The thorough screening of the MUTYH gene in a large French cohort of sporadic colorectal cancers.
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.
Küry
Sébastien
S
Laboratoire d'Etude de l'ADN, Faculté de Médecine de Nantes, 44035 France. Kury@univ-nantes.fr <Kury@univ-nantes.fr>
Buecher
Bruno
B
Robiou-du-Pont
Sébastien
S
Scoul
Catherine
C
Colman
Hélène
H
Lelièvre
Bénédicte
B
Olschwang
Sylviane
S
Le Houérou
Claire
C
Le Neel
Tanguy
T
Faroux
Roger
R
Ollivry
Jean
J
Lafraise
Bernard
B
Chupin
Louis-Dominique
LD
Bézieau
Stéphane
S
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
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase