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
Research background

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide. Lacking effective methods for screening, the early diagnosis of PDAC remains challenging leading to an extremely poor prognosis of PDAC.

Research motivation

Single nucleotide polymorphisms based genetic risk score (GRS) has been proven to provide independent inherited risk information in other cancers. GRS may be a promising way to select a high risk PDAC population for further screening.

Research objectives

We constructed a GRS based on 18 PDAC related single nucleotide polymorphisms, and we evaluated the effectiveness of GRS in the prediction of PDAC risk.

Research methods

We used personal genotyping data to calculate individual GRS. GRS was also weighted by population odds ratio. Final GRS was evaluated for the prediction of PDAC risk in the general Chinese population.

Research results

GRS was significantly associated with PDAC risk after being adjusted for age and sex (odds ratio = 1.36, 95% confidence interval: 1.06-1.74, P = 0.015). Higher GRS indicated a higher risk for PDAC (odds ratio = 2.29, 95% confidence interval: 1.25-4.21, P = 0.007, highest decile vs lowest decile). The area under the curve for GRS for PDAC risk was 0.5675.

Research conclusions

GRS was an independent predictor of PDAC. As reflecting inherited risks, patients with higher GRS would have higher risks of PDAC in the study population.

Research perspectives

GRS could provide independent risk information for PDAC. Further cohort study with a larger sample size may focus on the optimal PDAC risk prediction model built with both GRS and nongenetic factors.