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OCR for page 5
2 Approach to the Study
This report suggests useful directions for research into the
relationship between diet, nutrition, and cancer. From the beginning
of its study, the committee was cognizant of the widely held belief
among scientists that research is most vigorous when it is the product
of individual choices by investigators, rather than the result of a
preconceived strategy. However, when research has an important and
defined practical objective, the committee believes that there is
justification for concentrating a part of the overall research effort
on questions that are recognized to be central to further progress
toward that objective. In approaching its task, the committee adopted
the strategy described in the following paragraphs.
The assessment of the literature in the committee's first report
(National Research Council, 1982) served as the primary guide to the
identification of needed research. As indicated in that earlier report,
the evidence associating some dietary constituents to carcinogenesis
was judged to be sufficiently convincing to allow the committee not
only to formulate conclusions about their carcinogenic or inhibitory
effects but also to propose interim dietary guidelines toward reducing
the risk of certain cancers. Among these dietary components are total
dietary fat; certain fruits, vegetables, and whole grain cereals; cured,
pickled, and smoked foods; and alcoholic beverages. No firm conclusions
could be reached on other dietary constituents.
The committee recognized, however, that by working solely from its
first report, it would be identifying only those gaps in knowledge that
were implied by the already published literature. To gain assurance
that it was not overlooking as yet unpublished work on new avenues of
research that might have an important bearing on the relationship
between diet and cancer, and to obtain insights from other researchers
in the field, the committee constituted an informal panel of more than
100 distinguished scientists knowledgeable about cancer, nutrition, and
related areas. These panelists were asked to contribute their sugges-
tions for research. In addition, approximately one-third of the nearly
70 investigators who responded by sending suggestions were invited to
meet with the committee at a miniconference devoted to exploring ideas
for fruitful research. The resulting long lists of suggestions were
consolidated and combined with the suggestions generated by the com-
mittee. Priority items were then selected.
This report contains both general and specific recommendations,
reflecting the relative state of knowledge in each area. Unlike the
committeets first report, which was suitable for the general scienti-
fic community, this report is directed primarily to investigators
in the field and to institutions that support them.
5
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6 DIET, NUTRITION, AND CANCER: DIRECTIONS FOR RESEARCH
In the chapters that follow, the committee makes three kinds of
recommendations for future research. One set of recommendations
derives directly from gaps in the current state of knowledge about the
effects of specific dietary components. Where conclusions are uncer-
tain, simply because information is incomplete, recommendations are
directed toward supplying missing data. Where the uncertainty stems
from the imprecision of the data, there are recommendations for meth-
odological improvement. Where several causal factors seem to be
operating, there are recommendations that their interactions be
studied. Such recommendations only highlight what would be obvious
to an experienced investigator.
A second set of recommendations arises from the fact that there
are multiple etiological factors in carcinogenesis, including combi-
nations of dietary components, complex steps in cancer progression, and
a multiplicity of cancer types. This complexity has led the committee
to make recommendations for long-term, multifaceted studies that are
necessarily large and therefore unavoidably expensive. Such studies
are likely to be most informative when they can be conducted under
especially favorable circumstances. For example, high risk human
populations may be studied under circumstances that permit simulta-
neous study of multiple risk factors. Information from such studies
could be supplemented with laboratory data derived from a suitable
animal model.
A third kind of recommendation calls attention to the need for
behavioral and social studies. This stems from the finding in the com-
mittee's first report that most common cancers appear to be influenced
by diet--suggesting that, to a certain extent, individuals may be
able to influence their chances of getting cancer. However, knowledge
that a certain exposure strongly influences cancer is apparently not
sufficient to convince people to modify their behavior. For example,
it is clear that simply demonstrating a causal connection between smok-
ing and lung cancer has not eliminated the smoking habit. Therefore,
the committee has addressed the need for social and behavioral research
to supplement research in the area of physiology, pathology, cytology,
nutrition, and biochemistry.
This report deals primarily with research on diet, nutrition, and
cancer. The committee made no attempt to discuss other environmental
or genetic factors that are known to be associated with cancer. How-
ever, Chapter 3 briefly addresses the relationship between research on
the basic mechanisms of carcinogenesis and our overall understanding of
the ways that diet affects cancer. Although it is the committee's
judgment that research on diet and carcinogenesis can progress without
waiting for further discoveries in basic mechanisms, it is aware of the
need to press forward simultaneously with fundamental investigations,
particularly taking advantage of new opportunities afforded by recent
advances in cellular and molecular biology. Such fundamental research
is likely to improve not only our understanding of the impact of diet
OCR for page 7
Approach to the Study 7
and nutrition on carcinogenesis but also our ability to address~nany
aspects of the prevention and treatment of cancer.
Chapters 4 and 5 discuss methodological shortcomings regarded by
the committee as major hurdles in the comparison and interpretation
of data from both epidemiological and laboratory studies. Research
to refine methodology as well as to reexamine certain methodological
issues is recommended.
The next three chapters deal with specific dietary components.
Macroconstituents (i.e., total caloric intake, fats, protein, carbo-
hydrates, dietary fiber, and alcohol) are discussed in Chapter 6.
As noted in the first report, it often is difficult to separate the
effects of fat, protein, and carbohydrates. This is particularly
evident in studies to determine the effect of changing the total
caloric intake--which nay be accomplished by changes in the levels of
any or all of the three macronutrients. Compared to information that
has been provided by a multitude of studies on fats, less is known
about proteins and there are relatively few data on the effects of
different types of carbohydrates. Therefore, there is a need to
identify more clearly the effects of protein and carbohydrates, espe-
cially the individual components of dietary fiber. In its first
report, the committee concluded that the evidence relating fats and
certain alcoholic beverages to cancer is sufficiently convincing to
justify certain interim dietary guidelines; however, further research
i s needed to expand the data base for both of these dietary compo-
nents. It is also necessary to identify the effects of the indi-
vidual components of fat as well as the mechanisms by which a high
fat diet appears to increase the incidence of certain cancers.
Chapter 7 focuses on several microconstituents, i.e., vitamins,
minerals, and nonnutritive constituents, and on foods rich in these
substances that have been either identified in laboratory experiments
as inhibitors of carc~nogenes~s or associated in epidemiological
studies with a lower risk of cancer. We need to refine our knowledge
about the effects of these components, to identify the active consti-
tuents in fruits and vegetables, and to elucidate their mechanisms of
action.
Chapter 8 takes up two major subjects on which the committee did
not reach firm conclusions in its first report: (1) mutagens in foods
and (2) substances in foods that are naturally present (e.g., myco-
tox~ns), that are intentionally added (e.g., additives), or that
accidentally enter the food supply (e.g., pesticide residues). The
contribution of such substances to overall cancer risk cannot be fully
assessed for several reasons, including insufficient knowledge about
the exposure of humans, the absence of carcinogenicity test data on the
vast majority of these compounds, and our inability to estimate relia-
bly the risk from exposure, even to those chemicals that are known to
be carcinogenic. The committee emphasizes the need to obtain infor-
mation that will enable us to understand the relevance of dietary
OCR for page 8
8 DIET, NUTRITION, AND CANCER: DIRECTIONS FOR RESEARCH
mutagens to human health and to determine the level of risk posed by
mutagens, additives, and contaminants.
Although the committee makes no attempt in this report to focus
separately on research on methods to assess risk, this theme--the need
to quantify the level of risk--is encountered time and again, espe-
cially in discussing the applicability of results from laboratory
studies to human health. Clearly, there is a need to develop better
methods for assessing the risk to humans arising from the presence of
initiators and modifiers of carcinogenesis in the diet.
Chapter 9 examines how knowledge about diet and cancer can be
applied in the development of public health programs aimed at modify-
ing behavior to reduce cancer incidence. The committee believes that
studies of the factors that motivate change in consumer behavior will
be necessary if knowledge on diet and cancer is to yield benefit to
public health.
The first report of this committee contains extensive lists of
references. Since this second report draws heavily on the same litera-
ture, the citations herein are limited to studies not previously
described.
Representative terms from entire chapter:
total caloric
