[Our experience with the incidence of hereditary non-polyposis colorectal cancer]

Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is the most frequent genetic disease leading to colorectal malignancies. 3-5 percent of all colorectal cancer cases are related to Hereditary Non-Polyposis Colorectal Cancer. Currently there is no reliable data on the incidence of the disease in Hungary.

The family history of 809 patients with colorectal cancer was investigated between 1997 and 2006. Data collection was performed in a retrospective manner in the rst and in a prospective manner in the second phase of the study. Subsequent immunohistochemical and microsatellite instability analysis, and DNA sequencing was carried out to detect any underlying MMR gene mutation. Moreover, multiple ligation dependent probe amplication was applied for recognizing large deletions in MMR genes.

During the investigation 10 pathogenic mutations and several polymorphisms were found. Seven mutations were detected in families fulfilling the Amsterdam Criteria, while the remaining three fulfilled the Bethesda Criteria. In the second phase of the study -- which better reflects the real population characteristics -- six percent of our patients fulfilled completely the Amsterdam Criteria and we managed to nd pathogenic MMR gene mutations in 1,7 percent of our patients.

8 out of 10 pathogenic mutations were novel and published rst time by ourselves. No repeatedly occurring mutations were found in our patients. It seems that these genetic alterations are located sporadically on different exons of the involved MMR genes. Our mutation detection rate was 77 percent in the Amsterdam positive patients who were completely examined, which appears to be better than the published data in the relevant literature. Importantly, 30 percent of the mutation carrier could be missed applying only this single criteria system. In order to detect the highest number of HNPCC patients, we suggest using both the Amsterdam as well as the Bethesda Criteria.