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Etiology

Patients with Helicobacter pylori infection with CagA antibodies were at increased risk for gastric cancer

ACP J Club. 1997 Sep-Oct;127:50. doi:10.7326/ACPJC-1997-127-2-050


Source Citation

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 Mar;40:297-301.


Abstract

Objective

To determine whether an association exists between the CagA phenotype of Helicobacter pylori and risk for gastric cancer.

Design

Nested case-control study.

Setting

Kaiser Permanente Medical Care Program, United States.

Participants

242 persons from among 128 992 who had provided serum as part of a multiphasic health evaluation between 1964 and 1969. 103 participants had gastric cancer (cases) and were matched by 5-year birth cohort, sex, race, site, and date of serum collection to cohort members (controls) who had not developed cancer.

Assessment of risk factors

Serum samples from all participants, collected a mean of 14 years before the diagnosis of cancer in the case patients, were tested by ELISA for antibodies to the H. pylori CagA protein. Serum samples had been previously tested for pepsinogen I23. Other potential risk factors assessed were level of education, smoking status, and ABO blood group.

Main outcome measures

Risk for gastric cancer compared among patients with H. pylori infection with CagA antibodies, those with H. pylori without CagA antibodies, and those without H. pylori.

Main results

A total of 103 patients with gastric cancer (77 intestinal type and 26 diffuse type) and 139 control participants were tested for CagA antibodies. After adjustment for age, sex, race, and date of serum collection, patients with H. pylori infection with CagA antibodies were at an increased risk for developing gastric cancer compared with uninfected participants (odds ratio [OR] 5.8, 95% CI 2.6 to 13.0). This increased risk was shown for both intestinal-type cancer (OR 5.1, CI 2.1 to 12.1) and diffuse-type cancer (OR 10.1, CI 2.7 to 47.5). Patients with H. pylori infection without CagA antibodies were not at increased risk for developing gastric cancer compared with uninfected participants (OR 2.2, CI 0.9 to 5.4). However, this group had an increased risk for diffuse-type cancer (OR 9.0, CI 1.2 to 65.8) but not intestinal-type cancer (OR 1.4, CI 0.5 to 3.9). When pepsinogen I23 was added to the multivariate model of CagA, CagA seropositivity remained a significant risk factor for intestinal-type cancer. Low pepsinogen I23 (< 50 ng/mL) was strongly associated with the later development of both types of gastric cancer. Level of education, smoking status, and ABO blood group were not associated with gastric cancer.

Conclusion

Patients with Helicobacter pylori infection with CagA antibodies were at increased risk for gastric cancer.

Sources of funding: Merck and the Society for Epidemiologic Research; National Cancer Institute; OraVax (orv220 CagA antigen).

For article reprint: Dr. J. Parsonnet, HRP Building RM T225, Stanford University, Stanford, CA 94305-5092, USA. FAX 415-725-6951.


Commentary

Although infection with H. pylori is a risk factor for the development of gastric adenocarcinoma, most patients infected with H. pylori never develop gastric cancer. Recent efforts have attempted to identify factors that more precisely determine the risk for gastric cancer in persons infected with H. pylori. 1 putative factor is the H. pylori cytotoxin-associated gene, which encodes a variable size of protein called CagA.

The study by Parsonnet and colleagues used ELISA technology to confirm infection with CagA-positive H. pylori and showed that patients infected with CagA-positive H. pylori are at an increased risk for gastric cancer compared with those infected with CagA-negative H. pylori. The CagA-negative H. pylori infected patients also had an increased, although smaller, risk for gastric cancer. These findings support 2 previously published studies that showed an increase in the risk for gastric cancer in CagA-positive H. pylori infected patients (1, 2). It is important to note that the association between CagA-positivity and gastric cancer rarely reached statistical significance in the above studies. Further, some reports suggest that CagA-positive H. pylori is not associated with gastric cancer (2, 3). This lack of association was identified in Japanese and Chinese patients and raises the question of whether the link between CagA-positive H. pylori and gastric cancer may only be a marker in some populations.

Richard N. Fedorak, MD
University of AlbertaEdmonton, Alberta, Canada

Richard N. Fedorak, MD
University of Alberta
Edmonton, Alberta, Canada


References

1. Blaser MJ, Perez-Perez GI, Leanthous H, 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.

2. Mitchell HM, Hazaell SL, Li YY, Hu PJ. Serological response to specific Helicobacter pylori antigens: antibody against CagA antigen is not predictive of gastric cancer in a developing country. Am J Gastroenterol. 1996;91:1785-8.

3. Maeda S, Ogura K, Kanai F, et al. High prevalence of CagA-positive Helicobacter pylori in Japanese patients irrelevant to the presence of peptic ulcer and gastric cancer. Gastroenterology. 1997;112(Suppl):A205.