EXO1 variants occur commonly in normal population: evidence against a role in hereditary nonpolyposis colorectal cancer.
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.
Jagmohan-Changur
Shantie
S
Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands 2333.
Poikonen
Taija
T
Vilkki
Susa
S
Launonen
Virpi
V
Wikman
Friedrik
F
Orntoft
Torben F
TF
Møller
Pål
P
Vasen
Hans
H
Tops
Carli
C
Kolodner
Richard D
RD
Mecklin
Jukka-Pekka
JP
Järvinen
Heikki
H
Bevan
Stephen
S
Houlston
Richard S
RS
Aaltonen
Lauri A
LA
Fodde
Riccardo
R
Wijnen
Juul
J
Karhu
Auli
A
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
C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I; D045643:DNA Repair Enzymes