A hospital-based case-control study of stomach cancer in high – and low risk areas of the Federal Republic of Germany identified several possible diet- related risk factors (72). In addition to material collected from the case-control study, data on traditional habits going as far back as 1910 were analyzed. From the historical data, use of vegetables and legumes was associated with the low-risk area, whereas mashed potato, cabbage, and farinaceous dishes were dominant in the high-risk area. Cultivation and use of tomatoes began relatively late in the high-risk area. The traditional wood used for smoking in the low-risk area was beech; various woods, including spruce, were used in the high-risk area. From the case- control study, low intake of vitamin C, noncentralize water supply, refrigerator use for <25 y , and use of spruce wood for smoking meat at home were associated with increased risk of gastric cancer. These associations applied to both individuals and regions. A similar study in two Belgian provinces with contrasting gastric-cancer mortality retes indentified other dietary risk factors(73). Consumption of most raw or cooked vegetables and fresh fruit (especially apples) was protective, as was consumption of lean meat. Increased risk was associated with meal and flour products, including white bread, and sugar. In contrast to other vegetables, beans increased risk for gastric cancer; this, however, may support the findings for carbohydrate rich foods. Most sources of fat did not show a clear effect, but oils with a high ratio of polyunsaturated to saturated fatty acids were associated with decreased risk.
Another case-control study was conducted in four provinces of Spain (74). One was a low-risk area; the others had relatively high rates of gastric cancer. From 15 hospitals,354 cases of confirmed gastric adenocarcinoma were selected, along with a control for each from the same hospital matched by age, sex, and area of residence. Information on diet was btained from dietary histories and frequency questionnaires. Increased risk was associated with habitual consumption of preserved fish, cold cuts, and oily fruits. Cooked green vegetables, fresh noncitrus fruit, and dried fruit were protective. Effects were additive: high intakes of a protective food groups enhanced protection, and conversely. This observation may have practical implications for public health campaigns, because efforts to get people to eat more of some thing are generally more successful than exhortations to eat less of something. Preference for salty foods and addition of salt at the table were not associated with risk.
In Italy, gastric cancers I high- and low-risk areas may differ by histologic type (75). When 923 tumors were categorized according to the Lauren classification, intestinal types outnumbered diffuse by 3:1 in the high-risk north-central region, whereas the two types were equally abundant in low-risk areas. Intestinal types were also more common at older ages and in men. However, diet-related risks for the two types were similar: increased risk was associated with high intake of meat, dried or salted fish, seasoned cheeses, and traditional soups, whereas heavy consumption of fresh fruits and vegetables was protective. Indices for specific nutrients associated with the food groups showed the same risk patterns as the foods. Occurrence of both histologic types was inversely associated with socioeconomic status but urelated to cigarette smoking. Thus, despite other differences, the intestinal and diffuse types f gastric carcinoma appear to share common etiologic factors. Sixty-eight of the 923 tumors occurred in the gastric cardia (76). Compared with other gastric cancers, these were more common in men than in women and had a reater tendency to be associated with a family history of this cancer. Dietary risk factors were the same as for gastric cancer ingencral, considering the limited data for the cardia site. However, the proportion of cardia tumors in this study is much smaller than that reported by countries where sharp increases in the incidence of cancers of the cardia and lower esophagus have recently been noted, suggesting a need for research on environmental and host determinants of this emergent tumor.
Fresh fruits were significantly protective against gastric cancer in a smaller case-control study in rural Leon, Spain (77). Consumption of home-made sausages or home-cured meats conferred some risk, which reached statistical significance f the meat were smoked. There was a nonsignificant protective effect from consumption of fresh vegetables.
A prospective study of gastric cancer mortality in a cohort of initially healthy high-risk men suggested that excess gastric cancer risk in the North Central USA is partly due to foreign birth or having an immigrant parent from Scandinavia or Germany, where risk is also high (78). An association between low educational attainment and laboring or semiskilled occupations was found only for foreign-born and first- generation Americans. The strongest risk factor in this study was cigarette smoking, and it was dose-related; risk was also increased among pipe smokers and men who used smokeless tobacco. No excess risk was associated with drinking alcohol. When dietary factors were examined, none of the 7 food groups (meats, fish, dairy, breads, fruits, vegetables, cruciferous vegetables) was significantly associated with risk, but several of the 35 individual food items were risk factors: salted fish, bacon, milk, cooked cereal, and apples. One explanation offered for the surprising association between apple consumption and increased risk was that quantities of apples were customarily stored in conditions under which they could become moldy. Patulin, a mycotoxin contaminant found in apple products, induces sarcomas in rats at the injection site.
Kashmir has nonmigrant population of Muslims, Hindus, and Sikhs with distinctive personal and dietary habits (79). Overall its rate of esophagogastric cancer is very high, but the rate among Hindus is relatively low. Muslims and most Hindus do not drink alcohol, whereas alcohol consumption is common among Sikh men. Smoking is common among Hindu and Muslim men, and Nuslims frequently use snuff; Sikhs do not smoke. Up to 10 cups per day of salted tea, boiling hot, is drunk by Muslims; Hindus drink 2-4 cups per day of green tea boiled with spices. Most Kashmiries have an adequate intake of locally grown fruit. Their staple diet is boiled rice and a boiled leafy cruciferous vegetable. Most of them eat lamb. Other special food items are dried and pickled vegetables, sundried and smoked fish, red chilies, lotus stem, other local cegetables, mixed spice cake, saffron, and mawal (Celosia argentea, a vegetable food colorant). Because of the large number of gastric (996) and esophageal (1515) cancer diagnosed during the three-year study in a valley whose population is ~2.9 million, a study of dietary risk factors seems important.
Rapid social changes in Hong Kong during the past 20 years have produced considerable heterogeneity in exposure to possible etiologic factors for esophageal cancer, enhancing the likelihood of detecting both risk factors and protective factors for this tumor in a population whose risk is high by international standards (80). In a study of 400 patents hospitalized for esophageal cancer and 1598 hospital and clinic controls, interviewers questioned subjects about sociodemographic characteristics, smoking, drinking, tea and coffee consumption, and personal and family medical history. A food-frequency questionnaire inquired about past and recent consumption of 22 food items. The foolowing significant risk factors were identified by multivariate analysis: tobacco smoking, alcohol drinking, preference for high-temperature drinks and soups, infrequent consumption of green vegetables or citrus fruits, and consumption of pickled vegetables. Assuming that risk is multiplicative, the combined attributable risk is multiplicative, the combined attributable risk due to these exposure was 89% In preliminary analyses, protective trends were seen for carrots, tomatoes, and noncitrus fruits; low educational attainment and eating salted fish increased risk. Support was given to the assumption of multiplicative risk by a modeling study in Italy (81). In this study of 211 men with esophageal cancer and 712 controls, an additive model was inadequate for describing relative risk, but the data fitted a multiplicative model. Major risk factors were alcohol and tobacco consumption and a low β- carotene index. Retinol index had no association with risk. Case-patients were less educated and of lower social class than controls. The use of statistical modeling in studies such as this is discussed. In Transkei, extensive inquiries were made into the diet and social habits of 100 esophageal cancer patients and 100 controls (82). Regression analysis identified smoking, use of traditional medicines, and consumption of black nightshade (Solanum nigrum) as significant risk factors. Drinking traditional beer was not a risk factor. The findings are discussed in terms of the rapid increase in incidence of esophageal cancer in Transkei since 1950, which has accompanied population expansion, reduced availability of milk, meat, sorghum, and millet, and greater dependence on corn and perhaps wild vegetables.
Adams briefly reviewed the literature on relation-ships between hormones, fat, and breast cancer (83). He made the following points: (i) Japanese women have a much lower incidence of breast cancer than Americans, but the difference disappears within two generations when they migrate to the USA; (ii) positive association between breast cancer risk and intake of saturated fats is repeatedly seen in postmenopausal women; a similar association exists between breast cancer risk and body mass index, again only for postmenopausal women; and (iii) hormones, particularly estrogens, are thought to act as promoters of breast carcinogenesis. Experiments with rodents support observations in humans. When hormone profiles of American and Japanese women were compared, dehydroepiandrsterone sulfate (DHEAS) concentrations were significantly higher in the blood of Americans. An estrogen, 5 – androstene- 3β,17β-diol, is formed peripherally from this and in Western women peripherally from this and in Western women it reaches biologically active levels. Urinary metabolites of DHEAS, 11-deoxy-17 keto-steroids, were also higher in American women DHEAS, its metabolites, and incidence of breast cancer and leads Adams to hypothesize a direct link between diet, secretion of hormones (especially DHEAS), and development of breast cancer. He suggests that diet and body fat provide fatty acids that act directly or indirectly on the mammary gland and augment prolactin and DHEAS secretion, girls produced the opposite results and conclusions (84). When hormone levels of vegetarian (Seventh-DayAdventist) and nonvegetarian girls in the Chicago area were compared, vegetarians had somewhat higher DHEAS luteal and follicular levels than novegetarians, with a significant difference in the luteal phase of the menstrual cycle. The authors cited other evidence for an inverse relationship between DHEAS levels and breast cancer risk. Vegetarians in this study ingested significantly less total fat, saturated fat, sucrose, cholesterol, protein and caffeine and significantly more unsaturated fat and fiber than nonvegetarians, but none of these nutrients was associated with DHEAS. Nevertheless, the link be tween a vegetarian diet and DHEAS suggests how low-fat diets during adolescence may reduce subsequent breast cancer risk.
A review by Rose uses evidence from epidemiologic and animal studies to suggest how dietary fiber may modify the putative adverse influence of fat (85). The mechanisms by which fiber protects against breast cancer probably involve estrogen metabolism and bioactivity through effects of fiber on the enterophepatic circulation of estrogens, enhanced fecal excretion of estrogens, and actions of fiber-associated phytoestrogens. Phytoestrogens have weak estrogenic activity, but by competing with more potent estrogens for receptor binding sites they may exert a net antiestrogenic effect. Thus a diet rich in phytoestrogens might downregulate estrogen bioactivity and protect against breast cancer.
A case-control study in Moscow found that dietary factors are more important for postmen- pausal than premenopausal breat cancer (86). A decreased risk for postmenopausal breast cancer was associated with high intakes of cellulose, monosaccharides and disaccharides, vitamin C, β-caro-tene, and polyunsaturated fatty acids (PUFAs).High protein intake was a risk factor with a very high odds ratio but also very wide confidence limits. Alcohol was a risk factor for both premenopausal and postmenopausal women, but it reached significance only in the postmenopausal and postmenopausal case-patients and controls were discussed.
The role of diet in breast cancer development was evaluated in an Australian case-control study (87). Groups of 100 patients with breast cancer, benign epithelial hyperplasia, or fibrocystic disease and roughly 200 control subjects participated. Cancer patients and controls were matched by age and electoral district. Patients with fibrocystic disease were matched to those with benign epithelial hyperplasia, and these groups shared the same control. The authors hypothesized that dietary patterns of the group with fibrocystic disease (notconsidered a risk factor for cancer) would resemble dietary patterns of controls, whereas patients with benign epithelial hyperplasia (a probable precursor of malignancy) were expected to resemble cancer patients in their dietary patterns. The results supported this hypothesis. Consumption of red meat, “savory meals,” or starches increased risk of hyperplasia and neoplasia, whereas consumption of chicken and fish or fruit was protective.
A prospective case-cohort study conducted on the island of Guernsey found plasma selenium concentration to be at most a weak indicator of breast cancer risk (88). However, only a limited and moderate range of selenium exposures and a relatively short time span (10 years) were considered.
An epidemiological study of postmenopausal breast cancer in western New York confirmed that risk increases with a family history of breast cancer, a history of benign breast disease, high body mass (Quetelet) index, and age at first pregnancy and decreases with number of children and pregnancies (89). After adjustment for confounding factors, risk was highest among women with the lowest consumption of carotene or substances correlated with consumption of carotene. Risk was not associated with retinol ingestion or with fat intake, whether in terms of quantity or proportion of total energy intake.
In extending to 8 years the follow-up of nearly 90,000 women enrolled in a health study, Willett et al. Found no evidence to suggest a major adverse influence of total or saturated fat intake by middle-aged women on breast cancer risk (90). However, in this same study population, consumption of vitamin A (including supplements) and vitamin E showed inverse relationships with breast cancer risk(91). The association was significant for vitamin A but nonsignificant for vitamin E; both associations were slightly stronger for premenopausal than for postmenopausal women. No association was seen for vitamin C.
Death rates from breast cancer in southern Italy are low, but in northern Italy they have recently approached rates in the USA (92). Distinctive dietary patterns are found in these three areas. Southern Italy has the lowest consumption of meat, milk, and cheese and the highest consumption of fish, bread and baked goods, pastas, and vegetables. Notthern Italy has the highest consumption of cheese and fruits and the lowest consumption of cheese and fruits and the lowest consumption of fish. The USA has the highest consumption of meat, milk, and eggs and the lowest consumption of bread and baked goods and pastas. High consumption of olive oil characterizes southern Italy, whereas butter intake in northern Italy is three times higher than in the south and is similar to that in the USA. Vegetable oils other than olive oil were little used in Italy before 1970; since then they have come to represent more than one-third of the fats in both north and south.
In a case-control study of breast cancer in Argetina, where the mortality rate for this disease is high, information was obtained on demographic, socioeconomic, and reproductive variables, frequency of consumption of 40 food items, and methods of cooking (93). After nondietary risk factors were controlled for, weak positive associations were found between breast caner risk and intake of beef, fried foods, and > 3 eggs per week. The most likely reason for failure to find strong associations with dietary factors was lack of sufficient heterogeneity in nutritional exposures within the study population. The authors had expected to find a stronger relationship between breast cancer risk and beef consumption. Failure to find one may mean that non exists; however, beef consumption was high (generally>4 times per week) in both case and control groups.
Evidence is accumulating diet can influence survival of cancer patients as well as the initial development of their disease. However, a study of breas concer patients in Denmark found no prognostic significance for reproductive or hormonal risk factors, dietary variables, alcohol consumption, or smoking