Helicobacter pylori cytotoxin-associated genotype and gastric precancerous lesions.
BACKGROUND
Helicobacter pylori infection is associated with the development of gastric cancer. Although infection with an H. pylori strain containing the cytotoxin-associated (cag A) gene (a marker for a pathogenicity island) may increase the risk of atrophic gastritis and gastric cancer, the relationship of variants in pathogenic H. pylori genes to the severity and progression of precancerous lesions is not well defined.


METHODS
Gastric biopsy specimens were obtained at enrollment from 2145 participants in a chemoprevention trial in Tachira State, Venezuela, and examined histologically to determine the severity of precancerous lesions. The presence of H. pylori DNA in gastric biopsies and the strain type according to presence or absence of the cagA gene were detected by polymerase chain reaction and specific probes. The relationship between H. pylori DNA and histologic diagnosis was analyzed by polytomous logistic regression. Rates of progression and regression of precancerous lesions were determined from biopsies from additional annual gastroscopies (mean follow-up = 3.5 years). All statistical tests were two-sided.


RESULTS
At enrollment, there was a strong association between cagA-positive H. pylori infection and the severity of gastric precancerous lesions, but cagA-negative H. pylori was associated only with chronic gastritis. Using individuals with normal mucosa or superficial gastritis as control subjects, the odds ratio for dysplasia was 15.5 (95% confidence interval [CI] = 6.42 to 37.2) in cagA-positive individuals compared with uninfected individuals and 0.90 (95% CI = 0.37 to 2.17) for individuals infected with cagA-negative H. pylori compared with uninfected individuals. Individuals infected with cagA-positive H. pylori appeared more likely to experience progression (and less likely to experience regression) of precancerous lesions than those infected with cagA-negative H. pylori, but the differences did not attain statistical significance.


CONCLUSIONS
This large epidemiologic study shows a strong relationship between the presence of H. pylori DNA in gastric biopsies and the severity of precancerous lesions that is specific to cagA-positive strains. The association between H. pylori and gastric carcinoma may have been previously underestimated due to the poor accuracy of serologic H. pylori markers and lack of discrimination by cagA genotype.
Plummer
Martyn
M
International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France. plummer@iarc.fr
van Doorn
Leen-Jan
LJ
Franceschi
Silvia
S
Kleter
Bernhard
B
Canzian
Federico
F
Vivas
Jorge
J
Lopez
Gladys
G
Colin
Didier
D
Muñoz
Nubia
N
Kato
Ikuko
I
D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D001706:Biopsy; D003430:Cross-Sectional Studies; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D005756:Gastritis / Q000473:pathology*; D005838:Genotype; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics* / Q000382:microbiology*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori