title: Analysis of the base excision repair genes MTH1, OGG1 and MUTYH in patients with squamous oral carcinomas.
abstract: A number of environmental factors, such as tobacco and alcohol, have been implicated, through oxidative DNA damage, in the development of squamous cell carcinomas of the head and neck (SCCHN). Several pathways are involved in the repair of DNA lesions caused by oxidative stress, such as the base excision repair system (BER), which repairs mutation involving 8-oxoguanine and comprises the MUTYH, OGG1 and MTH1 genes. We analysed 29 patients, assessing germline polymorphisms or mutations in these genes by complete genomic sequencing of exons and adjacent intronic regions. Thirty healthy blood donors served as controls. No pathogenic germline mutations were identified. We found common and rare new variants in the coding and adjacent intronic regions. In summary, our data do not support a major role for MUTYH, OGG1 and MTH1 variants in the etiology of sporadic squamous oral/oropharyngeal carcinomas. This does not exclude the involvement of the three BER genes in the tumorigenesis of SCCHN through other mechanisms such as promotor hypermethylation, genomic rearrangements or mutations involving regulatory sequences.
authors.affiliation: Department of Surgical Research, Technische Universität Dresden, D-01307 Dresden, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Görgens
authors.forename: Annegret
authors.initials: A
authors.lastname: Müller
authors.forename: Stefan
authors.initials: S
authors.lastname: Krüger
authors.forename: Eberhard
authors.initials: E
authors.lastname: Kuhlisch
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Hans K
authors.initials: HK
authors.lastname: Schackert
authors.forename: Uwe
authors.initials: U
authors.lastname: Eckelt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D018095:Germ-Line Mutation; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009959:Oropharyngeal Neoplasms / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D010744:Phosphoric Monoester Hydrolases; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; C479058:oxoguanine glycosylase 1, human; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes