Cirrhosis pathogenesis: Polymorphism of glutathione S-transferase genes

We tested the association of deletion polymorphism in the GSTT1 and GSTM1 genes for glutathione S-transferases and the A313G single-nucleotide polymorphism in the GSTP1 gene with cirrhosis morbidity and 4-year survival rate among residents of the Tomsk region, West Siberia. The homozygous deletion of the GSTM1 gene (null genotype) proved to be a protective factor against alcoholic and mixed (viral and alcoholic) liver cirrhosis. The frequency of this genotype in patients of the combined group having cirrhosis of any etiology was 39.2%, in patients with alcoholic cirrhosis it was 39.0%, and in patients with mixed cirrhosis it was 34.2%. This genotype was much more frequent among patients of the control group: 64.6%. The GSTM1 null genotype and the GSTP1 A313G polymorphic variant correlated with survival rate. The survivors had a higher GSTM1 null genotype frequency than the dead patients, 46.6 and 30.2%, respectively; a higher frequency of the GSTP1 AA genotype, 63.1 and 40.5%; and a lower frequency of the GSTP1 AG (A313G) genotype (31.1 and 51.2%). The survival rate in patients with the GSTP1 AA genotype was 2.5 times as high as in GG or AG genotype carriers. In patients with the GSTM1 null genotype, the survival rate was twice as high as in patients without the deletion. The 4-year fatal case probability in patients having the heterozygous GSTP1 AG genotype was 2.3 times higher than in patients with the homozygous AA or GG genotypes.     

The glutathione S-transferase M1 and P1 polymorphisms and rheumatoid arthritis: a meta-analysis

The aim of this study was to determine whether the Glutathione S-transferase M1 (GSTM1) and P1 (GSTP1) polymorphisms confer susceptibility to rheumatoid arthritis (RA). Meta-analysis was performed on the associations between the GSTM1 and GSTP1 null genotypes and RA, and on the association between smoking or seropositive status and the GSTM1 null genotype in RA patients. Twelve studies involving 3,990 RA patients and 2,815 controls were included in the meta-analysis. All 12 studies examined the GSTM1 polymorphism and three the GSTP1 polymorphism. Meta-analysis of GSTM1 null polymorphism in 2,291 RA and 2,713 control subjects revealed no association between RA and the GSTM1 null genotype (OR?=?1.139, 95?% CI?=?0.914–1.419, p?=?0.246). Stratification by ethnicity indicated no association between the GSTM1 null genotype and RA in Asians or Europeans (OR?=?1.245, 95?% CI?=?0.729–2.124, p?=?0.422; OR?=?1.023, 95?% CI?=?0.794–1.318, p?=?0.863). Furthermore, there was no association between smoking and the GSTM1 null genotype (OR?=?0.943, 95?% CI?=?0.734–1.210, p?=?0.642). In addition, no association was found between seropositive status including anti-CCP (anti-citrullinated antibody) and/or RF (rheumatoid factor) and the GSTM1 null genotype. Meta-analysis of 915 RA and 1,082 controls revealed no association between RA and the GSTP1 null genotype (OR?=?0.965, 95?% CI?=?0.802–1.161, p?=?0.704). Furthermore, stratification by ethnicity indicated no association between the GSTP1 null genotype and RA in Europeans (OR?=?0.794, 95?% CI?=?0.594–1.061, p?=?0.119). This meta-analysis suggests that the GSTM1 and GSTP1 polymorphisms are not associated with the risk of RA. However, due to the small number of studies included and our inability to perform subgroup analysis by environmental factors, further studies are required to explore the roles played by GSTM1 and GSTP1 polymorphisms in the pathogenesis of RA.     

Impact of glutathione transferase M1, T1, and P1 gene polymorphisms in the genetic susceptibility of North Indian population to renal cell carcinoma

In this study, we investigated the association of GSTP1, GSTM1, and GSTP1 genetic variants with renal cell carcinoma (RCC) among North Indian patients. The difference in frequency of the GSTT1 null genotype between cases and control subjects was statistically significant (active ver. null, odds ratio [OR]=0.368; confidence intervals [CI] 95%=0.243-0.557, p=0.001). The differences in the frequency of GSTP1 genotypes were statistically significant (AA ver. AG/GG, OR=1.879; CI 95%=0.355-0.797, p=0.002). Higher allelic frequency of the GSTP1 G allele was associated with RCC cases (G ver. A allele, OR=1.534; 95% CI=1.159-2.030, p=0.003). The gene-gene interaction in terms of three-way combination of GSTM1 null, GSTT1 null, and GSTP1 (AG/GG) resulted in 4.5-fold increase in RCC risk (OR=4.452; 95% CI=2.220-9.294). Similarly, our study revealed that GST polymorphism might be a vital determinant of advancement to higher pathological stages and histological grades of RCC. Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to RCC and its progression.     

Association of glutathione S-transferase P1 gene polymorphism with the susceptibility of lung cancer

The conclusions of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) gene polymorphism and the risk of lung cancer are still debated. GSTP1 is one of the important mutant sites reported at present. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of lung cancer. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Forty-four reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and lung cancer susceptibility, consisting of 12,363 patients with lung cancer and 13,948 controls. The association between GSTPI G allele and lung cancer risk was found in this meta-analysis (OR 1.08, 95?% CI 1.02–1.15, P?=?0.01). However, the GG genotype and AA genotype were not associated with the susceptibility of lung cancer. Furthermore, there was no association between GSTP1 A/G gene polymorphism and the risk of lung cancer in Caucasians, and East-Asians. In conclusion, GSTP1 G allele is associated with the lung cancer susceptibility. However, more studies on the relationship between GSTP1 A/G gene polymorphism and the risk of lung cancer should be performed in the future.     

Genetic association between IL-27 rs153109 polymorphism and cancer risk in Chinese population: a meta-analysis

IL-27 plays an important role in anti-cancer activity. The -964A/G polymorphism in IL-27 gene has been implicated in susceptibility to cancer, but the results were conflicting. The aim of this study was to assess the association between this polymorphism and cancer risk. Pubmed and Wanfang database were searched for all publications concerning IL-27 -964A/G polymorphism and cancer risk. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of association. Statistical analysis was performed using Stata 11.0 software. A total of eight case–control studies including 2044 cancer cases and 2197 controls were identified. Overall, significant association between IL-27 -964A/G polymorphism and cancer risk was observed (GG versus AA: OR?=?1.26, 95% CI?=?1.03–1.52; GG versus AG?+?AA: OR?=?1.20, 95% CI?=?1.00–1.44). In subgroup analysis based on cancer type, significant association was found in colorectal cancer (GG versus AA: OR?=?1.55, 95% CI?=?1.07–2.27; AG versus AA: OR?=?1.31, 95% CI?=?1.02–1.67). The current meta-analysis suggests that IL-27 -964A/G polymorphism might enhance cancer risk. However, large-scale and well-designed studies are still needed to confirm the result of our meta-analysis. The association of IL-27 polymorphism with colorectal cancer may provide insight for future therapies.     

miR-499 rs3746444 polymorphism is associated with cancer development among Asians and related to breast cancer susceptibility

To derive a more precise estimation of the relationship between miR-499 rs3746444 polymorphism (A>G) and cancer risk, a meta-analysis was performed. A total of 9 studies including 6,077 cases and 7,199 controls were involved in this meta-analysis. Overall, no significantly elevated cancer risk was associated with miR-499 G allele when all studies were pooled into the meta-analysis (AG vs. AA: OR?=?1.14, 95?% CI?=?0.98–1.32; GG vs. AA: OR?=?1.12, 95?% CI?=?0.95–1.33; dominant model: OR?=?1.13, 95?% CI?=?0.99–1.29; recessive model: OR?=?1.05, 95?% CI?=?0.83–1.33). In the subgroup analysis by ethnicity, significantly increased risk was only found for Asians (dominant model: OR?=?1.22, 95?% CI?=?1.02–1.46). When stratified by study design, no statistically significantly elevated risks were found in hospital-based studies or population-based studies. In the subgroup analysis by cancer type, significant cancer risk change was only found for breast cancer when miR-499 G allele was included (dominant model: OR?=?1.13, 95?% CI?=?1.01–1.26). In conclusion, this meta-analysis suggests that the miR-499 rs3746444 polymorphism (A>G) is a low-penetrant risk factor for cancer development among Asians and may contribute to breast cancer susceptibility.     

A meta-analysis of the relationship between glutathione S-transferases gene polymorphism and hepatocellular carcinoma in Asian population

The results from the published studies on the association between glutathione S-transferases (GST) gene polymorphism and hepatocellular carcinoma (HCC) in Asian population are still conflicting. GSTM1, GSTT1 and GSTP1 are the mainly mutant sites reported at present. This meta-analysis was performed to evaluate the relationship between GST gene polymorphism and HCC risk in Asians. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) on February 1, 2012, and eligible investigations were synthesized using meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95?% confidence intervals (CI) were also calculated. Twenty-five investigations were identified for the analysis of association between polymorphic deletion of GSTM1 and HCC, consisting of 3,547 patients with HCC and 6,132 controls. There was a marked association between GSTM1 null genotype and HCC susceptibility (OR 1.48, 95?% CI 1.19–1.85, P?=?0.0004). GSTM1 null genotype was associated with HCC risk in Chinese. Furthermore, null genotype of GSTT1 was associated with HCC susceptibility in Asians. For the GSTM1–GSTT1 interaction analysis, the dual null genotype of GSTM1/GSTT1 was significantly associated with HCC susceptibility in Asian population. However, GSTP1 ile105?val gene polymorphism was not associated with HCC risk in Asian population. In conclusion, GSTM1/GSTT1 null genotype is associated with the HCC susceptibility. However, GSTP1 gene polymorphism is not associated with HCC risk.     

Association of monocyte chemoattractant protein-1 2518G/A gene polymorphism with diabetic nephropathy risk

Abstract

Results from the published studies on the association between monocyte chemoattractant protein-1 (MCP-1) ?2518 A/G gene polymorphism and diabetic nephropathy (DN) risk are still conflicting. This meta-analysis was performed to evaluate the relationship between MCP-1 A/G gene polymorphism and DN risk and to explore whether MCP-1 A allele, AA genotype or GG genotype could become a predictive marker for DN risk. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of 1 March 2014, and eligible investigations were synthesized using meta-analysis method. Four studies were identified for the analysis of association between MCP-1 A/G gene polymorphism and DN risk, and all the included studies were form Asian population. The association between MCP-1 A/G gene polymorphism and DN susceptibility was not found (A allele: OR?=?1.19; 95% CI: 0.97–1.45; p?=?0.10; AA genotype: OR?=?1.27; 95% CI: 0.95–1.70; p?=?0.11; GG genotype: OR?=?0.77; 95% CI: 0.57–1.05; p?=?0.10). In the sensitive analysis, according to the control source from hospital, we found that AA genotype was associated with the DN risk (OR?=?1.45; 95% CI: 1.05–2.00; p?=?0.02). However, other associations were not found in the sensitive analysis according to the control source from hospital or population. Our results indicate that AA homozygous might be a significant genetic molecular marker to predict the diabetes mellitus patients developing into DN. However, more investigations are required to further clarify this association.     

Single Nucleotide Polymorphism 8q24 rs13281615 and Risk of Breast Cancer: Meta-Analysis of More than 100,000 Cases

Background

The onset and progression of breast cancer (BC) is influenced by many factors, including the single nucleotide polymorphism (SNP) rs13281615 at 8q24. However, studies of the potential association between rs13281615 at 8q24 and risk of BC have given inconsistent results. We performed a meta-analysis to address this controversy.

Methods

PubMed, EMBASE and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Two curators independently extracted data, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the strength of the association between rs13281615 at 8q24 and risk of BC.

Results

Fourteen studies are included in the meta-analysis, involving 44,283 cases (5,170 Chinese and 39,113 mixed) and 55,756 controls (5,589 Chinese and 50,167 mixed). The GG and G-allele genotypes of rs13281615 at 8q24 are significantly associated with increased risk of BC (GG vs. AG+AA, OR 1.13, 95% CI 1.08–1.19, P<0.001; G-allele vs. A-allele, OR 1.10, 95% CI 1.06–1.14, P<0.001; GG vs. AA, OR 1.20, 95% CI 1.12–1.29, P<0.001). Conversely, the AA genotype is significantly associated with decreased risk of BC (AA vs. AG+GG, OR 0.89, 95% CI 0.84–0.93, P<0.001).

Conclusion

G-allele genotypes of rs13281615 at 8q24 polymorphism are a risk factor for developing BC, while the AA genotype is a protective factor. Further large and well-designed studies are required to confirm this conclusion.     

Association between the −1438G/A and T102C polymorphisms of 5-HT2A receptor gene and obstructive sleep apnea: a meta-analysis

The serotonin 2A (5-HT2A) receptor has been implicated in obstructive sleep apnea (OSA). Single nucleotide polymorphisms (SNPs) in the 5-HT2A gene have been found in OSA, the most common being ?1438G/A and T102C; however, studies of the association between 5-HT2A SNPs and OSA risk have reported inconsistent findings. A meta-analysis was performed to quantitatively review the association between ?1438G/A and T102C SNPs and OSA. Five studies, including 791 subjects for ?1438G/A genotype and 1,068 subjects for T102C genotype, were selected. Pooled data analysis of the ?1438G/A genotype indicated a significantly increased OSA risk was associated with two variant genotypes (AA vs. AG+GG: OR 3.023, 95 % CI 2.169–4.213, P = 0.506 for heterogeneity; A allele carriers vs. GG: OR 1.938, 95 % CI 0.879–4.274, P = 0.012 for heterogeneity). Stratification analysis by gender supported the association in males, but not females. For the T102C genotype, no significantly increased OSA risk was associated with the two variant genotypes (CC vs. CT+TT: OR 1.065, 95 % CI 0.787–1.442, P = 0.361 for heterogeneity; C allele carriers vs. TT: OR 0.979, 95 % CI 0.737–1.3, P = 0.9 for heterogeneity).In conclusions, meta-analysis indicated that the ?1438G/A, and not T102C, polymorphism of 5-HT2A is a positive risk factor of OSA, especially in males.     

Association of gene polymorphisms in MYH11 and TGF-β signaling with the susceptibility and clinical outcomes of DeBakey type III aortic dissection

To investigate the association of myosin heavy chain protein 11 (MYH11) and transforming growth factor β signaling-related gene polymorphisms with the susceptibility of DeBakey type III aortic dissection (AD) and its clinical outcomes. Four single-nucleotide polymorphism (SNPs) (MYH11 rs115364997, rs117593370, TGFB1 rs1800469, and TGFBR1 rs1626340) were analyzed in patients with DeBakey III AD (173) and healthy participants (335). Gene–gene and gene–environment interactions were evaluated using generalized multifactor dimensionality reduction. The patients were followed up for a median of 55.7 months. MYH11 rs115364997 G or TGFBR1 rs1626340 A carriers had an increased risk of DeBakey type III AD. MYH11, TGFB1, TGFBR1, and environment interactions contributed to the risk of DeBakey type III AD (cross-validation consistency?=?10/10, P?=?0.001). Dominant models of MYH11 rs115364997 AG?+?GG genotype (HR?=?2.443; 95%CI: 1.096–5.445, P?=?0.029), TGFB1 rs1800469 AG?+?GG (HR?=?2.303; 95%CI: 1.069–4.96, P?=?0.033) were associated with an increased risk of mortality in DeBakey type III AD. The dominant model of TGFB1 rs1800469 AG?+?GG genotype was associated with an increased risk of recurrence of chest pain in DeBakey type III AD (HR?=?1.566; 95%CI: 1.018–2.378, P?=?0.041). In conclusions, G carriers of MYH11 rs115364997 or TGFB1 rs1800469 may be the poor prognostic indicators of mortality and recurrent chest pain in DeBakey type III AD. The interactions of gene–gene and gene–environment are associated with the risk of DeBakey type III AD.

     

RAD51 polymorphisms and breast cancer risk

Breast cancer (BC) is one of the most common causes of death among women, and second in Iran. The objectives of this study were to determine the frequency of RAD51 G/C polymorphism in patients with breast cancer. We evaluated these polymorphisms and effects on the breast cancer risk association in a Iranian sporadic population-based case?Ccontrol study of 294 breast cancer cases and 315 controls using a PCR?CRFLP-based assay. Analyses of affected and controls show that homozygote genotype RAD51 GG has the highest frequency in both groups (33.3 in patients and 41.4 in control group). Genotype RAD51 GG most risk factor were in our population: [CC/GC odds ratio, 0.364 (95?% confidence interval; CI, 0.168?C0.788) p?=?0.009, CC/GG odds ratio, 0.828 (95?% CI, 0.411?C1.668) p?=?0.596], GG/GC odds ratio, 2.276 (95?% CI, 1.497?C3.460) p?=?0.001]. There was a significant association of breast cancer risk with RAD51 GG and CC polymorphism.     

CTLA4 A49G Polymorphism Shows Significant Association With Glioma Risk in a Chinese Population

Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) A49G is a polymorphism that is extensively studied in various cancers. To investigate whether it is associated with the occurrence of glioma in Chinese patients, we performed a case-control research study with 670 patients and 680 controls. In this group, we found that the genotype at this locus is significantly associated with glioma risk (GG vs. AA: P?=?0.045; GG?+?AG vs. AA: P?=?0.013). In some subgroups, G allele carriers are significantly less represented. We also observed significant correlations between the polymorphism genotype and glioma risk in patients with WHO histologic stages. We conclude that CTLA4 A49G might be a potential clinical biomarker for distinguishing persons with a high risk for developing gliomas.     

Association between GSTP1, GSTM1 and GSTT1 polymorphisms involved in xenobiotic metabolism and head and neck cancer development

Polymorphisms in the glutathione S-transferase superfamily genes that encodes enzymes involved in the phase II xenobiotic metabolism may lead head and neck cancer development. In this study we investigate the association of A313G and C341T GSTP1 polymorphisms, GSTM1 and GSTT1 null genotypes in the head and neck cancer development, interactions between these polymorphisms,the tumor histopathologic parameters and risk factors (smoking and drinking) were also evaluated in the case–control study. 775 individuals (261 patients/514 controls) were included in the study. Molecular analyzes were performed by PCR and PCR–RFLP; and statistical analyzes by Chi square and multiple logistic regression. Chi square test showed that only the genotype frequencies for GSTM1 and GSTT1 were in Hardy–Weinberg disequilibrium in both groups. Significant results with p ≤ 0.05 showed that age ≥ 48 years (OR = 11.87; 7.55–18.65), smoking (OR = 4.25; 2.70–6.69), drinking (OR = 1.59; 1.02–2.46) were possible predictors for the head and neck cancer development and the presence of A313G GSTP1 polymorphism (OR = 0.62; 0.42–0.92) decreased the risk for this disease. Individuals with the 313AG/GG GSTP1 and age ≥ 48 years (OR = 0.59; 0.38–0.91), male gender (OR = 0.54; 0.35–0.83), smokers (OR = 0.63; 0.40–0.99) and drinkers (OR = 0.57; 0.35–0.95); the GSTM1 null genotype and age < 48 years (OR = 2.46; 1.09–5.55); the GSTT1 null genotype and primary anatomical sites of pharynx (OR = 0.37; 0.17–0.79) and larynx (OR = 3.60; 1.93–6.72), can modulate the risk for the disease development. The variables age ≥ 48 years, smoking and drinking can be predictors for head and neck cancer development; moreover, A313G GSTP1 polymorphism, GSTM1 and GSTT1 null genotypes can modulate the risk for this disease.     

rs11567842 SNP in <Emphasis Type="Italic">SLC13A2</Emphasis> gene associates with hypocitraturia in Thai patients with nephrolithiasis

Hypocitraturia is a profound risk for kidney stone formation and recurrence. Sodium-dicarboxylate cotransporter-1 (NaDC-1) is a main transporter responsible for citrate reabsorption in renal proximal tubules. To investigate an association of sodium-dicarboxylate cotransporter-1 (NaDC-1) polymorphism with hypocitraturia in Thai patients with nephrolithiasis (NL). Exonic SNPs in NaDC-1 were screened in peripheral blood DNA of 13 NL patients. The rs11567842 (A/G) variant was found and further genotyped in 145 NL patients and 115 non-stone forming controls. NL patients had significantly lower level of urinary citrate than the controls. Based on logistic regression, hypocitraturia was significantly associated with urinary stone formation (adjusted OR 8.34, 95% CI 4.63–15.04). Significant association of urinary citrate level with rs11567842 genotype was found only in the NL group. NL patients with GG genotype had significantly higher urinary citrate than those with AA and AG genotypes. GG carrying patients had significantly reduced risk for hypocitraturia (adjusted OR 0.15; 95% CI 0.05–0.48, AA as reference). In selected 15 calcium oxalate stone patients, AA carriers had significantly higher intrarenal NaDC-1 mRNA than GG and AG carriers. Homozygous GG of rs11567842 SNP in NaDC-1 gene was a protective genotype for hypocitraturia in kidney stone patients. The findings suggested that patients with AA genotypes were more susceptible to hypocitraturia than those with GG, hence carrying a higher risk for kidney stone recurrence.     

Glutathione S-transferase M1, T1, and P1 genotypes and breast cancer risk: a study in a Portuguese population

Glutathione S-transferases are a superfamily of multifunctional enzymes that play a key role in Phase II metabolism, detoxifying therapeutic drugs, and various carcinogens by conjugation with glutathione. We undertook a case-control study in Central-Eastern Portuguese population to evaluate the association of null genotype in GSTM1 and GSTT1 along with the polymorphism in GSTP1 (A/G) and susceptibility to breast cancer. The population sample consisted of 85 patients with histological diagnosis of breast cancer and 102 healthy women. Genomic DNA was extracted from blood samples, and genotyping analyses were performed by PCR-based methods. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression. We found a increased breast cancer risk associated with GSTM1 null genotype (OR = 3.597; 95% CI = 1.849-6.999; P = 0.0001) and GSTT1 (OR = 2.592; 95% CI = 1.432-4.690; P = 0.002), but the presence of valine alleles compared to isoleucine alleles in codon 105 in GSTP1 did not increase the risk of breast cancer development. The two-way combination of GSTM1 and GTTT1 null genotypes resulted in 8-fold increase for breast cancer risk (OR = 8.287; 95% CI = 3.124-21.980; P = 0.0001) and the three-way combination of GSTP1 105AA/AG and null genotypes for both GSTM1 and GSTT1 resulted in 5-fold increase for breast cancer risk (OR = 5.040; 95% CI = 1.392-18.248; P = 0.016). Our results suggest that GSTM1 and GSTT1 null genotype alone, both combined or combined with GSTP1 valine alleles, are associated with higher susceptibility to breast cancer development.     

Association Study of Single Nucleotide Polymorphisms in XRCC1 Gene with the Risk of Gastric Cancer in Chinese Population

Gastric cancer is one of highly cancer-related deaths in the world. Previous evidence suggests that the X-ray repair cross-complementing group 1 gene (XRCC1) is one of the most important candidate genes for influencing gastric cancer risk. The objective of this study was to detect the potential association of genetic variants in XRCC1 gene with gastric cancer risk in Chinese Han population. In total, we enrolled 395 gastric cancer patients and 398 cancer-free controls in this study. The genotyping of c.910A>G and c.1804C>A genetic variants in XRCC1 gene were investigate by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and created restriction site-PCR (CRS-PCR) methods, respectively. We found the genotypes/alleles from these two genetic variants were statistically associated with the increased risk of gastric cancer (for c.910A>G, GG versus (vs.) AA: OR = 2.00, 95% CI 1.21-3.31; AG vs. AA: OR = 1.50, 95% CI 1.12-2.02; GG/AG vs. AA: OR = 1.59, 95% CI 1.20-2.10; GG vs. AG/AA: OR = 1.68, 95% CI 1.03-2.73; G vs. A: OR = 1.47, 95% CI 1.18-1.83; for c.1804C>A, AA vs. CC: OR = 2.68, 95% CI 1.46-4.94; AA vs. CA/CC: OR = 2.62, 95% CI 1.44-4.76; A vs. C: OR = 1.33, 95% CI 1.06-1.66). The allele-G of c.910A>G and allele-A of c.1804C>A genetic variants may contribute to gastric cancer susceptibility. These preliminary results indicate that these XRCC1 genetic variants are potentially related to gastric cancer susceptibility in Chinese Han population, and might be used as molecular markers.     

Relationship between Interleukin-10 ?1082A/G Polymorphism and Risk of Ischemic Stroke: A Meta-Analysis

Objective

To analyze the association between −1082A/G polymorphism in interleukin-10 (IL-10) gene and ischemic stroke (IS) risk by meta-analysis.

Methods

We carried out a systematic electronic search in PubMed, BIOSIS Previews, Science Direct, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Weipu database and WANGFANG Database. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to assess the strength of the association.

Results

7 studies were included. There was no significant association between IL-10 −1082A/G polymorphism and IS risk under all genetic models in overall estimates (A vs. G: OR = 1.23,95%CI = 0.85–1.79;AA vs. GG: OR = 1.01,95%CI = 0.47–2.19; AG vs. GG: OR = 0.76, 95%CI = 0.38–1.55; AA+AG vs. GG: OR = 0.89,95%CI = 0.46–1.73; AA vs. AG+GG: OR = 1.39, 95%CI = 0.91–2.13). Similarly, no associations were found in subgroup analysis based on ethnicity and source of controls. However, removing the study deviating from Hardy–Weinberg equilibrium (HWE) produced statistically significant associations for overall estimates under recessive model(AA VS. AG+GG OR 1.58, 95% CI 1.04–2.42) and among Asians in all genetic models (A VS.G OR 1.64, 95% CI 1.07–2.53; AA vs. GG OR1.91, 95% CI 1.31–2.80; AG vs. GG OR1.44, 95% CI 1.09–1.91; AA+AG vs. GG OR 1.54, 95% CI 1.18–2.01;AA VS. AG+GG OR 1.79, 95% CI 1.07–3.00). Even after Bonferroni correction, the associations were observed still significantly in Asians under the two models (AA vs. GG OR1.91, 95% CI 1.31–2.80, P = 0.0008; AA+AG vs. GG OR 1.54, 95% CI 1.18–2.01, P = 0.001).

Conclusion

This meta-analysis indicates that IL10 −1082 A/G polymorphism is associated with IS susceptibility in Asians and the −1082 A allele may increase risk of IS in Asians. Considering the sample size is small and between-study heterogeneity is remarkable, more studies with subtle design are warranted in future.     

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.     

Genetic Polymorphisms of GSTM1, GSTT1, and GSTP1 with Prostate Cancer Risk: A Meta-Analysis of 57 Studies

Background and Objectives

The GSTM1, GSTT1 and GSTP1 polymorphisms might be involved in inactivation of procarcinogens that contribute to the genesis and progression of cancers. However, studies investigating the association between GSTM1, GSTT1 or GSTP1 polymorphisms and prostate cancer (PCa) risk report conflicting results, therefore, we conducted a meta-analysis to re-examine the controversy.

Methods

Published literature from PubMed, Embase, Google Scholar and China National Knowledge Infrastructure (CNKI) were searched (updated to June 2, 2012). According to our inclusion criteria, studies that observed the association between GSTM1, GSTT1 or GSTP1 polymorphisms and PCa risk were included. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of PCa associated with GSTM1, GSTT1 and GSTP1 polymorphisms.

Results

Fifty-seven studies involving 11313 cases and 12934 controls were recruited. The overall OR, which was 1.2854 (95% CI = 1.1405–1.4487), revealed a significant risk of PCa and GSTM1 null genotype, and the similar results were observed when stratified by ethnicity and control source. Further, the more important is that the present study first reported the high risks of PCa for people who with dual null genotype of GSTM1 and GSTT1 (OR = 1.4353, 95% CI = 1.0345–1.9913), or who with GSTT1 null genotype and GSTP1 A131G polymorphism (OR = 1.7335, 95% CI = 1.1067–2.7152). But no association was determined between GSTT1 null genotype (OR = 1.102, 95% CI = 0.9596–1.2655) or GSTP1 A131G polymorphism (OR = 1.0845, 95% CI = 0.96–1.2251) and the PCa risk.

Conclusions

Our meta-analysis suggested that the people with GSTM1 null genotype, with dual null genotype of GSTM1 and GSTT1, or with GSTT1 null genotype and GSTP1 A131G polymorphism are associated with high risks of PCa, but no association was found between GSTT1 null genotype or GSTP1 A131G polymorphism and the risk of PCa. Further rigorous analytical studies are highly expected to confirm our conclusions and assess gene-environment interactions with PCa risk.