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- Title
Helicobacter pylon Cytotoxin-Associated Genotype and Gastric Precancerous Lesions.
- Authors
Plummer, Martyn; van Doorn, Leen-Jan; Franceschi, Silvia; Kleter, Bernhard; Canzian, Federico; Vivas, Jorge; Lopez, Gladys; Colin, Didier; Muñoz, Nubia; Kato, Ikuko
- Abstract
Background Helicobacter pylon infection is associated with the development of gastric cancer. Although infection with an H. pylon 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. pylon 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. pylon 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. pylon 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. pylon infection and the severity of gastric precancerous lesions, but cagA-negative H. pylon 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 [Cl] = 6.42 to 37.2) in cagA-positive individuals compared with uninfected individuals and 0.90 (95% Cl = 0.37 to 2.17) for individuals infected with cagA-negative H. pylon compared with uninfected individuals. Individuals infected with cagA-positive H. pylon appeared more likely to experience progression (and less likely to experience regression) of precancerous lesions than those infected with cagA-negative H. pylon, but the differences did not attain statistical significance. Conclusions This large epidemiologic study shows a strong relationship between the presence of H. pylon DNA in gastric biopsies and the severity of precancerous lesions that is specific to cagA-positive strains. The association between H. pylon and gastric carcinoma may have been previously underestimated due to the poor accuracy of serologic H. pylon markers and lack of discrimination by cagA genotype.
- Subjects
PRECANCEROUS conditions; GENETIC polymorphisms; HISTOPATHOLOGY; POLYMERASE chain reaction; DNA polymerases; CHEMOPREVENTION; STOMACH cancer
- Publication
JNCI: Journal of the National Cancer Institute, 2007, Vol 99, Issue 17, p1328
- ISSN
0027-8874
- Publication type
Article
- DOI
10.1093/jnci/djm120