Invited critical review DNA repair pathways and mitochondrial DNA mutations in gastrointestinal carcinogenesis

AbstractThis work focuses on the main DNA repair pathways, highlighting their role in gastrointestinal carcinogenesis and the role of mitochondrialDNA (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 incarcinogenesis in a subset of sporadic colorectal, gastric and esophageal cancers. Alterations in homologous recombination (HR) and non-homologo usend-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. Ye t onlyone 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 soundconclusions have yet been drawn regarding this issue in pancreatic cancer, although an mtDNAvariant at 16519 is believed to worsen the outcomeof pancreatic cancer patients, possibly because it is involved in altering cellular metabolism.© 2007 Elsevier B.V. All rights reserved.