Serum gamma-glutamyl transferase level is associated with the risk of pancreatic cystic neoplasms: A nationwide retrospective cohort study

doi:10.3748/wjg.v31.i40.110932

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

World J Gastroenterol. Oct 28, 2025; 31(40): 110932
Published online Oct 28, 2025. doi: 10.3748/wjg.v31.i40.110932

Serum gamma-glutamyl transferase level is associated with the risk of pancreatic cystic neoplasms: A nationwide retrospective cohort study

Min Woo Lee, Jin Myung Park, In Rae Cho, Kwang Hyun Chung, Bong Seong Kim, Jin Ho Choi, Woo Hyun Paik, Ji Kon Ryu, Kyungdo Han, Sang Hyub Lee

Min Woo Lee, In Rae Cho, Jin Ho Choi, Woo Hyun Paik, Ji Kon Ryu, Sang Hyub Lee, Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, South Korea

Jin Myung Park, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon 24289, South Korea

Kwang Hyun Chung, Department of Internal Medicine, Soon Chun Hyang University Hospital, Seoul 04401, South Korea

Bong Seong Kim, Kyungdo Han, Department of Statistics and Actuarial Science, Soongsil University, Seoul 06978, South Korea

Co-first authors: Min Woo Lee and Jin Myung Park.

Co-corresponding authors: Kyungdo Han and Sang Hyub Lee.

Author contributions: Lee MW and Park JM contributed equally as co-first authors, participated in the formal analysis, investigation, and wrote the original draft; Kim BS and Han K were responsible for developing the methodology; Cho IR, Chung KH, Choi JH, Paik WH, Ryu JK, Han K, and Lee SH participated in the review and editing; Han K and Lee SH designed the study and acquired funding, contributed equally as co-corresponding authors. All authors approved the final version to publish.

Institutional review board statement: This study was approved by the Institutional Review Board of Seoul National University Hospital, No. H-2406-052-1542.

Informed consent statement: The information on the subjects stored in the database was de-identified before the researchers accessed the data. Therefore, informed consent was waived for this study.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for 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.

Data sharing statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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: Sang Hyub Lee, MD, PhD, Professor, Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, South Korea. gidoctor@snu.ac.kr

Received: June 19, 2025
Revised: July 29, 2025
Accepted: September 16, 2025
Published online: October 28, 2025
Processing time: 130 Days and 17.2 Hours

Abstract

BACKGROUND

Gamma-glutamyl transferase (GGT) is a known surrogate marker of hepatic dysfunction and oxidative stress. It has recently been reported to be associated with metabolic diseases, cardiovascular diseases, and malignancies including pancreatic cancer. However, data on its association with pancreatic cystic neoplasm (PCN), is unknown.

AIM

To investigate the association of GGT with the incidence of PCN.

METHODS

In this nationwide retrospective cohort study, participants who received general health checkup by National Health Insurance Service in 2009 were included. Newly diagnosed PCNs from one year after the checkup to 2020 were identified. Participants were divided into quartiles based on GGT levels. Multivariable cox proportional hazard models estimated the risk of PCNs according to GGT quartiles (Q1-Q4). Subgroup analyses by age, sex, and comorbidities, and sensitivity analyses varying lag periods and GGT categorizations were performed.

RESULTS

There were 28940 cases of PCNs among 2655665 eligible participants. The incidence rate was 1.09 cases per 1000 person-years, with a median follow-up of 10.32 (interquartile range: 10.09-10.58) years. In multivariate regression analysis, adjusted hazard ratios for GGT quartiles using Q1 group as a reference were: 1.04 [95% confidence interval (CI): 1.005-1.075] for Q2, 1.065 (95%CI: 1.03-1.102) for Q3, and 1.109 (95%CI: 1.07-1.15) for Q4. Subgroup analysis showed consistent results across age, sex, and comorbidities. In sensitivity analyses, the association remained robust even at 3-year and 5-year lag periods. A clear dose-response relationship was also observed when using GGT deciles (All P for trend < 0.001).

CONCLUSION

Higher GGT level is associated with increased risk of PCNs. Therefore, serum GGT levels might have a role as a biomarker for the development of PCNs.

Keywords: Pancreatic cystic neoplasm; Gamma-glutamyl transferase; Biomarker; Cohort study; Epidemiology

Core Tip: Gamma-glutamyl transferase (GGT), a marker of oxidative stress and hepatic dysfunction, has been reported to be associated with metabolic diseases and malignancies including pancreatic cancer. However, its role in pancreatic cystic neoplasm (PCN) has not been investigated. In this nationwide retrospective cohort study of over 2.6 million people, higher serum GGT levels were independently associated with an increased risk of PCN. This association remained robust in subgroup and sensitivity analyses when adjusting for lag period and GGT categorization. This is the first large-scale study suggesting GGT as a potential biomarker for identifying individuals at high risk of PCN.