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

The lethal-7 (let-7) family members and their targets are involved in the development and progression of tumors. Let-7-related polymorphisms have been reported to be associated with tumorigenesis and prognosis. In gastric cancer, however, the related studies are limited.


To investigate the role of let-7-related microRNA polymorphisms in the tumorigenesis and prognosis of gastric cancer in a Chinese population.


A total of 898 gastric cancer patients and 992 tumor-free controls were recruited into this study from 2008 to 2013. Gastric cancer patients were followed periodically. Ten single nucleotide polymorphisms (SNPs) in the let-7 gene region or their target mRNAs were genotyped using the MassARRAY system and their associations with the risk for or overall survival of gastric cancer were analyzed.


All the ten SNPs were in Hardy-Weinberg equilibrium. The C allele of the rs3811463 polymorphism in the 3’-untranslated region (UTR) of LIN28A was associated with a lower risk of gastric cancer [odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.61-0.88, P = 0.001] after adjustment for age and Helicobacter pylori status. Seven hundred and thirty-five gastric cancer patients who had undergone radical tumorectomy were included in the survival analysis and their 5-year survival rate was 53.9% (95%CI: 50.1%-57.6%). The rs10889677 in the 3’-UTR of IL23R was corresponded to the prognosis of gastric cancer in a dose-response manner, in which the death risk increased by 25% [hazard ratio (HR) = 1.25, 95%CI: 1.04-1.45, P = 0.011] with each increase in the number of C alleles after controlling for other potential clinicopathological parameters.


The let-7-related polymorphism rs3811463 in LIN28A is associated with the susceptibility to gastric cancer and the let-7-related polymorphism rs10889677 in IL23R is associated with the prognosis of gastric cancer.

Keywords: Gastric cancer, Risk, Susceptibility, Prognosis, Polymorphism, Lethal-7, LIN28A, IL23R

Core tip: This study included a relatively large number of gastric cancer patients and tumor-free controls and explored the relationship of ten lethal-7 (let-7)-related single nucleotide polymorphisms with gastric carcinogenesis and prognosis. The results showed that the LIN28A rs3811463 polymorphism of the let-7 target was associated with the development of gastric cancer and that the IL23R rs10889677 polymorphism was related to the overall survival of gastric cancer patients in a dose-dependent manner. This study adds evidence that polymorphisms represent a genetic factor that modifies the susceptibility to and prognosis of gastric cancer.