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Helicobacter pylori cytotoxin-associated genotype and gastric precancerous lesions.
J Natl Cancer Inst 2007; 99(17):1328-34JNCI

Abstract

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.

Authors+Show Affiliations

International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France. plummer@iarc.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17728213

Citation

Plummer, Martyn, et al. "Helicobacter Pylori Cytotoxin-associated Genotype and Gastric Precancerous Lesions." Journal of the National Cancer Institute, vol. 99, no. 17, 2007, pp. 1328-34.
Plummer M, van Doorn LJ, Franceschi S, et al. Helicobacter pylori cytotoxin-associated genotype and gastric precancerous lesions. J Natl Cancer Inst. 2007;99(17):1328-34.
Plummer, M., van Doorn, L. J., Franceschi, S., Kleter, B., Canzian, F., Vivas, J., ... Kato, I. (2007). Helicobacter pylori cytotoxin-associated genotype and gastric precancerous lesions. Journal of the National Cancer Institute, 99(17), pp. 1328-34.
Plummer M, et al. Helicobacter Pylori Cytotoxin-associated Genotype and Gastric Precancerous Lesions. J Natl Cancer Inst. 2007 Sep 5;99(17):1328-34. PubMed PMID: 17728213.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Helicobacter pylori cytotoxin-associated genotype and gastric precancerous lesions. AU - Plummer,Martyn, AU - van Doorn,Leen-Jan, AU - Franceschi,Silvia, AU - Kleter,Bernhard, AU - Canzian,Federico, AU - Vivas,Jorge, AU - Lopez,Gladys, AU - Colin,Didier, AU - Muñoz,Nubia, AU - Kato,Ikuko, Y1 - 2007/08/28/ PY - 2007/8/31/pubmed PY - 2007/9/27/medline PY - 2007/8/31/entrez SP - 1328 EP - 34 JF - Journal of the National Cancer Institute JO - J. Natl. Cancer Inst. VL - 99 IS - 17 N2 - 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. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/17728213/Helicobacter_pylori_cytotoxin_associated_genotype_and_gastric_precancerous_lesions_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djm120 DB - PRIME DP - Unbound Medicine ER -