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5 Lipids (Fats and Cholesteroll EPIDEMIOLOGICAL EVIDENCE _ . Fats Of all the dietary factors that have been associated epidemiologi- cally with cancers of various sites, fat has probably been studied most thoroughly and produced the greatest frequency of direct associations. However, since dietary fat is highly correlated with the consumption of other nutrients that are present in the same foods, especially protein in Western diets, it is not always possible to attribute these associations to fat intake per se with absolute certainty. ~ _ Breast Cancer. Several international correlation studies have shown direct associations between per capita fat intake and breast cancer in- cidence or mortality (Armstrong and Doll, 1975; Carroll, 1975; Drasar and Irving, 1973; Gray et al., 1979; Hems, 1978; Knox, 1977~. In general, the correlations were higher for total fat than for the other dietary factors considered (e.g., animal protein, meat, specific fat components, and oils). Some of the similarities in the findings undoubtedly reflect the overlapping data sets used in these studies rather than reproduced results. In other correlation studies, intracountry data sets have been used to compare dietary fat intake and breast cancer. Gaskill et al. (1979) compared per capita intake of various foods by state within the United States with corresponding breast cancer mortality rates and found a significant direct correlation with fat intake when results from all states studied were combined. The correlation disappeared, however, when the southern states were excluded from the analysis or when they controlled for age at first marriage (as a reflection of age at first pregnancy) or median income. Their results suggested that dairy products as a class increased the risk of breast cancer. Hems (1980) noted that time trends for breast cancer mortality in England and Wales from 1911 to 1975 correlated best with corresponding per capita intake patterns for fat, sugar, and animal protein one decade earlier. In studies based on personal interview data, Kolonel et al. (1981) correlated individual consumption of fat with ethnic patterns of breast cancer incidence in Hawaii. These investigators found significant associations with total fat, with animal fat, and with both saturated and unsaturated fats. The findings of three case-control studies support a role for dietary fat in the risk for breast cancer. Phillips (1975) reported a direct association between frequency of consumption of high-fat foods and breast cancer in a study of 77 breast cancer cases and matched controls among 73 5-1

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74 DIET, NUTRITION, AND CANCER Seventh-Day Adventists in California. Miller et al. (1978) also found a weak direct association, but no evidence of a dose response, between total fat consumption (based on quantitative dietary histories) and breast cancer in a study of 400 cases and 400 matched neighborhood controls in Canada. In the third case-control study, Lubin et al. (1981) found signifi- cant increasing trends in relative risk with more frequent consumption of beef and other red meat, pork, and sweet desserts. Analysis of computed mean daily nutrient intake supported a link between breast cancer and consumption of animal fat and protein. Nomura _ al. (1978) compared the diets consumed by husbands of women with and without breast cancer. (The men were participants in a pro- spective cohort study of Japanese men in Hawaii.) These investigators reported a direct association between consumption of high fat diets by the husbands and breast cancer in their wives, who were assumed to have adhered to similar eating patterns. Prostate Cancer. Prostate cancer has also been associated epide- - miologically with fat intake. International data on mortality, but not incidence, indicate that there is a strong direct correlation of per capita total fat intake and cancer at this site (Armstrong and Doll, 1975~. Howell (1974) reported similar results from a study based on a rank correlation with mortality in 41 countries. In Hawaii, the inci- dence of prostate cancer in four ethnic groups was highly correlated with consumption of both animal and saturated fat (Kolonel et al., 1981~. In the mainland United States, Blair and Fraumeni (1978) corre- lated prostate cancer mortality by county with dietary variables. They observed that counties with a high risk for prostate cancer among whites had correspondingly high per capita fat intakes among the same population. Hirayama (1977) observed that one of the most notable dietary changes in Japan since 1950 is increased per capita fat intake and that this change parallels a striking increase in mortality from prostate cancer. Prostate cancer has been associated with dietary fat in two case- control studies. In an ongoing study based on 111 cases with prostate cancer and 111 matched hospital controls, Rotkin (1977) has found that the cases had consumed high fat foods with greater frequency than had the controls. Schuman et al. (1982) also reported a more frequent con- sumption of foods with high animal fat content by cases than by controls. Cancer of Other Reproductive Organs. Other reproductive organs for which there have been associations between dietary fat and cancer include the testes, corpus uteri, and ovary. Armstrong and Doll (1975) found direct correlations between per capita intake of total fat and incidence of cancer of the testes and corpus uteri and mortality from ovarian can- cer. Lingeman (1974) also correlated mortality from ovarian cancer with international data on fat intake. Kolonel et al. (1981) found a direct association between ethnic patterns of total, animal, saturated, and 5 - 2

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Lipids (Fats and Cholesterop 75 unsaturated fat consumption in Hawaii and incidence of cancer of the corpus uteri. Gastrointestinal Tract Cancer. Dietary fat has also been associated - with cancer at several sites in the gastrointestinal tract. In only one case-control study, however, has an association of stomach cancer with dietary fat been suggested. In that study, Higginson (1966) reported more frequent consumption of fried foods and greater use of animal fats in cooking by gastric cancer cases than by controls. Graham et al. (1972) failed to confirm this finding in a subsequent study of 168 gas- tric cancer cases matched to hospital controls. Although time-trend data in Japan (Hirayama, 1977) and one inter- national correlation study (Lea, 1967) have shown associations of fat intake with pancreatic cancer, most epidemiological data pertain to cancers of the large bowel. Armstrong and Doll (1975) reported direct correlations between colon and rectal cancer incidence and mortality and per capita intake of total fat, based on international data. Knox (1977) also reported a strong correlation between mortality from cancer of the large intestine (excluding rectum) and per capita total fat intake, and only a slightly weaker correlation between mortality from rectal cancer and intake of total fat and animal fat. After reviewing their data from an earlier study, Enig et al. (1979) retracted their original suggestion that colon cancer was directly cor- related with intake of total, saturated, and vegetable fat, but not with animal fat. gingham et al. (1979) calculated average intakes of nutrients by populations in different regions of Great Britain. They found no sig- nificant association of fat intake with mortality from colon and rectal cancers. Lyon and Sorenson (1978) also reported little difference in fat intake between the population of Utah (with a low risk for colon cancer) and that of the United States as a whole. The contrast between the strong international correlations and the lack of associations within countries is striking. One possible expla- nation is that the regional food intake data within a country are based on means of individual consumption data and, thus, may be too uniform to demonstrate any strong association with risk of colon or rectal cancer. In contrast, the variation in fat intake among countries is much greater, thereby facilitating the demonstration of associations. MacLennan et al. (1978) compared the diets of adult men in two Scandi- navian populations with different risks for colon cancer (high risk for Danes in Copenhagen and low risk for Finns in Kuopio). These studies, which were based on food diaries, indicated that the consumption of fat was similar for both groups, but that there were differences in fiber intake (see Chapter 8~. Reddy et al. (1978) also studied this low risk Finnish population and compared their diets to those of a high risk population in New York. They too found no difference between groups in 5 - 3

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76 DIET, NUTRITION, AND CANCER total fat intake, but noted that a higher proportion of total fat was consumed as dairy products by the Finns and as meat by the New Yorkers. This observation raises the possibility that the source as well as the quantity of dietary fat may be relevant. In a case-control study conducted in parallel with the study on breast cancer (described above), Phillips (1975) found a direct asso- ciation between colon cancer and the frequent consumption of high-fat foods by Seventh-Day Adventists. In a study of cases and hospital con- trols among blacks in California, Dales et al. (1978) observed a direct association between risk of colon cancer and frequent consumption of foods high in saturated fat. The association was strongest for those who consumed diets high in saturated fat and low in fiber content. Total fat consumption, estimated from frequency data, was also reported to be higher among large bowel cancer cases than among controls in a study conducted in Puerto Rico (Martinez et al., 1979~. Dietary histories were used to estimate nutrient intake in a case- control study conducted by Jain et al. (1980) in Canada. They reported a direct association (including a dose response) between risk of both colon and rectal cancer and consumption of fat, especially saturated fat. The elevated risks persisted after adjustment for other nutrients in the diet. Several reports on meat consumption are relevant to this discussion since meat can be an important source of dietary fat, especially satu- rated fat. Berg and Howell (1974) and Howell (1975) reported a high correlation between colon cancer mortality and meat intake (particularly beef), based on international per capita intake data. In Hawaii,investi- gators reported a direct association between frequency of meat, especially beef, consumption and large bowel cancer among Japanese cases and hospital controls (Haenszel et al., 1973~. This finding was not reproduced in studies conducted in Buffalo, New York (Graham et al., 1978) and in Japan (Haenszel et al., 1980), nor in parallel cohorts followed prospectively in Minnesota and Norway (Bjelke, 1978~. Furthermore, Enstrom (1975) has noted that trends in beef intake in the United States do not correlate with trends in the incidence of and mortality from colorectal cancer. Meat consumption has also been associated with pancreatic cancer. In a case-control study conducted in Japan, Ishii et al. (1968) found a direct association between meat consumption by men and mortality from pancreatic cancer. Their findings were based on responses to mailed questionnaires, most of which were completed by relatives of deceased cases. Hirayama (1977) reported a relative risk of 2.5 for daily meat intake and incidence of pancreatic cancer in a prospective cohort study of 265,118 Japanese. Summary. The results from a substantial number of epidemiological studies have indicated an association between dietary fat and cancers of the gastrointestinal tract (especially the large bowel) and of endocrine target organs (especially the breast and prostate). Some studies of

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Lipids (Fats and Cholesterol) 77 large bowel cancer were conducted on groups of relatively homogeneous populations, and some were not specifically designed to test the hypothe- sis that fat consumption is associated with colon cancer. The studies designed specifically to test this hypothesis (e.g., Dales et al., 1978; Jain et al., 1980) tended to show the most striking direct associations, especial ~ when the possible confounding effects of dietary fiber were considered. The evidence for cancer of the breast and prostate is more consistent than that for large bowel cancer. The results of the most thorough case-control study of breast cancer yet reported (Miller et al., 1978) were only weakly positive, however, partly reflecting the fact that recent food consumption was measured rather than dietary intake patterns earlier in life, which may have been the more relevant exposure period. (Studies of changing breast cancer incidence among Japanese migrants to the United States and their descendants, for example, suggest that early-life exposures are important determinants of breast cancer risk.) Cholesterol High-fat diets have been associated with atherosclerosis--a condition that has also been associated with elevated serum cholesterol levels. Therefore, there has been interest in studying the relationship of serum cholesterol levels as well as cholesterol intake to the incidence of can- cer. Most of the studies described below were designed to examine the association between cholesterol and cardiovascular disease, and were not specifically intended to measure cancer incidence or mortality. However, the opportunity provided by these long-term studies of cardiovascular disease in which serum cholesterol levels of the subjects were determined at the beginning of the study has resulted in a number of different re- ports on observed associations. Using per capita food intake data from 20 industrialized nations and simple correlation analysis, Liu et al. (1979) showed that there was a strong direct correlation between per capita intake of total fat and cholesterol and the mortality rate for colon cancer, but that there was an inverse correlation for fiber intake. Cross-classification showed a highly significant association for cholesterol, but not for fat or fiber. These investigators suggested that the data support a causal relationship between dietary cholesterol and colon cancer. Pearce and Dayton (1971) conducted an 8-year clinical trial in which groups of 422 and 424 men were fed a conventional diet or one containing high levels of polyunsaturated fat (to lower cholesterol levels), respec- tively. Incidence of cancer deaths in the groups on the experimental diet was higher. In a similar experiment conducted in Finland, Miettinen _ al. (1972) also found more carcinomas in the test group. A study group, convened to examine cancer incidence in men from five controlled trials of cholesterol-lowering diets, found little difference in relative risks (Ederer et al.. 1971). _ _ _ ~ _ 5-5 ad;

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78 DIET, NUTRITION, AND CANCER In other studies, clofibrate, a hypolipidemic agent, or a placebo was administered to more than 10,000 volunteers between 30 to 54 years of age whose serum cholesterol levels were in the top fertile (committee on Prin- ciple Investigators, 1978~. The total mortality from causes other than ischemic heart disease was substantially higher in the clofibrate group: there was a disproportionately large number of neoplasms of the gastroin- testinal tract and a few more neoplasms in the respiratory tract. How- ever, there were too few cancer deaths to demonstrate a statisticially significant difference among the test groups. In another study of the relationship between colon cancer and serum cholesterol, Rose _ al. (1974) observed that the initial levels of serum cholesterol in colon cancer patients were lower than expected. They also reported that serum cholesterol levels were higher in patients with cancer of the stomach, pancreas, liver, bile ducts, and rectum than in the con- trols. Bjelke (1974) reported a similar correlation between colon cancer and low levels of serum cholesterol. Nydegger and Butler (1972) examined total serum cholesterol levels in 186 controls and 122 subjects with malignant tumors. Their data also generally showed lower cholesterol levels in the cancer patients. Beaglehole et al. (1980) studied the relationship between serum cholesterol concentration and mortality in New Zealand Maoris over a period of 11 years. They found significant inverse relationships be- tween serum cholesterol concentrations and cancer mortality. In a 7.5-year follow-up study of London civil servants, Rose and Shipley (1980) observed that mortality from cancer at all sites was associated with a progressive decline in plasma cholesterol levels. These investigators grouped cancer deaths into those that occurred less than 2 years after the subjects entered the study and those that occurred from 2 to 7.5 years afterward. For the group in which deaths occurred within 2 years, the age-adjusted mortality rate for those with the lowest plasma cholesterol levels was more than double the rate for those with the highest levels. However, cancer deaths among those followed for longer than 2 years occurred at the same rate, regardless of plasma cholesterol level at entry into the study. The investigators concluded that the decline in cholesterol levels was probably a meta- bolic consequence of cancer, which, while unsuspected, was present when the subjects entered the study. In more than 5,000 subjects studied for 24 years in the Framingham Heart Study (Williams et al., 1981), an inverse relationship between serum cholesterol levels and cancer of the colon and other sites was ob- served in men but not in women. Kark et al. (1980) related serum cholesterol levels to cancer inci- dence in more than 3,000 individuals followed for as long as 14 years in Evans County, Georgia. Patients diagnosed as having cancer at any site at least 1 year following entry into the study had had entry serum cho- lesterol levels significantly lower than those in the noncancer patients. 5 - 6

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Lipids (Fats and Cholestero1) 79 This association was the same for black and white females and for black and white males, but was stronger in males of both races. The possibility that the presence of cancer may have been responsible for the lower serum cholesterol levels was investigated. Patients were categorized into three groups, depending on when evidence of cancer was first observed after entry into the study: within 1 year, from 1 to 6 years, and from 7 to 13 years. Initial serum cholesterol levels were higher in the first group than in the other two groups, but no differences were noted between the latter groups. Kark and colleagues also observed little difference in cholesterol levels in cases and controls when various cancer sites were grouped together. However, they did report low serum cholesterol levels in lung cancer- patients, whereas Stamler et al. (1968) observed that serum cholesterol levels were higher in lung cancer cases than in controls. A study conducted in Norway indicated that there was no over- all relationship between serum cholesterol levels and total cancer inci- dence (Westlund and Nicolaysen, 1972~. In the Honolulu Heart Study, 598 deaths were observed in 7,961 men whose cholesterol levels had been determined and who were followed for 9 years (Kagan et al., 1981~. The baseline serum cholesterol levels were directly associated with mortality from coronary heart disease but in- versely associated with total cancer mortality, mortality from cancers of the esophagus, colon, liver, and lung, and malignancies of the lymphatic and hematopoietic systems. In Yugoslavia, Kozarevic et al. (1981) related baseline serum choles- terol levels to mortality in 11,121 males over a 7-year period. The in- verse association between cancer deaths and serum cholesterol levels was not statistically significant. In the Puerto Rico Heart Health Programme, 9,824 men were followed for 8 years (Garcia-Palmieri et al., 1981~. Serum cholesterol levels mea- sured at the first examination were found to vary inversely with subse- quent mortality from cancer. Peterson _ al. (1981) followed 10,000 men in Sweden for a mean of 2.5 years. They found that deaths from neoplastic disease and other noncoronary heart disease peaked at low levels of serum cholesterol. In contrast, serum cholesterol was not associated with overall risk of death from cancer in three epidemiological studies of Chicago men (Dyer et al., 1981~. When cancer deaths were evaluated by site, there was a significant inverse association between serum cholesterol and deaths from sarcoma, leukemia, and Hodgkin's disease in the nearly 2,000 men studied for 17 years, but not for deaths from lung cancer, colorectal cancer, cancer of the oral cavity, pancreatic cancer, or all other can- cers combined. There was, however, a suggestion of a direct association for breast cancer in women. These studies have been assessed by Lilienfeld (1981) and by others, who concluded that the observed inverse correlations do not substantiate 5 - 7

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80 DIET, NUTRITION, AND CANCER any direct cause-and-effect relationship between low blood cholesterol levels and cancer. Only one case-control study has specifically evaluated serum choles- terol levels in cases of colon cancer and matched controls (Miller et _., 1981~. In 133 pairs matched by age and sex, serum cholesterol levels were lower for cases than for controls. However, following stratification by tumor stage, significant differences in cholesterol levels persisted only between cases with advanced tumors and controls. Furthermore, only women, not men, had significantly lower serum choles- terol levels with advancing disease. The lack of an association in early disease supports the concept that low serum cholesterol levels observed in colon cancer patients may be the result of a metabolic change accom- panying tumor growth and may not necessarily precede tumor formation. Miller et al. (1978) studied the association of dietary levels of cholesterol and breast cancer. They found no significant differences in estimated cholesterol consumption between cases and controls. In another case-control study, the same group found that cholesterol intake for males with rectal cancer and females with colon and rectal cancer was higher than for controls (Jain et al., 1980~. Although the relative risk for dietary cholesterol was significant at higher intakes for all male and female cases, compared to all controls, it was substantially less than the estimates of risk for other nutrients associated with intake of fat, especially saturated fat. There is an apparent conflict in the evidence, i.e., that an in- creased risk of cancer of the colon and other sites has been associated not only with dietary cholesterol (and simultaneous intake of other, possibly more relevant lipid components) but also with very low serum cholesterol levels. A possible explanation might be that a high intake of dietary fat (and/or cholesterol) by persons whose metabolism maintains low serum cholesterol results in reduced biosynthesis of cholesterol and a high rate of excretion for cholesterol breakdown products in the intestine (tin and Connor, 1980~. These breakdown products could serve as substrates for the intraluminal production of carcinogens by intes- tinal bacteria (Hill et al., 1971~. However, in metabolic studies con- ducted in hospital wails, low serum cholesterol is usually accompanied by excretion of low levels of bile acid. This observation is not compatible with the mechanisms normally proposed for the carcinogenic effect of dietary lipids. In summary, data pertaining to the association between serum cholesterol levels and total cancer incidence and mortality are incon- sistent. An inverse correlation between serum cholesterol levels and colon cancer in men has been noted in some studies, but not in all. It is not clear whether lower than normal serum cholesterol levels are the cause, or whether they reflect the metabolic consequences, of cancer. Thus, the data are inconclusive and do not point to a causal relationship between low cholesterol levels and risk of colon cancer. However, since 5 - 8

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Lipids (Fats and Cholesterop Sl they do suggest that low serum cholesterol levels may be a clue to some unknown factor, possibly something that is transported in the low density lipoprotein fraction of serum, these data and future findings should be examined carefully. RELATIONSHIP OF FECAL STEROID EXCRETION TO BOWEL CARCINOGENESIS The possibility that metabolites in the colon could provide a clue to the presence of malignancy has stimulated a number of investigators to study the level and spectrum of steroids in the feces of populations at low or high risk for colon cancer, as well as of animals fed colon car- cinogens together with various dietary regimens. The amounts of neutral and acidic fecal steroids correspond to the level of fat intake. How- ever, studies of the ratios of primary to secondary bile acids or the ratio of cholesterol to its metabolic products (i.e., coprostanol and coprostanone) have revealed no significant differences among the popula- tions studied (Moskovitz et al., i979; Mower et al., 1979; Reddy, 1979~. Recent comparisons of high risk and low risk populations, e.g., three socioeconomic groups in Hong Kong (Hill et al., 1979) and Finns and New Yorkers (Ready, 1979), suggest that the concentration of bile acids is elevated in feces of the groups that are at higher risk. Pioneering efforts by Hill and his colleagues (1971) pointed to an association between rates of mortality from colon cancer and fecal excretion of bile acids as well as the fecal degradation of cholesterol and its metabolizes. They revived an earlier concept, based on struc- tural and steric similarities, that bile acids might be transformed to the carcinogen 3-methylcholanthrene by anaerobic gut bacteria. In the studies leading to these earlier theories, deoxycholic acid was converted chemically to 3~ethylcholanthrene by Wieland and Dane (1933) and by Cook and Haslewood (1933~. Later, Fieser and Newman (1935) derived the same carcinogen from cholic acid. The chemical steps used in these studies were all reactions known to occur naturally, i.e., oxidation, hydrogena- tion, cyclization, and dehydrogenation, although laboratory conditions for the synthesis did not reproduce normally encountered biological conditions. Through the efforts of Hill, Reddy, Mastromarino, Narisawa, Nigro, their coworkers, and others, the concept has evolved that fecal bile acids and metabolizes of cholesterol may function as cocarcinogens, carcinogens, or promoters in tumorigenesis of the large bowel (Hill et al., 1971; Mastromarino et al., 1976; Narisawa et al., 1974; Nigro et al., 1973; Reddy and Wynder, 1973; Reddy et al., 1977a). To date, how- ever, no active carcinogen derived from bile acids has been isolated from human or animal feces. Reddy_al. (1977a) demonstrated that a fourfold increase in dietary fat (from 5% to 20%) given to rats increased the 24-hour fecal excretion 5 - 9

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82 DIET, NUTRITION, AND CANCER of neutral and acid sterols by 30% to 40% (based on body weight). Bac- terial conversion of primary to secondary bile acids occurred more exten- sively in rats fed the high fat diet than in those fed the low fat diet. The possibility that bile acids may have tumor-promoting effects is supported to some extent by the finding that bile acids affect cell ki- netics in the intestinal epithelium. Diversion of biliary and pancrea- tic secretions from the intestine decreases DNA synthesis and cell pro- liferation (Fry and Staffeldt, 1964; Ranken et al., 1971; Roy et al., 1975), whereas the administration of secondary bile acids increases cell proliferation in liver bile ducts and the biliary tract epithelium (Bagheri _ al., 1978~. Inhibition of DNA synthesis and cell prolifer- ation has also been observed in the rat colon following biliary diversion (Deschner and Raicht, 1979~. Possible promotional effects of bile acids on bowel tumorigenesis were suggested in studies initiated by Narisawa et al. (1974) and com- pleted, with a large sampling of bile acids, by Redly and colleagues (see review by Reddy _ al., 1980~. In these studies, N-methyl-N'- nitro-N-nitrosoguanidine (MNNG), which is a direct-acting carcinogen, was administered intrarectally to conventional or germfree rats for 2 weeks. During the subsequent 16 weeks, 20 mg doses of sodium cholate, sodium chenodeoxycholate, or sodium lithocholate in 0.5 ml of peanut oil were administered intrarectally to rats 3 times a week. No tumors were detected in the control groups. The total number of large bowel tumors in each of the conventional and germfree rats given intrarectal instilla- tions of bile salts was greater than in rats given MNNG without bile salts. These data also suggest that gut microflora was not required for the effect of bile acids to be manifested. In this study, the quantity of bile salts administered intrarectally was approximately 20 to 60 times higher than that normally excreted in the feces during a 24-hour period. Perhaps more importantly, the instillations at levels of approximately 100 mM were at least 10 times higher than the normal concentrations of these salts within the lumen of the bowel. Palmer (1979) observed that bile salts interact readily with mem- branes from artificial liposomes, bacteria, and mammalian cells. The well-studied cytotoxic effects of bile salts are invariably preceded by alterations in membrane permeability in red blood cells, in a variety of tissues, and in mucosal cells of both the large and the small intestine (Dawson and Isselbacher, 1960; Dietschy, 1967; Hoffman, 1967~. In one study, the effects of these salts upon permeability (and presumably cytotoxicity) in the gut were minimized when conjugated bile salts were added to the unconjugated bile salts in sufficiently high concentrations (Low-Beer _ al., 1970~. Thus, it cannot be determined whether the effects of intrarectally instilled unconjugated bile salts demonstrated classic tumor promotional activity or resulted from nonspecific damage and repair activity associated with increased cellular proliferation of the colonic mucosa induced by the high intraluminal concentration of the salts. 5-10

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Lipids (Fats and Cholesterol) 83 Cohen and associates studied the effect of bile acid on colon tumors induced by nitrosomethylurea (NMU) by feeding rats lab chow pellets with and without added bile acid. They observed that 0.2% cholic acid (Cohen et al., 1978), but not chenodeoxycholic acid (Raicht et al., 1975), in- creased the number of NMU-induced colon tumors, as compared to the num- ber of tumors in rats fed nonsupplemented pellets. In the dimethylhydra- zine (DMH) model, no effect on colon tumorigenesis was observed in rats fed 0.3% cholic acid in a semisynthetic diet (Broitman, 1981~. Evidence that increased quantities of bile acids in the colonic lumen were associated with an increase in azoxymethane (AOM)-induced colon tumorigenesis in rats was provided by Chomchai et al. (1974~. Williamson et al. (1979) showed that bile initiated prompt ileal hyperplasia in rats following intestinal resection with diversion of the pancreatic and bil- iarv ducts to the terminal ileum, i.e., pancreatobiliary diversion. Feeding cholestyramine to rats given AOM for tumor induction increased the average number of tumors in the large bowel but not in the small bowel (Nigro et al., 1973, 1977~. Vahouny et al. (1981) demonstrated that in- tralumina i nfusion of 165 AM of chol~c, deoxycholic, and chenodeoxycholic acids 1:1:1 twice daily for 5 days resulted in severe topological changes in the colonic mucosa. Thus, the enhancement of tumorigenesis observed at high concentra- tions of bile acids may be related to nonspecific effects of tissue injury. Tumor-enhancing effects of nonspecific injury have been attrib- uted to increased cellular proliferation, which accompanies inflammation and repair (Ryser, 1971~. EXPERIMENTAL EVIDENCE - The first demonstration that dietary fat could influence tumorigene- sis was reported by Watson and Mellanby (1930~. Most of these studies were conducted by increasing the level of dietary fat, which also led to an increase in the total intake of calories. Addition of 12.5% to 25.0% butter to a basal (3% fat) diet given to coal-tar-treated mice increased the incidence of skin tumors from 34% to 57%. Similarly, Lavik and Baumann (1941, 1943), who administered 3-methylcholanthrene topically to mice found that a basal diet, when supplemented with 15% fat (shortening), increased the yield of skin tumors from 12% to 83%. Fat was especially effective when fed 6 to 12 weeks after treatment with a carcinogen. Com- paring diets containing 10% corn oil, 10% coconut oil, or 10% lard for their ability to enhance tumors, these investigators observed a minor effect of unsaturation: the incidence of tumors at 5 months was 33% (for control diets), 61% (for added lard diets), 66% (for added coconut oil diets), and 76% (for added corn oil diets). Mammary Tumors Tannenbaum (1942) demonstrated that dietary fat enhanced the develop- ment of either chemically or spontaneously induced mammary tumors in mice. 5-11

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Lipids (Fats and Cholesterop 95 Broitman, S. A., J. J. Vitale, E. Vavrousek-Jakuba, and L. S. Gottlieb. 1977. Polyunsaturated fat, cholesterol and large bowel tumori- genesis. Cancer 40:2455-2463. Bull, A. W., B. K. Soullier, P. S. Wilson, M. T. Hayden, and N. D. Nigro. 1979. Promotion of azoxymethane-induced intestinal cancer by high-fat diet in rats. Cancer Res. 39:4956-4959. Carroll, K. K. 1975. Experimental evidence of dietary factors and hormone-dependent cancers. Cancer Res. 35:3374-3383. Carroll, K. K. 1980. Lipids and carcinogenesis. J. Environ. Pathol. Toxicol. 3~4~:253-271. Carroll, K. K., and G. J. Hopkins. 1979. Dietary polyunsaturated fat versus saturated fat in relation to mammary carcinogenesis. Lipids 14 :155-158. Carroll, K. K., and H. T. Khor. 1970. Effects of dietary fat and dose level of 7,12-dimethylbenz~o`)anthracene on mammary tumor incidence in rats. Cancer Res. 30:2260-2264. Carroll, K. K., and H. T. Khor. 1971. Effects of level and type of dietary fat on incidence of mammary tumors induced in female Sprague-Dawley rats by 7,12-dimethylbenz~oc~anthracene. Lipids 6:415-4 20. Carroll, K. K., and H. I. Khor. 1975. Dietary fat in relation to tumorigenesis. Prog. Biochem. Pharmacol. 10:308-353. Chan, P.-C., J. F. Head, L. A. Cohen, and E. L. Wynder. 1977. Influ- ence of dietary fat on the induction of mammary tumors by N-nitroso- methylurea: Associated hormone changes and differences between Sprague-Dawley and F344 rats. J. Natl. Cancer Inst. 59:1279-1283. Chomchai, C., N. Bhadrachari, and N. D. Nigro. 1974. The effect of bile on the induction of experimental intestinal tumors in rats. Dis. Colon Rectum 17:310-312. Cohen, B. I., R. F. Raicht, E. E. Deschner, E. Fazzini, M. Takahashi, and A. Sarwal. 1978. Effects of bile acids on induced colon cancer in rats. Proc. Am. Assoc. Cancer Res. Am. Soc. Clin. Oncol. 19:48. Abstract 190. Committee on Principle Investigators. 1978. A co-operative trial in the primary prevention of ischaemic heart disease using clofibrate. Br. Heart J. 1069-1118.

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96 DIET, NUTRITION, AND CANCER Cook, J. W., and G. A. D. Haslewood. 1933. The conversion of a bile acid into a hydrocarbon derived from 1:2-benzanthracene. J. Soc. Chem. Ind. London Rev. Sect. 52:758-759. Corwin, L. M., F. Varshavsky-Rose, and S. A. Broitman. 1979. Effect of dietary fats on tumorigenicity of two sarcoma cell lines. Cancer Res. 39:4350~4355 Cruse, J. P., M. R. Lewin, G. P. Ferulano, and C. G. Clark. 1978. Cocarcinogenic effects of dietary cholesterol in experimental colon cancer. Nature 276:822-825. Dales, L. G., G. D. Friedman, H. K. Dry, S. Grossman, and S. R. Williams. 1978. A case-control study of relationships of diet and other traits to colorectal cancer in American blacks. Am. J. Epidemiol. 109:132- 144. Dawson, A. M., and K. J. Isselbacher. 1960. Studies on lipid metabolism in the small intestine with observations on the role of bile salts. J. Clin. Invest. 39:730-740. Deschner, E. E., and R. F. Raicht. 1979. The influence of bile on the kinetic behavior of colonic epithelial cells of the rat. Gastro- enterology 76:1120. Abstract. Dietschy, J. M. 1967. Effects of bile salts on intermediate metabolism of the intestinal mucosa. Fed. Proc. Fed. Am. Soc. Exp. Biol. 26:1589-1598. Drasar, B. S., and D. Irving. 1973. Environmental factors and cancer of the colon and breast. Br. J. Cancer 27 :167-172. Dyer, A. R., J. Stamler, 0. Paul, R. B. Shekelle, J. A. Schoenberger, D. M. Berkson, M. Lepper, P. Collette, S. Shekelle, and H. A. Lindberg. 1981. Serum cholesterol and risk of death from cancer and other causes in three Chicago epidemiological studies. J. Chronic Dis. 34 :249-260. Ederer, F., P. Leren, 0. Turpeinen, and I. D. Frantz, Jr. 1971. Cancer among men on cholesterol-lowering diets: Experience from five clinical trials. Lancet 2:203-206. Enig, M. G., R. J. Munn, and M. Keeney. 1979. Response to letters. Fed. Proc. Fed. Am. Soc. Exp. Biol. 38:2437-2439. Enstrom, J. E. 1975. Colorectal cancer and consumption of beef and fat. Br. J. Cancer 32:4 32-4 39. 5-24

OCR for page 73
Lipids (Fats and Cholesterol) 97 Farber, E. 1973. Carcinogenesis--cellular evolution as a unifying thread: Presidential address. Cancer Res. 33:2537-2550. Fieser, L. F., and M. S. Newman. 1935. Methylcholanthrene from cholic acid. J. Am. Chem. Soc. 57:961. Fry, R. J. M., and E. Staffeldt. 1964. Effect of a diet containing sodium deoxycholate on the intestinal mucosa of the mouse. Nature 203:1396-1398. Garcia-Palmieri, M. R., P. D. Sortie, R. Costas, Jr., and R. J. Havlik. 1981. An apparent inverse relationship between serum cholesterol and cancer mortality in Puerto Rico. Am. J. Epidemiol. 114 :29-40. 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. 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. Mittleman, and G. Wilkinson. 1978. Diet in the epidemiology of cancer of the colon and rectum. J. Natl. Cancer Inst. 61:709-714. Gray, G. E., M. C. Pike, and B. E. Henderson. 1979. Breast-cancer incidence and mortality rates in different countries in relation to known risk factors and dietary practices. Br. J. Cancer 39:1-7. 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., F. B. Locke, and M. Segi. 1980. A case-control study of large bowel cancer in Japan. J. Natl. Cancer Inst. 64 :17-22. Hems, G. 1978. The contributions of diet and childbearing to breast- cancer rates. Br. J. Cancer 37:974-982. Hems, G. 1980. Associations between breast-cancer mortality rates, child-bearing and diet in the United Kingdom. Br. J. Cancer 41:429-437. Higginson, J. 1966. Etiological factors in gastrointestinal cancer in man. J. Natl. Cancer Inst. 37:527-545. Hill, M. J., B. S. Drasar, V. Aries, J. S. Crowther, G. Hawksworth, and R. E. O. Williams. 1971. Bacteria and aetiology of cancer of large bowel. Lancet 1:95-100. 5-25

OCR for page 73
98 DIET, NUTRITION, AND CANCER Hill, M., R. MacLennan, and K. Newcombe. 1979. Letter to the Editor: Diet and large bowel cancer in three socioeconomic groups in Hong Kong. Lancet 1:4 36. Hillyard, L. A., and S. Abraham. 1979. Effect of dietary polyun- saturated fatty acids on growth of mammary adenocarcinomas in mice and rats. Cancer Res. 39:4430-44 37. 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, Cold Spring Harbor, N.Y. Hoffman, A. F. 1967. The syndrome of ileal disease and the broken enterohepatic circulation: Cholerheic enteropathy. Gastroenter- ology 52:752-757. Hopkins, G. J., and K. K. Carroll. 1979. Relationship between amount and type of dietary fat in promotion of mammary carcinogenesis induced by 7, 12-dimethylbenz~a janthracene. J. Natl. Cancer Inst. 62:1009-1012. Hopkins, G. J., and C. E. West. 1976. Possible roles of dietary fats in carcinogenesis. Life Sci. 19 :1103-1116. Hopkins, G. J., and C. E. West. 1977. Effect of dietary polyun- saturated fat on the growth of a transplantable adenocarcinoma in C3HAVYfB mice. J. Natl. Cancer Inst. 58:753-756. 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. Ip, C. 1980. Ability of dietary fat to overcome the resistance of mature female rats to 7, 12-dimethylbenz~a janthracene-induced mammary tumorigenesis. Cancer Res. 40:2785-2789. Ishii, K., K. Nakamura, H. Ozaki, N. Yamada, and T. Takeuchi. 1968. [In Japanese.] [Epidemiological problems of pancreas cancer.] Jpn. J. Clin. Med. 26:1839-1842. 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. 5-26

OCR for page 73
Lipids (Fats and Cholesterol) 99 Kagan, A., D. L. McGee, K. Yano, G. G. Rhoads, and A. Nomura. 1981. Serum cholesterol and mortality in a Japanese-American population. Am. J. Epidemiol. 114:11-20. Kark, J. D., A. H. Smith, and C. G. Hames. 1980. The relationship of serum cholesterol to the incidence of cancer in Evans County, Georgia. J. Chronic Dis. 33:311-322. Kidwell, W. R., M. E. Monaco, M. S. Wicha, and G. S. Smith. 1978. Un- saturated fatty acid requirements for growth and survival of a rat mammary tumor cell line. Cancer Res. 38:4091-4100. King, J. T., C. B. Casas, and M. B. Visscher. 1949. The influence of estrogen on cancer incidence and adrenal changes in ovari- ectomized mice on calorie restriction. Cancer Res. 9:436-437. King, M. M., D. M. Bailey, D. D. Gibson, J. V. Pitha, and P. B. McCay. 1979. Incidence and growth of mammary tumors induced by 7,12-di- methylbenz~aJanthracene as related to the dietary content of fat and antioxidant. J. Natl. Cancer Inst. 63:657-663. Knox, E. G. 1977. Foods and diseases. Br. J. Prev. Sac. Med. 31:71- 80. Kolonel, L. N., J. H. Hankin, J. Lee, S. Y. Chu, A. M. Y. Nomura, and M. W. Hinds. 1981. Nutrient intakes in relation to cancer inci- dence in Hawaii. Br. J. Cancer. 44:332-339. Kozarevic, D. , D. McGee, N. Vo jvodic, T. Gordon, Z. Racic, W. Zukel, and T. Dawber. 1981. Serum cholesterol and mortality. The Yugoslavia cardiovascular disease study. Am. J. Epidemiol. 114:21-28. Lavik, P. S., and C. A. Baumann. 1941. Dietary fat and tumor forma- tion. Cancer Res. 1:181-187. Lavik, P. S., and C. A. Baumann. 1943. Further studies on tumor- promoting action of fat. Cancer Res. 3:749-756. Lea, A. J. 1967. Neoplasms and environmental factors. Ann. R. Coll. Surg. Engl. 41:432-438. Lilienfeld, A. M. 1981. The Humean fog: Cancer and cholesterol. Aln. J. Epidemiol. 114:1-4. Lin, D. S., and W. E. Connor. 1980. The long term effects of dietary cholesterol upon the plasma lipids, lipoproteins, cholesterol

OCR for page 73
DIET, NUTRITION, AND CANCER absorption, and the sterol balance in man: The demonstration of feedback inhibition of cholesterol biosynthesis and increased bile acid excretion. J. Lipid Res. 21:1042-1052. Lingeman, C. H. 1974. Etiology of cancer of the human ovary: A review. J. Nat1. Cancer Inst. 53:1603-1618. Liu, K., J. Stamler, D. Moss, D. Garside, V. Persky, and I. Soltero. 1979. Dietary cholesterol, fat, and fibre, and colon-cancer mortality. Lancet 2:782-785. Longnecker, D. S., D. B. Roebuck, J. D. Yager, Jr., H. S. Lilja, and B. Siegmund. 1981. Pancreatic carcinoma in azaserine-treated rats: Induction, classification and dietary modulation of incidence. Cancer 47:1562-1572. Low-Beer, T. S., R. E. Schneider, and W. O. Dobbins. 1970. Morpho- logical changes of the small-intestinal mucosa of guinea pig and hamster following incubation in vitro and perfusion in viva with unconjugated bile salts. Gut 11:486-492. Lubin, J. H., P. E. Burns, W. J. Blot, R. G. Ziegler, A. W. Lees, and J. F. Frau~neni, Jr. 1981. Dietary factors and breast cancer risk. Int. J. Cancer 28: 685-689. Lyon, J. L., and A. W. Sorenson. 1978. Colon cancer in a low-risk population. Am. J. Clin. Nutr. 31: 5227-5230. 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:S239-S242. Martinez, I., R. Torres, Z. Frias, J. R. Colon, and N. Fernandez. 1979. Factors associated with adenocarcinomas of the large bowel in Puerto Rico. Pp. 45-52 in J. M. Birch, ed. Advances in Medical Oncology, Research and Education. Volume 3, Epidemiology. Pergamon Press, Oxford, New York, Toronto, Sydney, Paris, and Frankfurt. Mastro~narino, A., B. S. Reddy, and E. L. Wynder. 1976. Metabolic epidemiology of colon cancer: Enzymic activity of fecal flora. Am. J. Clin. Nutr. 29 :1455-1460. McCay, P. B., M. King, L. E. Rikans, and J. V. Pitha. 1980. Inter- actions between dietary fats and antioxidants on DMBA-induced mammary carcinomas and on AAF-induced byperplastic nodules and hepatomas. J. Environ. Pathol. Toxicol. 3~4~:451-465. 5-28

OCR for page 73
Lipids (Fats and Cholesterol) 101 Miettinen, M., 0. Turpeinen, M. J. Karvonen, R. Elosuo, and E. Paavilainen. 1972. Effect of cholesterol-lowering diet on mortality from coronary heart-causes and other causes: A twelve-year clinical trial in men and women. Lancet 2:835-838. 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, S. R., P. I. Tartter, A. E. Papatestas, G. Slater, and A. H. Aufses, Jr. 1981. Serum cholesterol and human colon cancer. J. Natl. Cancer Inst. 67:297-300. Mohrhauer, H., and R. T. Holman. 1967. Metabolism of linoleic acid in relation to dietary saturated fatty acids in the rat. J. Nutr. 91:528-534. Moskovitz, M., C. White, R. N. Barnett, S. Stevens, E. Russell, D. Vargo, and M. H. Floch. 1979. Diet, fecal bile acids, and neutral sterols in carcinoma of the colon. Dig. Dis. Sci. 24:746-751. Mower, H. F., R. M. Ray, R. Shoff, G. N. Stemmermann, A. Nomura, G. A. Glober, S. Kamiyama, A. Shimada, and H. Yamakawa. 1979. Fecal bile acids in two Japanese populations with different colon cancer risks. Cancer Res. 39:328-331. Narisawa, T., N. E. Magadia, J. H. Weisburger, and E. L. Wynder. 1974. Promoting effect of bile acids on colon carcinogenesis after intrarectal instillation of N-methyl-N'-nitro-N-nitrosoguanidine in rats. J. Natl. Cancer Inst. 53:1093-1097. National Academy of Sciences. 1980. Pp. 13-15 in Toward Healthful Diets. Report prepared by the Food and Nutrition Board, National Academy of Sciences, Washington, D.C. Newberne, P. M., and E. Zeiger. 1978. Nutrition, carcinogenesis, and mutagenesis. Pp. 53-84 in W. G. Flamm and M. A. Mehlman, eds. Advances in Modern Toxicology. Volume 5, Mutagenesis. John Wiley and Sons, New York, London, Sydney, and Toronto. Newberne, P. M., J. Weigert, and N. Kula. 1979. Effects of dietary fat on hepatic mixed-function oxidases and hepatocellular carcinoma induced by aflatoxin B1 in rats. Cancer Res. 39:3986-3991. Nigro, N. D., N. Bhadrachari, and C. Chomchai. 1973. A rat model for studying colonic cancer: Effect of cholestyramine on induced tumors. Dis. Colon Rectum 16:438-443. 5-29

OCR for page 73
102 DIET, NUTRITION, AND CANCER Nigro, N. D., D. V. Singh, R. L. Campbell, and M. S. Pak. 1975. Effect of dietary beef fat on intestinal tumor formation by azoxymethane in rats. J. Natl. Cancer Inst. 54:439-442. Nigro, N. D., R. L. Campbell, J. S. Gantt, Y. N. Lin, and D. V. Singh. 1977. A comparison of the effects of the hypocholesteremic agents, cholestyramine and candicidin, on the induction of intestinal tumors in rats by azoxymethane. Cancer Res. 37:3198-3203. Nomura, A., B. E. Henderson, and J. Lee. 1978. Breast cancer and diet among the Japanese in Hawaii. Am. J. Clin. Nutr. 31:2020-2025. Nydegger, U. E., and R. E. Butler. 1972. Serum lipoprotein levels in patients with cancer. Cancer Res. 32:1756-1760. Palmer, R. H. 1979. Editorial: Bile acid heterogeneity and the gastrointestinal epithelium: From diarrhea to colon cancer. J. Lab. Clin. Med. 94:655-660. Pearce, M. L., and S. Dayton. 1971. Incidence of cancer in men on a diet high in polyunsaturated fat. Lance t 1:464-467. Peifer, J. J., and R. T. Holman. 1959. Effect of saturated fat upon essential fatty acid metabolism of the rat. J. Nutr. 68:155-168. Peterson, B., E. Trell, and N. H. Sternby. 1981. Low cholesterol level as risk factor for noncoronary death in middle-aged men. J. Am. Med. Assoc. 245:2056-2057. Phillips, R. L. 1975. Role of life-style and dietary habits in risk of cancer among Seventh-Day Adventists. Cancer Res. 35:3513-3522. Raicht, R. F., E. Deschner, and G. Salen. 1975. Bile acids regulate intestinal cell turnover. Gastroenterology 68:979. Abstract. Ranken, R., R. Wilson, and P. M. Bealmear. 1971. Increased turnover of intestinal mucosal cells of germfree mice induced by cholic acid. Proc. Soc. Exp. Biol. Med. 138:270-272. Reddy, B. S. 1979. Nutrition and colon cancer. Adv. Nutr. Res. 2: 199-218. Reddy, B. S., and K. Watanabe. 1979. Effect of cholesterol metabolites and promoting effect of lithocholic acid in colon carcinogenesis in germ-free and conventional F344 rats. Cancer Res. 39:1521-1524. Reddy, B. S., and E. L. Wynder. 1973. Large bowel carcinogenesis: Fecal constituents of populations with diverse incidence rates of colon cancer. J. Natl. Cancer Inst. 50:1437-1442. 5-30

OCR for page 73
Lipids (Fats and Cholesterol) 103 Reddy, B. S., J. H. Weisburger, and E. L. Wynder. 1974. Effects of dietary fat level and dimethylhydrazine on fecal acid and neutral sterol excretion and colon carcinogenesis in rats. J. Natl. Cancer Inst. 52:507-511. Reddy, B. S., S. Mangat, A. Sheinfil, J. H. Weisburger, and E. L. Wynder. 1977a. Effect of type and amount of dietary fat and 1,2-dimethylhydrazine on biliary bile acids, fecal bile acids, and neutral sterols in rats. Cancer Res. 37:2132-2137. Reddy, B. S., K. Watanabe, and J. H. Weisburger. 1977b. Effect of high-fat diet on colon carcinogenesis in F344 rats treated with 1,2-dimethylhydrazine, methylazoxymethanol acetate, or methylni- trosourea. Cancer Res. 37:4156-4159. Reddy, B. S., A. R. Hedges, K. Laakso, and E. L. Wynder. 1978. Metabolic epidemiology of large bowel cancer: Fecal bulk and constituents of high-risk North American and low-risk Finnish population. Cancer 42:2832-2838. Reddy, B. S., L. A. Cohen, G. D. McCoy, P. Hill, J. H. Weisburger, and E. L. Wynder. 1980. Nutrition and its relationship to cancer. Adv. Cancer Res. 32:237-345. Roebuck, B. D., J. D. Yager, Jr., and D. S. Longnecker. 1981. Dietary modulation of azaserine-induced pancreatic carcinogenesis in the rat. Cancer Res. 41:888-893. Rogers, A. E. 1975. Variable effects of a lipotrope-deficient, high-fat diet on chemical carcinogenesis in rats. Cancer Res. 35:2469-2474. Rogers, A. E., and P. M. Newberne. 1973. Dietary enhancement of intestinal carcinogenesis by dimethylhydrazine in rats. Nature 246:491-492. Rose, G., and M. J. Shipley. 1980. Plasma lipids and mortality: A source of error. Lancet 1:523-526. Rose, G., H. Blackburn, A. Keys, H. L. Taylor, W. B. Kannel, 0. Paul, D. D. Reid, and J. Stamler. 1974. Colon cancer and blood-choles- terol. Lancet 1:181-183. Rotkin, I. D. 1977. Studies in the epidemiology of prostatic cancer: Expanded sampling. Cancer Treat. Rep. 61:173-180. Roy, C. C., G. Laurendeau, G. Doyon, L. Chart rand, and M. R. Rivest. 1975. The effect of bile and of sodium taurocholate on the epithelial cell dynamics of the rat small intestine. Proc. Soc. Exp. Biol. Med. 149:1000-1004. 5-31

OCR for page 73
104 DIET, NUTRITION, AND CANCER Ryser, H. J.-P. 1971. Chemical carcinogenesis. N. Engl. J. Med. 285:721-734. Schuman, L. M., J. S. Mandell, 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, New York, and London. Silverman, J., C. J. Shellabarger, S. Holtzman, J. P. Stone, and J. H. Weisburger. 1980. Effect of dietary fat on X-ray-induced mammary cancer in Sprague-Dawley rats. J. Natl. Cancer Inst. 64:631-634. Stamler, J., D. M. Berkson, H. A. Linber, W. A. Miller, C. R. Soyugene, T. Tokish, and T. Whipple. 1968. Does hypercholesterolemia increase risk of lung cancer in cigarette smokers? Circulation Suppl. 6:188. Abstract. Sugai, M., L. A. Witting, H. TsuchIyama, and F. A. Kummerow. 1962. The effect of heated fat on the carcinogenic activity of 2-acetylaminofluorene. Cancer Res. 22:510-519. Tannenbaum, A. 1942. The genesis and growth of tumors. III. Effects of a high-fat diet. Cancer Res. 2:468-475. Tannenbaum, A. 1959. Nutrition and cancer. Pp. 517-562 in F. F. Hamburger, ed. The Physiopathology of Cancer, Second edition. Paul B. Hoeber, Inc., New York. Tannenbaum, A., and H. Silverstone. 1957. Nutrition and the genesis of tumours. Pp. 306-334 in R. W. Raven, ed. Cancer, Vol~e 1. Butterworth and Co., Ltd., London. Vahouny, G. V., M. M. Cassidy, F. Lightfoot, L. Grau, and D. Kritchevsky. 1981. Ultrastructural modifications of intestinal and colonic mucosa induced by free or bound bile acids. Cancer Res. 41:3764-3765. Watson, A. F., and E. Mellanby. 1930. Tar cancer in mice; Condition of skin when modified by external treatment or diet, as factors in influencing cancerous reaction. Br. J. Exp. Pathol. 11:311-322. Waxler, S. H. 1954. The effect of weight reduction on the occurrence of spontaneous mammary tumors in mice. J. Natl. Cancer Inst. 14:1253-1256. 5-32

OCR for page 73
Finials (Fats and Cholestero]) 105 Waxier, S. H., P. Tabar, and L. R. Melcher. 1953. Obesity and the tine of appearance of spontaneous mammary carcinoma in C3H mice. Cancer Res. 13:276-278. Westlund, K., and R. Nicolaysen. 1972. Ten-year mortality and morbidity related to serum cholesterol. Scand. J. Clin. Lab. Invest. Suppl. 127:1-24. White, F. R. 1961. The relationship between underfeeding and tumor formation, transplantation, and growth in rats and mice. Cancer Res. 21:281-290. White, F. R., J. White, G. B. Mider, M. G. Kelly, W. E. Heston, and P. W. David. 1944. Effect of caloric restriction on ~nammary-tu~nor formation in strain C3H mice and on the response of strain dba to painting with methylcholanthrene. J. Natl. Cancer Inst. 5:43-48. Wicha, M. S., L. A. Liotta, and W. R. Kidwell. 1979. Effects of free fatty acids on the growth of normal and neoplastic rat mammary epithelial cells. Cancer Res. 39: 426-435. Wieland, H., and E. Dane. 1933. [In German.] Untersuchungen uber die Konstitution der Gallensauren. LIT. Mitteilung uber die Haftstelle der Seitenkette. Hoppe Seylers Z. Physiol. Chem. 219:240-245. Williams, R. R., P. D. Sorlie, M. Feinleib, P. M. McNamara, W. B. Kannel, and T. R. Dawber. 1981. Cancer incidence by levels of cholesterol. J. Am. Med. Assoc. 245: 247-252. Williamson, R. C. N., F. L. R. Bauer, J. S. Ross, J. B. Watkins, and R. A. Malt. 1979. Enhanced colonic carcinogenesis with azoxy- ~nethane in rats after pancreaticobiliary diversion at mid small bowel. Gastroenterology 76: 1388-1392. 5 -33