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

NCT ID: NCT01593098

Last Updated: 2020-06-29

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 600 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-06-08
• Study Completion Date: 2025-12-31

Brief Summary

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

Detailed Description

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.

Conditions

Adenoma; CRC

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Exposed siblings

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

No interventions assigned to this group

unexposed siblings

Siblings (age \>40 and \<70) of individuals diagnosed with no polyp on screening colonoscopy who is age and sex matched to case.

No interventions assigned to this group

Eligibility Criteria

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
• Severe cardio-pulmonary or other medical co-morbidities that preclude safe colonoscopic examination

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Francis KL Chan

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Endoscopy Centre,Alice Ho Miu Ling Nethersole Hospital & Tai Po Hospital

Hong Kong, , China

Site Status: RECRUITING

Endocopy Center, Prince of Wales Hospital

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

China; Hong Kong

Central Contacts

Siew C Ng, PhD

Role: CONTACT

siewchienng@cuhk.edu.hk

(852)26373509

BingYee Suen, BHSc

Role: CONTACT

suenbingyee@cuhk.edu.hk

(853)26322931

Facility Contacts

James Lau, MD

Role: primary

jameslau@cuhk.edu.hk

852 2632 2931

Justin C Wu, MD

Role: primary

justinwu@cuhk.edu.hk

852 2632 3307

References

Ng SC, Lau JY, Chan FK, Suen BY, Tse YK, Hui AJ, Leung-Ki EL, Ching JY, Chan AW, Wong MC, Ng SS, To KF, Wu JC, Sung JJ. Risk of Advanced Adenomas in Siblings of Individuals With Advanced Adenomas: A Cross-Sectional Study. Gastroenterology. 2016 Mar;150(3):608-16; quiz e16-7. doi: 10.1053/j.gastro.2015.11.003. Epub 2015 Nov 14.

Reference Type: DERIVED

PMID: 26584600 (View on PubMed)

Other Identifiers

AN study

Identifier Type: -

Identifier Source: org_study_id