title: Association between cytokine gene polymorphisms and gastric precancerous lesions: systematic review and meta-analysis.
abstract: Polymorphisms within interleukin-1 (IL1) and tumor necrosis factor alpha (TNFA) gene clusters are associated with an increased risk of gastric cancer. However, their role in gastric precancerous lesions remains poorly understood. Our objective was to perform a meta-analysis of studies addressing the association between IL1B-511, IL1RN variable number of tandem repeat, and TNFA-308 gene polymorphisms and gastric precancerous lesions, including original data from Portugal and Mozambique. Published studies on the association between these cytokine gene polymorphisms and gastric precancerous lesions were identified by systematic review, and estimates of the association were combined using random-effects meta-analysis taking into account new data obtained from Portuguese volunteer shipyard workers (n = 215) and Mozambican dyspeptic patients (n = 96) who underwent endoscopic and pathologic evaluation following the same protocol. Odds ratio (OR) estimates for intestinal metaplasia were 2.83 [95% confidence interval (95% CI), 1.15-6.96] for the IL1RN*22 genotype, 1.86 (95% CI, 1.03-3.36) for IL1B-511 T carriers, and 0.59 (95% CI, 0.12-3.04) for the TNFA-308*AA genotype in the Portuguese sample. All Mozambican subjects with intestinal metaplasia were T carriers for IL1B-511 and none had the 2 allele for IL1RN. In meta-analysis, IL1RN*22 genotype was associated with an increased risk of gastric precancerous lesions (22 versus LL: OR, 2.27; 95% CI, 1.40-3.70; I(2) = 26.4%; 12 studies). No such association was found for the IL1B-511 (TT versus CC: OR, 1.34; 95% CI, 0.87-2.07; I(2) = 65.7%; 13 studies) or TNFA-308 genotypes (AA versus GG: OR, 0.93; 95% CI, 0.35-2.43; I(2) = 0.0%; 7 studies). The IL1RN*22 genotype seems to consistently increase the risk of gastric precancerous lesions, supporting a role for this polymorphism in the early stages of gastric carcinogenesis.
authors.affiliation: Serviço de Higiene e Epidemiologia, Faculdade de Medicina da Universidade do Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. barbarap@med.up.pt
authors.forename: Bárbara
authors.initials: B
authors.lastname: Peleteiro
authors.forename: Nuno
authors.initials: N
authors.lastname: Lunet
authors.forename: Carla
authors.initials: C
authors.lastname: Carrilho
authors.forename: Cecília
authors.initials: C
authors.lastname: Durães
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Machado
authors.forename: Carlo
authors.initials: C
authors.lastname: La Vecchia
authors.forename: Henrique
authors.initials: H
authors.lastname: Barros
mesh_terms: D016207:Cytokines / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D016207:Cytokines; C508585:IL1B protein, human; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha