Male Reproductive Cancers (eBook)
XIV, 346 Seiten
Springer New York (Verlag)
978-1-4419-0449-2 (ISBN)
Knowledge about cancer genetics is rapidly expanding, and has implications for all aspects of cancer research and treatment, including molecular causation, diagnosis, prevention, screening, and treatment.
Additionally, while cancer genetics has traditionally focused on mutational events that have their primary effect within the cancer cell, recently the focus has widened, with evidence of the importance of epigenetic events and of cellular interactions in cancer development. The role of common genetic variation in determining the range of individual susceptibility within the population is increasingly recognized, and is now being widely addressed using information from the Human Genome Project. These new research directions will highlight determinants of cancer that lie outside the cancer cell, suggest new targets for intervention, and inform the design of strategies for prevention in groups at increased risk.
Today, the NCI is putting more and more money into research into the genetics of cancer. The very first of the NCI's stated research priorities is a project called The Cancer Genome Atlas. The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing. The NCI and the NHGRI (National Human Genome Research Institute, where the series editor is employed) have each committed $50 million over three years to the TCGA Pilot Project.
This book proposes cover the latest findings in the genetics of male reproductive cancers; specifically cancers of the prostate and testes. The volume will cover the epidemiology of these cancers; model systems, pathology, molecular genetics, and inherited susceptibility.
Knowledge about cancer genetics is rapidly expanding, and has implications for all aspects of cancer research and treatment, including molecular causation, diagnosis, prevention, screening, and treatment.Additionally, while cancer genetics has traditionally focused on mutational events that have their primary effect within the cancer cell, recently the focus has widened, with evidence of the importance of epigenetic events and of cellular interactions in cancer development. The role of common genetic variation in determining the range of individual susceptibility within the population is increasingly recognized, and is now being widely addressed using information from the Human Genome Project. These new research directions will highlight determinants of cancer that lie outside the cancer cell, suggest new targets for intervention, and inform the design of strategies for prevention in groups at increased risk.Today, the NCI is putting more and more money into research into the genetics of cancer. The very first of the NCI's stated research priorities is a project called The Cancer Genome Atlas. The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing. The NCI and the NHGRI (National Human Genome Research Institute, where the series editor is employed) have each committed $50 million over three years to the TCGA Pilot Project.This book proposes cover the latest findings in the genetics of male reproductive cancers; specifically cancers of the prostate and testes. The volume will cover the epidemiology of these cancers; model systems, pathology, molecular genetics, and inherited susceptibility.
Anchor 1 1
Anchor 2 1
Foulkes_Ch01.pdf 13
Chapter 1 14
The Epidemiology of Prostate Cancer 14
1.1 Introduction 14
1.1.1 Prostate Structure and Function 15
1.1.2 Aspects of Prostate Pathology Relevant to Cancer Epidemiology 16
1.1.3 Prostate Cancer Diagnosis, Screening and Treatment 17
1.2 Descriptive Epidemiology 19
1.3 The Epidemiological Investigation of Causes 21
1.3.1 Environmental Factors Not Associated with Prostate Cancer 22
1.3.2 Environmental Factors Possibly Associated with Prostate Cancer 23
1.3.2.1 Soy, Other Legumes and Phytoestrogens 24
1.3.2.2 Cruciferous (Brassica) Vegetables 24
1.3.2.3 Carotenoids, Tocopherols and Other Vitamins 25
1.3.2.4 Animal-Based Foods, Fats and Related Exposures 27
1.3.2.5 Dairy Foods, Calcium and Vitamin D 30
1.3.2.6 Trace Elements and Vitamin Supplements 31
1.3.2.7 Dietary Patterns 33
1.3.2.8 Energy Balance, Obesity and Physical Activity 34
1.3.2.9 Sexual Behaviour and Infections 37
1.3.3 Host Factors Possibly Associated with Prostate Cancer 39
1.3.3.1 Sex Steroid Hormones 39
1.3.3.2 The IGF Axis and Growth Factors 41
1.3.3.3 Inflammation 43
1.3.3.4 Family History and Genetics 45
1.4 Conclusions 46
References 47
Foulkes_Ch02.pdf 61
Chapter 2 61
The Epidemiology of Testicular Cancer 61
2.1 Introduction 61
2.2 Histology and Precursor Lesions 61
2.3 Incidence and Mortality 62
2.3.1 Incidence: Age Patterns 62
2.3.2 Incidence: Racial and Geographic Patterns 62
2.3.3 Mortality 65
2.3.4 Migrant Patterns 65
2.4 Associated Medical Conditions 65
2.4.1 Cryptorchism 66
2.4.2 Subfertility 67
2.4.3 Microlithiasis 67
2.5 Perinatal Risk Factors 68
2.5.1 Birth Weight and Gestational Age 68
2.5.2 Maternal Age 68
2.5.3 Maternal Parity, Birth Order, Sibship Size 68
2.5.4 Maternal Smoking 69
2.5.5 Other Perinatal Factors 70
2.6 Maternal Endogenous Hormones 70
2.7 Maternal Exogenous Hormones 71
2.8 Endocrine-Disrupting Chemicals 71
2.9 Postnatal Risk Factors 73
2.9.1 Anthropometry 73
2.9.2 Age at Puberty 73
2.9.3 Nutrition 73
2.9.4 Endogenous Hormones in Men 74
2.9.5 Physical Activity 74
2.9.6 Socioeconomic Status and Urban/Rural Residence 75
2.9.7 Occupation 75
2.9.8 Viruses 76
2.9.9 Other Factors 77
2.10 Histologic Difference in Risk Factors 78
2.11 Family and Twin Studies 78
2.12 Cancer Risks Among Testicular Cancer Survivors 80
2.13 Conclusions 81
References 82
Foulkes_Ch03.pdf 94
Chapter 3 95
Prostate Cancer: A Pathological Perspective 95
3.1 Introduction 95
3.2 Microanatomy and Histology As Related to Neoplasia 96
3.3 Gross Features 97
3.4 Microscopic and Diagnostic Features 98
3.5 Immunophenotype 100
3.6 Gleason Histological Grading System 101
3.7 Pathological Prognostic Determinants other than Grading 105
3.8 Mode of Tumor Spreading 108
3.9 Iatrogenic Histological Changes Resulting from Therapy 109
3.9.1 Radiation Therapy Effect 109
3.9.2 Androgen-Deprivation Therapy Effect 110
3.10 Putative Precursor Lesions of Prostatic Adenocarcinoma 110
3.10.1 Prostatic Intraepithelial Neoplasia (PIN) 110
3.10.2 Atypical Adenomatous Hyperplasia (AAH) 112
3.10.3 Glandular Atrophy 112
3.11 Atypical Small Acinar Proliferation (ASAP) 113
3.12 Special Types of Prostatic Carcinoma 113
3.12.1 Ductal Adenocarcinoma 114
3.12.2 Mucinous Adenocarcinoma 114
3.12.3 Signet Ring Cell Carcinoma 114
3.12.4 Urothelial Carcinoma 115
3.12.5 Squamous Cell Carcinoma/Adenosquamous Carcinoma 116
3.12.6 Basal Cell Carcinoma 116
3.12.7 Small Cell Carcinoma 117
3.13 Emerging Biomarkers of Potential Prognostic Significance 117
3.14 Conclusions 119
References 120
Foulkes_Ch04.pdf 129
Chapter 4 129
Testicular Tumor Pathology 129
4.1 Introduction 129
4.2 Pathogenesis 129
4.3 Intratubular Germ Cell Neoplasia 130
4.4 Histologically Pure Germ Cell Tumors 131
4.4.1 Seminoma 131
4.5 Histologically Mixed Germ Cell Tumors 133
4.6 Tumor Markers 139
4.7 Staging 139
4.8 Sex Cord Stromal Tumors 141
4.9 Rete Testis Carcinoma 143
4.10 Epididymal Tumors 144
4.11 Mesothelial Neoplasms 144
4.12 Lymphoid Neoplasms 144
4.13 Metastatic Tumors 145
4.14 Conclusion 145
Foulkes_Ch05.pdf 148
Chapter 5 149
Somatic Molecular Genetics of Prostate Cancer 149
5.1 Introduction 149
5.2 Genetic Instability 150
5.3 Cytogenetics: Chromosomal Aberrations 151
5.4 Changes in Gene Expression 158
5.4.1 Loss of Function: Tumor and Metastasis Suppressor Genes 158
5.4.1.1 Chromosome 3 159
RASSF1A 159
5.4.1.2 Chromosome 6 159
SNORD50A 159
MAP3K7 160
5.4.1.3 Chromosome 8 160
NKX3.1 160
MSR1 161
5.4.1.4 Chromosome 10 161
PTEN 161
KLF6 162
ANXA7 162
5.4.1.5 Chromosome 11 163
CD44 163
KAI1 163
GSTP1 163
5.4.1.6 Chromosome 12 164
CDKN1B 164
CD9 165
5.4.1.7 Chromosome 13 165
RB1 165
5.4.1.8 Chromosome 16 166
ATBF1 166
CDH1 166
5.4.1.9 Chromosome 17 166
TP53 166
5.4.1.10 Other Downregulated Genes 167
5.4.2 Gain of Function: Oncogenes 167
5.4.2.1 Chromosome 3 168
CTNNB1 168
TLOC1/SEC62 168
5.4.2.2 Chromosome 5 168
AMACR 168
5.4.2.3 Chromosome 7 168
5.4.2.4 Chromosome 8 169
MYC 169
PSCA 169
5.4.2.5 Chromosome 10 169
KCNMA1 169
5.4.2.6 Chromosome 11 169
PSGR2 169
5.4.2.7 Chromosome 16 170
BCAR1 170
5.4.2.8 Chromosome 17 170
PRC17 170
5.4.2.9 Chromosome 18 170
BCL2 170
5.4.2.10 Chromosome 21 170
ERG and ETV1/TMPRSS2 170
5.4.2.11 Chromosome X 171
AR 171
5.4.2.12 Other Overexpressed genes 172
5.5 Conclusions 173
References 173
Foulkes_Ch06.pdf 187
Chapter 6 187
Molecular Genetics of Testicular Germ Cell Tumor 187
6.1 Introduction 187
6.2 Single Gene Changes in TGCT 189
6.3 Microsatellite Instability in TGCT 192
6.4 Epigenetics of TGCT 193
6.5 Expression Profiling Studies in TGCT 194
6.6 Chromosomal Changes in TGCT (Cytogenetics and Comparative Genomic Hybridization) 195
6.7 Other Biomarkers Studied in Association with Prognosis 197
6.8 Conclusions 198
References 198
Foulkes_Ch07.pdf 206
Chapter 7 207
Identification of Genetic Risk Factors for Prostate Cancer: Analytic Approaches Using Hereditary Prostate Cancer Families 207
7.1 Introduction 207
7.2 Establishing that Genetic Risk Factors Exist for Prostate Cancer 208
7.2.1 Segregation Analysis 209
7.3 Historical Approach for Identifying Susceptibility Genes 210
7.3.1 Parametric Linkage Analysis 211
7.3.2 Nonparametric Linkage Analysis 212
7.3.3 Genome-Wide Linkage Screens for Prostate Cancer 214
7.3.4 Linkage Analysis and Clinically Aggressive Disease 215
7.3.5 Aggressive Prostate Cancer 216
7.3.6 Genetic Modifiers of Prostate Cancer Severity – Study of Gleason Grade 217
7.4 Genetic Association Studies 218
7.4.1 Association Studies for Prostate Cancer in Regions Identified by Linkage Analysis 219
7.4.2 Candidate Gene-Based Association Studies for Prostate Cancer 220
7.5 Changing Focus 220
7.6 Genome-Wide Association Studies 222
7.7 Sample Selection Strategies for Genetic Association Studies 223
7.7.1 Case-Control and Cohort Designs 223
7.7.2 Controlling False-Positive Results Due to Population Stratification 224
7.7.3 Family-Based Association Studies 225
7.8 Conclusions 226
References 226
Foulkes_Ch08.pdf 233
Chapter 8 233
The Identification of Rare and Common Variants Which Predispose to Prostate Cancer 233
8.1 Introduction and Evidence for a Genetic Predisposition 233
8.2 Models of Susceptibility to Prostate Cancer 234
8.3 Association Studies 235
8.4 Results of GWAS in Prostate Cancer 235
8.5 Rare Variants 241
8.6 Conclusions 242
References 244
Foulkes_Ch09.pdf 253
Chapter 9 253
Prostate Cancer in Special Populations 253
9.1.1 Introduction 255
9.1.2 Risk Variants and Familial Factors in Prostate Cancer 255
9.1.3 Candidate Loci in Prostate Cancer 256
9.1.4 Chromosome 8q24 257
9.1.5 Chromosome 17q 258
9.1.6 Conclusion 259
Note Added in Proof 260
9.2.1 Introduction 263
9.2.2 NBS1 Gene 263
9.2.3 BRCA1 Gene 265
9.2.4 CHEK2 Gene 267
9.2.5 RNASEL and MSR1 Genes 268
9.2.6 Region 8q24 269
9.2.7 Conclusion 269
9.3.1 Introduction 272
9.3.2 Brca1 273
9.3.3 Brca2 274
9.3.4 Ribonuclease L 276
9.3.5 Chek2 277
9.3.6 Msr1 278
9.3.7 Chromosome 7 Locus 278
9.3.8 Additional Genome-Wide Studies 279
9.3.9 Other Loci 279
9.3.10 Conclusions 279
Introduction 284
Evidence that Genetic Factors Play a Critical Role in Prostate Cancer Outcomes Among African-Americans 284
The African-American Hereditary Prostate Cancer Study (1997–2000) 286
Clinical Characteristics of African-American Men in the AAHPC Study 286
Genome-Wide Linkage of 77 Families from the AAHPC 287
Compelling Evidence for a Prostate Cancer Gene at 22q12.3 – ICPCG 287
Genetic Variants at the 8q24 Locus in African-American Men 288
Conclusion 289
Note Added in Proof 289
References 290
Foulkes_Ch10.pdf 292
Chapter 10 292
Inherited Susceptibility of Aggressive Prostate Cancer 292
10.1 Introduction 292
10.2 Assessment of Prostate Cancer Aggressiveness 293
10.2.1 Staging 294
10.2.2 Grading 294
10.2.2.1 Reliability of Gleason Score 294
10.2.3 Other Measures of Aggressiveness 295
10.3 Non-genetic Risk Factors for Aggressive Prostate Cancer 295
10.3.1 Age and Ethnicity 295
10.3.2 Smoking, Alcohol, Physical Exercise, Obesity, and Diet 296
10.4 Family History and Prostate Cancer Aggressiveness 297
10.5 Segregation Analysis 298
10.6 Linkage Analysis 299
10.7 Association Studies 302
10.7.1 Candidate Gene Association Studies and Aggressiveness 302
10.7.1.1 Androgen Receptors 302
10.7.1.2 Vitamin D Receptors 304
10.7.1.3 Other Candidate Genes 305
10.7.2 Chromosome 8q24 306
10.8 Conclusion and Future Work 308
References 308
Foulkes_Ch11.pdf 319
Chapter 11 319
Susceptibility Alleles for Testicular Germ Cell Tumor 319
11.1 Introduction 319
11.2 Evidence for TGCT Susceptibility Alleles 320
11.3 Familial TGCT 321
11.4 Identifying TGCT Susceptibility Alleles – Genetic Linkage Analysis 324
11.4.1 Linkage to a Region at Xq27 326
11.4.2 Genome-Wide Linkage Analysis 326
11.5 The Y Chromosome 327
11.5.1 gr/gr as a Low-Penetrance Susceptibility Allele 327
11.5.2 Other Y Regions? 328
11.6 Evaluation of Candidate Genes for TGCT 329
11.6.1 The Androgen Receptor Gene 329
11.6.2 Dnd1 330
11.7 Association Studies 331
11.8 Identifying TGCT Susceptibility Alleles 331
11.9 Conclusion 333
References 333
Foulkes_BM1.pdf 338
Anchor 1 338
Erscheint lt. Verlag | 17.12.2009 |
---|---|
Reihe/Serie | Cancer Genetics | Cancer Genetics |
Zusatzinfo | XIV, 346 p. 23 illus., 5 illus. in color. |
Verlagsort | New York |
Sprache | englisch |
Themenwelt | Medizin / Pharmazie ► Medizinische Fachgebiete ► Onkologie |
Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie | |
Studium ► 1. Studienabschnitt (Vorklinik) ► Histologie / Embryologie | |
Studium ► 2. Studienabschnitt (Klinik) ► Humangenetik | |
Schlagworte | Allele • Cancer • carcinoma • Epidemiological • epidemiology • Genetics • Grading • Obesity • prevention |
ISBN-10 | 1-4419-0449-2 / 1441904492 |
ISBN-13 | 978-1-4419-0449-2 / 9781441904492 |
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