Case Control Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2018; 24(23): 2482-2490
Published online Jun 21, 2018. doi: 10.3748/wjg.v24.i23.2482
Association of twelve polymorphisms in three onco-lncRNA genes with hepatocellular cancer risk and prognosis: A case-control study
Ben-Gang Wang, Qian Xu, Zhi Lv, Xin-Xin Fang, Han-Xi Ding, Jing Wen, Yuan Yuan
Ben-Gang Wang, Qian Xu, Zhi Lv, Xin-Xin Fang, Han-Xi Ding, Jing Wen, Yuan Yuan, Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, Liaoning Province, China
Ben-Gang Wang, Hepatobiliary Surgery Department of General Surgery Institute, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Author contributions: Yuan Y conceived and designed this study; Wang BG, Lv Z, Fang XX, and Wen J preformed the experiments; Wang BG, Xu Q, and Ding HX were responsible for the data analysis and performed data interpretation; Wang BG wrote the paper; Lv Z and Yuan Y revised the manuscript.
Supported by the Natural Science Foundation of Liaoning Province in China, No. 20170541001.
Institutional review board statement: The study was approved by the ethics committee of the First Hospital of China Medical University.
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: All authors disclose no conflicts of interest that may bias their work.
STROBE statement: The guidelines of the STROBE Statement have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yuan Yuan, MD, PhD, Professor, Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, No.155 NanjingBei Street, Heping District, Shenyang 110001, Liaoning Province, China. yuanyuan@cmu.edu.cn
Telephone: +86-24-83282153 Fax: +86-24-83282383
Received: March 22, 2018
Peer-review started: March 23, 2018
First decision: April 10, 2018
Revised: April 17, 2018
Accepted: May 18, 2018
Article in press: May 18, 2018
Published online: June 21, 2018
Processing time: 84 Days and 19.2 Hours
Abstract
AIM

To evaluate the association of 12 tag single nucleotide polymorphisms (tagSNPs) in three onco-long non-coding RNA (lncRNA) genes (HOTTIP, CCAT2, MALAT1) with the risk and prognosis of hepatocellular cancer (HCC).

METHODS

Twelve tagSNPs covering the three onco-lncRNAs were genotyped by the KASP method in a total of 1338 samples, including 521 HCC patients and frequency-matched 817 controls. The samples were obtained from an unrelated Chinese population at the First Hospital of China Medical University from 2012-2015. The expression quantitative trait loci (eQTL) analyses were conducted to explore further the potential function of the promising SNPs.

RESULTS

Three SNPs in HOTTIP, one promoter SNP in MALAT1, and one haplotype of HOTTIP were associated with HCC risk. The HOTTIP rs17501292, rs2067087, and rs17427960 SNPs were increased to 1.55-, 1.20-, and 1.18-fold HCC risk under allelic models (P = 0.012, 0.017 and 0.049, respectively). MALAT1 rs4102217 SNP was increased to a 1.32-fold HCC risk under dominant models (P = 0.028). In addition, the two-way interaction of HOTTIP rs17501292-MALAT1 rs619586 polymorphisms showed a decreased effect on HCC risk (Pinteraction = 0.028, OR = 0.30) and epistasis with each other. HOTTIP rs3807598 variant genotype showed significantly longer survival time in HBV negative subgroup (P = 0.049, HR = 0.12), and MALAT1 rs591291 showed significantly better prognosis in female and HBV negative subgroups (P = 0.022, HR = 0.37; P = 0.042, HR = 0.25, respectively). In the study, no significant effect was observed in eQTL analysis.

CONCLUSION

Specific lncRNA (HOTTIP and MALAT1) SNPs have potential to be biomarkers for HCC risk and prognosis.

Keywords: Hepatocellular cancer; Single nucleotide polymorphism; Long non-coding RNA; Risk; Prognosis

Core tip: We aim to evaluate the association of twelve tag single nucleotide polymorphisms (tagSNPs) in three onco-lncRNA genes (HOTTIP, CCAT2, MALAT1) with the risk and prognosis of hepatocellular cancer (HCC). Twelve tagSNPs covering the three onco-lncRNAs were genotyped by the KASP method in a total of 1338 samples. We found three SNPs in HOTTIP, one promoter SNP in MALAT1 and one haplotype of HOTTIP gene were associated with HCC risk. In addition, HOTTIP rs3807598 variant genotype showed significantly longer survival time in hepatitis B virus (HBV) negative subgroup, and MALAT1 rs591291 showed significantly better prognosis in female and HBV negative subgroups.