Genetic variants in m⁶A regulators are associated with gastric cancer risk

N⁶-methyladenosine (m⁶A) modification plays a vital regulatory role in tumorigenesis and development. In this study, we determined that the mRNA expression of IGF2BP1, IGF2BP2 and IGF2BP3, as the m⁶A modification genes, was significantly increased in gastric cancer (GC) tissues. Using a logistic regression model, we found that novel single-nucleotide polymorphism (SNP) rs9906944 C > T in IGF2BP1 was remarkably associated with a decreased risk of GC in discovery stage (odds ratio (OR) = 0.75, 95% confidence interval (95% CI): 0.60-0.93, P = 8.51 × 10^-3). This finding was repeated in an independent Nanjing population (OR = 0.76, 95% CI: 0.59-0.98, P = 3.45 × 10^-2). The combined analysis including 2900 GC cases and 3,536 controls confirmed the association between rs9906944 C > T and GC risk (OR = 0.75, 95% CI: 0.64-0.88, P = 5.76 × 10^-4). Furthermore, we found that GC patients with higher IGF2BP1 mRNA expression level had prominent poorer overall survival (hazard ratio (HR) = 1.49, 95% CI: 1.16-1.91, logrank P = 1.50 × 10^-3). For the first time, our findings suggested the importance of genetic variants in m⁶A regulators in GC and indicated that IGF2BP1 plays a crucial role in GC. Genetic variants in m⁶A modification genes may be used for GC risk prediction.