Liver Function Biomarkers and Lung Cancer Risk: A Prospective Cohort Study in the UK Biobank

ABSTRACT Background As the primary organ of metabolism and detoxification, the liver may contribute to the pathogenesis of lung cancer. We aimed to illuminate the intricate link between liver function biomarkers and lung cancer risk, as well as delineate the role of smoking behavior within this association. Methods We investigated the associations of seven liver function biomarkers levels (alkaline phosphatase [ALP], alanine transaminase [ALT], total bilirubin [TBIL], albumin [ALB], gamma‐glutamyltransferase [GGT], aspartate transaminase [AST], and total protein [TP]) with lung cancer risk across the UK Biobank (N = 337 499) through restricted cubic splines and Cox proportional hazards models. Moreover, Mendelian randomization (MR) was utilized to evaluate the causal effect of smoking behavior on these biomarkers. Then a lung cancer risk prediction model was developed among smokers by backward stepwise logistic regression. Results During a median follow‐up of 13.3 years, 3003 lung cancer cases were identified. We found ALP levels positively associated with lung cancer risk, whereas ALT, TBIL, ALB, and AST were inversely correlated; TP exhibited a U‐shaped association, whereas GGT displayed a mirrored J‐shaped relationship. These associations were amplified among smokers. MR analysis indicated that smoking behavior could increase ALP (odds ratio [OR]: 1.05) and GGT (OR: 1.15) levels while decreasing TBIL (OR: 0.92), ALB (OR: 0.92), and TP (OR: 0.96) levels. The lung cancer risk model incorporating these biomarkers in smokers demonstrated robust discrimination. Conclusion Our finding provides perspectives and evidences towards the intricate crosstalk between the hepatic and pulmonary systems, as well as the processes through which tobacco catalyzes lung carcinogenesis.