IL1RN polymorphic gene and cagA-positive status independently increase the risk of noncardia gastric carcinoma.

Helicobacter pylori cagA-positive strains and host cytokine proinflammatory polymorphisms have been associated with gastric carcinoma. However, the individual role of each factor has not been evaluated yet. Our aim was to evaluate whether IL-1 gene cluster and tumor necrosis factor-alpha (TNFA)-307 polymorphisms, as well as cagA-positive status, are associated with gastric carcinoma in a non-Caucasian population by analyzing the data in logistic regression models. We evaluated 166 patients with noncardia gastric carcinoma and 541 blood donors. Among them, 702 were successfully genotyped for all cytokine studied: 166 with gastric carcinoma and 536 controls. The carcinoma patients were considered to be H. pylori-positive if culture alone or 2 among preformed urease test, stained smear or histologic section, serology, polymerase chain reaction (PCR) for ureA and urea breath test were positive. In blood donors, H. pylori status was based on enzyme-linked immunosorbent assay. The cagA status was determined by PCR or serology. IL1B-511/-31, IL1RN (interleukin-1 receptor antagonist) and TNFA-307 polymorphisms were genotyped by PCR, PCR with restriction fragment length polymorphism, or PCR with confronting 2-pair primers. We found that the IL1RN2 polymorphic allele (OR = 1.93) was associated with noncardia gastric carcinoma, even after inclusion of age, gender and cagA status in the logistic models. However, the cagA-positive status was the strongest independent factor associated with gastric carcinoma (OR = 11.89). The other polymorphisms were not significantly associated with the disease when they were evaluated in logistic models. This study provides evidence supporting the independent associations of cagA-positive H. pylori status and IL1RN polymorphisms with noncardia gastric carcinoma. (c) 2005 Wiley-Liss, Inc.