A Genetic Variant in Long Non-Coding RNA HULC Contributes to Risk of HBV-Related Hepatocellular Carcinoma in a Chinese Population

Yao Liu,Hongbing Shen,Li Liu,Yixin Zhang,Zhibin Hu,Shandong Pan,Jibin Liu,Jianguo Chen,Juan Wen,Xiangjun Zhai,Rui Medeiros

doi:10.1371/journal.pone.0035145

Abstract

BackgroundRecently, several studies have demonstrated that two long non-coding RNAs (lncRNAs), HULC and MALAT1, may participate in hepatocellular carcinoma (HCC) development and progression. However, genetic variations in the two lncRNAs and their associations with HCC susceptibility have not been reported. In this study, we hypothesized that single nucleotide polymorphisms (SNPs) in HULC and MALAT1 may contribute to HCC risk.MethodsWe conducted a case-control study and genotyped two SNPs, rs7763881 in HULC and rs619586 in MALAT1, in 1300 HBV positive HCC patients, 1344 HBV persistent carriers and 1344 subjects with HBV natural clearance to test the associations between the two SNPs and susceptibility to HCC and HBV chronic infection.ResultsThe variant genotypes of rs7763881 were significantly associated with decreased HCC risk in a dominant genetic model [AC/CC vs. AA: adjusted odds ration (OR) = 0.81, 95% confidence intervals (CIs) = 0.68–0.97, P = 0.022]. Furthermore, the variant genotypes of rs619586 was associated with decreased HCC risk with a borderline significance (AG/GG vs. AA: adjusted OR = 0.81, 95% CIs = 0.65–1.01, P = 0.057). However, no significant association was found between the two SNPs and HBV clearance.ConclusionsThe variant genotypes of rs7763881 in HULC may contribute to decreased susceptibility to HCC in HBV persistent carriers.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the seventh in women in the world, and the new cases of hepatocellular carcinoma (HCC) in developing countries accounted for almost 85% of all patients [1]
single nucleotide polymorphisms (SNPs) Selection and Genotyping Based on the data from Hapmap database and the criteria of minor allele frequency (MAF) . 0.05 in Han Chinese, we found five common SNPs in HULC, all of which are in high linkage disequilibrium (LD)
The drinking rate was significantly higher in HCC cases than that in controls

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the seventh in women in the world, and the new cases of HCC in developing countries accounted for almost 85% of all patients [1]. The major risk factors for HCC include chronic infections with the hepatitis B or C viruses, alcohol consumption, and foodstuff contamination with aflatoxins [2,3,4,5]. Only a small fraction of HBV persistent carriers developed HCC, suggesting genetic variation may play roles in the carcinogenesis of HCC after HBV infection. HBV persistent infection or HBV natural clearance may be influenced by complex factors of viral, host age, environmental and genetic makeups. Several studies have demonstrated that two long non-coding RNAs (lncRNAs), HULC and MALAT1, may participate in hepatocellular carcinoma (HCC) development and progression. We hypothesized that single nucleotide polymorphisms (SNPs) in HULC and MALAT1 may contribute to HCC risk

Methods

Results

Conclusion