DNA repair pathways and mitochondrial DNA mutations in gastrointestinal carcinogenesis.
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.
Basso
Daniela
D
Department of Laboratory Medicine, University-Hospital of Padova, Via Giustiniani 2, 35128 Padova, Italy.
Navaglia
Filippo
F
Fogar
Paola
P
Zambon
Carlo-Federico
CF
Greco
Eliana
E
Schiavon
Stefania
S
Fasolo
Michela
M
Stranges
Alessia
A
Falda
Alessandra
A
Padoan
Andrea
A
Fadi
Elisa
E
Pedrazzoli
Sergio
S
Plebani
Mario
M
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*
D004272:DNA, Mitochondrial