Journal of the National Cancer Institute Advance Access published online on August 28, 2007
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djm120
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© The Author 2007. Published by Oxford University Press.
ARTICLES |
Helicobacter pylori Cytotoxin-Associated Genotype and Gastric Precancerous Lesions
Affiliations of authors: International Agency for Research on Cancer, Lyon, France (MP, SF, FC, DC); DDL Diagnostic Laboratory, Fonteijnenburghlaan, Voorburg, The Netherlands (LJVD, BK); Genomic Epidemiology Group, Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany (FC); Cancer Control Center of Tachira State, San Cristobal, Venezuela (JV, GL); Instituto Nacional de Cancerología, Bogotá, Colombia (NM); Karmanos Cancer Institute, Detroit, MI (IK); Wayne State University, Detroit, MI (IK)
Correspondence to: Martyn Plummer, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France (e-mail: plummer{at}iarc.fr).
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.
| CONTEXT AND CAVEATS Prior knowledge Infection with the bacterium Heliobacter pylori is associated with the development of gastric cancer, but information on which specific strains of the bacterium are most strongly associated with precancerous lesions was lacking. Study design Gastric biopsy specimens from participants in a chemoprevention trial were used to assess the relationship between H. pylori genotype and severity of precancerous lesions. Contribution A strong positive association was observed between infection with H. pylori that tested positive for a genetic marker for a set of pathogenic genes and severe precancerous lesions. Implications The risk of advanced precancerous lesions conferred by H. pylori infection may have been underestimated previously due to failure to discriminate by H. pylori genotype. Limitations Further study will be needed to determine if the association of a H. pylori genotype with the risk of advanced precancerous lesions also holds for gastric cancer.
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Manuscript received January 19, 2007; revised June 11, 2007; accepted July 25, 2007.
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J Natl Cancer Inst 2007 99: 1277.
J Natl Cancer Inst 2007 99: 1277.
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