SUNLIGHT, VITAMIN D AND SKIN CANCER

Preface
Contents
Contributors
Part I: Introduction
	Chapter 1: Lessons Learned from Paleolithic Models and Evolution for Human Health: A Snap Shot on Beneficial Effects and Risks...
		References
Part II: UV-Induced Cutaneous Synthesis of Vitamin D and the Physiologic Consequences (I)
	Chapter 2: Sunlight, UV Radiation, Vitamin D, and Skin Cancer: How Much Sunlight Do We Need?
		Prehistorical Historic Perspective
		Photoproduction of Vitamin D3
		Factors Controlling Cutaneous Vitamin D Synthesis
		Sources and Metabolism of Vitamin D
		Role of Vitamin D in the Prevention of Chronic Diseases
		Vitamin D Deficiency Pandemic
		Sunlight, Vitamin D, and the Skin Cancer Conundrum
		Conclusion
		References
Part III: Solar Radiation, Vitamin D and Human Health
	Chapter 3: Vitamin D Status and Cancer Incidence, Survival, and Mortality
		Introduction
		25-hydroxyvitamin D, Cancer Incidence, Survival, and Mortality
			Colorectal Cancer
				Cancer Incidence
				Cancer Survival
			Prostate Cancer
				Cancer Incidence
				Cancer Survival and Mortality
			Breast Cancer
				Cancer Incidence
				Cancer Survival
			Other Cancer Types
				Cancer Incidence
				Cancer Survival and Mortality
		Vitamin D Intake Trials
			Randomized Controlled Trials (RCTs) of Vitamin D and Cancer Incidence
			RCTs of Vitamin D and Cancer Mortality
		Conclusions
		References
	Chapter 4: Vitamin D Receptor Polymorphisms and Cancer
		Introduction
		Materials and Methods
			Data Extraction and Data Analysis
			Exclusion Criteria
		Fok1 and Cancer
			Breast Cancer
			Prostate Cancer
			Colorectal Cancer
			Skin Cancer
			Ovarian Cancer
			Other Cancer Sites
		Bsm1 and Cancer
			Breast Cancer
			Prostate Cancer
			Colorectal Cancer
			Skin Cancer
			Ovarian Cancer
			Renal Cancer
			Lung Cancer
			Other Cancer Sites
		Taq1 and Cancer
			Breast Cancer
			Prostate Cancer
			Colorectal Cancer
			Skin Cancer
			Lung Cancer
			Other Cancers
		Apa1 and Cancer
			Breast Cancer
			Prostate Cancer
			Colorectal Cancer
			Skin Cancer
			Other Cancers
		Cdx2 and Cancer
			Breast Cancer
			Prostate Cancer
			Colorectal Cancer
			Other Cancers
		Conclusions and Discussion
		References
	Chapter 5: On the Relationship Between Sun Exposure and All-Cause Mortality
		Skin Cancer and All-Cause Mortality
		Plausible Explanations for the Inverse Relation Between Sun Exposure and CVD or Noncancer/Non-CVD Mortality
		Strengths and Limitations of the Inverse Relation Between Sun Exposure and All-Cause Death
		Public Health Implications
		References
	Chapter 6: Epidemiology of Skin Cancer: Update 2019
		Introduction
		Keratinocyte Skin Cancer
			Incidence of Keratinocyte Skin Cancer
			Basal Cell Carcinoma
			Squamous Cell Carcinoma
			Decrease of Mortality in Keratinocyte Skin Cancer
			Clinical Epidemiology of KSC
		Sun Exposure and Keratinocyte Skin Cancer
		Melanoma
			Increase of Melanoma Incidence in White Populations
			Stabilization of Mortality Rates
			Clinical Epidemiology
				Anatomic Site
				Histological Subtype
				Tumor Thickness
		Sun Exposure and Melanoma
			Population Attributable Fraction: UV Radiation and Melanoma
			Population Attributable Fraction: Global Estimates
		Conclusion
		References
Part IV: Epidemiology of Skin Cancer
	Chapter 7: Solar UV Exposure and Mortality from Skin Tumors: An Update
		Introduction
			Skin Cancer
			Incidence and Mortality of CMM
			Sun Exposure
			Anatomic Site
			UV and DNA Damage
		Relationships of Sun Exposure and Melanoma Mortality
		Vitamin D and Melanoma Mortality
		Vitamin D Receptors and Melanoma Mortality
		Vitamin D Supplements and Melanoma Mortality
		Conclusion
		References
	Chapter 8: Solarium Use and Risk for Malignant Melanoma: Many Open Questions, Not the Time to Close the Debate
		Introduction
		The Association Between Solarium Use and Melanoma Risk: Major Findings Focussing on a Recent Meta-analysis
			Study Characteristics of a Recent Meta-analysis (Table 8.1)
			Assessment of Study Quality, Level of Evidence and Grade of Recommendation
			Association Between Ever-Exposure to UV Radiation from a Solarium and Melanoma Risk
			Sensitivity Analyses Yielded Results Inconsistent with Main Finding
			Association of First Exposure to UV Radiation from a Solarium at Young Age with Melanoma Risk
			Association of High/Low Exposure to UV Radiation from a Solarium with Melanoma Risk
		Discussion
		References
		Further Readings
	Chapter 9: Molecular Biology of Basal and Squamous Cell Carcinomas
		Introduction
		Basal Cell Carcinoma: Epidemiology and Clinical Forms
		Squamous Cell Carcinoma: Epidemiology and Clinical Forms
		Risk Indicators
		Molecular Biology of Basal Cell Carcinomas
		Molecular Biology of Squamous Cell Carcinomas
		Emerging Treatment Options
		Conclusion
		References
Part V: Photocarcinogenesis of Skin Cancer
	Chapter 10: Human Papillomaviruses and Skin Cancer
		Introduction: Human Papillomaviruses and Cancer
		Human Papillomaviruses in Epidermodysplasia Verruciformis Patients
			Histology of EV Lesions and β-PV Genotypes
			Genus β-PV Epidemiology
			The β-PV Life Cycle
			The Genetic Defect in EV Patients
			EV-Like Disease
				Common Gamma-c or Jak3 Deficiency
				Immunosuppression in Organ Transplant Recipients (OTRs), Inherited T-Cell Defects, and HIV
			Local Immune Control and Immune Escape in EV Patients
			UV Light and β-PV as Cocarcinogens in EV Patients
				β-PV-Mediated Expansion of the Epithelial Progenitor Cell Compartment in EV Lesions
				UV-Induced p53 Mutations in EV Lesions
				β-HPV-Mediated Amplification of Inflammation in EV Lesions
		Functional Studies of Cutaneous PV in Animal Models
			ransgenic Mouse Models
			Evidence for a ``Hit-and-Run´´ Mechanism
		Molecular and Functional Studies of Human Genus β-Papillomaviruses In Vitro
			The β-PV E6 Oncoprotein
			The β-PV E7 Protein
		Conclusions
		References
	Chapter 11: The Immune System and Pathogenesis of Melanoma and Non-melanoma Skin Cancer
		Brief Introduction to Skin Immunology
		Immune System Failures and Cancer Development
		UV Radiation-Induced Immunosuppression and Skin Cancer
			UVR-Induced Mutagenesis
			UVR-Induced Immunosuppression
			UVR and Melanomagenesis
		Organ Transplantation, Immunosuppressive Therapies, and Skin Cancer
		Immunotherapy and Melanoma
		Conclusion
		References
	Chapter 12: Protection from Ultraviolet Damage and Photocarcinogenesis by Vitamin D Compounds
		Introduction
			Direct DNA Damage by UVB
			Indirect DNA Damage by Oxidative Stress
			Photoimmunosuppression
		DNA Damage Response in Eukaryotes
			DNA Repair Pathways
				Nucleotide Excision Repair (NER) Pathways
				Antioxidant Defences
				Base Excision Repair (BER)
		Compounds that Reduce Photolesions in the Skin
			Reduction of Photo Lesions
			Reduced Immunosuppression
			Reduced Photocarcinogenesis
		Vitamin D Signalling Pathways
			Classic/Genomic Pathway
			Nonclassic/Non-genomic Pathway
		Vitamin D Production and Metabolism
		Limitations of 1,25(OH)2D3 as a Photoprotective Agent
		Conclusion
		References
Part VI: The Relevance of the Vitamin D Endocrine System for Skin Cancer
	Chapter 13: The Role of Classical and Novel Forms of Vitamin D in the Pathogenesis and Progression of Nonmelanoma Skin Cancers
		Introduction to the Ultraviolet Spectrum of Solar Radiation
		Vitamin D in the Skin
			Vitamin D and Related Compounds in a Nutshell
			Phenotypic Effects of Active Forms of Vitamin D: An Overview
			Receptors for Vitamin D in the Skin
				Vitamin D Receptor (VDR)
				Other Receptors for Vitamin D: An Overview
		Nonmelanoma Skin Cancers
			Human Skin Cancer: An Overview
			Therapy of NMSC
		Vitamin D in Chemoprevention of NMSC
			Photoprotective Activity of Active Forms of Vitamin D3
			Chemoprevention Against UVR and Chemically Induced NMSC in Animal Models
			Vitamin D in Chemoprevention or Adjuvant Therapy in NMSC in Humans
		Perspective and Conclusions
		References
	Chapter 14: The Vitamin D Receptor as Tumor Suppressor in Skin
		Introduction
		Vitamin D Metabolism
		Vitamin D Receptor: Mechanism of Action
		Mechanisms of Tumor Suppression by Vitamin D: General
			Cell Cycle Regulation
			Growth Factors
			Apoptosis
			Oxidative Stress
			Prostaglandins
			Angiogenesis
			Immune System
		Mechanisms of Tumor Suppression by 1,25(OH)2D/VDR in the Epidermis
		Vitamin D Regulation of Epidermal Proliferation and Differentiation
			The Hedgehog (Hh) Pathway
			The Wnt/β-Catenin Pathway
			The Hyaluronan/CD44 Pathway
		Long Noncoding RNAs (LncRNAs)
		Vitamin D Regulation of Immune Function in the Skin
			Adaptive Immunity
			Innate Immunity
		Vitamin D Regulation of the DNA Damage Response
		Summary
		References
	Chapter 15: Crosstalk Between Vitamin D and p53 Signaling in Cancer: An Update
		Introduction
		VDR and the Vitamin D Endocrine System/Regulatory Network
		The p53 Family
		Crosstalk Between the VDR and the p53 Family in Cancer
		References
	Chapter 16: Sunlight, Vitamin D, and Xeroderma Pigmentosum
		Introduction
		UV-Induced DNA Damage
		Sunlight and Vitamin D
		Xeroderma Pigmentosum: Epidemiology
		Xeroderma Pigmentosum: Clinical Symptoms
		Xeroderma Pigmentosum: Disease-Causing Mechanisms
		Xeroderma Pigmentosum: Diagnostics
		Vitamin D and Xeroderma Pigmentosum
		Xeroderma Pigmentosum: Therapy
		Conclusion
		References
Part VII: Prevention and Management of Skin Cancer
	Chapter 17: Update: Solar UV Radiation, Vitamin D, and Skin Cancer Surveillance in Organ Transplant Recipients (OTRs)
		Introduction
		Increased Risk of Nonmelanoma Skin Cancer (NMSC) in Solid Organ Transplant Recipients
		Risk Factors Associated with the Development of Nonmelanoma Skin Cancer in Transplant Recipients
		The Aggressive Behavior of Nonmelanoma Skin Cancer in Transplant Recipients
		Organ Allograft Recipients Are at Increased Risk for Malignant Melanoma
		Increased Incidence and Prevalence of Other Types of Skin Cancer in Solid Organ Transplant Recipients
		Immunosuppressive Treatment
		Vitamin D Deficiency in Organ Transplant Recipients: An Underrecognized Risk Factor for a Broad Variety of Severe Diseases
		A Paradigm Shift in the Diagnosis and Management of Skin Malignancies in Solid Organ Transplant Recipients
			General Principles
			Sun Protection
		Types of Skin Lesions
			Actinic Keratosis and Other Intraepithelial Neoplasia
			SCC
			Low-Risk SCC
			High-Risk SCC
			Metastatic SCC
			BCC
			Malignant Melanoma (MM)
		Follow-Up
		Summary
		References
	Chapter 18: Sunscreens in the United States: Current Status and Future Outlook
		Introduction
			Background
		UV Radiation (UVR)
			UVR and US Skin Cancer Incidence
		UVR´s Biochemical Effects on the Skin
			Immunosuppression and Skin Cancer
			UV Immunosuppression and Carcinogenesis
		Mechanisms of Sun-Induced Skin Darkening or ``Tanning´´
			UVR on Tanning
			Visible Light and Infrared Radiation on Tanning
		Sunscreen
			Types of Sunscreens
			How Sunscreen Is Evaluated in the USA: Current and Upcoming Methods
				UVB Protection
				UVA Protection
				Substantivity
				Stability
			New FDA Labeling Requirements
			Upcoming Proposed FDA Labeling Requirements
		Evidence for the Efficacy of Sunscreens
			Protection from Immunosuppression
			Photoaging
			Squamous Cell Carcinomas
			Basal Cell Carcinomas
			Melanomas
		Current Recommendations from American Academy of Dermatology (AAD) and American Academy of Pediatrics (AAP)
		Sunscreen and Vitamin D
		Polyphenols
		Photolyases
		Conclusion
		References
	Chapter 19: A Handful of Sunscreen for Whole-Body Application
		Introduction
		Materials and Methods
		Results
		Discussion
		References
	Chapter 20: Ultraviolet Exposure Scenarios: Balancing Risks of Erythema and Benefits of Cutaneous Vitamin D Synthesis
		Introduction
		Differences Between Vitamin D Synthesis and Erythema
			Action Spectra
			Biological Endpoints
			Acute vs. Chronic Exposures
		Implications for UV Exposure
			Ambient Solar UV Radiation
			Solar Zenith Angle and the UV Spectrum
			Unprotected Skin Area
			Realistic Exposure Times
		Assessing the Erythema Risks of Exposures for Vitamin D Synthesis
		Global Model of Vitamin D and Erythema Potential
			Assumptions and Limitations
			Results
		UK Model for Avoidance of Vitamin D Deficiency
			Assumptions and Limitations
			Results
		Public Health and Personal Choice
			One Size Does Not Fit All
			Understanding the Options
		References
Part VIII: UV-Induced Cutaneous Synthesis of Vitamin D and the Physiologic Consequences - II. Promise and Outlook
	Chapter 21: The Paleolithic Nutrition Model in Relation to Ultraviolet Light and Vitamin D
		Introduction
		Adaptation
		Natural Selection
		Optimal Paleolithic Sun Exposure and Vitamin D Status
		Non-vitamin D Effects of Ultraviolet Light
		Conclusion
		References
Index