Clinical Implications of Molecular Diagnosis in Hereditary Nonpolyposis Colorectal Cancer

摘要

Hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary cancer predisposition accounting for approximately l%-5% of all colorectal cancers. Clinical management of HNPCC families is most challenging due to the following factors: (1) reduced penetrance of approximately 80%; (2) predisposition to cancer of the colorectum but also of the endometrium, urinary tract and small bowel; (3) broad inter- and intrafamilial heterogeneity; and (4) highly accelerated adenoma carcinoma sequence in the colorectum. To date, HNPCC may be defined either by the so-called Amsterdam I+II criteria or by detection of a mutation in one of the mismatch repair genes. Once the positive mutation has been identified, predictive testing of at-risk family members is available. Screening recommendations for clinically identified families, mutation carriers, and their unaffected at-risk relatives must be defined for clinical management. The question of prophylactic colectomy in HNPCC is also discussed.