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

Background/Aims Gamma-glutamyl transferase (GGT) is a known surrogate marker of hepatic dysfunction and oxidative stress. However, data on its association with pancreatic disease, especially pancreatic cystic neoplasm, is unknown. This study aimed to investigate the association of GGT with the incidence of pancreatic cystic neoplasm.

Participants who received general health checkup by National Health Insurance Service in 2009 were included. Newly diagnosed cases of pancreatic cystic neoplasms from one year after the health checkup to 2020, the end of the study period, were identified. Participants were divided into quartile groups based on GGT levels. Multivariable cox proportional hazard models were used to estimate the risk of pancreatic cystic neoplasms according to GGT quartile (Q1-Q4).

There were 28,940 cases of pancreatic cystic neoplasms among 2,655,665 eligible participants. The incidence rate was 1.09 cases per 1,000 person-years, with a median follow-up of 10.32 (IQR: 10.09-10.58) years. In multivariate regression analysis, adjusted hazard ratios for GGT quartiles using Q1 group as a reference were: 1.043 (95% CI: 1.009-1.079) for Q2, 1.075 (95% CI: 1.039-1.111) for Q3, and 1.138 (95% CI: 1.099-1.178) for Q4.

Higher GGT level was associated with increased risk of pancreatic cystic neoplasms. Therefore, serum GGT levels might have a role as a biomarker for the development of PCN. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study did not receive any funding Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Institutional Review Board (IRB) of Seoul National University Hospital (IRB No. H-2406-052-1542) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes • Institutional email and postal addresses Min Woo Lee, snuhimchief{at}snu.ac.kr, 101, Daehak-ro, Jongno-gu, Seoul, Republic of Korea [03080] Jin Myung Park, youreon.park{at}gmail.com, 156, Baengnyeong-ro, Chuncheon-si, Gangwon-do, Republic of Korea [24289] In Rae Cho, inrae0428{at}snu.ac.kr, 101, Daehak-ro, Jongno-gu, Seoul, Republic of Korea [03080] Kwang Hyun Chung, kwasay{at}gmail.com, 59, Daesagwan-ro, Yongsan-gu, Seoul, Republic of Korea [04401] Jin Ho Choi, jinhochoi{at}snu.ac.kr, 101, Daehak-ro, Jongno-gu, Seoul, Republic of Korea [03080] Woo Hyun Paik, iatrus{at}snu.ac.kr, 101, Daehak-ro, Jongno-gu, Seoul, Republic of Korea [03080] Ji Kon Ryu, jkryu{at}snu.ac.kr, 101, Daehak-ro, Jongno-gu, Seoul, Republic of Korea [03080] Bong Seoung Kim, qhdtjd12{at}gmail.com, 369, Sangdo-ro, Dongjak-gu, Seoul, Republic of Korea [06978] Kyung Do Han, hkd917{at}naver.com, 369, Sangdo-ro, Dongjak-gu, Seoul, Republic of Korea [06978] Sang Hyub Lee, gidoctor{at}snu.ac.kr, 101, Daehak-ro, Jongno-gu, Seoul, Republic of Korea [03080] • Author contribution The corresponding authors, Sang Hyub Lee and Kyung Do Han, have full access to all data of this study and take responsibility for the integrity of the data and the accuracy of the data analysis. Material preparation, data collection, and analysis were performed by Min Woo Lee and Jin Myung Park. The first draft of the manuscript was written by Min Woo Lee and Jin Myung Park. Data Availability All data produced in the present study are available upon reasonable request to the authors