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<p>Abstract</p> <p>Background</p> <p>To evaluate the prevalence of more virulent <it>H. pylori</it> genotypes in relatives of gastric cancer patients and in patients without family histories of gastric cancer.</p> <p>Methods</p> <p>We evaluated prospectively the prevalence of the infection by more virulent <it>H. pylori</it> strains in 60 relatives of gastric cancer patients comparing the results with those obtained from 49 patients without family histories of gastric cancer. <it>H. pylor</it>i status was determined by the urease test, histology and presence of <it>H. pylori ure</it>A. The cytotoxin associated gene (<it>cag</it>A), the <it>cag</it>A-EPIYA and vacuolating cytotoxin gene (<it>vac</it>A) were typed by PCR and the <it>cag</it>A EPIYA typing was confirmed by sequencing.</p> <p>Results</p> <p>The gastric cancer relatives were significant and independently more frequently colonized by <it>H. pylori</it> strains with higher numbers of CagA-EPIYA-C segments (OR = 4.23, 95%CI = 1.53–11.69) and with the most virulent s1m1 <it>vac</it>A genotype (OR = 2.80, 95%CI = 1.04–7.51). Higher numbers of EPIYA-C segments were associated with increased gastric corpus inflammation, foveolar hyperplasia and atrophy. Infection by s1m1 <it>vac</it>A genotype was associated with increased antral and corpus gastritis.</p> <p>Conclusions</p> <p>We demonstrated that relatives of gastric cancer patients are more frequently colonized by the most virulent <it>H. pylori cag</it>A and <it>vac</it>A genotypes, which may contribute to increase the risk of gastric cancer.</p>