Retrospective Cohort Study
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World J Gastrointest Oncol. Mar 15, 2023; 15(3): 523-532
Published online Mar 15, 2023. doi: 10.4251/wjgo.v15.i3.523
Risk of pancreatic cancer in individuals with celiac disease in the United States: A population-based matched cohort study
Arunkumar Krishnan, Yousaf Bashir Hadi, Sarah Shabih, Diptasree Mukherjee, Ruhee A Patel, Rushik Patel, Shailendra Singh, Shyam Thakkar
Arunkumar Krishnan, Yousaf Bashir Hadi, Sarah Shabih, Ruhee A Patel, Rushik Patel, Shailendra Singh, Shyam Thakkar, Section of Gastroenterology & Hepatology, West Virginia University School of Medicine, Morgantown, WV 26505, United States
Diptasree Mukherjee, Department of Medicine, Apex Institute of Medical Science, Kolkata 700075, West Bengal, India
Author contributions: Krishnan A conceptualized and designed the research and performed the formal analysis and interpretation of the data; Krishnan A and Hadi YB wrote the original draft and performed the review and editing of the draft; Krishnan A performed a critical revision of the manuscript; and all authors revised the manuscript for important intellectual content and approved the article’s final version, including the authorship list.
Institutional review board statement: TriNetX data have been granted a waiver from the Western institutional review board as a federated network since only aggregated counts and statistical summaries of de-identified information.
Informed consent statement: Not applicable for de-identified data.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
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: Arunkumar Krishnan, MBBS, Doctor, Section of Gastroenterology & Hepatology, West Virginia University School of Medicine, PO Box 9161, 5th Floor HSC, Room 5500, Morgantown, WV 26505, United States.
Received: November 11, 2022
Peer-review started: November 11, 2022
First decision: November 28, 2022
Revised: December 8, 2022
Accepted: February 10, 2023
Article in press: February 10, 2023
Published online: March 15, 2023
Research background

Studies have shown an increased risk for various malignancies, particularly lymphomas, small intestinal adenocarcinoma, and other gastrointestinal malignancies, in celiac disease (CD) patients. However, the magnitude of the risk of pancreatic cancer (PC) in association with CD is much less clear. Nevertheless, despite the magnitude of the risk remaining debatable, the unequivocal association between CD and PC remains.

Research motivation

Although malignancy occurring in the setting of CD has been well recognized; however, there is considerable, but not definitive, evidence that strict compliance to CD is associated with increased risk for the development of PC. Furthermore, owing to the lack of control for known risk factors of PC, any independent associations between these diseases cannot be assessed based on previous studies; given the high incidence of CD and the poor outcomes associated with PC, any such potential association warrants further investigation.

Research objectives

This study aimed to assess the risk of PC in patients with CD.

Research methods

A population-based, multicenter, propensity score-matched cohort study included 155877 patients with CD and 234103 patients without CD (non-CD, controls). To reduce confounding effects, we performed a 1:1 propensity score matching with each patient in the main group to a patient in the control group. The incidence of PC was estimated using a Cox proportional hazards model with a hazard ratio (HR) and 95% confidence interval (CI).

Research results

During the follow-up, 309 patients with CD developed PC, whereas 240 patients developed PC in the control group (HR = 1.29; 95%CI: 1.09-1.53). In the secondary analyses in the first year after diagnosis of CD, patients with CD were at a significant increase in risk for PC; 151 patients with CD had an incidence of PC compared with 96 incidences of PC among the patients in the non-CD control group (HR = 1.56; 95%CI: 1.20-2.01) and sensitivity analysis showed similar magnitude to the one generated in the primary and secondary analysis.

Research conclusions

This multicenter, propensity score-matched cohort study reveals that patients with CD are at increased risk of PC. Risk elevation persists beyond the first year after diagnosis to reference individuals without CD from the general population.

Research perspectives

We still know little about the risk factors and mechanisms contributing to developing malignancies among individuals. Further experimental data and long-term follow-up studies are required to elucidate the pathogenic mechanisms and to ensure better comprehension of the association between PC and CD.