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

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.