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Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 and * American Institute for Cancer Research, Washington, DC 20009
3To whom correspondence should be addressed. E-mail: vlwgo{at}mednet.ucla.edu.
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ABSTRACT |
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 TOP ABSTRACT LITERATURE CITED |
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KEY WORDS: • diet • cancer • prevention • evidence-based • genomic • medicine
Over the last 100 y, monumental scientific achievement and progress in medicine have transformed the practice of medicine and the health care delivery system. In 1910, the Flexner report highly criticized medical training in the United States and concluded that medical education be grounded in science (1). This report changed medical practice and defined the structures of medical education, research, and academic institutions.
The achievements and the advancements in modern medicine may be largely attributed to reductionism, a predominant theory in science based on understanding the whole in terms of its individual parts. The human body is organized into organ systems, tissues, cells, and cell elements that are further reduced to genetic and atomic components, and the established structure–function relationship is founded on the sciences of anatomy, physiology, biochemistry, molecular biology, and genetics. Disease is viewed as a failure of any one or more of these structures and functions of human physiology. Physicians systematically diagnose this breakdown and apply the appropriate treatment; for example, surgery is used to remove a diseased part or natural or synthetic pharmacological agents are administered to correct a dysfunction. This approach fostered a highly specialized practice of medicine, one that harnessed infection control and now uses technology and newly developed designer drugs to focus on organ-system disorders and diseases. In the postgenomic age, the inevitable current aim is to apply gene therapy to health promotion and disease prevention (2) (Fig. 1).
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Management of chronic disease through clinical research and patient trials produced new databases that are used to evaluate and to apply evidence to already established clinical practice guidelines. This has led to the advent of evidence-based medicine (4). In this new millennium, the public and its health care systems are faced with more chronic illnesses related to aging; lifestyle; environment; and dietary factors, such as cancer, diabetes, osteoporosis, cardiovascular, and other chronic illnesses (5). The complete sequencing of the human genome has signified the beginning of the postgenomic era, in which new technologies and techniques invoke a fundamental shift in biomedical education, research, and the practice of medicine (6,7). Medical practice now comprises health promotion and disease prevention and is on the verge of transformation as the scientific and medical communities move from evidence-based medicine to genomic medicine.
What is evidence-based medicine?
The current approach to clinical decision making in medical practice is based on the diagnosis of disease in consideration of signs and symptoms in correlation with the structure and the function of the organ system, established etiology, and recommended appropriate therapy. The physician is a patient’s main source of care, which is mostly reactive and relies, to a certain extent, on the experience, knowledge, and expertise of the physician. Physicians may refer their patients to specialized medical professionals for further care and treatment. With the development of evidence-based medicine, clinicians are able to consult the rich resources of current and past evidence and, subsequently, to draw the best conclusions to particular problems in clinical decision making. Clinical and scientific evidence inevitably reveals both what medicine knows and does not know, allowing clinicians to integrate the available evidence with their own clinical judgment to provide appropriate patient care. This follows with the definition by Sackett et al. (4) of evidence-based medicine as "the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of the individual patient. It means integrating individual clinical expertise with the best available external clinical evidence from systematic research." Therefore evidence-based medicine encompasses the systematic approach of formulating a question, developing literature search strategies, and evaluating and applying the evidence. Various databases and resources are now available; these include the Agency for Health Care Research and Quality: Evidence-Based Practice, the Cochrane Library, the National Guidelines Clearinghouse, and various practice guidelines developed by academic medical societies (8).
The evidence-based review process consists of a stepwise general procedure that includes 1) the development of an appropriate, focused, and clear measurable question from observations made during the patient encounter; 2) completion of literature searches; 3) determination of the quality of designs; 4) assessment of the comparability of source populations of cases and control studies; 5) recognition of whether controls for potential confounding factors and measurement errors were included; and, finally, 6) the search for evidence of any difference in effect by age, gender, or subsites of disease. The reviewer must also consider any evidence of a dose–response effect or heterogeneity effect between studies; the integration of evidence by pooled analysis or meta-analysis; and the evaluation of results and expert panel recommendations. The prevalence of evidence-based medicine has reached the realms of clinical decision making and medical school curricula, and insurance companies even draw on its invaluable resources to formulate their guidelines for client reimbursement. Furthermore, many clinicians consider evidence-based medicine a criterion standard, whereas others view it as a recipe for medicine.
Evidence-based review in diet and cancer prevention
The Food and Nutrition Board of the Institute of Medicine has used the applications of evidence-based reviews by expert panels to establish the Recommended Dietary Allowance of particular nutrients (9) and Dietary Reference Intakes (10). In 1982, the National Cancer Institute (NCI)4 Cancer Commission of the National Academy of Sciences and the Committee on Diet, Nutrition, and Cancer published a monumental report, Diet, Nutrition, and Cancer, through the National Research Commission (11). This comprehensive report provided available evidence and the subsequent conclusion that most major cancers are influenced by dietary patterns. In addition, Diet, Nutrition, and Cancer spurred various national recommendations for the development of research agendas on investigation of the diet–cancer link, including expansion of basic research on molecular and cellular nutrition, identification of foods and dietary constituents that may alter cancer risk, and elucidation of the mechanisms by which these dietary constituents modulate cancer risk. A chronology of the national agenda highlights and accomplishments in relation to the American Institute for Cancer Research (AICR) mission was presented previously (12).
In 1997, AICR and World Cancer Research Fund (WCRF) challenged an international expert panel to pursue the following goals: 1) review the scientific and other expert literature linking food, nutrition, food processing, dietary patterns, and related factors with human cancer risk from a global perspective; 2) devise a series of dietary and other recommendations suitable for all societies for reduction of cancer risk; and 3) consider both the feasibility and the policy implications of global implementation of these recommendations. The resulting AICR/WCRF report provided a global perspective on diet, nutrition, and recommendations for cancer prevention (13); the expert panel arrived at the scientific consensus that cancers are largely preventable and that the most effective methods for reducing risks are to avoid tobacco use, to consume an appropriate diet, and to limit exposure to occupational and other environmental carcinogens. Furthermore, the panel estimated that 30–40% of cancer cases worldwide are preventable by feasible dietary means. Subsequently, NCI completed specific evidence-based reviews for cancer prevention; the NCI database, accessible online, presents the levels of evidence (i.e., randomized trials, case-control, and cohort studies) and is routinely updated (14). The World Health Organization International Agency for Research Cancer (IARC) recently published a series of handbooks on cancer prevention in relation to dietary factors, including fruits and vegetables (15,16). This extensive review of evidence-based medicine prompted recommendations on diet and cancer prevention from various governmental and health organizations, and led to the development of current clinical practice guidelines, based on common evidence consensus and proposals by WCRF/AICR, NCI, and IARC. These are detailed below.
Body weight, weight gain, and physical activity. There is sufficient evidence in humans that avoidance of weight gain has a cancer-preventive effect with regard to cancers of colon, breast (postmenopausal), endometrium, kidney (renal cell), and esophagus (adenocarcinoma). For all other sites, evidence is inadequate. In addition, sufficient evidence exists for a preventive effect of physical activity on cancers of the colon and the breast. Evidence of this preventive effect on cancers of the endometrium and the prostate is still limited, and, for all other sites, the evidence is inadequate. The recommendations from IARC, WCRF/AICR, and NCI (13–16) are streamlined and consistent. These suggestions include maintaining body weight in the lower part of the desirable range (BMI between 18.5 and 25), avoiding weight gain of >5 kg during adult life, and weight loss of 5–10% in already overweight or obese subjects. Individuals should also be encouraged to perform moderate activity, such as brisk walking or cycling, for at least 30 min several days a week; such physical activity is also known to reduce the risk of chronic diseases, including coronary heart disease and diabetes.
Consumption of alcohol. WCRF/AICR and the NCI Physician Data Query (PDQ) database revealed convincing evidence that alcohol increases the risk of mouth, pharyngeal, laryngeal, and esophageal cancers, and that smoking greatly increases the risk. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) reported in 2003 that, compared with nondrinkers, women who consume an average of 1 drink per day appear to have a 10% increase in breast cancer risk (17). The risk may be higher for women on hormone replacement therapy or with a family history of breast cancer. Based on these findings, WCRF/AICR, NCI, NIAAA, and the American Cancer Society have stated that consumption of alcohol is not recommended and excessive consumption of alcohol is to be discouraged. For those who do drink alcohol, consumption should be restricted to <5% of total energy for men and <2.5% of total energy for women, or fewer than 2 drinks per day for men and one for women (13,14,17–19).
Consumption of fruits and vegetables. Reviews of the evidence on fruits and vegetables and cancer also resulted in similar findings by the IARC, NCI-PDQ, and WCRF/AICR. Consumption of fruits and vegetables lowers the risk of gastrointestinal cancers (mouth and pharynx, esophagus, stomach, and colorectal). However, there is limited evidence to this effect for cancers of the larynx, the lungs, the ovary, the bladder, and the kidneys. Research has shown that vegetables may have a protective effect against ovarian cancer and that fruit may have an effect on bladder cancer. At present, evidence is inadequate for all other cancer sites. WCRF/AICR thus promotes year-round consumption of a variety of vegetables and fruits that provide 7% or more of total energy and suggests consumption of 400–800 g (15–30 oz) or 5 or more servings per day of a variety of vegetables and fruits. In accordance, IARC (16) recommends consuming at least 400 g/d of a variety of fruits and vegetables, including fiber, and NCI suggests 5–9 servings/d (14). The Iowa Women’s Health Study investigated the effects of adhering to a healthy lifestyle and healthy weight, as well as increasing fruit and vegetable intake based on AICR cancer prevention recommendations, both independently and in conjunction with not smoking (20). The cohort revealed a substantial effect of these factors on reducing cancer incidence, with population-attributable risks (avoidable risks) of 22%; 95% CI: 12–30 for cancer incidence and 11%; 95% CI: –5–24 for cancer mortality (20). Adherence to the AICR cancer prevention recommendations thus has a significant and positive public health effect on cancer incidence and cancer mortality at the population level. These recommendations have now been incorporated into the 2005 U.S. Dietary Guidelines (21).
Genomic medicine
In 2001, the complete sequencing of the human genome marked the beginning of the postgenomic era, where new technologies and techniques are causing a fundamental shift in biomedical research and practice (22). This shift inevitably occurs at all levels of biological organization–from cells to organ systems–to integrate tissue and organ functions in spatial and temporal order. The scientific community and government funding agencies have identified a novel research direction to include the use of genomic, proteomic, and metabolomic technologies, along with the appropriate informatics tools and systems biology, to generate and analyze DNA, RNA, and metabolites in parallel, thus linking gene response, protein activity, and metabolite dynamics to determine molecular function (23). The future of nutrition sciences and its effective application lies in the elucidation of the relationships between diet and health, with the target goal being to improve health and to prevent disease. Genomics has produced a new generation of tools and strategies that will help nutrition scientists to cope with the truths of biological variation and to develop a health monitoring system capable of recognizing individual health and metabolic status (23). This personalized biochemical and metabolic profiling will guide dietary and lifestyle choices and help maintain the health of the individual. Genomic profiling, along with genetic testing to facilitate identification of presymptomatic individuals at risk for specific diseases, allows preventive and therapeutic intervention and is now a part of clinical practice (24). Therefore, the future of genomic medicine in clinical nutrition practice will have genomics, proteomics, and metabolomics used in conjunction with clinical information to screen and to diagnose patients, and the genetic-metabolic results will be integrated using bioinformatics to determine health status and to provide disease prevention strategies (25) (Fig. 2).
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Conclusions
Expert panels of the National Research Council, the NCI, the WCRF/AICR, and the World Health Organization IARC have carried out systematic evidence-based reviews on diet and cancer prevention. The results of these reviews form the current evidence-based recommendations for diet and cancer prevention. As the scientific and medical communities settle into the dawn of the postgenomic era, the gradual but steady transition from evidence-based medicine to genomic medicine will revolutionize health promotion, disease prevention, and the practice of medicine as a whole.
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FOOTNOTES |
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2 Sources of financial support and previous presentation of data: National Cancer Institute/UCLA Clinical Nutrition Research Unit Grant CA42710, NCI grant R25CA73914 and R25CAE96975, and the American Gastroenterological Association/Fiterman Foundation Award.
4 Abbreviations used: AICR, American Institute for Cancer Research; IARC, International Agency for Research Cancer; NCI, National Cancer Institute; NIAAA, National Institute on Alcohol Abuse and Alcoholism; PDQ, Physician Data Query; WCRF, World Cancer Research Fund.
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LITERATURE CITED |
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TOPABSTRACTLITERATURE CITED |
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