PO-063 Pre-diagnostic unconjugated bilirubin levels and colorectal cancer risk in the european prospective investigation into cancer and nutrition (EPIC)

Abstract

IntroductionUnconjugated Bilirubin (UCB), the end product of heme catabolism, is a powerful antioxidant. A mild chronic elevation of circulating UCB, known as Gilbert’s Syndrome (GS), is a relatively common condition affecting 5%–10% (depending on ethnicity and gender) of the adult population. Individuals with endogenously elevated UCB appear to be at lower risk of developing certain diseases where oxidative stress has been implicated in the disease process, such as cancer.Material and methodsWe investigated the association between pre-diagnostic plasma UCB concentrations and risk of colorectal cancer (CRC) development in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, a multicenter prospective study carried out in 23 centres from 10 European countries including 5 19 978 participants.Plasma UCB was measured by High Performance Liquid Chromatography (HPLC) in 1387 cases and 1387 controls matched on age, centre, follow-up time, time of blood collection, fasting status and menopausal status in women.Odds ratios (OR) and 95% confidence intervals (CI) for CRC risk were estimated using multivariable conditional logistic regression models stratified by sex, which were adjusted for potential confounders. UCB was Log2- transformed when used as a continuous variable to improve linearity.Results and discussionsIn a multivariable model that included potential confounding factors, higher Log2- transformed UCB, corresponding to a doubling of UCB concentration, was associated with increased CRC risk in men (OR=1.27; 95% CI: 1.05,1.52; p=0.01) whereas an inverse association with CRC risk was observed in women (OR=0.83; 95% CI: 0.70,0.99; p=0.04).ConclusionThese results suggest that higher levels of circulating UCB may confer protection against CRC in women but may elevate risk in men. Additional studies are necessary to confirm these findings and to further investigate potential underlying mechanisms for the role of circulating UCB in CRC development.