Tag SNPs in long non-coding RNA H19 contribute to susceptibility to gastric cancer in the Chinese Han population.

Chao Yang,Zekuan Xu,Li Yang,Xiang Ma,Ran Tang,Younan Wang,Dakui Luo,Yi Zhu

doi:10.18632/oncotarget.3840

Abstract

Long non-coding RNA (lncRNA) H19 is involved in tumor development, progression, and metastasis. This case-control study assessed the association between H19 genetic variants and susceptibility to gastric cancer (GC) in a Chinese Han population. We genotyped four lncRNA H19 single nucleotide polymorphisms (SNPs) (rs217727 C > T, rs2839698 C > T, rs3741216 A > T, rs3741219 T > C) in 500 GC patients and 500 healthy controls. Carriers of variant rs217727T and rs2839698T alleles showed increased GC risk (P = 0.008 and 0.011, respectively). Compared with the common genotype, CT + TT rs217727 and CT + TT rs2839698 genotypes were associated with significantly increased GC risk (P = 0.040, adjusted odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.01-1.71; P = 0.033, adjusted OR = 1.31, 95% CI = 1.02-1.69, respectively). Further stratified analyses revealed that the association between GC risk and variant genotypes of rs217727 was more profound in younger individuals (≤59 years) and non-smokers, while the association between risk and the rare rs2839698 genotype persisted in men and rural subjects. rs2839698 CT and TT genotypes were also associated with higher serum H19 mRNA levels compared with the CC genotype. These findings suggest that lncRNA H19 SNPs may contribute to susceptibility to GC.

Highlights

Gastric cancer (GC) ranks fourth in terms of incidence and second in terms of mortality among all cancers worldwide [1, 2]
To the best of our knowledge, this study provides the first investigation into associations between H19 polymorphisms and GC susceptibility in a Chinese Han population
Our data showed that the increased risk of GC associated with the variant genotypes of rs217727 was more pronounced in younger subjects than older subjects

Summary

Introduction

Gastric cancer (GC) ranks fourth in terms of incidence and second in terms of mortality among all cancers worldwide [1, 2]. The development of GC is a complex and multifactorial process involving a number of etiological factors and multiple genetic and epigenetic alterations [3, 4]. Helicobacter pylori infection, high salt intake, and tobacco smoking are the main environmental factors influencing its development [2], though genetic factors are thought to play important roles in gastric carcinogenesis [5]. LncRNA H19 is an imprinted gene located within the highly-conserved imprinted H19/insulin-like growth factor 2 (IGF2) locus on chromosome 11p15.5. Binding of the CCCTC-binding factor insulator protein to the nonmethylated allele of the DMR promotes H19 expression, whereas IGF2 is expressed from the methylated allele [15]

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Results

Conclusion