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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families.

PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and MSH6. The aims of the present study were to compare the risk of developing colorectal, endometrial, and other cancers between families with the various MMR-gene mutations. PATIENTS AND METHODS: Clinical and pathologic data were collected from 138 families with HNPCC. Mutation analyses were performed for all families. Survival analysis was used to calculate the cumulative risk of developing cancer in the various subsets of relatives. RESULTS: Mutations were identified in 79 families: 34 in MLH1, 40 in MSH2, and five in MSH6. The lifetime risk of developing cancer at any site was significantly higher for MSH2 mutation carriers than for MLH1 mutation carriers (P < .01). The risk of developing colorectal or endometrial cancer was higher in MSH2 mutation carriers than in MLH1 mutation carriers, but the difference was not significant (P = .13 and P = .057, respectively). MSH2 mutation carriers were found to have a significantly higher risk of developing cancer of the urinary tract (P < .05). The risk of developing cancer of the ovaries, stomach, and brain was also higher in the MSH2 mutation carriers than in the MLH1 mutation carriers, but the difference was not statistically significant. CONCLUSION: Pending large prospective studies, the extension of the current surveillance program in MSH2 mutation carriers with the inclusion of the urinary tract should be considered.[1]

References

  1. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. Vasen, H.F., Stormorken, A., Menko, F.H., Nagengast, F.M., Kleibeuker, J.H., Griffioen, G., Taal, B.G., Moller, P., Wijnen, J.T. J. Clin. Oncol. (2001) [Pubmed]
 
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