Gene–Nutrition Interaction in Gastric Cancer: miRNA-Related Polymorphisms in CTSF and NT5E, Dietary Exposures, and Site-Specific Risk

Background: Gastric cancer (GC) is a leading cause of cancer death in China, particularly in rural high-incidence areas. miRNA-related SNPs may interact with diet to influence GC risk. We therefore examined miRNA-related SNPs in COPS2, CTSF, and NT5E, together with their cognate miRNAs, and assessed their interactions with dietary factors in overall, cardia, and non-cardia GC. Methods: A 1:1 matched case-control study included 550 GC cases and 550 controls from a high-incidence county in Fujian, China. Eight miRNA-related SNPs were genotyped, and seven conforming to Hardy–Weinberg equilibrium were included in the final analysis. Conditional logistic regression and generalized multifactor dimensionality reduction (GMDR) were used to assess associations and interactions. Results: CTSF rs4576 was associated with increased overall and non-cardia GC risk. NT5E rs6913634 was associated with increased overall and cardia GC risk, whereas miR-30a rs2222722 was associated with increased risk of cardia GC only. GMDR identified hard-food preference, pickled vegetable intake, and rs4576 as the best interaction model for overall GC. A positive additive interaction was observed between rs4576 and hard-food preference (RERI = 1.65, 95% CI: 0.049–3.26). G-allele carriers with hard-food preference or pickled vegetable intake had markedly elevated joint risks. Conclusions: miRNA-related polymorphisms in CTSF and NT5E and in miR-30a showed subsite-related association patterns in this high-risk Chinese population; however, without formal between-subsite heterogeneity tests, these should be interpreted as observed patterns rather than established subtype-specific differences. Additionally, the preliminary positive additive interaction between rs4576 and hard-food preference points to a potential gene–diet interaction that warrants validation in independent populations before it can inform dietary prevention.