© 2003 Blackwell Publishing Ltd, Helicobacter , 8, 227–234 227 Volume 8 • Number 3 • 2003 HELICOBACTER Blackwell Publishing Ltd. Helicobacter pylori CagA Status, Mucosal Oxidative Damage and Gastritis Phenotype: A Potential Pathway to Cancer? Fabio Farinati, * Romilda Cardin, * Valentina M. Russo, † Graziella Busatto, ‡ Monica Franco * and Massimo Rugge † * Dipartimento di Scienze Chirurgiche e Gastroenterologiche – Sezione di Gastroenterologia, Università degli Studi di Padova; † Dipartimento di Scienze Oncologiche & Chirurgiche, III°Cattedra Anatomia Patologica, Università degli Studi di Padova; and ‡ Unità Operativa di Anatomia Patologica Azienda Ospedaliera Alta Padovana – Ospedale di Cittadella- Padova ABSTRACT Background. Oxidative DNA damage is associated with Helicobacter pylori infection, atrophy and intestinal metaplasia. H. pylori-cagA-positive strains are associated with the highest risk of gastric cancer. Aims. To ascertain whether cagA-positive H. pylori infection correlates with higher concentrations of 8OHdG and the presence of precancerous changes. Patients and Methods. 118 patients were studied (65M/53F, age 61 ± 14 years). Twelve were H. pylori- negative. Among the H. pylori-positive patients, 34 were cagA-positive and 40 were cagA negative. In 32 patients H. pylori had been eradicated at least 6 months before endoscopic sampling. The phenotype of the gastritis (atrophic com- pared with nonatrophic, with and without intestinal metaplasia) was scored in biopsy samples obtained from the antrum, corpus, and angularis incisura. In antral biopsy samples, 8-hydroxydeoxyguanosine was assessed by HPLC (electrochemical detector). CagA status was determined by PCR. Results. The highest scores for both mononuclear inflammation and activity of gastritis were significantly associated with cagA status ( p = 0.036 antrum and p = 0.02 corpus). cagA-positive infection significantly correlated with a higher prevalence of atrophic- metaplastic lesions ( p = 0.04). cagA-positive patients had higher 8-hydroxydeoxyguanosine levels than both cagA-negative and H. pylori-negative cases ( p = 0.01). The 8-hydroxydeoxyguanosine levels were significantly higher in multifocal atrophic gastritis ( p = 0.04). The odds ratio for cagA-positive patients having 8OHdG levels above a cut-off calculated on the basis of the ROC curves were 7.12, overall, reaching 11.25 when only patients younger than 50 were considered. Conclusions. cagA-positive patients were charac- terized: first, for higher scores for gastritis, activity and atrophic and metaplastic lesions; and second for greater oxidative DNA damage overall, at younger age and in the presence of multifocal atrophy. This setting may represent a cancer-prone biological context. T he biological heterogeneity of Helicobacter pylori is well recognized. Several putative virulence factors for H. pylori have been identi- fied, including vacA , iceA and particularly cagA , the cytotoxin-associated gene A, a gene encoding a high-molecular-weight immuno- dominant antigen [1–3]. Several studies have concluded that infec- tion with cagA -positive H. pylori strains is associated with higher levels of mononuclear and neutrophilic infiltrates, more severe atrophy, intestinal metaplasia and alterations in the gastric epithelial cell cycle, and apoptosis [4–7]. How- ever, there is no universal agreement on the link between H. pylori strains harboring cagA and the reportedly higher risk of precancerous lesions and cancer [8–11]. Indeed, Graham et al. [12] recently reported that the presence of a functional cagA pathogenicity island has no predictive value for the presence, or future development of a clinically significant outcome. In addition to the differences between bacterial strains, other factors (i.e. environment, diet and host) may influence the risk of developing gas- tric cancer [13,14]. On the whole, the exact role of H. pylori cagA status in the onset of gastric cancer is not well defined and may vary in rela- tion to different geographical areas [11,15,16]. Reprint requests to: Dr Fabio Farinati, Dipartimento di Scienze Chirurgiche e Gastroenterologiche, Sezione di Gastroenterologia, Policlinico Universitario, Via Giustiniani 2, 35128 Padova Italy.