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

Colorectal Cancer Clinical Trial

— NonAA  

Official title:

A Prospective Colonoscopic Study to Investigate Risk of Colorectal Neoplasms in First-degree Relatives of Patients With Non-advanced Adenomas (NonAA Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02521727
• Other study ID #: NonAA
• Status: Completed
• Start date: November 26, 2015
• Est. completion date: June 6, 2018

Study information

• Verified date: July 2018
• Source: Chinese University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer death worldwide. Based on data from the Hong Kong Cancer Registry in 2012, CRC is the second most common cancer in Hong Kong. It is one of the few cancers for which there are convincing data to support the benefits of screeColorectal cancer (CRC) is the third most common cancer and second leading cause of cancer death worldwide. Based on data from the Hong Kong Cancer Registry in 2012, CRC is the second most common cancer in Hong Kong. It is one of the few cancers for which there are convincing data to support the benefits of screening. Currently the removal of adenomas is the most effective way in reducing cancer incidence and mortality. International guidelines recommend screening for individuals at an average risk of CRC from the age of 50 years.

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. 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.

The molecular pathways leading to tumour development in familial colorectal neoplasms are likely to be different from sporadic cases. Development of new molecular based methods for early detection, prevention or treatment relies heavily on the understanding of the differences between sporadic and familial neoplasms. Identification of genetic mutations can also improve genetic diagnosis and screening protocol of an at risk population.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 828
• Est. completion date: June 6, 2018
• Est. primary completion date: June 6, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Adenoma
• Colorectal Adenoma
• Colorectal Cancer
• Colorectal Neoplasms
• Neoplasms

Locations

Country	Name	City	State
Hong Kong	Alice Ho Mel Ling Nethersole Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	number of participants having colorectal neoplasms	number of participants having colorectal neoplasms as confirmed by histological report)	one day
Secondary	number of participants having advanced neoplasms depending on site of non-advanced adenoma in proband	number of participants having advanced neoplasms (confirmed by histological report) based on site of non-advanced adenoma in proband	one day
Secondary	number of participants having advanced neoplasms based on the gender of the proband	number of participants having advanced neoplasms based on the number of participants having advanced neoplasms (confirmed by histological report) based on the gender of the proband	one day
Secondary	number of participants having advanced neoplasms based on age of the proband	number of participants having advanced neoplasms (confirmed by histological report) based on the age of the proband	one day