Lower Incidence of Colorectal Cancer and Later Age of Disease Onset in 27 Families With Pathogenic MSH6 Germline Mutations Compared With Families With MLH1 or MSH2 Mutations: The German Hereditary Nonpolyposis Colorectal Cancer Consortium
| العنوان: | Lower Incidence of Colorectal Cancer and Later Age of Disease Onset in 27 Families With Pathogenic MSH6 Germline Mutations Compared With Families With MLH1 or MSH2 Mutations: The German Hereditary Nonpolyposis Colorectal Cancer Consortium |
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| المؤلفون: | Josef Rüschoff, Markus Loeffler, Stefan Krüger, Karsten Schulmann, Christoph Engel, Johannes Gebert, Constanze Pagenstecher, Jens Plaschke, Magnus von Knebel Doeberitz, Elke Holinski-Feder, Hans K. Schackert, Elisabeth Mangold, Gabriela Moeslein |
| المصدر: | Journal of Clinical Oncology. 22:4486-4494 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Adult, Male, Oncology, congenital, hereditary, and neonatal diseases and abnormalities, Cancer Research, medicine.medical_specialty, DNA Repair, Base Pair Mismatch, Colorectal cancer, medicine.disease_cause, MLH1, Gastroenterology, Germline, Germline mutation, Risk Factors, Proto-Oncogene Proteins, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Age of Onset, neoplasms, Germ-Line Mutation, Adaptor Proteins, Signal Transducing, Aged, Mutation, business.industry, Incidence, Nuclear Proteins, nutritional and metabolic diseases, Middle Aged, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, Immunohistochemistry, digestive system diseases, Endometrial Neoplasms, Neoplasm Proteins, DNA-Binding Proteins, MSH6, MutS Homolog 2 Protein, Phenotype, MSH2, Female, Age of onset, Carrier Proteins, MutL Protein Homolog 1, business, Microsatellite Repeats |
| الوصف: | Purpose The aim of the study was the analysis of the involvement and phenotypic manifestations of MSH6 germline mutations in families suspected of hereditary nonpolyposis colorectal cancer (HNPCC). Patients and Methods Patients were preselected among 706 families by microsatellite instability, immunohistochemistry, and/or exclusion of MLH1 or MSH2 mutations and were subjected to MSH6 mutation analysis. Clinical and molecular data of MSH6 mutation families were compared with data from families with MLH1 and MSH2 mutations. Results We identified 27 families with 24 different pathogenic MSH6 germline mutations, representing 3.8% of the total of the families, and 14.7% of all families with DNA mismatch repair (MMR) gene mutations (n = 183). The median age of onset of colorectal cancer in putative mutation carriers was 10 years higher for MSH6 (54 years; 95% CI, 51 to 56) compared with MLH1 and MSH2 (44 years; 95% CI, 43 to 45; log-rank test, P = .0038). Relative to other malignant tumors, colorectal cancer was less frequent in MSH6 families compared with MLH1 and MSH2 families (Fisher's exact test, P < .001). In contrast, the frequency of non–HNPCC-associated tumors was increased (Fisher's exact test, P < .001). Conclusion Later age of disease onset and lower incidence of colorectal cancer may contribute to a lower proportion of identified MSH6 mutations in families suspected of HNPCC. However, in approximately half of these families, at least one patient developed colorectal or endometrial cancer in the fourth decade of life. Therefore, a surveillance program as stringent as that for families with MLH1 or MSH2 mutations is recommended. |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::22fbfad022f5ee638c837e9fe841df9dTest https://doi.org/10.1200/jco.2004.02.033Test |
| رقم الانضمام: | edsair.doi.dedup.....22fbfad022f5ee638c837e9fe841df9d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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