Abu Hannah
Slave of Allah
FAT AND CANCER
During the past five decades, the influence of dietary fat on the development of certain forms of cancer has led to the conclusion that there is a good positive correlation between the dietary pork fat consumption and cancer rates of the colon, breast, prostate. endometrium, pancreas, and of the biliary system.
These correlations have arisen from three kinds of evidence. First, descriptive epidemiologic studies which focus on the effect of fat, especially lard, on cancer incidence and mortality rates among different countries and among population groups who have different fat intake and different dietary habits such as the Seventh-Day Adventists. Second, evidence came from experimental studies. These experimental studies have been assisted by the discovery of several animal models in which a lesion mimicing human lesionscan be induced chemically. In these models, animals which have been fed a high lard diet developed more colon and breast tumors than animals fed low lard diets.
Third, strong evidence relating the etiology of the above-mentioned cancer to lard came from migrant studies. Within two to three generations, Japanese migrants to the U.S.A. experience an increase in cancer incidence rates. Breast cancer in Japanese-American women had risen to five times that of age-matched native Japanese women during the years 1969-1971 .The same is true for the Police immigrants to the United States These migrant studies exclude the possibility of genetic variations.
Current evidence indicates that the possible mechanisms by which dietary pork fat could playa promoting effect in human carcinogenesis could be through: 1) its effects on the production, activation, or inactivation of carcinogens by the intestinal flora, 2) its effect on the endogenous production, activation, or inactivation of carcinogens or 3) its effect on tissues to alter their susceptibility to carcinogenesis.
Correlation studies between different sources of fat and breast cancer concluded that the highest positive correlation was found for pork fat, followed by other animal fat intake and that a similar association could not be found for vegetable fat.
DIETARY FAT AND COLON CANCER
Cancer of the colon has been the subject of several epidemiologic, migrant, and experimental studies. The highest incidence rates are found in North America, New Zealand, and Western Europe (Fig.1). The lowest incidences are found in Africa, Asia, and Latin America.
Epidemiological studies have shown food preferences, especially fat, to be associated with high- and low-risk populations. Such correlations between fat intake and colon cancer mortality is supported by experimental evidence from animal models. A worldwide correlation between colon cancer incidence and total fat consumptions has been established (Fig. 2).
Migrant studies have shown that Japanese migrants to the U.S.A. experience an increase in colon cancer incidence rates from those rates common in Japan. This observation suggests that environmental factors, rather than genetic characteristics, account for a substantial part in the etiology of colon cancer. Comparative studies to search for factors that link the foods of individual groups within a small geographical area to their colon cancer risks indicated that the Seventh-Day Adventists, who do not consume pork and adhere to a vegetarian diet have 30-40% less colon cancer death rate of a comparable general population sample.
Similarly, the incidence of colon cancer in Mormons, who eat more whole-grain breads, fruit and vegetables and do not eat pork, also have lower colon cancer than other U.S. white population.
Wynder, et al and others, proposed that colon cancer incidence is mainly associated with total dietary fat. Gregor, et al proposed that fat acts as a promoter rather than an initiator during cancer development.
The mechanisms by which dietary fat causes colon cancer has been hypothesized to be as follows: 1) the amount of dietary fat determines both the concentration of acid and neutral sterol substrates in the large bowel and also the composition of the microflora acting on such substrates. 2) The gut microflora metabolizes acid and neutral sterols to carcinogens active in the large bowel. The bacteria alters the structure of colonic steroid and they become potential carcinogenic since their overall structure is similar to carcinogenic polycyclic aromatic hydrocarbons (PAH) and they may be converted chemically to 3-methylcholanthrene. Also, human gut flora have been shown to achieve partial aromatization of the sterol ring system, and full aromatization of the bile and nucleus would yield a carcinogen metabolite. Such microflora-mediated reactions are unlikely to yield polycyclic aromatic hydrocarbons from bile-salts but are more likely to yield products that act as colon tumor-promotors or co-carcinogens rather than as complete carcinogens.
Thus, a high-fat diet may not only change the composition of bile acids but also modify the activity of gut microflora which may,in turn,produce tumor-promoting substances from bile acids in the lumen of the colon.
Additional support to the role of dietary lard in the induction of colon cancer in man came from experimental studies in which intestinal tumors were induced chemically. Animals fed on a high-Iard (20%) diet developed more intestinal tumors and more metastasis than rats fed low-Iard diets (5%) (Table 1).
DIETARY FAT AND CANCER OF THE BREAST
Epidemiological studies have generated hypothesis for the etiology of breast cancer through international comparison of incidence, case-control studies, migration studies and experimental studies. Such studies have provided the basis for the influence of nutrition and fat, in particular on breast cancer incidence.
High breast cancer incidences are found in the U.S.A. and Western Europe and low rates in Asia, particularly Japan (Fig. 3).
The strongest evidence for environmental factors in the etiology of breast cancer is found in the results of migrant studies. Within two to three generations, Japanese migrants to the U.S.A. experienced an increase in cancer incidence rates from those common in Japan (Fig. 4). During 1969-1971 the incidence of breast cancer in Japanese-American women had risen to five times that of age-matched native Japanese women.
Alterations in dietary practice, especially the increase in pork fat intake, appear to be the factor that best accounts for the increase in breast cancer incidence.
A positive correlation between breast cancer mortality and daily per capita consumption of fat has been demonstrated by a number of researchers (Fig. 5). Hirayama correlated breast cancer incidence in 12 different districts of Japan with specific food consumption patterns. Of the food items studied, the highest positive correlation was found for pork followed by total animal fat intake.
Experimental studies showed that spontaneous breast tumor incidence rates in female DBA mice were )mall higher in those fed an isocaloric high-fat diets than those fed a low-fat diet and through all the experimental studies one point stands out clearly: high intake of dietary fat increases the incidence of mammary cancer in rodents.(Fig. 6)
The possible mechanism(s) by which dietary fat may exert its effect on breast cancer have been ~1nd postulated by Hopkins and West and others to be: a) direct effects at the level of the mammary gland. These effects are based on the physical and chemical properties of fat, the formation of lipid peroxides, alterations in membrane structure and/or function, and enhanced prostaglandin synthesis. Since polyunsaturated fatty acid (PUFA) is converted by free radical reactions to lipid peroxides, a model involving breast cancer and lipid peroxidation has been advanced. Lipid peroxidation has been associated with a variety of the pathological process including mutagenesis and carcinogenisis. It is possible that increased peroxidation of membrane lipids results in alterations in the function of transformed mammary cell membrane which, in turn, acid permit increased rates of growth, or that lipid peroxidation and free radical processes accompanying it are primarily associated with the activation of procarcinogens. Since lard contains 67% polyunsaturated fatty acid, its effect is more prominent in the process of carcinogenesis. b) Indirect effects of fat could be mediated by host systems remote from the mammary gland. In this case the dietary fat secondarily stimulates mammary full tumor growth by modifying the physiology of the host through altering the: 1) immune rejection responses, 2) ons mixed function oxidases, and 3) endocrine control system. Also, fat has an enhancing effect on breast cancer that development through altering the circulating prolactin levels but not estrogen levels. Prolactin is proposed to mediate the fat effect by virtue of its duel capacity as a liporegulatory hormone and as a promoter of mammary gut tumor development.
DIETARY FAT AND CANCER OF THE PROSTATE
Cancer of the prostate is common in the U.S. and western countries and uncommon in Japan and Africa (Fig. 7). One striking difference between diets in high- and low-risk areas is the fat intake (Fig. 8) which accounts for 40% of the daily calories in high-risk areas and 20% calories in low-risk areas.
Clinical studies have shown that the connecting link between dietary fat and the incidence of prostatic cancer is hormonally dependent. Any factor that affects hormonal secretion, retention, and, in particular, the sensitivity of the target organ and/or cells influences the frequency of this cancer. Since fat may modify hormonal systems, it has the potential of inhibiting or enhancing tumorogenesis.
DIETARY FAT AND ENDOMETRIAL CANCER
The incidence of endometrial cancer is highly correlated wth levels of fat consumption (Fig. 9). The of incidence of endometrial cancer is also highly correlated with those of breast cancer and colon cancer, which are also both thought possibly to be causally related to fat consumption.Epidemiologic studies have identified the following factors as associated with a high individual risk of endometrial cancer: obesity , early menarche, late menopause, diabetes mellitus, and excessive production of estrogen and all of these factors may be explicable through a common mechanism which is dietary excess of fat.The precise role of estrogens in the genesis of endometrial cancer is still uncertain. It has been suggested that estrone may be directly carcinogenic. It is possible, however, that excessive endometrial stimulation by estrogens may facilitate the action of other carcinogens. If this is the case and diet is the principal determinant of excessive estrogen production in women with endometrial cancer, then this is another example of an effect of diet on the susceptibility of a tissue to carcinogenesis.
Seventh-Day Adventist women in general (about 50% of whom are vegetarian) have about a 40% lower mortality from endometrical cancer than the general population. This is consistent with the role of fat in the incidence of endometrial cancer .
DIETARY FAT AND CANCER OF THE PANCREAS
Studies on imigrants have provided valuable information on the influence of fat in the genesis of pancreatic cancer. A study on Japanese immigrants to the U.S.A. showed that the standardized mortality rates, for pancreatic cancer was higher among Japanese Americans as compared with white Americans. Similarly, the rate incidence of pancreatic cancer among religious groups who adhere to non-pork diets, such as Seventh-Day Adventists, are all in the vicinity of 50-75% of the general rates.
The hypothesis for the etiology of pancreatic cancer by Wynder is that fat causes an increase in bile excretion which, in turn, may contain carcinogens and/or co-carcinogens and promoters and that this bile, refluxed into the pancreatic duct, may cause pancreatic cancer. Also, the effect of fats on the composition of the biliary bile acid have been shown to act as promoters.
During the past five decades, the influence of dietary fat on the development of certain forms of cancer has led to the conclusion that there is a good positive correlation between the dietary pork fat consumption and cancer rates of the colon, breast, prostate. endometrium, pancreas, and of the biliary system.
These correlations have arisen from three kinds of evidence. First, descriptive epidemiologic studies which focus on the effect of fat, especially lard, on cancer incidence and mortality rates among different countries and among population groups who have different fat intake and different dietary habits such as the Seventh-Day Adventists. Second, evidence came from experimental studies. These experimental studies have been assisted by the discovery of several animal models in which a lesion mimicing human lesionscan be induced chemically. In these models, animals which have been fed a high lard diet developed more colon and breast tumors than animals fed low lard diets.
Third, strong evidence relating the etiology of the above-mentioned cancer to lard came from migrant studies. Within two to three generations, Japanese migrants to the U.S.A. experience an increase in cancer incidence rates. Breast cancer in Japanese-American women had risen to five times that of age-matched native Japanese women during the years 1969-1971 .The same is true for the Police immigrants to the United States These migrant studies exclude the possibility of genetic variations.
Current evidence indicates that the possible mechanisms by which dietary pork fat could playa promoting effect in human carcinogenesis could be through: 1) its effects on the production, activation, or inactivation of carcinogens by the intestinal flora, 2) its effect on the endogenous production, activation, or inactivation of carcinogens or 3) its effect on tissues to alter their susceptibility to carcinogenesis.
Correlation studies between different sources of fat and breast cancer concluded that the highest positive correlation was found for pork fat, followed by other animal fat intake and that a similar association could not be found for vegetable fat.
DIETARY FAT AND COLON CANCER
Cancer of the colon has been the subject of several epidemiologic, migrant, and experimental studies. The highest incidence rates are found in North America, New Zealand, and Western Europe (Fig.1). The lowest incidences are found in Africa, Asia, and Latin America.
Epidemiological studies have shown food preferences, especially fat, to be associated with high- and low-risk populations. Such correlations between fat intake and colon cancer mortality is supported by experimental evidence from animal models. A worldwide correlation between colon cancer incidence and total fat consumptions has been established (Fig. 2).
Migrant studies have shown that Japanese migrants to the U.S.A. experience an increase in colon cancer incidence rates from those rates common in Japan. This observation suggests that environmental factors, rather than genetic characteristics, account for a substantial part in the etiology of colon cancer. Comparative studies to search for factors that link the foods of individual groups within a small geographical area to their colon cancer risks indicated that the Seventh-Day Adventists, who do not consume pork and adhere to a vegetarian diet have 30-40% less colon cancer death rate of a comparable general population sample.
Similarly, the incidence of colon cancer in Mormons, who eat more whole-grain breads, fruit and vegetables and do not eat pork, also have lower colon cancer than other U.S. white population.
Wynder, et al and others, proposed that colon cancer incidence is mainly associated with total dietary fat. Gregor, et al proposed that fat acts as a promoter rather than an initiator during cancer development.
The mechanisms by which dietary fat causes colon cancer has been hypothesized to be as follows: 1) the amount of dietary fat determines both the concentration of acid and neutral sterol substrates in the large bowel and also the composition of the microflora acting on such substrates. 2) The gut microflora metabolizes acid and neutral sterols to carcinogens active in the large bowel. The bacteria alters the structure of colonic steroid and they become potential carcinogenic since their overall structure is similar to carcinogenic polycyclic aromatic hydrocarbons (PAH) and they may be converted chemically to 3-methylcholanthrene. Also, human gut flora have been shown to achieve partial aromatization of the sterol ring system, and full aromatization of the bile and nucleus would yield a carcinogen metabolite. Such microflora-mediated reactions are unlikely to yield polycyclic aromatic hydrocarbons from bile-salts but are more likely to yield products that act as colon tumor-promotors or co-carcinogens rather than as complete carcinogens.
Thus, a high-fat diet may not only change the composition of bile acids but also modify the activity of gut microflora which may,in turn,produce tumor-promoting substances from bile acids in the lumen of the colon.
Additional support to the role of dietary lard in the induction of colon cancer in man came from experimental studies in which intestinal tumors were induced chemically. Animals fed on a high-Iard (20%) diet developed more intestinal tumors and more metastasis than rats fed low-Iard diets (5%) (Table 1).
DIETARY FAT AND CANCER OF THE BREAST
Epidemiological studies have generated hypothesis for the etiology of breast cancer through international comparison of incidence, case-control studies, migration studies and experimental studies. Such studies have provided the basis for the influence of nutrition and fat, in particular on breast cancer incidence.
High breast cancer incidences are found in the U.S.A. and Western Europe and low rates in Asia, particularly Japan (Fig. 3).
The strongest evidence for environmental factors in the etiology of breast cancer is found in the results of migrant studies. Within two to three generations, Japanese migrants to the U.S.A. experienced an increase in cancer incidence rates from those common in Japan (Fig. 4). During 1969-1971 the incidence of breast cancer in Japanese-American women had risen to five times that of age-matched native Japanese women.
Alterations in dietary practice, especially the increase in pork fat intake, appear to be the factor that best accounts for the increase in breast cancer incidence.
A positive correlation between breast cancer mortality and daily per capita consumption of fat has been demonstrated by a number of researchers (Fig. 5). Hirayama correlated breast cancer incidence in 12 different districts of Japan with specific food consumption patterns. Of the food items studied, the highest positive correlation was found for pork followed by total animal fat intake.
Experimental studies showed that spontaneous breast tumor incidence rates in female DBA mice were )mall higher in those fed an isocaloric high-fat diets than those fed a low-fat diet and through all the experimental studies one point stands out clearly: high intake of dietary fat increases the incidence of mammary cancer in rodents.(Fig. 6)
The possible mechanism(s) by which dietary fat may exert its effect on breast cancer have been ~1nd postulated by Hopkins and West and others to be: a) direct effects at the level of the mammary gland. These effects are based on the physical and chemical properties of fat, the formation of lipid peroxides, alterations in membrane structure and/or function, and enhanced prostaglandin synthesis. Since polyunsaturated fatty acid (PUFA) is converted by free radical reactions to lipid peroxides, a model involving breast cancer and lipid peroxidation has been advanced. Lipid peroxidation has been associated with a variety of the pathological process including mutagenesis and carcinogenisis. It is possible that increased peroxidation of membrane lipids results in alterations in the function of transformed mammary cell membrane which, in turn, acid permit increased rates of growth, or that lipid peroxidation and free radical processes accompanying it are primarily associated with the activation of procarcinogens. Since lard contains 67% polyunsaturated fatty acid, its effect is more prominent in the process of carcinogenesis. b) Indirect effects of fat could be mediated by host systems remote from the mammary gland. In this case the dietary fat secondarily stimulates mammary full tumor growth by modifying the physiology of the host through altering the: 1) immune rejection responses, 2) ons mixed function oxidases, and 3) endocrine control system. Also, fat has an enhancing effect on breast cancer that development through altering the circulating prolactin levels but not estrogen levels. Prolactin is proposed to mediate the fat effect by virtue of its duel capacity as a liporegulatory hormone and as a promoter of mammary gut tumor development.
DIETARY FAT AND CANCER OF THE PROSTATE
Cancer of the prostate is common in the U.S. and western countries and uncommon in Japan and Africa (Fig. 7). One striking difference between diets in high- and low-risk areas is the fat intake (Fig. 8) which accounts for 40% of the daily calories in high-risk areas and 20% calories in low-risk areas.
Clinical studies have shown that the connecting link between dietary fat and the incidence of prostatic cancer is hormonally dependent. Any factor that affects hormonal secretion, retention, and, in particular, the sensitivity of the target organ and/or cells influences the frequency of this cancer. Since fat may modify hormonal systems, it has the potential of inhibiting or enhancing tumorogenesis.
DIETARY FAT AND ENDOMETRIAL CANCER
The incidence of endometrial cancer is highly correlated wth levels of fat consumption (Fig. 9). The of incidence of endometrial cancer is also highly correlated with those of breast cancer and colon cancer, which are also both thought possibly to be causally related to fat consumption.Epidemiologic studies have identified the following factors as associated with a high individual risk of endometrial cancer: obesity , early menarche, late menopause, diabetes mellitus, and excessive production of estrogen and all of these factors may be explicable through a common mechanism which is dietary excess of fat.The precise role of estrogens in the genesis of endometrial cancer is still uncertain. It has been suggested that estrone may be directly carcinogenic. It is possible, however, that excessive endometrial stimulation by estrogens may facilitate the action of other carcinogens. If this is the case and diet is the principal determinant of excessive estrogen production in women with endometrial cancer, then this is another example of an effect of diet on the susceptibility of a tissue to carcinogenesis.
Seventh-Day Adventist women in general (about 50% of whom are vegetarian) have about a 40% lower mortality from endometrical cancer than the general population. This is consistent with the role of fat in the incidence of endometrial cancer .
DIETARY FAT AND CANCER OF THE PANCREAS
Studies on imigrants have provided valuable information on the influence of fat in the genesis of pancreatic cancer. A study on Japanese immigrants to the U.S.A. showed that the standardized mortality rates, for pancreatic cancer was higher among Japanese Americans as compared with white Americans. Similarly, the rate incidence of pancreatic cancer among religious groups who adhere to non-pork diets, such as Seventh-Day Adventists, are all in the vicinity of 50-75% of the general rates.
The hypothesis for the etiology of pancreatic cancer by Wynder is that fat causes an increase in bile excretion which, in turn, may contain carcinogens and/or co-carcinogens and promoters and that this bile, refluxed into the pancreatic duct, may cause pancreatic cancer. Also, the effect of fats on the composition of the biliary bile acid have been shown to act as promoters.
