[Current concepts in the genetics of hereditary and sporadic colorectal cancer and the role of genetics in patient management. Hereditary colorectal cancers].
Colorectal cancer (CRC) is the second leading cause of mortality of malignant diseases in Hungary and according to the incidence and prevalence of CRC Hungary is second among European countries. Hence, it is of outstanding interest to know the current concepts on pathogenesis and genetical background of CRC, as well as incorporate this knowledge in the everyday practice. In the first part of the review authors address the genetic background of hereditary colorectal cancer syndromes. In fact, a positive family history may be found in 20-30% and genetically defined trait (e.g. familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) and Peutz-Jeghers-syndrome (PJS)) is responsible for 3-5% of all colon cancers. Germline mutations of tumor suppressor gene, APC (5q21) are found in 70-90% of the cases. Until now more than 300 mutations were identified. Though a typical mutation was not found, the location of the mutation is associated to the clinical phenotype and prognosis. Of note, beside APC mutations, biallelic mutations of the MYH gene may be found in a subset of individuals with FAP. The diagnosis of HNPCC is based on family history and the presence of Amsterdam I-Il or Bethesda criteria. The genetic background and clinical phenotype of the syndrome is heterogeneous. Mutations of different mismatch repair genes (mainly hMLH1 or hMSH2) may be identified in most cases. Genetic testing is advised in first degree relatives of FAP patients, if genetic testing is not available colonoscopic surveillance should be done starting at the age of 10-12 years. Due to the high number of mutation genetic testing is difficult in HNPCC families and colonoscopic screening should be advised to affected families.
Semmelweis Egyetem, Altalános Orvostudományi Kar, I. Belgyógyászati Klinika, Budapest. kislakpet@bel1.sote.hu
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D048868:Adaptor Proteins, Signal Transducing; D011125:Adenomatous Polyposis Coli / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D017491:Genes, APC; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D015994:Incidence; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010580:Peutz-Jeghers Syndrome / Q000235:genetics; D011379:Prognosis
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein