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World J Gastroenterol. Aug 21, 2006; 12(31): 4943-4950
Published online Aug 21, 2006. doi: 10.3748/wjg.v12.i31.4943
Hereditary non-polyposis colorectal cancer: The rise and fall of a confusing term
Jeremy R Jass
Jeremy R Jass, Department of Pathology, McGill University, Montreal, Quebec, Canada
Author contributions: All authors contributed equally to the work.
Correspondence to: Jeremy R Jass, Department of Pathology, McGill University, Duff Medical Building, 3775 University Street, Montreal, Quebec H3A 2B4, Canada. jeremy.jass@mcgill.ca
Telephone: +1-514-3987192-00395 Fax: +1-514-3987446
Received: February 28, 2006
Revised: March 12, 2006
Accepted: March 21, 2006
Published online: August 21, 2006
Abstract

The term Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is a poor descriptor of the syndrome described by Lynch. Over the last decade, the term has been applied to heterogeneous groups of families meeting limited clinical criteria, for example the Amsterdam criteria. It is now apparent that not all Amsterdam criteria-positive families have the Lynch syndrome. The term HNPCC has also been applied to clinical scenarios in which CRCs with DNA microsatellite instability are diagnosed but in which there is no vertical transmission of an altered DNA mismatch repair (MMR) gene. A term that has multiple, mutually incompatible meanings is highly problematic, particularly when it may influence the management of an individual family. The Lynch syndrome is best understood as a hereditary predisposition to malignancy that is explained by a germline mutation in a DNA MMR gene. The diagnosis does not depend in an absolute sense on any particular family pedigree structure or age of onset of malignancy. Families with a strong family history of colorectal cancer that do not have Lynch syndrome have been grouped as ‘Familial Colorectal Cancer Type-X’. The first step in characterizing these cancer families is to distinguish them from Lynch syndrome. The term HNPCC no longer serves any useful purpose and should be phased out.

Keywords: Hereditary Non-Polyposis Colorectal Cancer; Colon; Cancer; Hereditary