0.001), compared with the Ile/Ile genotype; and that the risk for the GSTM1 null genotype was 1.54-fold (95% CI=1.31-1.80) (Z=5.32, P<0.001), compared with the GSTM1 present genotype. Therefore, in 46 published studies in Chinese populations, we found evidence of an association between the CYP1A1 variant and GSTM1 null genotypes and increased risk of lung cancer.     

Dietary isothiocyanates, GSTM1, GSTT1, NAT2 polymorphisms and bladder cancer risk

Isothiocyanates (ITCs) are nonnutrient compounds in cruciferous vegetables with anticarcinogenic properties. ITCs down-regulate cytochrome P-450 biotransformation enzyme levels, activate Phase II detoxifying enzymes and induce apoptosis. On the other hand, ITCs also serve as a substrate for GSTs. Experimental evidences suggest that ITCs have anticarcinogenic effect on bladder cancer. Therefore, we evaluated dietary intake of ITCs, GSTM1, GSTT1 and NAT2 polymorphisms, and bladder cancer risk in a case-control study. There were 697 newly diagnosed bladder cancer cases identified from The University of Texas M. D. Anderson Cancer Center and 708 healthy controls matched to cases by age (+/-5), gender and ethnicity. Participants underwent an in-person interview, in which epidemiologic and food frequency questionnaires were administered to collect demographic and dietary intake data. Median ITC intake per day was statistically significantly lower in cases than in controls (0.23 vs. 0.33, p < 0.001). High ITC intake was associated with 29% decreased risk of bladder cancer [Odds ratio (OR) = 0.71, 95% confidence interval (CI) = 0.57, 0.89]. The protective effect was more evident in older individuals (> or =64-years-old), men, ever smokers and heavy smokers in stratified analysis. Compared with NAT2 rapid acetylator, NAT2 slow acetylator had an increased risk of bladder cancer in Caucasians (OR = 1.31, 95% CI = 1.02, 1.69). There was no main effect associated with the GSTM1 or GSTT1 genotypes. The protective effect of ITCs against bladder cancer was not modified by GSTM1, GSTT1 or NAT2 genotypes. This is the first epidemiological report that ITCs from cruciferous vegetable consumption protect against bladder cancer.     

Genetic polymorphisms in glutathione S-transferases P1 (GSTP1) Ile105Val and prostate cancer risk: a systematic review and meta-analysis

Numerous epidemiological studies have evaluated the association between the glutathione S-transferases P1 (GSTP1) Ile105Val polymorphisms and prostate cancer (PCa) risk. However, these studies have yielded conflicting results. A comprehensive search was conducted through researching MEDLINE, PubMed, Web of Science, and EMBASE, and a total of 13 studies including 3,227 cases and 3,945 controls were identified. A meta-analysis was performed to obtain a summary of estimated odds ratios (ORs) and 95 % confidence intervals (CIs) of GSTP1 polymorphisms for PCa, with attention to study quality and publication bias. The GSTP1 Ile158Val variant genotypes are less associated with increased risk of PCa for the homozygote model (Val/Val vs Ile/Ile: OR?=?1.42; I ²? =?63.7 %; 95 % CI?=?1.02–1.97) and the recessive model (OR?=?1.41; I ²? =?45.5 %; 95 % CI?=?1.10–1.80). However, no associations were detected for other genetic models. In the stratified analysis by ethnicity, significant associations between GSTP1 Ile105Val polymorphism and PCa risk were also found among Caucasians for Val/Val vs Ile/Ile comparison (OR?=?1.22; I ²? =?0.0 %; 95 % CI?=?1.02–1.47) and for the recessive model (OR?=?1.26; I ²? =?0.0 %; 95 % CI?=?1.06–1.49), while there were no associations found for other genetic models. However, no associations were found in Asians and African-Americans for all genetic models when stratified by ethnicity. In conclusion, our meta-analysis provides evidence that GSTP1 Ile105Val gene polymorphisms contributed to PCa susceptibility.     

Genetic polymorphisms of CYP1A1, GSTM1 and GSTT1 genes and lung cancer risk

Genetic polymorphisms of the genes encoding for the xenobiotic metabolizing enzymes result in individual variations in the efficiency of detoxification of environmental carcinogens, and have been extensively associated with variable risk for lung neoplasms in different ethnic and environmental backgrounds. In this study, using PCR-RFLP based assays, we investigated the distribution of genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 genes in Greek lung cancer patients (N=122) and healthy controls (N=178). The frequency of CYP1A1 m1 homozygous genotype was 0.04 in patients and 0.02 in controls (detected in 4.10% of patients and in 1.69% of controls, respectively), that of GSTM1 null genotype was 0.52 in patients and 0.54 in controls, whereas those of GSTT1 null genotype was 0.17 and 0.11, in patients and controls, respectively. The GSTM1 null genotype was more frequent in adenocarcinoma, as well as in lung cancer patients with history of chronic obstructive pulmonary disease (COPD). The GSTT1 null genotype correlated with advanced age of the patients at the time of diagnosis. Three combinations of rare genotypes - in subjects carrying simultaneously deviations from the common genotype in more than one gene - were over-represented in lung cancer patients, compared to control population, and were furthermore significantly associated with history of heavy tobacco consumption in lung cancer patients. The results imply involvement of specific genotype combinations of CYP1A1, GSTM1 and GSTT1 alleles in the development of lung cancer in heavy smokers.     

GSTM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: A comprehensive meta-analysis

Glutathione S-transferases (GSTs) catalyse reactions between glutathione and lipophilic compounds with electrophilic centres, leading to neutralisation of toxic compounds, xenobiotics and products of oxidative stress. Controversy exists about whether GST polymorphisms (GSTM1 null/present genotype, GSTT1 null/present genotype, GSTP1 Ile105Val and GSTA11A/1B) represent risk factors for colorectal cancer. This meta-analysis aims to examine the associations between the above-mentioned polymorphisms and colorectal cancer risk. Forty-four studies were eligible for GSTM1 (11,998 colorectal cancer cases, 17,552 controls), 34 studies for GSTT1 (8596 cases, 13,589 controls), 19 studies for GSTP1 (5421 cases, 7671 controls) and four studies for GSTA1 polymorphism (1648 cases, 2039 controls). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. Separate analyses were conducted on Caucasian and Chinese populations. Where appropriate, sensitivity analysis concerning the deviation of genotype frequencies in controls from the Hardy–Weinberg equilibrium was performed. GSTM1 null allele carriers exhibited increased colorectal cancer risk in Caucasian populations (pooled OR = 1.150, 95% confidence interval (CI): 1.060–1.248, random effects); no significant association was detected for Chinese subjects (pooled OR = 1.025, 95% CI: 0.903–1.163, fixed effects). Similarly, GSTT1 null allele carriers exhibited increased colorectal cancer risk in Caucasian populations (pooled OR = 1.312, 95% CI: 1.119–1.538, random effects); the association in Chinese subjects was not significant (pooled OR = 1.068, 95% CI: 0.788–1.449, random effects). Concerning GSTP1 Ile105Val no significant associations were demonstrated in either race. GSTA11A/1B polymorphism was not associated with colorectal cancer risk. GSTM1 and GSTT1 null genotypes confer additional risk for colorectal cancer in Caucasian populations.