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ABSTRACT: CYP2C9 enzyme activity is involved in the metabolism of substances related to colorectal cancer (CRC), and it is functionally linked to a genetic polymorphism. Two allelic variants of the CYP2C9 gene, namely CYP2C9*2 and CYP2C9*3, differ from wild-type CYP2C9*1 by single amino acid substitutions. These mutated alleles encode enzymes with altered properties that are associated with impaired metabolism. In the past decade, a number of case-control studies have been carried out to investigate the relationship between the CYP2C9 polymorphism and CRC susceptibility, but the results were conflicting. To investigate this inconsistency, we performed a meta-analysis of 13 studies involving a total of 20,879 subjects for CYP2C9*2 and *3 polymorphisms to evaluate the effect of CYP2C9 on genetic susceptibility for CRC. Overall, the summary odds ratio of CRC was 0.94 (95%CI: 0.87-1.03, P = 0.18) and 1.00 (95%CI: 0.86-1.16, P = 0.99) for CYP2C9 *2 and *3 carriers, respectively. No significant results were observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. In the stratified analyses according to ethnicity, sample size, diagnostic criterion, HWE status and sex, no evidence of any gene-disease association was obtained. Our result suggest that the *2, *3 polymorphisms of CYP2C9 gene are not associated with CRC susceptibility.
PLoS ONE 01/2013; 8(4):e60607. · 4.09 Impact Factor
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ABSTRACT: Polymorphisms in genes involved in the metabolism of folate and methyl groups have been implicated with risk of digestive system cancer. Methionine synthase (MTR) plays a central role in folate metabolism, thereby affecting DNA methylation. The association between A2756G polymorphism (rs1805087) in MTR and digestive system cancer susceptibility was inconsistent in previous studies. To investigate this inconsistency, we performed this meta-analysis.
Databases including Pubmed, EMBASE, ISI Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Potential sources of heterogeneity were also assessed by subgroup analysis and meta-regression.
A total of 29 articles with 15,368 patients and 23,959 controls were included. We found no association between MTR A2756G polymorphism and digestive system cancer in overall population (G allele: OR = 1.03, 95% CI = 0.98-1.09, P = 0.25; dominant model: OR = 1.03, 95% CI = 0.97-1.10, P = 0.33; recessive model: OR = 1.02, 95% CI = 0.89-1.17, P = 0.79). In the stratified analyses according to cancer type, sample size and genotyping method, no evidence of any gene-disease association was obtained in almost all genetic models. However, marginal significant associations were found for East Asians and hospital-based studies.
This meta-analysis suggests that there is no significant association between the MTR A2756G polymorphism and digestive system cancer risk.
PLoS ONE 01/2013; 8(4):e61511. · 4.09 Impact Factor
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ABSTRACT: Paraoxonase 1 (PON1) is reported to have antioxidant and cardioprotective properties. The relationship between PON1 activity and coronary heart disease (CHD) risk in humans has been reported among various ethnic populations in the past decade. However, these studies have yielded contradictory results. To investigate this inconsistency, we conducted a meta-analysis of 43 studies involving a total of 20,629 subjects to evaluate the effect of PON1 activity on susceptibility for CHD. We also systematically explored potential sources of heterogeneity using subgroup analysis and meta-regression. Significant decreases paraoxonase activity of PON1 were observed in CHD patients compared with non-CHD controls with SMD of -0.78 (95% CI: -0.98, -0.57; P<0.001). Similar results were also found for arylesterase activity of PON1 with SMD of -0.50 (95% CI: -0.64, -0.36; P<0.001). In the subgroup analysis by ethnicity, CHD phenotype, sample size, source of controls, mean age and BMI of cases, significantly increased risks were also found. In addition, our analyses detected a possibility of publication bias with an overestimate of the true association by smaller studies. This meta-analysis demonstrated that decreasing in PON1 activity is a risk factor associated with increased CHD susceptibility. However, additional very large-scale studies are warranted to provide conclusive evidence on the effects of PON1 activity on risk of CHD.
Molecular Genetics and Metabolism 01/2012; 105(1):141-8. · 3.19 Impact Factor
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ABSTRACT: Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is involved in the stimulation of insulin action. Polymorphisms in the IGF2BP2 gene have been analyzed in numerous studies to assess the type 2 diabetes (T2D) risk attributed to these variants, but results are conflicting. To better understand the effect of rs4402960 polymorphism on T2D risk, we performed a comprehensive meta-analysis that included 35 published studies involving 70,261 cases and 100,567 controls. The relatively infrequent T variant was significantly associated with T2D with a per-allele odds ratio (OR) of 1.14 (95% confidence interval (CI): 1.12-1.16; p<10(-5)). Significant results were also observed for heterozygous (OR=1.17, 95% CI: 1.14-1.20; p<10(-5)) and homozygous (OR=1.23, 95% CI: 1.16-1.30; p<10(-5)) compared with wild type. In the subgroup analysis by ethnicity, significantly increased risks were found in East Asian, Caucasian and Indian populations. However, no significant associations were detected among other ethnicities. In the stratified analysis according to sample size, diagnostic criterion, mean body mass index, and age of cases significantly increased risks for the polymorphism were found in all genetic models. In conclusion, this meta-analysis suggests that rs4402960 polymorphism in IGF2BP2 is associated with elevated T2D risk, but these associations vary in different ethnic populations.
DNA and cell biology 10/2011; 31(5):713-20. · 2.28 Impact Factor
