A Prospective Study Into the Risk of Colorectal Neoplasms in Individuals With a Family History of Advanced Adenomas (Sibling AN Study)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Chinese University of Hong Kong
Sponsor:
Information provided by (Responsible Party):
Francis KL Chan, Chinese University of Hong Kong
ClinicalTrials.gov Identifier:
NCT01593098
First received: May 1, 2012
Last updated: April 9, 2014
Last verified: April 2014

May 1, 2012
April 9, 2014
May 2010
May 2015   (final data collection date for primary outcome measure)
Prevalence of adenoma and CRC [ Time Frame: 30 days ] [ Designated as safety issue: No ]
With informed consents, experienced colonoscopists will perform colonoscopy under intravenous sedation During colonoscopic examination, endoscopists are instructed to remove all raised lesions. The size, location and morphologic feature of each raised lesion will be recorded. The size is measured again an open biopsy forceps (6mm apart). To avoid observer bias, colonoscopists and pathologists will be blinded from patient's details regarding family history of CRC or advanced neoplasms. Our group performed the first screening study among average risk Hong Kong Chinese in the locality (28)
Prevalence of adenoma and CRC Prevalence of adenoma and CRC [ Time Frame: one year ] [ Designated as safety issue: No ]
With informed consents, experienced colonoscopists will perform colonoscopy under intravenous sedation During colonoscopic examination, endoscopists are instructed to remove all raised lesions. The size, location and morphologic feature of each raised lesion will be recorded. The size is measured again an open biopsy forceps (6mm apart). To avoid observer bias, colonoscopists and pathologists will be blinded from patient's details regarding family history of CRC or advanced neoplasms. Our group performed the first screening study among average risk Hong Kong Chinese in the locality (28)
Complete list of historical versions of study NCT01593098 on ClinicalTrials.gov Archive Site
  • Rate of advanced neoplasms depending on age of index case [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    same as primary outcome
  • Rate of advanced neoplasms depending on site of neoplasm [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    same as primary outcome
  • Differences in genetic profile between siblings of patients with advanced neoplasm and controls [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    same as primary outcome
  • Rate of advanced neoplasms depending on age of index case [ Time Frame: 1year ] [ Designated as safety issue: No ]
    same as primary outcome
  • Rate of advanced neoplasms depending on site of neoplasm [ Time Frame: one year ] [ Designated as safety issue: No ]
    same as primary outcome
  • Differences in genetic profile between siblings of patients with advanced neoplasm and controls [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    same as primary outcome
  • Detection of miRNA 21 and miRNA-92 of stool will be performed [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Stool samples will be collected prior to colonoscopy, and every 6 monthly for up to 3 years after polyp removal. Total RNA will be extracted from 0.2 to 0.3g stool, plasma and from biopsy tissues by TriZol LS agent and Qiagen microRNA purification kit. Detection of miRNA 21 and miRNA-92 will be performed using TaqMan microRNA expression assays. Absolute value of microRNA molecules will be evaluated using standard curves from dilution series of chemically synthesized RNA. All Polymerase chain reactions will be duplicated to ensure consistency and reproducibility of results.
Not Provided
Not Provided
 
A Prospective Study Into the Risk of Colorectal Neoplasms in Individuals With a Family History of Advanced Adenomas (Sibling AN Study)
A Prospective Study Into the Risk of Colorectal Neoplasms in Individuals With a Family History of Advanced Adenomas (Sibling AN Study)

To prospectively determine the prevalence of colorectal neoplasia in siblings of Hong Kong Chinese patients with advanced neoplasm compared with a sex and age-matched control population. To determine the molecular alteration profiles of colonic adenomas in siblings of patients with advanced neoplasm

The incidence of colorectal cancer (CRC) is rising rapidly in Hong Kong. It is the second commonest cancer in Hong Kong with more than 4000 new cases diagnosed in 2007, and it is also the second commonest cause of cancer death accounting for approximately 1,700 deaths per year. It has been estimated that 1 in 20 (5%) and 1 in 33 (3%) Hong Kong males and females, respectively, will develop CRC in their life time. (1) Data from the Hong Kong cancer registry showed that almost half of the cancer cases were stage III or IV disease at diagnosis which was associated with a worse prognosis(1), suggesting that earlier detection of CRC is important.

Genetic factors play an important role in the development of CRC. Approximately one fifth of CRC are associated with familial clustering(2), whilst hereditary syndromes including hereditary non- polyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) account for approximately six percent of CRC cases (3;4)

Individuals with a family history of CRC have an increased risk of developing colonic neoplasm (cancer and adenoma). Meta-analyses of epidemiological studies showed that FDR of patients with CRC have an approximately two to three-fold increase risk of developing CRC compared with the general population (5-9). [Table 1]. The frequency of adenomas (12-69%) is also higher in relatives of patients with CRC although most of the earlier data have been derived from cohort studies (10-16). In the recent two case-control studies, the choice of the control population has been questionable (17;18) [Table 2]. Our own case-control study of screening colonoscopy in FDR with CRC, compared with FDR of patients with a normal colonoscopy ( published in abstract form) showed that the prevalence of colonic adenomas was significantly higher in cases compared with controls (25.3% versus 15.6%) (19).

Colorectal adenomas are precursors of CRC, and FDR of individuals with colonic adenomas also have an increased risk of CRC as well as colonic adenomas (20;21) The risk of developing colorectal neoplasia in FDR of patients with adenoma is likely be influenced by the characteristics of the adenoma in the index case. Colonic adenomas have a higher malignancy potential when they are greater than 10mm in size, and / or contains a villous component or severe dysplasia (22). In one study, relative risk of CRC for FDR was higher in relatives of patients with large adenomas (>10mm) than in those with small adenomas (OR 2.1 and 1.2 respectively) (23). These findings have been reproduced in a recent study from France, which in addition showed that the risk was particularly high if the index case was younger than 60 years at diagnosis of a large adenoma, male or if they had a large adenoma in the left colon (24). In a separate study, relatives of patients with advanced neoplasm (OR1.62), but not those with small tubular adenomas (OR 1.26), have an increased risk of CRC (25).

Little is known about the prevalence of CRC and adenomas among siblings of individuals with advanced neoplasm in Hong Kong. Furthermore screening procedure for relatives of patients with high risk adenomas are not as well established as screening strategies for relatives of patients with CRC. This information is of important relevance in the formulation of an effective CRC screening strategy in Hong Kong (26). In a pilot screening project in 2001 among asymptomatic subjects of greater than 50 years old, the investigator have demonstrated an approximately 12% rate of advanced neoplasms using colonoscopy as a tool. Since 2008, asymptomatic subjects greater than 50 years old have been invited to undergo colonoscopy screening for CRC in PWH and AHNH hospital. To date about 1800 asymptomatic subjects have completed colonoscopy screening. This project provides the investigators with the opportunity to use an original design to determine the prevalence of colorectal neoplasia in siblings of patients with advanced neoplasm, compared with siblings of asymptomatic individuals who have had a negative screening colonoscopy during the same period of time.

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.

The investigators hypothesize that siblings of patients with advanced neoplasm have an increased risk of both CRC and adenomas. The investigator aim to quantify this risk, and to identify other individual patient or neoplasm characteristics that may contribute to this increased risk. In addition, the investigator aim to determine molecular alteration profiles of colonic adenoma in siblings of patients with advanced neoplasm.

Investigator's preliminary data showed that the rate of advanced adenomas in controls (siblings of with normal colonoscopy) was 2%. Earlier studies have shown that the odds ratio of having colorectal neoplasms in close relatives of subjects with adenomas varies from 2.5 to 4.7. Using a conservative calculation, we assume that the prevalence of advanced adenomas in controls to be 3% and we estimate a 2.5-fold increased risk of advanced adenomas in siblings of individuals with advanced adenomas. Accordingly the recruitment of a minimum of 293 cases and 586 controls will be required to achieve 80% power to detect difference at a 5% significance level. For this project, investigators will aim to screen 300 siblings of patients with advanced adenomas and 600 matched controls.

Observational
Observational Model: Case Control
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

colonic biopsies, blood, stool

Non-Probability Sample

residence of Hong Kong siblings with colonoscopy done Siblings of Patients with Advanced Neoplasm (case) siblings of patients with normal colonoscopy (control)

  • Adenoma
  • CRC
Not Provided
  • case
    Siblings (age >40 and <70) of individuals diagnosed with advanced neoplasm on screening colonoscopy. Advanced neoplasm is defined as adenomas≥10mm size, >25% villous features, severe dysplasia or carcinoma-in-situ
  • control
    Siblings (age >40 and <70) of individuals diagnosed with no polyp on screening colonoscopy who is age and sex matched to case.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
511
December 2015
May 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • (case) Siblings (age > 40 and < 70) of individuals diagnosed with advanced neoplasm on screening colonoscopy. Advanced neoplasm is defined as adenomas ≥ 10mm size, >25% villous features, severe dysplasia or carcinoma-in-situ
  • (control) Siblings of patients with negative findings on colonoscopy identified during the same study period, who are of the same age group as the studied cohort.

Exclusion Criteria:

  • A family history compatible with that of Hereditary Non-polyposis Colon Cancer (HNPCC) based on the Amsterdam criteria [Table 3].
  • Known Familial Adenomatous Polyposis (FAP) syndrome
  • Patients and siblings with known inflammatory bowel disease
  • Siblings that have undergone colonoscopy examinations in the past 5 years
  • Severe cardio-pulmonary or other medical co-morbidities that preclude safe colonoscopic examination
Both
40 Years to 70 Years
Yes
Contact: Siew C Ng, PhD (852)26373509 siewchienng@cuhk.edu.hk
Contact: BingYee Suen, BHSc (853)26322931 suenbingyee@cuhk.edu.hk
China
 
NCT01593098
AN study
No
Francis KL Chan, Chinese University of Hong Kong
Chinese University of Hong Kong
Not Provided
Not Provided
Chinese University of Hong Kong
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP