Serum bilirubin levels and risk of colorectal cancer in Korean adults: results from the Korean Genome and Epidemiology Study-Health Examinee (KoGES-HEXA) Cohort Study.

Background: Current evidence on associations between circulating bilirubin and colorectal cancer (CRC) risk is inconsistent.
Methods: In this prospective study, we investigated associations of pre-diagnostic circulating levels of total and indirect bilirubin with CRC risk in 78,467 Korean adults aged 40-78 years at recruitment, considering potential non-linearity and sex differences. Hazard ratios (HR) and 95% confidence intervals (CI) for associations with CRC risk were estimated with Cox proportional hazard regression.
Results: During a median 7.9-year follow-up, 539 incident CRC cases were recorded. In multivariable-adjusted models, higher levels of total bilirubin were associated with a 26% (CI: 42% to 7%) lower risk of CRC among men and women combined, comparing the highest with the lowest tertile (P-linear trend = 0.003). A U-shaped association was observed in men, with the lowest risk at approximately 0.8 mg/dL (=13.7 μmol/L) of total bilirubin (P for non-linearity = 0.01). Although the association was largely null in women, there was no evidence for effect modification by sex (P-interaction = 0.73). Associations between indirect bilirubin and CRC risk were similar.
Conclusions: Higher circulating levels of total and indirect bilirubin were inversely associated with the risk of CRC among Korean adults. The associations were strongly inverse and U-shaped among men.
Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate This research was conducted according to the principles expressed in the Declaration of Helsinki. All study participants provided informed consent. Ethical approval was obtained from the IRBs of Seoul National University and collaborating centres of the KoGES groups, and an additional ethical approval specifically for this project was obtained from the IRB of Seoul National University College of Medicine/Hospital (Reference no.: E1810-006-974). Consent for publication The manuscript does not contain any individual person’s data. All reasonable measures have been taken to ensure the anonymity of study participants.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)