title: Population differences concerning TNF-α gene polymorphisms in gastric carcinogenesis based on meta-analysis.
abstract: BACKGROUND
  Recent meta-analyses have studied population differences concerninginterleukin(IL)-1gene polymorphisms in gastric carcinogenesis. In addition to theIL-1gene cluster, candidate genes include those encoding the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. The aim of the study was to systematically review the role ofTNF-α-238andTNF-α-308gene polymorphisms (genotypes G/G, G/A, A/A) in gastric carcinogenesis by meta-analyzing all relevant studies to look for any differences concerning TNF-α gene polymorphisms in gastric carcinogenesis.
  
  
  METHODS
  Extensive English language medical literature searches for human studies were performed up to the end of May 2013, using suitable keywords. Pooled estimates [odds ratio (OR) with 95% confidence intervals (CI)] were obtained using the random-effects model. Heterogeneity between studies was evaluated with the Cochran Q test whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the adjusted rank correlation test.
  
  
  RESULTS
  In seventeen studies, from various countries, theTNF-α-308andTNF-α-238frequencies of genotypes G/G, G/A, A/A were examined in gastric cancer patients and controls. ForTNF-α-308frequency overall, the pooled ORs with 95%CI for genotype G/G, A/A and G/A were 0.837 (0.712-0.982), 1.430 (1.064-1.923) and 1.145 (0.973-1.348) with respective P values 0.029, 0.018 and 0.104. Subgroup analyses showed significant results for genotype G/G only in Asians [OR=0.774 (0.610-0.983), P=0.036].
  
  
  CONCLUSIONS
  In this meta-analysis there was an overall statistically significant increased cancer risk associated withTNF-α-308G/G and A/A genotypes. Subgroup analyses showed significant results for genotype G/G in Asians, whereas no such significant results were found for Caucasians and Hispanics.
authors.affiliation: Gastroenterology Clinic, Henry Dunant Hospital, Athens, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Rokkas
authors.affiliation: Gastroenterology Clinic, Henry Dunant Hospital, Athens, Greece.
authors.forename: Panos
authors.initials: P
authors.lastname: Sechopoulos
authors.affiliation: Gastroenterology Clinic, Henry Dunant Hospital, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pistiolas
authors.affiliation: Gastroenterology Clinic, Henry Dunant Hospital, Athens, Greece.
authors.forename: Fotis
authors.initials: F
authors.lastname: Kothonas
authors.affiliation: Gastroenterology Clinic, Henry Dunant Hospital, Athens, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Margantinis
authors.affiliation: Gastroenterology Clinic, Henry Dunant Hospital, Athens, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Koukoulis
keywords: TNF-α-238 gene; TNF-α-308 gene; gastric cancer; meta-analysis; polymorphism
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