title: DNA repair pathways and mitochondrial DNA mutations in gastrointestinal carcinogenesis.
abstract: This work focuses on the main DNA repair pathways, highlighting their role in gastrointestinal carcinogenesis and the role of mitochondrial DNA (mtDNA), mutations being described in several tumor types, including those of the gastrointestinal tract. The mismatch repair (MMR) system is inherently altered in patients with hereditary non-polyposis colorectal cancer, and plays a role in carcinogenesis in a subset of sporadic colorectal, gastric and esophageal cancers. Alterations in homologous recombination (HR) and non-homologous end-joining (NHEJ) also contribute to the development of pancreatic cancer. Gene polymorphisms of some X-ray cross-complementing (XRCCs), cofactor proteins involved in the base excision repair pathway, have been investigated in relation to gastric, colorectal and pancreatic cancer. Yet only one polymorphism, XRCC1 Arg194Trp, appears to be involved in smoking-related cancers and in early onset pancreatic cancer. Although evidence in the literature indicates that mtDNA somatic mutations play a role in gastric and colorectal carcinogenesis, no sound conclusions have yet been drawn regarding this issue in pancreatic cancer, although an mtDNA variant at 16519 is believed to worsen the outcome of pancreatic cancer patients, possibly because it is involved in altering cellular metabolism.
authors.affiliation: Department of Laboratory Medicine, University-Hospital of Padova, Via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Basso
authors.forename: Filippo
authors.initials: F
authors.lastname: Navaglia
authors.forename: Paola
authors.initials: P
authors.lastname: Fogar
authors.forename: Carlo-Federico
authors.initials: CF
authors.lastname: Zambon
authors.forename: Eliana
authors.initials: E
authors.lastname: Greco
authors.forename: Stefania
authors.initials: S
authors.lastname: Schiavon
authors.forename: Michela
authors.initials: M
authors.lastname: Fasolo
authors.forename: Alessia
authors.initials: A
authors.lastname: Stranges
authors.forename: Alessandra
authors.initials: A
authors.lastname: Falda
authors.forename: Andrea
authors.initials: A
authors.lastname: Padoan
authors.forename: Elisa
authors.initials: E
authors.lastname: Fadi
authors.forename: Sergio
authors.initials: S
authors.lastname: Pedrazzoli
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
mesh_terms: D000818:Animals; D053843:DNA Mismatch Repair; D004260:DNA Repair / Q000187:drug effects*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D004272:DNA, Mitochondrial