pylori-associated diseases   Univariate analysis Multivariate analysis   p OR 95% CI p Gastric cancer            - Increasing age < 10-3 1.04 1.03 - 1.06 < 10-3    - Female sex < 10-3 0.29 0.18 - 0.48 < 10-3    - High-risk EPIYA (ABCC or ABCCC) < 10-3 3.08 1.74 - 5.45 < 10-3 Duodenal ulcer            - Increasing age < 10-3 1.03 1.02 - 1.05 < 10-3    - Female sex 0.04 1.26 0.73 - 2.18 0.41    - High-risk EPIYA (ABCC GDC-0941 in vitro or ABCCC) 0.29 – - – The Hosmer-Lemeshow test showed good fitness of the model of gastric cancer (8 degrees of freedom, p = 0.86, with 10 steps) and duodenal ulcer (8 degrees of freedom, p = 0.25, with 10 steps). Because it might be speculated that the

number of EPIYA C motifs increases with increasing age, we also constructed a model BIBW2992 with the number of EPIYA C being the dependent variable and the age, sex and H. pylori-associated diseases as independent covariables. Increased EPIYA C segments did not associate with age (p = 0.13), sex (p = 0.66) and duodenal ulcer (p = 0.29) but remained associated with gastric cancer (p < 10-3, OR = 2.81; 95% CI = 1.64 - 4.82). Association between mixed strain colonization and diseases Mixed strain infection was observed in 57 (13.08%) patients and it was significantly more frequent in patients with gastric cancer (38/188, 20.2%) than in those with gastritis (14/136, 10.3%) with an OR for gastric carcinoma of 2.21 (95%CI

= 1.10 to 4.50). Otherwise, mixed infection was less LXH254 frequently observed in duodenal ulcer patients (5/112, 4.5%) with a trend to a negative association (p = 0.09). Association between the numbers of EPIYA C segments Methamphetamine and serum PGI levels The pepsinogen I serum levels were significantly higher (p = 0.01) in duodenal ulcer (mean 161.67 ± 102.36 μg/L) than in gastritis (100.37 ± 70.85 μg/L). The patients infected by CagA strains possessing two or three EPIYA C segments showed decreased levels of PGI when compared with those with infection by CagA strains possessing ≤ 1 EPIYA C segment (duodenal

ulcer: 179.67 ± 83.30 vs. 67.01 ± 34.30, respectively, p = 0.02 and gastritis: 109.26 ± 85.61 vs. 57.55 ± 34.61, respectively, p = 0.01). Association between the numbers of EPIYA C repeats and gastric histological alterations and tumour classification Increased number of EPIYA C segments was associated with the presence of precancerous lesions, either atrophy (p = 0.04) or intestinal metaplasia (p = 0.007), but not with the other histological parameters. Also, the infection by strains carrying increased EPIYA C motifs did not associate with intestinal or diffuse tumour type (p = 0.34). Discussion In this study, by evaluating a large series of patient, we demonstrated that those infected by CagA-positive H. pylori strains possessing more than one EPIYA C motif are at thrice-fold increased risk for developing gastric cancer.