Serum bilirubin subgroups and cancer risk: Insights with a focus on lung cancer.

Background: Bilirubin is a potent antioxidant that neutralizes reactive oxygen species (ROS). While previous studies have predominantly focused on the association between total bilirubin and cancer risk, this study evaluates the association of different bilirubin subgroups with cancer risk in men and women.

Methods: Data were derived from the Korean Cancer Prevention Study-II cohort, including 133,630 participants. Over a mean follow-up of 13.5 years, 9876 cancer cases were identified. Serum bilirubin levels (total, indirect, direct) were categorized into sex-specific quartiles and analyzed. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI), along with trend analyses.

Results: In men, a 1 standard deviation (SD) increase in total bilirubin was inversely associated with lung cancer risk (HR: 0.82, 95 % CI: 0.74-0.91), and direct bilirubin showed an inverse association (HR: 0.83, 95 % CI: 0.74-0.93). In contrast, in women, a 1 SD increase in total bilirubin was positively associated with lung cancer risk (HR: 1.15, 95 % CI: 1.00-1.32). Among male smokers, a 1 SD increase in total bilirubin (≥30 cigarettes/day) was inversely associated with lung cancer risk (HR: 0.73, 95 % CI: 0.55-0.97), and a 1 SD increase in direct bilirubin (10-19 cigarettes/day) showed an inverse association (HR: 0.79, 95 % CI: 0.63-0.99).

Conclusions: In men, both total and direct bilirubin levels were inversely associated with lung cancer risk, whereas in women, total bilirubin was positively associated with lung cancer risk.