Hereditary common cancers: Molecular and clinical genetics

This review focuses on the functional role and structural features of the g enes involved in common hereditary cancers. Most of these tumors are sporad ic and the genetic alterations responsible for their genesis take place ove r several cell generations; nevertheless, 5 to 10% of the human tumors are hereditary, with a rapid development. Cancer susceptibility genes have been classified as "gatekeepers" (e.g. RBI, ki-ras) and "carerakers" (e.g hMLH1 and hMSH2, BRCA1). The first step in identifying individuals at high risk of developing a specific inherited form of cancer, and who should therefore undergo genetic tests, is the detailed construction of family history (an accurate cancer family history that includes at least three generation pedi grees, an appropriate cancer risk assessment and an effective genetic couns eling). At present, the most useful methods of risk assessment ave those pe rformed on the following genes: BRCA1 and BRCA2 especially for hereditary b reast and ovarian cancer; hMLH1 and hMSH2 for hereditary non polyposis colo rectal cancer, APC for familial adenomatous polyposis, ret for medullary th yroid carcinoma, p53 for the Li-Fraumeni syndrome, p16 for melanoma and REI for retinoblastoma. In conclusion, the development of new diagnostic rests will permit a more accurate assessment of risk in individuals who have not so far shown any sign or symptom of the disease.