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OCR for page 1
Overview and
Major Recommendations
Many diseases now known to be associated with dietary imbalances
or toxic contaminants in food were once thought to arise from other
causes, ranging from 'bad air to disorders of the bodily humors.
Their associations with diet have tended to be worked out by the same
sequence of discoveries. First, a particular human disease is linked
to some aspect of diet, e.g., a lack of fresh vegetables or the fungal
contamination of grain. Alteration of the diet (by crude additions or
subtractions) is then shown to prevent or alleviate the disease. Sub-
sequently, someone succeeds in producing a similar disease in an animal
model E.g., scurvy in guinea pigs or mycotoxicoses in rats and mice),
which leads to the precise identification of the active components of
the diet (e.g., a nutrient or a toxic ingredient). Finally, laboratory
scientists discover the mechanism by which the nutrient or toxin
exerts its effects, although by this stage such details have become
mainly a matter of academic interest because the disease in question
has already been eradicated.
A similar sequence of discoveries has taken place in some branches
of cancer research. Chronic exposure to coal tar in mineral oil was
observed to cause skin cancer in humans more than a century before
laboratory investigators succeeded in producing cancers in rabbits by
painting their skin with coal tar. Once the cancer had been produced
experimentally, the active carcinogens in the tar--polycyclic aromatic
hydrocarbons--could be purified and identified, and later, their mecha-
nisms of action explained. By this time, however, skin cancer in humans
resulting from such exposure had long since been effectively abolished
by general improvements in working conditions in factories; however,
laboratory studies of these and other carcinogens have continued and
have provided important insights into the mechanisms of carc~nogenesis.
These historical examples may seem too simple for predicting the
the course of research to unravel interactions between a multifactorial
disease like cancer and a complex mixture like diet; but they may give
us some idea of what to expect. Although interest in the study of diet
and carcinogenesis can be traced to laboratory experiments performed
more than half a century ago, it seemed in the 1960's that we were
still in the first stages of the sequence described above. At that
time, despite evidence from early experiments that modification of
either total food intake or some dietary components could influence
carcinogenesis, the possibility that diet per se was a significant
factor in human cancer was still considered remote. Then epidemiolo-
gists linked the incidence of several common cancers, e.g., breast
cancer, with certain general dietary patterns. Laboratory scientists
followed up these observations by developing animal models for cancers
suspected of being affected by diet. Subsequently, epidemiologists
observed that the high incidence of breast cancer and certain other
1
OCR for page 2
2 DIET, NUTRITION, AND CANCER: DIRECTIONS FOR RESEARCH
cancers is associated with a diet high in fat or its components, and
laboratory investigators found that mammary cancers in certain species
were similarly modified by changes in the amounts and types of dietary
fat. Further studies may eventually permit isolation of the active
dietary constituents, definition of the exact mechanism for the effect
exerted by fat and other dietary components, and delineation of the
precise diets capable of counteracting some of these effects.
However, research on nutrition and carcinogenesis has not invari-
ably followed the sequence described above. Of the many hypotheses
generated by the results of early experiments in animals, only some have
been followed up by epidemiological studies. For example, clues about
the effect of the caloric content of the diet per _ on experimentally
induced carcinogenesis have remained largely unexplored. Similarly,
leads produced by international correlation studies of human popula-
tions have not always been followed up by more controlled epidemiologi-
cal and laboratory investigations. For example, the finding in the
mid-1960's that low selenium intake may be associated with increased
cancer incidence or mortality has been tested in well-controlled lab-
oratory experiments, but no controlled epidemiological studies (i.e.,
case-control or cohort studies) could be conducted because of a lack
of knowledge about the precise intake of selenium.
It is never possible to predict exactly where major discoveries
will be made, and any attempt to stipulate a particular sequence for
research on diet and cancer would tend to stifle creativity. There-
fore, the committee has been rather cautious in making suggestions.
Nevertheless, it may be desirable to plan the research on diet and
cancer in a logical but flexible conceptual framework that could
encompass all the sources of data, i.e., surveys to monitor expo-
sure, epidemiological studies, carcinogenesis bioassays in animals,
short-term tests for genotoxicity, short-term in vivo bioassays
to detect early biological indicators of carcinogenesis, and studies
designed to elucidate metabolic pathways or pathogenic mechanisms.
After completing an assessment of the literature in 1982, the Com-
mittee on Diet, Nutrition, and Cancer concluded that 'the differences
in the rates at which various cancers occur in different human popula-
tions are often correlated with differences in diet. The likelihood
that some of these correlations reflect causality is strengthened by
laboratory evidence that similar dietary patterns and components of
food also affect the incidence of certain cancers in animals. Thus,
concordance between epidemiological and laboratory data served as the
principal basis for the degree of certainty allotted to conclusions and
as the basis for the interim dietary guidelines proposed in the first
report. The selection of this criterion reflects the committee's con-
viction that persistent interaction between epidemiologists and labora-
tory investigators is necessary to provide a framework for future
research that will lead to a more definitive understanding of diet and
carcinogenesis.
OCR for page 3
Overview and Major Recommendations 3
STRATEGIC OBJECTIVES AND PRIORITIES FOR RESEARCH
The committee ha s operated on the principle that research on diet
and cancer should encompass the seven strategic objectives presented
below. From the numerous suggestions for research made in this report,
it wishes to call attention to certain general recommendations, which
are listed following the strategic objective to which they apply.
1. Identification of the foods and of the dietary macro- and
mirr~r~n.c~titilPntc th::~t alter the read of renter her] "lilr,;rl~t;~= of
their mechanisms of action.
In the first report, the assessment of the literature resulted in
the preliminary identification of four categories of dietary constit-
uents that are likely to affect the risk of cancer. These were satu-
rated and unsaturated fat; certain fruits, vegetables, and whole grain
cereals; smoked, cured, and pickled foods; and alcoholic beverages.
The committee recommends that when the epidemiological and experimental
evidence associating particular dietary components with cancer risk is
sufficiently convincing, studies should be undertaken to identify the
specific active constituents and their mechanisms of action. For
example, attempts should be made to identify the consitituents of
fruits and vegetables that are responsible for the observed reduction
in risk associated with their frequent consumption and to define the
mechanisms of action of those constituents (see Chapter 7~. Similarly,
studies should be pursued to elucidate the mechanisms by which a high
fat diet increases the incidence of certain cancers (see Chapter 6~.
Information from such studies would be useful in refining the interim
dietary guidelines recommended by the committee in its first report.
2. Improvement of the data base and the methodology for assess-
ing human exposure to foods and dietary constituents that may alter
the risk of cancer.
Better epidemiological methods should be developed to monitor and
quantify dietary exposures in human populations in order to establish
more clearly the relationship of dietary constituents and dietary
patterns to the occurrence of cancer. For example, innovative methods
are needed to measure past dietary intake. Furthermore, better
techniques should be sought to validate the data produced by all these
methods. Regular nutrition surveys to monitor dietary intake would
augment the data base for epidemiological studies of diet and cancer
(see Chapter 4~.
3. Identification of markers of exposure and early indicators
of the risk of cancer.
The committee recommends that attempts be made to identify early
biological or biochemical changes that reflect the ability of specific
OCR for page 4
4 DIET, NUTRITION, AND CANCER: DIRECTIONS FOR RESEARCH
dietary constituents or dietary patterns to alter the risk of cancer in
humans. For example, where neoplasia i s used as the sole end point,
investigations are severely limited by the long latency period between
"exposure" and "expression. " Therefore, one of the most pressing needs
is the development of short-ter~ test s that could identify early bio-
logical indicators of exposure to dietary constituents that affect
carcinogenesis (see Chapters 4, 5, and 7~.
4. Determination and quantif ication of the adverse or beneficial
effects of the foods and of the dietary macro- and microconstituents
. .
that affect the risk of cancer.
The committee recommends that efforts be continued to evaluate the
impact of potentially carcinogenic or inhibitory dietary constituents
on cancer risk. These studies should include a focus on substances
that can damage macromolecules, especially DNA; on those that can
enhance experimentally induced carcinogenesis, i.e., promoters and
cocarcinogens; and on those that can inhibit experimentally induced
carcinogenesis (see Chapters 5, 6, 7, and 8~.
5. Determination of the ranges of optimal intake of dietary macro-
and microconstituents.
Attention should be given to determining ranges of dietary macro-
and microconstituents that are optimal not merely for the prevention of
deficiency diseases but also for the promotion of other aspects of
health, including the reduction of the risk of cancer. For example, it
would be useful to establish a dose-response curve for selenium and to
define the optimal range of selenium intake, giving special attention
to the levels that might be needed to achieve a reduction in the risk
of certain cancers (see also Chapters 5, 6, and 7~.
6. Intervention to reduce the risk of cancer.
Intervention studies should be conducted using foods or food con-
stituents believed to be associated with a lower cancer risk, but only
when a substantial body of data indicates a high likelihood of benefit
without discernible risk. For example, attention might be given to
reducing the consumption of fat and/or adding specific fiber compo-
nents to the diet (see Chapter 6), and to the ingestion of different
levels of certain microconstituents or of foods containing potential
inhibitors (see Chapters 4 and 7~.
7. Application of knowledge about diet and cancer to programs in
public health.
To maximize the potential impact of public health programs to
reduce the risk of cancer, studies should be pursued to elucidate
factors that motivate people to modify their food habits. For example,
it would be useful to analyze bodies of longitudinal data to learn what
they reveal about factors that determine consumption patterns in dif-
ferent populations ~ see Chapter 9) .
Representative terms from entire chapter:
cancer risk
