Male Reproductive Cancers - Epidemiology, Pathology and Genetics

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Foulkes_Ch01.pdf

Chapter 1

The Epidemiology of Prostate Cancer

1.1 Introduction

1.1.1 Prostate Structure and Function

1.1.2 Aspects of Prostate Pathology Relevant to Cancer Epidemiology

1.1.3 Prostate Cancer Diagnosis, Screening and Treatment

1.2 Descriptive Epidemiology

1.3 The Epidemiological Investigation of Causes

1.3.1 Environmental Factors Not Associated with Prostate Cancer

1.3.2 Environmental Factors Possibly Associated with Prostate Cancer

1.3.2.1 Soy, Other Legumes and Phytoestrogens

1.3.2.2 Cruciferous (Brassica) Vegetables

1.3.2.3 Carotenoids, Tocopherols and Other Vitamins

1.3.2.4 Animal-Based Foods, Fats and Related Exposures

1.3.2.5 Dairy Foods, Calcium and Vitamin D

1.3.2.6 Trace Elements and Vitamin Supplements

1.3.2.7 Dietary Patterns

1.3.2.8 Energy Balance, Obesity and Physical Activity

1.3.2.9 Sexual Behaviour and Infections

1.3.3 Host Factors Possibly Associated with Prostate Cancer

1.3.3.1 Sex Steroid Hormones

1.3.3.2 The IGF Axis and Growth Factors

1.3.3.3 Inflammation

1.3.3.4 Family History and Genetics

1.4 Conclusions

References

Foulkes_Ch02.pdf

Chapter 2

The Epidemiology of Testicular Cancer

2.1 Introduction

2.2 Histology and Precursor Lesions

2.3 Incidence and Mortality

2.3.1 Incidence: Age Patterns

2.3.2 Incidence: Racial and Geographic Patterns

2.3.3 Mortality

2.3.4 Migrant Patterns

2.4 Associated Medical Conditions

2.4.1 Cryptorchism

2.4.2 Subfertility

2.4.3 Microlithiasis

2.5 Perinatal Risk Factors

2.5.1 Birth Weight and Gestational Age

2.5.2 Maternal Age

2.5.3 Maternal Parity, Birth Order, Sibship Size

2.5.4 Maternal Smoking

2.5.5 Other Perinatal Factors

2.6 Maternal Endogenous Hormones

2.7 Maternal Exogenous Hormones

2.8 Endocrine-Disrupting Chemicals

2.9 Postnatal Risk Factors

2.9.1 Anthropometry

2.9.2 Age at Puberty

2.9.3 Nutrition

2.9.4 Endogenous Hormones in Men

2.9.5 Physical Activity

2.9.6 Socioeconomic Status and Urban/Rural Residence

2.9.7 Occupation

2.9.8 Viruses

2.9.9 Other Factors

2.10 Histologic Difference in Risk Factors

2.11 Family and Twin Studies

2.12 Cancer Risks Among Testicular Cancer Survivors

2.13 Conclusions

References

Foulkes_Ch03.pdf

Chapter 3

Prostate Cancer: A Pathological Perspective

3.1 Introduction

3.2 Microanatomy and Histology As Related to Neoplasia

3.3 Gross Features

3.4 Microscopic and Diagnostic Features

3.5 Immunophenotype

3.6 Gleason Histological Grading System

3.7 Pathological Prognostic Determinants other than Grading

3.8 Mode of Tumor Spreading

3.9 Iatrogenic Histological Changes Resulting from Therapy

3.9.1 Radiation Therapy Effect

3.9.2 Androgen-Deprivation Therapy Effect

3.10 Putative Precursor Lesions of Prostatic Adenocarcinoma

3.10.1 Prostatic Intraepithelial Neoplasia (PIN)

3.10.2 Atypical Adenomatous Hyperplasia (AAH)

3.10.3 Glandular Atrophy

3.11 Atypical Small Acinar Proliferation (ASAP)

3.12 Special Types of Prostatic Carcinoma

3.12.1 Ductal Adenocarcinoma

3.12.2 Mucinous Adenocarcinoma

3.12.3 Signet Ring Cell Carcinoma

3.12.4 Urothelial Carcinoma

3.12.5 Squamous Cell Carcinoma/Adenosquamous Carcinoma

3.12.6 Basal Cell Carcinoma

3.12.7 Small Cell Carcinoma

3.13 Emerging Biomarkers of Potential Prognostic Significance

3.14 Conclusions

References

Foulkes_Ch04.pdf

Chapter 4

Testicular Tumor Pathology

4.1 Introduction

4.2 Pathogenesis

4.3 Intratubular Germ Cell Neoplasia

4.4 Histologically Pure Germ Cell Tumors

4.4.1 Seminoma

4.5 Histologically Mixed Germ Cell Tumors

4.6 Tumor Markers

4.7 Staging

4.8 Sex Cord Stromal Tumors

4.9 Rete Testis Carcinoma

4.10 Epididymal Tumors

4.11 Mesothelial Neoplasms

4.12 Lymphoid Neoplasms

4.13 Metastatic Tumors

4.14 Conclusion

Foulkes_Ch05.pdf

Chapter 5

Somatic Molecular Genetics of Prostate Cancer

5.1 Introduction

5.2 Genetic Instability

5.3 Cytogenetics: Chromosomal Aberrations

5.4 Changes in Gene Expression

5.4.1 Loss of Function: Tumor and Metastasis Suppressor Genes

5.4.1.1 Chromosome 3

RASSF1A

5.4.1.2 Chromosome 6

SNORD50A

MAP3K7

5.4.1.3 Chromosome 8

NKX3.1

MSR1

5.4.1.4 Chromosome 10

PTEN

KLF6

ANXA7

5.4.1.5 Chromosome 11

CD44

KAI1

GSTP1

5.4.1.6 Chromosome 12

CDKN1B

CD9

5.4.1.7 Chromosome 13

RB1

5.4.1.8 Chromosome 16

ATBF1

CDH1

5.4.1.9 Chromosome 17

TP53

5.4.1.10 Other Downregulated Genes

5.4.2 Gain of Function: Oncogenes

5.4.2.1 Chromosome 3

CTNNB1

TLOC1/SEC62

5.4.2.2 Chromosome 5

AMACR

5.4.2.3 Chromosome 7

5.4.2.4 Chromosome 8

MYC

PSCA

5.4.2.5 Chromosome 10

KCNMA1

5.4.2.6 Chromosome 11

PSGR2

5.4.2.7 Chromosome 16

BCAR1

5.4.2.8 Chromosome 17

PRC17

5.4.2.9 Chromosome 18

BCL2

5.4.2.10 Chromosome 21

ERG and ETV1/TMPRSS2

5.4.2.11 Chromosome X

AR

5.4.2.12 Other Overexpressed genes

5.5 Conclusions

References

Foulkes_Ch06.pdf

Chapter 6

Molecular Genetics of Testicular Germ Cell Tumor

6.1 Introduction

6.2 Single Gene Changes in TGCT

6.3 Microsatellite Instability in TGCT

6.4 Epigenetics of TGCT

6.5 Expression Profiling Studies in TGCT

6.6 Chromosomal Changes in TGCT (Cytogenetics and Comparative Genomic Hybridization)

6.7 Other Biomarkers Studied in Association with Prognosis

6.8 Conclusions

References

Foulkes_Ch07.pdf

Chapter 7

Identification of Genetic Risk Factors for Prostate Cancer: Analytic Approaches Using Hereditary Prostate Cancer Families

7.1 Introduction

7.2 Establishing that Genetic Risk Factors Exist for Prostate Cancer

7.2.1 Segregation Analysis

7.3 Historical Approach for Identifying Susceptibility Genes

7.3.1 Parametric Linkage Analysis

7.3.2 Nonparametric Linkage Analysis

7.3.3 Genome-Wide Linkage Screens for Prostate Cancer

7.3.4 Linkage Analysis and Clinically Aggressive Disease

7.3.5 Aggressive Prostate Cancer

7.3.6 Genetic Modifiers of Prostate Cancer Severity – Study of Gleason Grade

7.4 Genetic Association Studies

7.4.1 Association Studies for Prostate Cancer in Regions Identified by Linkage Analysis

7.4.2 Candidate Gene-Based Association Studies for Prostate Cancer

7.5 Changing Focus

7.6 Genome-Wide Association Studies

7.7 Sample Selection Strategies for Genetic Association Studies

7.7.1 Case-Control and Cohort Designs

7.7.2 Controlling False-Positive Results Due to Population Stratification

7.7.3 Family-Based Association Studies

7.8 Conclusions

References

Foulkes_Ch08.pdf

Chapter 8

The Identification of Rare and Common Variants Which Predispose to Prostate Cancer

8.1 Introduction and Evidence for a Genetic Predisposition

8.2 Models of Susceptibility to Prostate Cancer

8.3 Association Studies

8.4 Results of GWAS in Prostate Cancer

8.5 Rare Variants

8.6 Conclusions

References

Foulkes_Ch09.pdf

Chapter 9

Prostate Cancer in Special Populations

9.1.1 Introduction

9.1.2 Risk Variants and Familial Factors in Prostate Cancer

9.1.3 Candidate Loci in Prostate Cancer

9.1.4 Chromosome 8q24

9.1.5 Chromosome 17q

9.1.6 Conclusion

Note Added in Proof

9.2.1 Introduction

9.2.2 NBS1 Gene

9.2.3 BRCA1 Gene

9.2.4 CHEK2 Gene

9.2.5 RNASEL and MSR1 Genes

9.2.6 Region 8q24

9.2.7 Conclusion

9.3.1 Introduction

9.3.2 Brca1

9.3.3 Brca2

9.3.4 Ribonuclease L

9.3.5 Chek2

9.3.6 Msr1

9.3.7 Chromosome 7 Locus

9.3.8 Additional Genome-Wide Studies

9.3.9 Other Loci

9.3.10 Conclusions

Introduction

Evidence that Genetic Factors Play a Critical Role in Prostate Cancer Outcomes Among African-Americans

The African-American Hereditary Prostate Cancer Study (1997–2000)

Clinical Characteristics of African-American Men in the AAHPC Study

Genome-Wide Linkage of 77 Families from the AAHPC

Compelling Evidence for a Prostate Cancer Gene at 22q12.3 – ICPCG

Genetic Variants at the 8q24 Locus in African-American Men

Conclusion

Note Added in Proof

References

Foulkes_Ch10.pdf

Chapter 10

Inherited Susceptibility of Aggressive Prostate Cancer

10.1 Introduction

10.2 Assessment of Prostate Cancer Aggressiveness

10.2.1 Staging

10.2.2 Grading

10.2.2.1 Reliability of Gleason Score

10.2.3 Other Measures of Aggressiveness

10.3 Non-genetic Risk Factors for Aggressive Prostate Cancer

10.3.1 Age and Ethnicity

10.3.2 Smoking, Alcohol, Physical Exercise, Obesity, and Diet

10.4 Family History and Prostate Cancer Aggressiveness

10.5 Segregation Analysis

10.6 Linkage Analysis

10.7 Association Studies

10.7.1 Candidate Gene Association Studies and Aggressiveness

10.7.1.1 Androgen Receptors

10.7.1.2 Vitamin D Receptors

10.7.1.3 Other Candidate Genes

10.7.2 Chromosome 8q24

10.8 Conclusion and Future Work

References

Foulkes_Ch11.pdf

Chapter 11

Susceptibility Alleles for Testicular Germ Cell Tumor

11.1 Introduction

11.2 Evidence for TGCT Susceptibility Alleles

11.3 Familial TGCT

11.4 Identifying TGCT Susceptibility Alleles – Genetic Linkage Analysis

11.4.1 Linkage to a Region at Xq27

11.4.2 Genome-Wide Linkage Analysis

11.5 The Y Chromosome

11.5.1 gr/gr as a Low-Penetrance Susceptibility Allele

11.5.2 Other Y Regions?

11.6 Evaluation of Candidate Genes for TGCT

11.6.1 The Androgen Receptor Gene

11.6.2 Dnd1

11.7 Association Studies

11.8 Identifying TGCT Susceptibility Alleles

11.9 Conclusion

References

Foulkes_BM1.pdf

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