Mobiele menu

Molecular adenoma features to predict colorectal cancer risk

Projectomschrijving

Het voorkomen van overdiagnostiek na coloscopie

Doel

Na het verwijderen van een gevorderde darmpoliep vindt er met tussenposen een kijkonderzoek (coloscopie) plaats om te controleren of zich misschien een tumor ontwikkelt. Uit wetenschappelijk onderzoek is gebleken dat lang niet alle gevorderde poliepen zullen ontaarden in kanker, en dat poliepen die tot kanker leiden specifieke afwijkingen hebben in hun DNA. Wat is het risico op darmkanker bij patiënten waarbij een gevorderde poliep is weggehaald?

Aanpak/werkwijze

Er wordt gekeken naar de aanwezigheid van DNA afwijkingen in poliepen van patiënten die wel en die niet darmkanker ontwikkelen.

(Verwachte) resultaten

Het onderzoek moet leiden tot een test waarmee in de oorspronkelijke poliep bepaald kan worden of er in de toekomst een groot of een klein risico op darmkanker is. Bij een klein risico worden controle coloscopieën wellicht overbodig waardoor het aantal onnodige coloscopieën vermindert.

Verslagen


Samenvatting van de aanvraag

Problem description: The best way to reduce colorectal cancer (CRC) death is by early detection of the disease. This can be achieved in two ways, by screening asymptomatic individuals and by surveillance after detection and removal of at least one adenoma (post-polypectomy surveillance). To evaluate efficacy of CRC screening and surveillance on CRC-death reduction, intermediate endpoints are currently used. Advanced adenoma, defined on the basis of size and histology, is currently the most widely used intermediate endpoint. How well this intermediate endpoint reflects the long-term risk of dying from CRC is unclear. Although very prevalent, only approximately 5% of adenomas will progress to cancer. Experts agree that advanced adenomas as intermediate endpoint overestimate cancer risk, resulting in unnecessary surveillance colonoscopies. Hypothesis: We have shown that specific DNA copy number aberrations are associated with risk of adenoma-to-carcinoma progression and that these aberrations are present in only a subset of advanced adenomas. Therefore, we hypothesize that specific DNA copy number aberrations better predict the risk of developing cancer than the advanced adenoma phenotype, and thus are better intermediate endpoints for evaluating the risk of developing metachronous CRC. Aim: To investigate whether molecularly-defined high risk adenomas are better intermediate endpoints for post-polypectomy surveillance than the current advanced adenoma intermediate endpoint, by means of molecular profiling followed by Health Technology Assessment (HTA) modeling. Plan of investigation: In this study, we will compare the risk of individuals developing metachronous CRC during surveillance, when considering molecularly-defined high-risk adenomas versus advanced adenomas based on size and histology intermediate endpoints. We will: 1) characterize DNA copy number changes in a large retrospective series of advanced and non-advanced adenomas, for which long-term follow-up is available, 2) define which adenomas are molecularly high-risk, and 3) determine which individuals developed metachronous CRC. As all clinical tissues are readily available and standard available techniques are being used, the molecular analysis can be performed in a very timely manner. Based on these results, we will model surveillance strategies using molecularly-defined high-risk intermediate endpoints and compare it to current surveillance and define the best strategy to use. Expected outcome: This project will quantify the impact of using DNA copy number changes as intermediate endpoint in post-polypectomy surveillance. If molecularly-defined intermediate endpoints prove to be more accurate in assessing the risk of metachronous CRC than advanced adenomas do, then it will translate to less post-polypectomy colonoscopies and reduce patient burden (less discomfort and less complications). This will have a great impact on the efficacy of surveillance, reducing its costs and improving quality of life of patients. At the end of this project, we will have defined the optimal surveillance strategy, using molecular features as intermediate endpoints, which can form the basis for updating the surveillance guidelines. As the molecular intermediate endpoint can be determined by standard molecular analysis in tissues, standard application in post-polypectomy surveillance could be easily implemented.

Kenmerken

Projectnummer:
531002023
Looptijd: 100%
Looptijd: 100 %
2019
2022
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
B. Carvalho
Verantwoordelijke organisatie:
Nederlands Kanker Instituut