Japanese Journal of Clinical Oncology 32:275-276 (2002)
© 2002 Foundation for Promotion of Cancer Research
Editorial |
Challenging Epidemiological Strategy for Paradoxical Evidence on the Risk of Gastric Cancer from Helicobacter pylori Infection
Division of Epidemiology, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan
The incidence of gastric cancer in the northeast Asian countries Japan, Korea and China is the highest in the world. The age-adjusted incidence rates (AAIRs) are 10 times higher than those in non-Hispanic Whites and four times higher than those in Japanese immigrants in Los Angeles, USA (1). The overall incidence rates of gastric cancer in Japan have been decreasing according to the changing pattern of Japanese dietary habit after World War II (2). A large number of epidemiological studies during the last several decades investigated dietary factors in relation to gastric cancer risk in the world and revealed dominant dietary and beverage factors: high intake of salted foods; low consumption of fresh vegetables and fruit and habitual cigarette smoking. The worldwide epidemic pattern of gastric cancer is closely associated with the characteristic lifestyle pattern in each country and ethnic group. Japanese immigrants to the USA were influenced by the American social and natural environment and changed their way of life, especially their dietary habits, generation by generation.
In 1994, the International Agency for Research on Cancer (IARC) defined Helicobacter pylori as a carcinogenic agent of human gastric cancer based on sufficient evidence for positive relationships between H. pylori infection rate and risk impact of gastric cancer (3). As H. pylori emerged as a decisive carcinogenic agent for gastric cancer, many pathologists countered the arguments as follows: (1) lack of evidence from animal experiments regarding the carcinogenic agent of H. pylori products; (2) insufficient evidence for the spreading pattern of parasitic H. pylori in the gastric epithelium and further progression to gastric cancer; and (3) insufficient evidence for a population-based correlation between the infection rate of H. pylori and risk of gastric cancer throughout the world.
It is well known that H. pylori was a major cause of refractory ulcers of the stomach and duodenum before the eradication of H. pylori infection. Theoretically, H. pylori would play a complementary role in carcinogenicity as a predisposing factor of gastric cancer, e.g., chronic and atrophic gastritis. A long-term repeated inflammatory condition with H. pylori might enhance carcinogenic progression by independent exposure to non-specific carcinogenic agents; however, H. pylori itself gradually disappears with the progression of cancerous tissue. Current animal experiments using Mongolian gerbils clarified the first point above, that is, H. pylori promotes glandular gastric carcinogenesis after treatment with a chemical carcinogen, N-methyl-N-nitrosourea (MNU) (4), and furthermore, eradication of H. pylori infection diminished its enhancing effects on glandular gastric carcinogenicity with MNU administration (5).
With regard to the second of the above points, H. pylori gradually disappears in gastric membranes with progression of gastric atrophy, with concordant occurrence of gastric cancer as an outcome condition of H. pylori-related gastritis. A 10-year follow-up study of patients with chronic atrophic gastritis (CAG) mainly caused by H. pylori infection demonstrated a moderate increase in gastric cancer risk with the presence of CAG, and the risk was greatest among subjects with a moderate level of CAG at baseline (6). The attenuation of risk with the length of follow-up period after a peak at 4–6 years supported hypothetical evidence that incomplete and unstable CAG in the process of atrophy is potently associated with the development of gastric cancer.
Concerning the third point above, several pieces of evidence in Japan indicated concordance of H. pylori epidemics and risk of gastric cancer. The incidence rate of gastric cancer has been decreasing recently in concert with the decreasing trend of H. pylori infection in younger persons (7). The mode of infection is considered to be oral–oral and/or fecal–oral routes and the infection risk has diminished recently with improvements in sanitary conditions. In the northeast Asian countries, e.g. Japan, Korea and China, the incidence rate of gastric cancer is constantly high whereas it is extremely low in southeast Asia, especially in Indonesia, even though the infection rate of H. pylori among the general population is not very different from that among Japanese. Different exposure levels to other related risk factors, e.g. intake of salt and consumption of vegetables and fruit, could explain these discrepant epidemics of gastric cancer in Asian countries; however, further comprehensive epidemiological studies should be extended to clarify such a paradoxical feature.
The incidence rate of gastric cancer in Japanese immigrants in Brazil is relatively high in the world, but slightly lower than that of the original Japanese in Japan. Probably variations of ecological background and additionally H. pylori epidemic patterns in Brazil influence the risk reduction of gastric cancer. When we discuss variations of risk factors for gastric cancer between Japanese and non-Japanese, comparative studies of the variations in genetic background in targeted groups is indispensable from the epidemiological point of view. In this issue of the journal, two case-control studies on gastric cancer compare risk and protective factors among Japanese immigrants and non-Japanese Brazilians (8,9). The authors report that cigarette smoking and low consumption of vegetables are risk factors for gastric cancer in non-Japanese Brazilians. The introduction of habitual intake of beef consumption in Brazil may elevate the risk of gastric cancer among Japanese immigrants and their descendants. Furthermore, high intake of fruit is a common protective factor against gastric cancer in both Japanese immigrants and non-Japanese Brazilians. We expect sequential and comprehensive epidemiological analyses of changing patterns of gastric cancer risk, ecological background of general lifestyles and frequency distribution of H. pylori infection in the targeted general population in Brazil. Such a comparative study on risk and protective factors for gastric cancer between original residents and immigrants in Brazil certainly provides useful information for further prevention programs.
Recently, biological evidence has indicated that the variable virulence of H. pylori depending on strain may influence the infection rate and also progression risk of gastric cancer. H. pylori strains are divided into two groups according to productivity of a cytotoxin-associated antigen (Cag A), and strains with Cag A production have stronger virulence than strains without Cag A production (10). On the other hand, host-specific factors depending on genetic polymorphisms might be more important to explain the discrepant distribution of H. pylori carriers and gastric cancer patients. A new challenge is represented by an epidemiological strategy for paradoxical evidence on the risk of gastric cancer by H. pylori infection. Molecular epidemiological studies disclosed variations of the susceptibility to gastric cancer through gene polymorphisms of chemical metabolites, detoxifying enzymes and then modification of H. pylori infection. Current human genetic studies suggest that cancer onset and its progression are associated with host-specific factors such as those designated genetic susceptibility. With regard to relationships between human genetic polymorphism and susceptibility of H. pylori infection, polymorphism of two fucosyltransferase genes, Lewis (Le) and Secretor (Se) genes, are associated with the presence of anti-H. pylori IgG antibody and Le and Se genotypes affect the risk of H. pylori infection (11). In terms of gene–environment interaction, several gene polymorphisms influence the infectivity of H. pylori in a host accompanied by specific lifestyles. Interleukin 1 (IL-1) is one candidate for this discussion (12). The polymorphism of IL-1B C-31T is associated with vulnerability to persistent H. pylori infection, and that the vulnerability is modified by habitual smoking in Japan and the available evidence are consistent in Japanese in Brazil (13).
These host-specific genetic factors are the basis of sensitivity and resistance against H. pylori infection and the development of gastric cancer among individuals in a population. The final goal of epidemiological studies is the establishment of preventive measures and the implementation of cancer control requires modification of the behavior and culture in a targeted group.
In conclusion, reduction of the general risk of gastric cancer requires alterations to lifestyle in some respects, and to this end we must collaborate with and enlist the aid of behavioral scientists, utilizing their comprehensive knowledge of the culture of a targeted group.
REFERENCES
1 Parkin D, Whelan S, Ferlay J, Raymond L, Joung J. Cancer Incidence in Five Continents, Vol. VII. IARC Scientific Publications No. 143. Lyon: IARC 1997.
2 Tominaga S. Decreasing trend of gastric cancer in Japan. Jpn J Cancer Res 1987;78:1–10.[Web of Science][Medline]
3 International Agency for Research on Cancer. Infection with Helicobacter pylori. In Schistosomes, Liver Flukes and Helicobacter pylori. IARC Scientific Publications No. 61. Lyon: IARC 1994; 177–240.
4 Shimizu N, Inada Y, Nakanishi H, Tsukamoto T, Ikehara Y, Kaminishi M, et al. Helicobacter pylori infection enhances glandular carcinogenesis in Mongolian gerbils treated with chemical carcinogens. Carcinogenesis 1999;20:669–76.
5 Shimizu N, Ikehara Y, Inada Y, Nakanishi H, Tsukamoto T, Nozaki K, et al. Eradication diminishes enhancing effects of Helicobacter pylori infection on glandular carcinogenesis in Mongolian gerbils. Cancer Res 2000;60:1512–4.
6 Inoue M, Tajima K, Matsuura A, Suzuki T, Ohashi K, Nakamura S, et al. Severity of chronic atrophic gastritis and subsequent gastric cancer occurrence: a 10-year prospective cohort study in Japan. Cancer Lett 2000;161:105–22.[Web of Science][Medline]
7 Kikuchi S, Nakajima T, Kobayashi O, Yamazaki T, Kikuchi M, Mori K, et al. Effect of age on the relationship between gastric cancer and Helicobacter pylori. Jpn J Cancer Res 2000;91:774–9.[Web of Science][Medline]
8 Nishimoto IN, Hamada GS, Kowalski LP, Rodrigues JG, Iriya K, Sasazuki S, et al. Risk factors for stomach cancer in Brazil (I): a case-control study among non-Japanese Brazilians in São Paulo. Jpn J Clin Oncol 2002;32:277–83.
9 Hamada GS, Kowalski LP, Nishimoto IN, Rodrigues JJG, Iriya K, Sasazuki S, et al. Risk factors for stomach cancer in Brazil (II): a case-control study among Japanese Brazilians in São Paulo. Jpn J Clin Oncol 2002;32:284–90.
10 Covacci JE, Censini S, Bugnoli M, Petracca R, Burroni D, Macchia G, et al. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci USA 1993;90:5791–5.
11 Ikehara Y, Nishihara S, Yasutomi H, Kitamura T, Matuo K, Shimizu N, et al. Polymorphisms of two fucosyltransferase genes (Lewis and Secretor genes) involving type I Lewis antigen are associated with the presence of anti-Helicobacter pylori IgG antibody. Cancer Epidemiol Biomarkers Prev 2001;10:971–7.
12 Hamajima N, Matsuo K, Saito T, Tajima K, Okuma K, Yamao K, et al. Interleukin 1 polymorphism, lifestyle factors and Helicobacer pylori infection. Jpn J Cancer Res 2001;92:383–9.[Web of Science][Medline]
13 Hamajima N, Ito H, Matsuo K, Tajima K, Tominaga S. Helicobacter pylori seropositivity, the interleukin 1B polymorphism and smoking among first-visit outpatients. Asian Pacific J Cancer Prev 2002;3:23–8.
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