Dietary
fats
Kenneth
and cancer3
K Carroll
ABSTRACT
Evidence
relating
such
as the breast
and
is provided
that
animals
readily data
colon
fed high-fat
diets
dietary
fat to cancer
at sites
by experiments
develop
cancer
showing
at these
sites
more
ever,
than do animals fed low-fat diets and by epidemiological from different countries showing strong positive correlations
between
cancer
incidence
and
mortality,
and
level
ofdietary
fat.
Experiments
on animals have indicated that polyunsaturated vegetable oils promote cancer more effectively than do saturated fats or polyunsaturated fish oils, whereas in the epidemiological data, total dietary fat correlates with cancer incidence and mortality
at least
as well
as does
any
particular
type
of fat.
the rats fed the high-corn-oil diet developed mammary tumors as did rats in the other analysis
DMBA
content
twice
of the
as many
(4). How-
mammary
glands
of
animals on the different diets provided little support for the original idea that dietary fat might affect the distribution and/or metabolism of the carcinogen (5). The observation that dietary fat affected the tumor yield stimulated our interest in the possibility that it might influence breast cancer
in humans,
ferent
countries
breast
Case-
of the
about
two groups
cancer
and
examination
showed
of data
a strong
mortality
and
positive
dietary
collected
from
correlation
fat available
dif-
between
for consumption
control and cohort studies have not shown strong indications ofa relationship between dietary fat and cancer, perhaps because
(6).
ofmethodological
that showed that high-fat diets increased the incidence and yield of mammary cancer in mice and rats (8, 9). This was an active field ofinvestigation during the l940s and 1950s but then interest waned, presumably because epidemiological data on humans were not available at that time and the results ofthe experiments on animals had no perceived relevance to human cancer.
difficulties
ofevidence
continues
low-fat
diet
can
reduce
the
Am J C/in
cancer.
KEY
WORDS
etary
fat,
inherent
to indicate
Nutr
Breast,
risk
studies.
long-term
of
The
weight
adherence
some
fats,
pancreas, saturated
to a
common
types
of
prostate,
cancer,
di-
fat,
fish
oil
Introduction
Dietary
The role ofdietary fats in cancer has been under investigation in our laboratory for the past 25 y. The work originated from studies
by one
of my
colleagues,
ER
Plunkett,
EB Gammal, who were investigating on mammary cancer in rats. For this purpose the tumors with 7,l2-dimethylbenz(a)anthracene student,
described whether in the
by Huggins the hormonal mammary
and
his graduate
effects of hormones they were inducing (DMBA), as
et al (1). They were interested treatment affected the levels
gland,
and
I and
one
in knowing of carcinogen
of my graduate
the
carcinogenic As a first
mammary carried diets
exposure
mammary
compounds. approach to determining
tumors out
containing
oil or coconut
of the
by DMBA
an experiment 0.5% oil (high
was related in which
corn
whether rats
oil (low-fat)
polyunsaturated
to these induction
of
to its fat solubility,
we
were or 20%
fed semipurified of either
or saturated
the time ofweaning and given a single intragastric at 50 d of age (1). The results of this experiment 10645
the
from
dose of DMBA showed that
Am J C/in Nuir
was
noted
at about
l991;53:1064S-7S.
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/4/1064S/4715101 by Emil Unanue on 08 August 2018
mammary
the
same
time
by Lea
cancer
studies
The combined evidence from periments on animals stimulated project,
with
ferent
types
the
aim
and
levels
human epidemiology and cxus to continue work on the
of investigating ofdietary
further
fat and
the
effects
attempting
of dif-
to determine
of action.
carried
out
with
Hun-Teik
Khor,
a graduate
student
from Malaysia, showed that the tumor yield could be enhanced by feeding a high-fat diet only after giving the carcinogen, indicating
that
affecting
initiation
ofdifferent
dietary
had
little
fat
was
fats increased
effect
acting
as a promoter
of tumors (10). Experiments fats also confirmed the earlier
dietary
polyunsaturated
(1 1). These
tumor studies
yields and
the
rather
than
with a variety indication that
while
saturated
available
fats
epidemio-
logical data are summarized in two review articles ( 1 2, 13). It seemed probable that the differing effects of polyunsaturated and saturated fats were related to differences in their content
I
corn
fat)
Experimental
Studies
students,
epithelium
fat and
its mechanism
B Muhlstock, assisted them in developing an assay of DMBA for this purpose (2). DMBA is a fat-soluble compound that induces mammary cancer quite specifically in young female rats. In attempting to explain this specificity of polycyclic hydrocarbons, Dao et al (3) suggested that because oftheir solubility in fat, they accumulate and persist in the adipose tissue of the mammary gland, thus increasing
correlation
(7) for cancer at several different sites, including the breast. A search of the literature also revealed earlier studies
199 1;53: 10645-75.
colon,
polyunsaturated
in such that
This
tario, 2
From the Department of Biochemistry, University London, Ontario, Canada. Supported by the Dairy Bureau of Canada.
of Western
of
On-
3 Address reprint requests to KK Carroll, Department of Biochemistry, University of Western Ontario, London, Ontario NA 5Cl , Canada.
Printed
in USA.
© 1991 American
Society
for Clinical
Nutrition
DIETARY linoleic
acid,
since
essential
fatty
This
verified
was
vegetable
this
acid
oil,
n-6
that
work and
small
and
quently,
the
type
dietary
both
a high
of dietary fats
mortality
this
apparent
the
diets
countries
effect,
so that
fat and
breast
amount
rather
than
not
promote
Similar
and
Because
fish
and
acids,
the
observed studies
mainly
be due in which
vegetable Effects
high olive
on
to inhibit
effects
mixtures
mammary
which
fatty fatty
on mammary
fatty
acids
results of oleic
to promote
some
of the
but
in mice,
not with
oleic
found acid.
with olive oil may be influenced acid.
Rapeseed
(22: 1n-9)
did
periments
(1 1), but the
fatty
oils
on tu-
acids.
Sub-
not
acid
replaced same acids
a newer by
extent affected
a high
mammary
oleic
variety acid
as did olive mammary
inves-
obtained
with
(18: ln-9).
tumorigen-
that it was et al (25),
much less in studies
association possible
other
than
content
in which oil (26).
with
that
results
in our
most the
ex-
of the erucic
tumor
yield
A fat containing
tumorigenesis
acid
in much
to 38% the
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/4/1064S/4715101 by Emil Unanue on 08 August 2018
the
yield
oil
showed
content of mamthat
tumors it contains
less than
promotion,
oftocotrienols the
it
induced but other
compared
with
results.
are,
cancer
diet
ofdietary
fat (20).
diets
is derived
from
specific
and
effects
animals. The fats and oils whose
This
of particular with
the
the amount
be because
the
of sources,
which
fatty
These
acids.
results
latter often involve unique composition
effects of particular of case-control and
it appears
than
may
a variety
compatible
mortality
countries,
as well as or better
type
therefore,
incidence
in various
of studies
on
the feeding of makes it easier
fatty acids. cohort studies
have
generally
failed to provide strong support for an association between dietary fat and breast cancer (30-34). However, this does not invalidate the hypothesis that dietary fat is an important factor there
in dietary
are methodological
problems
habits
between
people
corngenetic small
at sites
within
ofthe
early
tumors, tumors diets.
More
experimental
recently,
studies
the
The
effects
results
that
fed high-fat
diets. In this case, there the effects of saturated the
have
these
can-
a higher with
incidence those
fed
fat on colon
tumors
investigated
extensively
tumors
compared
also develop
with
those
inmore
fed low-fat
is less indication of differences between fats and polyunsaturated vegetable oils
requirement
to be less than
been
fat and
in mice by polycyclic 1 3, 38). As with mam-
compared
of dietary
showed
on dietary
showed
fed high-fat
carcinogens
in animals
and
than
induced light (9,
consistently
in animals
by various 40).
other
studies
the results
(41),
living
(35-37).
mary
readily
such
a country
on skin cancer or by ultraviolet
duced
with
in different countries; and the be more important in comparing
cer were done hydrocarbons ofskin low-fat
associated
include the difficulty of measuring dietary fat inin terms ofpast intake; the smaller differences
pared to people living component, which can
seems
its content
of erucic
of the
to obscure
to distinguish The results
(39,
veg-
tumorigenesis
increased
In
be because for tumor
fat correlates
Experimenta/
a
may
influence
Dietary fat and cancer the mammary gland
polyunsaturated
a positive It seems
with
been
mammary
by factors
oil with
promote
oils
dietary
specific
populations
of
palm
acid
on breast
fat content
Most
proportion effects
have were
more
total
vegetable
of vegetable
content
tumors
acid
trans
fatty
a relatively high the promoting
etable oils (1 1), but Cohen et al (24) found effective in rats treated with NMU. Tinsley
about
fish
of n-6
variable
a high
it appeared
was
(22)
polyunsaturated
has
as did
acid
Cave
(NMU).
polyunsaturated
Somewhat
esis as effectively
of oleic
oil
tumorigenesis
of dietary
tumorigenesis
our experiments,
linoleic
adding
of fish
and
that
has a high
increase on
content
may
data
studies. These take, particularly
however,
of polyunsaturated
of monounsaturated
as well. oil,
amounts
the
not
by feeding
is in agreement
studies
In comparing
because
yield
oil (23).
content
tigated
larger
to deficiency
the
as did
studies,
ofn-6
oil and fish oil were fed showed that of fish oil was required to counteract the
extent
Later
n-3
be-
amount
increased
by Jurkowski
amounts
for
be attributed
by N-methylurea
inhibitory
may
sequent
induced
that
acid
of a small
same
(16).
basis
oils,
experimental individual
fat (20).
fat
appeared
contain
could
addition
reported
the
as its higher
This
of mammary
This
such
not enhanced
(28).
studies
oflinoleic
vegetable
findings
( 1 2). However,
(29).
level
cis monounsaturated
oil, which
did
development
by DMBA
with
acids
coconut
acids,
(1 1). Recent
promote
fat in human
breast
that fatty
tumors
tends
fatty
observations
not
ofany
(19).
correlation
of dietary
the
for
effective
linoleic
mortality
containing
small
a certain
in animals,
on
positive
to saturated
instead
oils
relatively
morigenesis
our
fat with
in rats was
saturated
Epidemio/ogica/
for
with
data sufficient
type
oil
were
tumors
cancer
(27). tumorigenesis
of medium-chain
other
to
required
no correlation
cancer
diets
results
for mammary
found
be explained
to about
feeding
were
mammary
the
vegetable
that
fat and
acid
observed
not
support
to be more
oil
tumors
polyunsaturated
provided
tumorigenesis
experiments, fish
seemed
fats were
the
dietary
In one of our early
this ofdietary
contain
to the
of polyunsaturated
acid with
epidemiological
tween
showed
with
factors,
Subse-
increased
effect
as did the corresponding
the optimal
oflinoleic
fat on mammary
could
of most
calories.
10655
medium-chain
in rats
tumor
of linoleic
amount
fatty
in human
of mammary
level
that
amounts
results
fat showed
dichotomy
maximum
way
does
of tumors
and
in promoting
polyunsaturated
cancer
this
These
polyunsaturated
saturated
acids
as
studies
evidence of total
yield
polyunsaturated
effect
Although
when and
of fat.
that
of n-6
maximal
that
of fat in the diet,
suggestion
amount
increasing
of 4-5%
incidence
levels
provided
with
to a level
reported the
on
(21).
fatty acids Mammary
such
by systematic
who
increased
up
Ip (18)
depend
did
same
(14).
that this greatly increased cancer in the DMBA rat
extended
(17),
yield
diet
increasing
than
fats
CANCER
is an
of polyunsaturated
to saturated
AND
mary
provided,
our
itself,
subsequently
was
in the
was
amounts
acid
and showing mammary
his colleagues
incidence acid
acid by animals
16).
This oflp
polyunsaturated
be synthesized
by adding
or of linoleic
coconut oil or beeftallow, their ability to promote model(l5,
(w-6)
cannot
FATS
for
n-6
it is for mammary
case for mammary tumors, however, tumors was inhibited by high levels Effects of dietary fat on pancreatic
polyunsaturated tumors
fatty (42).
the development of fish oil in the lesions induced
As was
acid the
of colon diet (43). in rats by
azaserine have been investigated as well. The level of n-6 fatty acid required for maximum effect appears to be higher than it is for mammary found
tumors
to be inhibitory
(44). (45).
Again,
high
levels
of fish oil were
1066S
CARROLL
It has proven difficult prostate cancer suitable but Pollard and Luckert velopment
of prostate
to develop an experimental model of for studying effects of dietary fat (46), (47) reported some evidence that decancer
in rats
is stimulated
by a high-fat
diet. Epidemio/ogical
studies
Comparison
of data
itive
correlations
pancreas,
and
(1 3, 48).
This
prostate
between
cancer,
these
the
have
not provided
dietary
fat and
However,
has shown
cancers
to incidence
above.
(55-57). studies
respect
described
studies
cancer
countries fat and
complements
studies
Case-control prostate
different dietary
with
evidence
experimental association
from
between
view
that
obtained
in the
12.
strong
colorectal
be less capable
poscolon,
and mortality
results
evidence
cancer
as discussed
may
of the
of an
(49-54)
or
earlier
for breast
ofdemonstrating
such
associations.
Conclusions The
strongly
held
fluence on cancer such as the breast
incidence and colon
dietary
and (58),
fat has
mortality, has been
by the lack of support from case-control However, the reports of the US surgeon Committee on Diet and views of recent evidence, cancer suggested scientific
are probably
Health both
influenced
fat intake of adult populations other chronic diseases.
an important
particularly tempered
by dietary
and cohort general (59)
fat. Prentice
may provide the only whether a reduction
can reduce
in-
at sites somewhat
(60), which are based conclude that certain
that an intervention trial approach to determining
studies. and the on overtypes
of
et al (37) possible in the
the risk of these
and A
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