title: EXO1 variants occur commonly in normal population: evidence against a role in hereditary nonpolyposis colorectal cancer.
abstract: Mutations in the currently known mismatch repair genes cannot explain all cases of hereditary nonpolyposis colorectal cancer (HNPCC), and novel predisposing genes are actively sought. Recently, mutations in the DNA repair gene EXO1 have been implicated in HNPCC. One truncating and several missense changes were observed in familial colorectal cancer (CRC) cases but not in controls. We evaluated a series of European CRC patients and population controls to clarify whether EXO1 variants may indeed predispose to familial CRC. Several variants observed in patients were also observed in controls with similar frequencies, including the truncating variant proposed previously to be a disease-causing mutation. Thus, little evidence was obtained to support a major causative role of EXO1 in HNPCC, although we cannot exclude a role for EXO1 as a low penetrance cancer susceptibility or modifying gene.
authors.affiliation: Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands 2333.
authors.forename: Shantie
authors.initials: S
authors.lastname: Jagmohan-Changur
authors.forename: Taija
authors.initials: T
authors.lastname: Poikonen
authors.forename: Susa
authors.initials: S
authors.lastname: Vilkki
authors.forename: Virpi
authors.initials: V
authors.lastname: Launonen
authors.forename: Friedrik
authors.initials: F
authors.lastname: Wikman
authors.forename: Torben F
authors.initials: TF
authors.lastname: Orntoft
authors.forename: Pål
authors.initials: P
authors.lastname: Møller
authors.forename: Hans
authors.initials: H
authors.lastname: Vasen
authors.forename: Carli
authors.initials: C
authors.lastname: Tops
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kolodner
authors.forename: Jukka-Pekka
authors.initials: JP
authors.lastname: Mecklin
authors.forename: Heikki
authors.initials: H
authors.lastname: Järvinen
authors.forename: Stephen
authors.initials: S
authors.lastname: Bevan
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fodde
authors.forename: Juul
authors.initials: J
authors.lastname: Wijnen
authors.forename: Auli
authors.initials: A
authors.lastname: Karhu
mesh_terms: D000595:Amino Acid Sequence; D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D045643:DNA Repair Enzymes; D005090:Exodeoxyribonucleases / Q000235:genetics*; D005190:Family; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D012016:Reference Values; D015183:Restriction Mapping; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I; D045643:DNA Repair Enzymes