PURPOSE: Cancer morbidity and mortality can be dramatically reduced by colonoscopic screening of individuals with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, creating a need to identify HNPCC. We studied how HNPCC identification should be carried out on a large scale in a sensitive and efficient manner. PATIENTS AND METHODS: Colorectal cancer specimens from consecutive newly diagnosed patients were studied for microsatellite instability (MSI). Germline mutations in the MLH1 and MSH2 genes were searched for in MSI(+) individuals. RESULTS: Among 535 colorectal cancer patients, 66 (12%) were MSI(+). Among these, 18 (3.4% of the total) had disease-causing germline mutations in MLH1 or MSH2. Among these 18 patients, five were less than 50 years old, seven had a previous or synchronous colorectal or endometrial cancer, and 15 had at least one first-degree relative with colorectal or endometrial cancer. Notably, 17 (94%) of 18 patients had at least one of these three features, which were present in 22% of all 535 patients. Combining these data with a previous study of 509 patients, mutation-positive HNPCC accounts for 28 (2.7%) of 1,044 cases of colorectal cancer, predicting a greater than one in 740 incidence of mutation-positive individuals in this population. CONCLUSION: Large-scale molecular screening for HNPCC can be done by the described two-stage procedure of MSI determination followed by mutation analysis. Efficiency can be greatly improved by using three high-risk features to select 22% of all patients for MSI analysis, whereby only 6% need to have mutation analysis. Sensitivity is only slightly impaired by this procedure.
PURPOSE:Cancer morbidity and mortality can be dramatically reduced by colonoscopic screening of individuals with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, creating a need to identify HNPCC. We studied how HNPCC identification should be carried out on a large scale in a sensitive and efficient manner. PATIENTS AND METHODS: Colorectal cancer specimens from consecutive newly diagnosed patients were studied for microsatellite instability (MSI). Germline mutations in the MLH1 and MSH2 genes were searched for in MSI(+) individuals. RESULTS: Among 535 colorectal cancerpatients, 66 (12%) were MSI(+). Among these, 18 (3.4% of the total) had disease-causing germline mutations in MLH1 or MSH2. Among these 18 patients, five were less than 50 years old, seven had a previous or synchronous colorectal or endometrial cancer, and 15 had at least one first-degree relative with colorectal or endometrial cancer. Notably, 17 (94%) of 18 patients had at least one of these three features, which were present in 22% of all 535 patients. Combining these data with a previous study of 509 patients, mutation-positive HNPCC accounts for 28 (2.7%) of 1,044 cases of colorectal cancer, predicting a greater than one in 740 incidence of mutation-positive individuals in this population. CONCLUSION: Large-scale molecular screening for HNPCC can be done by the described two-stage procedure of MSI determination followed by mutation analysis. Efficiency can be greatly improved by using three high-risk features to select 22% of all patients for MSI analysis, whereby only 6% need to have mutation analysis. Sensitivity is only slightly impaired by this procedure.
Authors: R C Niessen; M J W Berends; Y Wu; R H Sijmons; H Hollema; M J L Ligtenberg; H E K de Walle; E G E de Vries; A Karrenbeld; C H C M Buys; A G J van der Zee; R M W Hofstra; J H Kleibeuker Journal: Gut Date: 2006-04-24 Impact factor: 23.059
Authors: Iina Niittymäki; Eevi Kaasinen; Sari Tuupanen; Auli Karhu; Heikki Järvinen; Jukka-Pekka Mecklin; Ian P M Tomlinson; Maria Chiara Di Bernardo; Richard S Houlston; Lauri A Aaltonen Journal: Cancer Epidemiol Biomarkers Prev Date: 2010-05-25 Impact factor: 4.254
Authors: E Urso; M Agostini; S Pucciarelli; M Rugge; R Bertorelle; I Maretto; C Bedin; E D'Angelo; C Mescoli; M Zorzi; A Viel; G Bruttocao; B Ferraro; F Erroi; P Contin; G L De Salvo; D Nitti Journal: Tumour Biol Date: 2012-01-26
Authors: Fernando S Velayos; Suk-Hwan Lee; Hongming Qiu; Sharon Dykes; Raymond Yiu; Jonathan P Terdiman; Julio Garcia-Aguilar Journal: J Gastrointest Surg Date: 2005-03 Impact factor: 3.452