Negative correlation of high serum bilirubin with cancer development in adults without hepatobiliary disease

This study aimed to evaluate whether serum bilirubin levels were associated with cancer development in a population without liver disease.

A retrospective longitudinal study was performed by including participants who underwent a health checkup at St. Luke's International Hospital in Tokyo from 2005 to 2019. We excluded those with liver diseases or prior history of cancer at baseline. All participants were classified into four groups according to their total bilirubin (T-Bil) level: very low (<0.5 mg/dl), low (≥0.5 mg/dl, <1.0 mg/dl), intermediate (≥1.0 mg/dl, <1.5 mg/dl), and high (≥1.5 mg/dl). Our primary outcome was to observe cancer development. This study received IRB approval (19-R041).

A total of 77 855 patients were included. During a median follow-up of 1751 days, 5110 participants developed some type of cancer during the study period. Compared to the very-low group, odds ratio (OR) for developing any type of cancer in a concentration-dependent manner decreased as the T-Bil category shifted to higher groups: OR 0.89, 95% confidence interval (CI) 0.79-1.01 for low group; OR 0.81, 95% CI 0.71-0.94 for intermediate group, and OR 0.80, 95% CI 0.65-0.99 for high group. In terms of secondary outcome, neoplasms of the female genital organs showed the same trend; OR 0.69, 95% CI 0.51-0.93 for low group; OR 0.63, 95% CI 0.44-0.92 for intermediate group, and OR 0.52, 95% CI 0.24-1.09 for high group.

Increased serum bilirubin negatively correlated with cancer development in a concentration-dependent manner, especially for neoplasms of the female genital organs.