A putative microRNA binding site polymorphism rs61882771 in the CD44 3'-UTR is associated with the risk of gastric cancer

rs61882771 polymorphism in the CD44 3'-UTR in gastric cancer

Abstract

Objectives: Single nucleotide polymorphisms (SNPs) in potential microRNA (miRNA) binding sites in the 3'-UTR of target genes may dysregulate the target gene expression and subsequently contribute to the susceptibility to cancers. The cluster of differentiation 44 (CD44) is a surface gastric cancer stem cell marker and its 3'-UTR variants have been the subject of previous cancer risk association studies. However, this research provides the first evidence on the relationship between the rs61882771 (c.*2046T>C), located on microRNA-binding sites in the 3′-UTR of CD44 and gastric cancer.

Materials and methods: 252 gastric cancer patients and 216 non-cancer controls were included in the present work. High-resolution melting curve (HRM) analysis and following sequencing were used to screen genotyping of the SNP rs61882771.

Results: This case–control study indicated that individuals carrying an allele of C in rs61882771 showed a significant association with the higher risk for GC compared with subjects carrying TT genotype (CT vs TT, OR=2.66, 95% CI=1.74-4.07, P<0.001; CC vs TT, OR=3.03, 95% CI=1.84-5.00, P<0.001; CT + CC vs TT, OR=2.79, 95% CI=1.91-4.09, P<0.001). Similarly, a significant difference in the allelic frequencies was found between GC patient and control groups (C vs T, OR=2.08, 95% CI=1.59-2.72, P<0.001). Furthermore, bioinformatic analysis using an online tool indicated that the rs61882771 variant may alter miRNAs capability to bind the 3'-UTR of CD44.

Conclusion: Consistent with the in silico analysis, our data suggest that polymorphism of the miRNA binding site in the CD44 3'-UTR (rs61882771) modify gastric cancer susceptibility.