HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER (LYNCH SYNDROME) - AN UPDATED REVIEW

BACKGROUND. Hereditary nonpolyposis colorectal cancer (HNPCC) dates to Aldred Warthin's description of Family G a century ago. The phenotype features an excess of early onset colorectal carcinoma (CRC) with a p ropensity to involve the proximal colon, and a variety of extracolonic cancers, particularly carcinoma of the endometrium, ovary, stomach, s mall bowel, ureter, and renal pelvis. The recent discovery that HNPCC patients carry germline mutations in DNA mismatch repair genes has eng endered great interest in the syndrome. METHODS. This is a description of HNPCC based on the authors' experience with more than 170 families and a review of the world literature. RESULTS, This review describes the genotypic and phenotypic features of HNPCC. The distinctive natura l history of the syndrome is discussed in light of the recent discover y that ineffective DNA mismatch repair is the principal abnormality in affected individuals. CONCLUSIONS. Clinical and molecular genetic kno wledge about HNPCC is now available to physicians, and should enable t hem to provide highly targeted surveillance and management for patient s with a high cancer risk. Genetic counseling can prove lifesaving. Th e study of HNPCC will likely contribute to knowledge about the causes and control of common forms of cancer in the general population. (C) 1 996 American Cancer Society.