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

NCT01075893 | Completed

• 1 other identifier: McCallum-001
• Study Type: observational
• Target: 11
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

Colorectal cancer; Stem cells; Ulcerative colitis; Polyps

Outcome Measures

Primary Outcomes (1)

• Number of stem cells in the colonic crypt

  On day of endoscopy

Secondary Outcomes (1)

• Stem cell position in colonic crypt

  On day of endoscopy

Study Arms (3)

Adenomatous polyp

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

Patients found to have endoscopically and histological normal mucosa.

Ulcerative colitis

Patients who are under surveillance for known ulcerative colitis will be used to test those patients at higher risk of colorectal.

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients referred for lower gastrointestinal (GI) endoscopy at a participating centre will be considered for inclusion. Patients with a previous adenomatous polyp resection under surveillance will be considered for inclusion to the polyp group. Patients with ulcerative colitis under surveillance will be considered for inclusion to the ulcerative colitis group.

You may qualify if:

• Referred for endoscopy at participating centre

You may not qualify if:

• 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

Sponsors & Collaborators

• Newcastle University: lead
• Northumbria Healthcare NHS Foundation Trust: collaborator

Study Sites (2)

Wansbeck General Hospital

Ashington, Tyne & Wear, NE63 9JJ, United Kingdom

Location

North Tyneside Hospital

North Shields, Tyne & Wear, NE29 8NH, United Kingdom

Location

Related Publications (2)

• Dronamraju SS, Coxhead JM, Kelly SB, Burn J, Mathers JC. Cell kinetics and gene expression changes in colorectal cancer patients given resistant starch: a randomised controlled trial. Gut. 2009 Mar;58(3):413-20. doi: 10.1136/gut.2008.162933. Epub 2008 Oct 31.

  PMID: 18978177 BACKGROUND

• Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007 Oct 25;449(7165):1003-7. doi: 10.1038/nature06196. Epub 2007 Oct 14.

  PMID: 17934449 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Rectal pinch biopsies - x 9 (10 cm from anal verge)

MeSH Terms

Conditions

Colorectal Neoplasms; Colitis, Ulcerative; Polyps

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Colitis; Gastroenteritis; Inflammatory Bowel Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Iain JD McCallum, MBChB MRCS

  Newcastle University, UK

  PRINCIPAL INVESTIGATOR

• John C Mathers, PhD

  Newcastle University, UK

  STUDY CHAIR

• Seamus B Kelly, MD FRCS

  Newcastle University, UK

  STUDY DIRECTOR

• Mike Bradburn, MD FRCS

  Northumbria NHS foundation trust

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2010
• First Posted: February 25, 2010
• Study Start: February 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: October 31, 2017

Record last verified: 2016-03

Locations

GB (2)