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Predicting what happens after surgery for patients with FAP, a rare genetic condition that increases risk of bowel cancer

Lead researcher: Miss Roshani Patel

Location: Imperial College London

Grant award: £16,250

Dates: April 2019 to April 2020

Familial adenomatous polyposis (FAP) is a rare genetic condition that greatly increases a person’s chance of developing bowel cancer. Roshani Patel, our Bowel Cancer UK/RCS Research Fellow, explored why some people with FAP are still at risk of developing bowel cancer following surgery.

The challenge

People with FAP have a large number of pre-cancerous growths (polyps) in the lining of the bowel, which means they have a very high chance of developing bowel cancer in the large bowel. Most people with FAP will have surgery to remove all or part of the large bowel, as a way of preventing bowel cancer. As part of this process, surgeons sometimes create a ‘pouch’ from the small bowel, which acts like a rectum and means people can still go to the toilet in the usual way. This type of surgery is known as restorative proctocolectomy. Before the pouch is made FAP patients don’t have small bowel polyps. However, 10 years after surgery around half of these patients will have developed polyps in their pouch. This means they may need further treatment and are at risk of developing cancer. At the moment we can’t predict which patients might go on to develop polyps and therefore who would benefit from extra monitoring, which can be invasive and expensive.

The science behind the project

Miss Patel used a variety of methods, including studying cells, growing 'miniguts', genetics and computer modelling in the lab to investigate why these polyps develop. She also looked into how the organisms and other substances inside the pouch (such as bacteria and bile) might influence how polyps turn into cancer.

Results

By looking at patient data, Miss Patel developed a scoring system to predict 10-year risk, which can be used to decide how much monitoring patients need after their surgery. She also looked at the genetic “fingerprints” of mutations in polyps and saw differences between the upper and lower parts of the pouch.

If you like, you can find out more about this work by reading this key research article, published by the researchers.

Other impact

Miss Patel attended the 2019 InSiGHT meeting of the International Society for Gastrointestinal Hereditary Tumours and presented several papers, sharing her research on FAP and pouches.

She has also collaborated with other departments and institutes to access more patient samples and further develop techniques.

What difference will this project make?

There are several different types of surgery that someone with FAP could have. Improving knowledge of the longer-term consequences of pouch surgery means better, more tailored decisions about surgery can be made and improved planning of post-surgery surveillance, reducing the chances of cancer developing in the future. Greater understanding about how and why polyps develop into cancer in this group of patients could also help improve understanding of how bowel cancer develops in the general population. This research therefore has the potential to benefit many more people affected by bowel cancer.

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