Oxidative DNA damage in gastric cancer: CagA status and OGG1 gene polymorphism.
Oxidative DNA damage is thought to play an important part in the pathogenesis of H. pylori-induced mucosal damage. 8-OHdG is a sensitive marker of DNA oxidation and is repaired by a polymorphic glycosylase (OGG1) more effectively than by OGG1-Cys(326). The aims of this study were to ascertain the respective roles of H. pylori, cagA status and OGG1 polymorphism in determining 8-OHdG levels in benign and premalignant stomach diseases and in gastric cancer (GC). The study involved 50 GC patients (for whom both neoplastic tissue and surrounding mucosa were available), 35 with intestinal metaplasia and atrophy (IMA) and 43 controls. H. pylori and cagA status were determined by histology and polymerase chain reaction for urease and cagA. 8-OHdG was assayed using HPLC with an electrochemical detector (HPLC-ED). The OGG1 1245C-->G transversion was identified using RFLP analyses. 8-OHdG levels were significantly higher in GC, with no differences in relation to H. pylori or cagA status. OGG1 polymorphism was documented in 34% of GC (15 Ser/Cys, 2 Cys/Cys). OGG1 1245C-->G polymorphism was detected in 54% of IMA patients, but only 16% of controls (p = 0.0004) and coincided with significantly higher 8-OHdG levels. In the multivariate analysis, 8-OHdG levels were predicted by histotype and OGG1 status. OGG1 1245C-->G polymorphism was common in both GC and IMA, but very rare in controls, and correlated more closely with 8-OHdG levels than do H. pylori infection or cagA status.
Farinati
Fabio
F
Dipartimento di Scienze Chirurgiche e Gastroenterologiche, Università di Padova, Padova, Italy. fabio.farinati@unipd.it
Cardin
Romilda
R
Bortolami
Marina
M
Nitti
Donato
D
Basso
Daniela
D
de Bernard
Marina
M
Cassaro
Mauro
M
Sergio
Adriana
A
Rugge
Massimo
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001284:Atrophy / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005757:Gastritis, Atrophic / Q000378:metabolism; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D007422:Intestines / Q000473:pathology*; D008297:Male; D008679:Metaplasia / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D014510:Urease / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D014408:Biomarkers, Tumor; C080866:cagA protein, Helicobacter pylori; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D014510:Urease; D003849:Deoxyguanosine