Population-based molecular detection of hereditary nonpolyposis colorectal cancer - PubMed (original) (raw)

. 2000 Jun;18(11):2193-200.

doi: 10.1200/JCO.2000.18.11.2193.

A Loukola, P Kristo, H Kääriäinen, H Ahtola, M Eskelinen, N Härkönen, R Julkunen, E Kangas, S Ojala, J Tulikoura, E Valkamo, H Järvinen, J P Mecklin, L A Aaltonen, A de la Chapelle

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Population-based molecular detection of hereditary nonpolyposis colorectal cancer

R Salovaara et al. J Clin Oncol. 2000 Jun.

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Abstract

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.

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