DIET, NUTRITION AND CANCER IN JAPAN S. TOMINAGA * and I. KATO Division of Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan

ABSTRACT A number of epidemiological and experimental studies have revealed that dietary habits and nutrition are one of the major risk factors for cancer. Dietary habits and nutrition are related to cancer in various ways and many factors are involved in the development of cancer. These include large intakes of salted foods and pickled vegetables, and too low intakes of fresh vegetables and fruits which are known to be major risk factors for stomach cancer. A large intake of green-yellow vegetables is known to be a protective factor against cancer of the stomach, lung and some other sites. In Japan the westernization of dietary habits and nutrition may have contributed to the changes in the mortality of several kinds of cancers which have been observed in Japan in recent years. Further improvements of dietary habits and nutrition intake are important and will be effective for primary prevention of cancer. Key words: Diet, Nutrition, Cancer, Epidemiology, Prevention, Japan

INTRODUCTION

From many epidemiological and experimental studies, diet has been considered the most important risk factor in the etiology of cancer (Wynder & Gori, 1977, Doll & Peto, 1981). Thus, the elucidation of dietary risk factors is of primary importance and improvements of dietary habits may contribute greatly to the primary prevention of cancer. However, foods/nutrients are related to cancer in many and complicated ways. The relation between foods/nutrients and cancer varies with the site of the cancer. The cancer incidence/mortality may vary from country to country and from time to time, often reflecting geographical variations and temporal changes of foods/nutrients intake. In this paper epidemiological studies on the relation between foods/ nutrients and cancer will be reviewed with special reference to changing patterns of cancer and diet in Japan (Tominaga & Kato, 1990). *Address for correspondence: Suketami Tominaga, M.D., Director, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusda-ku, Nagoaya 464, Japan. Fax No.: 81 52 763 5233. 125

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RELATIONSHIP BETWEEN FOODS AND CANCER

Important among various risk factors for cancer are the following (Tominaga, 1983): (1) Some kinds of foods (such as bracken fern, coltsfoot, dandelion, and cycad) contain carcinogens, but most of them are considered of low carcinogenicity for humans when consumed in normal amounts. (2) Grains (such as peanuts and corn) growing in the hot and humid countries are contaminated with carcinogenic mycotoxins such as aflatoxin B1 produced by Aspergillus flavus etc. (3) Some kinds of food additives such as AF2 and butter yellow are mutagenic and carcinogenic (but they have been prohibited for food use). (4) Some types of mutagens/carcinogens (such as Trp-p-1, Trp-p-2, Glup-1, Glu-p-2, MeiQ, MeiQx etc) are produced by heating foods. (5) From foods or their components which are non-carcinogenic, some types of carcinogens are formed in the gastrointestinal tract. For example, nitrosoamines are formed in the mouth or stomach when nitrites contained in the saliva and foods, or nitrites produced by reduction of nitrates contained in pickled vegetables and some other foods, react with the low grade amines contained in the meat of fish, etc. (6) A high fat and low fiber diet is regarded as a high risk factor for colorectal cancer through abnormal metabolism of bile acids. (7) Concentrated salt is regarded as a high risk factor for stomach cancer, from epidemiological and experimental studies. (8) Vitamin A, beta-carotene and vitamin C have inhibitory effects for carcinogenesis. (9) It is possible that poor nutritional status increases susceptibility to virus infection (including infection by oncogenic viruses). Over-nutrition may promote cancer growth. In addition to these factors, the hardness and volume of foods, eating practices (such as chewing and regularity of meals), and the methods of preserving foods (salting, smoking, refrigeration and freezing) have been suspected of being related to carcinogenesis directly and indirectly (Tominaga, 1983). DIETARY RISK FACTORS FOR THE MAJOR SITES OF CANCER IN JAPAN

Table 1 summarizes dietary risk factors for selected cancers which are frequent or increasing in Japan. For stomach cancer, salted foods, fish (especially salted or dried fish), large amounts of rice, hot drinks and foods, and irregular meals are high risk factors, as well as broiled meats, smoked foods, and pickled vegetables, whereas milk and dairy products, raw vegetables, fruits, and miso soup (soy bean paste soup) are low risk factors (Tominaga, 1983). Miso soup has been

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127 TABLE 1 Dietary risk factors for selected cancers Site of cancer

High risk factors

Low risk factors

Stomach

Salty foods Fish (salted or dried) Large amounts of rice (grains as a staple food) Hot drinks and foods Irregular meals

Milk & dairy products Raw vegetables Fruits Miso soup (?)

Colo-rectum

High fat diet Low fiber diet Beer (rectal cancer) Low level of serum cholesterol (?)

Fiber-rich diet (grains, pulse, etc.) Good protein-rich diet (cheese, beef, etc.)

Oesophagus

Alcoholic beverages Hot drinks and foods Diet poor in protein, vitamins and minerals

Vegetables, fruits Diet rich in good protein, vitamins, and minerals

Breast

High fat/calorie diet (especially in adolescence)

Lung

Cholesterol

Green-yellow vegetables Carotene, vitamin A

reported to reduce the risk of stomach cancer (Hirayama, 1982), but the mechanism of action and the causal relationship is not clear. For colorectal cancer (especially colon cancer), several risk factors have been reported. Among these a high fat/low fiber diet is considered the most important. A high fat diet increases secretion of bile acids and the subsequent formation of secondary bile acids which are suspected of acting as promoters. On the other hand, a low fiber diet is suspected of potentiating the effects of promoters and carcinogens by changing the intestinal bacterial flora and the concentration and stagnation of feces. Although a positive correlation between per capita beer consumption and rectal cancer among brewery workers was reported in western countries, the relationship between beer and rectal cancer has not been confirmed in Japan. Although a low level of serum cholesterol has been reported as a high risk factor for colon cancer, it is likely that this is a result, rather than a cause (from early lesions or antecedent lesions of colon cancer) and the causal relationship between them has still to be elucidated. For oesophageal cancer, alcoholic beverages have commonly been observed as high risk factors through studies conducted in both Japan and elsewhere. A diet poor in protein, vitamins and minerals is also regarded as a high risk factor. Besides dietary habits, smoking also carries a high risk, and for oesophageal cancer the risk has been reported to be higher in smokers who also drink.

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For breast cancer, a high fat or high calorie diet, especially in adolescence, has been considered to be a high risk factor for postmenopausal breast cancer. Early menarche and large height and weight have been observed as high risk factors for breast cancer, and these factors may also reflect overnutrition during the growing period. As to the risk factors for lung cancer, many epidemiological studies have demonstrated that smoking is the most important. Among dietary items, green-yellow vegetables, vitamin A and beta carotene have been reported as low risk factors, whereas a high cholesterol intake has been reported to increase the risk of lung cancer (Hinds, 1983), but the relationship has not been confirmed in other studies. CHRONOLOGICAL CORRELATIONS BETWEEN FOODS/NUTRIENT INTAKE AND CANCER MORTALITY IN JAPAN

In Japan, stomach cancer is still the most common cancer, but its mortality has been markedly declining in the last three decades. Figure 1 shows the age-adjusted mortality rates for selected sites of cancer in Japan from 1950 to 1987 (Tominaga & Kato, 1990). Uterine cancer, which was also common in the past has shown a more marked decline in the last several decades and Male

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Relative changes in the cancer mortality in Japan compared to the values for

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at present it is at about one fifth of the highest level. In females, cancers of the liver and oesophagus are also going down. On the other hand, cancers of the lung, prostate, pancreas, biliary tract, colon, and ovary have been increasing in recent years in Japan. Breast cancer too shows a gradually increasing trend. Cancers of the rectum and oesophagus (males) are stable. The reasons for the marked changes over time in the mortality of cancer in Japan are not clear, but it is most likely that they have derived from changes in environmental risk factors, especially dietary habits and smoking/ drinking habits. Based on the data of the National Nutritional Survey conducted in Japan annually, the relative changes in food/nutrient intake from 1950 to 1987 were examined in Figure 2 (Tominaga & Kato, 1990). Among foods, the intake of milk/milk products increased most, followed by meats, eggs, oils & fats and fruits, while the intakes of cereals, pickles and potatoes decreased. The intake of fish & shellfish and beans were relatively constant and showed only a slight increase. Among nutrients, the intake of fat increased most, followed by animal protein, calcium, vitamin A and vitamin B2. The calorie intake has been constant and recently has rather decreased. The intakes of vitamin B 1, salt, vegetable protein and carbohydrate decreased. A factor analysis was applied to the data of cancer mortality rates and food/nutrient intakes. The first factor obtained from the factor analysis was regarded as a "westernization factor"; milk/milk products, meats, fat, animal protein, oils/fats, calcium, fruits, vitamin C, eggs, fish & shellfish Foods 20

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Relative changes in foods/nutrients intakes in Japan compared to the values for

1950.

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and cancers of the colon, ovary, rectum, pancreas, breast and prostate. Located at the opposite end were carbohydrate, cereals, vegetable protein, fiber, pickles and cancers of the stomach and esophagus (Tominaga & Ka to, 1990). Correlation analyses on foods/nutrients intake and cancer mortality rates yielded in the same grouping as the factor analysis. There should be some time-lag before changes in food/nutrient affect cancer mortality. To estimate this statistically, the maximum correlation coefficient was calculated between food/nutrient intake and cancer mortality for different lag-times (0 to 20 years). The maximum correlation coefficients between intakes of cereals and fat and mortality rates of cancers of the stomach, oesophagus, colon, breast, ovary and prostate and "the statistical time-lag" which gave the largest correlation coefficient are shown in Table 2. This statistically estimated time-lag was approximately 10 years with the range of 4 to 16 years. The maximum correlation coefficient was greater than +0.97 or less than -0.97. A significant correlation does not necessarily mean a causal relationship. This could be a spurious or indirect correlation through other factors. We should consider factors other than dietary habits which have changed during the same period and have possibly influenced the cancer incidence and mortality. It is possible that the improvements in cancer treatment and cancer screening programs may have decreased some sites of cancer mortalities, but the trends in cancer incidence from a population-based cancer registry are generally consistent with trends in cancer mortality (Hanai & Fujimoto, 1984). Thus, it is unlikely that cancer screening has influenced the cancer mortality significantly. The improvements of diagnostic methods may have contributed to the increase of some sites of cancer incidence such as pancreas and ovary by reducing misdiagnosis. Other changes in life style, such as increases in tobacco and alcohol consumption ~nd changes in reproductive behaviour such as a decrease in TABLE 2 Maximum correlation coefficients between cancer mortalities and foods/nutrients intakes preceding some lag-time Cereals

Fat

Site of cancer

Sex

r

Year

Stomach

M F M M F F F M

0.994 0.992 0.985 -0.991 -0.990 -0.986 -0.987 -0.974

8 9 10 7 9 6 4 15

Oesophagus Colon Breast Ovary Prostate

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r

Year

-0.991 -0.992 -0.998 0.986 0.987 0.984 0.987 0.970

10 12 11 12 9 8 8 16

131

the number of children and an evaluation of age at the first birth may have also increased the cancer incidence, especially tobacco and/or alcoholrelated cancers and hormone-related cancers. Results from correlation studies are usually used for hypothesis generation, but they may also be useful for identifying risk factors which are relatively homogeneous within a population, but which differ greatly between populations or periods. The present study on chronological correlations between food/nutrient intakes and cancer mortalities in Japan confirmed the importance of diet in the aetiology of cancer. However, further observations and analyses are necessary to confirm the relationship between food/nutrient intakes and cancer mortality. DESIRABLE DIETARY HABITS FOR CANCER PREVENTION

Many epidemiological and experimental studies have suggested that diet is one of the most important risk factors of cancer. It may be possible to prevent the incidence of cancer to some extent by improvements of dietary habits. Considering previous epidemiological studies, and traditional as well as recent dietary habits in Japan, the following points in dietary habits are recommended for cancer prevention: (1) To reduce the intake of salted foods, (2) To avoid too much fat, especially animal fat, (3) To take large amounts of raw vegetables, green-yellow vegetables and fruits, (4) To take a well-balanced diet, and (5) To take meals regularly and chew foods well. It is considered that these recommendations may also contribute to primary prevention of cardio-vascular diseases and health promotion. REFERENCES Doll, R. and Peto, R. (1981), The cause of cancer: Quantitative estimates of avoidable risks of cancer in the United States. J. Nat/ Cancer Inst. 66: 1192-1308. Hanai, A. and Fujimoto, I. (1984), Changing patterns of cancer incidence. Jpn. J. Cancer Chemother. 11: 367-376. Hinds, M.W. eta! (1963), Dietary cholesterol and lung cancer risk among men in Hawaii. Am. J. C/in. Nutr. 37: 192-193. Hirayama, T. (1982), Relationship of soy bean soup intake to gastric cancer risk. Nutrition and Cancer 3: 223-233. Ministry of Health and Welfare of Japan, Health and Welfare Statistics and Information Department (ed) (1989), Vital Statistics 1987 Vol. 1, Koseitokei Kyokai, Tokyo. Ministry of Health and Welfare, Bureau of Public Health (ed) (1951-1989), Kokumin-Eiyono-Genjo (current status of national nutrition) 1949-1987, Dai-ichi Shuppan, Tokyo (in Japanese). Tominaga, S. (1983), Cancer and dietary habits. In: Data Book of Food, Nutrition & Health (Ed. Association of Nutrition Survey), Ishiyaku-Shuppan-Kabushikikaisha, Tokyo, pp. 135-141 (in Japanese). Tominaga, S. (1987), Diet and cancer. Asian Medical Journal. 30: 268-274. Tominaga, S. and Kato, I. (1990), Changing patterns of cancer and diet in Japan. In: Recent

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Progress in Research on Nutrition and Cancer. (Eds. Mettlin, C. & Aoki, K.), Wiley-Lis, Inc., New York, pp. 1-10. Wynder, E.L. and Gori, G.B. (1977), Contribution of the environment to cancer incidence: An epidemiologic exercise. J. Nat/ Cancer Inst. 58: 825-832.

Nutrition and Health, 1992, Vol. 8, pp. 125-132 0260-1061192 $10 © 1992 A B Academic Publishers. Printed in Great Britain

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Diet, nutrition and cancer in Japan.

A number of epidemiological and experimental studies have revealed that dietary habits and nutrition are one of the major risk factors for cancer. Die...
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