Hereditary non-polyposis colorectal cancer: clinical and molecular evidence for a new entity of hereditary colorectal cancer
Open Access
- 28 May 2005
- Vol. 54 (12), 1733-1740
- https://doi.org/10.1136/gut.2004.060905
Abstract
Background: Hereditary non-polyposis colorectal cancer (HNPCC) is clinically defined by familial clustering of colorectal cancer and other associated tumours. Methods: By thorough molecular and clinical evaluation of 41 families, two different groups were characterised: group 1, 25 families with truncating mutations in MLH1 or MSH2 (12 novel mutations); and group 2, 16 Amsterdam positive families without mutations in these genes and without microsatellite instability in their corresponding tumours. Results: Significant clinical differences between these two groups were found. Firstly, earlier age of onset for all colorectal cancers (median 41 v 55 years; pv 56 years; p = 0.022) was observed, comparing groups 1 and 2. Secondly, 68% of the index colorectal cancers were localised proximally of the splenic flexure in group 1 compared with 14% in group 2 (pConclusion: These data show that HNPCC includes at least two entities with clinical and molecular differences. This will have implications for surveillance programmes and for cancer research.Keywords
This publication has 30 references indexed in Scilit:
- Immunohistochemistry Versus Microsatellite Instability Testing in Phenotyping Colorectal TumorsJournal of Clinical Oncology, 2002
- The colon cancer burden of genetically defined hereditary nonpolyposis colon cancerGastroenterology, 2001
- The Frequency of Hereditary Defective Mismatch Repair in a Prospective Series of Unselected Colorectal CarcinomasAmerican Journal of Human Genetics, 2001
- Hereditary Nonpolyposis Colorectal Cancer in 95 Families: Differences and Similarities between Mutation-Positive and Mutation-Negative KindredsAmerican Journal of Human Genetics, 2001
- DHPLC mutation analysis of the hereditary nonpolyposis colon cancer (HNPCC) genes hMLH1 and hMSH2Journal of Biochemical and Biophysical Methods, 2001
- Replication error phenotype in colorectal cancer ReplyGut, 2000
- Prediction of a mismatch repair gene defect by microsatellite instability and immunohistochemical analysis in endometrial tumours from HNPCC patientsThe Journal of Pathology, 2000
- Chromosomal alterations in ulcerative colitis-related and sporadic colorectal cancers by comparative genomic hybridizationHuman Pathology, 2000
- Genetic susceptibility to non-polyposis colorectal cancer.1999
- Influence of selection criteria on mutation detection in patients with hereditary nonpolyposis colorectal cancerCancer, 1999