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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