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Departments of Food Science, Nutritional Sciences and Biochemistry, University of Missouri, Columbia, MO 65211 and * Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202-3972
2To whom correspondence should be addressed. E-mail: macdonaldr{at}missouri.edu.
Dietary components have long been associated with both cancer prevention and promotion. In 1982 the Committee on Diet, Nutrition and Cancer of the National Research Council published a comprehensive report on the role of diet, nutrition and cancer (1
). This report reviewed the substantial epidemiological evidence of a diversity of cancer incidence among cultures with differing food consumption patterns, as well as experimental evidence in animal models. In the executive summary, the committee recommended lowered intake of total fats and increased intake of plant foods that provide fiber, vitamins, minerals and nonnutritive components. In response to this publication, much emphasis has been placed on public health messages to reduce fat and increase plant food intake as a means of reducing cancer risk. The American Institute for Cancer Research and the World Cancer Fund recently compiled a comprehensive review of diet and cancer relationships (2
) that identified dietary factors and their association with specific types of cancers. Consumption of vegetables was associated with reduced risk of those cancers with high incidence in the United States, including lung, breast, prostate and colon. The evidence was strongest for correlations between high vegetable consumption and reduced cancer of the lung and colon and less so for breast and prostate. For each of the cancers, total fat was identified as being possibly related to increased risk.
Epidemiological evidence has provided clues to the relationships between dietary factors and cancer incidence but by their very nature are incapable of supporting cause-and-effect conclusions for a set of diseases in which the causative factors are still poorly understood. Willett (3
) recently described the changing view of diet and cancer relationships that have occurred during the past 20 y. He outlined evidence that dietary fat may not be as significant a factor in cancer of the breast as was first defined. This conclusion was based on several studies, including a pooled analysis of several prospective studies of 351,821 women in which dietary fat intake was not associated with breast cancer risk (4
). Furthermore, the relationship between fiber intake and colorectal cancer risk was not supported by newer studies (5
). One limiting factor in epidemiological studies is the inability to identify cellular mechanisms through which dietary components affect the carcinogenic pathway. Hence, experimental evidence at the molecular, cellular and organismal levels is required to define diet and cancer relationships.
The carcinogenic process requires initiation of DNA damage, promotion of cells harboring the mutation and progression of the abnormal cell growth. Tumors must also induce angiogenesis to provide nutrients and remove wastes from the growing cell mass. Through this process, tumor cells acquire specific characteristics that distinguish them from normal somatic cells (6
). Numerous growth factors, hormones and molecules that regulate cellular signaling events are involved in the carcinogenic process (7
). Dietary factors potentially affect each phase of the carcinogenic process; however, a comprehensive understanding of the role of diet in cancer is far from achieved. Advances in technology have provided nutrition researchers with tools to more fully define diet and cancer relationships. With these tools the molecular targets of nutrients and nonnutritive dietary components in the carcinogenic process are beginning to be identified. In line with the concept of developing a "new paradigm in nutrition research" (8
), integration of molecular biology and genetics with nutrition research is essential for characterizing dietary influences on cancer.
The symposium "Diet, Growth Factors and Cancer’ brought together scientists with diverse expertise to discuss aspects of the carcinogenic process that are influenced by dietary factors. Dr. Gary Johanning, from the University of Alabama at Birmingham, discussed the role of vitamin status on DNA methylation. Hypomethylation is an established characteristic of cancer cell DNA, with the degree of hypomethylation increasing from normal through benign, primary and secondary malignancy in some cancers. Johanning and colleagues have observed that tissue vitamin levels are associated with global DNA methylation status, thus identifying a cellular mechanism for vitamins in the carcinogenic process. Dr. Kenneth Soprano, from the Temple University School of Medicine, discussed the role of retinoid receptors in squamous cell carcinomas (SCCs).3 Retinoids are known to inhibit development of a number of different types of tumors, and retinoid analogs are of increasing interest as cancer therapeutics. By using transfection of dominant negative mutant receptors into cultured cells lines, Soprano and colleagues concluded that the growth inhibitory response of SCC cells to retinoid treatment is mediated by RARs in general and specifically retinoic acid receptor (RAR-
). Dr. Mary Beth Martin, from the Georgetown University, discussed the cross-talk between the insulin-like growth factor (IGF) and estrogen receptors (ERs). Based on evidence from Martin’s group in breast cancer cells, IGF-I regulates both the expression and activity of ER-
in part through the phosphatidylinositol 3-kinase/Akt pathway. Dr. Rayudu Gopalakrishna, from the University of Southern California Keck School of Medicine, discussed the role of antioxidants in mediating the activity of protein kinase C (PKC). Gopalakrihsna presented evidence that methylselenol, a postulated cancer-preventive compound, reacts with PKC-bound tumor-promoting fatty acid hydroperoxide and that the locally generated methylseleninic acid causes specific inactivation of PKC in cells. Dr. Leonard Augenlicht, from the Albert Einstein Cancer Center, discussed key genes involved in colon cancer and their response to short chain fatty acids and chemopreventive agents. Augenlicht and co-workers used microarray analysis on human tissue and transgenic animal models to characterize the response of genes to these compounds. Microarray analysis is an extremely powerful tool that allows simultaneous estimation of the expression of thousands of known and unknown genes, thus permitting time-dependent analyses to determine sequence of changes in gene expression and identification of classes of genes that are altered at various phases of the carcinogenic process. Dr. Gary Posner, from the Johns Hopkins University, presented a summary of his research on vitamin D analogs that have been created for cancer chemoprevention. The most promising of these compounds are available for preclinical toxicological and pharmacological testing.
The symposium was organized by the American Society for Nutritional Sciences Diet and Cancer Research Interest Section. Funding for the symposium was provided by the American Institute for Cancer Research, the Campbell Soup Company and Kraft Foods.
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FOOTNOTES |
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3 Abbreviations used: ER, estrogen receptor; IGF, insulin-like growth factor; PKC, protein kinase C; RAR, retinoic acid receptor; SCC, squamous cell carcinoma.
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LITERATURE CITED |
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 TOPINTRODUCTION LITERATURE CITED |
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1. Committee on Diet, Nutrition and Cancer (1982) Diet, Nutrition and Cancer. Assembly of Life Sciences, National Research Council 1982 National Academy Press Washington, DC.
2. World Cancer Research Fund/American Institute for Cancer Research (1997) Food, Nutrition and the Prevention of Cancer: A Global Perspective 1997 Banta Book Group Menasha, WI.
3. Willett, W. C. (2001) Diet and cancer: One view at the start of the millennium. Cancer Epidemiol. Biomarker Prev. 10:3-8.
4. Smith-Warner, S. A., Spiegelman, D., Adami, H.-O, Beeson, W. L., van den Brandt, P. A., Folsom, A. R., Fraser, G. E., Freudenheim, J. L., Goldbohm, R. A., Graham, S., Kushi, L. H., Miller, A. B., Rohan, T. E., Speizer, F. E., Toniolo, P., Willett, W. C., Wolk, A., Zeleniuch-Jacquotte, A. & Hunter, D. J. (2001) Types of dietary fat and breast cancer: A pooled analysis of cohort studies. Int. J. Cancer 92:767-774.[Medline]
5. Smith-Warner, S. A., Spiegelman, D., Yaun, S. S., Adami, H.-O, Beeson, W. L., van den Brandt, P. A., Folsom, A. R., Fraser, G. E., Freudenheim, J. L., Goldbohm, R. A., Graham, S., Miller, A. B., Potter, J. D., Rohan, T. E., Speizer, F. E., Toniolo, P., Willett, W. C., Wolk, A., Zeleniuch-Jacquotte, A. & Hunter, D. J. (2001) Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies. J. Am. Med. Assoc. 285:769-776.
6. Evan, G. I. & Vousden, K. H. (2001) Proliferation, cell cycle and apoptosis in cancer. Nature (Lond.) 411:342-348.[Medline]
7. Ponder, B. A. J. (2001) Cancer genetics. Nature (Lond.) 411:336-341.[Medline]
8. Greenwald, P., Milner, J. A. & Clifford, C. K. (2000) Creating a new paradigm in nutrition research within the National Cancer Institute. J. Nutr. 130:3103-3105.
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