Clinical findings with implications for genetic testing in families with clustering of colorectal cancer
| العنوان: | Clinical findings with implications for genetic testing in families with clustering of colorectal cancer |
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| المؤلفون: | P M Khan, Lucio Bertario, Adri Mulder, C Schaap, Ketil Heimdal, Han G. Brunner, Pål Møller, Riccardo Fodde, C. Tops, P. Goetz, Gerrit Griffioen, J.G. Post, Juul T. Wijnen, Dick Lindhout, Martijn H. Breuning, Fokko N. Nagengast, Jaran Apold, van Leeuwen-Cornelisse, Rolf H. Sijmons, Egbert Bakker, Marie Luise Bisgaard, Ahjt Brocker-Vriends, A Meijers-Heijboer, B. G. Taal, Aeilko H. Zwinderman, Fred H. Menko, Jan H. Kleibeuker, H. F. A. Vasen, H. van der Klift |
| المساهمون: | Other departments, Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| المصدر: | ResearcherID New England journal of medicine, 339(8), 511-518. Massachussetts Medical Society New England Journal of Medicine, 339(8), 511-518. MASSACHUSETTS MEDICAL SOC |
| سنة النشر: | 1998 |
| مصطلحات موضوعية: | Oncology, Male, APC GENE, DNA Repair, Colorectal cancer, MICROSATELLITE INSTABILITY, DNA Mutational Analysis, MUTATION ANALYSIS, medicine.disease_cause, Neoplasms, Multiple Primary, PMS2, Cluster Analysis, Genetics, Mutation, medicine.diagnostic_test, COLON-CANCER, Age Factors, GRADIENT-GEL-ELECTROPHORESIS, Nuclear Proteins, General Medicine, Middle Aged, Electrophoresis, Gel, Pulsed-Field, Neoplasm Proteins, DNA-Binding Proteins, POLYPOSIS, MutS Homolog 2 Protein, Female, Colorectal Neoplasms, MutL Protein Homolog 1, Adult, medicine.medical_specialty, Amsterdam criteria, congenital, hereditary, and neonatal diseases and abnormalities, HNPCC, MLH1, Internal medicine, Proto-Oncogene Proteins, medicine, Humans, Genetic Testing, neoplasms, Genetic testing, Adaptor Proteins, Signal Transducing, Aged, RECEPTOR, business.industry, nutritional and metabolic diseases, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, digestive system diseases, Endometrial Neoplasms, MSH6, HOMOLOG, Logistic Models, MSH2, Multivariate Analysis, MAJORITY, business, Carrier Proteins |
| الوصف: | Background Germ-line mutations in DNA mismatch-repair genes (MSH2, MLH1, PIMS1, PMS2, and MSH6) cause susceptibility to hereditary nonpolyposis colorectal cancer. We assessed the prevalence of MSH2 and MLH1 mutations in families suspected of having hereditary nonpolyposis colorectal cancer and evaluated whether clinical findings can predict the outcome of genetic testing. Methods We used denaturing gradient gel electrophoresis to identify MSH2 and MLH1 mutations in 184 kindreds with familiar clustering of colorectal cancer or other cancers associated with hereditary nonpolyposis colorectal cancer. Information on the site of cancer, the age at diagnosis, and the number of affected family members was obtained from all families. Results Mutations of MSH2 or MLH1 were found in 47 of the 184 kindreds (26 percent). Clinical factors associated with these mutations were early age at diagnosis of colorectal cancer, the occurrence in the kindred of endometrial cancer or tumors of the small intestine, a higher number of family members with colorectal or endometrial cancer, the presence of multiple colorectal cancers or both colorectal and endometrial cancers in a single family member, and fulfillment of the Amsterdam criteria for the diagnosis of hereditary nonpolyposis colorectal cancer (at least three family members in two or more successive generations must have colorectal cancer, one of whom is a first-degree relative of the other two; cancer must be diagnosed before the age of 50 in at least one family member; and familial adenomatous polyposis must be ruled out). Multivariate analysis showed that a younger age at diagnosis of colorectal cancer, fulfillment of the Amsterdam criteria, and the presence of endometrial cancer in the kindred were independent predictors of germ-line mutations of MSH2 or MLH1. These results were used to devise a logistic model for estimating the likelihood of a mutation in MSH2 and MLH1. Conclusions Assessment of clinical findings can improve the rate of detection of mutations of DNA mismatch-repair genes in families suspected of having hereditary nonpolyposis colorectal cancer. (N Engl J Med 1998;339:511-8.) (C)1998, Massachusetts Medical Society. |
| تدمد: | 0028-4793 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5bca113090b3a1a1d7c066d495ccb1c0Test https://pubmed.ncbi.nlm.nih.gov/9709044Test |
| حقوق: | RESTRICTED |
| رقم الانضمام: | edsair.doi.dedup.....5bca113090b3a1a1d7c066d495ccb1c0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00284793 |
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