title: The thorough screening of the MUTYH gene in a large French cohort of sporadic colorectal cancers.
abstract: The MUTYH gene encodes a key glycosylase of the base-excision repair system that is involved in maintaining genomic DNA stability against oxidative damage. Biallelic germline MUTYH mutations have been proved to greatly predispose to non-familial adenomatous polyposis (FAP) and non-hereditary non-polyposis colorectal cancer (HNPCC) familial recessive forms of colorectal cancer with multiple adenomas. To date, there is still much debate over the impact of monoallelic germline MUTYH mutations on colorectal carcinogenesis. To evaluate their role in the susceptibility to sporadic colon and rectum cancers, we screened 1024 French sporadic colorectal cancer cases and 1121 French healthy controls for Caucasian MUTYH-associated polyposis mutations, including already known mutations p.Gly382Asp and p.Tyr165Cys, and new mutation p.Val479Phe. We observed a nonstatistically significant association between these MUTYH mutations at a heterozygous state and an increase in colorectal cancer risk (odds ratio [OR] 1.26, 95% confidence interval [CI] 0.70-2.27). As a result, we conclude that heterozygous MUTYH mutations do not play a major role in sporadic colorectal carcinogenesis although a modest effect on this process cannot be ruled out.
authors.affiliation: Laboratoire d'Etude de l'ADN, Faculté de Médecine de Nantes, 44035 France. Kury@univ-nantes.fr <Kury@univ-nantes.fr>
authors.forename: Sébastien
authors.initials: S
authors.lastname: Küry
authors.forename: Bruno
authors.initials: B
authors.lastname: Buecher
authors.forename: Sébastien
authors.initials: S
authors.lastname: Robiou-du-Pont
authors.forename: Catherine
authors.initials: C
authors.lastname: Scoul
authors.forename: Hélène
authors.initials: H
authors.lastname: Colman
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Lelièvre
authors.forename: Sylviane
authors.initials: S
authors.lastname: Olschwang
authors.forename: Claire
authors.initials: C
authors.lastname: Le Houérou
authors.forename: Tanguy
authors.initials: T
authors.lastname: Le Neel
authors.forename: Roger
authors.initials: R
authors.lastname: Faroux
authors.forename: Jean
authors.initials: J
authors.lastname: Ollivry
authors.forename: Bernard
authors.initials: B
authors.lastname: Lafraise
authors.forename: Louis-Dominique
authors.initials: LD
authors.lastname: Chupin
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bézieau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase