Nutrition and Cancer Prevention

From Molecular Mechanisms to Dietary Recommendations

Thomas Prates Ong, Fernando Salvador Moreno, Gary Williamson, Alejandro G Marangoni, Juliet A Gerrard, Thomas Prates Ong, Fernando Salvador Moreno

• Publisher: Royal Society of Chemistry
• Year: 2019
• ISBN:
  9781788019187
• Edition: 1
• Topic: Medicine
• Subtopic: Nutrition, Dietics & Bariatrics

Cancer is a major global public health problem. Among different environmental and lifestyle factors contributing to cancer risk, diet is a key one. On the one hand, obesity and increased consumption of red and processed meat, ethanol, sugar and saturated fatty acids are associated with increased cancer risk. On the other hand, consumption of micronutrients such as vitamin D, selenium, zinc, folate and bioactive compounds from fruits and vegetables is associated with decreased risk.
Written by an influential, international team of experts, this book presents and discusses current topics on nutrition and cancer prevention. It covers both nutritional influences on different cancers plus specific chapters on the commonly occurring cancers. Nutritional genomics-based studies show that some dietary components modulate carcinogenesis through complex cellular and molecular mechanisms. A better understanding of these different cellular and molecular mechanisms is needed to establish efficient dietary recommendations for cancer prevention. This book will provide such an understanding, serving as an important book for all those working in nutritional health, food science and cancer research.

CHAPTER 1

Introduction to Diet, Nutrition and Cancer

T. P. Ong* and F. S. Moreno

University of São Paulo, Faculty of Pharmaceutical Sciences, Department of Food and Experimental Nutrition, and Food Research Center (FoRC), São Paulo, 05508-000, Brazil
*Corresponding contributor. Email: [email protected]

Cancer is an enormous burden for both developed and developing countries. This is illustrated by data from GLOBOCAN 2012, produced by the International Agency for Research on Cancer (IARC),¹ indicating the worldwide occurrence in 2012 of approximately 14.1 million new cancer cases and 8.2 million deaths due to the disease.² Cancer is a major global cause of death and the projected increase in the burden to societies is associated with growth and aging of population, as well as increased prevalence of established risk factors including smoking, reproductive changes, physical inactivity, obesity and poor diet.² Thus, prevention should be a major focus for cancer control.³ In this context, dietary approaches are promising.⁴

Although it is frequently assumed that the hypothesis that nutrition could be a cause of cancer started to be considered around the 1940s, evidence indicates that professional interest in the diet, nutrition and cancer association can be traced back to the 1800s.⁵ A landmark publication in the field was the article by Doll and Peto from 1981, where they estimated that 35% of cancer was attributed to diet.⁶ Although some⁷ have reviewed this original estimate and proposed lower figures (i.e., 20%), Doll and Peto’s findings were key to increase awareness of the influence of nutritional factors on cancer development. Since then, intense research has been conducted at the epidemiological, clinical and experimental levels.^8,9 Accumulated data indicate that diet and nutrition and cancer association is very complex and several aspects are yet not clear. For example, it has been pointed out that the estimation of dietary influence on cancer risk should further take into account early life nutrition, as developmental stages such as in utero life, early childhood and puberty may represent particularly vulnerable periods for cancer development in adulthood.¹⁰ According to the World Health Organization,³ 30–50% of all cancers are preventable through reduction of exposure to risk factors (tobacco, environmental pollution, occupational carcinogens, infections and alcohol) and adoption of healthy lifestyles (physical exercise, healthy diet and weight).

In addition to the timing of food consumption, other factors that further complicate the elucidation of nutritional modulation of carcinogenesis include the great diversity of dietary components (i.e., more than 5 000 flavonoids have been identified in fruits and vegetables), the concentrations of which in foodstuffs can vary according to farming, harvesting, transporting and cooking conditions.^11,12 Furthermore, for those nutritional factors associated with decreased (fruits and vegetables, vitamin D, folic acid, selenium, zinc, polyphenols and carotenoids, among others) or increased (red and processed meat, alcohol, saturated fatty acids and obesity, among others) cancer risk, the exact underlying cellular and molecular mechanisms are still not clear.^13–22 More recently, nutrient–gene interactions (nutritional genomics), including epigenetics,^23–25 stem cells as cellular targets^26,27 and the intestinal microbiota,^28,29 have emerged as key factors that should be considered in order to better understand diet, nutrition and cancer and thus establish nutritional recommendations for cancer prevention.

Ingestion of fruits and vegetables is associated with cancer prevention.^30–32 These protective effects have been ascribed to the presence of several bioactive compounds.^33,34 In Chapter 2, the role of bioactive food compounds in cancer prevention is covered. These natural substances are widely distributed in plant-based foods such as fruits, vegetables, whole grains and beans. They originate from the secondary metabolism of plants, belong to different classes, such as polyphenols, terpenoids, allyl compounds and isothiocyanates, among others, and exert different cancer preventive effects. The molecular mechanisms underlying their protective effects are discussed and include modulation of phase I and II carcinogen metabolizing enzymes, regulation of gene expression through activation of nuclear receptors, interference with cell signaling pathways and modulation of epigenetic processes such as DNA methylation and histone post-translational modifications. Such complex mechanisms of action by bioactive food components could be associated with the cancer prevention effects of whole grains, fruits, vegetables and beans. Major limitations concerning establishing recommended levels of intake of these compounds are discussed and include limited information on their levels in foods and their bioavailability, which is influenced by individual genetic backgrounds and intestinal microbiota.

Among different micronutrients with cancer prevention potential, vitamin D can be highlighted.^35,36 Chapter 3 covers the role of vitamin D in obesity, an established risk factor for cancer, and in cancer prevention itself. An overview of the nutritional/physiological roles of vitamin D is provided with emphasis on its metabolism. Evidence of the cancer preventive potential of vitamin D based on epidemiological and intervention studies is then discussed. Inhibition of cell proliferation, induction of apoptosis and cell differentiation, and inhibition of angiogenesis, migration and invasion of tumor cells have been indicated as potential vitamin D anticancer actions. The impact of different polymorphisms in the vitamin D receptor (VDR) gene on cancer risk is then discussed. This gene codes for the nuclear receptor that mediates the genomic actions of vitamin D. Alterations in VDR expression or conformation could impair the cancer preventive actions of vitamin D. In addition, the actions of vitamin D at the epigenetic level are presented.

Selenium represents one of the most studied nutrients with cancer prevention potential.^37,38 This aspect of selenium’s beneficial effects is covered in Chapter 4. Selenium is found in both organic and inorganic forms, which present different bioavailability and metabolic pathways. These aspects are first discussed. Nutritional recommendations, food sources and biomarkers of selenium status are then covered. Epidemiological evidence linking selenium and cancer prevention is also provided and conflicting results between outcomes from the two main randomized clinical trials – the Nutritional Prevention of Cancer and the Selenium and Vitamin E Cancer Prevention trials – are discussed. The different outcomes from these clinical trials could be related to differences in genetic background. Thus, polymorphisms in key genes involved in selenium’s cancer prevention actions, such as those coding different antioxidant glutathione peroxidases, are suggested to increase the risk of different cancers, including breast, prostate and colorectal cancers. Furthermore, the proposed mechanisms underlying selenium’s cancer preventive actions are discussed, including those at the epigenetic level.

Zinc represents another micronutrient with cancer prevention activity³⁹ and this is discussed in Chapter 5. The nutritional importance of zinc is first discussed. It is an essential micronutrient that exerts key biological functions at the structural, catalytic and regulatory levels, modulating oxidative stress response, genomic stability, immunological function, DNA repair, cell proliferation and apoptosis, all of which are deregulated during carcinogenesis. Thus, disturbances in zinc homeostasis could increase the risk of cancer development. The impact of zin...