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American Institute for Cancer Research, Washington, DC 20009 and * Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095
3To whom correspondence should be addressed. E-mail: research{at}aicr.org.
Nearly 400 people attended the annual International Research Conference on Food, Nutrition, and Cancer sponsored by the American Institute for Cancer Research/World Cancer Research Fund International (AICR/WCRF),4 held July 14–15, 2005, in Washington, DC. Marilyn Gentry, president of AICR and WCRF, opened the conference. This year’s event included plenary sessions, split sessions, and 90 poster presentations that addressed a wide range of topics in many different disciplines of diet–cancer research now being investigated around the world. A progress update on the preparation of the second WCRF/AICR Expert Report Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective was given during the conference luncheon. Evidence linking food, nutrition, and physical activity to the risk of developing cancer will be obtained from 17 systematic literature reviews (SLRs) of >20 cancer sites and a literature review of cancer survivor research. To date, several of these SLRs have been completed and reviewed; all SLRs are expected to be completed by July 2006. The WCRF/AICR Expert Panel is currently meeting to review the SLRs and will issue conclusions and recommendations in its final report, scheduled for publication in October 2007.
The conference’s keynote address focused on the need to develop a comprehensive framework for studying how the many genetic and epigenetic influences present across an individual’s lifetime factor into the cancer process. This framework, called the life-course approach to cancer, is concerned with critical stages during growth and development that serve as checkpoints, when nutrition and related factors can modulate structure and function at the cellular and tissue levels in ways that increase or decrease risk. Variable methylation and demethylation of DNA is one such process that can be programmed in utero via small changes in maternal diet. Understanding how this and other critical factors such as rate of growth, body composition, and lifestyle interact to influence cancer risk within and across generations is an important area of research.
The conference’s first plenary session covered various aspects of the life-course approach to cancer. The first presentation of this session was a review of the scientific evidence suggesting that a combination of factors in early life, including specific environmental, nutritional, and metabolic exposures, as well as accelerated growth and obesogenic diets, may confer increased risk for several cancers. Thus, to have the greatest effect on cancer incidence, nutritional interventions should focus on reducing risk during pregnancy, childhood, puberty, and other critical windows of opportunity. Another presentation discussed the effect of timing of exposure on the chemopreventive effects of vitamins A and D in breast tissue. By determining when, during breast development and malignancy, exposure is most efficacious, it may be possible to pinpoint the underlying mechanisms whereby vitamins A and D exert their anticancer influence. The effect of prepubertal (n-3) PUFA dietary levels on breast cancer risk in rats was the subject of another presentation. Rats fed prepubertal diets low in (n-3) PUFAs had decreased breast cancer risk, whereas rats fed prepubertal diets high in (n-3) PUFAs had increased breast cancer risk; the proposed underlying mechanisms were discussed. The last presentation in these sessions focused on research showing that rats fed the soy component genistein during the prepubertal period or during both puberty and adulthood experienced fewer chemically induced mammary tumors than did rats exposed to genistein during either pregnancy or adulthood alone.
An afternoon split session detailed recent research on several specific phytochemicals and the mechanisms of action whereby they have been shown to exert anticancer effects. The first presentation of the session proposed several molecular targets associated with the cell signaling network, including specific redox-sensitive transcription factors involved in the inflammatory response. The speaker discussed how phytochemical components of turmeric, ginger, chili peppers, green tea, and several other dietary factors interact with these targets to alter or correct undesired cellular functions via anti-inflammatory or antioxidative activity. Another presentation reported on the ability of freeze-dried berries to inhibit chemically derived cancer in the esophagus, colon, and oral cavity in rodents. Extracts of black raspberries were shown to downregulate genes involved in cell proliferation. A Phase I trial showed that black raspberries are well tolerated and that the active components are absorbed in detectable quantities in the plasma. Several clinical trials are now underway that measure the effect of black raspberries on selected biomarkers in the human oral cavity and gastrointestinal tract. The next presentation examined how different pathways involved in signal transduction may be targeted by compounds found in green tea, grapes, rice, and ginger. The next speaker presented evidence for a novel mechanism whereby the active component of green tea, epigallocatechin gallate (EGCG), targets and binds directly to the promiscuous protein hsp90, suggesting that EGCG may be able to exert its anticancer effects in many different cell types. The final presentation proposed that several phytochemicals found in citrus fruits, including auraptene and zerumbone, are potent inhibitors of the enzyme cyclooxygenase-2 and thus are promising chemopreventive agents for inflammation-associated carcinogenesis.
The second split session highlighted findings from animal models used in nutrition and cancer prevention studies and examined their relevance and applicability to human cancer. The first presentation detailed a novel model of malignant melanoma in which mice are responsive to a single neonatal dose of UV radiation and prone to development of lesions in stages similar to human disease. Sunscreen-based prevention studies are currently underway. Another presentation detailed work using the ferret model in studying the role of carotenoids in lung cancer. Ferrets offer an excellent model for such investigations because, unlike other animal species, they are able to absorb levels of intact carotenoids that are commensurate with those in humans. Another presentation focused on the use of the Min mouse model to study the effect of exercise on bowel cancer development. Min mice carry a damaged copy of the Apc gene and develop multiple polyps in the gut spontaneously; the number, size, and location of these polyps can be altered by environmental influences such as diet and exercise. The family of genes known as retinoic acid receptors (RARs) was the subject of another presentation. These factors control the expression of hundreds of other genes, and one form, RAR ß, has been shown to induce breast tumor cell death. Researchers are using a mouse model of human breast cancer and expression-profiling technology to examine cellular processes regulated by RAR ß. The last presenter discussed the many challenges associated with the available animal models for prostate cancer.
During the morning of the second day of the conference, a split session focused on research charting how vitamins, minerals, and phytochemicals combine with specific cellular and molecular structures, and with one another, to keep the cancer process at bay. The first presentation detailed ongoing research that is investigating how folate status, riboflavin status, and a particular genetic polymorphism interact to modulate risk at different cancer sites. Another presenter discussed new research on the interaction of aging and folate depletion, which synergistically alters folate metabolism in the rodent colon in a manner that predisposes for cancer. The researcher noted that folate supplementation can reverse the observed procarcinogenic effects. Next, research was presented showing that crambene and indole 3-carbinol, phytochemicals found in cruciferous vegetables, provide enhanced protection from carcinogen-induced cancer in rats in an additive and possibly synergistic fashion, but only in doses higher than are encountered in the diet. Another presentation offered a novel mechanism for the well-documented anticancer activity of the phytochemical sulforaphane. Despite being considered an antioxidant, sulforaphane has now been shown to induce apoptosis in prostate cancer cells by producing reactive oxygen species. In the final presentation of this session, research was presented showing that EGCG induces changes in gene expression that promote a more normal epithelial phenotype. The researcher noted that EGCG specifically prevents the cell signaling cascade that leads mouse mammary tumors induced by dimethylbenz[a]anthracene to become more invasive.
The mapping of the human genome has revolutionized many fields of science, and the study of the link between diet and cancer is no different. A split session on the second day of the conference focused on new discoveries in nutrigenomics, an emerging discipline concerned with understanding how dietary factors directly and indirectly interact with an individual’s genes. The opening presentation dealt with metabonomics, the scientific approach seeking to measure, model, and metabolically characterize whole-animal systems in time. Metabonomic data contain information related to genetic and environmental factors and are proving to be powerful tools for the diagnosis and study of underlying mechanisms. Another presentation dealt with the genetic manipulation of genes in a mouse model and how such efforts shed light on how a complex network of genes preserve and modulate homeostasis in the functioning of the rat intestine. Next, the concept of constraint-based modeling, which states that an observed phenotype is the combined consequence of genetic inheritance, individual metabolic structures and pathways, and environmental influences, was discussed in depth.
Another presentation dealt with the use of a specific technology—microarrays containing cloned DNA fragments that are enriched with CpG dinucleotides relative to the entire genome—and how this technology enables a more targeted and efficient examination of important methylation changes. The final presentation in the nutrigenomics split session focused on genetic variations in genes for selenoproteins that cause a structural and functional change linked to increased cancer risk. Ongoing research seeks to determine whether selenium supplementation may enable cells to correct such errors in DNA sequencing.
The final plenary session of the conference involved studies and concepts on the frontiers of current diet–cancer science. The first presentation discussed recent results from the European Prospective Investigation into Cancer (EPIC) study, which is examining dietary patterns and specific nutrients that may protect against cancer. The results highlighted at this year’s conference concerned the relation between blood levels of male and female sex hormones and breast cancer risk among study subjects. Significant positive associations with serum androgen levels and a significant negative association with serum progesterone were reported. EPIC results also show that hormonal replacement therapy with natural (nonsynthetic) progesterone does not increase breast cancer risk. Another presentation outlined how the use of nanotechnology will advance cancer prevention research. A variety of initiatives are underway that seek to adapt nanotechnology to genetic profiling, early imaging, and other clinical uses. Next, a presentation examined the postgenomic era, with its ever-increasing understanding of complex diet–gene interactions and the application of genomic technologies to investigate new biomarkers characterizing the metabolic genotype-phenotype continuum. It is hoped that this new knowledge will give rise to personalized dietary recommendations for cancer prevention. In the conference’s concluding lecture, a data analyst discussed the many challenges posed by the use of microarrays and outlined the points of consensus that have emerged as researchers struggle to adapt established scientific and statistical methods to new technology that can simultaneously measure an enormous number of variables.
AICR is a member of the WCRF global network, which provides a wide range of education programs to help people make changes for lower cancer risk and supports innovative research in prevention and treatment worldwide.
FOOTNOTES
1 Published in a supplement to The Journal of Nutrition. Presented as part of the International Research Conference on Food, Nutrition, and Cancer held in Washington, DC, July 14–15, 2005. This conference was organized by the American Institute for Cancer Research and the World Cancer Research Fund International and sponsored by (in alphabetical order) California Avocado Commission; California Walnut Commission; Campbell Soup Company; The Cranberry Institute; Danisco USA, Inc.; The Hormel Institute; National Fisheries Institute; The Solae Company; and United Soybean Board. Guest editors for this symposium were Vay Liang W. Go, Ritva R. Butrum, and Helen A. Norman. Guest Editor Disclosure: R. R. Butrum and H. Norman are employed by conference sponsor American Institute for Cancer Research; V.L.W. Go, no relationships to disclose. 
2 Author Disclosure: R. R. Butrum and H. Norman are employed by conference sponsor American Institute for Cancer Research; V.L.W. Go, no relationship to disclose.
4 Abbreviations used: AICR, American Institute for Cancer Research; EGCG, epigallocatechin gallate; EPIC, European Prospective Investigation into Cancer; RAR, retinoic acid receptor; SLR, systematic literature review; WCRF, World Cancer Research Fund International.
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