Hereditary colorectal cancer: clinical consequences of predictive molecular testing

The continuing increase in knowledge about the genetic basis of carcinogene sis has led to diverse efforts to exploit this knowledge clinically, primar ily in the form of predictive genetic testing. In conjunction with family h istory, gene tests are intended to improve individual cancer risk assessmen t. The objectives of predictive molecular testing are to identify the disea se-causing germline mutation in an index person who has already developed t he disease and to distinguish asymptomatic mutation carriers from non-mutat ion carriers within a given cancer-prone family. At present, genetic testin g for colorectal cancer risk, primarily in form of DNA sequencing, is appli ed in familial adenomatous polyposis (FAP) and hereditary nonpolyposis colo rectal cancer (HNPCC). In these inherited colorectal tumor syndromes determ ining the genetic status may result in an individually tailored surveillanc e program and prophylactic treatment. The implications of genetic testing f or the clinical management of disease, both of mutation and non-mutation ca rriers, in familial adenomatous polyposis and hereditary nonpolyposis color ectal cancer families are discussed.