Abstract

Objectives: MicroRNAs are post-transcriptional gene regulators with important biological roles. Nucleotide variants in microRNA genes may result in changes in their expression and function that could contribute to the physiopathology of cancer. We aimed to identify microRNA genetic variants with a role in Gastric Cancer susceptibility through genetic association studies in a European cohort. Methods: 21 microRNA allele variants, four located in the seed, three in the mature and fourteen in the precursor of 20 microRNAs were genotyped. Genetic association with Gastric Cancer anatomical and histological subtypes was performed in 365 cases and 1,284 matched controls within the -European Prospective Investigation into Cancer and Nutrition- cohort using logistic regression. Differences in the expression between alleles were investigated using RT-qPCR after over-expression of the microRNA allele variants in HeLa cells. Luciferase-based gene reporter assays were used to validate microRNA-target gene interactions predicted by the PITA algorithm.