© 2003 by Oxford University Press
Journal of the National Cancer Institute, Vol. 95, No. 10, 760,
May 21, 2003
© 2003 Oxford University Press
CORRESPONDENCE |
Re: Helicobacter pylori and Interleukin 1 Genotyping: An Opportunity to Identify High-Risk Individuals for Gastric Carcinoma
Affiliations of authors: F. Kamangar, Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, and Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; P. Limburg, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN; P. Taylor, S. Dawsey, Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute.
Correspondence to: Farin Kamangar, M.D., M.P.H., Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, 6116 Executive Blvd., Rm. 705, Bethesda, MD 20892-8314 (e-mail: kamangaf{at}mail.nih.gov).
In a recently published case–control study, Figueiredo et al. (1) reported that vacAs1-, vacAm1-, and cagA-positive strains of Helicobacter pylori were associated with increased gastric cancer (GC) risk, particularly among individuals with select interleukin 1 gene polymorphisms. The accompanying editorial (2) noted that the identification of key pathogenetic factors involved in H. pylori-associated gastric carcinogenesis may lead to more effective prevention and/or treatment strategies. However, several aspects of the study by Figueiredo et al. warrant further attention before these data can be appropriately interpreted. Most notably, the strain-type-specific GC risks observed in this study were much higher than those reported in previous investigations (3–5). For example, colonization rates for cagA-positive versus cagA-negative H. pylori strains among GC case patients were 15-fold higher than those in non-atrophic gastritis control subjects (odds ratio [OR] = 15, 95% confidence interval = 7.4 to 29). In contrast, other studies (that have made the same comparison) have reported OR estimates ranging from 1.2 to 3 (3–5). Explanations for these discrepant findings in risk estimates were not comprehensively addressed in the Figueiredo et al. study. However, several study design features raise concerns that nonpathogenetic factors may have played a contributing role in these discrepant findings.
First, because no reference was made to covariate adjustment in the logistic regression analyses, simple confounding by age or sex (both of which differed markedly between GC case patients and control subjects) may have occurred. Second, because neither the case patients (i.e., hospitalized patients) nor the control subjects (i.e., shipyard workers) were likely to be representative of the general reference population, selection bias may have occurred. Third, based on the large percentage of GC case patients (41%) who had inadequate material for H. pylori genotyping, additional selection bias might have been introduced. Fourth, the detection of H. pylori strain types by tissue genotyping may have been a more sensitive technique than standard serum antibody measurements used in other studies. This last possibility represents a potential strength of the study by Figueiredo et al. (1); however, this increased sensitivity does not appear to be the primary determinant of atypical risk estimates. For example, if the sensitivity for cagA tissue genotyping and cagA serum antibody measurements are assumed to be 100% and 70%, respectively (6), then adopting the former assay method to reanalyze data from a previous study by our group (3) would only have been expected to increase the risk estimate for GC among cagA-positive subjects versus cagA-negative subjects from 1.2 to 1.6. Clearly, this revised risk estimate is still much lower than the GC risk estimate associated with cagA-positive H. pylori colonization in the study by Figueiredo et al (1).
One additional factor to consider is that cagA-positive strains of H. pylori may be more sensitive to gastric acid than cagA-negative strains (7). Thus, differential acid susceptibility could further contribute to a higher cagA-positive H. pylori colonization rate among GC patients than in non-atrophic gastritis control subjects without necessarily implying a causal association.
In summary, although we found the data presented by Figueiredo et al. (1) to be interesting, the conclusions reached by the investigators may have been based on somewhat generous risk estimates from a highly select subject population. Further investigation of bacterial and host genotyping in H. pylori-associated GC in well-designed, population-based prospective studies may afford additional clarity.
REFERENCES
1 Figueiredo C, Machado JC, Pharoah P, Seruca R, Sousa S, Carvalho R, et al. Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst 2002;94:1680–7.
2 Blaser MJ. Polymorphic bacteria persisting in polymorphic hosts: assessing Helicobacter pylori-related risks for gastric cancer. J Natl Cancer Inst 2002;94:1662–3.
3 Limburg P, Qiao Y, Mark S, Wang G, Perez-Perez G, Blaser M, et al. Helicobacter pylori seropositivity and subsite-specific gastric cancer risks in Linxian, China. J Natl Cancer Inst 2001;93:226–33.
4 Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH, et al. Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 1995;55:2111–5.
5 Parsonnet J, Friedman GD, Orentreich N, Vogelman H. Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut 1997;40:297–301.
6 Figueiredo C, Quint W, Nouhan N, van den Munckhof H, Herbrink P, Scherpenisse J, et al. Assessment of Helicobacter pylori vacA and cagA genotypes and host serological response. J Clin Microbiol 2001;39:1339–44.
7 Karita M, Blaser MJ. Acid-tolerance response in Helicobacter pylori and differences between cagA+ and cagA-strains. J Infect Dis 1998;178:231–9.
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