Energy Balance and Cancer – serie

Energy Balance and Cancer, Epidemiology and Overview is the first in a series of monographs to address the multiple facets of the world wide pandemic of overweight and obesity and its relation to cancer. This volume, authored by leading experts in their perspective fields, provides a broad and comprehensive overview of the problem from the epidemiologic viewpoint with focus on both general and special populations as well as a description of potential molecular mechanisms and reviews of the latest studies of factors impacting the association of energy balance and cancer including the effects of genetics, caloric restriction, exercise, behavior and the built environment.The collected chapters and the authors contributing to this initial volume represent a transdisciplinary approach to analyze and develop novel approaches to understand and solve what, up to now, is a globally refractory problem. The book is written to be understandable and informative to individuals from all concerned disciplines. It should serve to orient students, investigators, nutritionists, public health officials, community planners, clinicians and policy makers to the extent of the problem, its multiple dimensions and potential approaches for research and corrective interventions.

The World Health Organization estimates that 25 percent of common cancers can be prevented through regular physical activity and weight control. Common cancers linked to overweight/obesity and a sedentary lifestyle include breast, colon, endometrium, pancreas, renal, esophageal, and several others. There are several plausible mechanisms linking lack of physical activity and increased adiposity to cancer risk, supported by results from animal experiments and human intervention studies.

This book reviews the epidemiological associations between insulin resistance and cancer. This is followed by reviews of animal models which support this relationship and provide insight into potential mechanisms. Several chapters then provide detailed examination of the cellular and molecular changes characterizing the insulin resistant state, such as hyperinsulinemia, abnormal metabolism and hormone signaling, and how these interact with various tumor characteristics. For example some tumors present increased quantities of the fetal form of the insulin receptor, unique regulation of oxidative (Krebs’ cycle) metabolism (Warburg effect), as well as mutations in various relevant signaling pathways. Finally, the clinical implications of these data are integrated with considerations of insulin “sensitization” and potential metabolic interventions to prevent and treat cancer. It should be noted that while a number of cancers are associated with obesity the authors here have focused primarily on breast cancer as a key and significant model.

The gastrointestinal track provides one of the distinct systems where multiple malignancies, including adenocarcinoma of the pancreas, esophagus and colon are each associated with obesity. This unique association is covered in this volume of Energy Balance and Cancer from the epidemiologic, biologic and potential etiologic viewpoint. The focus on possible dietary contribution as well as the role of exercise in prevention and therapy is presented in both animal model and patient based studies. Special focus is provided also on the role of genetic mutations and inflammatory pathways as drivers of these obesity related gastrointestinal malignancies. Overall, this volume on Energy Balance and Gastrointestinal Malignancies should be valuable to Epidemiologists, Gastroenterologists and Oncologists, as well as to students and researchers from multiple disciplines interested in understanding and disrupting the association between obesity and cancer.

The obesity pandemic continues to increase on a world-wide basis with over 70% of the United States population being either overweight or obese. Hematologic malignancies have recently been identified among the obesity associated malignancies spanning the lifespan from childhood to the elderly and include leukemia, myeloma, lymphoma and others. In addition to the etiologic association between obesity and hematologic malignancies, the presence of obesity has profound effects on therapy by impacting pharmacokinetics of chemotherapeutic agents, dose, adipocyte metabolism and drug distribution. These may be particularly important in hematopoietic stem cell transplantation. Another important aspect of the association of obesity with hematologic malignancies is the increased incidence of obesity in children who successfully complete therapy for acute lymphoblastic leukemia. This and other observations indicate important relations between the hematopoietic systems and fat metabolism. This volume on Energy Balance in Hematologic Malignancies will provide an important volume in this series and a basis for better understanding etiology, mechanisms, therapeutics implications and experimental approaches. This volume of energy balance and cancer will focus on the relation of obesity to hematologic malignancies, the epidemiology, potential mechanisms, and thereapeutic considerations including effects on pharmacologic and physical approaches as well as the delayed effects of therapy on energy balance.

Energy Balance and Cancer, Epidemiology and Overview is the first in a series of monographs to address the multiple facets of the world wide pandemic of overweight and obesity and its relation to cancer. This volume, authored by leading experts in their perspective fields, provides a broad and comprehensive overview of the problem from the epidemiologic viewpoint with focus on both general and special populations as well as a description of potential molecular mechanisms and reviews of the latest studies of factors impacting the association of energy balance and cancer including the effects of genetics, caloric restriction, exercise, behavior and the built environment.The collected chapters and the authors contributing to this initial volume represent a transdisciplinary approach to analyze and develop novel approaches to understand and solve what, up to now, is a globally refractory problem. The book is written to be understandable and informative to individuals from all concerned disciplines. It should serve to orient students, investigators, nutritionists, public health officials, community planners, clinicians and policy makers to the extent of the problem, its multiple dimensions and potential approaches for research and corrective interventions.

The World Health Organization estimates that 25 percent of common cancers can be prevented through regular physical activity and weight control. Common cancers linked to overweight/obesity and a sedentary lifestyle include breast, colon, endometrium, pancreas, renal, esophageal, and several others. There are several plausible mechanisms linking lack of physical activity and increased adiposity to cancer risk, supported by results from animal experiments and human intervention studies.

This book reviews the epidemiological associations between insulin resistance and cancer. This is followed by reviews of animal models which support this relationship and provide insight into potential mechanisms. Several chapters then provide detailed examination of the cellular and molecular changes characterizing the insulin resistant state, such as hyperinsulinemia, abnormal metabolism and hormone signaling, and how these interact with various tumor characteristics. For example some tumors present increased quantities of the fetal form of the insulin receptor, unique regulation of oxidative (Krebs’ cycle) metabolism (Warburg effect), as well as mutations in various relevant signaling pathways. Finally, the clinical implications of these data are integrated with considerations of insulin “sensitization” and potential metabolic interventions to prevent and treat cancer. It should be noted that while a number of cancers are associated with obesity the authors here have focused primarily on breast cancer as a key and significant model.

​​ While it is well established that the worldwide pandemic of overweight and obesity has profound effects on promoting cancer, it is now recognized that an alternative aspect of energy balance, namely physical activity and exercise have significant beneficial effects on all aspects of cancer across the spectrum from prevention through treatment and extending through survivorship. Moreover, salutary effects of physical activity and exercise extend across the age span from youth to old age and occur at all stages of cancer extending into palliative care.   While the effect of physical activity and exercise on cancer may be partially mediated through obesity control, it is clear that considerable research is required and is ongoing at both the molecular and clinical levels to better understand the associated mechanisms and to develop optimal exercise strategies.   This volume will contain chapters on the effect of exercise on biological pathways in tumor growth, state art exercise strategies and cutting edge research focused on different cancers and patient groups. It will provide an important volume in this series on energy balance and cancer and a basis for ongoing research, experimental approaches and application of evidence based practices to clinical care for patients with cancer.​

In addition to its metabolic and endocrinologic effects, obesity and adipose tissue have now been shown to be associated with low grade inflammation resulting in cellular and humoral inflammatory factors of which the latter may act by endocrine, paracrine and autocrine mechanisms. These inflammatory mediators have increasingly been suggested as contributing to the obesity link to carcinogenesis and cancer promotion. This volume of Energy Balance and Cancer will focus on recent developments and cutting edge research pointing to inflammation and inflammatory factors as key mediators of this linkage. The volume first provides information on inflammation as an important link between obesity and insulin resistance, which is in itself linked to promotion of cancer through hyperinsulinemia. The volume then covers some of the most important mechanisms by which obesity leads to inflammation, including the novel inflammasome concept, alterations in chromatin structure, circulating inflammatory factors, unique cellular interactions between adipocytes and macrophages and the direct link of dietary fat to inflammation and cancer. Overall, this volume will provide important insight to help understand how inflammation may help modulate the linkage between obesity and cancer and serve as a platform for developing future research in this area.

Sleep has recently been recognized as a critical determinant of energy balance regulating, restoration and repair of many of the physiologic and psychologic processes involved in modulating energy intake and utilization. In addition to having an impact on obesity, sleep abnormalities, both quantitative and qualitative, have now been shown to have significant effects on obesity associated comorbidities, including metabolic syndrome, premalignant lesions and cancer. Sleep problems and fatigue also constitute a significant challenge for the ever expanding group of cancer survivors. Moreover, circadian misalignment, such as that experienced by "shift workers" has been shown to be associated with an increased incidence of several malignancies including, breast, colorectal and prostate cancer, consistent with the increasing recognition of the role of clock genes in the metabolic processes. Of increasing concern is the accelerating incidence of sleep disorders in childhood, their association with childhood obesity and associated abnormalities of circulating cytokines, adipokines and metabolic factors, many of which are implicated as etiologic mediators of the connection between obesity and cancer.Extensive studies have now been initiated to investigate the mechanisms by which disturbances in sleep duration, sleep continuity and sleep related breathing affect circadian rhythm, central and peripheral tissue oxygenation and metabolism, quality and quantity of dietary intake and circulating inflammatory cytokines and regulatory hormones. This volume aims to present the latest research on sleep, sleep disturbance and its correlation to obesity and cancer.

The gastrointestinal track provides one of the distinct systems where multiple malignancies, including adenocarcinoma of the pancreas, esophagus and colon are each associated with obesity. This unique association is covered in this volume of Energy Balance and Cancer from the epidemiologic, biologic and potential etiologic viewpoint. The focus on possible dietary contribution as well as the role of exercise in prevention and therapy is presented in both animal model and patient based studies. Special focus is provided also on the role of genetic mutations and inflammatory pathways as drivers of these obesity related gastrointestinal malignancies. Overall, this volume on Energy Balance and Gastrointestinal Malignancies should be valuable to Epidemiologists, Gastroenterologists and Oncologists, as well as to students and researchers from multiple disciplines interested in understanding and disrupting the association between obesity and cancer.

In addition to its metabolic and endocrinologic effects, obesity and adipose tissue have now been shown to be associated with low grade inflammation resulting in cellular and humoral inflammatory factors of which the latter may act by endocrine, paracrine and autocrine mechanisms. These inflammatory mediators have increasingly been suggested as contributing to the obesity link to carcinogenesis and cancer promotion. This volume of Energy Balance and Cancer will focus on recent developments and cutting edge research pointing to inflammation and inflammatory factors as key mediators of this linkage. The volume first provides information on inflammation as an important link between obesity and insulin resistance, which is in itself linked to promotion of cancer through hyperinsulinemia. The volume then covers some of the most important mechanisms by which obesity leads to inflammation, including the novel inflammasome concept, alterations in chromatin structure, circulating inflammatory factors, unique cellular interactions between adipocytes and macrophages and the direct link of dietary fat to inflammation and cancer. Overall, this volume will provide important insight to help understand how inflammation may help modulate the linkage between obesity and cancer and serve as a platform for developing future research in this area.

The obesity pandemic continues to increase on a world-wide basis with over 70% of the United States population being either overweight or obese. Hematologic malignancies have recently been identified among the obesity associated malignancies spanning the lifespan from childhood to the elderly and include leukemia, myeloma, lymphoma and others. In addition to the etiologic association between obesity and hematologic malignancies, the presence of obesity has profound effects on therapy by impacting pharmacokinetics of chemotherapeutic agents, dose, adipocyte metabolism and drug distribution. These may be particularly important in hematopoietic stem cell transplantation. Another important aspect of the association of obesity with hematologic malignancies is the increased incidence of obesity in children who successfully complete therapy for acute lymphoblastic leukemia. This and other observations indicate important relations between the hematopoietic systems and fat metabolism. This volume on Energy Balance in Hematologic Malignancies will provide an important volume in this series and a basis for better understanding etiology, mechanisms, therapeutics implications and experimental approaches. This volume of energy balance and cancer will focus on the relation of obesity to hematologic malignancies, the epidemiology, potential mechanisms, and thereapeutic considerations including effects on pharmacologic and physical approaches as well as the delayed effects of therapy on energy balance.

​​ While it is well established that the worldwide pandemic of overweight and obesity has profound effects on promoting cancer, it is now recognized that an alternative aspect of energy balance, namely physical activity and exercise have significant beneficial effects on all aspects of cancer across the spectrum from prevention through treatment and extending through survivorship. Moreover, salutary effects of physical activity and exercise extend across the age span from youth to old age and occur at all stages of cancer extending into palliative care.   While the effect of physical activity and exercise on cancer may be partially mediated through obesity control, it is clear that considerable research is required and is ongoing at both the molecular and clinical levels to better understand the associated mechanisms and to develop optimal exercise strategies.   This volume will contain chapters on the effect of exercise on biological pathways in tumor growth, state art exercise strategies and cutting edge research focused on different cancers and patient groups. It will provide an important volume in this series on energy balance and cancer and a basis for ongoing research, experimental approaches and application of evidence based practices to clinical care for patients with cancer.​

Sleep has recently been recognized as a critical determinant of energy balance regulating, restoration and repair of many of the physiologic and psychologic processes involved in modulating energy intake and utilization. In addition to having an impact on obesity, sleep abnormalities, both quantitative and qualitative, have now been shown to have significant effects on obesity associated comorbidities, including metabolic syndrome, premalignant lesions and cancer. Sleep problems and fatigue also constitute a significant challenge for the ever expanding group of cancer survivors. Moreover, circadian misalignment, such as that experienced by "shift workers" has been shown to be associated with an increased incidence of several malignancies including, breast, colorectal and prostate cancer, consistent with the increasing recognition of the role of clock genes in the metabolic processes. Of increasing concern is the accelerating incidence of sleep disorders in childhood, their association with childhood obesity and associated abnormalities of circulating cytokines, adipokines and metabolic factors, many of which are implicated as etiologic mediators of the connection between obesity and cancer.Extensive studies have now been initiated to investigate the mechanisms by which disturbances in sleep duration, sleep continuity and sleep related breathing affect circadian rhythm, central and peripheral tissue oxygenation and metabolism, quality and quantity of dietary intake and circulating inflammatory cytokines and regulatory hormones. This volume aims to present the latest research on sleep, sleep disturbance and its correlation to obesity and cancer.

Cancer occurs in specific places and spaces, each of which have identifiable geographic coordinates, characterized by unique natural, built and social characteristics, all of which contribute significantly to cancer across the spectrum from etiology through diagnosis, treatment and outcomes. In the first volume of this series, published in 2010, a single chapter was focused on these geographic influences. Since then, the field of geospatial studies of cancer prevention and control has exploded in approaches and applications. Accordingly, this volume focuses on what has now become a very specific research endeavor, Geospatial Factors Impacting Breast Cancer. The book provides important insights into this relatively new and rapidly developing field. It should be of value to all students of the Energy Balance & Cancer Series and a wide-ranging introduction to problems in cancer prevention and control for geographers, demographers and other researchers with a geospatial perspective. Moreover, it provides important information for all oncologists, endocrinologists, and behavioral modification professionals to better understand their patients in the context of their environment. It should also provide important considerations for physicians, scientists, public health professionals and disparity investigator planning clinical trials, community interventions and community planning.

Cancer occurs in specific places and spaces, each of which have identifiable geographic coordinates, characterized by unique natural, built and social characteristics, all of which contribute significantly to cancer across the spectrum from etiology through diagnosis, treatment and outcomes.

​​​​This volume reviews disparities in cancer genetics, etiology, treatment and survivorship that are associated with differences in energy balance and how those differences and disparities may be affected by geography, socioeconomic status, ethnicity, biology, behavior and others. State-of-the-art strategies are outlined to alter these problems at the individual, community and policy levels. The book provides a comprehensive assessment of the multiple contributions of disparities in energy balance and how they affect cancer. this volume should constitute a valuable resource to disparity focused investigators at all levels and serves an important guide to professionals that deal with these issues, especially those who determine and implement policy.

This volume provides a transdisciplinary and translational review of many of the leading murine models used to study the mechanisms, mediators and biomarkers linking energy balance to cancer. It provides a review of murine models that should be of interest to basic, clinical and applied research investigators as well as nutrition scientists and students that work in cancer prevention, cancer control and treatment. The worldwide obesity pandemic has been extensively studied by epidemiologic and observational studies and even, in some cases, by randomized controlled trials. However, the development and control of obesity, its comorbidities and its impact on cancer usually occurs over such long periods that it is difficult, if not impossible to conduct randomized controlled trials in humans to investigate environmental contributions to obesity, energy balance and their impact on cancer. In contrast, model organisms, especially mice and rats, provide valuable assets for performing these studies under rigorously controlled conditions and in sufficient numbers to provide statistically significant results. In this volume, many of the leading and new murine models used to study the mechanisms and mediators linking cancer with obesity, sleep, exercise, their modification by environment and how they may continue to be used to further elucidate these relations as well as to explore preclinical aspects of prevention and/or therapeutic intervention are considered. This volume provides an important compilation and analysis of major experimental systems and principles for further preclinical research with translational impact on energy balance and cancer.

​​​​This volume reviews disparities in cancer genetics, etiology, treatment and survivorship that are associated with differences in energy balance and how those differences and disparities may be affected by geography, socioeconomic status, ethnicity, biology, behavior and others. State-of-the-art strategies are outlined to alter these problems at the individual, community and policy levels. The book provides a comprehensive assessment of the multiple contributions of disparities in energy balance and how they affect cancer. this volume should constitute a valuable resource to disparity focused investigators at all levels and serves an important guide to professionals that deal with these issues, especially those who determine and implement policy.

This volume provides a transdisciplinary and translational review of many of the leading murine models used to study the mechanisms, mediators and biomarkers linking energy balance to cancer. It provides a review of murine models that should be of interest to basic, clinical and applied research investigators as well as nutrition scientists and students that work in cancer prevention, cancer control and treatment. The worldwide obesity pandemic has been extensively studied by epidemiologic and observational studies and even, in some cases, by randomized controlled trials. However, the development and control of obesity, its comorbidities and its impact on cancer usually occurs over such long periods that it is difficult, if not impossible to conduct randomized controlled trials in humans to investigate environmental contributions to obesity, energy balance and their impact on cancer. In contrast, model organisms, especially mice and rats, provide valuable assets for performing these studies under rigorously controlled conditions and in sufficient numbers to provide statistically significant results. In this volume, many of the leading and new murine models used to study the mechanisms and mediators linking cancer with obesity, sleep, exercise, their modification by environment and how they may continue to be used to further elucidate these relations as well as to explore preclinical aspects of prevention and/or therapeutic intervention are considered. This volume provides an important compilation and analysis of major experimental systems and principles for further preclinical research with translational impact on energy balance and cancer.

This volume of Energy Balance and Cancer provides state-of-the-art descriptions of the rapidly evolving science of epigenetics and how it may explain mechanisms by which alterations in energy balance such as obesity and physical activity may impact cancer. In addition to chapters explaining the processes mediating epigenetic regulation, the volume contains a series of chapters explaining how environmental influences including early life events, nutrition, exercise and microbiota may induce epigenetic changes that can affect carcinogenesis. The following chapters describe epigenetic relations of energy balance to cancer in distinct organ systems including esophagus, colon, prostate and breast. Epigenetics, Energy Balance and Cancer provides a valuable resource for students, research investigators and clinicians seeking to better understand these processes as well as a basis for novel translational and transdisciplinary approaches to further elucidate these processes and develop preventive and therapeutic strategies.

Adipocytokines provide the circuitry by which adipose tissue communicates among its component cells which include adipocytes, stromal cells, immune cells and vascular elements, with adipose tissue depots in other locations throughout the body and with other tissues in order to regulate physiologic processes of energy intake, utilization, and distribution. Since disturbances, both qualitative and quantitative, in adipocytokine function contribute significantly to many of the comorbidities associated with obesity, including diabetes, cardiovascular disease and cancer, this volume, which discusses most of the major adipocytokines independently and collectively and their roles in normal and pathologic processes, should be useful to all individuals seeking a deeper understanding of these processes. Moreover, it provides a valuable complement to the series on Energy Balance and Cancer, in which each volume is focused on a specific aspect of this process, which now constitutesan expanding problem as the obesity pandemic continues and more of the population reaches the age where cancer is most prevalent. This volume should provide a valuable resource to all clinicians and scientists engaged in caring for susceptible patients and in exploring the relation between energy balance and cancer as well as an important platform to providing the background for research development.

Gynecologic malignancies, especially endometrial and ovarian cancers are among the most important and most severely affected by obesity. This volume of Energy Balance and Cancer, written by the world’s leading experts in this field, is arranged to provide a transdisciplinary assessment of the pertinent issues, results of relevant research on mechanisms, and control, strategies for dealing with affected patients and improving outcomes and future research needs. The volume comprehensively covers the epidemiology linking obesity to endometrial and ovarian cancer as well as the public awareness of this critical problem. Subsequent chapters explain biologic aspects of linkages between energy balance and gynecologic malignancies. The volume further outlines strategies to disrupt the linkage between obesity and gynecologic malignancies and concludes with a series of chapters focused on management strategies for obese patients with gynecologic malignancies. This volume provides a valuable resource for all physicians, scientists and other transdisciplinary investigators and practitioners interested and involved in energy balance and cancer. It should be a particularly useful guide to optimize outcomes for all practitioners dealing with patients with gynecologic malignancies challenged by energy balance issues. Moreover, it should serve as a useful guide to students and investigators interested in conducting further research on defining and disrupting the important linkage between energy balance and gynecologic malignancies.

This volume provides a comprehensive treatise on the latest studies linking prostate cancer with energy balance, which together constitute a major challenge and opportunity for research scientists and clinicians especially those dealing with the expanding population of older men confronted with obesity and associated comorbidities. This volume should be a valuable resource to physicians, oncologists, urologists, endocrinologists, nurses, nutritionists, dieticians, and exercise therapists dealing with men with energy balance issues and/or questions regarding the linkage between energy balance and cancer. Moreover, this volume should serve as an important resource for cancer researchers especially for scientists studying lifestyle modification and prevention strategies to better understand and disrupt the linkage between obesity and cancer.

This volume of Energy Balance and Cancer provides state-of-the-art descriptions of the rapidly evolving science of epigenetics and how it may explain mechanisms by which alterations in energy balance such as obesity and physical activity may impact cancer.

Adipocytokines provide the circuitry by which adipose tissue communicates among its component cells which include adipocytes, stromal cells, immune cells and vascular elements, with adipose tissue depots in other locations throughout the body and with other tissues in order to regulate physiologic processes of energy intake, utilization, and distribution. Since disturbances, both qualitative and quantitative, in adipocytokine function contribute significantly to many of the comorbidities associated with obesity, including diabetes, cardiovascular disease and cancer, this volume, which discusses most of the major adipocytokines independently and collectively and their roles in normal and pathologic processes, should be useful to all individuals seeking a deeper understanding of these processes. Moreover, it provides a valuable complement to the series on Energy Balance and Cancer, in which each volume is focused on a specific aspect of this process, which now constitutesan expanding problem as the obesity pandemic continues and more of the population reaches the age where cancer is most prevalent. This volume should provide a valuable resource to all clinicians and scientists engaged in caring for susceptible patients and in exploring the relation between energy balance and cancer as well as an important platform to providing the background for research development.

The volume further outlines strategies to disrupt the linkage between obesity and gynecologic malignancies and concludes with a series of chapters focused on management strategies for obese patients with gynecologic malignancies.