A miR-29c binding site genetic variant in the 3'-untranslated region of LAMTOR3 gene is associated with gastric cancer risk

Abstract

Single nucleotide polymorphisms (SNPs) in the 3'-untranslated regions (UTRs) targeted by putative mircoRNAs (miRNAs) could influence the susceptibility of cancer. Recently, miR-29c has been reported to be down-regulated in gastric cancer (GC) and serve as a tumor suppressor that regulated tumor progression. The present study was aimed at investigating whether the miR-29c binding site SNPs within the 3'-UTRs of target genes affected the gastric cancer risk. Using bioinformatics tools, we chose three SNPs (IGHMBP2 rs3750980, LAMTOR3 rs11944405 and WWOX rs2288035) located in miR-29c binding sites. We genotyped these three SNPs to assess their associations with GC risk in a case-control study comprising 753 GC cases and 950 controls. Among these three SNPs, we found a significantly decreased risk of GC associated with the LAMTOR3 rs11944405 T>C polymorphism [TC vs. TT, adjusted odds ratio (OR)=0.79, 95% confidence interval (CI)=0.63-0.99; TC/CC vs. TT, adjusted OR=0.81, 95% CI=0.65-1.00]. The significant association was also presented in the subgroup analysis by age (≤65), sex (female), depth of invasion (T3/T4), lymph node metastasis (N1-3), distant metastasis (M0) and TNM stage (III/IV). However, no significant association was detected for IGHMBP2 rs3750980 and WWOX rs2288035. Our results suggested that the LAMTOR3 rs11944405 polymorphism may be a potential biomarker for genetic susceptibility to GC.

Keywords: Gastric cancer; Genetic susceptibility; LAMTOR3; Single nucleotide polymorphism; miR-29c.