Emerging studies have suggested that bilirubin, particularly unconjugated bilirubin (UCB), has substantial anti-inflammatory and antioxidant properties that protect against oxidative stress-associated diseases such as cancer. Few observational studies have investigated the etiological role of bilirubin in colorectal cancer (CRC) development. In this case-control study, nested in the population-based prospective cohort of the Cooperative Health Research in the Region of Augsburg (KORA) study in south Germany, pre-diagnostic circulating UCB concentrations were measured by high-performance liquid chromatography in 77 CRC cases and their individually matched controls. Multivariable unconditional logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for associations between log-transformed UCB levels (log-UCB), standardized per one-standard-deviation (one-SD) increment, and CRC risk. The models were a priori stratified by sex based on previous evidence. In the fully adjusted models, each one-SD increment in log-UCB was indicative of a positive association with CRC risk (OR, 1.20; 95% CI, 0.52-2.79) among men, and of an inverse association (OR, 0.76; 95% CI, 0.34-1.84) among women (P-heterogeneity = 0.4 for differences between men and women). We found little evidence for sex-specific associations of circulating bilirubin with CRC risk, and further studies are needed to confirm or refute the potential associations.
GrantsState of Bavaria Helmholtz Zentrum Munchen, German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF) European Commission, BBMRI-LPC (FP7) Austrian Science Fund (FWF) French National Cancer Institute (INCa)