Distinct clinical features associated with microsatellite instability in colorectal cancers of young patients

The Hong Kong Chinese population has an unusually high incidence of colorec tal cancer in the young, suggestive of hereditary susceptibility. To search for a genetic basis for this predisposition, we studied the incidence of m icrosatellite instability (MSI) in paraffin-embedded colectomy specimens of 124 young (<50 years old) Chinese colorectal cancer patients referred to t he Hong Kong Hereditary Gastrointestinal Cancer Registry from 1995 to 1998, By medical record review and personal interview, we searched for distinct clinical features associated with the manifestation of MSI in this group of patients. For patients with MSI tumours, brood was taken for detection of germline mutation in 2 mismatch repair (MMR) genes. MSI was present in 33 t umours from 23 males and 10 females (26.6%), Ongoing mutation analysis has so far identified MMR gene mutations in 8 patients with MSI tumours, The in cidence of MSI increased significantly with decreasing age at cancer diagno sis. For patients aged 30 to 49, MSI tumours were located mainly at the pro ximal colon. However, for exceptionally young patients (<30 years), MSI tum ours tended to be at the distal large bower. This observation suggested a d ifferential activity of the MMR pathway in colorectal carcinogenesis in dif ferent age groups. On multivariate analysis, young age at cancer diagnosis, proximal tumour location, a strong family history of colorectal cancer, an d a personal history of metachronous cancer were independent predictors for MSI status. This knowledge may have an impact on the management of young c olorectal cancer patients and their families. (C) 2000 Wiley-Liss, Inc.