Novel Risk Associations between microRNA Polymorphisms and Gastric Cancer in a Chilean Population.

ABSTRACT

Gastric cancer (GC) is the fifth leading cause of cancer deaths in the world, with variations across geographical regions and ethnicities. Emerging evidence indicates that miRNA expression is dysregulated in GC and its polymorphisms may contribute to these variations, which has yet to be explored in Latin American populations. In a case-control study of 310 GC patients and 311 healthy donors from Chile, we assessed the association of 279 polymorphisms in 242 miRNA genes. Two novel polymorphisms were found to be associated with GC rs4822739C>G (miR-548j) and rs701213T>C (miR-4427). Additionally, rs1553867776T>TCCCCA (miR-4274) and rs12416605C>T (miR-938) were associated with intestinal-type GC, and rs4822739C>G (miR-548j) and rs1439619T>G (miR-3175) with TNM I-II stage. The polymorphisms rs6149511T> TGAAGGGCTCCA (miR-6891), rs404337G>A (miR-8084), and rs1439619T>G (miR-3175) were identified among H.pylori-infected GC patients and rs7500280T>C (miR-4719) and rs1439619T>G (miR-3175) were found among H. pylori cagPAI+ infected GC cases. Prediction analysis suggests that seven polymorphisms could alter the secondary structure of the miRNA, and the other one is located in the seed region of miR-938. Targets of miRNAs are enriched in GC pathways, suggesting a possible biological effect. In this study, we identified seven novel associations and replicated one previously described in Caucasian population. These findings contribute to the understanding of miRNA genetic polymorphisms in the GC pathogenesis.