Gastroenterology

Gastroenterology

Volume 121, Issue 4, October 2001, Pages 784-791
Gastroenterology

Alimentary Tract
Helicobacter pylori in gastric cancer established by CagA immunoblot as a marker of past infection

https://doi.org/10.1053/gast.2001.27999Get rights and content

Abstract

Background & Aims: Helicobacter pylori may disappear spontaneously with progressing precancerous changes and invalidate serologic studies of its association with gastric cancer. We reestimated the strength of the H. pylori–gastric cancer relationship, using both conventional immunoglobulin (Ig) G enzyme-linked immunosorbent assay (ELISA) and immunoblot (against cytotoxin-associated antigen A [CagA] antibodies that prevail longer after eradication) to detect past H. pylori exposure more relevant for time at cancer initiation. Methods: In our population-based case-control study, the seroprevalence among 298 gastric adenocarcinoma cases was 72% (IgG ELISA) and 91% (immunoblot) vs. 55% and 56% among 244 controls frequency-matched for age and gender. Results: Using IgG ELISA only, the adjusted OR for noncardia gastric cancer among H. pylori–positive subjects was 2.2 (95% confidence interval [CI], 1.4–3.6). When ELISA−/CagA+ subjects (odds ratio [OR], 68.0) were removed from the reference, the OR rose to 21.0 (95% CI, 8.3–53.4) and the previous effect modification by age disappeared. ELISA+/CagA− subjects had an OR of 5.0 (95% CI, 1.1–23.6). There were no associations with cardia cancer. Conclusions: The weaker H. pylori–cancer relationships in studies based on IgG ELISA rather than CagA may be caused by misclassification of relevant exposure. A much stronger relationship emerges with more accurate exposure classification. In the general Swedish population, 71% of noncardia adenocarcinomas were attributable to H. pylori.

GASTROENTEROLOGY 2001;121:784-791

Section snippets

Materials and methods

This study was part of a larger, population-based case-control study, the design of which has been described in detail previously.13 The study base of the larger study, and equally of the present report, consisted of all native Swedes aged 40–79 years, living in 2 geographic areas in Sweden with a total population of 1.3 million, from February 1989 through January 1995.

Results

The distributions of age, gender, SES, and other variables that might affect the probability of H. pylori infection, as well as cancer type and site among case patients, were very similar among subjects in the serologic substudy and all subjects included in the larger population-based study, allaying concerns of selection bias (Table 1).Patients with gastric adenocarcinoma had a higher prevalence of H. pylori antibodies than the control subjects; 72% vs. 55% were H. pylori positive according to

Discussion

Quite in agreement with recent meta-analyses,2, 3, 4 our population-based study showed an approximate 2-fold excess risk of noncardia cancer among seropositive individuals when a conventional IgG ELISA serology was used. Like most investigators,5, 6, 21 we found no association with risk of cardia cancer. Also in conformity with the majority of,8, 22 but not all,17, 23 previous studies, a stronger association emerged when antibodies to CagA were used as markers of H. pylori exposure. This has

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    Address requests for reprints to: Anna Mia Ekström, M.D., M.P.H., Ph.D., Department of Medical Epidemiology, Karolinska Institutet, Box 281, S-171 77 Stockholm, Sweden. e-mail: [email protected]; fax: (46) 8-314975.

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