title: Proportion and phenotype of MYH-associated colorectal neoplasia in a population-based series of Finnish colorectal cancer patients.
abstract: Recessively inherited mutations in the base excision repair gene MYH have recently been associated with predisposition to colorectal adenomas and cancer in materials selected for occurrence of multiple adenomas. In particular, variants Y165C and G382D have been shown to play a role in Caucasian patients. To evaluate the contribution of MYH mutations to colorectal cancer burden on the population level, and to examine the MYH-associated phenotype in an unselected series of colorectal cancer patients, we determined the frequencies of Y165C and G382D MYH mutations in a population-based series of 1042 Finnish colorectal cancer patients. Four (0.4%) patients had both MYH alleles mutated. Although all these patients had multiple adenomatous polyps, the phenotypes tended to be less extreme than in previous studies on selected cases. The lowest number of colorectal adenomas at the time of cancer diagnosis was five. Cases with one mutant MYH allele were subjected to sequencing of all exons to detect possible Finnish founder mutations, but no additional changes were detected. The Y165C and G382D variants were not present in 424 Finnish cancer-free controls showing that MYH mutations are not enriched in the population. As evaluated against national Finnish Polyposis Registry data MYH-associated colorectal cancer appears to be as common as colorectal cancer associated with familial adenomatous polyposis.
authors.affiliation: Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 3, Helsinki, FIN-00014, Finland.
authors.forename: Susa
authors.initials: S
authors.lastname: Enholm
authors.forename: Tuija
authors.initials: T
authors.lastname: Hienonen
authors.forename: Anu
authors.initials: A
authors.lastname: Suomalainen
authors.forename: Lara
authors.initials: L
authors.lastname: Lipton
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
authors.forename: Vesa
authors.initials: V
authors.lastname: Kärjä
authors.forename: Matti
authors.initials: M
authors.lastname: Eskelinen
authors.forename: Jukka-Pekka
authors.initials: JP
authors.lastname: Mecklin
authors.forename: Auli
authors.initials: A
authors.lastname: Karhu
authors.forename: Heikki J
authors.initials: HJ
authors.lastname: Järvinen
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Aaltonen
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000150:complications; D000328:Adult; D000368:Aged; D000483:Alleles; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D045647:DNA Glycosylases; D005260:Female; D005387:Finland; D005787:Gene Frequency; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000235:genetics*; D010641:Phenotype
chemical_list: D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C061738:mutY adenine glycosylase