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Cancer

In this chapter, the committee summarizes the role of dietary factors as they relate to the risks of various forms of cancer. Since the evidence regarding specific dietary constituents is discussed in detail in earlier chapters, it is only briefly summarized here. Some discussion of other risk factors for these cancers is included to put the role of diet in perspective. Epidemiologic data as well as supportive evidence from animal studies and from research on mechanisms of carcinogenesis are reviewed. Although the results of experiments in animals cannot be quantitatively extrapolated to humans, they provide evidence on the biologic plausibility of observed correlations between specific dietary constituents and cancer incidence or mortality in epidemiologic studies.

Trends in Cancer Incidence in the United States and the Role of Diet

Devesa et al. (1987) reviewed trends in the incidence of and mortality from specific forms of cancer in the white populations of five areas of the United States from 1947 to 1984. Overall trends were dominated by the well-known rise in lung cancer, clearly a direct result of exposure to tobacco smoke. The authors suggested that lung cancer rates in people with little or no exposure to tobacco smoke may also have increased, but the evidence is not conclusive. Large increases in incidence were also found for melanoma of the skin, cancer of the prostate and testis, and non-Hodgkin's lymphoma. Smaller increases were found for cancers of the liver, kidney, colon, urinary bladder, and breast. Major decreases in incidence were observed for cancer of the stomach and for invasive cancer of the cervix. The combined impact of improved detection standards, diagnostic ability, and reporting on the published cancer incidence rates could not be precisely measured. It is unlikely that these factors were of major importance, however, except possibly for cancers of the cervix and breast.

Some investigators have estimated the overall impact of diet on total cancer incidence and mortality. Such estimates are based on a combination of evidence regarding established relationships between dietary factors and cancer risk, the dramatic shifts in site-specific cancer rates among migrants to the United States, secular trends in cancer for which a dietary etiology is likely, supportive evidence from animal experiments, and lack of more persuasive alternative hypotheses. Doll and Peto (1981) estimated that approximately 35% (range, 10 to 70%) of all cancer mortality in the United States is related to diet, whereas Wynder and Gori (1977) estimated that 40% of cancer incidence among men and nearly 60% among women is related to diet. Because few



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Page 593 22— Cancer In this chapter, the committee summarizes the role of dietary factors as they relate to the risks of various forms of cancer. Since the evidence regarding specific dietary constituents is discussed in detail in earlier chapters, it is only briefly summarized here. Some discussion of other risk factors for these cancers is included to put the role of diet in perspective. Epidemiologic data as well as supportive evidence from animal studies and from research on mechanisms of carcinogenesis are reviewed. Although the results of experiments in animals cannot be quantitatively extrapolated to humans, they provide evidence on the biologic plausibility of observed correlations between specific dietary constituents and cancer incidence or mortality in epidemiologic studies. Trends in Cancer Incidence in the United States and the Role of Diet Devesa et al. (1987) reviewed trends in the incidence of and mortality from specific forms of cancer in the white populations of five areas of the United States from 1947 to 1984. Overall trends were dominated by the well-known rise in lung cancer, clearly a direct result of exposure to tobacco smoke. The authors suggested that lung cancer rates in people with little or no exposure to tobacco smoke may also have increased, but the evidence is not conclusive. Large increases in incidence were also found for melanoma of the skin, cancer of the prostate and testis, and non-Hodgkin's lymphoma. Smaller increases were found for cancers of the liver, kidney, colon, urinary bladder, and breast. Major decreases in incidence were observed for cancer of the stomach and for invasive cancer of the cervix. The combined impact of improved detection standards, diagnostic ability, and reporting on the published cancer incidence rates could not be precisely measured. It is unlikely that these factors were of major importance, however, except possibly for cancers of the cervix and breast. Some investigators have estimated the overall impact of diet on total cancer incidence and mortality. Such estimates are based on a combination of evidence regarding established relationships between dietary factors and cancer risk, the dramatic shifts in site-specific cancer rates among migrants to the United States, secular trends in cancer for which a dietary etiology is likely, supportive evidence from animal experiments, and lack of more persuasive alternative hypotheses. Doll and Peto (1981) estimated that approximately 35% (range, 10 to 70%) of all cancer mortality in the United States is related to diet, whereas Wynder and Gori (1977) estimated that 40% of cancer incidence among men and nearly 60% among women is related to diet. Because few

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Page 594 relationships between specific dietary components and cancer risk are well established, it is not possible to quantify the contribution of diet to individual cancers (and thus to total cancer rates) more precisely. Nevertheless, these estimates help to emphasize the importance of diet in the etiology and prevention of cancer in the United States today. Evidence Associating Dietary Factors with Cancer at Specific Sites Epidemiologic Studies The discussion in this section is presented by specific cancer sites because the dietary associations are not the same for all cancer types. See Chapters 6 through 17 for more detailed review of evidence by dietary components. Esophageal Cancer Correlation analyses have shown direct associations between consumption of alcoholic beverages and esophageal cancer in Western countries (Breslow and Enstrom, 1974; Chilvers et al., 1979; Hinds et al., 1980; Kolonel et al., 1980; Lyon et al., 1980; Schoenberg et al., 1971). Case-control and cohort studies have also provided consistent evidence of an association between alcohol consumption and risk of esophageal cancer (Hakulinen et al., 1974; Potter et al., 1981; Williams and Horn, 1977). Alcohol consumption appears to act synergistically with cigarette smoking to increase the risk. Wynder and Bross (1961) found that increases in the use of alcohol and tobacco were associated with an increased risk of squamous cell carcinoma of the esophagus and that alcohol and tobacco exert a multiplicative effect. Similar effects have been observed in Paris (Schwartz et al., 1962), Puerto Rico (Martinez, 1969), Brittany (Tuyns et al., 1977), and Normandy (Tuyns, 1983). Alcohol also seems to have an independent effect on cancer risk in the absence of smoking (Keller, 1980). In correlation studies conducted in different parts of the world, investigators have found positive associations between esophageal cancer and several dietary factors, including (1) low intakes of lentils, green vegetables, fresh fruits, animal protein, vitamins A and C, riboflavin, nicotinic acid, magnesium, calcium, zinc, and molybdenum; (2) high intakes of pickles, pickled vegetables, and moldy foods containing N-nitroso compounds; and (3) consumption of very hot foods and beverages (de Jong et al., 1974; Hormozdiari et al., 1975; Joint Iran-IARC Study Group, 1977; Thurnham et al., 1982; van Rensburg, 1981; Yang, 1980; Zaridze et al., 1985). Many of these findings have been supported by the results of case-control studies (Cook-Mozaffari, 1979; de Jong et al., 1974; Mettlin et al., 1981). The reported associations are consistent with the general hypothesis that certain nutrient deficiencies, such as found in many high-risk populations, including heavy alcohol drinkers, might increase the susceptibility of the esophageal epithelium to neoplastic transformation (van Rensburg, 1981). In the esophageal epithelium  of humans, for example, riboflavin deficiency causes lesions that may be precursors of cancer (Foy and Mbaya, 1977), although an intervention trial with riboflavin (and zinc and retinol) in a high-risk Chinese population failed to show any effect of these nutrients (Muñoz et al., 1985). In summary, esophageal cancer is associated with the use of tobacco and alcohol individually, but especially with their combined use. Studies suggest that consumption of certain types of preserved foods increases risk and that several vitamins and minerals are protective against esophageal cancer, but the reasons for these relationships are not yet clearly established. Stomach Cancer A high incidence of stomach cancer is found in South America, Japan, and other parts of Asia, but not in North America or Western Europe where the rates are low and still decreasing (Stukonis, 1978; Waterhouse et al., 1976). In the United States, stomach cancer rates are now among the lowest in the world, whereas in 1930, this was the leading cause of cancer death for men and the second leading cause in women (Page and Asire, 1985). Gastric cancer incidence has recently begun to decrease in Japan, and a gradual decline in incidence over several generations has been noted among Japanese migrants to Hawaii (Kolonel et al., 1980). It seems most likely that these trends are related to changes in food consumption patterns, since several dietary factors have been implicated in gastric cancer risk. Several correlation and case-control studies have shown positive associations between gastric cancer and the consumption of dried, salted fish, smoked fish, or pickled vegetables (e.g., Dungal, 1966; Haenszel et al., 1976; Hirayama, 1967; Joossens and Geboers, 1987; Risch et al., 1985). These foods contain high concentrations of salt,

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Page 595 nitrates, and nitrites. Other investigators have reported associations between gastric cancer and nitrate levels in the drinking water supplies of populations in such settings as Chile (Armijo and Coulson,  1975;  Zaldivar,  1977),  Colombia (Correa et al., 1976; Tannenbaum et al., 1979), and England (Hill et al., 1973). In a case-control study in Canada, Risch et al. (1985) found a significant association between nitrite consumption and stomach cancer risk. The above findings support a hypothesis that gastric cancer is related to the reduction of nitrates to nitrites in the stomach and the subsequent formation of N-nitroso compounds (NRC, 1981). A high intake of salt might facilitate this process either by irritating the gastric mucosa, which is then more susceptible to carcinogenic transformation, or by inducing atrophic gastritis, leading to colonization of the stomach with bacteria that can nitrosate dietary precursors to form nitrosamines (Correa et al., 1976). Chronic gastritis has been associated with gastric cancer risk in Japan (Imai et al., 1971). A second major dietary association with stomach cancer has been a protective effect of fresh fruits, vegetables, and vitamins, especially vitamin C. Several case-control and correlation studies have shown  this inverse relationship (Bjelke, 1978; Correa et al., 1985; Graham et al., 1972; Haenszel and Correa, 1975; Higginson, 1966; Kolonel et al., 1981; Risch et al., 1985), which is consistent with the ability of ascorbic acid to inhibit the formation of carcinogenic N-nitroso compounds (Mirvish et al., 1972). Evidence relating certain other dietary components to stomach cancer risk is uncertain because of an inadequate replication of results. This evidence includes a direct association with carbohydrates and high-starch foods in two studies (Modan et al., 1974; Risch et al., 1985), a direct association with fried foods (Higginson, 1966), an inverse association with milk (Hirayama, 1977), and an inverse association with dietary fiber (Modan et al., 1974; Risch et al., 1985). Some studies suggest that stomach cancer risk is increased by alcoholic beverage consumption (Correa et al., 1985; Hoey et al., 1981), but others do not suggest it (Acheson and Doll, 1964; Graham et al., 1972; Haenszel et al., 1972; Tuyns et al., 1982). In summary, stomach cancer is associated with diets comprising large amounts of salt-preserved foods (that possibly contain precursors of nitrosamines) and low levels of fresh fruits and vegetables (acting as possible inhibitors of nitrosamine formation). Dietary shifts away from this pattern could explain the great decline in stomach cancer mortality in the United States over the past 50 years, but the evidence is not conclusive. Colorectal Cancer International data show a strong correlation between the incidence of colorectal cancer and cancers of the breast, endometrium, ovary, and, to a lesser extent, prostate. Within the United States, mortality from colorectal cancer is higher in the north and in urban areas than in other parts of the country (Haenszel and Dawson, 1965). Although the incidence of and mortality from this cancer have been relatively stable over the past 30 to 40 years, there has been a recent decline in mortality among females and possibly the beginning of a decline among males. In epidemiologic studies, the risk of colorectal cancer has been associated with the fat and fiber content of the diet, but other dietary constituents have also been implicated. Several correlation and case-control studies demonstrate positive associations between the risk for colorectal (primarily colon) cancer and dietary fat (Armstrong and Doll, 1975; Carroll and Khor, 1975; Dales et al., 1979; Drasar and Irving, 1973; Graham et al., 1988; Howe et al., 1986; McKeown-Eyssen and Bright-See, 1984; Miller et al., 1983; Pickle et al., 1984; Wynder, 1975). In several other studies, positive associations have been found between meat consumption and this cancer (Haenszel et al., 1973; Hirayama, 1979; Howell, 1975; Knox, 1977; Manousos et al., 1983; Pickle et al., 1984). Conversely, many other studies have shown no relationship between fat or meat intake and colorectal cancer (e.g., Enstrom, 1975; Graham et al., 1978; Haenszel et al., 1980; Kinlen, 1982; Lyon and Sorenson, 1978; Modan et al., 1975). The studies not showing a positive correlation usually included narrow ranges of fat intake. In general, the data suggest that if this association is real, saturated rather than unsaturated fatty acids are responsible. Two other major dietary components—protein and calories—have been positively associated with colorectal cancer risk in some studies (Armstrong and Doll, 1975; Carroll and Khor, 1975; Gregor et al., 1969; Jain et al., 1980; Kune et al., 1987; Lyon et al., 1987; Macquart-Moulin et al., 1986; Potter and McMichael, 1986; Thind, 1986) but not in all (Bingham et al., 1979; International Agency for Research on Cancer Intestinal Microecology Group, 1977; Jensen et al., 1982; Tuyns et al., 1987). Since it is not possible to separate

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Page 596 clearly the effects of these variables in epidemiologic analyses, it remains possible that dietary fats are not the only relevant factor. Two recent case-control studies in Europe suggest that monounsaturated fatty acids may actually have a protective effect against colorectal cancer (Macquart-Moulin et al., 1986; Tuyns et al., 1987), but this finding needs further confirmation. Few studies have examined the relationship between dietary cholesterol and colorectal cancer, but one correlation study (Liu et al., 1979) and one case-control study (Jain et al., 1980) did show a positive effect. Furthermore, the correlation of high levels of meat consumption with colorectal cancer implies a positive association with dietary cholesterol. Reports that very low serum cholesterol levels are associated with an increased risk of colon cancer in some male cohorts have not been reproduced in a substantial number of similar cohorts; in some of these studies, the association has appeared to be due to undiagnosed colon cancer in the early years of observation (McMichael et al., 1984). A relationship of diet to these low  levels of serum  cholesterol has not been established, and present evidence does not support a causal relationship between low serum cholesterol and colon cancer. The data relating dietary fiber to colorectal cancer are equivocal. Although several case-control and correlation studies have shown inverse relationships between the intake of high-fiber foods and colon cancer risk (Bjelke, 1978; Dales et al., 1979; Modan et al., 1975; Phillips, 1975), these foods (vegetables to a large extent) are rich sources of other nutritive and nonnutritive constituents with potential cancer-inhibiting properties. Thus, the observed effects cannot be attributed to fiber per se. The results of the few studies that attempted to assess the intake of fiber itself have also not been consistent. Some correlation and case-control studies (Bingham et al., 1985; Bjelke, 1978; Jensen et al., 1982; Kune et al., 1987; MacLennan et al., 1978; Malhotra, 1977; McKeown-Eyssen and Bright-See, 1984) support the hypothesis of a protective effect from dietary fiber, whereas other studies (Howe et al., 1986; Potter and McMichael, 1986; Smith et al., 1985) do not. The study by Potter and McMichael (1986) even suggests a direct association among females. Certain other dietary components have been associated with colorectal cancer in some studies. A few investigators reported inverse relationships with the intake of vitamin A or with the consumption of vegetables that were not necessarily high in fiber content (Bjelke, 1978; Macquart-Moulin et al., 1986; Phillips, 1975). Although some studies show protective effects of vitamin C and calcium (Garland et al., 1985; Macquart-Moulin et al., 1986; Potter and McMichael, 1986), others do not (Heilbrun et al., 1986; Jain et al., 1980; Tuyns et al., 1987). Several case-control and cohort studies suggest an association between alcohol intake and colorectal cancer, especially with rectal cancer (Bjelke, 1978; Dean et al., 1979; Kabat et al., 1986; -Kune et al., 1987; Pollack et al., 1984; Tuyns et al., 1982). In some studies, colorectal cancer was associated with the consumption of alcoholic beverages in general. In others, there was an association with beer consumption specifically. Other studies did not find this relationship with alcohol (Dales et al., 1979; Graham et al., 1978; Jensen, 1979; Miller et al., 1983; Modan et al., 1975). In summary, the data on diet and colorectal cancer are inconsistent, perhaps because of differences in the populations studied or in the dietary methodology used to assess intake. In general, increased risk of colorectal cancer appears to be associated with a dietary pattern consisting of a high fat intake (particularly saturated fats) and low vegetable intake. It is not clear whether dietary fiber per se is protective or whether the apparent protective effects in some studies are due to other food constituents such as vitamin C or calcium. Colorectal cancer risk may be increased by the consumption of alcoholic beverages, especially beer. Liver Cancer Primary liver cancer is relatively rare in the United States and most Western countries, but it is common in sub-Saharan Africa and Southeast Asia, where it is associated primarily with exposure to hepatitis B virus infection in early life and with consumption of foods contaminated with aflatoxins. Limited evidence links liver cancer to other possible dietary risk factors, including pyrrolizidine alkaloids, safrole, and cycasin (Anthony, 1977). In Africa, liver cancer incidence and mortality by geographic area or among different population groups have been correlated with aflatoxin contamination of foodstuffs (Alpert et al., 1971; Peers et al., 1976; van Rensburg et al., 1974). Similar geographic correlations have been found in China (Armstrong, 1980), Thailand  (Shank  et al., 1972a,b; Wogan, 1975), Taiwan (Tung and Ling, 1968), and in a case-control study in the Philippines (Bulatao-Jayme et al., 1982).

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Page 597 Numerous reports have documented a high correlation between primary liver cancer and infection with hepatitis B virus, which has a worldwide distribution similar to that of aflatoxins (Chien et al., 1981). This association was confirmed in a large prospective cohort in Taiwan (Beasley et al., 1981). Alcohol has been suggested as an etiologic agent for liver cancer in Western countries. Although liver cancer is associated with cirrhosis of the liver, which is in turn associated with heavy alcohol consumption, direct epidemiologic evidence linking alcohol to primary liver cancer is limited. Some studies show an association (Hakulinen et al., 1974; Inaba et al., 1984; Jensen, 1979; Yu et al., 1983), and others do not (Monson and Lyon, 1975; Nicholls et al., 1974; Pell and D'Alonzo, 1973; Robinette et al., 1979; Schmidt and de Lint, 1972; Trichopoulos et al., 1987). In summary, liver cancer risk is most clearly associated with early-life infection with hepatitis B virus. Aflatoxins are also an etiologic factor, possibly in association with hepatitis B virus infection, in the high-risk areas of Africa and Southeast Asia. In Western countries, some studies show an association between heavy alcohol consumption and this cancer. Pancreatic Cancer An increasing trend in the incidence of pancreatic cancer in the United States over the past 20 to 30 years now appears to be stabilizing. In general, pancreatic cancer occurs more commonly in higher socioeconomic groups and is most clearly associated with cigarette smoking as a risk factor (DHEW, 1979). Pancreatic cancer has been associated with meat consumption in some studies (Hirayama, 1977; Ishii et al., 1968; Mack et al., 1986) but not in others (Gold et al., 1985; Norell et al., 1986). In a case-control study conducted in Boston, MacMahon et al. (1981) found a dose-response relationship between pancreatic cancer and coffee consumption, but in a subsequent study by some of the same authors (Hsieh et al., 1986), other case-control studies (Gold et al., 1985; Mack et al., 1986; Norell et al., 1986; Wynder et al., 1983), and large cohort studies in the United States (Whittemore et al., 1983) and Norway (Heuch et al., 1983), no consistent evidence was found to support this association. Some studies have related cancer of the pancreas to alcohol consumption (Blot et al., 1978; Burch and Ansari, 1968; Cubilla and Fitzgerald, 1978; Dorken, 1964), but most have not—even among alcoholics (Hakulinen et al., 1974; MacMahon et al., 1981; Monson and Lyon, 1975; Tuyns et al., 1982; Williams and Horm, 1977; Wynder et al., 1973). In summary, only cigarette smoking has been clearly established as a major risk factor for pancreatic cancer. Lung Cancer In most technologically advanced countries, lung cancer is the leading cause of death from cancer among men, and it is rapidly approaching this status among women (Miller, 1980). The most important causal factor is cigarette smoking (DHEW, 1979). Lung cancer risk in males is clearly increased by certain occupational exposures (e.g., to asbestos, nickel, chromate, gamma-radiation), several of which have been shown to interact synergistically with smoking (Fraumeni, 1975). In females, cigarette smoking appears to be the only major contributor to lung cancer incidence in most Western countries. Although most studies of dietary factors and lung cancer have controlled for cigarette smoking, possible interactions between tobacco and dietary factors have received little attention. A prospective study in Norway showed that dietary vitamin A was inversely associated with lung cancer (Bjelke, 1975; Kvale et al., 1983). This result was supported by hospital-based studies in the United States (Mettlin and Graham, 1979) and in the United Kingdom (Gregor et al., 1980). Other studies (Byers et al., 1987; Hinds et al., 1984; Samet et al., 1985; Shekelle et al., 1981; Ziegler et al., 1984) suggest that the relevant dietary constituent may be b-carotene rather than retinol. This is consistent with several reports of an inverse association between lung cancer and the frequency of eating green or yellow vegetables (Hirayama, 1979; MacLennan et al., 1977). In prospective studies (Menkes et al., 1986; Nomura et al., 1985), the concentration of b-carotene in serum was inversely associated with the risk of lung cancer. Early reports of a similar inverse association for serum  retinol were not confirmed by subsequent studies (Friedman et al., 1986; Kark et al., 1981; Menkes et al., 1986; Peleg et al., 1984; Salonen et al., 1985; Wald et al., 1980, 1986). No effect of dietary vitamin C on lung cancer risk has been found (Byers et al., 1987; Hinds et al., 1984; Kvale et al., 1983; Mettlin et al., 1981). Dietary fats (Byers et al., 1987; Wynder et al., 1987) and dietary cholesterol (Hinds et al., 1983) have been positively associated with lung cancer risk. In summary, the main causal factor for lung cancer is cigarette smoke. Occupational exposures

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Page 598 to asbestos, nickel, radiation, and other agents also increase risk, and some of these have been shown to interact synergistically with smoking. Frequent consumption of green and yellow vegetables (leading to a high intake of b-carotene and other constituents in such foods) appears to be protective against lung cancer. Breast Cancer Breast cancer is a common cause of death among U.S. women. This cancer is more common in Caucasians than in other racial groups, although rates have been rising among blacks, Hispanics, and women of Asian origin. Descriptive epidemiologic studies suggest that some aspects of lifestyle are related to the incidence of breast cancer. For example, breast cancer incidence among Japanese migrant women in Hawaii is much higher than that in Japan and is even higher in their daughters born in Hawaii (Kolonel et al., 1980). Breast cancer risks are closely correlated with hormonal activity, and diet might be a major contributing factor through its effects on hormonal pathways and levels (MacMahon et al., 1973). A role of dietary factors is supported by descriptive epidemiologic studies, correlation studies, case-control and cohort studies, and evaluations of nutrition-mediated risk factors. Correlation studies provide evidence of a direct association between breast cancer mortality and the intake of calories, fats, and specific sources of dietary fats, such as milk and beef (Armstrong and Doll, 1975; Carroll and Khor, 1975; Gaskill et al., 1979). Some studies show an inverse correlation between the intake of carbohydrates or fiber and the risk of breast cancer (Adelcreutz et al., 1982; Lubin et al., 1986). Several case-control studies associate breast cancer risk with dietary constituents, especially fats. Lubin et al. (1981) and Phillips (1975) reported an association between the frequency of consumption of high-fat foods and breast cancer. Miller et al. (1978) found a positive association with total fat consumption in pre- and postmenopausal women and weaker associations with saturated fats and cholesterol in the premenopausal women, the strongest association relating to saturated fat intake (Howe, 1985). A  similar association with dietary saturated fats was found by Hirohata et al. (1987). Lubin et al. (1986) reported an increased risk of breast cancer among women who consumed a diet containing high levels of fats and animal protein and low levels of fiber; Hislop et al. (1986) found a positive association with intake of fat-containing foods, especially whole milk and beef; and Talamini et al. (1984) associated moderately increased risks with indices of fat intake. However, not all studies show these relationships (Graham et al., 1982; Hirohata et al., 1985; Willett et al., 1987a). Several studies relate alcohol consumption to the risk of breast cancer in women (Begg et al., 1983; Byers and Funch, 1982; Hiatt and Bawol, 1984; Lê et al., 1986; Schatzkin et al., 1987; Willett et al., 1987b). However, it is unlikely that this association, even if established as causal, could account for a substantial fraction of the female breast cancer incidence in most populations. Certain  nutrition-mediated  factors, notably body weight, height, and obesity (as reflected by body mass indices), have also been associated with breast cancer risk, primarily among postmenopausal women (de Waard et al., 1977; Lubin et al., 1985; Paffenbarger et al., 1980; Talamini et al., 1984). Height may be the best of these measures for predicting breast cancer risk (de Waard et al., 1977), but most studies show that the strongest association is with body mass index. However, these anthropometric measures have not been associated with risk in all populations (Kolonel et al., 1986). In summary, breast cancer risk has been associated with the high-calorie Western diet, and dietary fat is the nutrient for which the data are strongest. However, the evidence is not conclusive, and other dietary factors may also be involved. Alcohol consumption may also be a risk factor for this cancer. Endometrial Cancer Endometrial cancer has been correlated with cancers of the breast, ovary, colon, and rectum (Miller, 1978). It tends to be more common in the United States than in other parts of the world and is more frequent in Caucasian women of higher socioeconomic status. The only well-established cause for this cancer is the use of exogenous estrogens at the high dosages commonly prescribed some years ago. Both noninsulin-dependent diabetes mellitus (NIDDM) and hypertension have been associated with this cancer (Elwood et al., 1977; La Vecchia et al., 1986). An association between endometrial cancer risk and excess weight was reported in several studies (Elwood et al., 1977; Henderson et al., 1983; Jensen, 1986; La Vecchia et al., 1986; Lew and Garfinkel, 1979; Wynder et al., 1966), and a hormonal mechanism has been postulated for this association (Henderson et al.,

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Page 599 1982). A protective effect of fiber has been reported (La Vecchia et al., 1986) but not confirmed. In summary, endometrial cancer can be caused by exogenous estrogen hormones and is associated with obesity, hypertension, and NIDDM. Possible dietary risk factors for this cancer have not been established. Ovarian Cancer Ovarian cancer is more common in the United States and other Western countries than in Asia, and it occurs more frequently in countries where breast, colon, and endometrial cancers tend to occur. It tends to be more common in higher socioeconomic groups and less frequent in women who use oral contraceptives (Casagrande et al., 1979; Cramer et al., 1982; Nasca et al., 1984; Weiss et al., 1981). Cramer et al. (1984) found that women with ovarian cancer consumed much greater amounts of animal fat and considerably less vegetable fat than did control subjects, whereas Byers et al. (1983) found no association. Weight and height, which in part reflect diet, were weakly but positively associated with ovarian cancer in one case-control study (Tzonou et al., 1984), but not in others (Annegers et al., 1979; Byers et al., 1983; Hildreth et al., 1981). Two case-control studies showed an association between coffee drinking and increased risk of ovarian cancer (La Vecchia et al., 1984; Trichopoulos et al., 1981), but a third study failed to detect this association (Byers et al., 1983); this matter remains unresolved. In summary, ovarian cancer has been inversely related to oral contraceptive use, but no dietary associations have been established. Bladder Cancer Bladder cancer is more common in the United States than in many other parts of the world. It occurs more frequently in men than in women and in people of lower socioeconomic status. Bladder cancer risk is increased among cigarette smokers and among certain occupational groups exposed to certain chemicals, notably b-naphthylamine and benzidine. One cohort study showed a statistically significant association between coffee drinking and death from  bladder cancer (Snowdon and Phillips, 1984), and several case-control studies found that coffee was associated with elevated risks among males (Mettlin and Graham, 1979) and females (Cole, 1971; Fraumeni et al., 1971; Howe et al., 1980; Simon et al., 1975). Other studies found only a weak association with coffee (Hartge et al., 1983; Marrett et al., 1983; Rebelakos et al., 1985), and several found no evidence of an association (Jacobson et al., 1986; Jensen et al., 1986; Morrison et al., 1982; Nomura et al., 1986; Ohno et al., 1985). Since the relative risks in most of the positive studies were low (<2.0) and few studies showed a dose-response relationship, this association is unlikely to be causal. Residual confounding by cigarette smoking may explain the apparent effect. Conflicting findings have been reported for nonnutritive sweeteners and bladder cancer (see Chapter 17). Overall, however, it appears that use of such sweeteners does not measurably increase the risk of bladder cancer (Howe et al., in press). There is limited epidemiologic evidence pertaining to the association of other dietary exposures with bladder cancer. Armstrong and Doll (1975) found a direct association of bladder cancer mortality with per-capita intake of fats and oils, particularly among women, but this association has not been confirmed in other studies. One case-control study (Mettlin and Graham, 1979) suggested an inverse association with carrots, milk, and an index of vitamin A intake, whereas another (Risch et al., 1988) showed no evidence of a protective effect of retinol or b-carotene, but an increased risk from consumption of dietary cholesterol. Although a direct association between beer intake and bladder cancer mortality in men was reported in a correlation study (Breslow and Enstrom, 1974), this finding has not been confirmed in case-control studies (Brownson et al., 1987; Thomas et al., 1983). In summary, bladder cancer risk is clearly related to the use of cigarettes and to certain occupational exposures, such as benzidine and b-naphthylamine. Its relationship to dietary factors is less clear. Possible associations with coffee drinking, artificial sweetener use, and alcoholic beverage consumption have not been confirmed. Prostate Cancer Cancer of the prostate is common in the United States, and rates among black males are especially high. This cancer is relatively rare in males under 45 years. International incidence and mortality data generally show a positive correlation of prostate cancer with cancers of several other sites associated with diet, including cancers of the breast, corpus uteri, and colon (Berg, 1975; Howell, 1974; Wynder et al., 1971). Certain popula-

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Page 600 tions provide interesting exceptions, however: Mormons in Utah have high prostate but relatively low breast cancer incidence rates, whereas the native Polynesians of Hawaii have low prostate but high breast cancer incidence rates (Kolonel, 1980; Lyon et al., 1976). Although male hormones appear to contribute to the risk for this disease, little is known about the etiology of prostate cancer. Some investigators have suggested a causal relationship to aspects of sexual behavior or to a venereally transmitted virus, but no convincing evidence supports these hypotheses (Mandel and Schuman, 1980; Ross et al., 1983). Three dietary components appear to be related to this disease: fats, vitamin A, and the trace element cadmium. Several inter- and intracountry analyses show positive correlations between mortality from prostate cancer and per-capita intake of total fat (Armstrong and Doll, 1975; Blair and Fraumeni, 1978; Howell, 1974). These findings have been confirmed in several analytical studies showing an association of prostate cancer with the intake of high-fat foods (Rotkin, 1977; Schuman et al., 1982; Snowdon et al., 1984), as well as intake of fats per se (Graham et al., 1983; Heshmat et al., 1985; Kolonel et al., 1988). Although studies of certain other cancers suggest that vitamin A (particularly b-carotene) may be a protective factor, case-control studies of prostate cancer have tended to identify vitamin A as a risk factor, especially among men age 70 years and older (Graham et al., 1983; Heshmat et al., 1985; Kolonel et al., 1987). In the study by Kolonel et al. (1987), the effect was specific for carotenes, not for retinol. A few studies based on food frequency data suggest inverse associations with the intake of some carotene-containing vegetables (Ross et al., 1983; Schuman et al., 1982). Occupational exposure to cadmium has been associated with an increased risk for prostate cancer, but the  evidence  is not consistent (Friberg et al., 1986). The evidence regarding dietary cadmium  is also equivocal. Some geographic analyses of estimated per-capita intakes or levels in drinking water or soil showed positive associations (Bako et al., 1982; Berg and Burbank, 1972; Schrauzer et al., 1977), whereas others did not (Inskip et al., 1982; Shigematsu, 1984). In one case-control study, Kolonel and Winkelstein (1977) found no effect of cadmium from dietary sources. Cadmium levels in prostate tissue of men with prostate cancer were higher than in men with benign prostatic hypertrophy or normal prostate glands (Feustel and Wennrich, 1986; Feustel et al., 1982). Increased weight or obesity has been positively associated with prostate cancer (Lew and Garfinkel, 1979; Snowdon et al., 1984; Talamini et al., 1986), but not in all studies (Kolonel et al., 1988). In summary, prostate cancer risk appears to be higher in men consuming high-fat diets. A possible direct association with dietary vitamin A (notably carotenes) needs further confirmation. The effect of exposure to cadmium, either occupational or dietary, is not established. Animal Studies Animal models have been used extensively to study the effects of different dietary components on carcinogens. By using defined diets in such studies, it is possible to distinguish among the effects of different dietary constituents and to study mechanisms of action—both of which are difficult to accomplish in studies of humans. For this reason, and because there are no animal models for some cancer sites of importance in humans, this section is organized by dietary constituent rather than by cancer site. Fats Animal studies relating diet to carcinogenesis have been largely concerned with effects of dietary fats (Ip et al., 1986a; NRC, 1982). Tumors of the skin, mammary gland, colon, and pancreas develop more readily in animals fed high-fat diets than in those fed low-fat diets. Recent studies of treatment with carcinogens have been conducted in rats and, to a lesser extent, in mice and a few other species. Dietary fats appear to act primarily during the promotion stage of carcinogenesis, but the exact mechanism of action is not known and may depend on the tumor site (see Chapter 7). Polyunsaturated vegetable oils promote tumorigenesis more effectively than saturated fats, apparently because of a requirement for w-6 essential fatty acids, but a high level of dietary fats is also required for maximum effect (Ip, 1987). Fish oils, whose polyunsaturated fatty acids belong mainly to the w-3 family, do not promote and may inhibit tumorigenesis at high levels of intake. However, a relatively large amount of fish oil is required to counteract the promoting effect of polyunsaturated vegetable oils (Cave and Jurkowski, 1987; O'Connor et al., 1987). Other types of fatty acids, including monounsaturated, medium-chain saturated, and trans fatty acids, do not appear to have

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Page 601 specific promoting effects on carcinogenesis in animals (Cohen et al., 1986a,b; Ip et al., 1986b). The fact that high-fat diets promote carcinogenesis in animals more effectively than low-fat diets supports the positive correlation between dietary fats and cancer incidence and mortality shown by epidemiologic data for different countries (Armstrong and Doll, 1975; Carroll and Khor, 1975) and in several case-control studies and suggests a causal relationship (see Chapter 7 for a detailed discussion). The consumption of monounsaturated fats in the form of olive oil has been suggested as a reason for the relatively low cancer rates in Mediterranean countries where fat intake is nevertheless quite high (Cohen, 1987). The mechanism  of action of dietary fats has been studied most extensively as it relates to mammary cancer (Welsch, 1987). This is reviewed in Chapter 7 and is summarized only briefly here. Although hormonal mechanisms are clearly important for breast cancer development, early suggestions that dietary fats might work through a hormonal mechanism now seem unlikely. Several other putative mechanisms relate to the requirement for w-6 essential fatty acids. Evidence that the promoting effect can be prevented by prostaglandin synthesis inhibitors and that fish oils containing w-3 fatty acids do not promote carcinogenesis suggest that prostaglandins may be involved. However, not all prostaglandin synthesis inhibitors counteract the promoting effect (Carter et al., 1987), and the extreme susceptibility of the w-3 fatty acids in fish oil to oxidation may give rise to products other than prostaglandins that act as inhibitors of carcinogenesis (Carroll, in press). Polyunsaturated fatty acids are characteristic components of the phospholipids of cellular membranes and are supplied entirely by the diet. Thus, dietary fats have the potential to alter the fatty acid composition  of membrane phospholipids, thereby changing the fluidity of cell membranes and affecting other properties that could influence the potential for cellular growth, for example, immune responses, intercellular communication mediated by gap junctions, and responsiveness to growth factors such as protein kinase C (Welsch, 1987). As indicated in Chapter 7, cancer mortality is positively correlated with total dietary fats but not with polyunsaturated fats. Why, then, is a high level of total dietary fat necessary for cancer promotion in animals in addition to the requirement for polyunsaturated fats? The promotional effect may result from the increased intake of energy from high-fat, high-calorie diets. Recent studies indicate that caloric restriction may inhibit carcinogenesis in animals even when the diet is high in fats (Klurfeld et al., 1987; Pariza and Boutwell, 1987), but it has not been demonstrated conclusively that excessive energy intake per se promotes carcinogenesis (see Chapter 6). Different mechanisms may be involved in the promotion of carcinogenesis at specific sites. For example, dietary fats may enhance colon cancer by increasing the colonic concentration of secondary bile acids that act as tumor promoters (see Chapter 7). Protein Dietary animal protein tends to be associated with dietary fat. In humans, therefore, animal protein and fats are correlated similarly with cancer incidence and mortality. The greater emphasis on dietary fat is due in part to the consistency of the evidence that high-fat diets are associated with increased tumor incidence and tumor yield in animal models; however, effects of dietary protein have also been investigated in a substantial number of experiments in animals (NRC, 1982; see also Chapter 8). Diets with a low protein content have usually been found to suppress carcinogenesis, and a tumor-enhancing effect is generally observed at protein levels of 20 to 25%. Higher levels produce no further enhancement and may be inhibitory, possibly because of decreased food intake (NRC, 1982; Visek, 1986). Dietary protein appears to enhance tumorigenesis only when there is amino acid balance. Thus, the effect is not due to specific amino acids or to amino acid imbalance (NRC, 1982). It was at first suggested that the effects of dietary protein on hepatomas were due to a modification in aflatoxin B metabolism, but later studies suggest that effects occurring after initiation may be important (Appleton and Campbell, 1983; Campbell, 1983). Other studies show that the effect of dietary protein is so marked that the development of preneoplastic lesions is chiefly determined by protein intake, regardless of the level of aflatoxins consumed (Dunaif and Campbell, 1987). Low-protein diets are associated with inhibition of the growth of transplanted tumors, perhaps in conjunction with cellular immune function (see Chapter 8). Carbohydrates There have been relatively few studies of dietary carbohydrates in relation to carcinogenesis, but

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Page 602 there is some evidence that rats fed sucrose or dextrose develop mammary tumors more readily than those fed lactose, starches, or dextrin (NRC, 1982; see also Chapter 9). This is of interest in connection with epidemiologic data suggesting a weak correlation between dietary sugar and breast cancer incidence and mortality. Fiber The role of dietary fiber has been investigated in animals primarily in relation to colon cancer. The original hypothesis was that dietary fiber inhibits colon carcinogenesis by adsorption or dilution of potential carcinogens or promoters in the colon or by decreasing colonic transit time, thereby reducing the length of exposure. Experimental studies have given variable results, however. Some types of fiber inhibit carcinogenesis, whereas others actually increase the yield of colon cancers (NRC, 1982; see also Chapter 10). Fat-Soluble Vitamins Extensive studies in animals show that retinoids can prevent cancer at such sites as the skin, mammary gland, and bladder, although no effect or even increased susceptibility has been reported in several instances. There is also some evidence that carotenoids can decrease the incidence of tumors in laboratory animals (see Chapter 11). Retinoids induce cell differentiation and may act directly on nonneoplastic cells to suppress malignant transformation. They also counteract the effects of phorbol esters and inhibit the proliferative effects of growth factors. Investigators have sought novel synthetic retinoids because the naturally occurring compounds are quite toxic at doses that inhibit carcinogenesis. The antioxidant properties of vitamin E have stimulated interest in its possible anticarcinogenic properties, but experiments have yielded largely negative results. These studies, and research showing that vitamin K may have some effects on tumorigenesis in animals, are discussed in Chapter II. Water-Soluble Vitamins Most of the water-soluble vitamins have been investigated in relation to cancer in animals (see Chapter 12). Vitamin C may prevent carcinogenesis by preventing the formation of N-nitroso compounds or by enhancing cellular immunity, but experiments to test its effects in tumor models have produced variable results (Glatthaar et al., 1986). Esophageal cancer has been associated with riboflavin deficiency in humans, and experiments in animals have provided some supporting evidence (Rivlin, 1986). Rats fed diets deficient in lipotropes (choline, methionine, folate) are prone to develop liver tumors (Ghoshal et al., 1986; Newberne, 1986), perhaps because the deficient diet increases the initiating potency of carcinogens or serves as a promoter. Possible mechanisms include hypomethylation of DNA and alterations in membrane phospholipids, leading to structural and functional changes in membranes and increased peroxidation of membrane lipids (Shinozuka et al., 1986). Trace Elements Selenium inhibits virally and chemically induced tumors as well as transplanted tumors in animals and is effective during both initiation and proliferative phases of tumorigenesis (Ip, 1985, 1986; Milner, 1985, 1986). Various mechanisms for this inhibitory effect have been proposed. Selenium may prevent the activation of carcinogens such as dimethylbenzanthracene (DMBA) and may modify RNA transcription or translation (Milner, 1986). Its effect on the in vivo activation of aflatoxin B1 to form covalent DNA adducts is equivocal (Chen et al., 1982a,b). The main function of selenium is to induce and maintain the enzyme glutathione peroxidase, which prevents cellular damage by catabolizing organic peroxides, but this function does not seem to be responsible for its chemopreventive effects (Medina, 1986). Other possible mechanisms of action include inhibition of DNA  synthesis and enhancement of immune responses (Ip, 1985). Dietary zinc deficiency has not been associated with an increased incidence of esophageal carcinoma in humans (see Chapter 14). In animals, zinc deficiency increases the incidence of esophageal carcinoma induced by methylbenzylnitrosamine (MBN), which requires metabolic activation. Zinc acts as a noncompetitive inhibitor of cytochrome P450 activity, and zinc deficiency activates the cytochrome P450-dependent metabolism of MBN, which may explain how zinc deficiency enhances the carcinogenic potential of this compound (Barch and Iannaccone, 1986). On the other hand, zinc is required for growth of both normal and neoplastic tissues, and zinc deficiency reduces the incidence of tumors induced in animals by 3-methylcholanthrene and 4-nitroquinoline-N-oxide (Barch and Iannaccone, 1986). Zinc deficiency affects immunocompetence and influences many other aspects of metabolism, including nucleic acid and protein synthesis.

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Page 603 Testicular tumors have been induced by direct injection of zinc. Excessive dietary zinc can sometimes enhance carcinogenesis, perhaps because it is required for synthesis of DNA, but in other animal models, excess zinc inhibits tumor formation. Other studies reviewed in Chapter 14 also demonstrate that zinc deficiency can either enhance or inhibit tumor growth, indicating that different mechanisms are involved. The role of zinc in carcinogenesis is complex and poorly defined (Kasprzak and Waalkes, 1986). In rats fed an iodine-deficient diet, follicular adenomas of the thyroid develop by 12 months and follicular carcinomas by 18 months, probably because the iodine deficiency causes chronic hypersecretion of thyroid-stimulating hormone. Iodine deficiency, goitrogenic compounds, and thyroid toxins all act as potent tumor promoters in animals. These findings are not consistent with the weight of epidemiologic evidence, which does not show increased risk of thyroid cancer associated with goiter or living in iodine-deficient areas (see Chapter 14). Some elements, such as iron and molybdenum, have been shown to enhance or inhibit cancer in different experiments. Others, such as chromium, manganese, and cadmium, were found to be mutagenic in short-term assays. In general, the relevance of these trace element studies to cancer in humans is not clear (see also Chapter 14). Minerals Salt has been implicated as a promoter of gastric cancer (Joossens and Geboers, 1987). Some experiments in animals indicate that dietary salt facilitates both initiation and promotion of gastric cancer (Takahashi, 1986; Takahashi et al., 1983). It may act by irritating and possibly damaging the gastric mucosa. (See Chapter 15 for further discussion of salt.) Dietary calcium has been reported to increase the incidence of tumors in some animals (Kasprzak and Waalkes, 1986), whereas other studies focused on its possible protective effects in colon carcinogenesis (Bruce, 1987; Newmark et al., 1984). Calcium may bind bile acids and fatty acids, thereby preventing them  from acting as tumor promoters, but in experiments on azoxymethane-induced colon tumors, rats fed a high-calcium diet developed more tumors than did those fed a low-calcium diet (Bull et al., 1987). On the other hand, Appleton et al. (1987) reported that calcium supplementation reduces colonic crypt-cell production rates and prevents the increase in intestinal tumor yields produced by enterectomy in rats treated with azoxymethane. Pence and Buddingh (1987) also reported that supplemental calcium  or vitamin D3 inhibits the promotion by dietary fats of intestinal cancer induced in rats by 1,2-dimethylhydrazine. Furthermore, there is evidence that dietary calcium can reduce the yield of mammary tumors induced in rats by DMBA (Jacobson et al., 1987). Nonnutritive Dietary Components Animal studies of some of the constituents of coffee and tea, such as caffeine, phenolic compounds, and tannic acid, have yielded mixed results about the ability of these constituents to produce tumorigenesis (see Chapter 17). Nonnutritive sweeteners have been the subject of several long-term studies in animal cancer models. Two-generation studies have provided evidence of a positive association between dietary saccharin and bladder cancer in rats, and saccharin was also shown to have tumor-promoting and cocarcinogenic potential for bladder cancer induced in rats by other chemicals. Cyclamate does not appear to be carcinogenic in rats (NRC, 1985), but it may enhance the carcinogenic effect of other substances on the bladder. Aspartame has not been implicated as a bladder carcinogen, and there is conflicting evidence with regard to its effects on brain neoplasms in animals (see Chapter 17). There is no conclusive evidence that nitrates or nitrites are carcinogenic in animals, but nitrites may interact with other dietary components to produce N-nitroso  compounds (NRC, 1981). These compounds require metabolic activation to be mutagenic or carcinogenic, but can then induce a variety of tumors; however, there are large differences in the susceptibility of different species and different tissues (Lijinsky, 1986). The formation of N-nitroso compounds can be enhanced by a variety of ions present in food, especially thiocyanate and iodine, but can be prevented by other dietary components, including ascorbic acid and a-tocopherol. Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT)—food additives that are widely used as preservatives and antioxidants—have been studied extensively in animal cancer models. BHA can induce tumors of the forestomach, but can also inhibit the activity of a variety of carcinogens (see Chapter 17), perhaps by preferential enhancement of hepatic detoxifying mechanisms. Unlike other antioxidants, however, BHT administered after carcinogens may increase the number of tumors.

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Page 604 Other nonnutritive components of foods studied for their cancer potential in animals are polychlorinated  biphenyls, polybrominated  biphenyls, polycyclic aromatic hydrocarbons, diethylstilbestrol, and various food colors (see Chapter 17). In addition to studies involving feeding trials of animals, many of these compounds have been investigated in short-term tests for genotoxicity and mutagenesis (Chapter 17). Positive results are frequently obtained, but Ames et al. (1987) emphasize that naturally occurring components of the diet often have mutagenic properties. Because these components may be associated with protective substances, it is difficult to assess the relative risks of these various mutagenic compounds in the overall context of human cancer. Summary Although the contribution of diet to the total incidence of and mortality from  cancer in the United States cannot be determined with certainty, it seems reasonable that approximately one-third of all cancer mortality may be related to diet. Over the past 30 years, the incidence of cancer at some sites associated with diet (e.g., breast, colon, prostate) has increased modestly, whereas for other sites (most notably the stomach), it has decreased substantially. Cancers of the gastrointestinal tract have been positively associated in epidemiologic studies with a variety of dietary exposures, e.g., esophageal cancer with alcohol consumption (particularly combined with tobacco use), stomach cancer with a high intake of foods preserved with salt, colorectal cancer with dietary fats and alcoholic beverages (particularly beer), and liver cancer with aflatoxin-contaminated foods and possibly heavy alcohol consumption (but most strongly with hepatitis B virus infection). Inverse associations with some of these cancers have been noted for other dietary components, e.g., fresh fruits and vegetables (possibly reflecting vitamin C intake) with stomach cancer, and a high intake of vegetables (possibly reflecting intake of certain vitamins, components of fiber, or nonnutritive constituents) with colorectal cancer. Cancers of the lung and bladder are most clearly associated with exposure to cigarette tobacco and certain industrial chemicals. Foods of plant origin, especially fruits, and green and yellow vegetables, rich in b-carotene (and other carotenoids) appear to exert a protective effect against lung cancer, but this effect could be due to some other constituent of these foods. Cancers of the breast and prostate have been positively associated with dietary fats. Animal experiments support this positive association, but the epidemiologic evidence is not totally consistent. Alcohol consumption may also be a risk factor for breast cancer. Cancer of the endometrium is clearly associated with obesity, but no specific dietary risk factors for this cancer have been established. Many of these epidemiologic associations are supported by evidence from experiments in animals. For example, high-fat diets clearly promote mammary and colon carcinogenesis in animals, whereas retinoids and selenium can inhibit experimentally induced tumors at several sites. Nitrites have been shown to interact with other dietary components to produce carcinogenic N-nitroso compounds. However, data on the carcinogenicity of most components of the human diet are quite limited. Although one or more mechanisms have been proposed for the carcinogenic effects of specific dietary factors, the exact mechanisms of carcinogenesis in humans are not yet established for any diet-related cancer. Directions for Research · Methodology Although a considerable amount of research is being focused on the relationship of dietary constituents to cancer, few associations have been established with certainty. Progress in this field could be greatly facilitated by methodological improvements in several areas. For example, innovative methods for dietary assessment in population samples, including the identification of meaningful and practical biologic markers of exposure, might yield more reliable estimates of intake and less inconsistency among studies. Improvement is also needed in the quality and comprehensiveness of the food composition data bases used in this research, for example, those used to estimate the vitamin A and fiber content of foods. ·Intervention Trials To date, epidemiologic studies on diet and cancer in humans have been largely observational, i.e., intercountry comparisons, studies on migrants, or case-control and cohort studies. Although some findings are supported by animal studies, the results of such studies cannot be quantitatively extrapolated to humans. Furthermore, there are not always suitable animal models. Thus, to obtain definitive information on the role of diet and cancer in humans, it would be desirable to conduct intervention trials in which diets are modified in specific ways and the subjects

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Page 605 are monitored for sufficient time to determine the impact on the incidence of cancer in a number of different sites. Such trials should be planned carefully on the basis of epidemiologic and experimental evidence; efforts should be made to identify the best study populations and the modifications in dietary patterns that most warrant investigation. Although intervention trials are likely to be very expensive, the magnitude of the health problem and the lack of satisfactory treatments for many major types of cancer warrant such an investment of human and financial resources. · Genetic Determinants  The role of genetic factors, particularly as they modify individual responses to environmental (dietary) exposures, has not been studied much. Research in this area might clarify some of the poorly understood relationships between dietary components and cancer. · Quantitative Relationships The quantitative nature of the relationship between food constituents and cancer risk is as yet little understood. Such information will be necessary if the public is to be given more precise dietary recommendations than are currently possible. · Mechanisms of Action Mechanisms of action for most dietary factors that affect cancer risk in humans are not completely understood. Elucidation of these mechanisms would help to establish the causal nature of some diet-cancer associations, but this information is not essential to the formulation of policy. References Acheson, E.D., and R. Doll. 1964. Dietary factors in carcinoma of the stomach: a study of 100 cases and 200 controls. Gut 5:126-131. Adelcreutz, H., T. Fotsis, R. Heikkinea, J.T. Dwyer, M. Woods, B.R. Goldin, and S.L. Gorbach. 1982. Excretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian postmenopausal women and in women with breast cancer. Lancet 2:1295-1299. Alpert, M.E., M.S. Hutt, G.N. Wogan, and C.S. Davidson. 1971. Association between aflatoxin content of food and hepatoma frequency in Uganda. Cancer 28:253-260. Ames, B.N., R. Magaw, and L.S. Gold. 1987. Ranking possible carcinogenic hazards. Science 236:271-280. Annegers, J.F., H. Strom, D.G. Decker, M.B. Dockerty, and W.M. O'Fallon. 1979. Ovarian cancer: incidence and case-control study. Cancer 43:723-729. Anthony, P.P. 1977. Cancer of the liver: pathogenesis and recent aetiological factors. Trans. R. Soc. Trop. Med. Hyg. 71:466-470. Appleton, B.S., and T.C. Campbell. 1983. Dietary protein intervention during the postdosing phase of aflatoxin B1-induced hepatic preneoplastic lesion development. J. Natl. Cancer Inst. 70:547-549. Appleton, G.V., P.W. Davies, J.B Bristol, and R.C. Williamson. 1987. Inhibition of intestinal carcinogenesis by dietary supplementation with calcium. Br. J. Surg. 74:523-525. Armijo, R., and A.H. Coulson. 1975. Epidemiology of stomach cancer in Chile—the role of nitrogen fertilizers. Int. J. Epidemiol. 4:301-309. Armstrong, B. 1980. The epidemiology of cancer in the People's Republic of China. Int. J. Epidemiol. 9:305-315. Armstrong, B., and R. Doll. 1975. Environmental factors and cancer incidence and mortality in different countries, with specific reference to dietary practices. Int. J. Cancer 15:617-631. Bako, G., E.S. Smith, J. Hanson, and R. Dewar. 1982. The geographical distribution of high cadmium concentrations in the environment and prostate cancer in Alberta. Can. J. Public Health 73:92-94. Barch, D.H., and P.M. Iannaccone. 1986. Role of zinc deficiency in carcinogenesis. Pp. 517-527 in LA. Poirier, P.M. Newberne, and M.W. Pariza, eds. Essential Nutrients in Carcinogenesis. Advances in Experimental Biology and Medicine, Vol. 206. Plenum Press, New York. Beasley, R.P., L.Y. Hwang, C.C. Lin, and C.S. Chien. 1981. Hepatocellular carcinoma and hepatitis B virus: a prospective study of 22,707 men in Taiwan. Lancet 2:1129-1133. Begg, C.B., A.M. Walker, B. Wessen, and M. Zelen. 1983. Alcohol consumption and breast cancer. Lancet 1:293-294. Berg, J.W. 1975. Can nutrition explain the pattern of international epidemiology of hormone-dependent cancers? Cancer Res. 35:3345-3350. Berg, J.W., and F. Burbank. 1972. Correlations between carcinogenic trace metals in water supplies and cancer mortality. Ann. N.Y. Acad. Sci. 199:249-264. Bingham, S., D.R. Williams, T.J. Cole, and W.P. James. 1979. Dietary fibre and regional large-bowel cancer mortality in Britain. Br. J. Cancer 40:456-463. Bingham, S.A., D.R. Williams, and J.H. Cummings. 1985. Dietary fibre consumption in Britain: new estimates and their relation to large bowel cancer mortality. Br. J. Cancer 52:399-402. Bjelke, E. 1975. Dietary vitamin A and human lung cancer. Int. J. Cancer 15:561-565. Bjelke, E. 1978. Dietary factors and the epidemiology of cancer of the stomach and large bowel. Aktuel. Ernaehrungsmed. Klin. Prax. Suppl. 2:10-17. Blair, A., and J.F. Fraumeni, Jr. 1978. Geographic patterns of prostate cancer in the United States. J. Natl. Cancer Inst. 61:1379-1384. Blot, W.J., J.F. Fraumeni, Jr., and B.J. Stone. 1978. Geographic correlates of pancreas cancer in the United States. Cancer 42:373-380. Breslow, N.E., and J.E. Engstrom. 1974. Geographic correlations between cancer mortality rates and alcohol-tobacco consumption in the United States. J. Natl. Cancer Inst. 53: 631-639. Brownson, R.C., .C. Chang, and .R. Davis. 1987. Occupation, smoking, and alcohol in the epidemiology of bladder cancer. Am. J. Public Health 77:1298-1300. Bruce, W.R. 1987. Recent hypotheses for the origin of colon cancer. Cancer Res. 47:4237-4242. Bulatao-Jayme, J., E.M. Almero, M.C.A. Castro, M.T. Jardeleza, and L.A. Salamat. 1982. A case-control dietary study of primary liver cancer risk from aflatoxin exposure. Int. J. Epidemiol. 11:112-119. Bull, A., R.P. Bird, W.R. Bruce, N. Nigro, and A. Medine.

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Page 606 1987. Effect of calcium on azoxymethane induced intestinal tumors in rats. Gastroenterology 92:1332. Burch, G.E., and A. Ansari. 1968. Chronic alcoholism and carcinoma of the pancreas: a correlative hypothesis. Arch. Intern. Med. 122:273-275. Byers, T., and D.P. Funch. 1982. Alcohol and breast cancer. Lancet 1:799-800. Byers, T., J. Marshall, S. Graham, C. Mettlin, and M. Swanson. 1983. A case-control study of dietary and nondietary factors in ovarian cancer. J. Natl. Cancer Inst. 71: 681-686. Byers, T.E., S. Graham, B.P. Haughey, J.R. Marshall, and M.K. Swanson. 1987. Diet and lung cancer risk: findings from the Western New York Diet Study. Am. J. Epidemiol. 125:351-363. Campbell, T.C. 1983. Mycotoxins. Pp. 187-197 in E.L. Wynder, G.A. Leveille, J.H. Weisburger, and G.E. Livingston, eds. Environmental Aspects of Cancer: The Role of Macro and Micro Components of Foods. Food and Nutrition Press, Inc., Westport, Conn. Carroll, K.K. In press. Experimental and epidemiological evidence on marine lipids and carcinogenesis. Health Effects of Omega-3 Fatty Acids. Proceedings of MIT Sea Grant College Program Lecture Seminar Series. Marcel Dekker, Inc. Carroll, K.K., and H.T. Khor. 1975. Dietary fat in relation to tumorigenesis. Prog. Biochem. Pharmacol. 10:308-353. Carter, C.A., M.M. Ip, and C. Ip. 1987. Response of mammary carcinogenesis to dietary linoleate and fat levels and its modulation by prostaglandin synthesis inhibitors. Pp. 253-260 in W.E.M. Lands, ed. Proceedings of the AOCS Short Course on Polyunsaturated Fatty Acids and Eicosanoids. American Oil Chemists' Society, Champaign, Ill. Casagrande, J.T., E.W. Louie, M.C. Pike, S. Roy, R.K. Ross, and B.E. Henderson. 1979. ''Incessant ovulation" and ovarian cancer. Lancet 2:170-173. Cave, W.T., Jr., and J.J. Jurkowski. 1987. Comparative effects of omega-3 and omega-6 dietary lipids on rat mammary tumor development. Pp. 261-266 in W.E.M. Lands, ed. Proceedings of the AOCS Short Course on Polyunsaturated Fatty Acids and Eicosanoids. American Oil Chemists' Society, Champaign, Ill. Chen, J., M.P. Goetchius, G.F. Combs, Jr., and T.C. Campbell. 1982a. Effects of dietary selenium and vitamin E on covalent binding of aflatoxin to chick liver cell macromolecules. J. Nutr. 112:350-355. Chen, J., M.P. Goetchius, T.C. Campbell, and G.F. Combs, Jr. 1982b. Effects of dietary selenium and vitamin E on hepatic mixed-function oxidase activities and in vivo covalent binding of aflatoxin B1 in rats. J. Nutr. 112:324-331. Chien, M.C., M.J. Tong, K.J. Lo, J.K. Lee, D.R. Milich, G.N. Vyas, and B.L. Murphy. 1981. Hepatitis B viral markers in patients with primary hepatocellular carcinoma in Taiwan. J. Natl. Cancer Inst. 66:475-479. Chilvers, C., P. Fraser, and V. Beral. 1979. Alcohol and oesophageal cancer: an assessment of the evidence from routinely collected data. J. Epidemiol. Community Health 33:127-133. Cohen, L.A. 1987. Differing effects of high-fat diets rich in polyunsaturated, monounsaturated, or medium chain saturated fatty acids on rat mammary tumor promotion. Pp. 241-247 in W.E.M. Lands, ed. Proceedings of the AOCS Short Course on Polyunsaturated Fatty Acids and Eicosanoids. American Oil Chemists' Society, Champaign, Ill. Cohen, L.A., D.O. Thompson, Y. Maeura, K. Choi, M.E. Blank, and D.P. Rose. 1986a. Dietary fat and mammary cancer. I. Promoting effects of different dietary fats on N-nitrosomethylurea-induced rat mammary tumorigenesis. J. Natl. Cancer Inst. 77:33-42. Cohen, LA., D.O. Thompson, K. Choi, R.A. Karmali, and D.P. Rose. 1986b. Dietary fat and mammary cancer. II. Modulation of serum and tumor lipid composition and tumor prostaglandins by different dietary fats: association with tumor incidence patterns. J. Natl. Cancer Inst. 77:43-51. Cole, P. 1971. Coffee-drinking and cancer of the lower urinary tract. Lancet 1:1335-1337. Cook-Mozaffari, P. 1979. The epidemiology of cancer of the oesophagus. Nutr. Cancer 1:51-60. Correa, P., C. Cuello, E. Duque, L.C. Burbano, F.T. Garcia, O. Bolanos, C. Brown, and W. Haenszel. 1976. Gastric cancer in Colombia. III. Natural history of precursor lesions. J. Natl. Cancer. Inst. 57:1027-1035. Correa, P., E. Fontham, L.W. Pickle, V. Chen, Y.P. Lin, and W. Haenszel. 1985. Dietary determinants of gastric cancer in south Louisiana inhabitants. J. Natl. Cancer. Inst. 75: 645654. Cramer, D.W., G.B. Hutchison, W.R. Welch, R.E. Scully, and R.C. Knapp. 1982. Factors affecting the association of oral contraceptives and ovarian cancer. N. Engl. J. Med. 307:1047-1051. Cramer, D.W., W.R. Welch, G.B. Hutchinson, W. Willett, and R.E. Scully. 1984. Dietary animal fat in relation to ovarian cancer risk. Obstet. Gynecol. 63:833-838. Cubilla, A.L., and P.J. Fitzgerald. 1978. Pancreas cancer (non-endocrine): a review—part II. Clin. Bull. 8:143-155. Dales, L.G., G.D. Friedman, H.K. Ury, S. Grossman, and S.R. Williams. 1979. A case-control study of relationships of diet and other traits to colorectal cancer in American blacks. Am. J. Epidemiol. 109:132-144. Dean, G., R. MacLennan, H. McLoughlin, and E. Shelley. 1979. Causes of death of blue-collar workers at a Dublin brewery, 1954-1973. Br. J. Cancer 40:581-589. de Jong, U.W., N. Breslow, J.G. Hong, M. Sridharan, and K. Shanmugaratnam. 1974. Aetiological factors in oesophageal cancer in Singapore Chinese. Int. J. Cancer 13:291-303. Devesa, S.S., D.T. Silverman, J.L. Young, Jr., E.S. Pollack, C.C. Brown, J.W. Horm, C.L. Percy, M.H. Myers, F.W. McKay, and J.F. Fraumeni, Jr. 1987. Cancer incidence and mortality trends among whites in the United States, 1947-1984. J. Natl. Cancer Inst. 79:701-770. de Waard, F., J.P. Cornelis, K. Aoki, and M. Yoshida. 1977. Breast cancer incidence according to weight and height in two cities of the Netherlands and in Aichi prefecture, Japan. Cancer 40:1269-1275. DHEW  (Department of Health, Education, and Welfare). 1979. Smoking and Health: A  Report of the Surgeon General. DHEW  Publ. No. (PHS) 79-50066. Office on Smoking and Health, Office of the Assistant Secretary for Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Rockville, Md. 1164 pp. Doll, R., and R. Peto. 1981. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J. Natl. Cancer Inst. 66:1191-1308. Dörken, H. 1964. Einige Daten bei 280 Patienten mit Pankreaskrebs. Häufigkeit, Vor- und Begleitkrankheiten, exogene Faktoren. Gastroenterologia 102:46-77.

OCR for page 593
Page 607 Drasar, B.S.. and D. Irving. 1973. Environmental factors and cancer of the colon and breast. Br. J. Cancer 27:167-172. Dunaif, G.E., and T.C. Campbell. 1987. Relative contribution of dietary protein level and aflatoxin B. dose in generation of presumptive preneoplastic foci in rat liver. J. Natl. Cancer Inst. 78:365-369. Dungal, N. 1966. Stomach cancer in Iceland. Can. Cancer Conf. 6:441-450. Elwood, J.M., P. Cole, K.J. Rothman, and S.D. Kaplan. 1977. Epidemiology of endometrial cancer. J. Natl. Cancer Inst. 59:1055-1060. Enstrom, J.E. 1975. Colorectal cancer and consumption of beef and fat. Br. J. Cancer 32:432-439. Feustel, A., and R. Wennrich. 1986. Zinc and cadmium plasma and erythrocyte levels in prostatic carcinoma, BPH, urological malignancies, and inflammations. Prostate 8:75-79. Feustel, A., R. Wennrich, D. Steiniger, and P. Klauss. 1982. Zinc and cadmium concentration in prostatic carcinoma of different histological grading in comparison to normal prostate tissue and adenofibromyomatosis (BPH). Urol. Res. 10: 301-303. Foy, H., and V. Mbaya. 1977. Riboflavin. Prog. Food Nutr. Sci. 2:357-394. Fraumeni, J.F., Jr. 1975. Respiratory carcinogenesis: an epidemiologic appraisal. J. Natl. Cancer Inst. 55:1039-1046. Fraumeni, J.F., Jr., J. Scotto, and L.J. Dunham. 1971. Coffee-drinking and bladder cancer. Lancet 2:1204. Friberg, L., C.G. Elinder, T. Kjellström, and G.F. Nordberg. 1986. Cadmium and Health: A Toxicological and Epidemiological Appraisal, Vol. II. Effects and Response. CRC Press, Boca Raton, Fla. 307 pp. Friedman, G.D., W.S. Blaner, D.S. Goodman, J.H. Vogelman, J.L. Brind, R. Hoover, B.H. Fireman, and N. Orentreich. 1986. Serum retinol and retinol-binding protein levels do not predict subsequent lung cancer. Am. J. Epidemiol. 123:781-789. Garland, C., R.B. Shekelle, E. Barrett-Connor, M.H. Criqui, A.H. Rossof, and O. Paul. 1985. Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men. Lancet 1:307-308. Gaskill, S.P., W.L. McGuire, C.K. Osborne, and M.P. Stern. 1979. Breast cancer mortality and diet in the United States. Cancer Res. 39:3628-3637. Ghoshal, A.K., D.S.R. Sarma, and E. Farber. 1986. Ethionine in the analysis of the possible separate roles of methionine and choline deficiencies in carcinogenesis. Pp. 283-292 in L.A. Poirier, P.M. Newberne, and M.W. Pariza, eds. Essential Nutrients in Carcinogenesis. Advances in Experimental Biology and Medicine, Vol. 206. Plenum Press, New York. Glatthaar, B.E., D.H. Hornig, and U. Moser. 1986. The role of ascorbic acid in carcinogenesis. Pp. 357-377 in L.A. Poirier, P.M. Newberne, and M.W. Pariza, eds. Essential Nutrients in Carcinogenesis. Advances in Experimental Biology and Medicine, Vol. 206. Plenum Press, New York. Gold, E.B., L. Gordis, M.D. Diener, R. Seltser, J.K. Boitnott, T.E. Bynum, and D.F. Hutcheon. 1985. Diet and other risk factors for cancer of the pancreas. Cancer 55:460-467. Graham, S., W. Schotz, and P. Martino. 1972. Alimentary factors in the epidemiology of gastric cancer. Cancer 30: 927-938. Graham, S., H. Dayal, M. Swanson, A. Mittelman, and G. Wilkinson. 1978. Diet in the epidemiology of cancer of the colon and rectum. J. Natl. Cancer Inst. 61:709-714. Graham, S., J. Marshall, C. Mettlin, T. Rzepka, T. Nemoto, and T. Byers. 1982. Diet in the epidemiology of breast cancer. Am. J. Epidemiol. 116:68-75. Graham, S., B. Haughey, J. Marshall, R. Priore, T. Byers, T. Rzepka, C. Mettlin, and J.E. Pontes. 1983. Diet in the epidemiology of carcinoma of the prostate gland. J. Natl. Cancer Inst. 70:687-692. Graham, S., J. Marshall, B. Haughey, A. Mittelman, M. Swanson, M. Zielezny, T. Byers, G. Wilkinson, and D. West. 1988. Dietary epidemiology of cancer of the colon in western New York. Am. J. Epidemiol. 128:490-503. Gregor, O., R. Toman, and F. Prusova. 1969. Gastrointestinal cancer and nutrition. Gut 10:1031-1034. Gregor, A., P.N. Lee, F.J.C. Roe; M.J. Wilson, and A. Melton. 1980. Comparison of dietary histories in lung cancer cases and controls with special reference to vitamin A. Nutr. Cancer 2:93-97. Haenszel, W., and P. Correa. 1975. Developments in the epidemiology of stomach cancer over the past decade. Cancer Res. 35:3452-3459. Haenszel, W., and E.A. Dawson. 1965. A note on mortality from cancer of the colon and rectum in the United States. Cancer 18:265-272. Haenszel, W., M. Kurihara, M. Segi, and R.K. Lee. 1972. Stomach cancer among Japanese in Hawaii. J. Natl. Cancer Inst. 49:969-988. Haenszel, W., J.W. Berg, M. Segi, M. Kurihara, and F.B. Locke. 1973. Large-bowel cancer in Hawaiian Japanese. J. Natl. Cancer Inst. 51:1765-1779. Haenszel, W., M. Kurihara, F.B. Locke, K. Shimuzu, and M. Segi. 1976. Stomach cancer in Japan. J. Natl. Cancer Inst. 56:265-274. Haenszel, W., F.B. Locke, and M. Segi. 1980. A case-control study of large bowel cancer in Japan. J. Natl. Cancer Inst. 64:17-22. Hakulinen, T., L. Lehtimaki, M. Lehtonen, and L. Teppo. 1974. Cancer morbidity among two male cohorts with increased alcohol consumption in Finland. J. Natl. Cancer Inst. 52:1711-1714. Hartge, P., R. Hoover, D.W. West, and J.L. Lyon. 1983. Coffee drinking and risk of bladder cancer. J. Natl. Cancer Inst. 70:1021-1026. Heilbrun, L.K., J.H. Hankin, A.M.Y. Nomura, and G.N. Stemmermann. 1986. Colon cancer and dietary fat, phosphorus, and calcium in Hawaiian-Japanese men. Am. J. Clin. Nutr. 43:306-309. Henderson, B.E., R.K. Ross, M.C. Pike, and  J.T. Casagrande. 1982. Endogenous hormones as a major factor in human cancer. Cancer Res. 42:3232-3239. Henderson, B.E., J.T. Casagrande, M.C. Pike, T. Mack, and I. Rosario. 1983. The epidemiology of endometrial cancer in young women. Br. J. Cancer 47:749-756. Heshmat, M.Y., L. Kaul, J. Kovi, M.A. Jackson, A.G. Jackson, G.W. Jones, M. Edson, J.P. Enterline, R.G. Worrell, and S.L. Perry. 1985. Nutrition and prostate cancer: a case-control study. Prostate 6:7-17. Heuch, I., G. Kvale, B.K. Jacobsen, and E. Bjelke. 1983. Use of alcohol, tobacco and coffee, and risk of pancreatic cancer. Br. J. Cancer 48:637-643. Hiatt, R.A., and R.D. Bawol. 1984. Alcoholic beverage consumption and breast cancer incidence. Am. J. Epidemiol. 120:676-83. Higginson, J. 1966. Etiological factors in gastrointestinal cancer in man. J. Natl. Cancer Inst. 37:527-545.

OCR for page 593
Page 608 Hildreth, N.G., J.L. Kelsey, V.A. LiVolsi, D.B. Fischer, T.R. Holford, E.D. Mostow, P.E. Schwartz, and C. White. 1981. An epidemiologic study of epithelial carcinoma of the ovary. Am. J. Epidemiol. 114:398-405. Hill, M.J., G. Hawksworth, and G. Tattersall. 1973. Bacteria, nitrosamines, and cancer of the stomach. Br. J. Cancer 28: 562-567. Hinds, M.W., L.N. Kolonel, J. Lee, and T. Hirohata. 1980. Associations between cancer incidence and alcohol/cigarette consumption among five ethnic groups in Hawaii. Br. J. Cancer 41:929-940. Hinds, M.W., L.N. Kolonel, J.H. Hankin, and . Lee. 1983. Dietary cholesterol and lung cancer risk in a multiethnic population in Hawaii. Int. J. Cancer 32:727-732. Hinds, M.W., L.N. Kolonel, J.H. Hankin, and J. Lee. 1984. Dietary vitamin A, carotene, vitamin C and risk of lung cancer in Hawaii. Am. J. Epidemiol. 119:227-237. Hirayama, T. 1967. The epidemiology of cancer of the stomach in Japan with special reference to the role of diet. Pp. 37-49 in R.J.C. Harris, ed. Proceedings of the 9th International Cancer Congress. UICC Monograph Series, Vol. 10. Springer-Verlag, Berlin. Hirayama, T. 1977. Changing patterns of cancer in Japan with special reference to the decrease in stomach cancer mortality. Pp. 55-75 in H.H. Hiatt, J.D. Watson, and J.A. Winsten, eds. Origins of Human Cancer. Book A, Incidence of Cancer in Humans. Cold Spring Harbor Laboratory, New York. Hirayama, T. 1979. Diet and cancer. Nutr. Cancer 1:67-81. Hirohata, T., T. Shigematsu, A.M. Nomura, Y. Nomura, A. Horie, and I. Hirohata. 1985. Occurrence of breast cancer in relation to diet and reproductive history: a case-control study in Fukuoka, Japan. Natl. Cancer Inst. Monogr. 69:187-190. Hirohata, T., A.M. Nomura, J.H. Hankin, L.N. Kolonel, and J. Lee. 1987. An epidemiologic study on the association between diet and breast cancer. J. Natl. Cancer Inst. 78:595-600. Hislop, T.G., A.J. Coldman, J.M. Elwood, G. Brauer, and L. Kan. 1986. Childhood and recent eating patterns and risk of breast cancer. Cancer Detect. Prev. 9:47-58. Hoey, J., C. Montvernay, and R. Lambert. 1981. Wine and tobacco: risk factors for gastric cancer in France. Am. J. Epidemiol. 113:668-674. Hormozdiari, H., N.E. Day, B. Aramesh, and E. Mahboubi. 1975. Dietary factors and esophageal cancer in the Caspian Littoral of Iran. Cancer Res. 35:3493-3498. Howe, G.R. 1985. The use of polytomous dual response data to increase power in case-control studies: an application to the association between dietary fat and breast cancer. J. Chronic Dis. 38:663-670. Howe, G.R., J.D. Burch, A.B. Miller, G.M. Cook, J. Esteve, B. Morrison, P. Gordon, L.W. Chambers, G. Fodor, and G.M. Winsor. 1980. Tobacco use, occupation, coffee, various nutrients, and bladder cancer. J. Natl. Cancer Inst. 64:701-713. Howe, G.R., A.B. Miller, and M. Jain. 1986. Re: "Total energy intake: implications for epidemiologic analyses." Am. J. Epidemiol. 124:157-159. Howe, G.R., J.D. Burch, and H.A. Risch. In press. Artificial sweeteners, caloric intake and cancer: the epidemiologic evidence. Prev. Med. Howell, M.A. 1974. Factor analysis of international cancer mortality data and per capita food consumption. Br. J. Cancer 29:328-336. Howell, M.A. 1975. Diet as an etiological factor in the development of cancers of the colon and rectum. J. Chronic Dis. 28:67-80. Hsieh, C.C., B. MacMahon, S. Yen, D. Trichopoulos, K. Warren, and G. Nardi. 1986. Coffee and pancreatic cancer (chapter 2). N. Engl. J. Med. 315:587-589. Imai, T., T. Kubo, and H. Watanabe. 1971. Chronic gastritis in Japanese with reference to high incidence of gastric carcinoma. J. Natl. Cancer Inst. 47:179-195. Inaba, Y., N. Maruchi, M. Matsuda, N. Yoshihara, and S.I. Yamamoto. 1984. A case-control study on liver cancer with special emphasis on the possible aetiological role of schistosomiasis. Int. J. Epidemiol. 13:408-412. Inskip, H., V. Beral, and M. McDowall. 1982. Mortality of Shipham residents: 40-year follow-up. Lancet 1:896-899. International Agency for Research on Cancer Intestinal Microecology Group. 1977. Dietary fibre, transit-time, faecal bacteria, steroids, and colon cancer in two Scandinavian populations. Lancet 2:207-211. Ip, C. 1985. Selenium inhibition of chemical carcinogenesis. Fed. Proc. 44:2573-2578. Ip, C. 1986. The chemopreventive role of selenium in carcinogenesis. Pp. 431-447 in L.A. Poirier, P.M. Newberne, and M.W. Pariza, eds. Essential Nutrients in Carcinogenesis. Advances in Experimental Biology and Medicine, Vol. 206. Plenum Press, New York. Ip, C. 1987. Fat and essential fatty acids in mammary carcinogenesis. Am. J. Clin. Nutr. 45 suppl. 1:218-224. Ip, C., D.F. Birt, A.E. Rogers, and C. Mettlin, eds. 1986a. Progress in Clinical and Biological Research, Vol. 222. Dietary Fat and Cancer. Alan R. Liss, New York. 885 pp. Ip, C., M.M. Ip, and P. Sylvester. 1986b. Relevance of trans fatty acids and fish oil in animal tumorigenesis studies. Pp. 283-294 in C. Ip, D.F. Birt, A.E. Rogers, and C. Mettlin, eds. Progress in Clinical and Biological Research, Vol. 222. Dietary Fat and Cancer. Alan R. Liss, New York. Ishii, K., K. Nakamura, H. Ozaki, N. Yamada, and T. Takeuchi. 1968. Epidemiological problems of pancreas cancer. Jpn. J. Clin. Med. 26:1839-1842. Jacobsen, B.K., E. Bjelke, G. Kvale, and I. Heuch. 1986. Coffee drinking, mortality and cancer incidence: results from a Norwegian prospective study. J. Natl. Cancer Inst. 76:823-831. Jacobson, E.A., R. Russell, H.L Newmark, M.A. Amer, and K.K. Carroll. 1987. Fat, calcium and tumor development in dimethylbenz[a]anthracene  (DMBA)-treated  rats. Proc. Can. Fed. Biol. Sci. 30:112. Jain, M., G.M. Cook, F.G. Davis, M.G. Grace, G.R. Howe, and A.B. Miller. 1980. A case-control study of diet and colo-rectal cancer. Int. J. Cancer. 26:757-768. Jensen, H. 1986. Relationship of premorbid state of nutrition to endometrial carcinoma. Acta Obstet. Gynecol. Scand. 65:301-306. Jensen, O.M. 1979. Cancer morbidity and causes of death among Danish brewery workers. Int. J. Cancer 23:454-463. Jensen, O.M., R. MacLennan, and J. Wahrendorf. 1982. Diet, bowel function, fecal characteristics, and large bowel cancer in Denmark and Finland. Nutr. Cancer 4:5-19. Jensen, O.M., J. Wahrendorf, J.B. Knudsen, and B.L. Sorenson. 1986. The Copenhagen case-control study of bladder cancer. II. The effect of coffee and other beverages. Int. J. Cancer 37:651-657. Joint Iran-International Agency for Research on Cancer Study Group. 1977. Esophageal cancer studies in the Caspian

OCR for page 593
Page 609 Littoral of Iran: results of population studies—a prodrome. J. Natl. Cancer Inst. 59:1127-1138. Joossens, J.V., and J. Geboers. 1987. Dietary salt and risks to health. Am. J. Clin. Nutr. 45:1277-1288. Kabat, G.C., C.P. Howson, and E.L. Wynder. 1986. Beer consumption and rectal cancer. Int. J. Epidemiol. 15:494-501. Kark, J.D., A.H. Smith, B.R. Switzer, and C.G. Hames. 1981. Serum vitamin A (retinol) and cancer incidence in Evans County, Georgia. J. Natl. Cancer Inst. 66:7-16. Kasprzak, K.S., and M.P. Waalkes. 1986. The role of calcium, magnesium, and zinc in carcinogenesis. Pp. 497-515 in L.A. Poirier, P.M. Newberne, and M.W. Pariza, eds. Essential Nutrients in Carcinogenesis. Advances in Experimental Biology and Medicine, Vol. 206. Plenum Press, New York. Keller, A.Z. 1980. The epidemiology of esophageal cancer in the West. Prev. Med. 9:607-612. Kinlen, L.J. 1982. Meat and fat consumption and cancer mortality: a study of strict religious orders in Britain. Lancet 1:946-949. Klurfeld, D.M., M.M. Weber, and D. Kritchevsky. 1987. Inhibition of chemically induced mammary and colon tumor promotion by caloric restriction in rats fed increased dietary fat. Cancer Res. 47:2759-2762. Knox, E.G. 1977. Foods and diseases. Br. J. Prev. Soc. Med. 31:71-80. Kolonel, L.N. 1980. Cancer patterns of four ethnic groups in Hawaii. J. Natl. Cancer Inst. 65:1127-1139. Kolonel, L.N., and W. Winkelstein, Jr. 1977. Cadmium and prostatic carcinoma. Lancet 2:566-567. Kolonel, L.N., M.W. Hinds, and J.H. Hankin. 1980. Cancer patterns among migrant and native-born Japanese in Hawaii in relation to smoking, drinking, and dietary habits. Pp. 327-340 in H.V. Gelboin, M. MacMahon, T. Matsushima, T. Sugimura, S. Takayama, and H. Takebe, eds. Genetic and Environmental Factors in Experimental and Human Cancer. Japan Scientific Societies Press, Tokyo. Kolonel, L.N., A.M. Nomura, T. Hirohata, J.H. Hankin, and M.W. Hinds. 1981. Association of diet and place of birth with stomach cancer incidence in Hawaii Japanese and Caucasians. Am. J. Clin. Nutr. 34:2478-2485. Kolonel, L.N., A.M. Nomura, J. Lee, and T. Hirohata. 1986. Anthropometric indicators of breast cancer risk in postmenopausal women in Hawaii. Nutr. Cancer 8:247-256. Kolonel, L.N., J.H. Hankin, and C.N. Yoshizawa. 1987. Vitamin A and prostate cancer in elderly men: enhancement of risk. Cancer Res. 47:2982-2985. Kolonel, LN., C.N. Yoshizawa, and J.H. Hankin. 1988. Diet and prostatic cancer: a case-control study in Hawaii. Am. J. Epidemiol. 127:999-1012. Kune, S., G.A. Kune, and L.F. Watson. 1987. Case-control study of dietary etiological factors: the Melbourne Colorectal Cancer Study. Nutr. Cancer 9:21-42. Kvale, G., E. Bjelke, and J.J. Gart. 1983. Dietary habits and lung cancer risk. Int. J. Cancer 31:397-405. La Vecchia, C., S. Franceschi, A. Decarli, A. Gentile, P. Liati, M. Regello, and G. Tognoni. 1984. Coffee drinking and risk of epithelial ovarian cancer. Int. J. Cancer 33:559-562. La Vecchia, C., A. Decarli, M. Fasoli, and A. Gentile. 1986. Nutrition and diet in the etiology of endometrial cancer. Cancer 57:1248-1253. Lê, M.G., L.H. Moulton, C. Hill, and A. Kramar. 1986. Consumption of dairy produce and alcohol in a case-control study of breast cancer. J. Natl. Cancer Inst. 77:633-636. Lew, E.A., and L. Garfinkel. 1979. Variations in mortality by weight among 750,000 men and women. J. Chronic Dis. 32: 563-576. Lijinsky, W. 1986. The significance of N-nitroso compounds as environmental carcinogens. J. Environ. Sci. Health C4:1-45. Liu, K., J. Stamler, D. Moss, D. Garside, V. Persky, and I. Soltero. 1979. Dietary cholesterol, fat, and fibre, and colon-cancer mortality. An analysis of international data. Lancet 2:782-785. Lubin, J.H., P.E. Burns, W.J. Blot, R.G. Ziegler, A.W. Lees, and J.F. Fraumeni, Jr. 1981. Dietary factors and breast cancer risk. Int. J. Cancer 28:685-689. Lubin, F., A.M. Ruder, Y. Wax, and B. Modan. 1985. Overweight and changes in weight throughout adult life in breast cancer etiology. A case-control study. Am. J. Epidemiol. 122:579-588. Lubin, F., Y. Wax, and B. Modan. 1986. Role of fat, animal protein, and dietary fiber in breast cancer etiology: a case-control study. J. Natl. Cancer Inst. 77:605-612. Lyon, J.L., and A.W. Sorenson. 1978. Colon cancer in a low-risk population. Am. J. Clin. Nutr. 31 suppl. 10: S227-S230. Lyon, J.L., M.R. Klauber, J.W. Gardner, and C.R. Smart. 1976. Cancer incidence in Mormons and non-Mormons in Utah, 1966-1970. N. Engl. J. Med. 294:129-133. Lyon, J.L., J.W. Gardner, and D.W. West. 1980. Cancer risk and lifestyle: cancer among Mormons (1967-1975). Pp. 273-290 in H.V. Gelboin, B. MacMahon, T. Matsushima, T. Sugimura, S. Takayama, and H. Takebe, eds. Genetic and Environmental Factors in Experimental and Human Cancer. Japan Scientific Societies Press, Tokyo. Lyon, J.L., A.W. Mahoney, D.W. West, J.W. Gardner, K.R. Smith, A.W. Sorenson, and W. Stanish. 1987. Energy intake: its relationship to colon cancer risk. J. Natl. Cancer Inst. 78:853-861. Mack, T.M., M.C. Yu, R. Hanisch, and B.E. Henderson. 1986. Pancreas cancer and smoking, beverage consumption, and past medical history. J. Natl. Cancer Inst. 76:49-60. MacLennan, R., J. Da Costa, N.E. Day, C.H. Law, Y.K. Ng, and K. Shanmugaratnam. 1977. Risk factors for lung cancer in Singapore Chinese, a population with high female incidence rates. Int. J. Cancer 20:854-860. MacLennan, R., O.M. Jensen, J. Mosbech, and H. Vuori. 1978. Diet, transit time, stool weight, and colon cancer in two Scandinavian populations. Am. J. Clin. Nutr. 31 suppl. 10:S239-S242. MacMahon, B., P. Cole, and J. Brown. 1973. Etiology of human breast cancer: a review. J. Natl. Cancer Inst. 50:21-42. MacMahon, B., S. Yen, D. Trichopoulos, K. Warren, and G. Nardi. 1981. Coffee and cancer of the pancreas. N. Engl. J. Med. 304:630-633. Macquart-Moulin, G., E. Riboli, J. Cornee, B. Charnay, P. Berthezene, and N. Day. 1986. Case-control study on colorectal cancer and diet in Marseilles. Int. J. Cancer 38: 183-191. Malhotra, S.L. 1977. Dietary factors in a study of colon cancer from cancer registry, with special reference to the role of saliva, milk and fermented milk products and vegetable fibre. Med. Hypotheses 3:122-126. Mandel, J.S., and L.M. Schuman. 1980. Epidemiology of cancer of the prostate. Pp. 1-83 in A.M. Lilienfeld, ed.

OCR for page 593
Page 610 Reviews in Cancer Epidemiology, Vol. 1. Elsevier/North-Holland, New York. Manousos, O., N.E. Day, D. Trichopoulos, F. Gerovassilis, A. Tzonou, and A. Polychronopoulou. 1983. Diet and colorectal cancer: a case-control study in Greece. Int. J. Cancer 32:1-5. Marrett, L.D., S.D. Walter, and J.W. Meigs. 1983. Coffee drinking and bladder cancer in Connecticut. Am. J. Epidemiol. 117:113-127. Martinez, I. 1969. Factors associated with cancer of the esophagus, mouth, and pharynx in Puerto Rico. J. Natl. Cancer Inst. 42:1069-1094. McKeown-Eyssen, G.E., and E. Bright-See. 1984. Dietary factors in colon cancer: international relationships. Nutr. Cancer 6:160-170. McMichael, A.J., O.M. Jensen, D.M. Parkin, and D.G. Zaridze. 1984. Dietary and endogenous cholesterol and human cancer. Epidemiol. Rev. 6:192-216. Medina, D. 1986. Mechanisms of selenium  inhibition of tumorigenesis. Pp. 465-472 in L.A. Poirier, P.M. Newberne, and M.W. Pariza, eds. Essential Nutrients in Carcinogenesis. Advances in Experimental Biology and Medicine, Vol. 206. Plenum Press, New York. Menkes, M.S., G.W. Comstock, J.P. Vuilleumier, K.J. Helsing, A.A. Rider, and R. Brookmeyer. 1986. Serum beta-carotene, vitamins A and E, selenium, and the risk of lung cancer. N. Engl. J. Med. 315:1250-1254. Mettlin, C., and S. Graham. 1979. Dietary risk factors in human bladder cancer. Am. J. Epidemiol. 110:255-263. Mettlin, C., S. Graham, R. Priore, J. Marshall, and M. Swanson. 1981. Diet and cancer of the esophagus. Nutr. Cancer 2:143-147. Miller, A.B. 1978. An overview of hormone-associated cancer. Cancer Res. 38:3985-3990. Miller, A.B. 1980. Epidemiology and etiology of lung cancer. Pp. 9-26 in H.H. Hansen and M. Roth, eds. Lung Cancer 1980. Excerpta Medica, Amsterdam. Miller, A.B., A. Kelly, N.W. Choi, V. Matthews, R.W. Morgan, L. Munan, J.D. Burch, J. Feather, G.R. Howe, and M. Jain. 1978. A study of diet and breast cancer. Am. J. Epidemiol. 107:499-509. Miller, A.B., G.R. Howe, M. Jain, K.J.P. Craib, and. L. Harrison. 1983. Food items and food groups as risk factors in a case-control study of diet and colo-rectal cancer. Int. J. Cancer 32:155-161. Milner, J.A. 1985. Effect of selenium on virally induced and transplantable tumor models. Fed. Proc. 44:2568-2572. Milner, J.A. 1986. Inhibition of chemical carcinogenesis and tumorigenesis by selenium. Pp. 449-463 in LA. Poirier, P.M. Newberne, and M.W. Pariza, eds. Essential Nutrients in Carcinogenesis. Advances in Experimental Medicine and Biology, Vol. 206. Plenum Press, New York. Mirvish, S.S., L. Wallcave, M. Eagen, and P. Shubik. 1972. Ascorbate-nitrite reaction: possible means of blocking the formation of carcinogenic N-nitroso compounds. Science 177:65-68. Modan, B., F. Lubin, V. Barell, R.A. Greenberg, M. Modan, and S. Graham. 1974. The role of starches in the etiology of gastric cancer. Cancer 34:2087-2092. Modan, B., V. Barell, F. Lubin, M. Modan, R.A. Greenberg, and S. Graham. 1975. Low-fiber intake as an etiologic factor in cancer of the colon. J. Natl. Cancer Inst. 55:15-18. Monson, R.R., and J.L Lyon. 1975. Proportional mortality among alcoholics. Cancer 36:1077-1079. Morrison, A.S., J.E. Buring, W.G. Verhoek, K. Aoki, I. Leck, Y. Ohno, and K. Obata. 1982. Coffee drinking and cancer of the lower urinary tract. J. Natl. Cancer Inst. 68:91-94. Muñoz, N., J. Wahrendorf, L.J. Bang, M. Crespi, D.I. Thurnham, N.E. Day, Z.H. Ji, A. Grassi, L.W. Yan, L.G. Lin, L.Y. Quan, Z.C. Yun, Z.S. Fang, L.J. Yao, P. Correa, G.T. O'Conor, and X. Bosch. 1985. No effect of riboflavine, retinol, and zinc on prevalence of precancerous lesions of oesophagus. Randomised double-blind intervention study in high-risk population of China. Lancet 2:111-114. Nasca, P.C., P. Greenwald, S. Chorost, R. Richart, and T. Caputo. 1984. An epidemiologic case-control study of ovarian cancer and reproductive factors. Am. J. Epidemiol. 119:705-713. Newberne, P.M. 1986. Lipotropic factors and oncogenesis. Pp. 223-251 in L.A. Poirier, P.M. Newberne, and M.W. Pariza, eds. Essential Nutrients in Carcinogenesis. Advances in Experimental Biology and Medicine, Vol. 206. Plenum Press, New York. Newmark, H.L., M.J. Wargovich, and W.R. Bruce. 1984. Colon cancer and dietary fat, phosphate, and calcium: a hypothesis. J. Natl. Cancer Inst. 72:1323-1325. Nicholls, P., G. Edwards, and E. Kyle. 1974. Alcoholics admitted to four hospitals in England. II. General and cause-specific mortality. Q. J. Stud. Alcohol 35:841-855. Nomura, A.M., G.N. Stemmermann, L.K. Heilbrun, R.M. Salkeld, and J.P. Vuilleumier. 1985. Serum vitamin levels and the risk of cancer of specific sites to men of Japanese ancestry in Hawaii. Cancer Res. 45:2369-2372. Nomura, A., L.K. Heilbrun, and G.N. Stemmermann. 1986. Prospective study of coffee consumption and the risk of cancer. J. Natl. Cancer Inst. 76:587-590. Norell, S.E., A. Ahlbom, R. Erwald, G. Jacobson, I. Lindberg-Navier, R. Olin, B. Tornberg, and K.L. Wiechel. 1986. Diet and pancreatic cancer: a case-control study. Am. J. Epidemiol. 124:894-902. NRC (National Research Council). 1981. The Health Effects of Nitrate, Nitrite, and N-Nitroso Compounds. Report of the Committee on Nitrite and Alternative Curing Agents in Food, Assembly of Life Sciences. National Academy Press, Washington, D.C. 544 pp. NRC (National Research Council). 1982. Diet, Nutrition, and Cancer. Report of the Committee on Diet, Nutrition, and Cancer, Assembly of Life Sciences. National Academy Press, Washington, D.C. 478 pp. NRC (National Research Council). 1985. Evaluation of Cyclamate for Carcinogenicity. Report of the Committee on the Evaluation of Cyclamate for Carcinogenicity, Commission on Life Sciences. National Academy Press, Washington, D.C. 196 pp. O'Connor, T.P., B.C. Roebuck, and T.C. Campbell. 1987. Effect of varying dietary omega-3:omega-6 fatty acid ratio on L-azaserine induced preneoplastic development in rat pancrease. Pp. 238-240 in W.E.M. Lands, ed. Proceedings of the AOCS Short Course on Polyunsaturated Fatty Acids and Eicosanoids. American Oil Chemists' Society, Champaign, Ill. Ohno, Y., K. Aoki, K. Obata, and A.S. Morrison. 1985. Case-control study of urinary bladder cancer in metropolitan Nagoya. Natl. Cancer Inst. Monogr. 69:229-234. Paffenbarger, R.S., J.B. Kampert, and H.G. Chang. 1980. Characteristics that predict risk of breast cancer before and after the menopause. Am. J. Epidemiol. 112:258-268.

OCR for page 593
Page 611 Page, H.S., and A.J. Asire. 1985. Cancer Rates and Risks, 3rd ed. DHHS Publ. No. (NIH) 85-691. National Institutes of Health, Public Health Service, U.S. Department of Health and Human Services, Bethesda, Md. 136 pp. Pariza, M.W., and R.K. Boutwell. 1987. Historical perspective: calories and energy expenditure in carcinogenesis. Am. J. Clin. Nutr. 45 suppl. 1:151-156. Peers, F.G., G.A. Gilman, and C.A. Linsell. 1976. Dietary aflatoxins and human liver cancer. A study in Swaziland. Int. J. Cancer 17:167-176. Peleg, I., S. Heyden, M. Knowles, and C.G. Hames. 1984. Serum retinol and risk of subsequent cancer: extension of the Evans County, Georgia, study. J. Natl. Cancer Inst. 73: 1455-1458. Pell, S., and A. D'Alonzo. 1973. A five-year mortality study of alcoholics. J. Occup. Med. 15:120-125. Pence, B.C., and F. Buddingh. 1987. Inhibition of dietary fat promotion of colon carcinogenesis by supplemental calcium or vitamin D. Proc. Am. Assoc. Cancer Res. 28:154. Phillips, R.L. 1975. Role of life-style and dietary habits in risk of cancer among Seventh-Day Adventists. Cancer Res. 35: 3513-3522. Pickle, L.W., M.H. Greene, R.G. Ziegler, A. Toledo, R. Hoover, H.T. Lynch, and J.F. Fraumeni, Jr. 1984. Colorectal cancer in rural Nebraska. Cancer Res. 44:363-369. Pollack, E.S., A.M. Nomura, L.K. Heilbrun, G.N. Stemmermann, and S.B. Green. 1984. Prospective study of alcohol consumption and cancer. N. Engl. J. Med. 310:617-621. Potter, J.D., and A.J. McMichael. 1986. Diet and cancer of the colon and rectum: a case-control study. J. Natl. Cancer Inst. 76:557-569. Pottern, L.M., I.E. Morris, W.J. Blot, R.G. Ziegler, and J.F. Fraumeni, Jr. 1981. Esophageal cancer among black men in Washington, D.C. 1. Alcohol, tobacco, and other risk factors. J. Natl. Cancer Inst. 67:777-783. Rebelakos, A., D. Trichopoulos, A. Tzonou, X. Zavitsanos, E. Velonakis, and A. Trichopoulos. 1985. Tobacco smoking, coffee drinking, and occupation as risk factors for bladder cancer in Greece. J. Natl. Cancer Inst. 75:455-461. Risch, H.A., M. Jain, N.W. Choi, J.G. Fodor, C.J. Pfeiffer, G.R. Howe, L.W. Harrison, K.J. Craib, and A.B. Miller. 1985. Dietary factors and the incidence of cancer of the stomach. Am. J. Epidemiol. 122:947-959. Risch, H.A., J.D. Burch, A.B. Miller, G.B. Hill, R. Steele, and G.R. Howe. 1988. Dietary factors and the incidence of cancer of the urinary bladder. Am. J. Epidemiol. 127:1179-1191. Rivlin, R.S. 1986. Riboflavin. Pp. 349-355 in L.A. Poirier, P.M. Newberne, and M.W. Pariza, eds. Essential Nutrients in Carcinogenesis. Advances in Experimental Biology and Medicine, Vol. 206. Plenum Press, New York. Robinette, C.D., Z. Hrubec, and J.F. Fraumeni. 1979. Chronic alcoholism and subsequent mortality in World War II veterans. Am. J. Epidemiol. 109:687-700. Ross, R.K., A. Paganini-Hill, and B.E. Henderson. 1983. The etiology of prostate cancer: what does the epidemiology suggest? Prostate 4:333-344. Rotkin, I.D. 1977. Studies in the epidemiology of prostatic cancer: expanded sampling. Cancer Treat. Rep. 61:173-180. Salonen, J.T., R. Salonen, R. Lappetelainen, P.H. Maenpaa, G. Alfthan, and P. Puska. 1985. Risk of cancer in relation to serum concentrations of selenium and vitamins A and E: matched case-control analysis of prospective data. Br. Med. J. 290:417-420. Samet, J.M., B.J. Skipper, C.G. Humble, and D.R. Pathak. 1985. Lung cancer risk and vitamin A consumption in New Mexico. Am. Rev. Respir. Dis. 131:198-202. Schatzkin, A., D.Y. Jones, R.N. Hoover, P.R. Taylor, L.A. Brinton, R.G. Ziegler, E.B. Harvey, C.L. Carter, L.M. Licitra, M.C. Dufour, and D.B. Larson. 1987. Alcohol consumption and breast cancer in the epidemiologic followup study of the first National Health and Nutrition Examination Survey. N. Engl. J. Med. 316:1169-1173. Schmidt, W., and J. de Lint. 1972. Causes of death of alcoholics. Q. J. Stud. Alcohol, Part A 33:171-185. Schoenberg, B.S., J.C. Bailar III, and J.F. Fraumeni, Jr. 1971. Certain mortality patterns of esophageal cancer in the United States, 1930-67. J. Natl. Cancer Inst. 46:63-73. Schrauzer, G.N., D.A. White, and C.J. Schneider. 1977. Cancer mortality correlation studies—IV: associations with dietary intakes and blood levels of certain trace elements, notably Se-antagonists. Bioinorg. Chem. 7:35-56. Schuman, L.M., J.S. Mandel, A. Radke, U. Seal, and F. Halberg. 1982. Some selected features of the epidemiology of prostatic cancer: Minneapolis-St. Paul, Minnesota case-control study, 1976-1979. Pp. 345-354 in K. Magnus, ed. Trends in Cancer Incidence: Causes and Practical Implications. Hemisphere Publishing Corp., Washington, D.C. Schwartz, D., J. Lellouch, R. Flamant, and P.F. Denoix. 1962. Alcohol and cancer. Results of a retrospective investigation. Rev. Franc. Etud. Clin. Biol. 7:590-604. Shank, R.C., J.E Gordon, G.N. Wogan, A. Nondasuta, and B. Subhamani. 1972a. Dietary aflatoxins and human liver cancer. III. Field survey of rural Thai families for ingested aflatoxins. Food Cosmet. Toxicol. 10:71-84. Shank, R.C., N. Bhamarapravati, J.E. Gordon, and G.N. Wogan. 1972b. Dietary aflatoxins and human liver cancer. IV. Incidence of primary liver cancer in two municipal populations of Thailand. Food Cosmet. Toxicol. 10:171-179. Shekelle, R.B., M. Lepper, S. Liu, C. Maliza, W.J. Raynor, Jr., A.H. Rossof, O. Paul, A.M. Shryock, and J. Stamler. 1981. Dietary vitamin A and risk of cancer in the Western Electric study. Lancet 2:1186-1190. Shigematsu, I. 1984. The epidemiological approach to cadmium pollution in Japan. Ann. Acad. Med. Singapore 13: 231-236. Shinozuka, H., S.L. Katyal, and M.I.R. Perera. 1986. Choline deficiency and chemical carcinogenesis. Pp. 253-267 in L.A. Poirier, P.M. Newberne, and M.W. Pariza, eds. Essential Nutrients in Carcinogenesis. Advances in Experimental Biology and Medicine, Vol. 206. Plenum Press, New York. Simon, D., S. Yen, and P. Cole. 1975. Coffee drinking and cancer of the lower urinary tract. J. Natl. Cancer Inst. 54: 587-591. Smith, A.H., N.E. Pearce, and J.G. Joseph. 1985. Major colorectal aetiological hypotheses do not explain mortality trends among Maori and non-Maori New Zealanders. Int. J. Epidemiol. 14:79-85. Snowdon, D.A., and R.L. Phillips. 1984. Coffee consumption and risk of fatal cancers. Am. J. Public Health 74:820-823. Snowdon, D.A., R.L. Phillips, and-W. Choi. 1984. Diet, obesity and risk of fatal prostate cancer. Am. J. Epidemiol. 120:244-250. Stukonis, M.K. 1978. Cancer Incidence Cumulative Rates—International Comparison Based on Data from "Cancer Incidence in Five Continents." IARC Technical Report

OCR for page 593
Page 612 No. 78/002. International Agency for Research on Cancer, Lyon, France. 54 pp. Takahashi, M. 1986. Enhancing effect of a high salt diet on gastrointestinal carcinogenesis. Gan No Rinsho 32:667-673. Takahashi, M., T. Kokubo, F. Furukawa, Y. Kurokawa, M. Tatematsu, and Y. Hayashi. 1983. Effect of high salt diet on rat gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine. Gann 74:28-34. Talamini, R., C. La Vecchia, A. Decarli, S. Francechi, E. Grattoni, E. Grigoletto, A. Liberati, and G. Tognoni. 1984. Social factors, diet and breast cancer in northern Italian population. Br. J. Cancer 49:723-729. Talamini, R., C. La Vecchia, A. Decarli, E. Negri, and S. Francechi. 1986. Nutrition, social factors and prostatic cancer in Northern Italian population. Br. J. Cancer 53:817-821. Tannenbaum, S.R., D. Moran, W. Rand, C. Cuello, and P. Correa. 1979. Gastric cancer in Colombia. IV. Nitrite and other ions in gastric contents of residents from a high-risk region. J. Natl. Cancer Inst. 62:9-12. Thind, I.S. 1986. Diet and cancer—an international study. Int. J. Epidemiol. 15:160-163. Thomas, D.B., C.N. Uhl, and P. Hartge. 1983. Bladder cancer and alcoholic beverage consumption. Am. J. Epidemiol. 118:720-727. Thurnham, D.I., P. Rathakette, K.M. Hambidge, N. Muñoz, and M. Crespi. 1982. Riboflavin, vitamin A, and zinc status in Chinese subjects in a high-risk area for oesophageal cancer in China. Hum. Nutr. Clin. Nutr. 36:337-349. Trichopoulos, D., M. Papapostolou, and A. Polychronopoulou. 1981. Coffee and ovarian cancer. Int. J. Cancer 28: 691-693. Trichopoulos, D., N.E. Day, E. Kaklamani, A. Tzonou, N. Munoz, X. Zavitsanos, Y. Koumantaki, and A. Trichopoulou. 1987. Hepatitis B virus, tobacco smoking, and ethanol consumption in the etiology of hepatocellular carcinoma. Int. J. Cancer 39:45-49. Tung, T.C., and K.H. Ling. 1968. Study on aflatoxin in foodstuffs in Taiwan. J. Vitaminol. 14:48-52. Tuyns, A.J. 1983. Oesophageal cancer in non-smoking drinkers and in non-drinking smokers. Int. J. Cancer 32:443-444. Tuyns, A.J., G. Péquinot, and O.M. Jensen. 1977. Le cancer de l'oesophage en Ille-et-Vilaine en fonction des niveaux de consommation d'alcool et de tabac. Des risques qui se multiplient. Bull. Cancer 64:45-60. Tuyns, A.J., G. Péquignot, M. Gignoux, and A. Valla. 1982. Cancers of the digestive tract, alcohol and tobacco. Int. J. Cancer. 30:9-11. Tuyns, A.J., M. Haelterman, and R. Kaaks. 1987. Colorectal cancer and the intake of nutrients: oligosaccharides are a risk factor, fats are not. A case-control study in Belgium. Nutr. Cancer 10:181-196. Tzonou, A., N.E. Day, D. Trichopoulos, A. Walker, M. Saliaraki, M. Papapostolou, and A. Polychronopoulou. 1984. The epidemiology of ovarian cancer in Greece: a case-control study. Eur. J. Cancer Clin. Oncol. 20:1045-1052. van Rensburg, S.J. 1981. Epidemiologic and dietary evidence for a specific nutritional predisposition to esophageal cancer. J. Natl. Cancer Inst. 67:243-251. van Rensburg, S.J., J.J. van der Watt, I.F.H. Purchase, L.P. Coutinho, and R. Markham. 1974. Primary liver cancer rate and aflatoxin intake in a high cancer area. S. Afr. Med. J. 48:2508a-2508d. Visek, W.J. 1986. Dietary protein and experimental carcinogenesis. Pp. 163-186 in L.A. Poirier, P.M. Newberne, and M.W. Pariza, eds. Essential Nutrients in Carcinogenesis. Advances in Experimental Medicine and Biology, Vol. 206. Plenum Press, New York. Wald, N., M. Idle, J. Boreham, and A. Bailey. 1980. Low serum-vitamin-A and subsequent risk of cancer. Preliminary results of a prospective study. Lancet 2:813-815. Wald, N., J. Boreham, and A. Bailey. 1986. Serum retinol and subsequent risk of cancer. Br. J. Cancer 54:957-961. Waterhouse, J., C. Muir, P. Correa, and J. Powell, eds. 1976. Cancer Incidence in Five Continents: Vol. III—1976. IARC Scientific Publ. No. 15. International Agency for Research on Cancer, Lyon, France. 584 pp. Weiss, N.S., J.L. Lyon, J.M. Liff, W.M. Vollmer, and J.R. Daling. 1981. Incidence of ovarian cancer in relation to the use of oral contraceptives. Int. J. Cancer. 28:669-671. Welsch, C.W. 1987. Enhancement of mammary tumorigenesis by dietary fat: review of potential mechanisms. Am. J. Clin. Nutr. 45 suppl. 1:192-202. Whittemore, A.S., R.S. Paffenbarger, Jr., K. Anderson, and J. Halpren. 1983. Early precursors of pancreatic cancer in college men. J. Chronic Dis. 36:251-256. Willett, W.C., M.J. Stampfer, G.A. Colditz, B.A. Rosner, C.H. Hennekens, and F.E. Speizer. 1987a. Dietary fat and the risk of breast cancer. N. Engl. J. Med. 316:22-28. Willett, W.C., M.J. Stampfer, G.A. Colditz, B.A. Rosner, C.H. Hennekens, and F.E. Speizer. 1987b. Moderate alcohol consumption and the risk of breast cancer. N. Engl. J. Med. 316:1174-1180. Williams, R.R., and J.W. Horm. 1977. Association of cancer sites with tobacco and alcohol consumption and socioeconomic status of patients: interview study from the Third National Cancer Survey. J. Natl. Cancer Inst. 58:525-547. Wogan, G.N. 1975. Dietary factors and special epidemiological situations of liver cancer in Thailand and Africa. Cancer Res. 35:3499-3502. Wynder, E.L. 1975. The epidemiology of large bowel cancer. Cancer Res. 35:3388-3394. Wynder, E.L., and I.J. Bross. 1961. A study of etiological factors in cancer of the esophagus. Cancer 14:389-413. Wynder, E.L., and G.B. Gori. 1977. Contribution of the environment to cancer incidence: an epidemiologic exercise. J. Natl. Cancer Inst. 58:825-832. Wynder, EL., G.C. Escher, and N. Mantel. 1966. An epidemiological investigation of cancer of the endometrium. Cancer 19:489-520. Wynder, E.L, K. Mabuchi, and W.F. Whitmore, Jr. 1971. Epidemiology of cancer of the prostate. Cancer 28:344-360. Wynder, E.L., K. Mabuchi, N. Maruchi, and J.G. Fortner. 1973. Epidemiology of cancer of the pancreas. J. Natl. Cancer Inst. 50:645-667. Wynder, E.L., N.E. Hall, and M. Polansky. 1983. Epidemiology of coffee and pancreatic cancer. Cancer Res. 43:3900-3906. Wynder, EL., J.R. Hebert, and G.C. Kabat. 1987. Association of dietary fat and lung cancer. J. Natl. Cancer Inst. 79: 631-637. Yang, C.S. 1980. Research on esophageal cancer in China: a review. Cancer Res. 40:2633-2644. Yu, M.C., T. Mack, R. Hanisch, R.L. Peters, B.E. Henderson, and M.C. Pike. 1983. Hepatitis, alcohol consumption,

OCR for page 593
Page 613 cigarette smoking, and hepatocellular carcinoma in Los Angeles. Cancer Res. 43:6077-6079. Zaldivar, R. 1977. Nitrate fertilizers as environmental pollutants: positive correlation between nitrates (NaNO3 and KNO3) used per unit area and stomach cancer mortality rates. Experientia 33:264-265. Zaridze, D.G., M. Blettner, N.N. Trapeznikov, J.P. Kuvshinov, E.G. Matiakin, B.P. Poljakov, B.K. Poddubni, S.M. Parshikova, V.I. Rottenberg, F.S. Chamrakulov, M.M. Chodjaeva, H.F. Stich, M.P. Rosin, D.I. Thurnham, D. Hoffmann, and K.D. Brunnemann. 1985. Survey of a population with a high incidence of oral and oesophageal cancer. Int. J. Cancer 36:153-158. Ziegler, R.G., T.J. Mason, A. Stemhagen, R. Hoover, J.B. Schoenberg, G. Gridley, P.W. Virgo, R. Altman, and J.F. Fraumeni, Jr. 1984. Dietary carotene and vitamin A and risk of lung cancer among white men in New Jersey. J. Natl. Cancer Inst. 73:1429-1435.

OCR for page 593