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Interleukin-1B Polymorphisms and Gastric Cancer Risk—A Meta-analysis

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Farin Kamangar, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6120 Executive Boulevard, Room 3034, Bethesda, MD 20892-7232. Phone: 301-594-2936; Fax: 301-496-6829. E-mail: kamangaf{at}mail.nih.gov

Some studies have reported that proinflammatory polymorphisms in interleukin-1B (IL-1B) and IL-1 receptor antagonist (IL-1RN) genes are associated with increased gastric cancer risk. However, other studies have shown null or inverse associations. This meta-analysis reviews and summarizes published evidence for these associations. Searching the PubMed Database yielded 35 studies that reported on the association between IL-1B –511 C>T, IL-1B –31 T>C, or IL-1RN variable number tandem repeat polymorphisms and gastric cancer risk. Q-statistics and I² statistics were calculated to examine heterogeneity. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were calculated in the random-effects model using the DerSimonian-Laird method. For all gastric cancers, the overall ORs (95% CIs) for IL-1B –511 CT versus CC and TT versus CC genotypes were 1.07 (0.91-1.25) and 1.16 (0.95-1.42), respectively. ORs (95% CIs) for the association between IL-1B –31 CT versus TT and CC versus TT genotypes were 0.99 (0.83-1.19) and 0.98 (0.78-1.21), respectively. For the associations between IL-1RN and gastric cancer, ORs (95% CIs) for *2/L versus LL and *2/*2 versus L/L were 1.15 (0.96-1.38) and 1.23 (0.79-1.92). For each of the examined associations, there was significant heterogeneity among studies; P_{heterogeneity} 0.001 and I² ranged from 0.54 to 0.71. Noncardia cancers showed stronger associations with IL-1B –511 CT or TT and IL1-RN *2/*2 genotypes, but limiting the analysis to intestinal-type cancers, studies conducted in Western countries, or studies in which polymorphisms were in Hardy-Weinberg equilibrium, made no material difference in the results. The overall associations between IL-1B or IL-1RN proinflammatory polymorphisms and gastric cancer were null but several studies showed an association. The sources of this variation are unclear. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1920–8)

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