Cooney Male Reproductive Cancers

Epidemiology, Pathology and Genetics
1. Auflage 2009
ISBN: 978-1-4419-0449-2
Verlag: Springer-Verlag
Format: PDF
Kopierschutz: Wasserzeichen (»Systemvoraussetzungen)

E-Book, Englisch, 346 Seiten

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.

Autoren/Hrsg.

Cooney, Kathleen

Inhaltsverzeichnis

1.1;Anchor 1;1
1.2;Anchor 2;1
2;Foulkes_Ch01.pdf;13
2.1;Chapter 1;14
2.1.1;The Epidemiology of Prostate Cancer;14
2.1.1.1;1.1 Introduction;14
2.1.1.1.1;1.1.1 Prostate Structure and Function;15
2.1.1.1.2;1.1.2 Aspects of Prostate Pathology Relevant to Cancer Epidemiology;16
2.1.1.1.3;1.1.3 Prostate Cancer Diagnosis, Screening and Treatment;17
2.1.1.2;1.2 Descriptive Epidemiology;19
2.1.1.3;1.3 The Epidemiological Investigation of Causes;21
2.1.1.3.1;1.3.1 Environmental Factors Not Associated with Prostate Cancer;22
2.1.1.3.2;1.3.2 Environmental Factors Possibly Associated with Prostate Cancer;23
2.1.1.3.2.1;1.3.2.1 Soy, Other Legumes and Phytoestrogens;24
2.1.1.3.2.2;1.3.2.2 Cruciferous (Brassica) Vegetables;24
2.1.1.3.2.3;1.3.2.3 Carotenoids, Tocopherols and Other Vitamins;25
2.1.1.3.2.4;1.3.2.4 Animal-Based Foods, Fats and Related Exposures;27
2.1.1.3.2.5;1.3.2.5 Dairy Foods, Calcium and Vitamin D;30
2.1.1.3.2.6;1.3.2.6 Trace Elements and Vitamin Supplements;31
2.1.1.3.2.7;1.3.2.7 Dietary Patterns;33
2.1.1.3.2.8;1.3.2.8 Energy Balance, Obesity and Physical Activity;34
2.1.1.3.2.9;1.3.2.9 Sexual Behaviour and Infections;37
2.1.1.3.3;1.3.3 Host Factors Possibly Associated with Prostate Cancer;39
2.1.1.3.3.1;1.3.3.1 Sex Steroid Hormones;39
2.1.1.3.3.2;1.3.3.2 The IGF Axis and Growth Factors;41
2.1.1.3.3.3;1.3.3.3 Inflammation;43
2.1.1.3.3.4;1.3.3.4 Family History and Genetics;45
2.1.1.4;1.4 Conclusions;46
2.1.2;References;47
3;Foulkes_Ch02.pdf;61
3.1;Chapter 2;61
3.1.1;The Epidemiology of Testicular Cancer;61
3.1.1.1;2.1 Introduction;61
3.1.1.2;2.2 Histology and Precursor Lesions;61
3.1.1.3;2.3 Incidence and Mortality;62
3.1.1.3.1;2.3.1 Incidence: Age Patterns;62
3.1.1.3.2;2.3.2 Incidence: Racial and Geographic Patterns;62
3.1.1.3.3;2.3.3 Mortality;65
3.1.1.3.4;2.3.4 Migrant Patterns;65
3.1.1.4;2.4 Associated Medical Conditions;65
3.1.1.4.1;2.4.1 Cryptorchism;66
3.1.1.4.2;2.4.2 Subfertility;67
3.1.1.4.3;2.4.3 Microlithiasis;67
3.1.1.5;2.5 Perinatal Risk Factors;68
3.1.1.5.1;2.5.1 Birth Weight and Gestational Age;68
3.1.1.5.2;2.5.2 Maternal Age;68
3.1.1.5.3;2.5.3 Maternal Parity, Birth Order, Sibship Size;68
3.1.1.5.4;2.5.4 Maternal Smoking;69
3.1.1.5.5;2.5.5 Other Perinatal Factors;70
3.1.1.6;2.6 Maternal Endogenous Hormones;70
3.1.1.7;2.7 Maternal Exogenous Hormones;71
3.1.1.8;2.8 Endocrine-Disrupting Chemicals;71
3.1.1.9;2.9 Postnatal Risk Factors;73
3.1.1.9.1;2.9.1 Anthropometry;73
3.1.1.9.2;2.9.2 Age at Puberty;73
3.1.1.9.3;2.9.3 Nutrition;73
3.1.1.9.4;2.9.4 Endogenous Hormones in Men;74
3.1.1.9.5;2.9.5 Physical Activity;74
3.1.1.9.6;2.9.6 Socioeconomic Status and Urban/Rural Residence;75
3.1.1.9.7;2.9.7 Occupation;75
3.1.1.9.8;2.9.8 Viruses;76
3.1.1.9.9;2.9.9 Other Factors;77
3.1.1.10;2.10 Histologic Difference in Risk Factors;78
3.1.1.11;2.11 Family and Twin Studies;78
3.1.1.12;2.12 Cancer Risks Among Testicular Cancer Survivors;80
3.1.1.13;2.13 Conclusions;81
3.1.2;References;82
4;Foulkes_Ch03.pdf;94
4.1;Chapter 3;95
4.1.1;Prostate Cancer: A Pathological Perspective;95
4.1.1.1;3.1 Introduction;95
4.1.1.2;3.2 Microanatomy and Histology As Related to Neoplasia;96
4.1.1.3;3.3 Gross Features;97
4.1.1.4;3.4 Microscopic and Diagnostic Features;98
4.1.1.5;3.5 Immunophenotype;100
4.1.1.6;3.6 Gleason Histological Grading System;101
4.1.1.7;3.7 Pathological Prognostic Determinants other than Grading;105
4.1.1.8;3.8 Mode of Tumor Spreading;108
4.1.1.9;3.9 Iatrogenic Histological Changes Resulting from Therapy;109
4.1.1.9.1;3.9.1 Radiation Therapy Effect;109
4.1.1.9.2;3.9.2 Androgen-Deprivation Therapy Effect;110
4.1.1.10;3.10 Putative Precursor Lesions of Prostatic Adenocarcinoma;110
4.1.1.10.1;3.10.1 Prostatic Intraepithelial Neoplasia (PIN);110
4.1.1.10.2;3.10.2 Atypical Adenomatous Hyperplasia (AAH);112
4.1.1.10.3;3.10.3 Glandular Atrophy;112
4.1.1.11;3.11 Atypical Small Acinar Proliferation (ASAP);113
4.1.1.12;3.12 Special Types of Prostatic Carcinoma;113
4.1.1.12.1;3.12.1 Ductal Adenocarcinoma;114
4.1.1.12.2;3.12.2 Mucinous Adenocarcinoma;114
4.1.1.12.3;3.12.3 Signet Ring Cell Carcinoma;114
4.1.1.12.4;3.12.4 Urothelial Carcinoma;115
4.1.1.12.5;3.12.5 Squamous Cell Carcinoma/Adenosquamous Carcinoma;116
4.1.1.12.6;3.12.6 Basal Cell Carcinoma;116
4.1.1.12.7;3.12.7 Small Cell Carcinoma;117
4.1.1.13;3.13 Emerging Biomarkers of Potential Prognostic Significance;117
4.1.1.14;3.14 Conclusions;119
4.1.2;References;120
5;Foulkes_Ch04.pdf;129
5.1;Chapter 4;129
5.1.1;Testicular Tumor Pathology;129
5.1.1.1;4.1 Introduction;129
5.1.1.2;4.2 Pathogenesis;129
5.1.1.3;4.3 Intratubular Germ Cell Neoplasia;130
5.1.1.4;4.4 Histologically Pure Germ Cell Tumors;131
5.1.1.4.1;4.4.1 Seminoma;131
5.1.1.5;4.5 Histologically Mixed Germ Cell Tumors;133
5.1.1.6;4.6 Tumor Markers;139
5.1.1.7;4.7 Staging;139
5.1.1.8;4.8 Sex Cord Stromal Tumors;141
5.1.1.9;4.9 Rete Testis Carcinoma;143
5.1.1.10;4.10 Epididymal Tumors;144
5.1.1.11;4.11 Mesothelial Neoplasms;144
5.1.1.12;4.12 Lymphoid Neoplasms;144
5.1.1.13;4.13 Metastatic Tumors;145
5.1.1.14;4.14 Conclusion;145
6;Foulkes_Ch05.pdf;148
6.1;Chapter 5;149
6.1.1;Somatic Molecular Genetics of Prostate Cancer;149
6.1.1.1;5.1 Introduction;149
6.1.1.2;5.2 Genetic Instability;150
6.1.1.3;5.3 Cytogenetics: Chromosomal Aberrations;151
6.1.1.4;5.4 Changes in Gene Expression;158
6.1.1.4.1;5.4.1 Loss of Function: Tumor and Metastasis Suppressor Genes;158
6.1.1.4.1.1;5.4.1.1 Chromosome 3;159
6.1.1.4.1.1.1;RASSF1A;159
6.1.1.4.1.2;5.4.1.2 Chromosome 6;159
6.1.1.4.1.2.1;SNORD50A;159
6.1.1.4.1.2.2;MAP3K7;160
6.1.1.4.1.3;5.4.1.3 Chromosome 8;160
6.1.1.4.1.3.1;NKX3.1;160
6.1.1.4.1.3.2;MSR1;161
6.1.1.4.1.4;5.4.1.4 Chromosome 10;161
6.1.1.4.1.4.1;PTEN;161
6.1.1.4.1.4.2;KLF6;162
6.1.1.4.1.4.3;ANXA7;162
6.1.1.4.1.5;5.4.1.5 Chromosome 11;163
6.1.1.4.1.5.1;CD44;163
6.1.1.4.1.5.2;KAI1;163
6.1.1.4.1.5.3;GSTP1;163
6.1.1.4.1.6;5.4.1.6 Chromosome 12;164
6.1.1.4.1.6.1;CDKN1B;164
6.1.1.4.1.6.2;CD9;165
6.1.1.4.1.7;5.4.1.7 Chromosome 13;165
6.1.1.4.1.7.1;RB1;165
6.1.1.4.1.8;5.4.1.8 Chromosome 16;166
6.1.1.4.1.8.1;ATBF1;166
6.1.1.4.1.8.2;CDH1;166
6.1.1.4.1.9;5.4.1.9 Chromosome 17;166
6.1.1.4.1.9.1;TP53;166
6.1.1.4.1.10;5.4.1.10 Other Downregulated Genes;167
6.1.1.4.2;5.4.2 Gain of Function: Oncogenes;167
6.1.1.4.2.1;5.4.2.1 Chromosome 3;168
6.1.1.4.2.1.1;CTNNB1;168
6.1.1.4.2.1.2;TLOC1/SEC62;168
6.1.1.4.2.2;5.4.2.2 Chromosome 5;168
6.1.1.4.2.2.1;AMACR;168
6.1.1.4.2.3;5.4.2.3 Chromosome 7;168
6.1.1.4.2.4;5.4.2.4 Chromosome 8;169
6.1.1.4.2.4.1;MYC;169
6.1.1.4.2.4.2;PSCA;169
6.1.1.4.2.5;5.4.2.5 Chromosome 10;169
6.1.1.4.2.5.1;KCNMA1;169
6.1.1.4.2.6;5.4.2.6 Chromosome 11;169
6.1.1.4.2.6.1;PSGR2;169
6.1.1.4.2.7;5.4.2.7 Chromosome 16;170
6.1.1.4.2.7.1;BCAR1;170
6.1.1.4.2.8;5.4.2.8 Chromosome 17;170
6.1.1.4.2.8.1;PRC17;170
6.1.1.4.2.9;5.4.2.9 Chromosome 18;170
6.1.1.4.2.9.1;BCL2;170
6.1.1.4.2.10;5.4.2.10 Chromosome 21;170
6.1.1.4.2.10.1;ERG and ETV1/TMPRSS2;170
6.1.1.4.2.11;5.4.2.11 Chromosome X;171
6.1.1.4.2.11.1;AR;171
6.1.1.4.2.12;5.4.2.12 Other Overexpressed genes;172
6.1.1.5;5.5 Conclusions;173
6.1.2;References;173
7;Foulkes_Ch06.pdf;187
7.1;Chapter 6;187
7.1.1;Molecular Genetics of Testicular Germ Cell Tumor;187
7.1.1.1;6.1 Introduction;187
7.1.1.2;6.2 Single Gene Changes in TGCT;189
7.1.1.3;6.3 Microsatellite Instability in TGCT;192
7.1.1.4;6.4 Epigenetics of TGCT;193
7.1.1.5;6.5 Expression Profiling Studies in TGCT;194
7.1.1.6;6.6 Chromosomal Changes in TGCT (Cytogenetics and Comparative Genomic Hybridization);195
7.1.1.7;6.7 Other Biomarkers Studied in Association with Prognosis;197
7.1.1.8;6.8 Conclusions;198
7.1.2;References;198
8;Foulkes_Ch07.pdf;206
8.1;Chapter 7;207
8.1.1;Identification of Genetic Risk Factors for Prostate Cancer: Analytic Approaches Using Hereditary Prostate Cancer Families;207
8.1.1.1;7.1 Introduction;207
8.1.1.2;7.2 Establishing that Genetic Risk Factors Exist for Prostate Cancer;208
8.1.1.2.1;7.2.1 Segregation Analysis;209
8.1.1.3;7.3 Historical Approach for Identifying Susceptibility Genes;210
8.1.1.3.1;7.3.1 Parametric Linkage Analysis;211
8.1.1.3.2;7.3.2 Nonparametric Linkage Analysis;212
8.1.1.3.3;7.3.3 Genome-Wide Linkage Screens for Prostate Cancer;214
8.1.1.3.4;7.3.4 Linkage Analysis and Clinically Aggressive Disease;215
8.1.1.3.5;7.3.5 Aggressive Prostate Cancer;216
8.1.1.3.6;7.3.6 Genetic Modifiers of Prostate Cancer Severity – Study of Gleason Grade;217
8.1.1.4;7.4 Genetic Association Studies;218
8.1.1.4.1;7.4.1 Association Studies for Prostate Cancer in Regions Identified by Linkage Analysis;219
8.1.1.4.2;7.4.2 Candidate Gene-Based Association Studies for Prostate Cancer;220
8.1.1.5;7.5 Changing Focus;220
8.1.1.6;7.6 Genome-Wide Association Studies;222
8.1.1.7;7.7 Sample Selection Strategies for Genetic Association Studies;223
8.1.1.7.1;7.7.1 Case-Control and Cohort Designs;223
8.1.1.7.2;7.7.2 Controlling False-Positive Results Due to Population Stratification;224
8.1.1.7.3;7.7.3 Family-Based Association Studies;225
8.1.1.8;7.8 Conclusions;226
8.1.2;References;226
9;Foulkes_Ch08.pdf;233
9.1;Chapter 8;233
9.1.1;The Identification of Rare and Common Variants Which Predispose to Prostate Cancer;233
9.1.1.1;8.1 Introduction and Evidence for a Genetic Predisposition;233
9.1.1.2;8.2 Models of Susceptibility to Prostate Cancer;234
9.1.1.3;8.3 Association Studies;235
9.1.1.4;8.4 Results of GWAS in Prostate Cancer;235
9.1.1.5;8.5 Rare Variants;241
9.1.1.6;8.6 Conclusions;242
9.1.2;References;244
10;Foulkes_Ch09.pdf;253
10.1;Chapter 9;253
10.1.1;Prostate Cancer in Special Populations;253
10.1.1.1;9.1.1 Introduction;255
10.1.1.2;9.1.2 Risk Variants and Familial Factors in Prostate Cancer;255
10.1.1.3;9.1.3 Candidate Loci in Prostate Cancer;256
10.1.1.4;9.1.4 Chromosome 8q24;257
10.1.1.5;9.1.5 Chromosome 17q;258
10.1.1.6;9.1.6 Conclusion;259
10.1.1.7;Note Added in Proof;260
10.1.1.8;9.2.1 Introduction;263
10.1.1.9;9.2.2 NBS1 Gene;263
10.1.1.10;9.2.3 BRCA1 Gene;265
10.1.1.11;9.2.4 CHEK2 Gene;267
10.1.1.12;9.2.5 RNASEL and MSR1 Genes;268
10.1.1.13;9.2.6 Region 8q24;269
10.1.1.14;9.2.7 Conclusion;269
10.1.1.15;9.3.1 Introduction;272
10.1.1.16;9.3.2 Brca1;273
10.1.1.17;9.3.3 Brca2;274
10.1.1.18;9.3.4 Ribonuclease L;276
10.1.1.19;9.3.5 Chek2;277
10.1.1.20;9.3.6 Msr1;278
10.1.1.21;9.3.7 Chromosome 7 Locus;278
10.1.1.22;9.3.8 Additional Genome-Wide Studies;279
10.1.1.23;9.3.9 Other Loci;279
10.1.1.24;9.3.10 Conclusions;279
10.1.1.25;Introduction;284
10.1.1.26;Evidence that Genetic Factors Play a Critical Role in Prostate Cancer Outcomes Among African-Americans;284
10.1.1.27;The African-American Hereditary Prostate Cancer Study (1997–2000);286
10.1.1.28;Clinical Characteristics of African-American Men in the AAHPC Study;286
10.1.1.29;Genome-Wide Linkage of 77 Families from the AAHPC;287
10.1.1.30;Compelling Evidence for a Prostate Cancer Gene at 22q12.3 – ICPCG;287
10.1.1.31;Genetic Variants at the 8q24 Locus in African-American Men;288
10.1.1.32;Conclusion;289
10.1.1.33;Note Added in Proof;289
10.1.2;References;290
11;Foulkes_Ch10.pdf;292
11.1;Chapter 10;292
11.1.1;Inherited Susceptibility of Aggressive Prostate Cancer;292
11.1.1.1;10.1 Introduction;292
11.1.1.2;10.2 Assessment of Prostate Cancer Aggressiveness;293
11.1.1.2.1;10.2.1 Staging;294
11.1.1.2.2;10.2.2 Grading;294
11.1.1.2.2.1;10.2.2.1 Reliability of Gleason Score;294
11.1.1.2.3;10.2.3 Other Measures of Aggressiveness;295
11.1.1.3;10.3 Non-genetic Risk Factors for Aggressive Prostate Cancer;295
11.1.1.3.1;10.3.1 Age and Ethnicity;295
11.1.1.3.2;10.3.2 Smoking, Alcohol, Physical Exercise, Obesity, and Diet;296
11.1.1.4;10.4 Family History and Prostate Cancer Aggressiveness;297
11.1.1.5;10.5 Segregation Analysis;298
11.1.1.6;10.6 Linkage Analysis;299
11.1.1.7;10.7 Association Studies;302
11.1.1.7.1;10.7.1 Candidate Gene Association Studies and Aggressiveness;302
11.1.1.7.1.1;10.7.1.1 Androgen Receptors;302
11.1.1.7.1.2;10.7.1.2 Vitamin D Receptors;304
11.1.1.7.1.3;10.7.1.3 Other Candidate Genes;305
11.1.1.7.2;10.7.2 Chromosome 8q24;306
11.1.1.8;10.8 Conclusion and Future Work;308
11.1.2;References;308
12;Foulkes_Ch11.pdf;319
12.1;Chapter 11;319
12.1.1;Susceptibility Alleles for Testicular Germ Cell Tumor;319
12.1.1.1;11.1 Introduction;319
12.1.1.2;11.2 Evidence for TGCT Susceptibility Alleles;320
12.1.1.3;11.3 Familial TGCT;321
12.1.1.4;11.4 Identifying TGCT Susceptibility Alleles – Genetic Linkage Analysis;324
12.1.1.4.1;11.4.1 Linkage to a Region at Xq27;326
12.1.1.4.2;11.4.2 Genome-Wide Linkage Analysis;326
12.1.1.5;11.5 The Y Chromosome;327
12.1.1.5.1;11.5.1 gr/gr as a Low-Penetrance Susceptibility Allele;327
12.1.1.5.2;11.5.2 Other Y Regions?;328
12.1.1.6;11.6 Evaluation of Candidate Genes for TGCT;329
12.1.1.6.1;11.6.1 The Androgen Receptor Gene;329
12.1.1.6.2;11.6.2 Dnd1;330
12.1.1.7;11.7 Association Studies;331
12.1.1.8;11.8 Identifying TGCT Susceptibility Alleles;331
12.1.1.9;11.9 Conclusion;333
12.1.2;References;333
13;Foulkes_BM1.pdf;338
13.1;Anchor 1;338