Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2020; 26(22): 3076-3086
Published online Jun 14, 2020. doi: 10.3748/wjg.v26.i22.3076
Single-nucleotide polymorphisms based genetic risk score in the prediction of pancreatic cancer risk
Xiao-Yi Wang, Hai-Tao Chen, Rong Na, De-Ke Jiang, Xiao-Ling Lin, Feng Yang, Chen Jin, De-Liang Fu, Jian-Feng Xu
Xiao-Yi Wang, Feng Yang, Chen Jin, De-Liang Fu, Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai 200040, China
Hai-Tao Chen, De-Ke Jiang, State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Rong Na, Shanghai Medical College, Fudan University, Shanghai 200043, China
Rong Na, Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
Xiao-Ling Lin, State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai 200433, China
Jian-Feng Xu, Program for Personalized Cancer Care and Department of Surgery, North Shore University Health System, Evanston, IL 60201, United States
Author contributions: Wang XY, Chen HT and Na R contributed equally to this study; Wang XY, Na R, Xu JF, Fu DL, Jin C and Yang F designed the research; Wang XY, Chen HT, Na R and Lin XL performed the research; Xu JF and Chen HT contributed analytic methods; Jiang DK and Xu JF contributed control group data; Wang XY, Chen HT and Lin XL analyzed the data; Wang XY and Na R wrote the paper.
Institutional review board statement: The study was reviewed and approved by the Shanghai Huashan Hospital Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
STROBE statement: The authors have read the STROBE Statement Checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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:
Corresponding author: De-Liang Fu, MD, PhD, Doctor, Professor, Surgical Oncologist, Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University, No. 12, Central Urumqi Road, Shanghai 200040, China.
Received: December 30, 2019
Peer-review started: December 30, 2019
First decision: January 11, 2020
Revised: April 29, 2020
Accepted: May 13, 2020
Article in press: May 13, 2020
Published online: June 14, 2020

Disease-related single nucleotide polymorphisms (SNPs) based genetic risk score (GRS) has been proven to provide independent inherited risk other than family history in multiple cancer types.


To evaluate the potential of GRS in the prediction of pancreatic cancer risk.


In this case-control study (254 cases and 1200 controls), we aimed to evaluate the association between GRS and pancreatic ductal adenocarcinoma (PDAC) risk in the Chinese population. The GRS was calculated based on the genotype information of 18 PDAC-related SNPs for each study subject (personal genotyping information of the SNPs) and was weighted by external odd ratios (ORs).


GRS was significantly different in cases and controls (1.96 ± 3.84 in PDACs vs 1.09 ± 0.94 in controls, P < 0.0001). Logistic regression revealed GRS to be associated with PDAC risk [OR = 1.23, 95% confidence interval (CI): 1.13-1.34, P < 0.0001]. GRS remained significantly associated with PDAC (OR = 1.36, 95%CI: 1.06-1.74, P = 0.015) after adjusting for age and sex. Further analysis revealed an association of increased risk for PDAC with higher GRS. Compared with low GRS (< 1.0), subjects with high GRS (2.0) were 99% more likely to have PDAC (OR: 1.99, 95%CI: 1.30-3.04, P = 0.002). Participants with intermediate GRS (1.0-1.9) were 39% more likely to have PDAC (OR: 1.39, 95%CI: 1.03-1.84, P = 0.031). A positive trend was observed (P trend = 0.0006).


GRS based on PDAC-associated SNPs could provide independent information on PDAC risk and may be used to predict a high risk PDAC population.

Keywords: Pancreatic cancer, Single nucleotide polymorphisms, Genetic risk score, Chinese population, Genome-wide association study

Core tip: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with no effective method for early diagnosis and high-risk population screening. In this pioneer study, we evaluated single nucleotide polymorphisms based genetic risk score (GRS) in the prediction of PDAC risk. Our results revealed that GRS was significantly associated with PDAC. Compared with low GRS (< 1.0), subjects with high GRS (2.0) were 99% more likely to be PDAC. Although further verification is needed, our study suggested that GRS was an independent risk factor for PDAC.