title: Oxidative DNA damage in human esophageal cancer: clinicopathological analysis of 8-hydroxydeoxyguanosine and its repair enzyme.
abstract: Both internal and external oxidative stresses act on DNA and can induce carcinogenesis. 8-hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and it leads to transversion mutations and carcinogenesis. 8-OHdG is excision-repaired by 8-OHdG DNA glycosylase (OGG1). The purpose of this study is to clarify the effect of oxidative DNA damage and repair enzymes on esophageal carcinogenesis. The levels of 8-OHdG and OGG1 were immunohistochemically evaluated in resected specimens, including squamous cell carcinoma (SCC) in 97 patients with esophageal cancer. Higher levels of 8-OHdG in normal esophageal epithelium were associated with a higher smoking index (P = 0.0464). The 8-OHdG level was higher in cancerous areas than in normal epithelia (P = 0.0061), whereas OGG1 expression was weaker in cancerous areas than in normal epithelia (P < 0.0001). An increase of OGG1 expression in normal epithelium was observed as 8-OHdG levels increased (P = 0.0011). However, this correlation was not observed in cancerous areas. High OGG1 expression in the cytoplasm was related to deeper tumors (P = 0.0023), node metastasis (P = 0.0065) and stage (P = 0.0019). Oxidative DNA damage, which is attributable to smoking as well as disturbances in DNA repair systems, appears to be closely related to esophageal carcinogenesis and its progression.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kubo
authors.forename: M
authors.initials: M
authors.lastname: Morita
authors.forename: Y
authors.initials: Y
authors.lastname: Nakashima
authors.forename: H
authors.initials: H
authors.lastname: Kitao
authors.forename: A
authors.initials: A
authors.lastname: Egashira
authors.forename: H
authors.initials: H
authors.lastname: Saeki
authors.forename: E
authors.initials: E
authors.lastname: Oki
authors.forename: Y
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Y
authors.initials: Y
authors.lastname: Oda
authors.forename: Y
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D004249:DNA Damage; D045647:DNA Glycosylases / Q000032:analysis*; D045643:DNA Repair Enzymes / Q000032:analysis; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004848:Epithelium / Q000201:enzymology; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D004947:Esophagus / Q000201:enzymology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018384:Oxidative Stress; D012907:Smoking
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D045643:DNA Repair Enzymes; D003849:Deoxyguanosine
keywords: 8-OHdG DNA glycosylase; 8-hydroxydeoxyguanosine; base excision repair; esophageal cancer; oxidative DNA damage