Genetic anticipation in Swedish Lynch syndrome families

by Jenny von Salom é, Philip S. Boonstra, Masoud Karimi, Gustav Silander, Marie Stenmark-Askmalm, Samuel Gebre-Medhin, Christos Aravidis, Mef Nilbert, Annika Lindblom, Kristina Lagerstedt-Robinson Among hereditary colorectal cancer predisposing syndromes, Lynch syndrome (LS) caused by mutations in DNA mismatch repair genesMLH1,MSH2,MSH6 orPMS2 is the most common. Patients with LS have an increased risk of early onset colon and endometrial cancer, but also other tumors that generally have an earlier onset compared to the general population. However, age at first primary cancer varies within families and genetic anticipation, i.e. decreasing age at onset in successive generations, has been suggested in LS. Anticipation is a well-known phenomenon in e.g neurodegenerative diseases and several reports have studied anticipation in heritable cancer. The purpose of this study is to determine whether anticipation can be shown in a large cohort of Swedish LS families referred to the regional departments of clinical genetics in Lund, Stockholm, Link öping, Uppsala and Umeå between the years 1990–2013. We analyzed a homogenous group of mutation carriers, utilizing information from both affected and non-affected family members. In total, 239 families with a mismatch repair gene mutation (96MLH1 families, 90MSH2 families including one family with anEPCAM –MSH2 deletion, 39MSH6 families, 12PMS2 families, and 2MLH1+PMS2 families) comprising 1028 at-risk carriers were identified among...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research