ABSTRACT
The interleukin (IL)-1ß-511 C/T polymorphism has been shown to be functional and to contribute to the risk of gastric cancer. However, the relationship between the IL-1ß-511 C/T polymorphism and gastric carcinogenesis remains inconclusive. A systematical electronic search was conducted of the MEDLINE, EMBASE, and CENTRAL databases. A random and a fixed effects model were exploited to estimate summary odds ratios and 95 % confidence intervals. Subgroup and sensitivity analyses were carried out with respect to ethnicity, quality assessment scores, control sources, genotyping methods, cancer histopathology and location, and Helicobacter pylori (H. pylori) infection. A total of 45 studies containing 9,066 cases of gastric cancer and 11,192 control subjects satisfied the inclusion criteria. The IL-1ß-511 C/T polymorphism was found to enhance the risk of stomach cancer for overall and HWE-satisfying studies. Asians showed a positive relationship in both the overall and HWE-satisfying groups, whereas Caucasians did not. Based on subgroup analysis, H. pylori infection and genotype analysis using PCR-RFLP methods increase the association between IL-1ß-511 T allele carrier and risk of stomach cancer. A positive relationship was found between the IL-1ß-511 C/T SNP and stomach carcinoma susceptibility, and the results suggest that Asian ethnicity, H. pylori infection and methodologically, PCR-RFLP genotyping strengthen this relationship. Reflecting on prevalence of H. pylori in Asian countries, additional studies on the IL-1ß-511 C/T SNP in the context of ethnicity and H. pylori infection may provide key insights into the mechanism underlying gastric cancer carcinogenesis. It was found PCR-RFLP is the most reliable genotyping method, and thus, it is recommendable to adopt it to determine the presence of the IL-1ß-511 C/T SNP.
Subject(s)
Genetic Predisposition to Disease , Helicobacter Infections/complications , Interleukin-1beta/genetics , Polymorphism, Single Nucleotide/genetics , Racial Groups/genetics , Stomach Neoplasms/genetics , Stomach Neoplasms/microbiology , Helicobacter pylori/physiology , Humans , Linkage Disequilibrium/genetics , Publication Bias , Risk Factors , Stomach Neoplasms/ethnologyABSTRACT
OBJECTIVE: Tumor necrosis factor-alpha (TNF-α) has been found to be associated with gastric carcinogenesis, but individually published results have been inconclusive. The aim of this study was to explore the relationship between the TNF-α-308 G/A polymorphism and gastric cancer risk. METHODS: MEDLINE, EMBASE and the COCHRANE library databases were searched for relevant articles to identify all available data. The odds ratios (ORs) with 95% confidence intervals (95% CIs) from each study were used to assess the association between the TNF-α-308 G/A polymorphism and gastric cancer risk. RESULTS: This meta-analysis included 30 studies (32 datasets) involving 7009 gastric cancer cases and 12,119 control subjects. Overall, a significant association was found between the TNF-α-308 G/A polymorphism and gastric cancer in AA+GA vs. GG (dominant contrast model) (OR=1.20, 95% CI=1.07-1.34, p=0.001). With stratification based on ethnicity, the TNF-α-308 G/A polymorphism was correlated with gastric cancer risk in Caucasians, using the dominant contrast model (OR=0.74, 95% CI=0.57-0.96, p=0.02), but not in East Asians and other ethnic groups. In the comprehensive subgroup analysis, a significant association was also found in recent articles (published after 2005), population-based high-quality studies, hospital-based high-quality studies, studies using the TaqMan method and non-cardia subgroups. However, the TNF-α-308 G/A polymorphism was not associated with specific histological types of gastric cancer risk. CONCLUSIONS: The TNF-α-308 G/A polymorphism may contribute to susceptibility to gastric cancer in Caucasians, especially for non-cardia gastric cancer, as most strongly demonstrated in high-quality studies and in studies using the TaqMan genotyping method. Furthermore, we recommend the TaqMan method as the preferred genotyping method in DNA polymorphism studies.
Subject(s)
Genetic Association Studies , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide/genetics , Stomach Neoplasms/genetics , Tumor Necrosis Factor-alpha/genetics , Ethnicity/genetics , Genetic Heterogeneity , Humans , Publication Bias , Risk FactorsABSTRACT
We performed a systematic review and meta-analysis of the association between the glutathione S-transferase T1 (GSTT1) deletion polymorphism and gastric cancer risk in populations from different ethnic backgrounds, based on a comprehensive literature search of the MEDLINE, EMBASE, and COCHRANE libraries. Thirty-six individual case-control studies comprising 7,689 gastric cancer cases and 12,445 controls were included in our meta-analysis. Overall, the GSTT1 null genotype appeared to increase gastric cancer risk (OR 1.17, 95% CI 1.06-1.31, p = 0.003). While Caucasian populations showed an association between the GSTT1 deletion polymorphism and gastric cancer risk (OR 1.27, 95% CI 1.05-1.52, p = 0.01), Asian populations did not show such an association (p = 0.11). When stratified by quality assessment scores, a significant association between the GSTT1 deletion polymorphism and gastric cancer risk was observed only in the Caucasian high quality subgroup (OR 1.27 95% CI 1.01-1.60, p = 0.05). Null genotypes for both GSTT1 and GSTM1 deletion polymorphisms also increased gastric cancer risk (OR 1.37, 95% CI 1.04-1.80, p = 0.03). Our study suggests that the GSTT1 null genotype is associated with a significant increase in gastric cancer risk in Caucasians, but not in Asians. Further well-designed studies are required to confirm the association between GSTT1 polymorphisms and gastric cancer risk in relation to various clinicopathological factors in different ethnic groups, especially Caucasians.