Helicobacter pylori infection increased the risk for gastric carcinoma among Japanese American men
ACP J Club. 1992 Jan-Feb;116:26. doi:10.7326/ACPJC-1992-116-1-026
Related Content in this Issue
• Companion Abstract and Commentary: Helicobacter pylori infection increased the risk for gastric carcinoma
Nomura A, Stemmermann GN, Chyou PH, et al. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med. 1991 Oct 17;325:1132-6.
To investigate Helicobacter pylori infection as a precursor of gastric carcinoma in Japanese American men.
Case-control study nested within a cohort followed since the late 1960s.
The cohort was identified by the Honolulu Heart Program through 1942 draft registration files.
8006 (72%) of 11 148 Japanese American men born from 1900 to 1919 were examined from 1965 to 1968; 7498 (94%) were re-examined and serum samples were taken between 1967 and 1970. From 1968 to 1989, 137 men had gastric carcinoma diagnosed histologically. The 111 men who had given a sufficient serum sample were matched by age and date of serum collection to live members of the cohort who had not had a gastrectomy before the serum collection or a history of peptic ulcer disease (739 men). A further 1868 potential controls were excluded because of a history of or presence of cardiovascular disease or other cancer.
Assessment of risk factors
Serum samples were assayed by enzyme-linked immunosorbent assay (ELISA; Pyloristat kit) for immunoglobulin G (IgG) antibodies to H. pylori. The source of the samples was masked. Cut points for IgG antibody ratios were ≥ 1.00 (positive) and < 0.80 (negative). 2 cases had indeterminate samples (0.99 to 0.80) and were excluded from the study, leaving 109 pairs in the analysis. In the first examination, information on potential risk factors had been collected, including serum cholesterol and glucose values and blood pressure.
Main outcome measure
Association between H. pylori and gastric carcinoma (intestinal and diffuse).
103 (94%) of 109 men with gastric carcinoma had a positive test for H. pylori compared with 83 (76%) controls (odds ratio [OR] 6.0, 95% CI 2.1 to 17.3, P < 0.001); the estimated population-attributable risk for gastric carcinoma due to H. pylori infection was 63% (CI 37% to 89%). 75 (93%) of 81 men with intestinal-type carcinoma were infected, compared with 61 (75%) controls (OR 4.5, CI 1.5 to 13.3). All patients with diffuse carcinoma (n = 23) were infected, compared with 17 controls (74%, approximate OR 6.0, CI 1.1 to 63.5). There were no differences in baseline demographic or laboratory values between the cases and controls.
Infection with Helicobacter pylori increased the risk for gastric carcinoma within 22 years in Japanese American men.
Sources of funding: National Cancer Institute; Department of Veterans Affairs; Procter & Gamble Company; royalty interest in Pyloristat kits.
Address for article reprint: Dr. A. Nomura, Japan-Hawaii Cancer Study, Kuakini Medical Center, 347 North Kuakini Street, Honolulu, HI 96817, USA.
These 2 case-control studies demonstrate an increased rate of previous exposure to H. pylori among persons with gastric cancer. Unresolved, however, is whether H. pylori has a causal role in gastric cancer. Because H. pylori is so common (occurring in up to 50% of older persons in the United States and in even higher proportions in other countries), it is clearly not sufficient to cause cancer—other features must contribute. Approximately 75% and 60% of the controls were positive for H. pylori in the studies by Nomura and colleagues and Parsonnet and colleagues, respectively. At most, then, H. pylori may be a contributing cause of gastric cancer. Such a relation would be clinically important by suggesting that eradication of H. pylori might prevent cancer. A similar relation of "necessary but not sufficient" may also explain H. pylori's role in peptic ulcer disease (1). However, as Parsonnet and colleagues explain, it is an alternative possibility that " H. pylori might just be a marker [and not a cause] for an increased risk of cancer" if a yet-unidentified factor increases the susceptibility to cancer and to colonization with H. pylori.
The clinical implications of these studies are not clear as a causal relationship is not established. Thus, we do not know whether eradication of H. pylori would reduce cancer risk. Furthermore, any effort to eradicate H. pylori would necessarily involve an enormous number of persons who would need to be treated and re-treated over many years.
Although neither of these studies was designed to permit conclusions regarding the benefits of eradicating H. pylori, some can be inferred. If H. pylori eradication were possible in selected individuals and this resulted in the prevention of gastric carcinoma, the data from Nomura and coworkers provide an optimistic estimate that one would need to treat at least 44 patients to prevent 1 cancer. However, this does not take into account the resources required to identify infected individuals or how long and how often these 44 individuals (who will not develop cancer) will have to be treated over a 20-year period.
In summary, then, these studies provide provocative evidence that H. pylori does precede gastric cancer; duodenal ulcer disease may similarly be preceded by H. pylori. However, the evidence does not yet support a causal role. At most, H. pylori may be "necessary but not sufficient" as a cause. Alternatively, the association may simply be coincidental. We shall watch with interest as the H. pylori story unfolds over the next several years.
David F. Ransohoff, MD
University of North Carolina at Chapel Hill School of MedicineChapel Hill, North Carolina, USA
David F. Ransohoff, MD
University of North Carolina at Chapel Hill School of Medicine
Chapel Hill, North Carolina, USA