Meta-analysis of the association of glutathione S-transferase T1 null/presence gene polymorphism with the risk of gastric carcinoma

A possible association of glutathione S-transferase T1 (GSTT1) null/presence gene polymorphism and an increased risk of developing gastric carcinoma is still unclear and hotly debated. This investigation was performed to assess the association of the GSTT1 null/presence gene polymorphism with the risk of gastric carcinoma via a meta-analysis to increase sample size and statistical significance. PubMed, Cochrane Library and CBM-disc (China Biological Medicine Database) were searched on March 1, 2013, association reports were identified, and eligible studies were recruited and synthesized. Fifty-two reports were found to be suitable for this meta-analysis for the association of the GSTT1 null genotype with gastric carcinoma risk. The results showed that there was a significantly increased gastric carcinoma risk when the GSTT1 null genotype was present in the overall population (OR 1.21, 95 % CI 1.11–1.32, P < 0.0001), Caucasians (OR 1.25, 95 % CI 1.05–1.48, P = 0.01), East-Asians (OR 1.18, 95 % CI 1.06–1.31, P = 0.003), and Chinese (OR 1.24, 95 % CI 1.07–1.44, P = 0.005). However, no statistically relevant association could be established for the Indian ethnic group (OR 1.33, 95 % CI 0.94–1.90, P = 0.11). In conclusion, the GSTT1 null genotype is associated with an increased gastric carcinoma risk in the overall population, Caucasians, East-Asians, and Chinese.     

A meta-analysis of the relationship between glutathione S-transferase T1 null/presence gene polymorphism and the risk of lung cancer including 31802 subjects

The relationship between glutathione S-transferase T1 (GSTT1) null/presence gene polymorphism and the risk of lung cancer from the published reports are still conflicting. This study was conducted to evaluate the relationship between GSTT1 null/presence gene polymorphism and the risk of lung cancer using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on July 1, 2012, and eligible investigations were included and synthesized using meta-analysis method. 51 reports were recruited into this meta-analysis for the association of null genotype of GSTT1 with lung cancer susceptibility, consisting of 15,140 patients with lung cancer and 16,662 controls. There was a marked association between GSTT1 null genotype and lung cancer risk in overall populations (OR = 1.15, 95 % CI 1.04–1.27, P = 0.007). Furthermore, GSTT1 null genotype was associated with the lung cancer risk in Asians (OR = 1.47, 95 % CI 1.23–1.76, P < 0.0001). However, GSTT1 null genotype was not associated with the risk of lung cancer in Caucasians, Brazilian population and Africans. In conclusion, GSTT1 null genotype is associated with the lung cancer in overall populations and in Asians.     

Significant association of glutathione S-transferase T1 null genotype with esophageal cancer risk: a meta-analysis

Recent studies on the association between glutathione S-transferase T1 (GSTT1) polymorphism and risk of esophageal cancer showed inconclusive results. To clarify this possible association, we conducted a meta-analysis of published studies. Data were collected from the following electronic databases: Pubmed, Embase, and Chinese Biomedical Database (CBM). The odds ratio (OR) and its 95 % confidence interval (95 % CI) was used to assess the strength of this association. We summarized the data on the association between GSTT1 null genotype and risk of esophageal cancer in the overall population, and performed subgroup analyses by ethnicity. Finally, a total of 24 independent studies including a total of 7,801 subjects (2,965 cases and 4,836 controls) were eligible for meta-analysis. In the overall analysis, there was no significant association between GSTT1 null genotype and esophageal cancer risk (OR = 1.15, 95 % CI 0.99–1.33, P = 0.067). However, meta-analysis of adjusted ORs showed a significant association between GSTT1 null genotype and increased risk of esophageal cancer (OR = 1.30, 95 % CI 1.08–1.56, P = 0.005). Subgroup analyses by ethnicity showed there was an obvious association between GSTT1 null genotype and increased risk of esophageal cancer in East Asians (OR = 1.24, 95 % CI 1.10–1.39, P < 0.001), but not in Caucasians (OR = 0.89, 95 % CI 0.71–1.11, P = 0.300). There was no obvious risk of publication bias in this meta-analysis (Egger’s test, P = 0.784). This meta-analysis demonstrates that GSTT1 null genotype is independently associated with increased risk of esophageal cancer, and a race-specific effect may exist in this association.     

Significant association between GSTT1 null genotype and risk of asthma during childhood in Caucasians

Asthma is a complex multifactorial disorder and its management requires a better understanding of its various pathogenesis and mechanisms. Previous studies assessing the association between glutathione S-transferase T1 (GSTT1) null genotype and asthma risk during childhood reported conflicting results. To get a more precise estimation of the association between GSTT1 null genotype and risk of asthma during childhood, we performed a meta-analysis of 16 studies with a total of 18,558 subjects. Subgroup analyses were performed by ethnicity. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 %CI) was used to assess the association. Overall, there was a significant association between GSTT1 null genotype and increased risk of children asthma (OR = 1.25, 95 % CI, 1.02–1.54; P = 0.032). Subgroup analyses showed GSTT1 null genotype was associated with increased risk of children asthma in Caucasians (OR = 1.46, 95 % CI, 1.04–2.03; P = 0.027), but not in Asians (OR = 1.03, 95 % CI, 0.55–1.94; P = 0.928) and Africans (OR = 1.33, 95 % CI, 0.92–1.91; P = 0.127). There was no evidence of publication bias in the subgroup analysis of Caucasians. In conclusion, there is a significant association between GSTT1 null genotype and risk of asthma during childhood in Caucasians. More well-designed epidemiological studies are needed to further assess this association in Asians and Africans.     

Significant association between GSTT1 null genotype and susceptibility to pancreatic cancer

Many studies have investigated the association between glutathione S-transferase T1 (GSTT1) polymorphism and risk for pancreatic cancer, but those studies have yielded contradictory findings on the association. We performed a comprehensive search in the PubMed, EMBASE, and the Chinese National Knowledge Infrastructure databases to identify relevant studies. A meta-analysis was performed to examine the association between GSTT1 polymorphism and susceptibility to pancreatic cancer by calculating the pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs). Eight studies involving a total of 4,437 individuals were included. Overall, significantly increased pancreatic cancer risk was associated with GSTT1 null genotype when all studies were pooled into the meta-analysis (random effects OR = 1.61, 95 % CI 1.06–2.44; P = 0.025). Significantly increased risk of pancreatic cancer was also found for GSTT1 null genotype in Asians when stratified by ethnicity (fixed effects OR = 2.67, 95 % CI 1.74–4.09; P < 0.001). The findings demonstrate that GSTT1 null genotype have a modest effect on the genetic susceptibility to pancreatic cancer, and GSTT1 null genotype is associated with increased risk of pancreatic cancer.     

CYP1A1 MspI polymorphism is associated with prostate cancer susceptibility: evidence from a meta-analysis

Cytochrome P450 1A1 (CYP1A1), an important phase I xenobiotic metabolizing enzyme, is responsible for metabolizing numerous carcinogens, particularly polycyclic aromatic hydrocarbons. The genetic polymorphism of CYP1A1 at the site of MspI (CYP1A1 MspI) has been implicated in prostate cancer risk, but the results of individual studies remain conflicting and inconclusive. The aim of this meta-analysis was to investigate the association of CYP1A1 MspI polymorphism with prostate cancer risk more precisely. We performed a comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases from their inception up to September 20, 2012 for relevant publications. The pooled odds ratios with the corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the association of CYP1A1 MspI polymorphism with prostate cancer risk. In addition, stratified analyses by ethnicity and sensitivity analyses were conducted for further estimation. Sixteen eligible publications with 6,411 subjects were finally included into the meta-analysis after checking the retrieved papers. Overall, meta-analysis of total studies suggested that individuals carrying the TC genotype and a combined C genotype (CC + TC) were more susceptible to prostate cancer (OR_{TC vs. TT} = 1.33, 95 % CI 1.10–1.61, P _OR = 0.004; OR_{CC+TC vs. TT} = 1.27, 95 % CI 1.05–1.55, P _OR = 0.016). Stratified analysis of high quality studies also confirmed the significant association (OR_{TC vs. TT} = 1.32, 95 % CI 1.04–1.67, P _OR = 0.024; OR_{CC+TC vs. TT} = 1.30, 95 % CI 1.02–1.66, P _OR = 0.035). In subgroup analyses by ethnicity, a significant association between the CYP1A1 MspI polymorphism and risk of prostate cancer was found among Asians (OR_{TC vs. TT} = 1.44, 95 % CI 1.20–1.72, P _OR < 0.001; OR_{CC+TC vs. TT} = 1.33, 95 % CI 1.12–1.58, P _OR = 0.001), but not in Caucasians or mixed populations. The meta-analysis suggests an important role of the CYP1A1 MspI polymorphism in the risk of developing prostate cancer, especially in Asians.     

Meta-analysis on the association of nucleotide excision repair gene XPD A751C variant and cancer susceptibility among Indian population

Polymorphism A751C (A>C) in XPD gene has shown susceptibility to many cancers in Indian population; however the results of these studies are inconclusive. Thus, we performed this meta-analysis to estimate the association between XPD A751C polymorphism and overall cancer susceptibility. We quantitavely synthesized all published studies of the association between XPD A751C polymorphism and cancer risk. Pooled odds ratios (ORs) and 95 % CI were estimated for allele contrast, homozygous, heterozygous, dominant and recessive genetic model. A total of thirteen studies including 3,599 controls and 3,087 cancer cases were identified and analyzed. Overall significant results were observed for C allele carrier (C vs. A: p = 0.001; OR 1.372, 95 % CI 1.172–1.605) variant homozygous (CC vs. AA: p = 0.001; OR 1.691, 95 % CI 1.280–2.233) and heterozygous (AC vs. AA: p = 0.001; OR 1.453, 95 % CI 1.215–1.737) genotypes. Similarly dominant (CC+AC vs. AA: p = 0.001; OR 1.512, 95 % CI 1.244–1.839) and recessive (CC vs. AA+AC: p = 0.001; OR 1.429, 95 % CI 1.151–1.774) genetic models also demonstrated risk of developing cancer. This meta-analysis suggested that XPD A751C polymorphism likely contribute to cancer susceptibility in Indian population. Further studies about gene–gene and gene–environment interactions are required.     

The association between MTHFR C677T polymorphism and ovarian cancer risk: a meta-analysis of 18, 628 individuals

Methylenetetrahydrofolate reductase (MTHFR) enzyme plays an important role in folate metabolism and MTHFR polymorphisms have been suggested to be associated with risk of various cancers. MTHFR C677T polymorphism is a common genetic alteration and may affect the host susceptibility to ovarian cancer. The aim of this study was to investigate the association between MTHFR C677T polymorphism and ovarian cancer risk by performing a meta-analysis. Pubmed, Embase, Web of Science and Chinese Biomedical Database (CBM) databases were searched for case–control studies investigating the association between MTHFR C677T polymorphism and ovarian cancer. Odds ratio (OR) and its 95 % confidence interval (95 % CI) was used to assess this possible association. 13 individual case–control studies from 10 publications with a total of 18, 628 subjects (5, 932 cases and 12, 696 controls) were included into this meta-analysis. Meta-analyses showed there was no association between MTHFR C677T polymorphism and ovarian cancer risk in Caucasians under all five genetic models (All P values for the pooled ORs were more than 0.05), whereas there was an obvious association between MTHFR C677T polymorphism and ovarian cancer risk in Asians under four genetic models (for T vs C, OR (95 % CI) = 1.38(1.19–1.61); for TT vs CC, OR (95 % CI) = 2.32(1.63–3.29); for TT vs TC+CC, OR (95 % CI) = 2.04(1.47–2.85); for TT+TC vs CC, OR (95 % CI) = 1.36(1.12–1.65)). Subgroup analyses suggested ethnicity was the major source of heterogeneity. This meta-analysis supports an association between MTHFR C677T polymorphism and ovarian cancer risk, and there might be a race-specific effect in this association. Further studies with large sample size and careful design are needed to identify this association more comprehensively.     

Association between the NBS1 Glu185Gln polymorphism and lung cancer risk: a systemic review and meta-analysis

Nijmegen Breakage Syndrome protein 1 (NBS1) is one of the most important DNA repair proteins playing important roles in maintaining the genomic stability of NDA. Previous studies regarding the association between NBS1 8360G>C (Glu185Gln) polymorphism and lung cancer reported conflicting results. To derive a more precise estimation of this association, a systemic review and meta-analysis was performed. We performed a meta-analysis using eligible case–control studies to summarize the data on the association between the NBS1 Glu185Gln polymorphism and lung cancer risk. Odds ratios (ORs) with corresponding 95 % confidence intervals (95 %CIs) were pooled to assess the association between NBS1 Glu185Gln polymorphism and lung cancer risk. Six case–control studies with a total of 2,348 lung cancer cases and 2,401 controls without canner were included into the meta-analysis. Overall, there was an association between NBS1 Glu185Gln polymorphism and lung cancer risk under the dominant comparison model (fixed-effects OR _{GluGln/GlnGln vs. GluGlu}  = 1.21, 95 % CI 1.07–1.37, P = 0.002, I ² = 8.1 %). Subgroup analysis by race suggested a significant association between NBS1 Glu185Gln polymorphism and lung cancer risk in Asians (fixed-effects OR _{GluGlnGlnGln vs. GluGlu}  = 1.22, 95 % CI 1.06–1.41, P = 0.005) but not in Caucasians (fixed-effects OR _{GluGlnGlnGln vs. GluGlu}  = 1.17, 95 % CI 0.91–1.50, P = 0.220). This meta-analysis supports that there is an association between NBS1 Glu185Gln polymorphism and lung cancer risk. More studies are needed to further verify this association.     

Association between glutathione S-transferases M1, T1 and P1 gene polymorphisms and prostate cancer in Koreans

Prostate cancer (PCa) is the most commonly diagnosed cancer in the developed world, and the incidence of this cancer is rising rapidly in many countries. Several polymorphic genes encoding enzymes involved carcinogenesis have been studied as potential risk factor of prostate cancer. Genetic polymorphisms in glutathione S-transferases M1 (GSTM1), T1 (GSTT1) and P1 (GSTP1) genes have been constantly reported to have a meaningful effect on prostate cancer risk. But other surveys of this relationship have yielded inconsistent results. To assess the possible contribution of the GSTM1, GSTT1, and GSTP1 gene polymorphisms in prostate cancer, we performed a population-based study of 139 prostate cancer patients and 115 healthy controls based on their genotype distributions of the genes. There were no differences in distributions of genotype frequencies of GSTM1 and GSTP1 polymorphisms between prostate cancer patients and controls (OR 1.60, 95 % CI 0.886–2.860 for GSTM1 and OR 1.38, 95 % CI 0.739–2.577 for GSTP1). In contrast, the distribution of GSTT1-null genotype is significantly different between the prostate cancer case and controls (OR 0.26, 95 % CI 0.128–0.518, p < 0.001). Meanwhile, GSTP1 I/V and V/V genotypes were significantly associated with prostate cancer where the PSA level was more than 10.0 (OR 2.73, 95 % CI 1.319–5.639, p = 0.006). Thus, our data imply that the GSTT1-null genotype may not be a risk factor but a protective factor of prostate cancer and GSTP1 Val allele is a risk factor for the prostate cancer where the PSA level was high, although functional studies with larger sample size are necessary to elucidate these findings.     

Null genotype of GSTT1 contributes to increased Parkinson’s disease risk in Caucasians: evidence from a meta-analysis

Conflicting results in previous case–control studies on the association between Glutathione S-transferase T1 (GSTT1) gene polymorphism and Parkinson’s disease (PD) risk have been reported, so we conducted this meta-analysis. We searched and extracted data from 3 Chinese and 3 English web-based electronic databases to evaluate the associations by odds ratio (OR) and its 95 % confidence interval (CI) under the recessive genetic comparison model (null genotype vs. present genotype). We also conducted subgroup analyses by ethnicity and adjusted status of OR, respectively. Meta-analyses and subgroup analyses of larger studies (sample size ≥300) were also reanalyzed. When 18 eligible studies (3,963 PD cases and 5,472 controls) were pooled to analyze the association, we found no statistically significant result (OR 1.24, 95 % CI 0.96–1.60). In the subgroup analyses by ethnicity, there was statistically significant association between the null genotype of GSTT1 and PD risk among Caucasians, while the associations were not found among Asians and Latinos. In the subgroup analyses by adjusted status of OR, there were no significant associations both in studies with crude OR and adjusted OR. Meta-analyses and subgroup analyses of larger studies (sample size ≥300) were also confirmed the associations mentioned above. Power analysis indicated only meta-analysis of Caucasians had enough evidence to claim the association. In conclusion, the meta-analysis suggests that the null genotype of GSTT1 contributes to PD risk in Caucasians, and no association in Asians is needed more studies to confirm.     

A meta-analysis of the association of glutathione S-transferase P1 gene polymorphism with the susceptibility of breast cancer

Glutathione S-transferase P1 (GSTP1) is one of the important mutant sites for the cancer risk at present. The conclusions of the published reports on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer are still debated. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of breast cancer. The association reports were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. 35 investigations were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and breast cancer susceptibility, consisting of 40,347 subjects (18,665 patients with breast cancer and 21,682 controls). The association between GSTP1 A/G gene polymorphism and breast cancer risk was not found for overall population, Caucasians and Africans. Interestingly, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer in Asians (G allele: OR = 1.10, 95 % CI: 1.04–1.17, P = 0.001; GG genotype: OR = 1.36, 95 % CI: 1.14–1.62, P = 0.0008; AA genotype: OR = 0.92, 95 % CI: 0.85–0.98, P = 0.02). Furthermore, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer for the analysis of the controls from hospital. In conclusion, GSTP1 A/G gene polymorphism is associated with the breast cancer susceptibility in Asians. However, more studies on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer should be performed in further.     

Glutathione S-transferases gene polymorphisms and risk of male idiopathic infertility: a systematic review and meta-analysis

The Glutathione S-transferases (GSTs) polymorphisms have been implicated in susceptibility to male idiopathic infertility, but study results are still controversial. To investigate the genetic associations between GSTs polymorphisms and risk of male idiopathic infertility, a systematic review and meta-analysis were performed. Meta-analysis was performed by pooling odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) form studies in electronic databases up to March 16, 2012. Glutathione S-transferase M 1 (GSTM1) null genotype, Glutathione S-transferase T 1 (GSTT1) null genotype, and dual null genotype of GSTM1/GSTT1 were analyzed independently. 14 eligible studies with a total of 1,845 idiopathic infertility males and 1,729 controls were included. There were 13 studies on GSTM1 polymorphism, 10 ones on GSTT1 polymorphism and 5 ones on GSTM1-GSTT1 interaction analysis. Meta-analyses of total relevant studies showed GSTM1 null genotype was significantly associated with an increased risk of male idiopathic infertility (OR = 1.40, 95 % CI 1.07–1.84, P _OR = 0.015). The GSTM1-GSTT1 interaction analysis showed dual null genotype of GSTM1/GSTT1 was also significantly associated with increased risk of male idiopathic infertility (OR = 1.85, 95 % CI 1.07–3.21, P _OR = 0.028). Subgroup analyses by ethnicity showed the associations above were still statistically significant in Caucasians (For GSTM1, OR = 1.51, 95 % CI 1.11–2.05, P _OR = 0.009; For GSTM1/GSTT1, OR = 2.10, 95 % CI 1.51–2.91, P _OR < 0.001). This meta-analysis suggests GSTM1 null genotype contributes to increased risk of male idiopathic infertility in Caucasians, and males with dual null genotype of GSTM1/GSTT1 are particularly susceptible to developing idiopathic infertility.     

Association between the receptor for advanced glycation end products gene polymorphisms and coronary artery disease

Receptor for advanced glycation end products (RAGE) is a cell-surface molecule member of the immunoglobulin superfamily and thought to play a critical role in diabetic atherosclerosis. A growing body of studies has been conducted to determine the extent to which the variants of RAGE gene influence the risk of coronary artery disease (CAD). However, these have reported conflicting results. To investigate this inconsistency, we performed a comprehensive meta-analysis on the associations between the RAGE ?374T/A, ?429T/C, and Gly82Ser polymorphisms and the risk of CAD. A total of 4,402 cases and 6,081 controls from 17 published case–control studies were included. The overall odds ratio (OR) of CAD was 0.99 (95 % CI 0.87–1.13), 1.06 (95 % CI 0.95–1.18) and 1.12 (95 % CI 0.90–1.39) for ?374A, ?429C, and the minor S allele of the Gly82Ser polymorphism, respectively. Similarly, no significant results were observed for these polymorphisms using dominant model. However, when stratified by diabetic/non-diabetic status of the CAD patients, we found significant association among Caucasian type two diabetic CAD patients with the ?374A allele [OR 1.39, 95 % CI 1.10–1.76, P(Z) = 0.006], while no association was detected between the ?374T/A polymorphism and non-diabetic CAD in Caucasians [OR 0.79, 95 % CI 0.58–1.07, P(Z) = 0.13]. In conclusion, this meta-analysis suggested that possession of the ?374A allele may be a risk factor in CAD among Caucasian patients with type two diabetes.     

The Cdx-2 polymorphism in the VDR gene is associated with increased risk of cancer: a meta-analysis

The Cdx-2 polymorphism in VDR gene has been extensively investigated for association with cancer risk, however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of the Cdx-2 polymorphism in VDR and cancer risk by meta-analysis. All eligible case–control studies were searched in Pubmed, Embase, CNKI and Wanfang databases. Odds ratios (OR) with the 95 % confidence intervals (CI) were used to assess the association. A total of 12,906 cases and 13,700 controls in 18 case–control studies were included. The results indicated that the AA homozygote carriers had a 16 % increased risk of cancer, when compared with the homozygote GG and heterozygote AG (OR = 1.16, 95 % CI 1.05–1.29 for AA vs. GG+AG). In the subgroup analysis by ethnicity, significant elevated risks were associated with AA homozygote carriers in Caucasians (OR = 1.16, 95 % CI 1.01–1.33, and P = 0.04) and African Americans (OR = 1.31, 95 % CI 1.07–1.61, and P = 0.01). In the subgroup analysis by cancer types, the polymorphism was associated with increased risk of breast cancer (OR = 1.23, 95 % CI 1.04–1.46, and P = 0.02). This meta-analysis suggested that the Cdx-2 polymorphism of VDR gene would be a risk factor for cancer. To further evaluate gene-to-gene and gene-to-environmental interactions between polymorphisms of VDR gene and cancer risk, more studies with large groups of patients are required.     

VEGF +936C/T and +460C/T gene polymorphisms and oral cancer risk: a meta-analysis

Many studies have examined the association between the VEGF +936C/T (rs833061) and +460C/T (rs3025039) gene polymorphisms and oral cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, we performed a meta-analysis. The PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched for case–control studies that were published up to January 2013. Data were extracted and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated. Ultimately, six studies were included, comprising 1006 oral cancer cases and 1016 controls. Overall, the pooled OR for VEGF +936 T allele carriers (TC + TT) versus the wild-type homozygotes (CC) was 1.28 (95 % CI 1.04–1.58; P = 0.228 for heterogeneity), the pooled OR for TT versus CC was 1.64 (95 % CI 1.34–1.98; P = 0.315 for heterogeneity), and the pooled OR for the T allele versus the C allele was 1.42 (95 % CI 1.22–1.76; P = 0.286 for heterogeneity). In the stratified analysis by ethnicity, significant risks were found among Caucasians but not Asians. However, there were no associations between VEGF +460C/T and oral cancer risk in only two of the included studies. In conclusion, this meta-analysis demonstrates that the VEGF +936 T allele may be associated with an increased risk of oral cancer, especially among Caucasian populations.     

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.     

Association of the Hypoxia Inducible Factor-1α Gene Polymorphisms with Gastric Cancer in Tibetans

To determine how single nucleotide polymorphisms (SNPs) in the hypoxia inducible factor-1α (HIF-1α) gene coding regions affect gastric cancer, the authors conducted an association study of the HIF-1α polymorphisms C1772T and G1790A for a Tibet population. DNA was extracted from peripheral blood of 87 gastric cancer patients and 106 controls and analyzed using the polymerase chain reaction/ligase detection reaction test for HIF-1α polymorphisms. There was a significant increase in the frequency of the GA 1790 genotype in patients with gastric cancer compared with healthy controls (OR 2.93; 95% CI 1.06–8.06). The genotype frequency of the HIF-1α G1790A allele A is higher in gastric cancer groups than in controls (OR 2.78; 95% CI 1.03–7.45). As for the C1772T polymorphism, no positive correlation was found between gastric cancer patients and controls (P = 0.06). Our results suggest that the HIF-1α G1790A polymorphism may be associated with gastric cancer in Tibetans.     

The association between the Lys751Gln polymorphism in the XPD gene and the risk of bladder cancer

The Lys751Gln polymorphism in the XPD gene have been suggested as a risk factor for bladder cancer, however the results were inconclusive. The aim of the current study is to assess the association by meta-analysis. A total of 15 case–control studies concerning the association between the XPD Lys751Gln polymorphism and bladder cancer risk were included in the meta-analysis. The results suggested that the Lys751Gln polymorphism was not associated with an increased risk of bladder cancer in the dominant model (OR = 1.03, 95 % CI 0.95–1.11, P = 0.53 for Lys/Gln+Gln/Gln vs. Lys/Lys) in overall analysis. In the subgroup analysis by ethnicity, no significant association was found in Caucasians or Asians. Other comparatives suggested a slight significant association between the polymorphism with the risk of bladder cancer in the recessive comparative (OR = 1.14, 95 % CI 1.02–1.29, P = 0.03). The current meta-analysis indicated that the Lys751Gln polymorphism in the XPD gene might be a risk factor for bladder cancer. In the future, more large-scale case–control studies are needed to validate our results.     

Effect of CDKN2A/B rs4977756 polymorphism on glioma risk: a meta-analysis of 16 studies including 24077 participants

So far, epidemiological studies have been performed to investigate the association of CDKN2A/B rs4977756 polymorphism and glioma risk. However, the results from different studies remain inconsistent. To clarify these conflicts and to quantitatively evaluate the effect of rs4977756 polymorphism on glioma risk, a meta-analysis was conducted using relevant published clinical studies about rs4977756 polymorphisms and glioma risk. Relevant studies concerning the association between rs4977756 polymorphism and risk of glioma were included in this meta-analysis. Odds ratio (OR) and 95 % confidence interval (CI) were calculated under fixed or random effects models when appropriate. Subgroup analyses were performed by race. This meta-analysis included 13 studies with a total of 8129 cases and 15,858 controls. The pooled results showed that there was an obvious association of CDKN2A/B rs4977756 polymorphism with risk of glioma in all four comparison models (dominant model/AG + GG vs. AA: OR = 1.36, 95 %CI = 1.20–1.54, p < 0.01; heterozygote comparison/AG vs. AA: OR = 1.31, 95 %CI = 1.12–1.53, p < 0.01; homozygote comparison/GG versus AA: OR = 1.49, 95 %CI = 1.36–1.64, p < 0.01; additive model/G vs. A: OR = 1.23, 95 %CI = 1.18–1.28, p < 0.01, respectively). For the subgroup analyses of ethnicities, similar results were observed in Caucasians. However, the association was not found between rs4977756 polymorphism and the risk of glioma in all models for the Asian studies. The CDKN2A/B rs4977756 polymorphism is obvious increase the risk of glioma in Caucasians. Future studies are needed to confirm the results in other ethnic populations.