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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

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

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 Summary:

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% versu
Sponsor: Chinese University of Hong Kong

Current Primary Outcome: Prevalence of adenoma and CRC [ Time Frame: 30 days ]

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)


Original Primary Outcome: Prevalence of adenoma and CRC Prevalence of adenoma and CRC [ Time Frame: one year ]

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)


Current Secondary Outcome:

  • Rate of advanced neoplasms depending on age of index case [ Time Frame: 30 days ]
    same as primary outcome
  • Rate of advanced neoplasms depending on site of neoplasm [ Time Frame: 30 days ]
    same as primary outcome
  • Differences in genetic profile between siblings of patients with advanced neoplasm and controls [ Time Frame: 30 days ]
    same as primary outcome


Original Secondary Outcome:

  • Rate of advanced neoplasms depending on age of index case [ Time Frame: 1year ]
    same as primary outcome
  • Rate of advanced neoplasms depending on site of neoplasm [ Time Frame: one year ]
    same as primary outcome
  • Differences in genetic profile between siblings of patients with advanced neoplasm and controls [ Time Frame: 1 year ]
    same as primary outcome
  • Detection of miRNA 21 and miRNA-92 of stool will be performed [ Time Frame: 3 years ]
    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.


Information By: Chinese University of Hong Kong

Dates:
Date Received: May 1, 2012
Date Started: May 2010
Date Completion: December 2019
Last Updated: April 20, 2017
Last Verified: April 2017