Green Tea and the Risk of Gastric Cancer in Japan

Original Article

Green Tea and the Risk of Gastric Cancer in Japan

Yoshitaka Tsubono, M.D., Yoshikazu Nishino, M.D., Shoko Komatsu, M.D., Chung-Cheng Hsieh, Sc.D., Seiki Kanemura, M.D., Ichiro Tsuji, M.D., Haruo Nakatsuka, Ph.D., Akira Fukao, M.D., Hiroshi Satoh, M.D., and Shigeru Hisamichi, M.D.
N Engl J Med 2001; 344:632-636
March 1, 2001

Background
Although laboratory experiments and case–control studies have suggested that the consumption of green tea provides protection against gastric cancer, few prospective studies have been performed.

Methods
In January 1984, a total of 26,311 residents in three municipalities of Miyagi Prefecture, in northern Japan (11,902 men and 14,409 women 40 years of age or older), completed a self-administered questionnaire that included questions about the frequency of consumption of green tea. During 199,748 person-years of follow-up, through December 1992, we identified 419 cases of gastric cancer (in 296 men and 123 women). We used Cox regression to estimate the relative risk of gastric cancer according to the consumption of green tea.

Results
Green-tea consumption was not associated with the risk of gastric cancer. After adjustment for sex, age, presence or absence of a history of peptic ulcer, smoking status, alcohol consumption, other dietary elements, and type of health insurance, the relative risks associated with drinking one or two, three or four, and five or more cups of green tea per day, as compared with less than one cup per day, were 1.1 (95 percent confidence interval, 0.8 to 1.6), 1.0 (95 percent confidence interval, 0.7 to 1.4), and 1.2 (95 percent confidence interval, 0.9 to 1.6), respectively (P for trend=0.13). The results were similar after the 117 cases of gastric cancer that were diagnosed in the first three years of follow-up had been excluded, with respective relative risks of 1.2 (95 percent confidence interval, 0.8 to 1.8), 1.0 (95 percent confidence interval, 0.7 to 1.5), and 1.4 (95 percent confidence interval, 1.0 to 1.9) (P for trend=0.07).

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Discussion

Our study had several methodologic advantages over prior studies of green tea and the risk of gastric cancer. We recruited subjects from the general population, and there was a large variation in green-tea consumption among our subjects. In addition, we assessed the consumption of green tea and other variables before cases of gastric cancer and other diseases were diagnosed, thus avoiding recall bias. The questionnaire used to measure green-tea consumption had a reasonably high level of validity and reproducibility. A large number of cases of gastric cancer were identified, because the incidence rate in the study region was high and the period of follow-up was reasonably long.

Our study had some limitations. Our food-frequency questionnaire included only a limited number of items and could not be used to calculate the consumption of total energy and other nutrients. Although we adjusted for the consumption of dietary items other than green tea as much as possible, we could not exclude the possibility of residual confounding by other dietary characteristics.

We did not obtain information on the presence or absence of a history of infection with Helicobacter pylori, a strong risk factor for gastric cancer.16 The prevalence of H. pylori seropositivity (determined by the presence of IgG antibodies) among subjects 55 to 64 years of age in the study area was 88 percent in men and 87 percent in women.17 The subjects with chronic gastritis caused by H. pylori infection might have limited their consumption of foods and beverages, including green tea. Some studies have suggested an antibacterial effect of green tea,18,19 which may apply to H. pylori. In either case, the prevalence of infection would have been lower in the subjects with higher intakes of green tea. Thus, we believe it is unlikely that the failure to account for H. pylori infection masked an inverse association between the risk of gastric cancer and the consumption of green tea.

Another concern is that 16 percent of the participants were lost to follow-up. Nevertheless, the proportion did not differ according to the category of green-tea consumption. Therefore, we believe that loss to follow-up did not have a substantial effect on the observed associations between the consumption of green tea and the risk of gastric cancer.
Our findings are in general agreement with those of a prospective study of Japanese persons in Hawaii, which found no inverse association between green-tea consumption and gastric cancer.12 Although in that study there was a nonsignificant increase in the risk of gastric cancer among subjects with higher levels of green-tea consumption, the number of cases of gastric cancer was relatively small (108).

Our results contradict those of most case–control studies, which show an inverse association between the risk of gastric cancer and the consumption of green tea.5-10 In these retrospective investigations, some patients with gastric cancer might have decreased their consumption of green tea before the diagnosis because of their abdominal symptoms. This change in practice might have biased their recall of past intake in such a way that they underestimated their true consumption, resulting in spurious inverse associations. Epidemiologic studies have found that patients with gastric cancer decrease their consumption of tea two years before the diagnosis20 and that the accuracy of the recall of an earlier diet is strongly influenced by the recent diet.21 This bias would partly explain the difference in the findings between prospective and case–control studies.

We also found that there was no association between the risk of gastric cancer and the consumption of black tea or coffee. These results are consistent with the findings of a review conducted by the World Cancer Research Fund, which concluded that probably neither beverage is associated with a decreased or increased risk of gastric cancer.22
In conclusion, in a prospective cohort study, we found no association — inverse or otherwise — between the consumption of green tea and the risk of gastric cancer in Japan.
Supported in part by grants from the Japanese Ministry of Health and Welfare and the Japanese Ministry of Education, Science, and Culture.

Source Information
From the Divisions of Epidemiology (Y.T., Y.N., S. Kanemura, I.T., S.H.) and Environmental Health Sciences (H.S.), Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; the Department of Nutrition, Harvard School of Public Health, Boston (Y.T.); the Faculty of Physical Education, Sendai College, Miyagi, Japan (S. Komatsu); the Division of Biostatistics and Epidemiology, Cancer Center, University of Massachusetts Medical Center, Worcester (C.-C.H.); Miyagi University School of Nursing, Sendai, Japan (H.N.); and the Department of Public Health, Yamagata University School of Medicine, Yamagata, Japan (A.F.).

Address reprint requests to Dr. Tsubono at the Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan, or at ytsubono@metamedica.com.

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