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SHR Neuro Krebs Kardio Lipid

Hendriks, YM; Wagner, A; Morreau, H; Menko, F; Stormorken, A; Quehenberger, F; Sandkuijl, L; Møller, P; Genuardi, M; Van Houwelingen, H; Tops, C; Van Puijenbroek, M; Verkuijlen, P; Kenter, G; Van Mil, A; Meijers-Heijboer, H; Tan, GB; Breuning, MH; Fodde, R; Wijnen, JT; Bröcker-Vriends, AH; Vasen, H.
Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance.
Gastroenterology. 2004; 127(1):17-25
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Autor/innen der Med Uni Graz:
Quehenberger Franz

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BACKGROUND & AIMS: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is caused by a mutated mismatch repair (MMR) gene. The aim of our study was to determine the cumulative risk of developing cancer in a large series of MSH6 mutation carriers. METHODS: Mutation analysis was performed in 20 families with a germline mutation in MSH6. We compared the cancer risks between MSH6 and MLH1/MSH2 mutation carriers. Microsatellite instability (MSI) analysis and immunohistochemistry (IHC) were performed in the available tumors. RESULTS: A total of 146 MSH6 mutation carriers were identified. In these carriers, the cumulative risk for colorectal carcinoma was 69% for men, 30% for women, and 71% for endometrial carcinoma at 70 years of age. The risk for all HNPCC-related tumors was significantly lower in MSH6 than in MLH1 or MSH2 mutation carriers (P = 0.002). In female MSH6 mutation carriers, the risk for colorectal cancer was significantly lower (P = 0.0049) and the risk for endometrial cancer significantly higher (P = 0.02) than in MLH1 and MSH2 mutation carriers. In male carriers, the risk for colorectal cancer was lower in MSH6 mutation carriers, but the difference was not significant (P = 0.0854). MSI analysis in colorectal tumors had a sensitivity of 86% in predicting a MMR defect. IHC in all tumors had a sensitivity of 90% in predicting a mutation in MSH6. CONCLUSIONS: We recommend starting colonoscopic surveillance in female MSH6 mutation carriers from age 30 years. Prophylactic hysterectomy might be considered in carriers older than 50 years. MSI and IHC analysis are sensitive tools to identify families eligible for MSH6 mutation analysis.
Find related publications in this database (using NLM MeSH Indexing)
Adaptor Proteins, Signal Transducing -
Adult -
Aged -
Carrier Proteins -
Chromosomal Instability - genetics
Colorectal Neoplasms, Hereditary Nonpolyposis - complications
DNA-Binding Proteins - genetics
Family - genetics
Female - genetics
Genetic Phenomena - genetics
Genetic Services - genetics
Germ-Line Mutation - genetics
Humans - genetics
Immunohistochemistry - genetics
Male - genetics
Microsatellite Repeats - genetics
Middle Aged - genetics
Neoplasm Proteins - genetics
Neoplasms - etiology
Nuclear Proteins - etiology
Risk - etiology

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