About the PhD thesis

Inflammatory bowel disease (IBD) is a complex chronic inflammatory condition which can result in debilitating symptoms, extraintestinal manifestations and increase the risk of comorbidities. Aetiology of IBD is largely unknown, and greatly varying disease paths suggest complex interplays with environmental factors.
The aims of the studies compiled in this thesis were to evaluate the risk of cancer as an IBD co-morbidity and to elucidate molecular changes in metabolic fingerprint associated with IBD onset.

We performed a systematic review and meta-analysis on risk of cancer in paediatric-onset IBD populations. Following PRISMA guidelines, we systematically searched MEDLINE and Embase and assessed the risk of bias and quality of included studies by means of the Newcastle-Ottawa Scale. To assess rate of cancer overall and by IBD subtype, random-effects model meta-analysis was conducted using the inverse-variance method, calculating pooled relative rates.
Secondly, based on the nationwide Danish registers we performed a population-based study to evaluate the risk of anorectal cancer in fistulising Crohn’s disease.
Finally, we analysed the composition of small metabolite molecules in serum samples by means of liquid chromatography-mass spectrometry (LC-MS) with the aim of defining a profile of the metabolome several years before time of diagnosis with IBD.

Both the systematic review (study I) and the population-based register study (study II) showed an increased risk of cancer associated with paediatric-on-set IBD and fistulising Crohn’s disease, respectively. The untargeted metabolomic analysis found a number of metabolites and specific subclasses to be significantly associated with later development of IBD and was able to predict later development of IBD using machine learning. Inflammatory bowel disease has a complex molecular aetiology that presents several years before clinical onset and time of diagnosis. These same complex molecular processes that lead to aberrant inflammation may also increase the risk of cancer as a later comorbidity.