THE CagL Glu59 POLYMORPHISM OF H. pylori IS ASSOCIATED WITH AN INCREASED RISK OF GASTRIC CANCER. PRELIMINARY RESULTS FROM AN ITALIAN MULTICENTER STUDY

BACKGROUND: The risk of H. pylori-associated gastric cancer is increased when the infecting strain bears the cag-pathogenicity island or the s1/m1 vacA gene polymorphisms. A recent report showed that coding polymorphisms of cagL gene, belonging to the cag-pathogenicity island, are associated with gastric cancer risk in Taiwanese patients. Our study was aimed to evaluate this association in Italian subjects infected by Western H. pylori strains. METHODS: we retrospectively selected 206 patients infected by H. pylori (98 bearing the cag-pathogenicity island), 44 with gastric cancer (23 males, 21 females; mean age \ub1 SD: 67.6 \ub1 13 years) and 162 with benign H. pylori associated pathologies (control group) (26 male, 33 female; mean age \ub1 SD: 50.6 \ub1 14.1 years). Histology was used to diagnose gastric cancer and, in control group, to evaluate inflammation, activity, intestinal metaplasia and bacterial load. H. pylori was cultured from gastric specimens and genomic DNA extracted from isolates. CagL aminoacidic polymorphisms at residues 58 and 59, cagA gene presence as well as vacA s1 and m1 polymorphisms were determined by direct sequencing and PCR respectively. RESULTS: Gastric cancer was associated with infections sustained by strains bearing cagA gene (chi square=37.83, p<0.0001) and the s1/m1 vacA polymorphisms (chi square=27.15, p<0.0001 and chi square=26.64, p<0.0001 respectively). All cagA positive and s1/m1 vacA strains possessed the cagL gene. Considering these virulent strains (cagA/cagL positive and s1/m1 vacA) the glutammic acid at residue 59 of CagL protein (Glu59) was significantly more frequent among gastric cancer patients than controls (61.5% and 40.7% respectively) (chi square=4.089, p<0.05). At logistic regression analysis cagL Glu59 was confirmed to be a significant independent predictor of gastric cancer (p