Gene-environment interaction in hereditary nonpolyposis colorectal cancer with implications for diagnosis and genetic testing.
Hereditary nonpolyposis colorectal cancer (Lynch syndrome) is an autosomal dominant disease caused by mutations in the mismatch repair genes in particular in MLHI, MSH2 and MSH6.
The disease is characterized by the development of colorectal, endometrial cancer and several other cancers.
There is evidence that the clinical expression of the disease varies from one country to another.
This variation might affect not only the application of criteria proposed to identify families but also clinical risk factors reported to predict the outcome of genetic testing.
Data on site of the cancer, age at diagnosis and pathology were collected from 155 families with suspected HNPCC known at the Korean and Dutch HNPCC registries.
DGGE, SSCP and DNA-sequencing were performed to identify MSH2, MLH1 and MSH6 mutations.
A total of 33 Korean and 42 Dutch families met the clinical criteria for HNPCC.
Germline mutations in the MMR-genes were found in 23 Korean and 24 Dutch families.
In families that met the Amsterdam criteria, and also in those associated with MLH 1 mutations, more cancers of the stomach and pancreas were observed in the Korean families than in the Dutch HNPCC families ; in relative terms, the incidence of cancers of the endometrium in the Korean families was lower.
Multivariate analysis showed that an early age at diagnosis, and the occurrence of pancreatic cancer were independent predictive factors of germline mutations in MLH1, MSH2 and MSH6 in the Korean subset of families.
Mots-clés Pascal : Tumeur maligne, Côlon, Rectum, Héréditaire, Mutation, Lignée germinale, Gène, Réparation, Mésappariement base, Incidence, Facteur risque, Epidémiologie, Génétique, Diagnostic, Pancréas, Endomètre, Corée, Asie, Pays Bas, Europe, Etude comparative, Homme, Appareil digestif pathologie, Intestin pathologie, Côlon pathologie, Rectum pathologie, Utérus pathologie, Appareil génital femelle pathologie, Pancréas pathologie, Maladie héréditaire, Gène MLH1, Lynch syndrome, Gène MLH2, Gène MLH6
Mots-clés Pascal anglais : Malignant tumor, Colon, Rectum, Hereditary, Mutation, Germ line, Gene, Repair, Base mismatching, Incidence, Risk factor, Epidemiology, Genetics, Diagnosis, Pancreas, Endometrium, Korea, Asia, Netherlands, Europe, Comparative study, Human, Digestive diseases, Intestinal disease, Colonic disease, Rectal disease, Uterine diseases, Female genital diseases, Pancreatic disease, Genetic disease
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 99-0488050
Code Inist : 002B13B01. Création : 22/03/2000.