Nutrigenomics and Cancer
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M. Ardekani, Ali
Ph.D., Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran, P.O. Box: 19615-1177, Tel: +98 21 22432020, Fax: +98 21 22432021, E-mail: Ardekani@avicenna.ac.ir
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Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR , Tehran, Iran
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Jabbari, Sepideh
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Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR , Tehran, Iran
Abstract: Cancer incidence is projected to increase in the future and an effectual preventive strategy is required to face this challenge. Alteration of dietary habits is potentially an effective approach for reducing cancer risk. Assessment of biological effects of a specific food or bioactive component that is linked to cancer and prediction of individual susceptibility as a function of nutrient-nutrient interactions and genetics is an essential element to evaluate the beneficiaries of dietary interventions. In general, the use of biomarkers to evaluate individuals susceptibilities to cancer must be easily accessible and reliable. However, the response of individuals to bioactive food components depends not only on the effective concentration of the bioactive food components, but also on the target tissues. This fact makes the response of individuals to food components vary from one individual to another. Nutrigenomics focuses on the understanding of interactions between genes and diet in an individual and how the response to bioactive food components is influenced by an individual’s genes. Nutrients have shown to affect gene expression and to induce changes in DNA and protein molecules. Nutrigenomic approaches provide an opportunity to study how gene expression is regulated by nutrients and how nutrition affects gene variations and epigenetic events. Finding the components involved in interactions between genes and diet in an individual can potentially help identify target molecules important in preventing and/or reducing the symptoms of cancer.
Introduction :
It is believed that dietary habits as an important modifiable environmental factor, influence cancer risk and tumor behavior. It is estimated that diet influences about 30-40% of all cancer cases, however, the actual percentage is not known and depends on the specific type of cancer and the specific com-ponents of diet (1).
Many studies indicate that breast, prostate, liver, colon and lung cancers are linked to the dietary intakes (2). However, the linkage has not shown to be consistent perhaps due to the multifactorial and complex nature of cancer and the specificity of dietary constituents and their effects on genetic path-ways. Although excess calories are generally linked to enhanced cancer risk, many bio-active components in food can potentially provide protection at several stages during cancer development (2). Some of these bio-active components such as calcium, zinc, selenium, folate, vitamins C, D and E, caro-tenoids, flavonoids, indoles, allyl sulfur com-pounds, conjugated linoleic acid and N-3 fatty acids may influence carcinogen metabolism, cell signaling, cell cycle control, apoptosis, hormonal balance and angiogenesis (3). Studies of variations in cancer incidence among and within populations under similar dietary habits suggest that an individual’s res-ponse to food may reflect genetic predisposi-tion of an individual as well as differences in gene and protein expression patterns in the individual. Recently the effects of nutrition on DNA methylation and the role of epigenetic events in cancer prevention have also been reviewed (4).
Biology of cancer
Malignant cells are characterized by the upregulation or activation of many signaling pathways that are involved in proliferation, apoptosis, invasion and angiogenesis (5). In malignancy, many proteins and pathways are observed to be up regulated and opposing malignant behavior of cells.
Hanahan and Weinberg (6) have summar-ized the derangements in signaling that are required for the formation of a fully invasive tumor. These include:
- Self-sufficiency in growth signals or ac-tivation of growth signals without the need for exogenous signals
- Insensitivity to proliferation inhibiting sig-nals
- Activation of survival pathways
- Indefinite replication which leads to avoi-dance of terminal differentiation or sense-cence
- Angiogenesis initiation
- Invasion and metastasis
During the carcinogenic process, multiple oncogenic mutations occur that are often functionally redundant. It has been suggested that no single pathway appears to be the cause of cancer, therefore, multiple dietary and/or chemical interventions are likely to prevent cancer growth (5,7).
Individual foods and their constituents
Evidences suggest that foods offer advan-tages over their isolated constituents in treat-ment of cancer. This may be due to presence of multiple bioactive compounds within the food that exert additive or synergistic effects. For example, in treatment of human lung cancer cells which undergo apoptosis, whole green tea is more effective than the individual constituents of the green tea in inhibiting TNF-a release (8). These effects appear to be mediated through enhanced incorporation of the tea polyphenols into the cells. In a rat study in which prostate carcinogenesis was induced by N-methyl-N-nitrosourea (NMU)- testosterone, tomato powder was shown to inhibit carcinogenesis. These effects were suspected to be at the levels of absorption, retention, or metabolism (9). In another study a fat-soluble extract from vegetable powder was found to be more efficacious than ß-carotene in inhibiting cell proliferation in a lung cancer cell line (10). There have been also cases wherein, the foods were found not to be as effective as their isolated components, suggesting that the food may contain constituents that inhibit the cellular response. Although the mechanisms involved in these processes are no
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