Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2019; 25(8): 1012-1023
Published online Feb 28, 2019. doi: 10.3748/wjg.v25.i8.1012
Lethal-7-related polymorphisms are associated with susceptibility to and prognosis of gastric cancer
Zhi-Fang Jia, Dong-Hui Cao, Yan-Hua Wu, Mei-Shan Jin, Yu-Chen Pan, Xue-Yuan Cao, Jing Jiang
Zhi-Fang Jia, Dong-Hui Cao, Yan-Hua Wu, Yu-Chen Pan, Jing Jiang, Division of Clinical Research, the First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Mei-Shan Jin, Division of Pathology, the First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Xue-Yuan Cao, Department of Gastrointestinal Surgery, the First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Author contributions: Jiang J and Cao XY designed the research; Jia ZF, Cao DH, Wu YH, Pan YC, and Jin MS performed the research; Jia ZF and Jiang J analyzed the data; Jia ZF wrote the manuscript; Jiang J and Cao XY revised the manuscript.
Supported by National Natural Science Foundation of China, No. 81703293, 81673145, and No. 81373084; the Research Program of the Education Department of Jilin Province, No. 2016487; the Scientific and Technological Development Program of Jilin Province, No. 20180414055GH.
Institutional review board statement: This study was reviewed and approved the Ethics Committee of the First Hospital of Jilin University (Changchun, China).
Informed consent statement: All the subjects gave written informed consent to participate in the study before enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The items that should be included in reports of observational studies were checked and the file of STROBE statement was uploaded.
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/
Corresponding author: Jing Jiang, PhD, Professor, Statistician, Division of Clinical Research, the First Hospital of Jilin University, No. 71, Xinmin Street, Changchun 130021, Jilin Province, China. jiangjing19702000@jlu.edu.cn
Telephone: +86-431-81875408 Fax: +86-431-85654528
Received: December 4, 2018
Peer-review started: December 6, 2018
First decision: January 6, 2019
Revised: January 18, 2019
Accepted: January 26, 2019
Article in press: January 26, 2019
Published online: February 28, 2019
Research background

Gastric cancer (GC) is one of the most common malignancies worldwide. Despite the advances in diagnosis and treatment of GC in recent decades, prognosis of GC patients is still poor. It is of great importance to identify biomarkers that could be helpful in the improvement of screening of high-risk individuals, early diagnosis, and predicting outcome for the individualized therapy.

Research motivation

The microRNA lethal-7 (let-7) often exhibits tumor-suppressor functions in tumorigenesis. Single nucleotide polymorphisms (SNPs) in the let-7 gene region or let-7 target genes have been reported to modulate the risk of several cancers including breast cancer and lung cancer. In GC, the related studies are limited

Research objectives

By including a relatively large number of GC patients, this study aimed to determine the role of let-7-related polymorphisms in GC in a Chinese population.

Research methods

From 2008 to 2013, 898 consecutive GC patients and 992 tumor-free controls were recruited into the study. GC patients were followed periodically to determine their prognosis. Ten SNPs in the let-7 gene region or their target mRNAs were genotyped using MassArray system and the associations with the risk or overall survival of GC were analyzed.

Research results

Two SNPs in let-7 target genes were associated with GC in a dose-dependent manner. Rs3811463 in the 3’-UTR of LIN28A was associated with lower risk of GC and the risk was reduced by 26% with each increase of the C allele of rs3811463. The rs10889677 in the 3’-UTR of IL23R was corresponded to the prognosis of GC, and the death risk increased by 25% with each increment of the C allele of rs10889677, after controlling for clinicopathological parameters.

Research conclusions

Let-7-related SNPs were related to GC. The rs3811463 in LIN28A is associated with the susceptibility to and rs10889677 in IL23R is associated with the prognosis of GC.

Research perspectives

Our research adds evidence that polymorphisms represent a genetic factor to modify the susceptibility to and prognosis of GC. The underlying mechanisms of the associations should be elucidated in future studies.