Bilirubin is not associated with urinary bladder cancer risk and prognosis: A Mendelian Randomization Study in the UK Biobank

BackgroundMutations in UGT1A gene have been associated with the development and prognosis of urinary bladder cancer (UBC). UGT1A proteins are involved in a spectrum of detoxification processes, hence the biological mechanism between UGT1A and UBC is difficult to elucidate. Concurrently, mild hyperbilirubinemia, caused by alterations in UGT1A, has been associated with multiple health outcomes. We have investigated the potential effect of mild hyperbilirubinemia on UBC risk and prognosis, using a Mendelian Randomization (MR) approach in the UK Biobank. MethodsData on 1,281 UBC patients and 4,071 controls was available for a two-stage least squares MR estimation with rs6742078 as an instrumental variable. First, linear regression was fitted to establish the relationship between the rs6742078 and bilirubin levels (total and unconjugated). Secondly, bilirubin values were used to predict tested outcomes under a logistic model. Both stages were adjusted for participant sex, smoking status, and age. ResultsMR analysis showed no significant effects of bilirubin levels on UBC risk (total bilirubin: OR=1.02, 95% CI: 0.99-1.04; unconjugated bilirubin: OR=1.02, 95% CI: 0.99-1.05). No effects were observed for events of UBC recurrence, progression, or survival. ConclusionOur study suggests mild hyperbilirubinemia is not associated with urinary bladder cancer risk and prognosis.