Objective The true incidence of HNPCC can only be determined by direct mutational analysis of unbiased prospective series of individuals. This will be accomplished by acquiring tumour and normal tissue from the great majority of all patients with colorectal carcinoma or adenoma in a 1.25 million subpopulation of Finland and the entire 260,000 population of the Modena district. These specimens will be analyzed for mutations in the known DNA mismatch repair genes; the initial screening of likely HNPCC cases will be by determining microsatellite instability status of the tutors. Germline mutations characteristic of HNPCC are present when normal tissue is heterozygous for the mutation. The number of specimens studied after 2-year prospective collection periods will be approximately 1360 carcinomas and 3400 adenomas. The number of germline mutations found will directly determine the incidence of HNPCC in these populations. To determine the type of mutation and genotype-phenotype correlations members of families already diagnosed with HNPCC will be analyzed. The partners have contacts with a total of 142 such families comprising 440 affected individuals and 1214 individuals over the age of 18 with a 50% genetic risk of being a mutation carrier. In each family the responsible gene mutation will be determined; a convenient test for that mutation designed, and all consenting patients and at-risk individuals counselled, tested, and re-counselled. Once the mutation status of each individual is determined, the natural history of the disease will be re-examined by correlating the mutation status with the penetrance, expressivity, and organ spectrum of involvement. Methods for the counselling and handling of mutation carriers will be designed and tested. Fields of science humanitieshistory and archaeologyhistorynatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicineoncologycolorectal cancernatural sciencesbiological sciencesgeneticsmutation Programme(s) FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998 Topic(s) 5.3 - Role of gene and gene products in disease aetiology and pathogenesis Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator N/A EU contribution No data Address 3,Haartmaninkatu 00014 Helsinki Finland See on map Total cost No data Participants (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all KAROLINSKA INSTITUTE Sweden EU contribution No data Address Karolinska Hospital 171 76 STOCKHOLM See on map Total cost No data UNIVERSITY OF MODENA AND REGGIO EMILIA Italy EU contribution No data Address 71,Largo del Pozzo 71 41100 Modena See on map Total cost No data
