Association of genetic polymorphisms in ADH and ALDH2 with risk of coronary artery disease and myocardial infarction: A meta-analysis

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for alcohol metabolism in humans. Emerging evidences have shown that functional polymorphisms in ADH and ALDH genes might play a critical role in increasing coronary artery disease (CAD) and myocardial infarction (MI) risks; however, individually published studies showed inconclusive results. The aim of this meta-analysis is to evaluate the associations between the genetic polymorphisms of ADH and ALDH genes with susceptibility to CAD and MI. A literature search was conducted on PubMed, Embase, Web of Science and Chinese BioMedical databases from inception through December 1st, 2012. Crude relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Twelve case–control studies were included with a total of 9616 subjects, including 2053 CAD patients, 1436 MI patients, and 6127 healthy controls. Meta-analysis showed that mutant genotypes (GA + AA) of the rs671 polymorphism in the ALDH2 gene were associated with increased risk of both CAD and MI (CAD: RR = 1.20, 95%CI: 1.03–1.40, P = 0.021; MI: RR = 1.32, 95%CI: 1.11–1.57, P = 0.002). However, there were no significant associations of ADH genetic polymorphisms to CAD and MI risks (CAD: RR = 0.92, 95%CI: 0.73–1.15, P = 0.445; MI: RR = 0.93, 95%CI: 0.84–1.03, P = 0.148). In conclusion, this meta-analysis provides strong evidence that ALDH2 rs671 polymorphism may be associated with increased risks of CAD and MI. However, further studies are still needed to accurately determine whether ADH genetic polymorphisms are associated with susceptibility to CAD and MI.     

Null genotypes of GSTM1 and GSTT1 contribute to increased risk of diabetes mellitus: A meta-analysis

Diabetes mellitus (DM) is a common disease which results from various causes including genetic and environmental factors. Glutathione S-Transferase M1 (GSTM1) and Glutathione S-Transferase T1 (GSTT1) genes are polymorphic in human and the null genotypes lead to the absence of enzyme function. Many studies assessed the associations between GSTM1/GSTT1 null genotypes and DM risk but reported conflicting results. In order to get a more precise estimate of the associations of GSTM1/GSTT1 null genotypes with DM risk, we performed this meta-analysis. Published literature from PubMed, Embase and China Biology Medicine (CBM) databases was searched for eligible studies. Pooled odds ratios (OR) and corresponding 95% confidence intervals (95%CI) were calculated using a fixed- or random-effects model. 11 publications (a total of 2577 cases and 4572 controls) were finally included into this meta-analysis. Meta-analyses indicated that null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1–GSTT1 were all associated with increased risk of DM (GSTM1: OR _{random-effects} = 1.60, 95%CI 1.10–2.34, P_OR = 0.014; GSTT1: OR _{random-effects} = 1.47, 95%CI 1.12–1.92, P_OR = 0.005; GSTM1–GSTT1: OR _{fixed-effects} = 1.83, 95%CI 1.30–2.59, P_OR = 0.001). Subgroup by ethnicity suggested significant associations between null genotypes of GSTM1 and GSTT1 and DM risk among Asians (GSTM1: OR _{random-effects} = 1.77, 95%CI 1.24–2.53, P_OR = 0.002; GSTT1: OR _{random-effects} = 1.58, 95%CI 1.09–2.27, P_OR = 0.015). This meta-analysis suggests null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1–GSTT1 are all associated with increased risk of DM, and null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1–GSTT1 are potential biomarkers of DM.     

Role of CYP1A2*1F polymorphism in cancer risk: Evidence from a meta-analysis of 46 case–control studies

Background

Emerging evidence showed that the common polymorphism (CYP1A2*1F, rs762551 C → A) in the promoter region of the CYP1A2 gene might be associated with susceptibility to cancer in humans. But individually published results were inconclusive. The aim of this meta-analysis is to investigate the association between CYP1A2*1F polymorphism and cancer risk.

Methods

The Pubmed, Embase, Web of Science and Chinese BioMedical databases were searched for all articles published up to September 1st, 2012. Statistical analyses were performed using the STATA 12.0 software.

Results

Forty-six case–control studies were included with a total of 22,993 cancer cases and 28,420 healthy controls. Meta-analysis results showed that the A allele of CYP1A2*1F polymorphism was associated with a decreased cancer risk (odds ratio [OR] = 0.92, 95% confidence interval [CI]: 0.87–0.98, P = 0.013). In the subgroup analysis by cancer types, the A allele of CYP1A2*1F polymorphism may increase the risk of breast cancer (OR = 1.05, 95% CI: 1.01–1.10, P = 0.024), and is also associated with a decreased risk of ovarian cancer (OR = 0.70, 95% CI: 0.54–0.89, P = 0.004). However, similar results were not found in lung, colorectal, bladder, endometrial, pancreatic and gastric cancers. Further subgroup analysis by ethnicity also showed a significant association between the A allele of CYP1A2*1F polymorphism and a decreased cancer risk among Caucasian populations (OR = 0.91, 95% CI: 0.84–0.98, P = 0.014); but no significant associations were observed among Asian populations.

Conclusions

Results from the current meta-analysis indicate that the A allele of CYP1A2*1F polymorphism may be associated with breast and ovarian cancer risk, especially among Caucasian populations.     

Association between -251A>T polymorphism in the interleukin-8 gene and oral cancer risk: A meta-analysis

Background

Emerging evidence showed that the most common functional polymorphism (-251A>T, rs4073) in the promoter region of the interleukin-8 (IL-8) gene is involved in the regulation of the activities of interleukin-8, thus increasing an individual's susceptibility to oral cancer; but individually published results are inconclusive. The aim of this meta-analysis was to investigate the associations between IL-8 -251A>T polymorphism and oral cancer risk.

Methods

The PubMed, Embase, Web of Science and CBM databases were searched for all articles published up to October 1st, 2012 that addressed IL-8 -251A>T polymorphism and oral cancer risk. Statistical analyses were performed using STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.

Results

Six case–control studies were included with a total of 1324 oral cancer cases and 1879 healthy controls. When all available studies were pooled into the meta-analysis, the results showed that the AA and AT genotypes of IL-8 -251A>T polymorphism were associated with increased risk of oral cancer (OR = 1.23, 95% CI: 1.03–1.46, P = 0.025; OR = 1.25, 95% CI: 1.07–1.47, P = 0.006; respectively). In the subgroup analysis by ethnicity, significant associations were observed between the AA and AT genotypes of IL-8 -251A>T polymorphism and increased risk of oral cancer among Caucasian populations (OR = 1.40, 95% CI: 1.14–1.72, P = 0.001; OR = 1.29, 95% CI: 1.06–1.57, P = 0.011; respectively). However, no statistically significant associations were found between IL-8 -251A>T polymorphism and oral cancer risk among Asian populations.

Conclusions

Results from the current meta-analysis indicate that the AA and AT genotypes of IL-8 -251A>T polymorphism might increase the risk of oral cancer, especially among Caucasian populations.     

Association of p53 Arg72Pro polymorphism with bladder cancer: A meta-analysis

Background

p53 tumor suppressor gene Arg72Pro polymorphism has been associated with bladder cancer. However, results were inconsistent. We performed this meta-analysis to estimate the association between p53 Arg72Pro polymorphism and bladder cancer.

Methods

Electronic search of PubMed was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association.

Results

The final meta-analysis included 14 published studies with 2176 bladder cancer cases and 2798 controls. The results suggested that the variant genotype was associated with the bladder cancer risk (additive model: OR = 1.72, 95% CI: 1.036–1.325, P = 0.011; dominant model: OR = 1.268, 95% CI: 1.003–1.602, P = 0.047) in Asian subgroup. However, the association was not significant between this polymorphism and bladder cancer risk in Caucasian (additive model: OR = 0.773, 95% CI: 0.564–1.059, P = 0.109; dominant model: OR = 0.685, 95% CI: 0.418–1.124, P = 0.134).

Conclusion

This meta-analysis suggests that p53 Arg72Pro polymorphism is associated with increased risk of bladder cancer in Asians. To validate the association between this polymorphism and bladder cancer, further studies with larger participants worldwide are needed.     

Association of XRCC1 Arg399Gln polymorphism with bladder cancer susceptibility: A meta-analysis

Genetic variations in DNA repair genes are thought to modify DNA repair capacity and may to be related to cancer susceptibility. However, epidemiological study results have been inconsistent. In this meta-analysis, we assessed 24 case–control studies of association between the X-ray repair cross complementing group 1 (XRCC1) Arg399Gln polymorphism and bladder cancer susceptibility in the general population and in Asian and non-Asian subgroups. A moderately significant association with bladder cancer risk was found for AG vs GG (OR = 1.110, 95% CI = 1.018–1.210). No significant associations with bladder cancer risk were found for AA vs GG (OR = 0.942, 95% CI = 0.823–1.077), the dominant model AA/AG vs GG (OR = 1.075, 95% CI = 0.990–1.167) and the recessive model AA vs AG/GG(OR = 0.890, 95% CI = 0.788–1.005). In subgroup analysis, a moderately significant association was also found for AG vs GG (OR = 1.091, 95% CI = 1.008–1.180) in non-Asian subgroup. The analysis suggests that the XRCC1 Arg399Gln polymorphism might be a moderate risk factor for bladder cancer, especially in non-Asian population.     

Lack of association between EGF + 61A>G polymorphism and melanoma susceptibility in Caucasians: A HuGE review and meta-analysis

Emerging evidence showed that the common polymorphism (+ 61A>G, rs4444903) in the promoter region of epidermal growth factor (EGF) gene might be associated with melanoma susceptibility in humans. But individually published results are inconclusive. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis is to derive a more precise estimation of the association between EGF + 61A>G polymorphism and melanoma risk. The PubMed, Embase, Web of Science and CBM databases were searched for all articles published up to July 1st, 2012. Seven case–control studies were included with a total of 2367 melanoma cases and 4184 healthy controls. Meta-analysis results showed that there was no significant relationship between EGF + 61A>G polymorphism and the risk of melanoma (G vs A: odds ratio [OR] = 1.08, 95% confidence interval [CI]: 0.91–1.28, P = 0.386; GG + AG vs AA: OR = 1.05, 95%CI: 0.88–1.26, P = 0.580; GG vs AA + AG: OR = 1.10, 95%CI: 0.81–1.49, P = 0.552; GG vs AA: OR = 1.06, 95%CI: 0.80–1.41, P = 0.700; GG vs AG: OR = 1.12, 95%CI: 0.81–1.56, P = 0.494). Further subgroup analyses based on source of controls, country, detection samples, genotype methods, and Breslow thickness of tumor, we also found no significant association between EGF + 61A>G polymorphism and melanoma risk. In conclusion, this meta-analysis indicates that EGF + 61A>G polymorphism might not be a primary determinant in melanoma development and progression; EGF gene might be expected to interact with other genes in different signaling pathways to initiate and promote the carcinogenic process.     

The associations between the Val158Met in the catechol-O-methyltransferase (COMT) gene and the risk of uterine leiomyoma (ULM)

The Val158Met polymorphism of the COMT gene has been implicated in susceptibility to uterine leiomyoma (ULM), but the reported results were inconclusive. The aim of the study was to evaluate the Val158Met polymorphism of the COMT gene and the risk of ULM by meta-analysis. A comprehensive electronic search for relevant articles was conducted in Pubmed, Embase, CNKI, Wanfang, and Weipu databases. Statistical analysis was performed by using the Revman4.2 software and Stata10.0 software. A total of 7 articles including 12 case–control studies were identified in this meta-analysis. The results showed that the polymorphism was associated with decreased risk of ULM (Met/Met + Val/Met vs. Met/Met: OR = 0.84, 95% CI = 0.70–0.99, Z = 2.07, p = 0.04). In the subgroup analyses by ethnicity, significant decreased risk was found among the black populations (OR = 0.68, 95% CI = 0.48–0.97, Z = 2.15, p = 0.03). The current meta-analysis suggested that the Val158Met polymorphism in the COMT gene was associated with decreased risk of ULM, especially in the black population. Future studies are needed to validate our conclusions.     

Meta-analysis supports association of a functional SNP (rs1801133) in the MTHFR gene with Parkinson's disease

The MTHFR is a candidate risk gene for Parkinson's disease (PD), and a functional SNP (rs1801133) in the coding region of this gene has been investigated for the associations with the illness extensively among worldwide populations, but overall the results were inconsistent. Here, to assess the relationship between rs1801133 and risk of PD in general populations, we conducted a systematic meta-analysis by combining all available case–control samples in European and Asian populations, with a total of 1820 PD cases and 7530 healthy controls, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for rs1801133 and PD were calculated using the Mantel–Haenszel method with a fixed-effect model. Overall, rs1801133 was significantly associated with the risk of PD (allelic model, pooled OR = 1.212 for T allele, 95% CI = 1.097–1.340, p-value = 0.0002). When stratifying for ethnicity, significant association was also observed in European (allelic model, pooled OR = 1.187 for T allele, 95% CI = 1.058–1.332, p-value = 0.004) and Asian samples (allelic model, pooled OR = 1.293 for T allele, 95% CI = 1.058–1.580, p-value = 0.012) respectively. In addition, rs1801133 was also significantly associated with MTHFR mRNA expression in both CEU (European, p-value = 0.0149) and CHB (Chinese, p-value = 0.0178) HapMap populations. Collectively, our meta-analysis suggests that rs1801133 is significantly associated with susceptibility to PD in European and Asian populations, and MTHFR is likely an authentic risk gene for PD.     

The interleukin-4 − 589C/T polymorphism and the risk of asthma: A meta-analysis including 7345 cases and 7819 controls

Background

A number of studies assessed the association of − 589C/T polymorphism in the promoter region of interleukin-4 (IL-4) with asthma in different populations. However, the results were contradictory. A meta-analysis was conducted to investigate the association between polymorphism in the IL-4 and asthma susceptibility.

Methods

Databases including Pubmed, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.

Results

Thirty-four studies involving 7345 cases and 7819 controls were included. Overall, significant association between − 589C/T polymorphism and asthma was observed for TT + CT vs. CC (OR = 1.26; 95% CI 1.12–1.42; P = 0.0001; I² = 26%). In the subgroup analysis by ethnicity, significant associations were found among Asians (OR = 1.36; 95% CI 1.07–1.73; P = 0.01; I² = 0%) and Caucasians (OR = 1.30; 95% CI 1.09–1.54; P = 0.004; I² = 53%) but not among African Americans (OR = 1.20; 95% CI 0.72–2.00; P = 0.48; I² = 48%). In the subgroup analysis by atopic status, no significant association was found among atopic asthma patients (OR = 1.20; 95% CI 0.92–1.34; P = 0.27; I² = 6%) and non-atopic asthma patients (OR = 0.97; 95% CI 0.73–1.28; P = 0.81; I² = 0%).

Conclusions

This meta-analysis suggested that the IL-4 − 589C/T polymorphism was a risk factor of asthma.     

Poly (AT) deletion/insertion polymorphism of the XPC gene contributes to urinary system cancer susceptibility: A meta-analysis

Numerous studies have investigated the association between xeroderma pigmentosum complementation group C (XPC) poly (AT) deletion/insertion (PAT −/+) polymorphism and cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis based on 32 publications including 10,214 cases and 11,302 controls to acquire a more robust estimation of the relationship. We searched publications from MEDLINE, EMBASE and CBM which assessed the associations between XPC PAT −/+ polymorphism and cancer risk. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model. We found that individuals carrying the PAT +/+ genotype have significantly increased cancer risk (PAT +/+ vs. PAT −/−: OR = 1.18, 95% CI = 1.03–1.35 and recessive model: OR = 1.19, 95% CI = 1.06–1.33). Further stratification analysis showed a significantly increased risk for prostate cancer (PAT +/+ vs. PAT −/−: OR = 2.20, 95% CI = 1.39–3.48, recessive model: OR = 2.07, 95% CI = 1.33–3.23 and PAT + vs. PAT −: OR = 1.39, 95% CI = 1.12–1.71), bladder cancer (recessive model: OR = 1.33, 95% CI = 1.03–1.72), Caucasian ethnicity (recessive model: OR = 1.21, 95% CI = 1.02–1.43), population-based studies (recessive model: OR = 1.23, 95% CI = 1.05–1.43) and studies with relatively large sample size (PAT +/+ vs. PAT −/−: OR = 1.18, 95% CI = 1.04–1.35 and recessive model: OR = 1.20, 95% CI = 1.08–1.33). Despite some limitations, this meta-analysis established solid statistical evidence for the association between the XPC PAT +/+ genotype and cancer risk, especially for urinary system cancer, but this association warrants further validation in single large studies.     

Role of RASSF1A promoter methylation in the pathogenesis of hepatocellular carcinoma: a meta-analysis of 21 cohort studies

We carried out the current meta-analysis aiming to comprehensively assess the potential role of RASSF1A aberrant promoter methylation in the pathogenesis of hepatocellular carcinoma (HCC). A range of electronic databases were searched: Web of Science (1945–2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966–2013), EMBASE (1980–2013), CINAHL (1982–2013) and the Chinese Biomedical Database (CBM) (1982–2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude risk difference (RD) with their 95 % confidence interval (95 % CI) was calculated. In the present meta-analysis, 21 clinical cohort studies with a total of 1,205 HCC patients were included. The results of our meta-analysis illustrated that the frequency of RASSF1A promoter methylation in cancer tissues were significantly higher than those of normal, adjacent and benign tissues (cancer tissues vs. normal tissues: RD = 0.63, 95 % CI 0.53–0.73, P < 0.001; cancer tissues vs. adjacent tissues: RD = 0.43, 95 % CI 0.33–0.53, P < 0.001; cancer tissues vs. benign tissues: RD = 0.48, 95 % CI 038–0.58, P < 0.001; respectively). Further subgroup by ethnicity demonstrated that RASSF1A aberrant promoter methylation was correlated with the pathogenesis of HCC among both Asians and Caucasians (all P < 0.05). The current meta-analysis suggests that RASSF1A aberrant promoter methylation may be implicated in the pathogenesis of HCC. Thus, detection of RASSF1A promoter methylation may be a helpful and valuable biomarker for diagnosis and prognosis of HCC.     

Current evidence on the relationship between five polymorphisms in the matrix metalloproteinases (MMP) gene and lung cancer risk: A meta-analysis

Purpose

Matrix metalloproteinase (MMP) 1, MMP2, MMP3 and MMP9 are important members of the MMP family. Recently, many studies have been carried out on the association between polymorphisms of MMP1-1607 1G/2G, MMP2-735 C/T, MMP2-1306 C/T, MMP3-1171 5A/6A and MMP9-1562 C/T and lung cancer risk. However the results of these studies remained inconclusive due to conflicting results from different case–control studies. To clarify these associations, we conducted a meta-analysis.

Methods

We conducted a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database (date from Jan 2000 to Aug 2012). Overall and subgroup analysis by the ethnicity of study population was carried out. Odds ratio (OR) with 95% confidence interval (95%CI) was used to assess the strength of the association.

Results

There were 17 studies involving five polymorphic sites in four MMP genes. For MMP1-1607,increased lung cancer risk was found under dominant model (MMP1-1607 1G/2G: OR = 1.14, 95%CI = 1.03–1.26, P = 0.01), but not in the Caucasian population. For MMP2-1306 C/T, T polymorphism decreased lung cancer risk under dominant and recessive models (dominant, OR = 0.63, 95%CI = 0.46–0.88, P = 0.0006; recessive, OR = 0.61, 95%CI = 0.38–0.99, P = 0.04). For MMP9-1562 C/T, TT genotype decreased this risk under the recessive model (OR = 0.38, 95%CI = 0.19–0.75, P = 0.005), but not in the Asian population. For MMP2-735 C/T and MMP3-1171 5A/6A, there was no association between this polymorphism and lung cancer risk under the dominant and recessive models.

Conclusions

MMP1-1607 1G/2G polymorphism increased lung cancer risk in Asians. It was also found thatMMP2-1306 C/T polymorphism decreased lung cancer risk in Asians, while MMP9-1562 C/T polymorphism decreased lung cancer risk in Caucasians. No significant difference was found in any genotype of MMP2-735 C/T and MMP3-1171 5A/6A. Further studies with larger sample sizes should be carried out.     

The effect of XPD/ERCC2 Lys751Gln polymorphism on acute leukemia risk: A systematic review and meta-analysis

Aims

Epidemiological studies have assessed the association between xeroderma pigmentosum group D (XPD) Lys751Gln and acute leukemia risk with conflicting results. We performed this meta-analysis to derive a more precise estimation of the relationship. Pooled odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the strength of the association.

Results

Ten published case–control studies including a total of 1494 cases and 2259 controls were identified. Overall, significant risk effects of Lys751Gln genotype was found under the dominant model (OR = 1.16; 95% CI = 1.01–1.34; P = 0.032). When stratified by clinical types, the variant genotype was associated with the acute myeloid leukemia (AML) risk under the heterozygote comparison (OR = 1.20; 95% CI = 1.00–1.43; P = 0.048), the homozygote comparison (OR = 1.35; 95% CI = 1.05–1.74; P = 0.019) and the dominant model (OR = 1.23; 95% CI = 1.04–1.45; P = 0.015), respectively. Furthermore, significantly increased risks were also pronounced in Caucasian AML patients (the homozygote comparison: OR = 1.38; 95% CI = 1.07–1.78; P = 0.013; the dominant model: OR = 1.23; 95% CI = 1.03–1.46; P = 0.020; and the recessive model: OR = 1.26; 95% CI = 1.00–1.60; P = 0.050). No evident heterogeneities were observed for the overall data under all genetic models. In addition, no statistical evidence for publication bias was found using the method of Begg's and Egger's tests.

Conclusion

This meta-analysis suggested that XPD Lys751Gln polymorphism might be a risk factor for AML and Caucasian acute leukemia patients.     

Promoter polymorphisms in DNA repair gene ERCC5 and susceptibility to gastric cancer in Chinese

Genetic variations in excision repair cross-complementing group 5 (ERCC5) might influence individual vulnerability to gastric cancer (GC). We investigated effects of two putatively functional polymorphisms in ERCC5 promoter region, rs751402 (+ 25A > G) and rs2296147 (+ 202C > T), and their potential interaction with environment factors on the risk of developing GC. We performed a sex- and age-matched case–control design with 400 GC cases and 400 healthy controls for rs751402 and 403 GC cases and 403 healthy controls for rs2296147. Our results showed that rs751402 were associated with increased GC risk (AA vs. GG: OR = 1.99, 95%CI: 1.20–3.31, P = 0.008; AG + AA vs. GG: OR = 1.41, 95%CI: 1.07–1.86, P = 0.016), and rs2296147 was also associated with increased cancer risk (CC vs. TT: OR = 2.17, 95%CI: 1.04–4.54, P = 0.039; CC vs. CT + TT: OR = 2.26, 95%CI: 1.09–4.69, P = 0.028). In a stratified analysis, rs751402 (AG + AA vs. GG: OR = 1.44, 95%CI: 1.02–2.02, P = 0.037) and rs2296147 (CC vs. CT + TT: OR = 2.33, 95%CI: 1.00–5.44, P = 0.050) were also found to be associated with diffuse-type GC risk. The most common GT haplotype (rs751402–rs2296147) showed protective effect for GC development (OR = 0.73, 95%CI: 0.58–0.91, P = 0.005), and especially for diffuse-type GC (OR = 0.68, 95%CI: 0.52–0.90, P = 0.006). Genetic effects on increased GC risk seemed to be enhanced by Helicobacter pylori infection, smoking and alcohol drinking, with corresponding adjusted ORs of 4.57, 2.42 and 2.50 for the rs751402 AG/AA variants, and of 5.32, 3.20 and 6.87 for the rs2296147 CC variant, but their interaction effects on GC risk didn't reach statistically significance. ERCC5 rs751402 and rs2296147 polymorphisms might alter the risk of developing GC and especially the diffuse subtype. Further validation of our results in larger populations and additional studies evaluating their function impact are required.     

Association of interleukin-13 SNP rs20541 with allergic rhinitis risk: A meta-analysis

Studies investigating the association between interleukin-13 (IL-13) single nucleotide polymorphism (SNP) rs20541 and allergic rhinitis (AR) risk have reported conflicting results. The aim of the present study was to conduct a meta-analysis assessing the possible association of IL-13 SNP rs20541 with AR risk. Eight studies were included in the present meta-analysis (2153 cases and 3931 controls). The combined results based on all studies showed that IL-13 SNP rs20541 was associated with increased AR risk (Gln versus Arg: odds ratio (OR) = 1.18, 95% confidence interval (CI) = 1.08–1.30; Gln/Gln versus Arg/Arg: OR = 1.52, 95% CI = 1.20–1.92; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.19, 95% CI = 1.06–1.33; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.42, 95% CI = 1.13–1.79). When stratifying for race, IL-13 SNP rs20541 exhibited increased AR risk in Asians (Gln versus Arg: OR = 1.20, 95% CI = 1.06–1.36; Gln/Gln versus Arg/Arg: OR = 1.57, 95% CI = 1.17–2.12; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.22, 95% CI = 1.04–1.44; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.45, 95% CI = 1.09–1.93), while no significant association was detected in Caucasians (Gln versus Arg: OR = 1.28, 95% CI = 0.93 ~ 1.78; Gln/Gln versus Arg/Arg: OR = 1.42, 95% CI = 0.96–2.11; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.35, 95% CI = 0.89–2.05; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.37, 95% CI = 0.93–2.02). This meta-analysis supported that IL-13 SNP rs20541 was associated with AR, particularly in Asians.     

Relationship between CCR2-V64I polymorphism and cancer risk: A meta-analysis

Background and objectives

The role of CCR2-V64I polymorphism in various cancers has been reported in many studies. However, results from published studies on the association between CCR2-V64I polymorphism and cancer risk are conflicting. Therefore, we performed a meta-analysis to estimate the overall cancer risk associated with the polymorphism.

Methods

Electronic searches of PubMed and EMBASE were conducted for all publications on the association between this variant and cancer. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association.

Results

Sixteen studies with 2661 cancer patients and 5801 healthy controls were included. Overall, significant association was found between the CCR2-V64I polymorphism and cancer risk (OR = 1.84, 95% CI = 1.35–2.51, AA vs GA/GG, P = 0.37). In the subgroup analysis stratified by cancer types, there was a significant association between this polymorphism and bladder cancer (OR = 2.06, 95% CI = 1.02–4.15, AA vs GA/GG, P = 0.11), cervical cancer (OR = 3.34, 95% CI = 1.48–7.50, AA vs GG, P = 0.56), and oral cancer (OR = 2.04, 95% CI = 1.46–2.84, GA vs GG, P = 0.70). In the subgroup analysis stratified by ethnicities, an increased cancer risk was also found in Europeans (OR = 2.31, 95% CI = 1.45–3.68, AA vs GA/GG, P = 0.16) and Asians (OR = 1.88, 95% CI = 1.12–3.16, AA vs GA/GG, P = 0.92).

Conclusion

This meta-analysis suggested that CCR2-V64I polymorphism may contribute to an increased risk of cancer.     

Genetic association of interleukin-10 promoter polymorphisms and susceptibility to diffuse large B-cell lymphoma: A meta-analysis

Published data on the association between interleukin-10 (IL-10) gene polymorphisms and diffuse large B-cell lymphoma (DLBCL) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed, focusing on four major IL-10 gene variants in the promoter region: –3575T/A, –1082A/G, –819C/T and –592C/A. We applied the false discovery rate (FDR) method to adjust for multiple testing. A significant association between IL-10 –3575T/A polymorphism and the risk of DLBCL was observed in the pooled 10 case–control studies (A vs. T: OR = 1.16, 95% CI = 1.08–1.25, P < 0.0001; AA + TA vs. TT: OR = 1.20, 95% CI = 1.08–1.33, P = 0.0009; AA vs. TA + TT: OR = 1.25, 95% CI = 1.09–1.44, P = 0.001). The results indicated that carriers of –1082G allele (–1082GG/GA genotypes) had a nearly 30% increased risk of DLBCL, as compared with carriers of –1082AA genotype (GG + GA vs. AA: OR = 1.30, 95% CI = 1.08–1.57, P = 0.005). When P-values were not adjusted for multiple testing, the risk was significantly decreased among people with –592AA genotype (AA vs. AC + CC: OR = 0.63, 95% CI = 0.43–0.94, P = 0.02), while carriers with –819TT genotype also modestly weakened the DLBCL susceptibility at a marginal level of significance (TT vs. CT + CC: OR = 0.59, 95% CI = 0.35–0.99, P = 0.05). However, these associations were not significant after correction for multiple testing. This meta-analysis suggests that IL-10 –3575A allele confers a greater risk to DLBCL susceptibility, while –1082A/G polymorphism also has significant association with DLBCL risk. These results may help to further clarify the malignancy-risk gene signature of DLBCL, and thus have prognostic and predictive value especially for early-stage DLBCL.     

Association of MTHFR and PPARγ2 gene polymorphisms in relation to type 2 diabetes mellitus cases among north Indian population

Background

Type 2 diabetes mellitus is a multifactorial and polygenic disease, which is considered as a major life threatening problem all over the world. There has been a worldwide effort in the identification of susceptibility genes for type 2 diabetes mellitus and its complications. At present, adequate data is not available dealing with MTHFR (rs1801133) and PPARγ2 (rs1801282) gene polymorphisms and its association with type 2 diabetes mellitus cases among north Indian populations. Thus, we conceived the need for further studies to investigate MTHFR and PPARγ2 gene polymorphisms and their susceptibility to type 2 diabetes mellitus in north Indian population.

Materials and methods

In this study, a total 175 subjects including 87 type 2 diabetes mellitus cases and 88 controls were enrolled. MTHFR and PPARγ2 gene polymorphisms in the cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP).

Results

The MTHFR gene CC, CT, TT genotype frequencies obtained were 40%, 43%, and 17% in type 2 diabetes mellitus cases and 56%, 29%, and 15% in healthy controls respectively. The OR for CC was 0.54 (95%CI 0.29–0.98, P = 0.041, χ2 = 4.18, power = 0.98), for CT 1.76 (95%CI 0.94–3.30, P = 0.07, χ2 = 3.2, power = 0.96), and for TT 1.2 (95%CI 0.53–2.70, P = 0.66, χ2 = 0.198, power = 0.76). The PPARγ2 gene GG CG, CC genotype frequencies obtained were 28%, 41%, and 31% in cases and 40%, 39%, and 21% in healthy controls respectively. OR for GG was 0.58 (95%CI 0.30–1.09, P = 0.08, χ2 = 2.9, power = 0.96), for CG 1.12 (95%CI 0.61–2.05, P = 0.71, χ2 = 0.137, power = 0.778), and for CC 1.63 (95%CI 0.82–3.23, P = 0.156, χ2 = 2.01, power = 0.92).

Conclusion

It might be recommended that MTHFR CC genotype seems to be a good marker for the early identification of population at risk of type 2 diabetes mellitus. While we have detected significant difference in allelic frequencies of PPARγ2 C (Proline) and G (Alanine), but at genotypic level significant difference was not detected in this case–control study. Further study with larger groups may be required to validate the study.