Med. Oncol. & Tumor Pharmacother. Vol. 7. No, 2/3, pp. 199-208, 1990

0736-01 I8/90 $3.00 + .00 Pergamon Press plc

Printed in Great Britain

STRATEGIES

FOR CANCER

PREVENTION

THROUGH

DIET MODIFICATION

P E T E R G R E E N W A L D , * LUISE L I G H T , t S H A R O N S. McDONALD72 and H A R R I E T R. STERNS *Division of Cancer Prevention and Control, National Cancer Institute, National Institutes of Health, Building 31, Room 10A52, Bethesda, MD 20892, U.S.A. ; tDivision of Cancer Prevention and Control, National Cancer Institute, Executive Plaza North, Room 200, Rockville, MD 20852, U.S.A,; SProspect Associates, 1801 Rockville Pike, Suite 500, Rockville, MD 20852, U.S.A. (Received 21 September 1989; accepted 5 October 1989) Diet and c a n c e r r e s e a r c h at the National C a n c e r Institute has grown from a budget of $2.5 million in 1974 to $55 million in 1988. T h e emphasis is partially on d e m o n s t r a t i o n s of prevention strategies and c h e m o p r e v e n t i o n trials. Studies to disseminate dietary goals in practical ways are u n d e r t a k e n with the aid of the food i n d u s t r y .

DIET-RELATED CANCER PREVENTION RESEARCH AT THE NATIONAL CANCER INSTITUTE

STRATEGIES FOR CANCER PREVENTION THROUGH DIET MODIFICATION

With the exception of smoking, dietary habits are the most significant lifestyle factor associated with cancer risk. 1.2 Therefore, dietary interventions have a great potential for reducing cancer incidence in the general population. Although many questions about the role of diet in the etiology of cancer have yet to be answered, there are sufficient epidemiologic and experimental research results to justify an optimistic and aggressive approach to nutrition-related research. Excessive intake of fat, calories, alcohol, and salt-cured, smoked, and pickled foods has been associated with increased risk for certain cancers. Frequent consumption of high-fiber foods such as whole grain cereals and fruits and vegetables has been associated with decreased cancer risk. 2"3 Dietary change represents a major part of NCI's cancer prevention objectives. This paper examines strategies for cancer prevention through diet modification, with emphasis on the translation of basic scientific knowledge into effective applications that can result in increased public health benefits. The discussion addresses diet and chemoprevention-related cancer prevention research at the National Cancer Institute (NCI); the formulation of interim dietary guidelines; channels for delivering dietary guidance to the public to promote consumer diet modification; and the potential influence of biotechnology and the changing food supply on lowering cancer incidence.

The diet-related cancer prevention research budget at NCI has grown from an annual expenditure of $2.5 million in 1974 to more than $55 million in 1988 (Fig. 1). Sufficient evidence, outlined below, has already accumulated to develop and test several hypotheses in clinical cancer prevention (intervention) trials with selected macronutrients and other cancer-inhibiting agents.

Diet and cancer research

The major focus of diet and cancer research at NCI is to identify, test, and implement cancer control and prevention strategies. The overall objective is achieved through intramural and extramural basic and clinical studies and by nutrition-related health promotion research. All diet-related cancer prevention research is carried out in the context of NCI's systematic research strategy, which uses a five-phase decision making model, and emphasizes human interventions. In phase i of this model the hypotheses are developed; phase I1 ensures that accurate and valid methods are developed for implementation in controlled trials; phases III and IV test phase I hypotheses and validate methods developed in phase II for efficacy in controlled intervention trials; and phase V applies the proven 199

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intervention results of the efficacy studies in large demonstration studies. Well-designed clinical metabolic studies and controlled intervention trials use this strategy for assessing the pharmacokinetics and efficacy of promising multiple or single dietary components for cancer prevention. Laboratory or epidemiologic findings alone do not provide this direct evidence. In addition, behavioral research, an important component of clinical studies, is used to clarify the knowledge, attitudes, and beliefs that influence application of a chosen intervention. Two diet and cancer hypotheses that warrant further investigation by clinical studies are the contributory effect of high fat intake on breast cancer incidence and the inhibitory effect of dietary fiber on colon cancer incidence. Fat has been studied more extensively and associated more frequently with various cancers than any other dietary factor. Human population data show positive correlations between total dietary fat and caloric intake and cancer incidence, particularly for breast, prostate, and colorectal cancers, 2'4 The hypothesis that fiber may protect against colorectal cancer stems initially from observations in Africa, where the intake of dietary fiber is very high and there is relatively little cancer of the large intestine. 5 As a result, numerous other studies have explored a possible protective role of fiber. 6

Dietary fat Evidence of the association between dietary fat and breast cancer was judged to be more extensive than any other dietary factor. 2 Case-control studies 7--9and international correlation studies based on disappearance data show a consistent, direct association between dietary fat and breast cancer incidence or mortality 1~ that persists after controlling for height, weight, and age at menarche. In a comprehensive regression analysis of existing data, ~5 no other dietary factor (protein, alcohol, carbohydrate, vitamins, total calories) contributed significantly to variations in breast cancer incidence rates. Migrant and time-trend studies in England and Wales, 16'~7 Japan, ~s and the United States re'z~ support a temporal association between fat intake and breast cancer mortality. There is strong evidence that dietary fat influences the promotion stage of carcinogenesis, although the precise mechanism has not been elucidated.aS Numerous studies in rodents have reported that high-fat diets enhance spontaneous mammary tumors, 2t chemically induced tumors, 22"23 transplantable tumors, 24 and radiationinduced mammary tumors. :5 Based on this strong supporting evidence, NCI approved the concept of a randomized clinical trial, the Women's Health Trial (WriT), to determine

Strategies for cancer prevention whether a reduction in dietary fat from 40% to 20% of total calories among women ages 45 to 69 would reduce subsequent breast cancer incidence. A feasibility study was conducted to evaluate recruitment, compliance, methodology, and cost. 26 However, further consideration of the sample size, markers for compliance, confounding factors in some of the supporting epidemiologic studies, and statistical power of the proposed study raised doubts about the study design. It was recommended that the W H T not proceed as proposed. The need for a dietary intervention trial focusing on dietary fat intake and breast cancer reduction still exists. Refinement of the hypothesis, use of biological markers, and inclusion of other disease endpoints are potential design modifications that make the intervention concept more appealing. Direct evidence of the relationship between fat reduction and a change in cancer risk cannot be obtained any other way.

Dietary fiber The inhibitory effect of high dietary fiber consumption on colon cancer is strongly supported by epidemiologic and experimental data. In a comprehensive review of the epidemiologic literature, Greenwald et al. 6 noted that 32 of 40 epidemiologic studies, including international and national correlational, case-control, and time-trend studies, reported an inverse association between fiber-rich diets and colon cancer risk. A temporal association of low-fiber diets and colon cancer is readily demonstrated by time-trend studies 27'2s that indicate that migrant populations usually acquire the risk associated with their adoptive country. 19"2~ Not all studies are consistent. 3~ Differences may exist because dietary fibers from different food sources are heterogeneous mixtures of components, such as cellulose, hemicelluloses, pectins, gums, and lignin, and therefore may have varying physiological effects. In addition, fiber components are difficult to determine accurately in foods. It has also been difficult to separate the effects of dietary fibers from other dietary constituents (e.g. total calories, fats, vitamins, minerals, and nonnutritive components of fruits and vegetables) and from nondietary influences (e.g. socioeconomic status). Laboratory evidence on the effect of various fiber components on chemically induced colon cancer in rodents is contradictory. 3t Cancer inhibitory or enhancing effects are variously reported by different investigators testing the same fiber sources. Results in these experiments can be influenced markedly by experimental variables such as the type of fiber, the particular chemical carcinogen used, other dietary

201

factors (especially fat), and the route and dose of fiber/carcinogen administration. Of the many fiber sources tested, wheat bran, cellulose, and citrus fiber are generally found to inhibit colon cancer tumor yield or size. > Mechanisms proposed for the inhibitory role of fiber in colorectal carcinogenesis include reducing fecal mutagen concentrations by increasing fecal bulk, reducing the length of exposure by colonic mucosa to fecal mutagens by enhanced fecal transit time, and inhibiting fecal mutagen synthesis through fiber-induced changes in colonic pH or bacterial metabolism.

Vitamins and minerals Diets high in fruits and vegetables have been associated with lower incidences of cancers of the lung, colon, esophagus, and stomach, with the strongest association between consumption of betacarotene-rich foods and decreased lung cancer risk. 32 A recent review of the epidemiologic evidence evaluated cancer incidence and vitamin A or beta-carotene intake. 33 A significant increase in cancer risk at various sites was associated with low intake of vitamin A. Half of these studies reported risks for groups with low vitamin A intake to be about twice those of high intake groups. Epidemiological studies also suggest that foods containing vitamin C such as citrus fruits and certain vegetables may protect against stomach cancer. 34 Other evidence indicates that vitamins E, B,2, folic acid, and riboflavin may prevent the initiation or promotion of several cancers, but these findings are not conclusive. Epidemiologic and animal studies suggest that high calcium intake may protect against colon cancer and low selenium intake may increase the risk of cancers at several sites; 2 however, too few studies have been evaluated to determine the strength of the association.

Chemoprevention trials" More than 30 human chemoprevention trials supported by NCI are currently investigating cancer inhibition in medical and community settings. These clinical interventions are aimed at reducing cancer incidence in the population at large (e.g. healthy volunteers), individuals at very high risk (e.g. smokers also exposed to asbestos), individuals with precancerous lesions (e.g. colon polyps), and individuals at high risk for cancer recurrence (e.g. breast cancer). Two of these trials are assessing agent

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efficacy on cancer incidence at all sites. Other studies are assessing agents in persons at high risk for cancer of the oral cavity, cervix, colon, esophagus, lung or skin. Chemopreventive compounds under study, alone or in combination, are various vitamins, minerals, and/or fiber dietary supplements and several synthetic retinoids. Other promising agents currently undergoing preclinical testing will be prioritized and entered into clinical studies as resources permit. Endpoints in these studies include overall cancer incidence, incidence of specific cancers, rate of regression and/or progression of premalignant changes, and changes in cellular or biochemical indices associated with tumor promotion. Some of these studies are being conducted in collaboration with scientists from other countries. International collaborative trials such as those under way between the United States and Finland and the United States and the People's Republic of China are able to use unique circumstances such as study populations not available in the United States. For example, the large-scale intervention trial for the prevention of lung cancer undertaken by NCI and the Public Health Institute of Finland is comparing the effect of oral beta-carotene (20 mg day -1) and vitamin E (100 mg day -x) supplements alone and in combination versus a placebo in 28,000 mate heavy smokers ages 55 to 69. Results from this study should be available by 1992. Two collaborative studies in Linxian, China, an area with a particularly high incidence of esophageal cancer, are examining a test population of 30,000 men and women ages 40 to 69 receiving one to four times the recommended dietary allowance for specific combinations of vitamins and minerals (versus placebos) for their effect on reducing the incidence of this cancer. The second Linxian trial, with a similar study design, will examine the effect of multiple vitamins and minerals on a group of 3,400 men and women with severe esophageal dysplasia who are at high risk for esophageal cancer. Results from both studies will be available in the 1990s. 35 The results of a recent intervention trial indicate that isotretinoin is markedly effective in preventing new skin cancers in patients with xeroderma pigmentosum, a genetically inherited condition in which the defective repair of ultraviolet-damaged D N A results in a thousandfold increase in the frequency of skin cancer in this group compared with the general population. Although the high dosage used produced serious toxicities in some patients, protocol refinement and the development of new synthetic retinoids may lead to further reduction of cancer incidence in persons at high risk for this skin cancer. 36

A study initiated in 1985 is evaluating ascorbic acid and alpha-tocopherol and high-fiber (wheat bran) supplementation in a group of patients with familial adenomatous polyps who are at almost 100% risk of developing colon cancer. A limited degree of polyp regression was observed for the high-fiber group. 37 The experience with this intervention trial has implications not only for colon cancer prevention but also for the design and testing of cancer prevention strategies in general. Other studies recently undertaken include investigations of promising chemopreventive pharmaceuticals such as piroxicam, a nonsteroidal anti-inflammatory drug, in subjects with a history of colon polyps, and a breast cancer trial with the synthetic retinoid 4-hydroxyphenylretinamide for the prevention of primary contralateral breast lesions in women with a previous history of breast cancer. Pending positive results for these studies, larger scale trials will be undertaken. Of increasing interest to this area of research is the use of biological indicators or intermediate endpoint markers to predict subsequent cancer occurrence. Biological marker characterization has been applied to clinical chemoprevention studies, including biochemical, cellular, tissue, and genetic indicators of future cancer risk. Study protocols incorporating prevention markers require less resources (time and number of subjects) and may be more statistically precise than standard prevention trial designs with cancer as the endpoint. None of the biological markers or precancerous lesions under study have been statistically validated as accurate predictors of future cancer incidence. However, several markers exhibit strong evidence for reliability and specificity as premalignant indicators. Marker characterization is being applied to nutrition and chemopreventive interventions of the lung, oral cavity, colon, skin, esophagus, and cervix. Also there are innumerable potentially useful serum markers for use alone or in combination with other data for assessing cancer risk potential or subject compliance with a study protocol.

bzterirn dietary guidelines for cancer prevention Although many questions remain unanswered in the area of diet, nutrition, and cancer, NCI has a mandate to provide current information to a public that shows great interest in the role of dietary factors in cancer incidence. To meet public demand, NCI concluded that guidelines based on existing data should be formulated to provide practical healthful dietary guidance while further research on the

203

Strategies for cancer prevention

specific role of diet in cancer etiology is conducted 35,38 The first interim dietary principles with respect to cancer prevention were proposed by NC1 in 1979 and recommended a reduction in dietary fat, a generous intake of dietary fiber and fresh fruits and vegetables, avoidance of obesity, and moderate alcohol consumption. > In 1980, NCI commissioned the National Academy of Sciences (NAS) to conduct a comprehensive review of the scientific information relevant to the relationship of diet and cancer incidence and to develop recommendations consistent with good nutritional practices and likely to reduce cancer risk that could be communicated to the public. 4 The NAS Committee on Diet, Nutrition, and Cancer concluded that although a direct association between diet and cancer could not be made, the scientific evidence was sufficient to support formulation of interim guidelines. Several scientific organizations and G o v e r n m e n t agencies have formulated dietary guidelines for Americans to reduce cancer and heart disease risk and to promote overall health. Although specific guidelines may differ in detail among the groups, the guidelines recommended are consistent. The current NCI dietary guidelines for cancer prevention were partly derived from the 1982 NAS committee report and were supplemented by NCI workshops and a comprehensive review of fiber data. The NCI dietary guidelines are compared to other guidelines issued by other U.S. scientific organizations and government agencies in Table I, These guidelines are consistent with those formulated by the American Cancer Society (ACS), The NCI has continued to review and systematically evaluate new information on the diet and cancer relationship. When sufficient new information exists, dietary recommendations to reduce cancer risk will be reviewed and, if needed,

revised. A workshop for this purpose is planned for Autumn 1989. The dietary guidelines for cancer prevention are also consistent with the general recommendations of the 1988 Surgeon General's Report on Nutrition and H e a l t h ) ~ The report focuses on the relationship of diet and chronic disease incidence, including cancer. Intended primarily for nutrition policymakers, the report summarizes those scientific developments related to diet and nutrition that have widespread implications for human health. The report concludes that the American population consumes too much fat and too little complex carbohydrates, fiber, and fruits and vegetables.

Diet and cancer versus diet and heart disease

Translation of research results into dietary guidelines can be controversial when research findings are not consistent or conclusive, as is the case with the association of diet and cancer. Similar circumstances existed in the 1970s with respect to the causal relationship between diet and coronary heart disease ( C H D ) . At that time, evidence was clear that elevated serum cholesterol levels induce atherosclerosis, thereby increasing risk of heart attacks. Less clear, but suggestive data indicated that major dietary factors such as saturated fat and cholesterol influence serum cholesterol levels. Controversy over existing animal, epidemiologic, and clinical data that correlated dietary factors with heart disease and its associated risk factors was overcome by support for the widespread promulgation of dietary recommendations for the general population. In 1977, the Select Committee on Nutrition and H u m a n Needs of the U.S. Senate urged the adoption of the American Heart Association's 'Dietary

Table I. A Comparison of dietary guidelines: United States

Recommendations Fat Carbohydratetfiber Fruitslvegetables/grains Obesity Alcohol *National Academy of Sciences. tAmerican Cancer Society. ,+American Heart Association.

USDA/USDHHS, Dietary Guidelines for Americans, 1980, 1985 X X X X

NAS* 1982

ACS+ 1984

X

X

X

X X X

X

AHA~- NCI 1988 1988 X X X X

X X X X X

Surgeon General 1988 X X X X

NAS 1989 X X X X X

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Goals for the United States', which recommended reducing total fat consumption from 40% to 30% of caloric intake, saturated fat consumption to 10% of caloric intake, and cholesterol consumption to 300 mg day -~. Proponents of the dietary goals felt that the benefits of making recommendations outweighed the risks in postponing their promotion until conclusive data demonstrated that dietary modifications directly reduce the risk of heart disease. 4~ However, opponents discounted much of the data as inconclusive and believed that reduced morbidity and mortality should be demonstrated by clinical intervention trials before public recommendations were made. 42'43 Experts now agree that appropriate dietary modifications to reduce total serum cholesterol and lowdensity lipoprotein cholesterol levels also decrease the risk of atherosclerosis and coronary heart disease (CHD). Numerous recent investigations, including epidemiologic data and more than a dozen clinical trials, allow us to be reasonably assured that dietary measures will afford significant protection against CHD .2,44 The demonstration and acceptance of diet as a significant and controllable factor in reducing cancer risk is now seen as highly probable, if not conclusive. Therefore, the most prudent and beneficial course is to use existing knowledge and promote adherence to NCI's prudent dietary guidelines while continuing to investigate the issues of causality,

The need for dietary guidance Does the public really need dietary guidance? To answer this question and to assess the potential benefits from the dissemination of dietary guideline information, it is necessary to estimate how the actual dietary intake of individuals compares with recommended eating patterns. It is evident that the average American does not meet the 20 to 30 grams day -1 (g d -1) of dietary fiber intake recommended by NCI. Recently, Lanza et al. 45 reported the mean fiber intake in the U.S. adult population to be significantly lower (11 g d-1), based on 24 h recall food consumption data from 11,658 adults interviewed between 1976 and 1980 in the Second National Health and Nutrition Examination Survey (NHANES II). A marked racial effect was evident, with blacks having lower fiber intakes than whites in both sexes across all age groups. Patterson and Block, using the NHANES II data, evaluated the American diet with respect to the dietary guidelines aimed at reducing cancer risk by examining the consumption of foods thought to be protective or harmful with respect to cancer

incidence. 4~ Results indicate that the American diet does not include recommended amounts of fruits and vegetables, particularly cruciferous vegetables and those high in vitamins A and C, or recommended fiber from cereals, grains, and breads. U.S. diets include large amounts of smoked and salted meats such as bacon and sausages, which may increase cancer risk. On a single dietary recall day, percentages of respondents consuming any foods in recommended categories were : fruit, 59%; vegetables, 75 to 80%; cruciferous vegetables, 18%; fibrous vegetables, 20%; fruits/vegetables high in vitamin C, 28%; fruits/vegetables high in vitamin A, 20%; high-fiber cereals/whole grain breads, 16%; red meat, 55%; bacon and lunch meats, 43%. The diets of females, blacks, and older Americans approached the guidelines more closely than the diets of males, whites, and younger Americans. Based on this evaluation, there appears to be a widespread need for nutrition education to promote modification in dietary behavior.

USE OF INFORMATION CHANNELS TO REACH LARGE POPULATIONS One of NCI's continuing efforts is to establish appropriate channels to route information to the public, Such information channels for diet-related cancer prevention include the food marketplace, primary care settings, the workplace, schools, social organizations, churches, public health agencies, and NCI's Cancer Information Service (CIS) and Cancer Prevention Awareness Program (CPAP). Recently, the marketplace has been shown to be an important channel for motivating changes among the public. A number of supermarket nutrition programs have explored the potential for conducting in-store and multimedia nutrition education programs to modify behaviors related to fat, cholesterol, sodium, and calorie consumption. Two successful studies have been sponsored by the Minnesota Heart Health Program. Results from Shop Smart for Your Health, a study designed to inform consumers about low-fat, low-sodium products, indicated that 27% and 41% of respondents modified their food choices in two communities after participating in the study. 47 After the implementation of Lean Meats Make the Grade, a collaborative program with the meat industry, 80%-lean ground beef outsold 70%-lean ground beef in test stores and meat cuts for low-fat dishes such as stirfry were purchased more frequently. In the Washington, DC, area in 1984, Giant Food

Strategies for cancer prevention

Inc. (a supermarket chain), and the Food and Drug Administration developed the Special Diet Alert Program, which is designed to influence consumers to purchase specific name-brand products that are low or reduced in Sodium, calories, cholesterol or fat. Based on analyses of food sales data, sales of shelf-marked products increased 4 to 8% in test stores when compared with control stores. 4s'49 Based on the encouraging results from these supermarket intervention studies, Giant Food and NCI initiated the 'Eat for Health' study in 1986. This 4 year collaborative effort was designed to inform consumers about nutrition and health promotion related to cancer risk reduction, to encourage positive dietary behavior change, and to further test the effectiveness of the supermarket as a site for consumer education. Program materials included special shelf labels highlighting foods that are high in fiber and low in cholesterol, fat, calories, and sodium; a food guide containing nutrient information on selected food items that complements the shelf labels; a monthly bulletin containing nutrition tips and healthy recipes; radio, television, and newspaper campaigns; and other special contests and in-store programs. To assess the effectiveness of this campaign, sales data for more than 20,000 food items have been tracked in selected test stores before, during, and after the intervention period. Three surveys were used to assess changes in consumer knowledge, attitudes, and behaviors resulting from this program. Preliminary results show that this program has been successful in changing shopping behavior. Further development is planned to promote diet modification in minorities and other groups who were not effectively reached by the 'Eat for Health" program. Other important information channels are health professionals, especially physicians. Because physicians are seen as the most authoritative source of medical and health information, they can be very effective in promoting cancer prevention behaviors such as smoking cessation and dietary modification. In the case of dietary modification, qualified dietitians and nutritionists are important in complementing the physician's efforts. The worksite setting offers access to a substantial proportion of the adult population and includes social support systems to assist individuals in changing their behaviors. Worksites offer the opportunity to make lifestyle changes that support the messages related to health promotion and disease prevention. An increasing number of American companies have developed programs aimed at overall health and reduction of risk factors for major diseases such as cancer and cardiovascular disease that focus on diet

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modification and weight control. In addition, employers are participating in cancer education and early detection screening programs aimed especially at lung, colorectal, breast, and uterine cancer. Strategies that focus on identifying and treating high-risk adults often ignore younger individuals who may already have increased their physiological risk. More important~ the young may have adopted behaviors known to increase cancer risk, including the consumption of high-fat, low-fiber diets. Schoolbased intervention can be used to educate young people in elementary through high school about diet modification and other cancer-related risk factors, and achieving lifelong risk reduction. School programs may potentially influence long-term behaviors and consistently reach more youths than any other institutional program. The National Cancer Institute, with the American Cancer Society, has developed such a program, with tested classroom modules and training materials for teachers and school cafeteria workers. 5~ The Cancer Information Service, by maintaining regional cancer information centers accessible through a national toll-free telephone number (1800-4-CANCER), provides up-to-date information on all aspects of cancer to any health professional or interested individual. The Cancer Information Service uses NCI's Physician Data Query (PDQ) directory of patient and physician treatment information, which stores reviewed and documented information on state-of-the-art cancer treatment and clinical trials. The NCI is exploring the feasibility of supplementing PDQ with cancer prevention information. These efforts will include providing smoking cessation guidance to reduce the number of adult smokers and encouraging the selection of low-fat, high-fiber foods in the American diet. Introduced in 1984, the Cancer Prevention Awareness Program at NCI is a long-term public education program initiated by the Office of Cancer Communications to improve public knowledge and attitudes related to cancer prevention and to encourage individuals and special populations to adopt healthful behaviors that reduce cancer risk. Program messages emphasizing personal control of lifestyle factors such as diet, smoking, and sunlight exposure are disseminated by the mass media, the CIS, and a variety of health organizations. Diet and nutrition-related information materials distributed through this program are available in supermarkets and encourage the selection of a lowfat, high-fiber diet to reduce cancer risk. Other diet and health promotional efforts include health fairs, exhibits, video modules, and mass media discussions.

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BIOTECHNOLOGY AND THE CHANGING FOOD SUPPLY Effective strategies for diet modification depend to some degree on the wide availability and accessibility of appropriate types of foods and food products. Advances in food technology and processing such as canning and refrigeration have reduced food contamination and ensured a safe food supply. These advances are believed to have contributed in part to the declining incidence and mortality rates for gastric cancer over the past 50 years. Recent developments in agricultural and food biotechnology could have a dramatic effect on the proliferation of appropriate foods in the marketplace. The development of genetically engineered plants via gene transfer systems provides new opportunities for crop improvement and food product development. 51 The enhancement of characteristics such as taste, shelf life, or nutritive quality can be achieved through genetic engineering. The commercialization of genetically engineered crops and products is expected to revolutionize product improvements in agriculture and the food industry over the next several years. Some of the newly designed products may contain specialized starches to improve texture and storage properties or proteins with nutritionally balanced amino acid compositions. 52 In addition, regulation of softening and ripening enzymes can improve the postharvest quality of fruits and vegetables, making it possible to develop ripening-delayed cultivars with improved storage and handling characteristics. 51 Engineered microorganisms may be developed to produce 'natural' colors, flavors, texturizers, and nutrients in manufactured food products and make these ingredients less costly and more widely available. 53 Foodproducing animals are also being studied with a focus on growth, nutrition, reproduction, and genetic improvement to foster heritable characteristics such as reduced fat in pork and beef and reduced cholesterol in eggs. 54 Techniques for reducing the amount of and/or caloric value of fats and oils in foods have long been of interest to researchers. A recent advancement in this area is the development of the nonabsorbable fat substitute sucrose polyester (SPE). SPE has physical, culinary, and organoleptic properties similar to those of dietary fat, and its use has been shown to reduce serum cholesterol and low-density tipoprotein cholesterol levels in animals and humans, s5'56 Formed by the reaction of sucrose with long-chain fatty acids, Olestra, a commercial SPE, has the taste and consistency of vegetable oil and can be used in products such as salad dressings, margarines, ice cream, candy, and other snacks. Olestra may in-

crease excretion of bile acids that have been implicated in colon cancer development, but overconsumption can lead to anal leakage and interference with the absorption of fat-soluble vitamins. 5(~ Another recently developed fat substitute, Simplesse, is fabricated by heating and blending egg white or milk proteins. 57

Potential jor impact on cancer rates New technologies may reduce cancer risk because of their potential to change the nutrient or chemical constituents of foods. For example, of all the dietary components studied, fat intake offers the strongest evidence for a causal relationship with cancers of the breast, colon, and prostate. The development of low-calorie oils and fat substitutes could reduce the percentage of fat contained in many processed foods or provide alternatives with high appeal. For exampie, consumption of lower fat meats that are modified either genetically or by bovine growth hormones could reduce dietary fat intake in groups that are high meat consumers. Increased consumption of vegetables and other fiber-rich foods such as grains and legumes may be encouraged by the availability of higher quality and better tasting products, which are also improved by pest and disease resistance, controlled ripening, and optimization of nutrient content. For example, the desirability of a tomato that tastes vine-ripened or frozen fruits and vegetables with fresh-picked tastes and textures is likely to increase consumption, tn addition, future plant foods and products may be bioengineered to maximize the beneficial nutritive and nonnutritive constituents and to minimize those that may cause cancer. For example, the enzymatic treatment of carrot juice increased beta-carotene content from 7 percent to 60 percent while germination produced a tenfold increase in the vitamin C content of peas and beans, s~

Benefits of health sciences~industry cooperation The health consciousness of the U.S. population largely results from a concerted effort on the part of health professionals to educate consumers. Consumers are now more willing to make dietary choices that reflect their knowledge concerning the relationship between diet and disease, It is important for industry to understand and respond to the needs of consumers by providing health-promoting, safe foods. Therefore, cooperation between industry and the health sciences is essential for continued response to public health concerns.

Strategies f o r cancer p r e v e n t i o n

Due to concerns about dietary fat, beef consumption has dropped in recent years, providing impetus for breeders to raise leaner animals. 59 In 1984, the Kellogg Company, with NCI's approval, summarized the NCI dietary message on the back of the All Bran box (a high-fiber cereal) and developed media advertisements promoting the message. The NCI's toll-free telephone number and address were included so that consumers could easily get more information. Since that time, other companies have incorporated NCFs messages into their marketing programs. 6~ Cooperating with industry gives health science researchers, educators, and policymakers access to market research and sales data, providing them with insight concerning market trends for consumer food choices. This information serves as the basis for developing health and nutrition education strategies. More importantly, this cooperation will lead to the availability of nutritionally acceptable, palatable, and affordable food choices so that consumers can modify their diets according to dietary recommendations associated with health promotion and cancer prevention,

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CONCLUSION Although it is not conclusive, sufficient evidence exists to support the relationship between certain dietary factors and cancer risk reduction. With the development of an increased understanding of cancer etiology, refinements in public dietary guidance will continue to be made based on the scientific evidence. Considering the great variety of foods and food products currently in the marketplace due to advances in biotechnology, a knowledgeable consumer should be able to select a healthful diet. Preventing cancer through diet modification is a timely and challenging area for both research and its application and has exciting implications for public health benefits.

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REFERENCES

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1. Doll R, Peto R: The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. JNC1 66, 1191 (1981). 2. National Academy of Sciences, National Research Council~ Food and Nutrition Board: Diet and Health: lrnplications for Reducing Chronic Disease Risk. Council on Life Sciences, Washington, DC, National Academy Press (1989). 3. Palmer S: Diet, nutrition, and cancer. Prog Food Nutr Sci 9, 283 (1985). 4. National Academy of Sciences, National Research

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