Correspondence
Gastric Cancer in Japan
N Engl J Med 2008; 359:2393-2395November 27, 2008DOI: 10.1056/NEJMc081797
- Article
To the Editor:
In their Perspective article (July 31 issue),1 Forman and Pisani ask, “Why does gastric cancer occur so frequently in Japan?” One answer was proposed more than 30 years ago by Matsudo et al.,2 who detected talc in the normal gastric mucosa and in gastric cancers in Japanese patients and suggested a causal relationship.
Talc is used in Japan to polish rice, and it is customary to wash off the talc before cooking the rice. However, if the washing is insufficient, talc is ingested. Talc is a hydrated magnesium silicate with the chemical formula H2Mg3(SiO3)4 or Mg3Si4O10(OH)2. It is similar to asbestos, which has a well-established relationship to mesothelioma and lung cancer. Chrysotile, the most commonly used asbestos in the United States, is Mg3[Si2O5](OH)4.
2 ReferencesRichard E. Horowitz, M.D.
10122 Empyrean Way, Los Angeles, CA 90067
r.e. horowitz@ucla. edu 1
Forman D Pisani P
Full Text | Web of Science | Medline2
Matsudo H Hodgkin NM Tanaka A
Web of Science | Medline
To the Editor:
The high incidence of gastric cancer in East Asia is largely unexplained. Recent studies, however, indicate that it is partly related to the particular virulence of East Asian strains of Helicobacter pylori.1
The development of distal gastric cancer is closely linked to infection with H. pylori strains, which possess certain virulence factors such as the type IV secretion system, the cytotoxin VacA, or the adhesin BabA.1-3 The type IV secretion system–mediated translocation of bacterial macromolecules (e.g., CagA) into epithelia induces oncogenic and proinflammatory signaling, thereby promoting carcinogenesis.1,2
Virtually all East Asian H. pylori strains express or secrete BabA, CagA, and VacA, whereas in some Western populations, the proportion of these “triple-positive” strains is less than 50%.1-3 Furthermore, because of structural modifications, CagA expressed by East Asian H. pylori strains is biologically more active and consequently more strongly associated with the development of cancer than CagA from H. pylori in most other parts of the world.3
The evolution and predominance of more pathogenic H. pylori strains in East Asia reflect phylogeographic differentiation4 and show that the genetic diversity of H. pylori can be one cause of geographic differences in the incidence of gastric cancer.
4 ReferencesRoland Rad, M.D.
Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom
rr6@sanger.ac. uk 1
Atherton JC
CrossRef | Web of Science | Medline2
Hatakeyama M
CrossRef | Web of Science | Medline3
Rad R Gerhard M Lang R
Web of Science | Medline4
Linz B Balloux F Moodley Y
CrossRef | Web of Science | Medline
The authors reply: The correspondents describe two hypotheses addressing reasons for the particularly high risk of gastric cancer in Japan, one focusing on a putative dietary carcinogen, and the other on the virulence of specific East Asian strains of H. pylori. Both factors may be relevant, but as with many other proposed risk factors (e.g., N-nitroso compounds, iodine, antioxidants, and a high intake of salt), after decades of research, the epidemiologic evidence of their role in causation remains inconclusive. Only the role of H. pylori infection itself is definitely settled.
We wished to stress in our article that it is the combination of chronic inflammation caused by bacterial infection, possibly enhanced by high salt intake, and carcinogens that leads to cancer. Future studies should specifically address the notion that both are required to cause cancer. The study design and the ability to document exposure to a complex variety of carcinogens will be crucial. Retrospective case–control studies have proved to be too prone to information bias, in the case of dietary studies, and inadequate for the assessment of H. pylori–infection status. Prospective studies and experimental controlled interventions offer more potential. Given the stated hypothesis, a mixed factorial design that combines controlled eradication of H. pylori with the estimation of different levels of DNA-damaging carcinogens by means of urinary and plasma biomarkers would be the most cost-effective approach, particularly in Japan, where there is a high-quality infrastructure for clinical monitoring.
The issue of the interaction between H. pylori and other environmental factors is important because it can help in developing acceptable preventive policies. At present, the only established, modifiable causal factors involved in gastric cancer are H. pylori infection and, to a lesser extent, tobacco smoking. Proposals to prevent gastric cancer through large-scale programs of antibiotic administration have limited appeal because of concerns about overtreatment and the development of bacterial resistance, the uncertainty over the magnitude of benefit, and possible harm.
David Forman, Ph.D.
University of Leeds, Leeds LS9 7TF, United KingdomPaola Pisani, Spec.Stat.Med.
University of Oxford, Oxford OX3 7LF, United Kingdom- Citing Articles (1)
Citing Articles
1
Hansoo Park, Jong-Il Kim, Young Seok Ju, Omer Gokcumen, Ryan E Mills, Sheehyun Kim, Seungbok Lee, Dongwhan Suh, Dongwan Hong, Hyunseok Peter Kang, Yun Joo Yoo, Jong-Yeon Shin, Hyun-Jin Kim, Maryam Yavartanoo, Young Wha Chang, Jung-Sook Ha, Wilson Chong, Ga-Ram Hwang, Katayoon Darvishi, HyeRan Kim, Song Ju Yang, Kap-Seok Yang, Hyungtae Kim, Matthew E Hurles, Stephen W Scherer, Nigel P Carter, Chris Tyler-Smith, Charles Lee, Jeong-Sun Seo. (2010) Discovery of common Asian copy number variants using integrated high-resolution array CGH and massively parallel DNA sequencing. Nature Genetics 42, 400-405
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