Genetic testing in hereditary non-polyposis colorectal cancer families with a MSH2, MLH1, or MSH6 mutation

• Published in: Journal of medical genetics Vol. 39; no. 11; pp. 833 - 837
• Main Authors: Wagner, A, Tops, C, Wijnen, J T, Zwinderman, K, van der Meer, C, Kets, M, Niermeijer, M F, Klijn, J G M, Tibben, A, Vasen, H F A, Meijers-Heijboer, H
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01-11-2002; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adaptor Proteins, Signal Transducing; Adult; Age; Aged; Aged, 80 and over; Biological and medical sciences; Carrier Proteins; Colorectal cancer; Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; Counseling; Decision making; Deoxyribonucleic acid; DNA; DNA-Binding Proteins - genetics; Family Health; Gastroenterology. Liver. Pancreas. Abdomen; Genetic aspects; Genetic screening; Genetic Testing; Health risk assessment; Heterozygote; HNPCC; Humans; Letter to JMG; Medical genetics; Medical sciences; Middle Aged; Mortality; Multivariate Analysis; Mutation; MutL Protein Homolog 1; MutS Homolog 2 Protein; Neoplasm Proteins - genetics; Nuclear Proteins; Ovarian cancer; Proto-Oncogene Proteins - genetics; Risk Factors; Social aspects; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surveillance; Time Factors; Tumors; Womens health; Netherlands; Human; Rectal disease; Family study; Pathogenesis; Use; Malignant tumor; Medical screening; Genetic determinism; Genetic disease; Colonic disease; Genetic counseling; Gene; Germ line; Rectum; Digestive diseases; Intestinal disease; Colon; Mutation
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.39.11.833

1, 2 HNPCC is characterised by a high risk of developing colorectal cancer and endometrial cancer at a young age (cumulative lifetime risk 80-90% and 30-40%, respectively), and by an increased risk of developing various other tumour types, such as ovarian, uroepithelial, small intestine, biliary tract, stomach, brain, and skin cancers. 2- 5 Germline mutations in one of three mismatch repair genes (MSH2, MLH1, and MSH6) were found to be responsible for a majority of HNPCC families. 6- 9 Knowledge of the causative mutation in a particular HNPCC family enables the identification of at risk family members by genetic testing. 11, 12 The possibility of early detection of colorectal cancer by stool analysis using the genetic markers TP53, BAT26, and K-RAS raises expectations for the development of less invasive surveillance procedures. 13 Furthermore, intervention trials with non-steroidal anti-inflammatory drugs (NSAID) in subjects at risk for developing colorectal cancer are in progress. 14, 15 So far, studies on the use of genetic testing in HNPCC families have used families or subjects who had been registered for research purposes. 10, 16, 17 It is conceivable, however, that these research families represent a selected group of HNPCC families where decision making processes are different from those in families in a clinical setting.