title: [Identification and genetic counseling of people with HNPCC (hereditary nonpolyposis colorectal cancer): old and new research goals].
abstract: Hereditary non-polyposis colorectal cancer (HNPCC) is a relatively common autosomal dominantly inherited predisposition leading to a familial occurrence of cancer of the colon, rectum, endometrium and some other organs. Cancer mortality can be significantly reduced by appropriate intervention. The diagnosis of HNPCC is suspected on the basis of early onset and multiple foci of colorectal cancer (CRC), in many cases affecting the proximal part of the colon, and of endometrial cancer. It may be confirmed by molecular genetic analysis of the mismatch repair genes, especially hMLH1 and hMSH2. In spite of considerable progress in the understanding of hereditary colon cancer, many questions which are of basic importance for the identification and appropriate genetic counselling of gene carriers remain to be answered. HNPCC defined on clinical and genealogical grounds is by no means identical with the presence of mutated mismatch-repair genes. This impedes the identification of persons/families at increased cancer risk. Mutations of other, mainly as yet unidentified genes may lead to a similar phenotype. Not only heterogeneity of the predispositions underlying CRC, but also penetrance and expressivity of the identifiable mutations of the MMR-genes, have been explored only superficially. The process of carcinogenesis in the colon can follow different routes depending on the genetic background of the patients. Its investigation will open up new possibilities of cancer prevention. In addition, genetic counselling must be developed into a more "evidence"-based medical undertaking. These gaps in the understanding of hereditary CRC and in the care of persons at risk can only be overcome through structured collaboration between family doctors, medical specialists such as gastroenterologists, oncologists and surgeons, medical geneticists and basic researchers.
authors.affiliation: Abteilung Medizinische Genetik, Universitäts-Kinderspital beider Basel. Hansjakob.Mueller@unibas.ch
authors.forename: H
authors.initials: H
authors.lastname: Müller
authors.forename: Z
authors.initials: Z
authors.lastname: Dobbie
authors.forename: K
authors.initials: K
authors.lastname: Heinimann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics*; D004268:DNA-Binding Proteins; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D006801:Humans; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein