Abstract
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, 0.52â2.79) among men, and of an inverse association (OR, 0.76; 95% CI, 0.34â1.84) among women (Pheterogeneity = 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.
Highlights
Colorectal cancer (CRC) is one of the leading causes of cancer mortality worldwide
CRC is tightly associated with chronic inflammation, and inflammatory cells can trigger the production of reactive oxygen species (ROS), which can increase the risk of mutagenesis for nearby cancer cells [3,4]
We recently reported on associations between unconjugated bilirubin (UCB) and CRC risk in the European Prospective Investigation into Cancer and nutrition (EPIC) study and found that higher circulating UCB concentrations, as measured in our lab, were positively associated with CRC risk in men and inversely associated with risk in women [25]
Summary
Colorectal cancer (CRC) is one of the leading causes of cancer mortality worldwide. There were over 1.8 million new cases in 2018, and CRC rates are substantially higher in men than women [1].Oxidative stress, expressed as a constant increased reactive oxygen species (ROS) load, and inflammation are involved in the development of a variety of diseases including cancer [2].CRC is tightly associated with chronic inflammation, and inflammatory cells can trigger the production of ROS, which can increase the risk of mutagenesis for nearby cancer cells [3,4]. Colorectal cancer (CRC) is one of the leading causes of cancer mortality worldwide. There were over 1.8 million new cases in 2018, and CRC rates are substantially higher in men than women [1]. Oxidative stress, expressed as a constant increased reactive oxygen species (ROS) load, and inflammation are involved in the development of a variety of diseases including cancer [2]. CRC is tightly associated with chronic inflammation, and inflammatory cells can trigger the production of ROS, which can increase the risk of mutagenesis for nearby cancer cells [3,4]. CRC might be a candidate for prevention by anti-inflammatory and antioxidant agents. Emerging studies have suggested that endogenous bile pigments such as bilirubin, unconjugated bilirubin (UCB), have substantial anti-inflammatory and antioxidant properties that
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