Serum γ-glutamyl transferase as a novel risk indicator for lung cancer: insights from four million Koreans

Background: γ-glutamyl transferase (GGT) is associated with carcinogenesis, cancer progression, and metastasis. We investigated associations between serum GGT levels and lung cancer in the Korean general population. Methods: Individuals participating in the national health examination in 2012 were screened in the Korean National Health Information Database. Overall, 2,414,755 males and 2,032,241 females aged ≥ 20 years were followed up until December 2022. Of these individuals, 25,728 males and 11,706 females were diagnosed with lung cancer based on health-insurance claims. Serum GGT levels were categorized into quartiles Q1 (low)–Q4 (high) or deciles D1 (low)–D10 (high). Multivariate Cox proportional hazard models were used to estimate the adjusted hazard ratio (aHR) of risk factors for lung cancer. Results: In quartile categories, the highest quartile of serum GGT levels (Q4, males: ≥54 IU/L; females: ≥24 IU/L) had the highest incidence (males: 1.24/1,000 person-years; females: 0.79/1,000 person-years) and risk (males: aHR 1.37, 95% confidence interval [CI] 1.32–1.42; females: aHR 1.13, 95% CI 1.06–1.19) of lung cancer. In the decile categories, the incidence and risk of lung cancer increased with increasing serum GGT levels, resulting in the highest risk of lung cancer in the D10 category (males: ≥93 IU/L, aHR 1.57, 95% CI 1.48–1.67; females: ≥37 IU/L, aHR 1.20, 95% CI 1.10–1.31). Stratified analyses identified age (middle-aged/older adults), smoking status (never/former smokers), or alcohol consumption (non/mild alcohol drinkers [< 10 g/day]) to be prominently associated with higher lung cancer risks. Conclusions: Increased serum levels of GGT correlated with higher risk of lung cancer, even after adjusting for smoking status, alcohol consumption, and chronic liver disease. These effects were more prominent in never/former smokers and in non/mild alcohol drinkers. Clinical trial number: not applicable.