FREQUENCY OF HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER - A PROSPECTIVE MULTICENTER STUDY IN FINLAND

PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autos omal dominant cancer syndrome characterized by early onset of colorect al carcinomas (CRC). Recently, two HNPCC genes have been mapped and cl oned, one in the short arm of chromosome 2 and another in the short ar m of chromosome 3. There has been a major controversy about the freque ncy of HNPCC. The few estimates available have been based on series se lected by age or series representing local area. The purpose of the pr esent study was to design a nonselected, prospective, multicenter stud y, taking into account the family background and other risk factors of CRC. METHODS: The proportion of HNPCC of all (N = 406) CRC cases was evaluated in a prospective multicenter study. Family history and other risk factors were investigated over a 12-month period for all new CRC patients in ten hospitals. These cases constituted 23 percent of all CRCs diagnosed in Finland during the study period. RESULTS: Three (0.7 percent) cases of verified and seven (1.7 percent) cases of suspected HNPCC were identified, following the evaluation of all families with features indicative of susceptibility to cancer. The proportion of ide ntifiable risk factors of CRC was 5.8-7.5 percent (HNPCC, 0.7-2.4 perc ent; previous CRC, 3.4 percent; ulcerative colitis, 1.0 percent; famil ial adenomatous polyposis coli, 0.7 percent). CONCLUSION. This prospec tive multicenter study revealed that the frequency of hereditary color ectal cancer is lower than in some previous studies, when diagnosis is based on extensive pedigree analysis. This result with recent finding s of common ancestral founding mutation in Finnish HNPCC families indi cates that there may be geographic differences in the occurrence of HN PCC. However, this does not change the fact that identification of HNP CC-perhaps one of the most common inherited diseases identified in hum ans-has become a question of vital importance now when diagnosis of th e syndrome and large-scale screening of gene carriers using specific t ests are on the horizon.