The presence of the cytotoxin-associated gene (cagA) in Helicobacter pylori is associated with more severe precancerous gastric lesions, according to a report in the September 5th
Journal of the National Cancer Institute."The way H. pylori infection is measured may be very important," lead investigator Dr. Martyn Plummer from International Agency for Research on Cancer in Lyon, France, told Reuters Health. "Since detection of cagA DNA in gastric biopsies correlated strongly with clinical outcome in our study, this might be considered a gold standard against which other detection methods are judged."
Dr. Plummer and colleagues investigated the relationships among H. pylori infection, bacterial virulence-associated genotypes, and the severity of gastric precancerous lesions in patients at high risk for H. pylori infection and gastric cancer.
In a pilot study with 206 subjects, the researchers found that the prevalence of cagA was significantly higher among patients with more severe lesions (86 per cent) than among those with less severe lesions (59 per cent), the authors report.
Most cagA-positive patients with more severe lesions were infected with a vacA s1 or vacA m1 genotype, the report indicates, whereas most cagA-negative subjects were infected with a vacA s2 or an m2 genotype.
Next, the investigators examined 2145 frozen gastric biopsies from participants in a randomized trial in Venezuela. CagA-negative H. pylori-infected individuals had twice the rate of chronic gastritis as that of uninfected individuals, but the prevalence of more advanced lesions was similar in both groups.
CagA-positive H. pylori-infected individuals, however, had 4.33-fold higher rates of chronic gastritis and 15.5-fold higher rates of dysplasia, compared with uninfected individuals.
Compared with patients with cagA-negative genotypes, those with cagA-positive genotypes had twice the rate of chronic gastritis, 7.35 times the rate of intestinal metaplasia type II, and 16.7 times the rate of dysplasia.
Patients with cagA-positive genotypes also had higher rates of progression and lower rates of regression than did uninfected patients and patients with cagA-negative genotypes, the investigators say.
"This study shows a very strong association between current infection with cagA-positive strains of H. pylori and the severity of gastric precancerous lesions in a Latin American population at high risk of both H. pylori infection and gastric cancer," the researchers conclude.
"At this stage, it is premature to translate our findings into recommendations for clinical practice," Dr. Plummer cautioned. "The results need to be replicated, and we need to understand the role of cagA in gastric cancer cases, not just precancerous lesions."
"We also need to extend the results to gastric cancer cases and to understand the relationship between the detection of H. pylori DNA in gastric biopsies and antibodies to H. pylori antigens in serum.
