Clinical implications of molecular diagnosis in hereditary nonpolyposis colorectal cancer.
Hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary cancer predisposition accounting for approximately 1%-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.
Möslein
Gabriela
G
Department of Surgery, Heinrich-Heine University, Moorenstr. 5, 40225 Düsseldorf, Germany.
D000236:Adenoma / Q000175:diagnosis / Q000235:genetics; D020137:Base Pair Mismatch; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics*; D004260:DNA Repair; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D012306:Risk