Influence of environmental factors on gastrointestinal neoplasia in AP
Research type
Research Study
Full title
The influence of environmental factors on neoplasia in adenomatous polyposis (EnGNAP)
IRAS ID
221657
Contact name
Andrew Latchford
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
10 years, 0 months, 0 days
Research summary
Summary of Research
Adenomatous polyposis (AP) is a group of rare genetic disorders that account for less than 1% of all colorectal cancers. Affected patients inherit mutations in one of a number of genes including the adenomatous polyposis coli (APC) gene and the MYH gene and are predisposed to develop multiple pre-cancerous lesions (adenomas) throughout their gastrointestinal (GI) tract. They have almost 100% risk of colorectal cancer by the age of 30-40 years and a 90% risk of duodenal neoplasm with a 10% cancer risk.The current management of AP involves genetic screening, extensive prophylactic surgery in the teenage years followed by lifelong endoscopic GI surveillance. Despite this the recurrence of GI cancer is a significant cause of mortality in patients with AP and the cost of life-long surveillance and surgery is high for both patients and the NHS. Our research aims to investigate the role of environmental factors in AP by examining gut bacteria, cancer genetics, digestive secretions (bile), blood and urinary metabolites in patients with AP and healthy controls.
St Mark’s Hospital is the leading national centre in AP and hosts the longest running and largest polyposis registry in Europe. Following ethical approval, potential participants will be identified from the polyposis registry and NHS waiting lists at Northwick Park and St Mary’s Hospitals. Willing participants will be given information leaflets and time to consider their participation before consenting to the study. Participants would be invited to provide blood, urine and stool samples in the outpatient setting. Further permission would be sought to sample additional GI tissue from endoscopy and collect bile during routine planned endoscopy or surgery. Samples will be collected and analysed in the appropriate laboratories based at the Northwick Park Institute of Medical Research (including Curileum), St Mark’s Hospital, Imperial College London and the Bart’s Cancer Ins
Summary of Results
Our study has demonstrated that duodenal cancer in patients with familial adenomatous polyposis (FAP) (an inherited cancer condition) is not associated with genetic factors or gut bacteria. We have shown that fatty acid metabolism is disrupted in these patients and requires further investigation.We have developed new guidelines for the clinical management of gastric lesions and described the outcomes of surveillance and surgery of duodenal disease in patients with FAP. We have also described the outcomes and risk of ileoanal pouch cancer and management in this patient group.
We have demonstrated the feasibility of growing organoids (mini guts) from stem cells of the duodenum and ileoanal pouch from patients with FAP.
REC name
North West - Greater Manchester West Research Ethics Committee
REC reference
17/NW/0476
Date of REC Opinion
12 Sep 2017
REC opinion
Further Information Favourable Opinion