Lethal-7-related polymorphisms are associated with susceptibility to and prognosis of gastric cancer

BACKGROUND: The lethal-7 (let-7) family members and their targets are involved in the development and progression of tumors. Let-7-related polymorphisms have been reported to be associated with tumorigenesis and prognosis. In gastric cancer, however, the related studies are limited. AIM: To investigate the role of let-7-related microRNA polymorphisms in the tumorigenesis and prognosis of gastric cancer in a Chinese population. METHODS: A total of 898 gastric cancer patients and 992 tumor-free controls were recruited into this study from 2008 to 2013. Gastric cancer patients were followed periodically. Ten single nucleotide polymorphisms (SNPs) in the let-7 gene region or their target mRNAs were genotyped using the MassARRAY system and their associations with the risk for or overall survival of gastric cancer were analyzed. RESULTS: All the ten SNPs were in Hardy-Weinberg equilibrium. The C allele of the rs3811463 polymorphism in the 3’-untranslated region (UTR) of LIN28A was associated with a lower risk of gastric cancer [odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.61-0.88, P = 0.001] after adjustment for age and Helicobacter pylori status. Seven hundred and thirty-five gastric cancer patients who had undergone radical tumorectomy were included in the survival analysis and their 5-year survival rate was 53.9% (95%CI: 50.1%-57.6%). The rs10889677 in the 3’-UTR of IL23R was corresponded to the prognosis of gastric cancer in a dose-response manner, in which the death risk increased by 25% [hazard ratio (HR) = 1.25, 95%CI: 1.04-1.45, P = 0.011] with each increase in the number of C alleles after controlling for other potential clinicopathological parameters. CONCLUSION: The let-7-related polymorphism rs3811463 in LIN28A is associated with the susceptibility to gastric cancer and the let-7-related polymorphism rs10889677 in IL23R is associated with the prognosis of gastric cancer.