Retrospective Cohort Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2021; 27(2): 176-188
Published online Jan 14, 2021. doi: 10.3748/wjg.v27.i2.176
Repeatedly elevated γ-glutamyltransferase levels are associated with an increased incidence of digestive cancers: A population-based cohort study
Chang-Hoon Lee, Kyungdo Han, Da Hye Kim, Min-Sun Kwak
Chang-Hoon Lee, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea
Kyungdo Han, Department of Statistics and Actuarial Science, Soongsil University, Seoul 06978, South Korea
Da Hye Kim, Department of Biostatistics, College of Medicine, Catholic University of Korea, Seoul 06591, South Korea
Min-Sun Kwak, Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 06236, South Korea
Author contributions: Kwak MS and Lee CH contributed to the conception and design of the study, interpretation of the data, and drafting of the manuscript; Han K and Kim DH contributed to the acquisition of the data, statistical analysis, table and figure creation and critical revision of the manuscript for important intellectual content.
Institutional review board statement: This study protocol was exempted from review by the Seoul National University Hospital Institutional Review Board because of the retrospective design of the study, and the researchers accessed only de-identified open clinical data for analytical purposes (No. H-1912-022-1085).
Informed consent statement: The subjects’ information in the database was de-identified before the investigator accessed the data, thus informed consent was waived.
Conflict-of-interest statement: The authors declare no 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: Min-Sun Kwak, MD, PhD, Assistant Professor, Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39th FL. Gangnam Finance Center, 737 Yeoksam-dong, Gangnam-gu, Seoul 06236, South Korea.
Received: October 12, 2020
Peer-review started: October 12, 2020
First decision: November 23, 2020
Revised: December 5, 2020
Accepted: December 16, 2020
Article in press: December 16, 2020
Published online: January 14, 2021
Research background

The association between elevated γ-glutamyltransferase (GGT) at a certain point and incident cancer has been suggested; however, no study has studied the association between repeatedly elevated GGT and cancer incidence.

Research motivation

GGT levels are not fixed but dynamic, and many factors affect the level of GGT. Therefore, a single measurement of GGT does not fully reflect the current status of GGT, limiting the understanding of the actual relationship between GGT and diseases. We hypothesized that multiple measurements of GGT over several years could mitigate the limitations of a single measurement.

Research objectives

To elucidate whether repeatedly elevated GGT levels, which are commonly practiced in routine health examinations, can be used as a biomarker of subsequent incidence of digestive cancer.

Research methods

A population-based longitudinal cohort study was conducted with the participants who had undergone health screening from 2009 to 2012 and 4 consecutive previous examinations. GGT points were calculated as the number of times participants met the criteria of quartile 4 of GGT in four serial measurements (0-4 points). Multivariable Cox proportional hazard regression models were applied.

Research results

Among 3559109 participants, 43574 digestive cancers developed during a median of 6.8 years of follow-up. The incidence of total digestive cancers increased according to GGT points in a dose-response manner in men [adjusted hazard ratio (aHR) compared with those with 0 GGT points = 1.28 and 95% confidence interval (CI) = 1.24-1.33 in those with 1 point; aHR = 1.40 and 95%CI = 1.35-1.46 in those with 2 points; aHR = 1.52 and 95%CI = 1.46-1.58 in those with 3 points; aHR = 1.88 and 95%CI = 1.83-1.94 in those with 4 points; P for trend < 0.001]. This trend was more prominent in men than in women and those with healthy habits (no smoking, no alcohol consumption, and a low body mass index) than in those with unhealthy habits.

Research conclusions

Repeatedly elevated GGT levels were associated with an increased risk of incident digestive cancer in a dose-responsive manner, particularly in men and those with healthy habits.

Research perspectives

Repeated GGT measurements may be a good biomarker of incident digestive cancer and could help physicians identify high-risk populations.