Mutations 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.
Data 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.
MR 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.
Our study suggests mild hyperbilirubinemia is not associated with urinary bladder cancer risk and prognosis.
Germline prognostic markers and gene-environment interaction with smoking for urinary bladder cancer
It has been argued improvements in clinical management of urinary bladder cancer would provide most benefit to both patients and health systems. However, the inclusion of genetic information for disease prognostication has been challenging due to inconsistent findings and overall complexity of genetic variation and observed phenotypes. We aim to further explore the issue by investigating whether there are mutations associated with certain tumour and patient characteristics at the time of diagnosis (that can directly affect prognosis) or cancer recurrence itself. As it has been observed germline variation may have a different effect for smokers and non-smokers, we also aim to investigate whether there is evidence for gene-environment interaction with smoking for baseline characteristics of urinary bladder cancer and/or disease recurrence.
The project is set to last for until September 2019 and will provide evidence that may be further used to calibrate existing urinary bladder cancer management approaches.
|Lead investigator:||Nadezda Lipunova|
|Lead institution:||University of Birmingham|