H. pylori CagA protein with higher number of EPIYA-C segments or EPIYA-D motif has been associated with precancerous lesions and gastric cancer, which needs to be confirmed in different regions. Recently, it has also been shown that CagA contains polymorphic CM located downstream the EPIYA-C or D segment that mediates interaction of CagA with PAR1b/MARK2 and inhibits PAR1b kinase activity disrupting tight junctions and epithelial cell polarity. Because CagA+ status is associated with increased IL-1β, IL-8 and IL-12 release, studies attempting to demonstrate In Vitro associations between IL-8 levels and the number of EPIYA-C segments have been done, but the results are discordant. Here, we evaluated whether the number of EPIYA-C segments is associated with the risk of H. pylori-related diseases adjusting for gender and age. We also evaluate the type and number of CM sequences in respect to the risk of diseases and gastric cytokine levels. We studied 521 patients with gastritis (G, n=250, 114 cagA-), duodenal ulcer (DU, n=149, 19 cagA-) and gastric carcinoma (GC, n=125, all cagA+). The number of EPIYA-C segments and CM was determined by PCR followed by sequencing. The gastric levels of IL-1β, IL-8 and IL-12 were evaluated by ELISA (Biosource, Camarillo). Patients with GC (41%) were more often infected with strains with more than one EPIYA-C segment than the patients with G (18.5%) and DU (17.0%). In the logistic analysis, the number of EPIYA C segments (OR=3.05, 95%CI=1.64-5.66, p .23), DU (p>.29) and GC (p>.20). Neither the number nor the Eastern CM pattern was associated with the diseases or cytokine levels, but both associated with diffuse (90.1%, p=.01), but not intestinal (70.1%) tumor type. Infection with strains with more than one EPIYA-C segment was significantly associated with corpus intestinal metaplasia (p<.000) and atrophy (p=.02). In conclusion the number of EPIYA-C segments but not CM is associated with increased risk of GC. Although CagA enhances IL-8 and IL-12p70 gastric levels, the number of EPIYA-C segments and CM does not affect the cytokine production. Of note, increased Eastern CM that is associated with junctional cell defects was associated with diffuse type tumor. CNPq/FAPEMIG/INCT.