title: Gene susceptibility to oxidative damage: from single nucleotide polymorphisms to function.
abstract: Oxidative damage to DNA can cause mutations, and mutations can lead to cancer. DNA repair of oxidative damage should therefore play a pivotal role in defending humans against cancer. This is exemplified by the increased risk of colorectal cancer of patients with germ-line mutations of the oxidative damage DNA glycosylase MUTYH. In contrast to germ-line mutations in DNA repair genes, which cause a strong deficiency in DNA repair activity in all cell types, the role of single nucleotide polymorphisms (SNPs) in sporadic cancer is unclear also because deficiencies in DNA repair, if any, are expected to be much milder. Further slowing down progress are the paucity of accurate and reproducible functional assays and poor epidemiological design of many studies. This review will focus on the most common and widely studied SNPs of oxidative DNA damage repair proteins trying to bridge the information available on biochemical and structural features of the repair proteins with the functional effects of these variants and their potential impact on the pathogenesis of disease.
authors.affiliation: Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy. valeria.simonelli@iss.it
authors.forename: Valeria
authors.initials: V
authors.lastname: Simonelli
authors.forename: Filomena
authors.initials: F
authors.lastname: Mazzei
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: D'Errico
authors.forename: Eugenia
authors.initials: E
authors.lastname: Dogliotti
mesh_terms: D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics; D006801:Humans; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D017382:Reactive Oxygen Species; D045643:DNA Repair Enzymes