title: DNA repair dysfunction in gastrointestinal tract cancers.
abstract: The DNA repair system surveys the genome, which is always suffering from exposure to both exogenous as well as endogenous mutagens, to maintain the genetic information. The fact that the basis of this DNA repair system is highly conserved, from prokaryote to mammalian cells, suggests the importance of precise genome maintenance mechanisms for organisms. In the past 15 years, considerable progress has been made in understanding how repair processes interact and how disruptions of these mechanisms lead to the accumulation of mutations and carcinogenesis. In 1993, two groups reported that DNA mismatch repair could be associated with hereditary non-polyposis colorectal cancer, indicating a connection between faulty DNA repair function and cancer. More recently, an inherited disorder of DNA glycosylase, which removes mutagenic oxidized base from DNA, has been reported in individuals with a predisposition to multiple colorectal adenomas and carcinomas. This is the first report that directly indicates the role of the repair of oxidative DNA in human inherited cancer. Studies from gene knockout mice have elucidated the principal role of these repair systems in the process of carcinogenesis. Moreover, clinical samples derived from cancer patients have shown the direct involvement. This review focuses on the function of DNA mismatch repair and oxidative DNA/nucleotide repair among various DNA repair systems in cells, both of which are essentially involved in the carcinogenesis of gastrointestinal tract cancer.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. maehara@surg2.med.kyushu-u.ac.jp
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Akinori
authors.initials: A
authors.lastname: Egashira
authors.forename: Eiji
authors.initials: E
authors.lastname: Oki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Tsuzuki
mesh_terms: D000818:Animals; D004249:DNA Damage; D053843:DNA Mismatch Repair; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D006801:Humans; D051379:Mice; D023421:Models, Animal; D008954:Models, Biological; D010084:Oxidation-Reduction; D010641:Phenotype