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: rs4822739:C>G (miR-548j) and rs701213:T>C (miR-4427). Additionally, rs1553867776:T>TCCCCA (miR-4274) and rs12416605:C>T (miR-938) were associated with intestinal-type GC, and rs4822739:C>G (miR-548j) and rs1439619:T>G (miR-3175) with TNM I-II stage. The polymorphisms rs6149511:T> TGAAGGGCTCCA (miR-6891), rs404337:G>A (miR-8084), and rs1439619:T>G (miR-3175) were identified among H.pylori-infected GC patients and rs7500280:T>C (miR-4719) and rs1439619:T>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.

Gastric cancer actionable genomic alterations across diverse populations worldwide and pharmacogenomics strategies based on precision oncology

“…Understanding the impact of oncogenic variants across different ethnic groups is crucial as these variants can significantly influence the susceptibility to gastric cancer ( Cordova-Delgado et al, 2021 ; Gonzalez-Hormazabal et al, 2021 ; Landeros et al, 2021 ). This knowledge is essential for prioritizing therapeutic strategies and making informed decisions concerning healthcare economics, public health policies, and global preventive measures.…”

Non-Coding RNA as Biomarkers and Their Role in the Pathogenesis of Gastric Cancer—A Narrative Review

“…The authors demonstrated that the C allele of the mRNA-499 rs3746444 T>C SNP increased susceptibility to GC. Several other SNPs-miR-196a2 rs11614913, miR-27a rs895819, miR-499 rs3746444, miR-27a rs895819, miR-4427 rs701213, miR-548j rs4822739, miR-938 rs12416605, miR-4274 rs1553867776, miR-3175 rs1439619, miR-6891 rs6149511, miR-8084 rs404337, miR-4719 rs7500280 and miR-34b/c rs4938723-have been associated with an increased or decreased susceptibility to GC [58][59][60][61][62]. Interestingly, SNPs have been combined with other parameters to evaluate the correlation with gastric malignancy.…”

“…As mentioned above, miRNA SNPs could alter the RNA molecular structure. Landeros et al [61] showed that several polymorphisms alter miRNA structure. For example, the miR-6891 rs6149511:T>TGAAGGGCTCCA SNP significantly changes the loop terminal region.…”