Genetic polymorphisms of glutathione S-transferase M1 and bladder cancer risk: a meta-analysis of 26 studies

Studies investigating the association between glutathione S-transferase M1 (GSTM1) polymorphism and bladder cancer risk report conflicting results. The objective of this study was to quantitatively summarize the evidence for such a relationship. We performed a systematic search of the National Library of Medline and Embase databases. This meta-analysis included 26 case-control studies, which included 5029 bladder cancer cases and 6680 controls. The combined results based on all studies showed that the GSTM1 null genotype was associated with an increased risk of bladder cancer (OR = 1.46, 95% confidence interval [CI] = 1.35, 1.57). When stratifying for race, results were similar among Asians (OR = 1.60, 95% CI = 1.27, 2.01) and Caucasians (OR = 1.44, 95% CI = 1.33, 1.57) except Africans (OR = 1.25, 95% CI = 0.76, 2.06). When stratifying by the smoking, stage, grade, and histological type of bladder cancer, we found no statistical association. Our meta-analysis suggests that the GSTM1 null genotype is associated with a modest increase in the risk of bladder cancer.     

CDH1 promoter polymorphism and stomach cancer susceptibility

The relationship of stomach cancer susceptibility and the presence of E-cadherin (CDH1) promoter −160 C/A polymorphism had been reported with conflicting results. To further explore the association of this polymorphism with stomach cancer susceptibility, we performed an extensive search of relevant studies and carried out a meta-analysis to obtain a more precise estimate. A total of 16 studies including 2,611 cases and 3,788 controls were involved in this meta-analysis. When all studies involved, the meta-analysis results suggest no statistically significant association between CDH1 −160 C/A polymorphism and stomach cancer risk (CA vs. CC: OR = 1.01, 95% CI: 0.85–1.19; AA vs. CC: OR = 1.05, 95% CI: 0.75–1.46; dominant model: OR = 1.02, 95% CI: 0.86–1.20; recessive model: OR = 1.04, 95% CI: 0.76–1.41). When subgroup analyses were performed by ethnicity, the A-allele carriers conferred a decreased stomach cancer risk in Asians (AA vs. CC: OR = 0.67, 95% CI: 0.47–0.96; dominant model: OR = 0.85, 95% CI: 0.72–0.99), but no statistically significant association was found in Caucasians. In conclusion, this meta-analysis suggests that CDH1 −160 A-allele may play a protective role of stomach cancer development in Asians but not in Caucasians.     

Has-miR-146a polymorphism (rs2910164) and cancer risk: a meta-analysis of 19 case–control studies

Epidemiological studies have evaluated the association between has-miR-146a polymorphism (rs2910164) and cancer risk. However, published data are still inconclusive. Here, we performed a meta-analysis to assess the relationship between has-miR-146a polymorphism (rs2910164) and cancer susceptibility until May 8, 2010. Nineteen published case–control studies including a total of 10,496 cases and 12,885 controls were acquired. Overall, Increased cancer risk was found in domain model (OR = 1.18, 95% CI: 1.03–1.35) rather than in other genetic models when all studies were pooled into the meta-analysis. Stratified analysis shown that significant association between rs2910164 polymorphism and cancer susceptibility was present in Asians (OR = 1.14, 95% CI: 1.01–1.29 for CG vs. CC; OR = 1.19, 95% CI: 1.03–1.39 for GG + CG vs. CC), but not in Caucasian populations. In the subgroup analysis by cancer types, no significantly increased risk of breast, gastric, prostate or bladder cancer were found in any of the genetic models. In summary, this meta-analysis suggests that has-miR-146a polymorphism (rs2910164) is associated with increased cancer susceptibility in Asians. However, further well-designed studies with large sample size will be necessary to validate the risk identified in the current meta-analysis.     

Association of GSTM1 Null Allele with Prostate Cancer Risk: Evidence from 36 Case-Control Studies

Background

Glutathione S-transferase M1 (GSTM1) is thought to be involved in detoxifying several carcinogens and may play a vital role in tumorigenesis. Numerous studies have evaluated the association between GSTM1 null/present polymorphism and risk of prostate cancer (PCa). However, the results remain inconsistent. To derive a more precise estimation, we performed a meta-analysis.

Methodology/Principal Findings

A comprehensive search was conducted to identify all eligible case-control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The overall association was significant (OR = 1.28, 95% CI: 1.11–1.48, P = 0.001). Moreover, subgroup analyses showed GSTM1 null genotype significantly associated with PCa risk among Asians (OR = 1.35, 95% CI: 1.03–1.78, P = 0.03) but not among Caucasians (OR = 1.12, 95% CI: 0.96–1.31, P = 0.16). In addition, we did not find that smoking modified the genotype effect on the risk of PCa.

Conclusions/Significance

The present meta-analysis suggested that GSTM1 null allele was a low-penetrant risk factor for PCa among Asians.     

Meta-analyses of the effect of cytochrome P450 2E1 gene polymorphism on the risk of head and neck cancer

Many studies have investigated the association between the CYP2E1 5′-flanking region (RsaI/PstI) polymorphism and head and neck cancer susceptibility, but the results were conflicting. In this meta-analysis, we assessed 24 published studies involving 12,562 subjects of the association between CYP2E1 RsaI/PstI polymorphism and head and neck cancer risk. Using the fixed effects model, we found significant association between PstI/RsaI polymorphism and head and neck cancer risk [OR = 1.11 (95%CI: 1.00–1.22) for c2 allele (P = 0.04) and OR = 1.57 (95% CI: 1.14–2.15) for c2 homozygous (P = 0.006) compared with wild type homozygote]. Significant results were also found in East Asians and Mix populations when stratified by ethnicity. However, no significant associations were found for Caucasians in all genetic models. Stratified analyses according to source of controls, significant associations were found only in hospital base controls. In the subgroup analyses by tumor types, significant association was detected only in oral cancer group, while no significant associations among laryngeal- or pharyngeal- cancer subgroup. This meta-analysis suggests that the CYP2E1 RsaI/PstI polymorphism may be a risk factor for head and neck cancer in Asians and Mix population, and that different carcinogenic processes involved in the genesis of various tumor types may exist.     

Association of hOGG1 Ser326Cys polymorphism with gastric cancer risk: a meta-analysis

Studies investigating the association between human 8-oxoguanine glycosylase 1(hOGG1) Ser326Cys polymorphism and gastric cancer (GC) risk have reported conflicting results. We performed a meta-analysis of published case–control studies to better compare results between studies. 11 eligible studies with 2,180 GC cases and 3,985 controls were selected. There were 5 studies involving Caucasians and 5 studies involving Asians. The combined result based on all studies did not show significant difference in any genetics models. Ser/Cys + Cys/Cys versus Ser/Ser (OR = 0.91, 95% CI 0.81–1.03), Cys/Cys versus Ser/Cys + Ser/Ser (OR = 1.07, 95% CI 0.80–1.44), Ser/Cys versus Ser/Ser (OR = 0.91, 95% CI 0.80–1.03), Sys/Cys versus Ser/Cys (OR = 1.10, 95% CI 0.83–1.47), Cys/Cys versus Ser/Ser (OR = 0.99, 95% CI 0.74–1.34), Cys versus Ser (OR = 1.01, 95% CI 0.88–1.17).When stratifying for ethnicity, there was still no significant association found between hOGG1 Ser326Cys polymorphism and GC risk. Funnel plot and Egger’s test showed some evidence of publication bias on the basis of all studies. Two studies were the main reason because their samples were too small. However, the result of sensitivity analysis suggested that the influence of these two studies and one mixed population study on the pooled OR was weak. Our result could explain the association between hOGG1 Ser326Cys polymorphism and GC risk. In conclusion, we did not found the evidence that the Cys allele at codon 326 of hOGG1 could increase GC risk in our analysis.     

Polymorphisms of XRCC1 and gastric cancer susceptibility: a meta-analysis

Studies investigating the association between X-ray repair cross-complementing gene 1 (XRCC1) polymorphisms and gastric cancer (GC) risk have reported conflicting results. We performed a meta-analysis of published case–control and cohort studies to better compare results between studies. Published literature from PubMed, EMBASE, and China National Knowledge Infrastructure were retrieved. 18 studies with 3,915 GC cases and 6,759 controls were selected. For XRCC1 Arg194Trp polymorphism, we only found the Trp/Trp genotype carriers might be at high risk of GC (TT vs. CC+CT: OR = 1.31, 95%CI = 1.04–1.65). When stratifying for ethnicity, the results showed there was a significant difference in genotype distribution between GC cases and controls among Asians (especially, in Chinese population), but not among Caucasians. When stratifying for control sources, significant association between Arg194Trp polymorphism and GC risk was only observed in the hospital-based controls’ subgroup (TT vs. CC+CT: OR = 1.45, 95%CI = 1.13–1.87). Additionally, no significant association was detected in the gastric cardia cancer’s subgroup. The results of the overall meta-analysis did not suggest any association between Arg280His/Arg399Gln polymorphisms and GC susceptibility for all genetic models. There was no evidence for the association between these two gene polymorphisms and GC risk in subgroup analyses based on study design, ethnicity, country, tumor location, Helicobacter pylori infection and the Lauren’s classification of GC. In conclusion, XRCC1 Arg194Trp homozygous mutant genotype (Trp/Trp) was found to be associated with increased risk of GC.     

Association of p53 codon 72 polymorphism with prostate cancer: a meta-analysis

Relationship of prostate cancer with the polymorphism of p53 codon 72 was reported with inconsistent results. The purpose of this study was to quantitatively evaluate the association between p53 codon 72 polymorphism and prostate cancer susceptibility. We performed an extensive search of relevant studies and made a meta-analysis, including 8 studies with 815 prostate cancer cases and 1047 controls. The combined results showed that there were no significant differences in genotype distribution between prostate cancer cases and control on the basis of all studies, CC/GC versus GG (OR = 1.24, 95% CI: 0.93–1.65), GG/GC versus CC (OR = 0.96, 95% CI: 0.60–1.55), GC versus GG (OR = 1.27, 95% CI: 0.91–1.77), CC versus GG (OR = 1.25, 95% CI:0.74–2.12), GC versus CC (OR = 1.09, 95% CI: 0.63–1.87). When stratifying for the race, there were also no statistically significant differences in genotype distribution between prostate cancer cases and controls. This meta-analysis did not provide an evidence of confirming association between p53 codon 72 polymorphism and prostate cancer.     

The GSTM1 Null Genotype Increased Risk of Gastric Cancer: A Meta-Analysis Based on 46 Studies

Background

Glutathione S-transferases M1 (GSTM1) is an important phase II metabolizing enzyme. The null genotype of GSTM1 causes total loss of GSTM1 enzyme activity and numerous studies have investigated the association between GSTM1 null genotype and gastric cancer risk.

Methods

This meta-analysis was designed to investigate the relationship between GSTM1 null genotype and susceptibility to gastric cancer and assess the influence of Helicobacter pylori infection, smoking, Lauren’s classification, and other factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength.

Results

A total of 46 eligible studies were indentified and analyzed in this meta-analysis, including 8138 cases of gastric cancer and 13867 controls. Pooled results showed that the GSTM1 null genotype was associated with a significantly increased risk of gastric cancer (OR=1.217, 95% CI: 1.113-1.331, P_{heterogeneity}<0.001). Sub-group analysis suggested that the significant association was only observed in Asians (OR=1.273, 95%: 1.137-1.426, P_{heterogeneity} = 0.002), but not in Caucasians. The increased risk was found among H. pylori positive population (OR=1.928, 95% CI: 1.028-3.615, P_{heterogeneity}=0.065), while no association was found among H. pylori negative population (OR=0.969, 95% CI: 0.618-1.521, P_{heterogeneity}=0.168). For smoking status, the GSTM1 null genotype increased risk of gastric cancer in both ever-smokers and non-smokers. Source of control, sample size, location of tumor and Lauren’s classification did not modify the association.

Conclusions

In this meta-analysis based on 46 epidemiological studies, we show that the GSTM1 null genotype is associated with an increased risk of gastric cancer among Asians but not among Caucasians. H. pylori infection but not smoking status could modify the association.     

A genetic variant in microRNA-196a2 is associated with increased cancer risk: a meta-analysis

MicroRNAs (miRNAs) are small non-coding RNA molecules that function as negative regulators of gene expression. Common genetic variants (single nucleotide polymorphisms, SNPs) in miRNA genes may alter their expression or maturation resulting in varied functional consequences. Until now, several studies had evaluated the association between the polymorphisms in the hsa-miR-196a2 rs11614913 and cancer risk in diverse populations and in multiple types of cancer, with contradictory outcomes. Therefore, here we performed a meta-analysis to address the association between this polymorphism and cancer risk. A total of nine studies involving 6,540 cases and 7,562 controls were retrieved based on PubMed. Our analysis demonstrated that hsa-miR-196a2 rs11614913 CC genotype significantly increased the cancer risk in homozygote comparison model compared to TT genotype (OR = 1.18; 95% CI, 1.01–1.68). Moreover, significant association of this polymorphism with breast cancer was found based on homozygote comparison model (OR = 1.30; 95% CI, 1.01–1.26) and dominant model (OR = 1.11; 95% CI, 1.01–1.23). In addition, hsa-miR-196a2 rs11614913 CC genotype was significantly associated with cancer risk in Chinese and Indian (OR = 1.21; 95% CI, 1.05–1.40), but not in Caucasians (OR = 1.03; 95% CI, 0.89–1.19). Taken together, our results indicate that the polymorphism of hsa-miR-196a2 rs11614913 is associated with cancer susceptibility, especially with breast cancer and in Chinese and Indian populations.     

Association between Glutathione S-Transferase T1 Null Genotype and Gastric Cancer Risk: A Meta-Analysis of 48 Studies

Background

Glutathione S-transferases (GSTs) have proved to be involved in the detoxifying several carcinogens and may play an important role in carcinogenesis of cancer. Previous studies on the association between Glutathione S-transferase T1 (GSTT1) polymorphism and gastric cancer risk reported inconclusive results. To clarify the possible association, we conducted a meta-analysis of eligible studies.

Methods

We searched in the Pubmed, Embase, and Wangfang Medicine databases for studies assessing the association between GSTT1 null genotype and gastric cancer risk. The pooled odds ratio (OR) and its 95% confidence interval (95%CI) was calculated to assess the strength of the association. A total of 48 studies with a total of 24,440 individuals were ultimately eligible for meta-analysis.

Results

Overall, GSTT1 null genotype was significantly associated with increased risk of gastric cancer (Random-effect OR = 1.23, 95%CI 1.13–1.35, P _OR <0.001, I² = 45.5%). Significant association was also found in Caucasians, East Asians, and Indians (P _Caucasians = 0.010; P _{East Asians} = 0.003; P _Indians = 0.017). After adjusting for other confounding variables, GSTT1 null genotype was also significantly associated with increased risk of gastric cancer (Random-effect OR = 1.43, 95%CI 1.20–1.71, P _OR <0.001, I² = 48.1%).

Conclusion

The meta-analysis provides strong evidence for the significant association between GSTT1 null genotype and increased risk of gastric cancer.     

Genetic polymorphism of glutathione S-transferase T1 and the risk of colorectal cancer: A meta-analysis

Background: Studies investigating the association between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and risk of colorectal cancer have reported conflicting results. In order to clarify the effect of GSTT1 polymorphism on the risk of developing colorectal cancer, we carried out a meta-analysis using published data to obtain more precise estimates of risk. Methods: Electronic searches of PubMed and EMBASE were conducted to select studies for this meta-analysis. Papers were included if they were observational studies investigating the association between GSTT1 polymorphism and colorectal cancer risk. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of colorectal cancer associated with GSTT1 null genotype. Results: We identified 30 eligible studies, which included 7635 cases and 12,911 controls. The combined results based on all studies showed that there was a statistically significant link between GSTT1 null genotype and colorectal cancer risk (OR = 1.20, 95% CI = 1.03–1.40). In the analysis of ethnic groups, we observed distinct differences associated with GSTT1 null genotype, the pooled odds ratios for the GSTT1 polymorphism were 1.32 in Caucasians (95% CI = 1.09–1.58) and 1.03 in Asians (95% CI = 0.81–1.32). As far as concerned the interaction between GSTT1 genotype and colorectal cancer risk in relation to smoking history, there was no increase in risk for smokers or nonsmokers with the GSTT1 null genotype (smokers: OR = 1.13, 95% CI = 0.80–1.60, nonsmokers: OR = 0.99, 95% CI = 0.71–1.38). When stratifying by the location of colorectal cancer, we found that there was a statistically significant link in rectal cancer (OR = 1.50, 95% CI = 1.09–2.07), but not in colon cancer (OR = 1.33, 95% CI = 0.94–1.88). No associations could be detected between null GSTT1 polymorphism and age, sex, tumor stage and differentiation. Conclusion: Our current study demonstrates that GSTT1 null genotype is associated with an increased risk of colorectal cancer, specifically, among Caucasians.     

Quantitative assessment of the effect of ABCA1 R219K polymorphism on the risk of coronary heart disease

In the past decade, a number of case-control studies have been conducted to investigate the relationship between the ATP-binding cassette transporter A1 (ABCA1) R219K polymorphism and coronary heart disease (CHD). However, the results have been inconclusive. The purpose of the present study is to investigate whether this polymorphism confers significant susceptibility to CHD using a meta-analysis. PubMed, Embase and CNKI database were searched to get the genetic association studies. Then data were extracted. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated. Moreover, subgroup and sensitive analysis were performed. In total, 9,437 cases and 16,270 controls were involved in the meta-analysis. The K219 was significantly associated with CHD (OR = 0.80, 95% CI 0.69–0.92, P(Z) = 0.001). However, significant heterogeneity was present. Further subgroup analysis suggested ethnicity explained much heterogeneity. In Asians, K219 showed a strong protective effect and the pooled OR was 0.69 (95% CI 0.55–0.86 P(Z) = 0.0009). While in Caucasians the result was not significant (OR = 0.87, 95% CI 0.73–1.04, P(Z) = 0.12). In conclusion, our results indicate that the ABCA1 R219K polymorphism is a protective factor of CHD in Asians, but not in Caucasians.     

Ethnic differences in the association of the glutathione S-transferase T1 (GSTT1) null genotype and risk of gastric carcinoma: a systematic review and meta-analysis

We performed a systematic review and meta-analysis of the association between the glutathione S-transferase T1 (GSTT1) deletion polymorphism and gastric cancer risk in populations from different ethnic backgrounds, based on a comprehensive literature search of the MEDLINE, EMBASE, and COCHRANE libraries. Thirty-six individual case–control studies comprising 7,689 gastric cancer cases and 12,445 controls were included in our meta-analysis. Overall, the GSTT1 null genotype appeared to increase gastric cancer risk (OR 1.17, 95 % CI 1.06–1.31, p = 0.003). While Caucasian populations showed an association between the GSTT1 deletion polymorphism and gastric cancer risk (OR 1.27, 95 % CI 1.05–1.52, p = 0.01), Asian populations did not show such an association (p = 0.11). When stratified by quality assessment scores, a significant association between the GSTT1 deletion polymorphism and gastric cancer risk was observed only in the Caucasian high quality subgroup (OR 1.27 95 % CI 1.01–1.60, p = 0.05). Null genotypes for both GSTT1 and GSTM1 deletion polymorphisms also increased gastric cancer risk (OR 1.37, 95 % CI 1.04–1.80, p = 0.03). Our study suggests that the GSTT1 null genotype is associated with a significant increase in gastric cancer risk in Caucasians, but not in Asians. Further well-designed studies are required to confirm the association between GSTT1 polymorphisms and gastric cancer risk in relation to various clinicopathological factors in different ethnic groups, especially Caucasians.     

Association of IL-10-1082 promoter polymorphism with susceptibility to gastric cancer: evidence from 22 case–control studies

Evidence suggested that interleukin-10 (IL-10) may be involved in the etiology of gastric cancer (GC). However, epidemiological studies on the association between IL-10-1082 promoter polymorphism and GC risk are still ambiguous. To quantitatively summarize the evidence for such a relationship, we performed a meta-analysis. Systemic searches of the PubMed and Medline databases were performed, with the last report up to July 2011. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. 22 independent studies including 4,289 cases and 5,965 controls were involved in this meta-analysis. Obvious association was found when all studies were pooled into the meta-analysis (A vs. G: OR = 0.489, 95% CI = 0.335–0.713, P < 0.001). In the subgroup analysis by ethnicity, we observed significant associations in Asians (A vs. G: OR = 0.651, 95% CI = 0.506–0.838, P = 0.001; AA vs. GG: OR = 0.482, 95% CI = 0.328–0.709, P < 0.001; AA/AG vs. GG: OR = 0.711, 95% CI = 0.527–0.959, P = 0.025; AA vs. AG/GG: OR = 0.701, 95% CI = 0.520–0.944, P = 0.019) and Caucasians (A vs. G: OR = 0.365, 95% CI = 0.140–0.949, P = 0.039), but not in Latino population. When stratified analysis by control sources, our results indicated that A allele decreased approximately 48% risk among population-based studies (A vs. G: OR = 0.524, 95% CI = 0.374–0.733, P < 0.001). Taken together, this meta-analysis suggests that IL-10-1082 polymorphism is associated with GC risk.     

Association between ATM polymorphisms and cancer risk: a meta-analysis

To date, epidemiological studies have assessed the association between Ataxia-telangiectasia mutated (ATM) gene polymorphisms and cancer risk, including lung cancer, breast cancer, glioma and pancreatic cancer. However, the results of these studies remain controversial. We aimed to examine the associations between two SNPs (rs664143 and rs664677) and cancer risk by conducting a meta-analysis of case–control studies. A total of 12 publications were included in this meta-analysis, 8 for rs664143 and 7 for rs664677. Overall, rs664143 heterozygote carriers turned out to be associated with cancer risk (OR = 1.18, 95% CI 1.02–1.36). In the subgroup analysis by cancer type, we observed that the ATM rs664143 polymorphism was significantly associated with lung cancer risk (GA vs. GG: OR = 1.48, 95% CI 1.18–1.85, AA vs. GG: OR = 1.51, 95% CI 1.18–1.93) and rs664677 polymorphism was associated with decreased lung cancr risk and increased breast cancer risk (for lung cancer: TC vs. TT: OR = 0.76, 95% CI 0.62–0.92, CC vs. TT: OR = 0.80, 95% CI 0.64–0.99 and for breast cancer: TC vs. TT: OR = 1.42, 95% CI 1.17–1.73, CC vs. TT: OR = 1.51, 95% CI 1.21–1.87). In the subgroup analysis by region, we also observed that individuals with ATM rs664143 GA or AA genotype had an obvious increased cancer risk among Asian people (GA vs. GG: OR = 1.40, 95% CI 1.20–1.63, AA vs. GG: OR = 1.37, 95% CI 1.16–1.62). In conclusion, ATM rs664143 polymorphism was associated with cancer susceptibility. ATM rs664143 polymorphism was significantly associated with lung cancer risk. ATM rs664677 polymorphism was associated with decreased lung cancer risk as well as increased breast cancer risk.     

Glutathione S-Transferase Polymorphism Interactions with Smoking Status and HPV Infection in Cervical Cancer Risk: An Evidence-Based Meta-Analysis

Background

Human papillomavirus (HPV) infection is considered the major cause of cervical cancer (CC), but a number of infected women do not develop invasive lesions, suggesting the role of genetic susceptibility and environmental co-factors for cancer outbreak. 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

MEDLINE, EMBASE, and Cochrane databases were searched. All studies evaluating the association between GSTM1 polymorphisms and cervical cancer were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed-or random-effects model.

Results

A total of 23 case-control studies were included in the meta-analysis. The overall result showed that the association between GSTM1 null genotype and risk for cervical cancer was statistically significant (OR = 1.56; 95%CI, 1.39–1.75). Subgroup analyses were performed based on ethnicity, smoking and HPV infection. Our results showed that smokers with null GSTM1 genotype had higher risk of cervical cancer (OR = 2.27, 95%CI, 1.46–3.54). For the ethnicity stratification, significant increased risk of null GSTM1 genotype was found in Chinese and Indian population, but no increased risk in other population was found.

Conclusions

this meta-analysis provided strong evidence that the GSTM1 genotype is associated with CC development, especially in Chinese and Indian populations. Smoking and HPV infection modified the association between the null GSTM1 genotype and CC.     

Association of a LSP1 gene rs3817198T>C polymorphism with breast cancer risk: evidence from 33,920 cases and 35,671 controls

Published data on the association between lymphocyte-specific protein 1 (LSP1) rs3817198T>C polymorphism and breast cancer risk are inconclusive. Hence, we conducted a meta-analysis of the LSP1 gene and risk of breast cancer to obtain the most reliable estimate of the association. PubMed, Embase and Web of Science databases were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the strength of the association between the LSP1 rs3817198T>C polymorphism and risk of breast cancer. A total of seven eligible studies including 33,920 cases and 35,671 controls based on the search criteria were involved in this meta-analysis. The distributions of genotypes in the controls were all in agreement with Hardy–Weinberg equilibrium. We observed that the LSP1 rs3817198T>C polymorphism was significantly correlated with breast cancer risk when all studies were pooled into the meta-analysis (the allele contrast model: OR = 1.06, 95% CI = 1.04–1.08; the homozygote codominant: OR = 1.14, 95% CI = 1.01–1.28). In the stratified analysis by ethnicity, significant association was observed in Caucasians for CC versus TT homozygote codominant model (OR = 1.25; 95% CI = 1.03–1.52) and for the recessive model (OR = 1.22; 95% CI = 1.02–1.47). There was significant association observed in Africans for CC versus TT homozygote codominant model (OR = 0.45; 95% CI = 0.22–0.92) and for the recessive model (OR = 0.43; 95% CI=0.22–0.88). Also, significant association was observed in mixed ethnicities for CC versus TT homozygote codominant model (OR = 1.12; 95% CI = 1.05–1.19). When stratified by study design, statistically significantly elevated risk was found in nested case–control studies (CC vs. TT: OR = 1.12, 95% CI = 1.05–1.19). But no significant association was observed for all comparison models between LSP1 rs3817198T>C polymorphism and breast cancer risk in hospital-based and people-based studies. When stratified by BRCA1 mutation carriers status, statistically significantly elevated risk was found in this meta-analysis (the allele contrast model: OR = 1.07, 95% CI = 1.01–1.14; the dominant model: OR = 1.09, 95% CI = 1.00–1.18). And significant association was found in the BRCA2 mutation carriers in the allele contrast (OR = 1.11, 95% CI = 1.03–1.20), the homozygote codominant (OR = 1.23, 95% CI = 1.04–1.47), the heterozygote codominant (OR = 1.12, 95% CI = 1.00–1.25) and the dominant models (OR = 1.14, 95% CI = 1.03–1.27). There was significant association between LSP1 rs3817198T>C polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort in all comparison models (the allele contrast model: OR = 1.08, 95% CI = 1.03–1.13; CC vs. TT: OR = 1.16, 95% CI = 1.05–1.29; TC vs. TT: OR = 1.09, 95% CI = 1.01–1.16; the dominant model: OR = 1.10, 95% CI = 1.03–1.17; the recessive model: OR = 1.12, 95% CI = 1.01–1.23). In conclusion, this meta-analysis suggests that the LSP1 rs3817198T>C polymorphism is a low-penetrant risk factor for developing breast cancer but may not be in Africans.     

Are glutathione S-transferase polymorphisms (GSTM1, GSTT1) associated with primary open angle glaucoma? A meta-analysis

Background

Glutathione S-transferase (GST) variants have been considered as risk factors for the pathogenesis of primary open angle glaucoma (POAG). However, the results have been inconsistent. In this study, we performed a meta-analysis to assess the association between GSTM1 and GSTT1 null genotypes and the risk for POAG.

Methods

Published literature from PubMed and EMBASE databases was retrieved. All studies evaluating the association between GSTM1/GSTT1 variants and POAG were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effects model.

Results

14 studies (1711 POAG cases and 1537 controls) were included in the meta-analysis of GSTM1 genotypes and 10 studies (1306 POAG cases and 1114 controls) were included in the meta-analysis of GSTT1 genotypes. The overall result showed that the association between GSTM1 and GSTT1 null genotypes and risk for POAG was not statistically significant (GSTM1: OR = 1.19, 95% CI = 0.82–1.73, p = 0.361; GSTT1: OR = 1.26, 95% CI = 0.77–2.06, p = 0.365). The results by ethnicity showed that the association between the GSTM1 null genotype and risk for POAG is statistically significant in East Asians (OR = 1.41, 95% CI = 1.04–1.90, p = 0.026), but not in Caucasians (OR = 1.13, 95% CI = 0.69–1.84, p = 0.638) and Latin-American (OR = 1.09, 95% CI = 0.62–1.92, p = 0.767). In addition, there was no significant association of GSTT1 null genotype with risk for POAG in either ethnic population.

Conclusions

The present meta-analysis suggested that there might be a significant association of GSTM1 null genotype with POAG risk in East Asians.     

Glutathione S-transferase M1 and T1 gene polymorphism and COPD risk in smokers: an updated analysis

We evaluated the association between GSTM1 and GSTT1 gene polymorphisms and susceptibility to chronic obstructive pulmonary disease (COPD) in smokers. A meta-analysis of the published case–control studies was performed. Published literature was retrieved from PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI), with last update in February, 2011. Data were extracted and a fixed- or random-effects model was used to calculate pooled odds ratios with 95% confidence intervals depending on statistical heterogeneity. Fourteen eligible studies, comprising 1,665 COPD cases and 1,614 controls, were included in the meta-analysis. The combined analyses showed that there was a significant difference in GSTM1 genotype distribution between COPD cases and controls among Caucasians, but not among Asians. The combined GSTM1/GSTT1 null genotype conferred a 1.36-fold greater risk for COPD in Asian smokers. The GSTT1 null genotype alone was not associated with enhanced risk for COPD. The GSTM1 null genotype is significantly associated with an increasing susceptibility to COPD in Caucasian smokers, but not in Asian smokers. The GSTM1/GSTT1 null genotype is a significant risk factor for developing COPD in Asian smokers. The GSTT1 null genotype, however, was not associated with COPD.