Cancer and Inflammation Mechanisms

Chemical, Biological, and Clinical Aspects

Yusuke Hiraku, Shosuke Kawanishi, Hiroshi Ohshima, Yusuke Hiraku, Shosuke Kawanishi, Hiroshi Ohshima

• Publisher: Wiley
• Year: 2014
• ISBN:
  9781118826553
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Industrial & Technical Chemistry

A new perspective on the link between inflammation and cancer

Inflammation is the human body's normal biological response to threats in the modern world, as well as a defense against the harmful influence of pathogens, the environment, and poor nutrition. But what happens when the inflammatory response is triggered repeatedly and sustained for long periods of time? Cancer and Inflammation Mechanisms: Chemical, Biological, and Clinical Aspects discusses the mechanisms by which chronic inflammation can lead to cancer, the various causative agents, and possible prevention methods.

A compilation of the latest information coming out of the various fields of cancer research, this book provides a detailed look at inflammation-related carcinogenesis from the perspective of researchers at the forefront of the field. It takes an interdisciplinary approach to the topic, and provides comprehensive information about the major factors at work in inflammation, cancer, and the intersection of the two conditions. Topics include:

• A general overview of inflammation-related cancer
• The biochemistry of inflammation and its effects on DNA
• Molecular biology and the role of microRNA in carcinogenesis
• Specific causative agents including oncogenic viruses, asbestos, and nanomaterial
• Anti-inflammatories, nutraceuticals, and other preventative measures

A deeper understanding of the mechanisms behind inflammation-related carcinogenesis can lead to better patient outcomes by improving diagnostics and prevention, as well as altering the approach to treatment. Cancer and Inflammation Mechanisms: Chemical, Biological, and Clinical Aspects provides the knowledge base researchers need to push the field forward.

CHAPTER 1
INFECTION, INFLAMMATION, AND CANCER: OVERVIEW

Hiroshi Ohshima, Noriyuki Miyoshi, and Susumu Tomono

It has been estimated that about 2 million (16.1%) of the total 12.7 million new cancer cases in 2008 were attributable to infections (1). This percentage was higher in less-developed (22.9%) than in more-developed (7.4%) countries, and varied 10-fold by region from 3.3% in Australia and New Zealand to 32.7% in sub-Saharan Africa. Four major infections with Helicobacter pylori, hepatitis B and C viruses, and human papillomavirus are estimated to be responsible for 1.9 million cases of gastric, liver, and cervical cancer. Cervical cancer accounts for about half of the infection-related burden of cancer in women, and in men liver and gastric cancers account for over 80%. In addition, as shown in Table 1.1, chronic infection by a variety of viruses, bacteria, or parasites and tissue inflammation such as gastritis and hepatitis, which are often caused by chronic infection, are recognized risk factors for human cancers at various sites. Furthermore, the chronic inflammation induced by chemical and physical agents such as tobacco smoke and asbestos is also associated with an increased risk of cancer. Thus, chronic bronchitis and emphysema lead to increased risks of lung cancer. Inhalation of asbestos causes chronic lung and pleural inflammation and increases the risk of mesothelioma. Gastroesophageal reflux disease and Barrett's esophagus, which are caused by abdominal obesity, gastroesophageal reflux, and cigarette smoking, induce chronic inflammation and increase the risk of esophageal adenocarcinoma. Autoimmune and inflammatory diseases of uncertain etiology are also associated with an increased risk of cancer. For example, inflammatory bowel diseases such as Crohn's disease and ulcerative colitis are associated with an increased risk of colon cancer. There is an increased risk of pancreatic cancer in chronic pancreatitis. Thus, a significant fraction of the global cancer burden is attributable to chronic infection and inflammation. It is estimated that there would be about 21% fewer cases of cancer in developing countries and 9% fewer cases in developed countries if these known infectious diseases were prevented (2).

TABLE 1.1 Infection and Inflammatory Conditions as Risk Factors for Human Cancers

Cancer site	Infection/inflammation
Breast	Inflammatory breast cancer
Cervix	Human papillomaviruses, herpes simplex virus
Esophagus	Barrett's esophagitis, gastroesophageal reflux
Gallbladder and extrahepatic biliary ducts	Stone/cholecystitis, Salmonera typhimurium
Kaposi's sarcoma	Human immunodeficiency viruses
Large intestine (colon/rectum)	Inflammatory bowel diseases, Schistosomiasis japonicum
Leukemia/lymphoma	Human T-cell leukemia virus, Epstein–Barr virus, malaria
Liver /intrahepatic biliary ducts	Hepatitis viruses B and C, cirrhosis, Opistorchis viverrini, Clonorchis sinensis, Schistosomiasis japonicum
Lung	Cigarette smoke, particles (asbestos, silica dust, nanomaterials, etc.)
Nasopharynx	Epstein–Barr virus
Oral cavity	Leukoplakia
Pancreas	Pancreatitis
Pleura (mesothelioma)	Asbestos
Prostate	Proliferative inflammatory atrophy
Skin	Ultraviolet radiation, sunburn, human papillomaviruses
Stomach	Helicobacter pylori, chronic atrophic gastritis, Epstein–Barr virus
Thyroid	Thyroiditis
Urinary bladder	Stones, bacterial infections, Schistosomiasis haematobium

INFECTION, INFLAMMATION, AND CANCER: POSSIBLE MECHANISMS

Although various mechanisms have been proposed for infection- and inflammation-associated carcinogenesis, at many sites carcinogenic mechanisms associated with infection and inflammation have not been fully elucidated. Both direct and indirect mechanisms may be involved in carcinogenesis associated with infection. Direct mechanisms include integration of viral DNA into the human genome, which often results in alterations of host DNA (insertion, deletion, translocation, and amplification). Products of integrated viral DNA (e.g., the X protein of hepatitis B virus and the E6 and E7 proteins of human papillomavirus) interact with tumor suppressor gene products such as pRB, p53, and Bax, inactivating these proteins in host cells (see Chapters 12 and 13). Viral products such as the E6 and E7 proteins of human papillomavirus may also immortalize infected cells (e.g., human genital keratinocytes) and interact with transcription factors of host genes (e.g., activation of c-myc by the X protein of hepatitis B virus), deregulating the cell cycle, or cell growth and death. In contrast, indirect mechanisms include inflammation-related cellular and genetic alterations and viral-infection-induced immunosuppression (e.g., human immunodeficiency virus), which can increase the risks of some types of malignancy (e.g., Kaposi's sarcoma). It is likely that both direct (integration of viral DNA into host genome) and indirect (immunosuppression and inflammatory responses) mechanisms cooperate in various cases. This is evident because (1) many infectious agents associated with human cancer are ubiquitous and widely distributed, but only a small fraction of infected subjects develop cancer; (2) there is a long latency period between initial infection and cancer appearance; and (3) other lifestyle factors, such as smoking and dietary habits, are known to modify cancer risks associated with infection and inflammation.

PRODUCTION OF INFLAMMATORY MEDIATORS AND REACTIVE OXIDANTS

Inflammation is the normal physiological response to tissue injury. The cellular and tissue responses to injury can increase the blood supply and enhance vascular permeability and migration of white blood cells to damaged sites. Granulocytes, monocytes, and lymphocytes are recruited to the injured area and concomitantly produce soluble mediators such as acute-phase proteins, eicosanoids, interleukins, and cytokines. Cytokines can be divided into pro-inflammatory [interleukin (IL)-1, IL-6, IL-15, IL-17, and IL-23 and tumor necrosis factor (TNF)-α] and anti-inflammatory [IL-4, IL-10, IL-13, transforming growth factor (TGF)-β, and interferon (IFN)-α]. Pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 play an important role in inflammation and cancer development. These cytokines activate various transcription factors, such as nuclear factor (NF)-κB and signal transducer and activator of transcription (STAT) 3, which promote cell growth, suppress apoptotic cell death, and stimulate production of growth factors, cytokines, and a variety of oxidant-generating enzymes. Furthermore, these pro-inflammatory cytokines also activate multiple oncogenic pathways, such as the mitogen-activated protein kinase (MAPK) cascade, an important signaling pathway involved in various processes of carcinogenesis, such as cell proliferation and migration, and angiogenesis. Similarly, infection and inflammation activate multiple oncogenic pathways, such as the PI3K/AKT/GSK3β/STAT3 and ...

Table of contents

• Cover
• Titlepage
• Copyright
• Contents
• CONTRIBUTORS
• PREFACE
• CHAPTER 1 INFECTION, INFLAMMATION, AND CANCER: OVERVIEW
• CHAPTER 2 STEM CELL THEORY AND INFLAMMATION-RELATED CANCER
• CHAPTER 3 EPITHELIAL–MESENCHYMAL TRANSITION: A LINK BETWEEN CANCER AND INFLAMMATION
• CHAPTER 4 ROLE OF NITRATIVE DNA DAMAGE IN INFLAMMATION- RELATED CARCINOGENESIS
• CHAPTER 5 LIPID PEROXIDATION–DERIVED DNA ADDUCTS AND THE ROLE IN INFLAMMATION-RELATED CARCINOGENESIS
• CHAPTER 6 LEVEL OF INFLAMMATION-RELATED DNA ADDUCTS IN HUMAN TISSUES
• CHAPTER 7 TOLL-LIKE RECEPTORS: ROLE IN INFLAMMATION AND CANCER
• CHAPTER 8 INFLAMMASOMES AND INFLAMMATION
• CHAPTER 9 ACTIVATION-INDUCED CYTIDINE DEAMINASE: AN INTRINSIC GENOME MODULATOR IN INFLAMMATION-ASSOCIATED CANCER DEVELOPMENT
• CHAPTER 10 MicroRNA AND INFLAMMATION-RELATED CANCER
• CHAPTER 11 INFLAMMATION AS A NICHE FOR TUMOR PROGRESSION
• CHAPTER 12 HUMAN PAPILLOMAVIRUS AND CERVICAL CANCER
• CHAPTER 13 HEPATITIS VIRUSES AND HEPATOCELLULAR CARCINOMA
• CHAPTER 14 EPSTEIN–BARR VIRUS AND NASOPHARYNGEAL CARCINOMA
• CHAPTER 15 BARRETT'S ESOPHAGUS AND ESOPHAGEAL CANCER
• CHAPTER 16 ASBESTOS-INDUCED CHRONIC INFLAMMATION AND CANCER
• CHAPTER 17 NANOMATERIALS
• CHAPTER 18 INFLAMMATORY PATHWAYS OF RADIATION-INDUCED TISSUE INJURY
• CHAPTER 19 PHOTOCARCINOGENESIS AND INFLAMMATION
• CHAPTER 20 CHEMOPREVENTION OF COLORECTAL CANCER BY ANTI-INFLAMMATORY AGENTS
• CHAPTER 21 NUTRACEUTICALS AND COLON CANCER PREVENTION
• CHAPTER 22 CANCER CHEMOPREVENTION TARGETING COX-2 USING DIETARY PHYTOCHEMICALS
• CHAPTER 23 REGULATION OF INFLAMMATION-ASSOCIATED INTESTINAL DISEASES WITH PHYTOCHEMICALS
• INDEX
• End User License Agreement