Genetic variants in m6A modification genes are associated with esophageal squamous-cell carcinoma in the Chinese population.

N 6 -methyladenosine (m 6 A) is an abundant modification in RNAs that affects RNA metabolism, and it is reported to be closely related to cancer occurrence and metastasis. In this study, we focused on evaluating the associations between genetic variants in m 6 A modification genes and the risk of esophageal squamous-cell carcinoma (ESCC). By integrating data of our previous GWAS and the predictions of several annotation tools, we identified a single nucleotide polymorphism (SNP), rs2416282 in the promoter of YTHDC2, that was significantly associated with the susceptibility of ESCC (OR = 0.84, 95% CI: 0.77 - 0.92, P = 2.81 x 10-4). Through further functional experiments in vitro, we demonstrated that rs2416282 regulatedYTHDC2 expression. Knockdown ofYTHDC2 substantially promoted the proliferation rate of ESCC cells by affecting several cancer-related signaling pathways. Our results suggested that rs2416282 contributed to ESCC risk by regulatingYTHDC2 expression. This study provided us a valuable insight into the roles of genetic variants in m6A modification genes for ESCC susceptibility and may contribute to the prevention of this disease in the future.