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Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management.

Hereditary forms of colorectal cancer, as is the case with virtually all forms of hereditary cancer, show extensive phenotypic and genotypic heterogeneity, a phenomenon discussed throughout this special issue of Familial Cancer. Clearly, the family physician, oncology specialist, genetic counselor, and cancer geneticist must know fully the complexity of hereditary cancer syndromes, their differential diagnosis, in order to establish a diagnosis, direct highly-targeted surveillance and management, and then be able to communicate effectively with the molecular geneticist so that an at-risk patient's DNA can be tested in accord with the syndrome of concern. Thus, a family with features of the Lynch syndrome will merit microsatellite instability testing, consideration for immunohistochemistry evaluation, and mismatch repair gene testing, while, in contrast, a patient with FAP will require APC testing. However, other germline mutations, yet to be identified, may be important should testing for these mutations prove to be absent and, therein, unrewarding to the patient. Nevertheless, our position is that if the patient's family history is consistent with one of these syndromes, but a mutation is not found in the family, we still recommend the same surveillance and management strategies for patients from families with an established cancer-causing germline mutation. Our purpose in this paper is to provide a concise coverage of the major hereditary colorectal cancer syndromes, to discuss genetic counseling, molecular genetic evaluation, highly targeted surveillance and management, so that cancer control can be maximized for these high hereditary cancer risk patients.

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