Changes in Stem Cells of the Colon in Response to Increased Risk of Colorectal Cancer

Study Overview
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Brief Summary
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Colorectal cancer is a common disease worldwide. Increasing evidence is demonstrating that colorectal cancers arise from 'cancer stem cells.' Stem cells in the colon reside at the bottom of thousands of microscopic crypts throughout the wall of the colon. They create all the cells lining the bowel wall. These cells are created in the base of the crypt and ascend to the top acquiring the characteristics of mature cells of the bowel wall as they ascend. It is now thought that colorectal cancer cells arise from stem cells where the genetic material regulating growth and division of the stem cell has become defective. This leads to unregulated production of cells which in turn have defective genetic information and cancer formation. Prior studies have demonstrated that the earliest changes before a cancer develops are changes in cellular proliferation. Now that reliable markers to identify stem cells have been found, the researchers aim to investigate stem cell numbers and changes in distribution in those at normal risk of colorectal cancer and those at higher risk. The researchers hypothesise that changes in cellular proliferation at the top of the crypt in individuals at higher risk of colorectal cancer are due to a change in the number of stem cells in the crypt base.

Official Title
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Changes in Stem Cells of the Colon in Response to Increased Risk of Colorectal Cancer

Conditions
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Colorectal Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Referred for endoscopy at participating centre Exclusion Criteria: Age <16 or >85 Familial polyposis syndrome Lynch syndrome Known colorectal tumour Previous colorectal resection Pregnancy Chemotherapy in last 6 months Therapy with aspirin/other nonsteroidal anti-inflammatory drug (NSAID) Other immunosuppressive medication Incomplete left sided examination Colorectal carcinoma found at endoscopy Iatrogenic perforation at endoscopy Colorectal cancer on histology Microscopic colitis on histology For the colitis group Simple clinical colitis activity index (SCCAI) score > 5

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adenomatous polyp<br>Patients who have begun the polyp-cancer sequence (ie. are in polyp surveillance after excision of a prior adenomatous polyp) will be used to test those patients at higher risk of colorectal. | |
| Patients at normal risk of cancer<br>Patients found to have endoscopically and histological normal mucosa. | |
| Ulcerative colitis<br>Patients who are under surveillance for known ulcerative colitis will be used to test those patients at higher risk of colorectal. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of stem cells in the colonic crypt |  | On day of endoscopy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stem cell position in colonic crypt |  | On day of endoscopy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer, Stem cells, Ulcerative colitis, Polyps