Association between positive murine double minute 2 expression and clinicopathological characteristics of esophageal squamous cell carcinoma: a meta‐analysis

The correlations of murine double minute 2 (MDM2) T309G and esophageal cancer were elucidated because the association between MDM2 expression states and clinicopathological parameters of esophageal squamous cell carcinoma (ESCC) is controversial. We conducted a meta‐analysis on studies screened from PubMed, Web of Science, Embase, the Cochrane Library, and the Chinese Biomedical Literature Databases that were published before October 2014. All studies describing the association between MDM2 and ESCC were traced. Meta‐analysis was performed using the STATA software (Stata Corp., College Station, TX, USA). A total of 9 studies with 707 cases and 324 controls were included. MDM2 expression was higher in ESCC than in normal esophageal epithelium (odds ratio [OR] 10.38, 95% confidence interval [CI] 6.42–16.78, P < 0.001). High MDM2 expression was associated with early primary tumor stage (T1/T2 vs. T3/T4, OR 0.59, 95% CI 0.38–0.92, P = 0.018) and increased risk of regional lymph node metastasis (N0 vs. N1, OR 1.66, 95% CI 1.03–2.67, P = 0.039). However, no relationship was observed between MDM2 expression and the risk of distant metastasis (OR = 2.09, 95% CI 1.00–4.36, P = 0.050), and MDM2 was not significantly correlated with TP53 expression (OR 1.22, 95% CI 0.53–2.77, P = 0.643). Our analysis suggests that MDM2 acts as a potent marker of early primary tumor stage but higher risk of regional lymph node metastasis in ESCC. However, because of the limited number of studies included, the result should be further clarified by well‐designed prospective studies.     

Association between MDM2-SNP309 and hepatocellular carcinoma in Taiwanese population

AIM: To investigate the risk association and compare the onset age of hepatocellular carcinoma (HCC)patients in Taiwan with different genotypes of MDM2-SNP309.METHODS: We analyzed MDM2-SNP309 genotypes from 58 patients with HCC and 138 cancer-free healthy controls consecutively. Genotyping of MDM2-SNP309 was conducted by restriction fragment length polymorphism assay.RESULTS: The proportion of homozygous MDM2-SNP309 genotype (G/G) in cases and cancer-free healthy controls was similar (17.2% vs 16.7%). Multivariate analysis showed that the risk of G/G genotype of MDM2-SNP309 vs wild-type T/T genotype in patients with HCC was not significant (OR = 1.265, 95%CI = 0.074-21.77) after adjustment for sex, hepatitis B or C virus infection, age, and cardiovascular disease/diabetes. Nevertheless, there was a trend that GG genotype of MDM2-SNP309 might increase the risk in HCC patients infected with hepatitis virus (OR = 2.568,95% CI = 0.054-121.69). Besides, the homozygous MDM2-SNP309 genotype did not exhibit a significantly earlier age of onset for HCC.CONCLUSION: Current data suggest that the association between MDM2-SNP309 GG genotype and HCC is not significant, while the risk may be enhanced in patients infected by hepatitis virus in Taiwan.     

The PSCA polymorphisms derived from genome-wide association study are associated with risk of gastric cancer: a meta-analysis

Purpose

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol-anchored 123-aa protein related to the cell-proliferation inhibition and/or cell-death induction activity. Many studies had reported the role of PSCA rs2294008 C?>?T and rs2976392 G?>?A polymorphisms on gastric cancer risk.

Methods

To investigate a more precise estimation of the relationships, we performed a meta-analysis on 9 case–control studies included 10,746 cases and 9,158 controls. Odds ratios (ORs) and 95?% confidence intervals (CIs) were used to assess the strength of the association.

Results

For PSCA rs2294008 C?>?T polymorphism, there was a significantly increased risk of gastric cancer in all genetic models (TT/TC vs. CC: OR?=?1.61, 95?% CI?=?1.35–1.91; TT vs. TC/CC: OR?=?1.33, 95?% CI?=?1.24–1.42). Similar results were also observed for PSCA rs2976392 G?>?A polymorphism (AA/AG vs. GG: OR?=?1.69, 95?% CI?=?1.24–2.31; AA vs. AG/GG: OR?=?1.36, 95?% CI?=?1.24–1.50). In the stratified analysis by ethnicity of rs2294008, an increased gastric cancer risk was found in both Asians (TT vs. TC/CC: OR?=?1.31, 95?% CI?=?1.22–1.42) and Europeans (TT/TC vs. CC: OR?=?1.42, 95?% CI?=?1.18–1.71). Furthermore, when stratified by clinicopathologic characteristics of tumor location and histology, a higher risk on non-cardia compared with cardia gastric cancer (TT vs. TC/CC: OR?=?1.43, 95?% CI?=?1.12–1.83) as same as diffused compared with intestinal gastric cancer (TT vs. TC/CC: OR?=?1.29, 95?% CI?=?1.13–1.49) was observed.

Conclusion

These findings supported that PSCA rs2294008 C?>?T and rs2976392 G?>?A polymorphisms may contribute to the susceptibility to gastric cancer, particular in non-cardia or diffused gastric cancer.     

Relationship between apurinic endonuclease 1 Asp148Glu polymorphism and gastrointestinal cancer risk: An updated meta-analysis

AIM:To evaluate the relationship between apurinic endonuclease 1(APE1) Asp148 Glu polymorphism and the susceptibility to gastrointestinal(GI) cancers.METHODS:We searched Pub Med, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure(CNKI) databases updated on July 15, 2014 for relevant studies.Only case-control studies comparing APE1 Asp148 Glu polymorphism and GI cancer risk were included.We excluded studies reporting only standardized incidence ratios without control groups and those without detailed genotyping data.Meta-analysis was performed on 17 studies involving 4856 cancer patients and 6136 cancer-free controls.Review Manager version 5.1 was used to perform the meta-analysis.The pooled odds ratios(ORs) and 95% confidence intervals(CIs) were estimated under the allele contrast, homozygous, heterozygous, dominant and recessive genetic models.We also conducted subgroup analyses stratified by ethnicity and cancer type.Publication bias was evaluated using Begg's test.RESULTS:The meta-analysis showed a significant association between APE1 Asp148Glu polymorphism and GI cancer risk in three genetic models in the overall population(G vs T:OR=1.18;95%CI:1.05-1.32;TG vs TT:OR=1.28;95%CI:1.08-1.52;TG+GG vs TT:OR=1.32;95%CI:1.10-1.57).Stratified analysis by ethnicity revealed a statistically increased GI cancer risk in Asians(G vs T:OR=1.27;95%CI:1.07-1.51;GG vs TT:OR=1.58;95%CI:1.05-2.38;TG vs TT:OR=1.30;95%CI,1.01-1.67;and TG+GG vs TT:OR=1.38;95%CI:1.07-1.78),but not in Caucasians.Furthersubgroup analysis by cancer type indicated that APE1Asp148Glu polymorphism may contribute to gastric cancer risk.However,Asp148Glu has no significant association with colorectal or esophageal cancer risk in any genetic model.CONCLUSION:This meta-analysis suggests that the APE1 Asp148Glu polymorphism G allele is associated with an increased GI cancer risk,especially in gastric cancer.     

Association of Vitamin D Receptor Gene Polymorphism With the Risk of Nephrolithiasis

This study aimed to explore the relationship between vitamin D receptor (VDR) gene polymorphisms and the risk of nephrolithiasis. All relevant trials were searched from multiple databases according to predefined criteria, the pooled OR and corresponding 95% CI were analyzed using Stata software. Seventeen studies involving 2441 cases and 2296 controls were included. The pooled analysis showed that VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with nephrolithiasis susceptibility either in Asian and in Caucasians populations. VDR TaqI gene polymorphism was associated with nephrolithiasis in the overall populations (T vs. t: OR = 0.84, 95% CI: 0.73–0.95, P = 0.006; TT vs. Tt + tt: OR = 0.79, 95% CI: 0.66–0.95, P = 0.010). In Asian population, VDR TaqI gene polymorphism also was associated with nephrolithiasis susceptibility (TT vs. Tt + tt: OR = 0.72, 95% CI: 0.55–0.93, P = 0.012; Tt vs. TT + tt: OR = 1.43, 95% CI: 1.00–2.05, P = 0.048). But TaqI gene polymorphism was not associated with nephrolithiasis risk in Caucasian populations (T vs. t: OR = 0.85, 95% CI: 0.72–1.00, P = 0.051; TT vs. Tt + tt: OR = 0.87, 95% CI: 0.68–1.10, P = 0.245; tt vs. Tt + TT: OR = 1.32, 95% CI: 0.86–2.01, P = 0.206; Tt vs. TT+ tt: OR = 0.98, 95% CI: 0.70–1.38, P = 0.931). VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with the risk of nephrolithiasis either in Asian and Caucasians populations, but VDR TaqI gene polymorphism was associated with nephrolithiasis in the Asian subjects.     

The +252A/G polymorphism in the Lymphotoxin‐α gene increases the risk of asthma: A meta‐analysis

Background and Objective: A number of studies have shown that the +252A/G polymorphism (rs909253) in the lymphotoxin‐α (LT‐α) gene is implicated in susceptibility to asthma. However, the findings have been inconclusive. The aim of this study was to investigate the association between the +252A/G polymorphism in the LT‐α gene and the risk of asthma by performing a meta‐analysis. Methods: The Pubmed and Embase databases were searched for all studies relating to this polymorphism and the risk of asthma. Statistical analyses were performed using the Revman4.2 and STATA 10.0 software. Results: Thirteen case‐control studies that included a total of 2220 cases and 6428 controls were included in the meta‐analysis. There was no significant association between this polymorphism and the risk of asthma in the all‐combined analysis (odds ratio (OR) 1.14, 95% confidence interval (CI): 0.89–1.45 for GG+GA vs AA). In a subgroup analysis by ethnicity, no significant association with asthma risk was identified in Asians (OR 1.31, 95% CI: 0.97–1.77) or Europeans (OR 1.08, 95% CI: 0.77–1.53). In a subgroup analysis by age, a significantly increased risk was identified among adults (OR 1.25, 95% CI: 1.03–1.50) but not children (OR 1.04, 95% CI: 0.28–3.89). In a subgroup analysis by atopic status, a significantly elevated risk was identified among atopic (OR 1.55, 95% CI: 1.28–1.87) but not non‐atopic individuals (OR 0.94, 95% CI: 0.53–1.68). Conclusions: This meta‐analysis suggested that the +252A/G polymorphism in the LT‐α gene is a risk factor for asthma in adults and atopic populations.     

Association between the tumour necrosis factor-α-308G/A polymorphism and chronic obstructive pulmonary disease: an update

Background and objective: Previous studies have suggested that the ?308A allele in the tumour necrosis factor‐α (TNF‐α) gene promoter (rs1800629) may be a potential risk factor for COPD. However, more recent findings have been inconsistent. In the present study, a meta‐analysis was performed to assess the association between the TNF‐α?308G/A single nucleotide polymorphism (SNP) and the risk of COPD. Methods: Published studies were retrieved from PubMed, EMBASE and other databases. All studies assessing the association between the TNF‐α?308G/A SNP and the risk of COPD were assessed. Pooled ORs with 95% CIs were calculated. Results: In the 36 studies that met the inclusion criteria, 4975 patients and 6518 control subjects had been genotyped. The overall results showed that the association between the TNF‐α?308G/A SNP and the risk of COPD was statistically significant for Asians (OR = 2.36, 95% CI: 1.84–3.02, P < 0.0001) but not for Caucasians (OR = 1.07, 95% CI: 0.91–1.25, P = 0.438). As smoking is one of the most important risk factors for COPD, a second meta‐analysis that included only smokers (3018 patients and 2749 control subjects) was performed. This analysis confirmed that the association between the TNF‐α?308G/A SNP and COPD was statistically significant for Asians (OR = 1.72, 95% CI: 1.14–2.61, P = 0.011) but not for Caucasians (OR = 1.16, 95% CI: 0.86–1.56, P = 0.33). Conclusions: This meta‐analysis suggests that the TNF‐α?308A genotype is associated with an increased risk of COPD in Asian but not Caucasian populations. Further studies are necessary to evaluate the relationship between TNF‐α polymorphisms and the risk of COPD.     

Replication of results of genome‐wide association studies on esophageal squamous cell carcinoma susceptibility loci in a Korean population

Two recent genome‐wide association studies have identified that the rs2274223 single‐nucleotide polymorphism inphospholipase C epsilon 1 and the single‐nucleotide polymorphism rs13042395 in C20orf54 are involved in esophageal squamous cell carcinoma (ESCC) in Chinese populations. We hypothesized that genetic polymorphisms of phospholipase C epsilon 1 and C20orf54 are also associated with ESCC in a Korean population. The rs2274223 and rs13042395 genotyping was performed using high‐resolution melting analysis. The rs2274223 GG genotype was significantly associated with an increased risk of ESCC (odds ratio [OR] = 1.86, 95% confidence interval [CI] = 1.08–3.25) compared with the rs2274223 AA genotype. The rs13042395 G allele showed a significantly decreased risk of ESCC in the younger age group (OR = 0.71, 95% CI = 0.52–0.97) and no significant association in the older group (OR = 1.19, 95% CI = 0.87–1.62). We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case–control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.     

Elevated risk of colorectal cancer associated with the AA genotype of the cyclin D1 A870G polymorphism in an Indian population

Purpose: To investigate whether the common cyclin D1 (CCND1) A870G polymorphism is a risk factor for colorectal cancer (CRC) in an Indian population. Methods: In this study, 301 newly diagnosed CRC patients and 291 healthy control subjects were genotyped by the PCR-RFLP method. Genotype frequencies were compared between cases and controls, and the association of genotypes with CRC was studied. Results: The CCND1 870 A allele was more frequently observed in CRC patients than controls (0.63 vs. 0.56, P=0.01), and after adjustment for age, sex, smoking habits, family history, family income and the consumption of meat, fish, vegetables and fruit, an increased risk was observed for the AA genotype compared to the GG+AG genotype (OR=1.56; 95% CI: 1.10–2.21). The increased risk were also found for colon (OR=1.96; 95% CI: 1.08–3.57) and rectal cancer (OR=1.51; 95% CI: 1.04–2.19). No correlation was observed between genotypes and age of diagnosis of CRC (49.9, 48.7 and 49.4 years for the GG, AG and AA genotypes, respectively; P=0.84). Multivariate analysis also revealed a stronger positive association with the AA genotype among patients with high meat intake (OR=2.67; 95% CI: 1.29–5.51), and particularly significant inverse associations with the GG+AG genotypes were also found for those with high vegetable consumption (OR=0.46; 95% CI: 0.27–0.79 of 2–3 servings/day, and OR=0.31; 95% CI: 0.18–0.53 for >3 servings/day) and fish intake (OR=0.48; 95% CI: 0.28–0.82). Conclusion: These data support the hypothesis that the CCND1 A870G polymorphism may increase the risk of CRC in our Indian population.     

Association between transforming growth factor-β1 polymorphisms and hepatocellular cancer risk: A meta-analysis

Aim: The association between transforming growth factor‐β1 (TGF‐β1) gene polymorphisms and hepatocellular cancer (HCC) risk has been widely reported, but results were somewhat controversial. To derive a more precise estimation of the relationship between TGF‐β1 polymorphisms and HCC risk, we conducted a meta‐analysis of all available studies relating the C‐509T and/or T869C polymorphisms of the TGF‐β1 gene to the risk of developing HCC. Methods: Two investigators independently searched the MEDLINE, PubMed, Web of Science, Embase, CNKI (China National Knowledge Infrastructure) and CBM (Chinese Biomedical Literature database) for the period up to August 2011. Result: A total of nine case‐control articles were identified. Five studies with 1825 cases and 2869 controls for C‐509T polymorphism, and six studies with 536 cases and 1496 controls for T869C polymorphism were included. In the overall analysis, no significant association between the polymorphisms and risk of HCC was observed. Stratified analysis showed that significant association between C‐509T polymorphism and HCC was present only in controls with liver disease (T vs. C: odds ratio [OR] = 0.769, 95% confidence interval [CI] = 0.661–0.895; TT vs. CC: OR = 0.570, 95% CI = 0.412–0.788; TT/TC vs. CC: OR = 0.668, 95% CI = 0.523–0.854; TT vs. TC/CC: OR = 0.717, 95% CI = 0.550–0.934), but not in healthy controls. With respect to T869C polymorphism, only a decreased risk was found in recessive models in controls with liver disease. Conclusions: This meta‐analysis supports that the TGF‐β1 C‐509T polymorphism may act in a protecting role in HCC susceptibility in populations with related liver disease.     

Association of TNFSF4 polymorphisms with systemic lupus erythematosus: a meta-analysis

Abstract

Introduction To more precisely estimate the association between the tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene polymorphisms and systemic lupus erythematosus (SLE) risk, we surveyed studies on the association of the TNFSF4 rs2205960, rs1234315, rs844644, and rs844648 polymorphisms with SLE.

Methods A literature-based search was conducted to identify all relevant studies. A total of eight independent studies were identified and subsequently reviewed in the meta-analysis.

Results The meta-analysis showed an association between the TNFSF4 rs2205960 polymorphism and SLE in all subjects [ odds ratio (OR) 1.327, 95 % confidence interval (CI) 1.227–1.436, P < 0.001]. In a subgroup analysis by ethnicity, a significantly increased risk for SLE was associated with TNFSF4 rs2205960 T allele among patients of European (OR 1.254, 95 % CI 1.185–1.328, P < 0.001) and Asian ethnicity (OR 1.425, 95 % CI 1.352–1.501, P < 0.001). The meta-analysis of the rs1234315 polymorphism revealed no association between SLE and the rs1234315 T allele in all subjects (OR 1.167, 95 % CI 0.874–1.558, P = 0.296), but the results of the subgroup analysis revealed significant association in subjects of Asian ethnicity (OR 1.386, 95 % CI 1.318–1.458, P < 0.001). No association was found between the rs844644 and rs844648 polymorphisms and SLE.

Conclusion The results of our meta-analysis suggest that the TNFSF4 rs2205960 polymorphism may confer susceptibility to SLE in different populations and that the TNFSF4 rs1234315 polymorphism is associated with susceptibility to SLE in Asians.     

Polymorphisms in the transforming growth factor‐β1 gene and the risk of asthma: A meta‐analysis

Background and objective: Polymorphisms in the transforming growth factor‐β1 (TGF‐β1) gene have been implicated in susceptibility to asthma, but a large number of studies have reported inconclusive results. A meta‐analysis was performed to investigate the association between polymorphisms in the TGF‐β1 gene and asthma susceptibility. Methods: Searches were performed of Medline (Ovid), PubMed, the Chinese Biological Medicine Database (CBM), the Chinese Journals Full‐text Database (CNKI), the Cochrane Library Database and the Web of Science, covering all papers published up to 30 April 2009. Statistical analysis was performed using Revman4.2.8 and STATA10.0 software. Results: Two polymorphisms (?509C/T and 915G/C(G25C)) were investigated in 14 studies, involving 2979 asthma patients and 4941 control subjects. The results showed that individuals carrying the ?509T allele (TT+TC) had a 36% increased risk of asthma, when compared with homozygotes (?509CC) (OR 1.36, 95% CI: 1.12–1.65). However, there was no significant association with risk of asthma in carriers of the 915C allele (GC+CC) compared with 915GG homozygotes (OR 1.05, 95% CI: 0.65–1.70). In a subgroup analysis by ethnicity, the risk of asthma associated with the ?509T allele was significantly elevated among Asians (OR 1.50, 95% CI: 1.04–2.17) but not Caucasians (OR 1.16, 95% CI: 1.00–1.36). In a subgroup analysis by age, the ?509T allele was associated with a significantly elevated risk of asthma among adults (OR 1.45, 95% CI: 1.09–1.92) but not children (OR 1.19, 95% CI: 0.96–1.46). Conclusions: This meta‐analysis suggested that the ?509C/T polymorphism in the TGF‐β1 gene may be a risk factor for asthma. To further evaluate gene–gene and gene–environment interactions between polymorphisms in the TGF‐β1 gene and asthma susceptibility, more studies involving thousands of patients are required.     

Role of epoxide hydrolase 1 gene polymorphisms in esophageal cancer in a high‐risk area in India

Background and Aim: Microsomal epoxide hydrolase 1 (EPHX1) is involved in the metabolism of environmental and tobacco carcinogens. Tobacco smoking, betel quid chewing, and alcohol consumption are the major known risk factors for esophageal cancer. The present case‐control study evaluated the influence of EPHX1 genetic variations on esophageal cancer susceptibility in 142 patients and 185 healthy controls from a high‐incidence region of India where tobacco use and alcohol consumption are widespread and the users of these two substances are also betel quid chewers. Methods: EPHX1 polymorphic alleles (exon 3, Tyr113His and exon 4, His139Arg) were genotyped by polymerase chain reaction–restriction fragment length polymorphism method and direct sequencing. The results were analyzed using logistic regression to calculate odds ratios (OR) and confidence intervals (CI). Results: Patients with exon 4 genotypes (139His/Arg, 139Arg/Arg) and the 139Arg allele were significantly associated with a risk of esophageal cancer (OR_His139Arg 1.887, 95% CI = 1.112–3.201, P = 0.019; OR_Arg139Arg 7.140, 95% CI = 1.276–393.953, P = 0.025 and OR_Arg 1.83, 95% CI = 1.19–2.82, P = 0.003). The 139His/Arg genotype was a significant risk factor for esophageal cancer in tobacco chewers and betel quid chewers. Patients with the 139Arg/Arg genotype were at significantly higher risk for developing a well‐differentiated and moderately‐differentiated grade of tumor. In contrast, the 113His/His genotype of exon 3 was a significant protective factor for esophageal cancer in tobacco smokers (OR 0.291, 95% CI = 0.138–0.616, P = 0.001), betel quid chewers (OR 0.434, 95% CI = 0.236–0.797, P = 0.007), and alcohol users. Conclusion: EPHX1 exon 4 139His/Arg, and 139Arg/Arg genotypes were associated with a higher risk of esophageal cancer in a high‐risk area of India.     

A meta-analysis of the association between cytokine gene polymorphisms and systemic sclerosis

Abstract

We conducted a comprehensive meta-analysis to quantitatively evaluate the association of cytokine gene polymorphisms with systemic sclerosis (SSc) susceptibility. Electronic databases were used to identify published studies before July 2011. In total, 23 case–control studies including 3524 SSc cases and 6086 healthy controls were included in the meta-analysis. We examined the relationship between five gene polymorphisms [cytotoxic T lymphocyte associated antigen 4 (CTLA-4) ?1722T/C, CTLA-4 ?318C/T, CTLA-4 +49A/G, angiotensin-converting enzyme I/D, STAT-4 rs7574865] and susceptibility to SSc. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between SSc and STAT rs7574865 (TT vs. GG: OR 0.44, 95% CI 0.36–0.54; TT vs. TG + GG: OR 0.48, 95% CI 0.39–0.59; TT + TG vs. GG: OR 0.74, 95% CI 0.66–0.83; T vs. G: OR 0.72, 95% CI 0.66–0.79), but there were no other statistically significant associations with other gene polymorphisms. Our study suggested that SSc is associated with STAT gene rs7574865 polymorphism.     

Genetic Association Between NFKBIA -881A>G Polymorphism and Cancer Susceptibility

Several epidemiological studies have focused on the role of nuclear factor-kappa-B inhibitor-alpha (NFKBIA) -881 A>G polymorphism in cancer susceptibility. However, the published data have led to contentious results. This study was designed to examine the association between -881 A>G polymorphism and cancer risk.Comprehensive search of PubMed, Web of science and Embase, identified a total of 5 case-control studies. To assess the association, comparison among all subjects plus subgroup analysis by ethnicity was performed and odds ratio (OR) along with 95% confidence interval (CI) was calculated with the fixed-effect model or the random-effects model dependent on the heterogeneity.The pooling data consisting of 1965 cancer cases and 2717 cancer-free controls demonstrated no significant association with overall cancer risk. However, the subgroup of Asian populations showed statistical evidence for an increase in risk of cancer (GG vs. AA, OR, 2.14; 95% CI, 1.03–4.46; GG + GA vs. AA, OR, 1.22; 95% CI, 1.01–1.47; GG vs. GA + AA, OR, 2.09; 95% CI, 1.01–4.34).This investigation on the association of -881 A>G polymorphism and cancer susceptibility reveals that -881 A>G polymorphism may act as a candidate for cancer development in Asian populations.     

Association of MCP-1-2518A/G polymorphism with susceptibility to autoimmune diseases: a meta-analysis

We performed a meta-analysis to estimate whether combined evidence shows the association between the MCP-1-2518A/G polymorphism and susceptibility to autoimmune diseases. Relevant articles dated to July 2014 were acquired from the PubMed, EMBASE, ISI, and CNKI databases. The number of the genotypes and/or alleles for the MCP-1-2518A/G in cases and control subjects was extracted, and statistical analysis was conducted using STATA 11.2 software. Summary odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) were used to calculate the risk of autoimmune diseases with the MCP-1-2518A/G. Significant increased risk of autoimmune diseases could be found for A allele vs. G allele (OR?=?1.616, 95 % CI 1.027–2.542, P?=?0.038) and AA?+?AG vs. GG (OR?=?1.616, 95 % CI 1.027–2.542, P?=?0.038) in Asian patients with rheumatoid arthritis (RA), and for A allele vs. G allele (OR?=?1.383, 95 % CI 1.142–1.676, P?=?0.022) and AA vs. AG?+?GG (OR?=?1.575, 95 % CI 1.361–1.823, P?<?0.001) in European patients with Crohn’s disease (CD). In addition, when comparison of European patients with lupus nephritis (LN) and without LN, significant association between patients with LN and without LN also could be found for AA vs. AG?+?GG (OR?=?0.713, 95 % CI 0.545–0.933, P?=?0.014). This meta-analysis showed that the MCP-1-2518-A allele confers susceptibility to Asian patients with RA and European patients with CD.     

Lack of association between EPHX1 polymorphism and esophageal cancer risk: evidence from meta‐analysis

The microsomal epoxide hydrolase 1 (EPHX1) Tyr113His and His139Arg polymorphisms have been reported to be associated with esophageal cancer (EC) risk, yet the results of these previous results have been inconsistent or controversial. The objective of this study was to explore whether the EPHX1 Tyr113His and His139Arg polymorphisms confer risk to EC. The relevant studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct, and Chinese Biomedical Literature Database until May 2013. The association between the EPHX1 Tyr113His and His139Arg polymorphisms and EC risk was pooled by odds ratios (ORs) together with their 95% confidence intervals (95%CIs). A total of eight case–control studies with 1163 EC patients and 1868 controls (seven studies for both Tyr113His and His139Arg polymorphisms, one study only for Tyr113His polymorphism) were eventually identified. We found no association between EPHX1 Tyr113His and His139Arg polymorphisms and EC risk in overall population (For Tyr113His: His vs. Tyr: OR = 1.05, 95%CI = 0.95–1.15, P = 0.379; His/His vs. Tyr/Tyr: OR = 1.04, 95%CI = 0.88–1.22, P = 0.208; His/Tyr vs. Tyr/Tyr: OR = 0.96, 95%CI = 0.80–1.15, P = 0.577; His/His vs. His/Tyr + Tyr/Tyr: OR = 1.10, 95%CI = 0.96–1.26, P = 0.164; His/His + His/Tyr vs. Tyr/Tyr: OR = 1.01, 95%CI = 0.90–1.12, P = 0.543. For His139Arg: Arg vs. His: OR = 1.04, 95%CI = 0.94–1.14, P = 0.465; Arg/Arg vs. His/His: OR = 1.06, 95%CI = 0.91–1.24, P = 0.470; Arg/His vs. His/His: OR = 1.03, 95%CI = 0.91–1.16, P = 0.673; Arg/Arg vs. Arg/His + His/His: OR = 1.04, 95%CI = 0.85–1.27, P = 0.708; Arg/Arg + Arg/His vs. His/His: OR = 1.02, 95%CI = 0.93–1.13, P = 0.617). In subgroup analysis based on ethnicity, significant association has been found in neither EPHX1 Tyr113His nor His139Arg polymorphism. The current meta‐analysis suggests no evidence of association between the EPHX1 polymorphism and EC risk.     

Cytotoxic T-lymphocyte antigen 4 gene +49A/G polymorphism significantly associated with susceptibility to primary biliary cirrhosis: a meta-analysis

OBJECTIVE: To evaluate comprehensively the association of cytotoxic T‐lymphocyte antigen 4 (CTLA‐4) +49A/G polymorphism with susceptibility to primary biliary cirrhosis (PBC). METHODS: PubMed was used to search for the relevant published articles. The risk of PBC association with the CTLA‐4+49A/G polymorphism was estimated for each study in a random‐effects model. Odds ratio (OR) and 95% confidence interval (CI) were estimated for each study. Risks to PBC were estimated by stratified analysis in patients with different ethnicity and antimitochondrial antibody (AMA) status, as well as histological stages. RESULTS: A total of 12 articles were included in the study. An association between PBC and CTLA‐4 G allele was found, overall OR = 1.20, 95% CI 1.03–1.41 (P = 0.02). However, stratification by ethnicity indicated a significant association between the G allele and PBC in Asians (OR = 1.36, 95% CI 1.12–1.65, P = 0.002), but not in Caucasians (OR = 1.15, 95% CI 0.95–1.39, P = 0.15). Moreover, AMA positive patients carrying G allele were more susceptible to PBC compared with AMA negative patients (OR = 1.23, 95% CI 1.06–1.43, P = 0.007; OR = 0.98, 95% CI 0.71–1.34, P = 0.88, respectively). CONCLUSIONS: Polymorphism in exon 1 of CTLA‐4 gene at position 49 may act as a candidate of susceptibility locus to PBC. However, larger studies with participants of varying ethnicity and stratified by clinical and laboratory characteristics are needed to validate our findings.     

XPD Asp312Asn polymorphism is a risk factor for prostate cancer

Purpose

The association between Asp312Asn and Lys751Gln polymorphisms of Xeroderma pigmentosum Group D (XPD) and prostate cancer risk are still inconclusive. For better understanding of the effects of these two polymorphisms on prostate cancer risk, a meta-analysis was performed.

Methods

An extensive search was performed to identify all case–control studies investigating such association. The strength of association between these two polymorphisms and prostate cancer risk was assessed by odds ratio (OR) with the corresponding 95?% confidence interval (95?% CI).

Results

A total of seven case–control studies were identified, among which five studies (1,257 cases and 1,956 controls) were eligible for Asp312Asn polymorphism and six studies (1,451 cases and 2,375 controls) were eligible for Lys751Gln polymorphism. Asp312Asn polymorphism was associated with an increased risk of prostate cancer in additive and recessive genetic models (additive model: OR?=?1.68, 95?% CI?=?1.28–2.22, P?=?0.00; recessive model: OR?=?1.65, 95?% CI?=?1.27–2.15, P?=?0.00). In the subgroup analysis, Asp312Asn polymorphism was associated with an increased risk of prostate cancer among Asians in all three genetic models (additive model: OR?=?2.09, 95?% CI?=?1.39–3.14, P?=?0.00; dominant model: OR?=?1.49, 95?% CI?=?1.12–1.98, P?=?0.01; recessive model: OR?=?1.93, 95?% CI?=?1.31–2.83, P?=?0.00). However, no significant associations were found between Lys751Gln polymorphism and prostate cancer risk in the overall analyses or the subgroup analyses by ethnicity.

Conclusions

The results of this meta-analysis indicate that the XPD Asp312Asn polymorphism is a risk factor for prostate cancer development.     

Association between thromboxane A2 receptor polymorphisms and asthma risk: A meta-analysis

Objective: To determine whether there is an association between thromboxane A2 receptor (TBXA2R) gene polymorphisms (+924C/T and +795C/T) and asthma risk by conducting a meta-analysis. Data Sources: Pubmed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Wanfang database were searched (updated May 1, 2015). Study Selections: Articles evaluating the association between TBXA2R gene polymorphisms and asthma risk were selected. Results: A total of 7 studies on +924C/T polymorphism and 6 studies on +795C/T polymorphism were included in this meta-analysis. There was a significant association between TBXA2R +924C/T polymorphism and asthma risk in the recessive model (OR = 1.33, 95% CI = 1.01–1.75, P = 0.045). No significant association between +795C/T polymorphism and asthma risk in the overall population was demonstrated. In subgroup analyzes, significant association was observed in atopic asthma risk in the recessive model (OR = 1.43, 95% CI = 1.01–2.01, P = 0.043), but no significant association was found between TBXA2R +924C/T polymorphism and asthma risk in Asians (OR = 1.14, 95% CI = 0.80–1.63, P = 0.457). TBXA2R +795C/T polymorphism was associated with aspirin-intolerant asthma (AIA) risk when stratified by asthma subphenotype in the allelic model (OR = 1.30, 95% CI = 1.05–1.60, P = 0.014) and dominant model (OR = 1.50, 95% CI = 1.11–2.03, P = 0.008). Conclusion: Our results suggested that TBXA2R +924C/T polymorphism is associated with asthma risk, and +795C/T polymorphism may be a risk factor for AIA. Larger-scale and well-designed studies are required to validate the association identified in the current meta-analysis.