Published online Jan 14, 2021. doi: 10.3748/wjg.v27.i2.176
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
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.
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.
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.
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.
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.
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.
Repeated GGT measurements may be a good biomarker of incident digestive cancer and could help physicians identify high-risk populations.