CD226 rs727088A>G polymorphism increases the susceptibility to gastric cancer in Chinese populations

• We found that rs727088A>G polymorphism was associated with risk of GC.
• We found an effect of rs727088A>G on CD226 3′-UTR transcriptional activity.
• We found that a high risk effect of rs727088A>G was pronounced in smoking subjects.

Gastric cancer (GC) is one of the most common cancers worldwide, especially in Asia. The development of GC is a multifactorial process and numerous studies have linked genetic variation to GC risk. In this study, we evaluated the effects of single nucleotide polymorphisms (SNPs) of CD226 on GC susceptibility in Chinese populations including 687 cancer patients and 936 control subjects. We found that the G allele of the rs727088A>G polymorphism in the 3′-untranslated region of CD226 was significantly associated with risk of GC using logistic regression (P < 10− 3). GC patients who harbored the rs727088G allele had significantly increased cancer risk (odds ratio = 1.43, 95% confidence interval = 1.23–1.67) compared with those patients harboring the rs727088A allele. Moreover, functional relevance was further performed that individuals carrying the rs727088G allele were correlated with lower expression level of CD226 than individuals carrying the rs727088AA homozygous genotype. These findings indicated that functional polymorphism rs727088A>G in CD226 might modify the susceptibility for the development of GC.