Body size and non-muscle invasive bladder cancer outcome: what do the genes say?
Patients who are diagnosed with non-muscle invasive bladder cancer (NMIBC) have a high chance of a bladder tumour recurrence. Importantly, this recurrent tumour may progress into a more lethal muscle-invasive bladder tumour. That is why the treatment and follow-up program for NMIBC patients is intensive and burdensome.
Currently, it is not possible to accurately predict which patients will develop a recurrence or progression and which will not. Also, it is not well understood which biological processes affect the chances of tumour recurrence and progression.
The relation between the body size measure body mass index (BMI) and NMIBC outcome has been studied in a number of NMIBC patient groups but with inconclusive results. Also, there are almost no studies in NMIBC that look into other measures of body size and body-size related blood measurements like inflammation levels.
Aims and Objectives
We aim to generate evidence on the relation between body size and NMIBC outcome and on the mechanism by which body size affects NMIBC recurrence and progression risk.
Our objectives are to evaluate:
- the causal association between BMI and waist-hip ratio (WHR) and risk of NMIBC recurrence and progression, and
- whether the association between BMI and WHR and NMIBC outcome is due to differences in blood levels of insulin, adipokines or C-reactive protein, which are markers of metabolic and inflammatory activity.
How it will be done
One could study the associations mentioned above by directly measuring body size and inflammatory and metabolic blood levels in a group of NMIBC patients. However, it is then difficult to draw conclusions on causality of the associations due to the potentially disturbing effects of other (unmeasured) variables (e.g. smoking status).
To prevent these so-called biased or invalid results, we will measure body size measures and blood-based markers indirectly, by measuring the germline, heritable DNA variants that affect them. This is a so-called Mendelian randomization study, referring to the fact that this type of study mimics the randomized controlled trial, the gold-standard study design to obtain strong evidence on causal associations.
Importantly, the required data from large numbers of NMIBC patients for which germline DNA variation measurements and NMIBC outcome are available, are already to our disposal via existing collaborations (4,900 NMIBC patients). We will apply three different, well-established Mendelian randomization analyses to reach our objectives.
NMIBC is the major subtype of bladder cancer, the seventh most prevalent cancer worldwide. This project will provide important insights into the causal relation between body size, metabolic and inflammation markers, and risk of NMIBC recurrence and progression. This topic is ever more relevant given the increased proportion of people that are overweight or obese.
The insights resulting from our study can be used to elucidate if body size measurements and related blood-based markers can be used to improve the accuracy of the prediction of prognosis for NMIBC patients and whether changing body size or related blood markers through lifestyle or medical interventions can improve the prognosis for NMIBC patients.
We will efficiently use existing genetic data to generate evidence on the potential relation between body size and outcome in non-muscle invasive bladder cancer and create insights into its underlying mechanisms.
Dr Sita Vermeulen