Clinical-alimentary tractThe role of mismatch repair gene defects in the development of adenomas in patients with HNPCC
Section snippets
Patients and methods
In 1987, a registry of families with HNPCC was established in The Netherlands at The Netherlands Foundation for the Detection of Hereditary Tumors. The regulations of the registry have been described elsewhere.15 When an HNPCC family was registered, all members of that family were informed about the risk of developing colorectal cancer and were advised to participate in the surveillance program. Nowadays, counseling, mutation diagnostics, and presymptomatic testing occur in clinical genetic
Results
In the 86 families with a known MMR gene mutation, we identified 247 noncarriers and 249 carriers. The noncarriers constituted the control group. The characteristics of both groups are shown in Table 1. There were significantly more men in the control group, and the mean age at first colonoscopy was significant younger in the carriers. Moreover, the follow-up time (since first colonoscopy) and screening intervals were significantly different between both groups.
Discussion
The present study provides clinically important information on the development of adenomas in HNPCC. Carriers of an MMR gene defect developed adenomas more frequently than control subjects of the same age. In addition, carriers developed adenomas at a younger age than controls. The adenomas in the carriers were larger, and significantly higher proportions showed high-grade dysplasia and a tubulovillous architecture. In most of the adenomas in the carriers, immunohistochemical analysis showed
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