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OCR for page 106
6 Protein
Dietary protein has often been associated with cancers of the
breast, endometrium, prostate, colorectum, pancreas, and kidney.
However, since the major dietary sources of protein (such as meat)
contain a variety of other nutrients and nonnutritive components, the
association of protein with cancer at these sites may not be direct
but, rather, could reflect the action of another constituent
concurrently present in protein-rich foods.
EPIDEMIOLOGICAL EVIDENCE
Armstrong and Doll (1975) examined incidence rates for 27 cancers
in 23 countries and mortality rates for 14 cancers in 32 countries and
correlated them with the per capita intake of a wide range of dietary
constituents and other environmental factors. These investigators
reported relationships between many of these variables. For example,
the correlations of total protein and animal protein with total fat
were 0.70 and 0.93, respectively, whereas correlations with the gross
national product were 0.32 and 0.65. In a study that analyzed diet
histories of more than 4,000 subjects, Kolonel et al. (1981) observed
that the correlation between total protein and total fat consumption
was 0.7.
Breast Cancer
In the study by Armstrong and Doll (1975) mentioned above, per
capita intakes of total protein and animal protein were significantly
correlated with the incidence of and mortality from breast cancer. In
a similar study, Knox (1977) compared per capita intakes of individual
foods and nutrients with the chief causes of mortality in 20 different
countries: Canada, the United States, Japan, and 17 European countries.
His results also indicated that there was a strong correlation between
the per capita intake of animal protein and mortality from breast can-
cer. Armstrong and Doll (1975) found that there was a stronger asso-
ciation for animal protein than for total protein, and in both of these
studies, the correlations of breast cancer with per capita total fat
intake were generally as strong or stronger than those for animal
protein.
Hems (1978) correlated 1970-1971 mortality rates for breast cancer
in 41 countries with per capita food intake for 1964-1966. He found a
direct correlation with intake of protein, total fat, and calories from
animal products, independent of other components of the diet. However,
time-trend data for breast cancer mortality and per capita food intake
106
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Protein 107
in England and Wales supported the association with fat more strongly
than the association with protein (Hems, 1980~. Gray et al. (1979)
analyzed international incidence and mortality rates for breast cancer
in relation to per capita intake of animal protein. They found a
direct correlation, even after controlling for height, weight, and age
at menarche.
Gaskill et al. (1979) examined age-adjusted breast cancer mortality
in relation to per capita intake for certain foods by state within the
United States. Although they found a direct correlation between breast
cancer mortality and per capita protein intake, this finding was not
statistically significant after controlling for age at first marriage
(as an indicator of age at first pregnancy). Kolonel et al. (1981)
found a direct correlation between consumption of animal protein and
the incidence of breast cancer in five different ethnic groups in
Hawaii based on diet histories obtained by interview.
Of three case-control studies of diet and breast cancer, signi-
ficant direct associations with dietary fat only were found in two
(Miller et al., 1978; Phillips, 1975), whereas direct associations
with both animal fat and protein were found in the third (Lubin et
al., 1981~.
Large Bowel Cancer
Gregor et al. (1969) reported a direct correlation between per
capita intake of animal protein and mortality from intestinal cancer
in 28 countries. Armstrong and Doll (1975) observed that per capita
intake of total protein, animal protein, and total fat were all strong-
ly correlated with the incidence of and mortality from colon and rectal
cancer for both sexes. Their findings for cancer at these sites were
similar to those for breast cancer (i.e., there were stronger correla-
tions for total fat and for animal protein than for total protein).
These authors also reported a strong association between the intake
of eggs and cancer of the colon and rectum. This association was
greater than that for total protein. In contrast to these direct
correlations, gingham et al. (1979) found no significant association
for intakes of animal protein in a study correlating the average
intakes of foods, nutrients, and fiber in different regions of Great
Britian with the regional pattern of mortality from colon and rectal
cancers.
Jain et al. (1980) reported the only case-control study of large
bowel cancer in which protein was specifically examined. Although
these investigators found a direct association between consumption of
high levels of protein and risk of both colon and rectal cancer, they
found a stronger association for saturated fat.
The relationship of meat intake to risk of colorectal cancer has
been examined in a number of studies, but protein intake per se was not
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108
DIET, NUTRITION, AND CANCER
estimated in most of them. However, because meat is a major source
of protein in the Western diet, findings in these studies may reflect
associations with protein. Berg and Howell (1974) and Howell (1975)
correlated international mortality rates for colon cancer with per
capita intake data and found the strongest correlations for meat,
especially beef. In a study by Armstrong and Doll (1975), the corre-
lations were stronger for meat than for total protein and animal pro-
tein. In studies of the relationship between certain foods and cancer
of the large intestine, Knox (1977) reported the strongest correlations
for eggs, followed by beef, sugar, beer, and pork. In contrast, time-
trend data for per capita beef intake and colorectal cancer incidence
and mortality in the United States showed no clear association (Enstrom,
1975).
Haenszel et al. (1973) studied cases of large bowel cancer and
hospital controls among Japanese in Hawaii. They found an associa-
tion between cancer at this site and consumption of legumes, starches,
and meats. The association was strongest for beef. A similar study
among Japanese in Japan (Haenszel et al., 1980) did not reproduce these
findings, nor did parallel case-control studies conducted in Norway and
Minnesota (Bjelke, 1978) and at the Roswell Park Memorial Institute
(Graham _ al., 1978~. All four of these case-control studies relied
solely on frequency of consumption data for their assessments of
dietary intake.
A somewhat contradictory observation was reported by Hirayama
(1981), whose large-scale cohort study in Japan indicated that there
was a decrease in overall risk for cancer, including intestinal cancer,
in association with daily intake of meat.
Pancreatic Cancer
Lea (1967) examined the relationship between per capita intake of
foods and nutrients and cancer mortality resulting from up to 22 dif-
ferent types of neoplasms in each of 33 countries. One of the findings
was a strong direct correlation between intake of animal protein and
pancreatic cancer. This result was reproduced by Armstrong and Doll
(1975~. No case-control or cohort studies have confirmed this asso-
ciation specifically; however, a study of pancreatic cancer cases and
controls in Japan (Ishii et al., 1968), based on responses to a mailed
questionnaire completed mostly by relatives of deceased cases, showed
an association of the disease with consumption of high-meat diets
by men. Hirayama (1977) reported a relative risk of 2.5 for daily meat
intake and pancreatic cancer incidence in Japan in a cohort of 265,118
subjects followed prospectively. Since meat is a major source of
protein in the diet, these findings offer tentative support for the
results of correlation studies.
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Protein 109
Other Cancers
l
Armstrong and Doll (1975) found a strong correlation (correlation
coefficient = 0.8) between animal protein and the incidence of renal
cancer. However, in a subsequent case-control study, Armstrong et al.
(1976) found no clear association between renal cancer and consumption
frequencies for several foods containing animal protein (e.g., meat,
poultry, seafood, eggs, milk, and cheese).
The incidence of prostate cancer was significantly correlated
with consumption of total and animal protein in the study by Kolonel
_ al. (1981), whereas mortality from, but not the incidence of,
prostate cancer was similarly correlated in the study by Armstrong and
Doll (1975~. As noted in Chapter 5, Hirayama (1977) reported a sharp
increase in the intake of animal protein in Japan since 1950. During
this period, the incidence of prostate cancer in that country increased
correspondingly. The intake of meat, especially beef, has also been
correlated with mortality from prostate cancer (Armstrong and Doll,
1975; Howell, 1974).
The incidence of endometrial cancer has also been significantly
correlated with the intake of total protein (Armstrong and Doll, 1975;
Kolonel _ al., 1981~. This finding may simply reflect the high
correlation between the occurrence of endometrial cancer and breast
cancer, since the latter has also been associated with protein intake
(see Chapter 16~. No case-control studies have been conducted to
examine this association.
EXPERIMENTAL EVIDENCE
There is much less literature on results of laboratory studies to
determine the relationship between cancer and dietary protein than has
been published for certain other nutrients (e.g., fat). However, an
inhibitory effect of selected amino acid deficiencies on tumor re-
sponses in laboratory animals was claimed as early as 1936 (Voegtlin
and Maver, 1936; Voegtlin and Thompson, 1936~. During the subsequent
30 years, further studies concentrated primarily on the effect of
protein intake on experimental animal models. From the end of that
period to the present, attention became increasingly focused on
epidemiological studies.
In general, animals fed minimum amounts of protein required for
optimum growth have developed fewer tumors than comparable groups
fed 2 to 3 times the minimum requirements. Unfortunately, a number
of these earlier studies in animals are difficult to interpret for
several reasons: several factors were being varied at the same time
(Engel and Copeland, 1952a; Gilbert et al., 1958; Ross and Bras, 1965~;
dietary levels of the carcinogen were different in the high and low
dietary protein groups (Harris, 1947~; the total intake of food was
less for animals fed very high levels of protein (Gilbert et al., 1958;
6 - 4
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110 DIET, NUTRITION,AND CANCER
Tannenbaum and Silverstone, 1949), and tumor growth is known to be
inhibited at lower food (and lower calorie) intake (Ross et al., 1970;
Tannenbaum, 1945a,b); and a high dietary level of fat, which may have a
tumor-enhancing effect, was present in the experimental diet (Ross and
Bras, 1973~. Nonetheless, several of the earlier reports have pro-
vided useful information either because they were well controlled or
because they have been confirmed by other studies.
When considering the effect of dietary protein, it is important to
determine whether such an effect is specific for a particular amino
acid or is a general effect of protein. In a well-controlled study,
Silverstone and Tannenbaum (1951) reported that the spontaneous hepa-
tomas in C3H mice were less frequent (measured as percent of tumor-
bearing animals) in animals fed a 9% casein diet than in animals fed
18% or 45% casein diets. No significant difference in hepatomas was
observed for the latter two dietary groups. All three diets were
isocaloric and were fed to the mice at equivalent time intervals. In
additional experiments, this effect of protein was still marked when
the animals were fed diets that maintained their individual body
weights. Therefore, the investigators concluded that the effect of
protein was neither confounded with total food or caloric intake nor
related to the change in body weight. Adding 9% gelatin to the 9%
casein diet had little effect, whereas supplementation of that diet
with methionine and cystine (which is present in relatively low levels
in gelatin) increased the incidence of hepatomas to the level observed
for the mice fed the 18% casein diet. Therefore, it is the excess of
total protein or its adequacy as indicated by amino acid balance that
generates the increased tumor response. The addition of gelatin may
have resulted in extra total protein, but it did not compensate for the
growth-limiting sulfur amino acids. In one experiment, the effects of
an animal protein (casein) and a plant protein (isolated soy protein)
were compared, but no significant difference in tumor incidence was
noted (Carroll, 1975~.
In earlier studies, Larsen and Heston (1945) found that cystine
added to a low casein diet given to Strain A male mice increased the
incidence of spontaneous pulmonary tumors from 28% to 54%. White and
Andervont (1943) observed that female C3H mice fed a cystine-deficient
casein diet exhibited no mammary gland tumors after 22 months, but
almost all the animals quickly developed tumors after their diets were
supplemented with cystine. Similarly, White and White (1944) observed
that mammary tumors occurred in only 25% of C3H mice fed a lysine-
deficient gliadin diet but in nearly all of the mice when the diet was
supplemented with lysine. White et al. (1947) later showed that only
cystine (but not lysine and tryptophan) was able to enhance the inci-
dence of 3-methylcholanthrene-induced leukemia in casein-fed mice.
Thus, it appears that tumor enhancement by dietary protein occurs only
when there is amino acid balance, suggesting that the effect is not due
to specific amino acids or to amino acid imbalance.
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Protein 111
The effect of dietary protein on tumor incidence has been observed
both with and without pretreatment with chemical carcinogens. That is,
both spontaneous and chemically induced tumor responses may be influ-
enced by the level of dietary protein. These two kinds of responses
may not be distinct, since certain so-called spontaneous tumors may be
related to the prior ingestion of, or other exposure to, some unknown
initiator of carcinogenicity. For example, Newberne et al. (1966)
speculated that the occasional high incidence of liver tumors observed
in earlier studies may have been caused by aflatoxin contamination of
peanut meal fed to animals. Because it is now known that corn products
may be similarly contaminated, results of earlier studies using degermi
nated corn grit diets should also be reevaluated, especially when an
unexpectedly high incidence of liver tumors has been observed, as in
the study of Engel and Copeland (1951~. Similarly, the appearance of
some presumably spontaneous tumors may be due to the very potent
mutagens produced in heated or cooked foods (Sugimura, 1979~.
Spontaneous Tumors
Ross and coworkers conducted extensive studies with large numbers
of rats in order to examine the effects of diet on mortality patterns
and lifespan (Ross and Bras, 1965, 1973; Ross et al., 1970~. They
focused on the influence of total food, caloric, and protein intake on
the appearance of a variety of tumors of unknown etiology. The total
incidence of various types of tumors was directly related to the intake
of calories, and the tumors appeared sooner when the caloric intake was
high (Ross and Bras, 1965~.
Because the rats developed many types of tumors, the investigators
could not compare the effect of diet on specific types of tumors. The
highest number of any tumor type for any one diet was 11--the number of
fibrosarcomas observed among the 210 animals in the 30% casein diet
group. The authors did note, however, that in two groups with identi-
cal caloric intake, there were more tumors in the group with the higher
protein intake. In these studies, only two of the four treatment
groups differed in only one dietary variable--the ratio of casein to
sucrose. The diet with the higher ratio contained 30% casein; the one
with the lower ratio contained 8Z casein. All other comparisons among
the treatment groups were confounded by two or more simultaneous
variables.
In a later study, Ross et al. (1970) reported that the prevalence
of chromophobe adenomas of the anterior pituitary gland of male rats
was directly related to the level of dietary protein (10%, 22%, or 51%
casein). However, the tumor prevalence was 2.4% or less in each treat-
ment group, which would seem to invalidate any such conclusions More-
over, the simple composition of the diet used in these studies is now
believed to be inadequate for studies of this type (Anonymous, 1977~.
In their most recent study, Ross and Bras (1973) examined the effect
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112 DIET, NUTRITION, AND CANCER
10%, 22%, and 51% casein on the development of 58 types of tumors, none
of which involved more than 10% of the rats. They found that protein
had no effect on animals fed ad libitum, but that there were fewer
tumor-bearing animals in groups fed the lower protein diets if the
daily food intake was restricted to 6 g.
In addition to the studies by Silverstone and Tannenbaum (1951) and
White and Andervont (1943) described above, other reports that dietary
protein affects "spontaneous" tumors are those of Slonaker (1931),
White and White (1944), and Tannenbaum and Silverstone (1949~. Although
Ross and Bras (1973) have interpreted the work of Slonaker (1931) as
having demonstrated an inverse relationship between protein intake and
tumor incidence (mammary gland and ovarian tumors in female rats and
skin tumors in male rats), further inspection of Slonaker's report is
necessary. Slonaker (1931) stated that the diets contained 10%, 14%,
18%, 22%, and 26% protein, but he did not describe the composition of
the diets. Moreover, the numbers of tumor-bearing female animals were
5/20, 6/19, 5/17, 2/16, and 4/21 for the low to high protein groups,
and the author, without providing histological evidence, concluded that
the tumors "became cancer-like in appearance." For the males, skin
cancers were found in 1/22, 1/21, 1/17, 0/14, and 0/13 animals for the
low to high protein groups. Therefore, no firm conclusions can be
drawn concerning the association of protein intake with tumor appear-
ance.
Tannenbaum and Silverstone (1949) described a study in which diets
containing from 9% to 45% protein were fed ad libitum to an inbred
strain of mice. The incidence of spontaneous hepatomas in the animals
fed 9% casein diets was 11/44; in the animals fed 18% casein diets, it
was 28/46. However, no significant effect on either the incidence or
the average time of appearance was observed for the spontaneous mammary
tumors.
Chemically Induced Tumors
More studies have been conducted to determine the relationship of
dietary protein to chemically induced tumors than to spontaneous tumors.
When aflatoxin is fed with varying levels of protein, the inci-
dence of liver tumors is depressed at lower protein intakes. Madbavan
and Gopalan (1968) incubated weanling or young rats with aflatoxin
and then fed them either 5% or 20% casein diets for 1 year. They
observed that the incidence of hepatomas in the two groups was 0/12
and 15/30, respectively. These data summarize results from experi-
ments that used different protocols. Wells et al. (1976) fed diets
containing 8%, 22Z, or 30Z casein with 1.7 m ~ kg aflatoxin B1
(AFB1) to male weanling rats for 3 months, then the same diets
without AFB1 for as long as 1 year. Hepatomas were found in 0/16,
6/9, and 8/10 rats, respectively. This finding confirmed the results
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Protein 113
of Madhavan and Gopalan (1968~. Similarly, Temcharoen et al. (1978)
fed male rats an equal mixture of aflatoxin B1 and G1 along with
diets containing either 5% casein or 20% casein for 33 weeks. They
found 4/47 hepatoma-bearing animals in the low protein group and 7/49
in the higher protein group, which is not in accord with their con-
clusion that "in animals fed a low-protein diet, aflatoxin induced
extensive . . . carcinogenic effects." In contrast to the incidence
of hepatomas, the incidence of cystic lesions, cholangiofibrosis,
cirrhosis, and hyperplastic nodules was higher among the animals fed
the low protein diets. This appears to be in agreement with the ob-
servations of other investigators that the effect of the level of
dietary protein on aflatoxin-induced hepatotoxicity is the opposite of
its effect on aflatoxin-induced carcinogenesis (Madhavan and Gopalan,
1965, 1968).
The effect of dietary protein on the emergence of precancerous
lesions is not clear from these studies. Madhavan and Gopalan (1968)
reported fewer "preneoplastic lesions" in the animals fed the low pro-
tein diet. But Temcharoen _ al. (1978) observed more "hyperplastic
nodules" and other lesions in the low protein groups, suggesting that
their study might have been confounded by the simultaneous appearance
of toxic and carcinogenic lesions. Madhavan and Gopalan (1968)
administered aflatoxin early in their studies and then discontinued
further administration; Temcharoen _ al. (1978) appeared to have
administered the toxin throughout the study, although this was not
explicitly stated. Part of the confusion about the association of low
protein intake and the hepatocarcinogenicity of aflatoxin results from
the use of the terms hepatotoxicity and hepatocarcinogenesis. These
effects are different, and have been used without definition in some
reports. Each of the studies cited above (i.e., Madhavan and Gopalan,
1968; Temcharoen et al., 1978; Wells et al., 1976) is singularly
inconclusive, but collectively they support the hypothesis that a high
protein diet enhances aflatoxin-induced hepatocarcinogenesis.
Morris _ al. (1948) found that more tumors of a greater variety
appeared in rats treated with N-acetyl-2-aminofluorene (2-AAF) and fed
synthetic diets containing 18% and 24% casein than in similarly treated
animals fed diets containing 12% casein. Engel and Copeland (1952b)
observed that dietary protein did not affect 2-AAF-induced tumors in
rats fed ad libitum with diets containing 9% to 27% casein. There was,
however, a highly significant reduction in the incidence of mammary
tumors in rats fed diets containing 40% to 60% casein. When the 9% and
60% protein diets were pair-fed, i.e., fed to two matched groups, the
incidence of mammary tumors was 80% and 12%, respectively. Ad libitum
feeding of the 60% protein diet, however, overcame some of the inhibi-
tion (77% incidence), indicating inhibition of tumorigenesis by very
high protein diets can be overcome by increasing food intake. Harris
(1947) concluded that protein had no effect on carcinogenesis induced
either by 2-AAF or by aminofluorene (AF), which was applied to the
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114 DIET, NUTRITION, AND CANCER
skin. In the 2-AAF-treated rats, reduction in the total incidence of
tumors from 65% to 45% in males and from 80% to 70% in females resulted
from a modest reduction in dietary casein from 20% to 13%. In animals
receiving the low protein diet, the incidence of liver tumors was de-
pressed from 50% to 30% in males and frown 207 to 0 in females.
Walters and Roe (1964) injected nice within 24 hours of birth with
9,10-dimethyl-1,2-benzanthracene (DMBA) and then fed them diets con-
taining either 25% or between 10% and 15% casein. The animals fed the
higher level of casein developed significantly snore lung tumors. In
contrast, other reports showed that a reduction of the protein content
of the diet enhanced the formation of DMBA-induced hepato~nas (Elson,
1958; Miller et al., 1941; Silverstone, 1948) and mammary tumors
(Clinton _ al., 1979) in rats. Clinton et al. (1979) studied the
effect of dietary protein levels on the incidence of DMBA-induced mam-
mary tumors in rats and observed that the effect of protein depended on
whether the dietary treatment occurred before or after the ad~ninistra-
tion of the carcinogen.
Topping and Visek (1976) studied the effect of dietary protein on
the induction of adenocarcinomas of the small and large intestines of
rats by 1,2-dimethylhydrazine. They observed that the tumors were
larger and more numerous in the rats fed diets containing 15% and 22.5%
protein than in those given 7.5Z protein diets. Moreover, the 22.5%
protein diets also caused an earlier appearance of keratin-producing
papillomas of the sebaceous glands of the external ear.
Shay et al. (1964) studied the effect of dietary protein on tu~nori-
genesis induced by 3-~nethylcholanthrene. They observed an increase in
mammary adenocarcinomas in pretreated rats fed high levels of protein
(27% to 64% casein). In an earlier study, White et al. (1947) reported
that a high protein diet enhanced 3-methylcholanthrene-induced leukemia
In mice.
Extensive studies have been undertaken to determine the mechanism
by which dietary protein alters AFBl-induced tu~norigenesis. A low
protein intake depresses the mixed-function oxygenate (Mgbodile and
Campbell, 1972) responsible for AFB1 ~netabolis~n as well as the
in viva formation of AFB1-DNA covalent adducts (Preston et al.,
1976~. Although Campbell (1979) suggested that modification of AFB
metabolism was responsible for the effect of dietary protein on AFB1
tu~norigenicity, more recent studies indicate that the effect of dietary
protein on events occurring after initiation may be more important.
For example, the development of Y-gluta~nyl transpeptidase hepatocellu-
ular foci, which is an excellent early indicator of hepatocarcinogenesis
(Tsuda et al., 1980), is greatly depressed in rats fed a 57 casein diet
compared to rats fed a 20% casein diet, both given after the ad~ninis-
tration of AFB1 is completed (Appleton and Campbell, 1981~. This
postinitiation effect of the low protein diet was even capable of over-
coming the potential carcinogenic effects of a higher AFB1-DNA adduct
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Protein 115
level, which had been established by feeding high levels of protein
during AFB1 administration.
Tumor Transplantation Studies
Low protein diets have also been associated with the general
inhibition of the growth of transplanted tumors. Haley and Williamson
(1960) implanted HAD-1 tumors into rats fed a diet with no protein and
rats fed a 20% casein control diet. They observed that the resultant
tumors were smaller in the no protein diet group. Earlier, Babson
(1954) had found that increasing dietary casein from 0 to 18% increased
tumor growth rates in rats implanted either with the Sarcoma R-1 tumor
or the Flexner-Jobling carcinosarcoma. According to Devik et al.
(1950), there was a prolonged inflammatory reaction to the implantation
of the Walker carcinosarcoma 256 and incomplete connective tissue
encapsulation in animals fed 5% casein diets, compared to animals fed
20% casein diets.
White and Belkin (1945) studied the effect of low protein diets on
the "take" of implanted mammary carcinoma 15091a. Although the number
of takes was higher (16/31) in the protein-deficient group than in the
adequate dietary protein group (10/31), the growth rate at 3 weeks was
only 74% of the rate for the higher protein diet. These tumor implan-
tation studies were later summarized by White (1961~.
The mechanism for the inhibition of tumor growth by low protein
diets is not known. Jose and Good (1973) have proposed that the cellu-
lar immune response may be involved. This response is enhanced through
a deficiency of blocking serum antibody production at low levels of
protein intake.
An Evaluation of the Data from Animal Studies
The relationship of dietary protein to the carcinogenic process
does not appear to be straightforward. Levels of protein ranging from
those somewhat below the minimum required for optimum growth (approxi-
mately 5% of the diet) up to those generally consumed by mammals (15%
to 20%) have been studied most extensively. In many studies in animals,
diets with low protein (near or below the requirement for optimum
growth) have generally been shown to suppress the carcinogenic process
and the subsequent growth and development of tumors. The only apparent
exception to this effect is the increase in DMBA-induced tumor yield in
animals fed low protein diets. Although there is generally a tumor-
enhancing effect from 20% to 25% dietary protein, higher levels appear
either to produce no further enhancement or, in fact, to inhibit tumor-
igenesis (Appleton and Campbell, 1981; Engel and Copeland, 1952b; Ross
and Bras, 1973; Ross et al., 1970; Saxton et al., 1948; Tannenbaum and
Silverstone, 1949; Topping and Visek, 1976; Wells et al., 1976~. It is
not clear whether the general inhibition or the absence of effect on
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116 DIET, NUTRITION, AND CANCER
tumorigenesis at very high levels of dietary protein is due to a
reduced intake of food and total calories or whether it is due to other
adverse effects, e.g., renal toxicity due to high levels of protein.
SUMMARY
En idling al Phi r~ 1 Pvi H - nor
Epidemiological studies have suggested possible associations
between high levels of dietary protein and increased risk of cancers
at a number of different sites. However, the literature on protein is
much more limited than the literature concerning fats and cancer. In
addition, because of the very high correlation between fat and protein
intake in Western diets, and the more consistent and often stronger
association of these cancers with fat intake, it seems more likely
that dietary fat is the more active component. Nevertheless, the evi-
dence does not completely preclude an independent effect of protein.
Experimental Evidence
In laboratory experiments, the relationship of dietary protein to
carcinogenesis appears to depend upon the level of protein intake. In
most studies, carcinogenesis was suppressed by diets containing levels
of protein at or below the minimum required for optimum growth.
Chemically induced carcinogenesis appears to be enhanced as protein
intake is increased up to 2 or 3 times the normal requirement; however,
higher levels of protein begin to inhibit carcinogenesis. There is
some evidence to suggest that protein may affect the initiation phase
of carcinogenesis and/or the subsequent growth and development of the
tumor.
CONCLUSION
Thus, evidence from both epidemiological and laboratory studies
suggests that protein intake may be associated with an increased risk
of cancers of certain sites. Because of the relative paucity of data
on protein compared to fat, and the strong correlation between intakes
of fat and protein in the Western diet, the committee is unable to
arrive at a firm conclusion about an independent effect of protein.
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REFERENCES Protein 117
Anonymous. 1977. Report of the American Institute of Nutrition, Ad
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Appleton, B. S., and T. C. Campbell. 1981. Effects of dietary protein
level and phenobarbital (PB) on aflatoxin (AFBl)-induced hepatic
y-glutamyl transpeptidase (GOT) in the rat. Fed. Proc. Fed. Am.
Soc. Exp. Biol. 40:842. Abstract 3477.
Armstrong, B., and R. Doll. 1975. Environmental factors and cancer
incidence and mortality in different countries, with special
reference to dietary practices. Int. J. Cancer 15:617-631.
Armstrong, B., A. Garrod, and R. Doll. 1976. A retrospective study of
renal cancer with special reference to coffee and animal protein
consumption. Br. J. Cancer 33:127-136.
Babson, A. L. 1954. Some host-t~nor relationships with respect
to nitrogen. Cancer Res. 14:89-93.
Berg, J. W., and M. A. Howell. 1974. The geographic pathology of
bowel cancer. Cancer 34:805-814.
gingham, S., D. R. R. Williams, T. J. Cole, and W. P. T. James. 1979.
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Representative terms from entire chapter:
animal protein
