Correspondence

Helicobacter pylori and Gastric Lymphoma

N Engl J Med 1994; 331:746September 15, 1994

Article

To the Editor:

Parsonnet and colleagues (May 5 issue)1 reported an association between previous Helicobacter pylori infection and gastric lymphoma. Although H. pylori infects more than 50 percent of the people in the world, gastric lymphomas are very rare tumors, occurring in fewer than 10 people per million population. Some epidemiologic observations argue against an independent association between H. pylori and gastric lymphoma. The prevalence of H. pylori infection and deaths from gastric lymphoma vary in various regions. For example, although H. pylori infection is found in more than 85 percent of the Indian population, the rate of mortality from gastric and nongastric lymphoma is lower than in developed countries2,3. In the United States, the prevalence of H. pylori infection and the rate of mortality from gastric cancer and peptic ulcer have decreased steadily during the past 50 years, whereas deaths from non-Hodgkin's lymphoma, including gastric lymphoma, have risen3,4. The rate of mortality from lymphomas has been higher among whites in the United States, whereas the prevalence of H. pylori and deaths from gastric cancer are higher in the black and Hispanic populations.

K.M. Mohandas, M.D.
Medical College of St. Bartholomew's Hospital, London EC1M 6BQ, United Kingdom

4 References

1. 1

   Parsonnet J, Hansen S, Rodriguez L, et al. Helicobacter pylori infection and gastric lymphoma. N Engl J Med 1994;330:1267-1271
   Full Text | Web of Science | Medline

2. 2

   Graham DY, Adam E, Reddy GT, et al. Seroepidemiology of Helicobacter pylori infection in India: comparison of developing and developed countries. Dig Dis Sci 1991;36:1084-1088
   CrossRef | Web of Science | Medline

3. 3

   Devesa SS, Fears T. Non-Hodgkin's lymphoma time trends: United States and international data. Cancer Res 1992;52:Suppl:5432s-5440s
   Web of Science | Medline

4. 4

   Sonnenberg A. The US temporal and geographic variations of diseases related to Helicobacter pylori. Am J Public Health 1993;83:1006-1010
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Seeking to demonstrate or refute a causal link between an exposure and a disease by simply comparing the rates of the two in a specific population is fraught with hazard. This type of reasoning cannot take into account the confounders and interacting factors that may contribute to causality. A disease risk factor may be quite common in a group even though the incidence of the disease is not increased. A particular factor may not in itself be sufficient to cause disease but may require other host or environmental factors1. Although we do not dispute Mohandas's statistics on the prevalence of H. pylori and the incidence of gastric lymphoma, the lack of geographic and temporal correlation between the two may reflect differences in disease-related factors other than those related to H. pylori. For instance, gastric lymphoma may occur predominantly in persons infected with H. pylori who have an HLA type that is uncommon in India or in persons exposed to a hazardous chemical not used in India but whose use is on the rise in the industrialized West. Given the rarity of gastric lymphoma despite the high prevalence of H. pylori infection, we assume that other factors besides H. pylori must be important. Nevertheless, we have calculated that if this infection did not exist, two thirds of gastric lymphomas would not occur.

We think there can be little doubt that H. pylori is a causal factor in gastric lymphoma. Not only do epidemiologic studies from two distinct populations support the association, but also clinical studies show that low-grade lymphomas can be cured with therapy directed against the organism2. Studies of environmental and host-related codeterminants of disease may eventually help explain why a handful of persons with infection have lymphoma while the vast majority are spared.

Julie Parsonnet, M.D.
Stanford University School of Medicine, Stanford, CA 94305

Svein Hansen, M.D.
Cancer Registry of Norway, N-0310 Oslo, Norway

Gary D. Friedman, M.D.
Kaiser Permanente Medical Group, Oakland, CA 94116

2 References

1. 1

   Rothman KJ. Modern epidemiology. 1st ed. Boston: Little, Brown, 1986:7-23.
   

2. 2

   Wotherspoon AC, Doglioni C, Diss TC, et al. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 1993;342:575-577
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Massimo Rugge, Mauro Cassaro, Gioacchino Leandro, Raffaele Baffa, Claudio Avellini, Pantaleone Bufo, Vincenzo Stracca, Giuseppe Battaglia, Alfredo Fabiano, Antonio Guerini, Francesco Mario. (1996) Helicobacter pylori in promotion of gastric carcinogenesis. Digestive Diseases and Sciences 41:5, 950-955
   CrossRef