Polymorphisms in promoter regions of inflammatory cytokines have been widely studied, and potentially functional polymorphisms have been discovered. Conflicting results from meta-analyses of interleukin (IL)-1B and IL-10 polymorphisms show differences in gastric cancer susceptibilities between Caucasian and Asian populations. In particular, we note the suggestion of an allele flip in IL-1B and IL-10 gene polymorphisms. In Asian populations, the IL-1B-1464G/-511C/-31T haplotype indicates risk for gastric cancer, while the opposite haplotype, IL-1B-1464C/-511T/-31C is the risk-related allele in Caucasians. Furthermore, while IL-10-1082G/-819C/-592C is associated with gastric cancer in Asians, IL-10-1082A/-819T/-592T is linked to gastric cancer risk in Caucasians. These seemingly contradictory results may be attributed to distinct carcinogenic mechanisms underlying the different gastric cancer subtypes. The allele flip observed in IL-10 and gastric cancer appears to reflect allelic heterogeneity, similar to that observed in IL-1B. In this review, we focus on the allele flip phenomenon observed between different ethnic groups in an effort to resolve certain controversial results from recent studies on interleukin polymorphism. In addition, we re-emphasize the importance of stratifying gastric cancer subtypes based on anatomical site and Lauren classification to prevent false associations arising through dilution of true ones.
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