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.
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