To evaluate the association between gastric cancer susceptibility and inflammation-related gene polymorphisms, the authors conducted a series of meta-analyses using a predefined protocol. Genes investigated were those coding for the interleukin (IL) proteins (IL1B, IL1RN, IL8, and IL10) and for tumor necrosis factor-alpha. Gastric cancers were stratified by histologic subtype and anatomic subsite, by Helicobacter pylori infection status, by geographic location (Asian or non-Asian study population), and by a quantitative index of study quality. All published literature and meeting abstracts from the period 1990-2006 were considered. Results consistently supported increased cancer risk for IL1RN2 carriers; the increased risk was specific to non-Asian populations and was seen for intestinal and diffuse cancers, distal cancers, and, to a lesser extent, cardia cancers. Analyses restricted to high-quality studies or H. pylori-positive cases and controls also showed significant associations with both carrier status and homozygosity status. In Asian populations, reduced risk was observed in association with IL1B-31C carrier status. This effect was also observed in analyses restricted to high-quality studies. These results indicate the importance of stratification by anatomic site, histologic type, H. pylori infection, and country of origin. Study quality considerations, both laboratory and epidemiologic, can also affect results and may explain, in part, the variability in results published to date.