To Investigate Risk of Colorectal Neoplasms in First-degree Relatives of Patients With Non-advanced Adenomas

NCT02521727 | Completed DMC

• 1 other identifier: NonAA
• Study Type: observational
• Target: 828
• Locations: 1 country
• Sites: 2

Brief Summary

The risk of CRC in families of patients with CRC is well established, but it is less well-defined for families of patients with adenomas. Screening recommendations to families when an index subject has an adenoma on colonoscopy are not clear. Previous studies demonstrating an increased CRC risk in close relatives of subjects with adenomas were mostly limited by the lack of a suitable comparison group, did not offer colonoscopy to all relatives or did not have verification on true status of adenoma history in the relatives. A systematic review has reported that most studies cited for risk of CRC in relatives with adenomas have not addressed the intended question. Currently International guidelines recommended screening colonoscopy in close relatives and at a younger age when there is a proband with an adenoma, however this recommendation has not been fully supported by all societies due to the lack of robust evidence. This gap in knowledge highlights the need of well-designed and adequately powered studies to estimate the risk of colorectal neoplasms in subjects who have first-degree relatives with adenomas. Up to 30% of average risk asymptomatic individuals 50 years or older will have at least one adenoma. Based on current guidelines, nearly half the population will be counseled to undergo a colonoscopy from 40 years old based on a positive family history of adenoma. This will have enormous burden on the healthcare system if screening is implicated in all these individuals. Secondly, not all adenomas carry the same risk. Large or villous adenomas are associated with a nearly 70% increased risk of CRC in first degree relatives (FDR) whereas small adenomas may be associated with a modest increased risk 19. It is therefore important to determine the risk of colorectal neoplasms in families of subjects with non-advanced adenomas to justify more intensive screening in these individuals. Investigators hypothesize that first-degree relatives of patients with non-advanced adenoma have an increased risk of both CRC and adenomas. Investigators aim to quantify this risk, and to identify other individual patient or neoplasm characteristics that may contribute to this increased risk. In addition, Investigators aim to determine molecular alteration profiles of colonic adenoma in siblings of patients with advanced neoplasm.

Conditions

Colorectal Cancer; Colorectal Adenoma

Outcome Measures

Primary Outcomes (1)

• number of participants having advanced neoplasms.

  number of participants having advanced neoplasms, (included size of adenoma ≥1cm or villous structure, or high grade dysplasia as confirmed by histological report)

  one day

Secondary Outcomes (4)

• number of participants having colorectal neoplasms

  one day

• number of participants having advanced neoplasms depending on site of non-advanced adenoma in proband

  one day

• number of participants having advanced neoplasms based on the gender of the proband

  one day

• number of participants having advanced neoplasms based on age of the proband

  one day

Study Arms (2)

exposed siblings/children

Consecutive subjects with non-advanced adenomas will be identified from the colonoscopy database at Prince of Wales Hospital, Alice Ho Miu Ling Nethersole Hospital, Queen Elizabeth Hospital and the bowel cancer screening center at Siu Lek Yuen. Figure 1 illustrates subject recruitment flow chart. They will be consented to provide details on their number of FDR, their FDR contact details, and cause of death in FDR who are deceased. FDR aged 40 to 70 years of consecutive patients with newly diagnosed non-advanced adenomas confirmed from endoscopy and pathology reports will be contacted via phone and invited for an interview and a colonoscopy. COLONOSCOPY With informed consents, experienced colonoscopists (GI physicians, colorectal surgeons) will perform colonoscopy under intravenous sedation, midazolam and pethidine after adequate bowel preparation.

unexposed siblings/children

Subjects (Control) FDR aged 40 to 70 years of asymptomatic average risk subjects who had undergone a colonoscopy in our bowel cancer screening programme between 2010 and 2014 and found to have a normal colonoscopy will be invited to participate by phone and invitation letters, to attend a health talk and to undergo a colonoscopy. Confounding factors including use of drugs (aspirin and non-steroidal anti-inflammatory drugs), lifestyle factors (smoking, and diet questionnaire) and history of medical conditions (obesity with calculation of body mass index, diabetes, history of cardiovascular disease) between cases and controls will be recorded. COLONOSCOPY With informed consents, experienced colonoscopists (GI physicians, colorectal surgeons) will perform colonoscopy under intravenous sedation, midazolam and pethidine after adequate bowel preparation.

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

siblings of Hong Kong Chinese patients with advanced neoplasm compared with a sex and age-matched control population

You may qualify if:

• First-degree relatives (aged 40 to 70 years) of individuals diagnosed with non-advanced adenoma on screening colonoscopy as Cases
• FDR of patients with negative findings on colonoscopy identified during the same study period, who are of the same age group as the studied as Cohort

You may not qualify if:

• A FDR history of CRC
• A family history compatible with that of Hereditary Non-polyposis Colon Cancer (HNPCC) based on the Amsterdam criteria
• Known Familial Adenomatous Polyposis (FAP) syndrome
• Patients and siblings with known inflammatory bowel disease
• Undergone colonoscopy examinations in the past 5 years
• Severe cardio-pulmonary or other medical co-morbidities that preclude safe colonoscopic examination
• Pregnancy

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (2)

Alice Ho Mel Ling Nethersole Hospital

Hong Kong, 999077, Hong Kong

Location

Prince of Wales Hospital

Hong Kong, 999077, Hong Kong

Location

Related Publications (1)

• Ng SC, Kyaw MH, Suen BY, Tse YK, Wong MCS, Hui AJ, Tak HY, Lau JYW, Sung JJY, Chan FKL. Prospective colonoscopic study to investigate risk of colorectal neoplasms in first-degree relatives of patients with non-advanced adenomas. Gut. 2020 Feb;69(2):304-310. doi: 10.1136/gutjnl-2018-318117. Epub 2019 Apr 26.

  PMID: 31028155 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

stool, colonic mucosa

MeSH Terms

Conditions

Colorectal Neoplasms

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

Study Officials

• SIEW C NG, MD

  CUHK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 6, 2015
• First Posted: August 13, 2015
• Study Start: November 26, 2015
• Primary Completion: June 6, 2018
• Study Completion: June 6, 2018
• Last Updated: July 10, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

HK (2)