High Diversity of vacA and cagA Helicobacter pylori Genotypes in Patients with and without Gastric Cancer

Abstract

Background Helicobacter pylori is associated with chronic gastritis, peptic ulcers, and gastric cancer. The aim of this study was to assess the topographical distribution of H. pylori in the stomach as well as the vacA and cagA genotypes in patients with and without gastric cancer.Methodology/Principal FindingsThree gastric biopsies, from predetermined regions, were evaluated in 16 patients with gastric cancer and 14 patients with dyspeptic symptoms. From cancer patients, additional biopsy specimens were obtained from tumor centers and margins; among these samples, the presence of H. pylori vacA and cagA genotypes was evaluated. Positive H. pylori was 38% and 26% in biopsies obtained from the gastric cancer and non-cancer groups, respectively (p = 0.008), and 36% in tumor sites. In cancer patients, we found a preferential distribution of H. pylori in the fundus and corpus, whereas, in the non-cancer group, the distribution was uniform (p = 0.003). A majority of the biopsies were simultaneously cagA gene-positive and -negative. The fundus and corpus demonstrated a higher positivity rate for the cagA gene in the non-cancer group (p = 0.036). A mixture of cagA gene sizes was also significantly more frequent in this group (p = 0.003). Ninety-two percent of all the subjects showed more than one vacA gene genotype; s1b and m1 vacA genotypes were predominantly found in the gastric cancer group. The highest vacA-genotype signal-sequence diversity was found in the corpus and 5 cm from tumor margins.Conclusion/SignificanceHigh H. pylori colonization diversity, along with the cagA gene, was found predominantly in the fundus and corpus of patients with gastric cancer. The genotype diversity observed across systematic whole-organ and tumor sampling was remarkable. We find that there is insufficient evidence to support the association of one isolate with a specific disease, due to the multistrain nature of H. pylori infection shown in this work.

Novel vacA s1d signal sequence found in Helicobacter pylori from Mexican Children with Recurrent Abdominal Pain

“…This variability strongly impacts the virulence of the bacterium. Specific genotypes have been associated with the development of gastritis, peptic ulcers and stomach cancer [5][6][7][9][10][11][12][13][14][15]22]. The difference between genotypes of this bacterium is given by the presence or lack of gene blocks in the accessory genome within the plasticity zones of the chromosome and by the polymorphism of the nucleotide sequences in structural genes, such as the vacA gene, which encodes for the vacuolating cytotoxin [19][20][21].…”

“…Several studies show that infection by this microorganism is really a multicolonization of the gastric mucosa by different H. pylori strains with different genotypes. Therefore, it is not possible to attribute a particular genotype to disease outcome [11][12][13][14][15]. These same studies also indicate the presence of strains that were not characterized according to their signal sequence, referring to these strains as being non-typeable.…”

IgG Subclasses Against Helicobacter pylori Isolates: An important Tool for Disease Characterization

“…In this study, we used soluble proteins from twelve H. pylori strains (three clinical isolates from dyspeptic patients, two from chronic gastritis patients, three from patients with peptic ulcers, two from patients with gastric cancer and two reference strains [Hp 26695 (ATCC 700392) and Hp J99 (ATCC 700824)]) and 44 serum samples [from 12 patients with dyspepsia, five with peptic ulcer, 13 with bleeding peptic ulcers and 14 with gastric cancer (six with early and eight with advance gastric cancer)] that were obtained from two previous studies [14,15], in which patients with gastric or duodenal ulcers with ongoing or recent (<24 h) bleeding were recruited, as well two groups were included simultaneously in the study as controls: patients with non-bleeding peptic ulcers and those in whom an endoscopy was performed because of non-ulcer dyspepsia and ⁄ or gastro-oesophageal reflux. Patients were excluded if they were pregnant, were regular users of non-steroidal anti-inflammatory drugs (NSAIDs), were sporadic users of NSAIDs within the previous 2 weeks, were carriers of a chronic liver disease, had a history of bleeding portal hypertension or were unable to make their own decisions.…”

“…Soluble proteins from lysates of H. pylori strains (SPLHP). Helicobacter pylori strains were harvested in phosphatebuffered saline (PBS) supplemented with a CompleteÔ Table 1 Demographic characteristics of patients, from whom serum samples were taken in this study [14,15].…”

Genotyping pattern of the vacuolating cytotoxin A and cytotoxin associated gene A of the Helicobacter pylori strains detected in fecal samples of household dogs

“…9,10 The cagA gene has been detected in the specimens taken from the severe cases of peptic ulcer and gastritis. [9][10][11] Genotyping using these virulence markers is measured as one of the best methods for assess associations between H. pylori isolates from diverse clinical samples.…”