Is bilirubin a marker of vascular disease and/or cancer and is it a potential therapeutic target?

Normal aerobic metabolism is associated with reactive oxygen species (ROS) that can damage cellular macromolecules. Analogous free radicals are formed by exposure to ionizing radiation and many dietary products are considered to contain free radical generators. During the past 15 years epidemiological studies and animal experiments have identified bilirubin as a molecule at the crossroads of the protection of the body against ROS. The studies have focused on bilirubin as a biomarker of arterial disease. This review assesses the current state of evidence and sets the data in context. There is no definitive evidence from prospective studies of a causal protective effect from bilirubin in arterial disease or that various genetic polymorphisms, (particularly the 7/7 UGT1A1 repeat polymorphism) impacts coronary artery disease. There is no definitive evidence that high bilirubin levels confer protection against cancer. There is some preliminary evidence that bilirubin may have a protective effect in lung disease and stroke, but the reports have yet to be confirmed. The role of various genotypes of UGT1A1 and HMOX1, if any, in cancer is unclear.