Evidence-Based Medicine
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2022; 14(9): 1844-1855
Published online Sep 15, 2022. doi: 10.4251/wjgo.v14.i9.1844
Prediction of gastric cancer risk by a polygenic risk score of Helicobacter pylori
Xiao-Yu Wang, Li-Li Wang, Shu-Zhen Liang, Chao Yang, Lin Xu, Meng-Chao Yu, Yi-Xuan Wang, Quan-Jiang Dong
Xiao-Yu Wang, Li-Li Wang, Shu-Zhen Liang, Lin Xu, Meng-Chao Yu, Yi-Xuan Wang, Quan-Jiang Dong, Central Laboratories and Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China
Chao Yang, The Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200000, China
Author contributions: Yang C and Liang SZ collected sequencing data; Xu L and Yu MC analyzed the data; Wang XY wrote the manuscript; Wang LL and Wang YX wrote the discussion part of the manuscript; Dong QJ designed the research and supervised the manuscript; and all authors reviewed the manuscript and approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 31870777.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Quan-Jiang Dong, MD, PhD, Chief Doctor, Professor, Central Laboratories and Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghai Middle Road, Qingdao 266071, Shandong Province, China. allyking114@126.com
Received: March 14, 2022
Peer-review started: March 14, 2022
First decision: April 17, 2022
Revised: April 29, 2022
Accepted: August 15, 2022
Article in press: August 15, 2022
Published online: September 15, 2022
Processing time: 179 Days and 4.6 Hours
Abstract
BACKGROUND

Genetic variants of Helicobacter pylori (H. pylori) are involved in gastric cancer occurrence. Single nucleotide polymorphisms (SNPs) of H. pylori that are associated with gastric cancer have been reported. The combined effect of H. pylori SNPs on the risk of gastric cancer remains unclear.

AIM

To assess the performance of a polygenic risk score (PRS) based on H. pylori SNPs in predicting the risk of gastric cancer.

METHODS

A total of 15 gastric cancer-associated H. pylori SNPs were selected. The associations between these SNPs and gastric cancer were further validated in 1022 global strains with publicly available genome sequences. The PRS model was established based on the validated SNPs. The performance of the PRS for predicting the risk of gastric cancer was assessed in global strains using quintiles and random forest (RF) methods. The variation in the performance of the PRS among different populations of H. pylori was further examined.

RESULTS

Analyses of the association between selected SNPs and gastric cancer in the global dataset revealed that the risk allele frequencies of six SNPs were significantly higher in gastric cancer cases than non-gastric cancer cases. The PRS model constructed subsequently with these validated SNPs produced significantly higher scores in gastric cancer. The odds ratio (OR) value for gastric cancer gradually increased from the first to the fifth quintile of PRS, with the fifth quintile having an OR value as high as 9.76 (95% confidence interval: 5.84-16.29). The results of RF analyses indicated that the area under the curve (AUC) value for classifying gastric cancer and non-gastric cancer was 0.75, suggesting that the PRS based on H. pylori SNPs was capable of predicting the risk of gastric cancer. Assessing the performance of the PRS among different H. pylori populations demonstrated that it had good predictive power for cancer risk for hpEurope strains, with an AUC value of 0.78.

CONCLUSION

The PRS model based on H. pylori SNPs had a good performance for assessment of gastric cancer risk. It would be useful in the prediction of final consequences of the H. pylori infection and beneficial for the management of the infection in clinical settings.

Keywords: Polygenic risk scores, Helicobacter pylori, Gastric cancer, Single nucleotide polymorphism

Core Tip: Prediction of cancer risk is of importance in the clinical management of populations with a high risk of gastric cancer. This study constructed a polygenic risk score (PRS) model based on Helicobacter pylori (H. pylori) single nucleotide polymorphisms (SNPs) to predict the risk of gastric cancer. Associations between previously reported H. pylori SNPs and gastric cancer were validated in global strains. A PRS model constructed with validated SNPs had a high predictive power for gastric cancer at a global level and for individuals infected with hpEurope strains. It has potential for clinical use in the management of the H. pylori infection.