title: Association of MUTYH and MSH6 germline mutations in colorectal cancer patients.
abstract: Colorectal cancer (CRC) risk associated with germline monoallelic MUTYH mutations remains controversial, although a slightly increased risk for this disease has been suggested. MUTYH and MSH6 proteins act in cooperation during the DNA repair process. Based on this interaction, it was hypothesized that the combination of heterozygote germline mutations in both genes could result in an increased CRC risk. To further clarify the interaction between MUTYH and MSH6, we analyzed the prevalence of MSH6 mutations in a cohort of CRC patients and controls previously tested for MUTYH mutations: CRC patients with and without a monoallelic MUTYH mutation (group I, n = 26; group II, n = 50, respectively), and healthy carriers with a monoallelic MUTYH mutation (group III, n = 21). In group I, we found three patients (11.5%) with MSH6 mutations, a missense mutation (p.R635G), a change in the 3'UTR region (c.*4098A > C) and a nonsense mutation (p.Q982X). In group II and III, no mutations were detected. In CRC patients, MSH6 mutations were more frequently found in MUTYH mutation carriers than in noncarriers (11.5% vs. 0%, P = 0.037). CRC patients carrying monoallelic MUTYH mutations harbor more frequently concomitant MSH6 mutations than patients without them, thus suggesting that both genes could act cooperatively and confer together an increased CRC risk.
authors.affiliation: Gastroenterology Department, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Catalonia, Barcelona, Spain.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Giráldez
authors.forename: Francesc
authors.initials: F
authors.lastname: Balaguer
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldés
authors.forename: Ana
authors.initials: A
authors.lastname: Sanchez-de-Abajo
authors.forename: Nuria
authors.initials: N
authors.lastname: Gómez-Fernández
authors.forename: Clara
authors.initials: C
authors.lastname: Ruiz-Ponte
authors.forename: Jenifer
authors.initials: J
authors.lastname: Muñoz
authors.forename: Pilar
authors.initials: P
authors.lastname: Garre
authors.forename: Victoria
authors.initials: V
authors.lastname: Gonzalo
authors.forename: Leticia
authors.initials: L
authors.lastname: Moreira
authors.forename: Teresa
authors.initials: T
authors.lastname: Ocaña
authors.forename: Joan
authors.initials: J
authors.lastname: Clofent
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.forename: Montserrat
authors.initials: M
authors.lastname: Andreu
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Jover
authors.forename: Xavier
authors.initials: X
authors.lastname: Llor
authors.forename: Antoni
authors.initials: A
authors.lastname: Castells
authors.forename: Sergi
authors.initials: S
authors.lastname: Castellví-Bel
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016133:Polymerase Chain Reaction
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase
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