Diet, Nutrition, and Cancer (1982) / Chapter Skim
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3 Methodology
3 Methodology
Section A - The Relationship Between Nutrients and Cancer
Pages 30-65
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From page 30... ...
The possible relationships between diet and cancer have been investigated in studies of human populations and in laboratory experiments using various in vitro systems (to check substances for their ability to mutate bacteria and mutate or transform other cells) or animal models (to test substances directly for carcinogenicity)
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From page 31... ...
These studies, based on aggregate exposure data and observed outcomes, provide the next step in establishing meaningful associations. The crudest of these studies are ecological studies in which national per capita food intake is related to patterns of cancer incidence or mortality.
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Comparisons of diets for different population groups are generally based on one or two types of data: national per capita food intakes (also called food disappearance data) or household food inventories.
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From page 33... ...
Although national per capita intakes have been very useful in providing leads for further research, they are inaccurate as measures of food that has actually been eaten. They really only measure food that has "disappeared" into the food supply -- which is why they are sometimes called "food disappearance data." They do not account for food produced by individuals, for waste in stores, restaurants, or homes, or for differences in consumption within a country by different age and sex groups.
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From page 34... ...
They must also record estimated amounts of foods consumed away from home. Although the weighed diet record was long viewed as the ideal standard in estimating dietary intake, it requires, at a minimum, a great deal of interest and cooperation on the part of the subjects and, hence, selects for certain types of people.
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From page 35... ...
However, recent reports on vitamin A serum levels suggest that some such measurements may nevertheless be useful in predicting cancer risk in cohort studies (Cambien et al., 1980; Kark et al., 1980; Wald et al., 1980~. A particularly troublesome aspect of case-control studies using biological markers 3 - 6
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From page 36... ...
Analysis of Dietary Data. Regardless of the method used to collect food intake data, the reported foods must be grouped into categories before they can be analyzed.
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In prospective cohort studies, the investigator must collect current dietary data and then either wait (for up to 20 to 30 years) for the disease to appear or identify sufficiently large groups of subjects for whom there are adequate retrospective dietary data.
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From page 38... ...
The first two methods provide information about potential carcinogenicity, whereas the third provides direct evidence of carcinogenicity in laboratory animals. Analysis of Molecular Structure In a review of the large body of evidence pertaining to the role of structure-activity relationships in predicting carcinogenic activity, Miller (1970)
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From page 39... ...
, which utilizes several specifically constructed Salmonella typhimurium strains to detect various kinds of mutations and genetic damage (Ames et al., 1975~. It is generally agreed, but not without considerable controversy, that there is a high degree of correlation between the mutagenicity of compounds in the Salmonella/microsome assay and their carcinogenicity in laboratory animals (McCann and Ames, 1976; Purchase et al., 1978; Sugimura et al., 1976~.
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From page 40... ...
. The rationale for feeding very high doses of a substance in chronic bioassays is that the number of animals that develop cancer increases as the dose of the test substance is increased.
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From page 41... ...
Variables include animal species and strain, genetic characteristics of the test strains, the diet given to the animals, the chemical and physical characteristics of the test substances, the method of tissue examination, spontaneous rate of tumor formation in control animals, susceptibility to various carcinogens, dose response to a given carcinogen, and tissue specificity of a large number of carcinogens. Difficulties in Studying the Carcinogenicity and Mutagenicity of Food Constituents .
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From page 42... ...
This may be prohibitively expensive. Alterations in the diet or nutritional status do not appear to cause cancer directly in laboratory animals, but are only believed to modify the spontaneous rate of tumor formation or the induction and growth of cancer by specific carcinogens.
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From page 43... ...
Caloric restriction and total food intake have been reported to be important determinants of tumor yield (Silverstone and Tannenbaum, 1949; Tannenbaum, 1944, 1945; Waxier, 1960~. The difficulty in distinguishing between the effects from changes in total food intake and caloric intake is discussed in Chapter 4.
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From page 44... ...
Particular emphasis was given to the results of case-control or cohort studies that were designed to examine a specific hypothesis. In evaluating laboratory evidence, the committee placed more confidence in data derived from studies on more than one animal species or test system, on results that have been reproduced in different laboratories, and on the few data that indicate a gradient in response.
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From page 45... ...
Their interpretation may be further jeopardized by the lack of specificity of the methods for measuring intake and the uncertainty about whether the data reflect nutrient intake or whether current intake correlates well with past dietary patterns (which may be more relevant to carcinogenesis)
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From page 46... ...
The two approaches are complimentary and should be used in conjunction with each other as often as possible. The committee evaluated the evidence from all types of epidemiological studies and laboratory experiments, but had more confidence in data derived from case-control and cohort studies, in the results of experiments conducted in more than one animal species or test system, in results that had been reproduced in different laboratories, and in data that showed a dose response.
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From page 47... ...
1981. The reliability of retrospective dietary histories: Paper submitted to the Committee on Diet, Nutrition, and Cancer at the Workshop on Methodology for Dietary Studies in Cancer Epidemiology held at the National Academy of Sciences, Washington, D.C., May 20-21, 1981.
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1981. Assessing Changing Food Consumption Patterns.
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1976. The reproducibility of dietary intake data in a prospective study of gastrointestinal cancer.
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50 DIET, NUTRITION, AND CANCER Research Service, U
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These estimates, based on food disappearance data reported by Page and Friend (1978) , show that if nutrients alone are measured, the food supply appears to have undergone little overall change during this period.
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52 I Cal At: C
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From page 53... ...
However, these figures on the availability of a limited group of nutrients tend to obscure the extensive changes that have taken place in the food supply during the past 50 years. Some of these can be seen by examining the changes that have occurred in the contribution of various food groups to total calories (Figure A-1.
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54 o A so Pi in Y 0 c)
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, a major portion of that decline having occurred after 1948. Changes in the per capita intake of certain individual commodities are especially striking.
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3 27.5 63.5 29.7 30.6 5.4 1976 52.7 36.5 65.3 31.1 24.3 9.9 aAdapted from Page and Friend, 1978. These striking changes in the food supply need to be taken into account when one examines the relationship between diet and cancer.
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But in standard food composition tables prepared by the U.S. Department of Agriculture, only the amount of ascorbic acid used for food fortification is recorded.
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From page 58... ...
This might suggest that the food supply has contained an unchanging cluster of cancer-causing or protective substances throughout much of this period, despite the extensive changes in the composition and quantity of many of the foods consumed. It is also possible that any changes capable of affecting cancer rates (positively or negatively)
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From page 59... ...
Although there has been relatively little change in the overall percentage of calories derived from fat, protein, and carbohydrate, there have been marked shifts in consumption patterns from vegetable to animal protein, from complex to simple carbohydrates, and, as already noted, from animal to vegetable fats. The increase in per capita intake of fat from meat has compensated for a decline in the intake of dairy fats.
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From page 60... ...
is impossible to calculate given the lack of accurate data on home production. However, the documented decrease in the annual per capita intake of sweet potatoes, from 11.1 kg per person during 1976 to 2.4 kg during 1980, combined with the declining consumption of fresh dark green and deep yellow vegetables, has very likely decreased the intake of dietary fiber and naturally occurring 6-carotene, which recently have been studied for their possibly protective roles in carcinogenesis (Chapters 8 and 9~.
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From page 61... ...
There have been surprisingly few studies linking specific foods with either increases or decreases in cancer rates. Where there have been such studies, e.g., those on cruciferous vegetables, the data A-11
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From page 62... ...
Since all these dietary constituents increase and decrease simultaneously, it is difficult to determine which ones, if any, are involved when, for example, consumption of animal products and cancer rates decrease simultaneously or when control subjects consume more animal products than do cancer cases. Individual diets are not composed of isolated substances or even isolated foods but, rather, they contain thousands of unique combinations of nutrients and other compounds that comprise the individual food items.
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From page 63... ...
The relationship between these changes in the food supply and the incidence of cancer is not yet clear. The fact that the food supply has undergone major changes while the rates of cancer at most sites have been relatively constant may suggest that none of the changes has an effect on cancer incidence, that the changes have occurred too recently to produce an effect, or, more likely, that some changes have had a positive and some a negative impact.
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From page 64... ...
1974. Factor analysis of international cancer mortality data and per capita food consumption.
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From page 65... ...
pp. Ue S" International Trade Co _ fission.
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