Hereditary Colorectal Cancer (eBook)

Miguel A. Rodriguez-Bigas, Raul Cutait, Patrick M. Lynch, Ian Tomlinson, Hans F.A. Vasen (Herausgeber)

eBook Download: PDF

2010 | 2010
XVIII, 630 Seiten
Springer US (Verlag)
978-1-4419-6603-2 (ISBN)

Infos

Colorectal cancer is the third most commonly diagnosed cancer in the US and the third most recently linked to cancer deaths. The national annual incidence rate of colorectal cancer is approximately 148,000+, striking slightly more females than males. The lifetime risk of colorectal cancer is 5-6%, however patients with a familial risk (with two or more first or second degree relatives) make up 20% of the patients. Persons who carry genetic mutations linked to hereditary colorectal cancer are the most likely to develop the disease.

Inhalt

Preface 6
Contents 8
Contributors 12
Chapter 1: History: Familial Adenomatous Polyposis 21
1.1 Why Is History Important? 21
1.2 Early Descriptions 22
1.3 Foundation of Registries and Collaborative Groups 22
1.3.1 The Leeds Castle Polyposis Group and International Society for Gastrointestinal Hereditary Tumours 24
1.4 Development of Clinical Understanding of FAP 26
1.5 FAP as a Model of Sporadic Colorectal Cancer 26
1.6 Prophylactic Surgery 27
1.6.1 Post-operative Follow-up 28
1.6.2 Advances in Surgical Technique 28
1.6.3 Impact of Genetics on Surgical Choice 29
1.7 Gene Discovery 30
1.7.1 MYH-associated Polyposis 30
1.8 History into the Future 30
References 31
Chapter 2: Historical Aspects of Lynch Syndrome 33
2.1 Introduction 34
2.2 Discovery of Lynch Syndrome’s Natural History 38
2.3 1990s: Discovery of Mutations of the Mismatch Repair Genes in Lynch Syndrome 43
2.4 Microsatellite Instability and Immunohistochemistry Testing 44
2.5 Germline Epimutations as a Cause for Lynch Syndrome 45
2.5.1 2002: Identification of Germline Epimutation of MLH1 45
2.5.2 Phenotypic Features 46
2.5.3 A Newly Described Complication: Inheritance of MLH1 Germline Epimutations 48
2.5.4 Frequency and Screening in the HNPCC Population 50
2.5.5 2006: Familial Epimutations of MSH2 caused by upstream terminal deletions of EPCAM 51
2.5.6 Effectiveness of Surveillance 52
2.6 Mucosal Architecture 52
2.7 Value of Knowledge of Mutation Status 53
2.8 Prophylactic Colectomy 54
2.9 Prophylactic Hysterectomy and Oophorectomy 54
2.10 Summary 54
References 55
Chapter 3: Molecular Genetics of Familial Adenomatous Polyposis 62
3.1 Introduction 62
3.2 Some Historical Notes 63
3.3 Attenuated FAP 64
3.4 Structure of the APC Gene and Protein 64
3.5 APC and Wnt Pathway Regulation 65
3.6 Other Functional Domains of APC 66
3.7 Germline and Somatic APC Mutations 67
3.8 Genotype–Phenotype Associations in FAP 67
3.9 APC and “Just Right” Wnt Signalling 70
3.10 Missense APC Variants Including I1307K 71
3.11 APC Promoter Hypermethylation 72
3.12 APC Mutations in MYH-Associated Polyposis 72
3.13 Mouse Models of Intestinal Polyposis 73
3.14 Concluding Remarks 78
References 79
Chapter 4: DNA Mismatch Repair 84
4.1 DNA Damage and Repair 84
4.1.1 Types of DNA Damage and Specific Repair Mechanisms 85
4.1.1.1 Nucleotide Excision Repair 85
4.1.1.2 Base Excision Repair 85
4.1.1.3 DNA Mismatch Repair 86
4.1.2 Evolutionary Considerations in the DNA MMR System 86
4.1.3 Mismatch Recognition Proteins: The Mut-S Family 86
4.1.3.1 Mismatch Recognition in Prokaryotes 86
4.1.3.2 Stabilization of MutS Proteins 88
4.1.3.3 Recognition of Mismatched DNA by MutS Heterodimers 88
4.1.3.4 Other MutS Homologs 90
4.1.4 Matchmaker Proteins: The Mut-L Family 90
4.1.4.1 Molecular Matchmakers 91
4.1.4.2 Excision of the Error from the Mismatch, and Strand Discrimination 91
4.2 Microsatellite Instability 92
4.2.1 Microsatellites 92
4.2.2 Loss of DNA MMR Causes MSI 93
4.2.3 The Discovery of MSI in Colorectal Cancer 94
4.2.4 MSI Is Linked to Hereditary CRC 94
4.2.5 DNA MMR Genes and Lynch Syndrome 95
4.2.5.1 Major and Minor DNA MMR Genes 95
4.3 Molecular Targets of MSI in Cancer 96
4.4 Defective MSI in Non-Lynch Syndrome CRC 98
4.5 Hereditary CRC Without Defective DNA MMR (“Familial Colorectal Cancer, Type X”) 99
4.6 Pathological Downregulation of DNA MMR Activity 99
References 100
Chapter 5: Basic Sciences and Genetics: Hamartomatous Polyposis 103
5.1 Juvenile Polyposis 103
5.2 SMAD4 Mutations in JP 105
5.3 BMPR1A Mutations in JP 106
5.4 Cowden Syndrome 110
5.5 PTEN Mutations in CS 110
5.6 Bannayan–Riley–Ruvalcaba Syndrome 112
5.7 Peutz–Jeghers Syndrome 114
5.8 LKB1 Mutations in PJS Patients 115
5.9 PJS Genotype–Phenotype Associations 118
5.10 Mouse Models of PJS 120
5.11 Summary 120
References 121
Chapter 6: Hyperplastic Polyposis Syndrome: Colorectal Cancer Predisposition 126
6.1 Introduction 127
6.2 Hyperplastic Polyposis Syndrome 127
6.3 HPS and an Increased Risk of CRC: An Evolving Concept 129
6.4 Phenotypic Heterogeneity in HPS 130
6.5 Molecular Pathways in HPS 132
6.5.1 Historical Context 132
6.5.2 Serrated Pathway Changes in HPS 133
6.5.3 Molecular Heterogeneity in HPS 134
6.6 Serrated Pathway Cancers in the Population 134
6.7 Genetics of HPS 135
6.7.1 A General Cancer Predisposition? 139
6.8 Clinical Implications of HPS 139
6.9 Summary and Conclusion 140
References 140
Chapter 7: MUTYH-Associated Polyposis 147
7.1 Inherited Predisposition to Colorectal Cancer 147
7.1.1 Identification of an Unusual Mutator Phenotype in Family N 148
7.1.2 Base Excision Repair 148
7.1.3 Inherited Mutations in MUTYH Predispose to Colorectal Tumours 150
7.2 The Phenotype of MAP 151
7.2.1 Mutation Spectrum in MUTYH and Diagnostic Implications 152
7.3 The Pathway of MAP Tumourigenesis 152
7.4 Function of MutY/MUTYH 154
7.4.1 Functional Overlap with Other Repair Pathways 155
7.4.2 Functional Studies of MUTYH Missense Variants 155
7.5 Genetic Testing and Clinical Management of MAP 156
References 156
Chapter 8: Polymorphic Variation and Risk of Colorectal Cancer 161
8.1 Distribution of Polymorphisms and Linkage Disequilibrium in the Human Genome 162
8.2 The Association Study Design for Identifying Low Penetrance Cancer Susceptibility Alleles 163
8.2.1 Linkage Versus Association 163
8.2.2 Enriching for Genetic Susceptibility 163
8.2.3 Failure to Replicate Positive Associations 165
8.2.4 Population Stratification 165
8.3 Direct Association Studies for CRC Susceptibility Polymorphism Discovery 166
8.3.1 Carcinogen Metabolism Genes 166
8.3.2 Genes Involved in Folate Metabolism 167
8.3.3 Colonic Microenvironment Modifiers 167
8.3.4 Tumour Suppressor Genes and Oncogenes 170
8.3.5 Genes Involved in Inflammation 170
8.3.6 Genes Harbouring High Penetrance CRC Susceptibility Mutations 171
8.3.7 Other Genes 172
8.4 Meta-analyses of Direct Association Studies 172
8.5 Indirect Association Studies 175
8.6 Genome-Wide Association Studies 175
8.7 Gene–Environment and Gene–Gene Interactions 176
8.8 Polymorphisms and Efficacy of Chemopreventive and Chemotherapeutic Drugs 178
8.9 Conclusions 179
References 179
Chapter 9: The Pathologist and the Phenotype of Hereditary Colorectal Cancer 187
9.1 Linking Morphology, Behavior, and Genotype: The Central Challenge 187
9.2 Rarity and Phenotypic Complexity of Hereditary Colorectal Cancer Syndromes 189
9.3 Labeling a Mucosal Lesion as a Polyp: The Problem of Size 190
9.4 Labeling a Mucosal Lesion as a Polyp: The Problem of Flatness 192
9.5 Assessing Polyp Numbers 193
9.6 Anatomic Location of Polyps and Cancers 195
9.7 Classification of Colorectal Polyps 195
9.7.1 Neoplastic Versus Non-neoplastic Polyps 195
9.7.2 Variant Polyps 196
9.7.3 Mixed Polyps 196
9.7.4 Serrated Polyps 198
9.8 Types of Colorectal Cancer 199
9.9 Comprehensive Description of Phenotype: A Difficult Task 200
9.10 Checklist for Description of Phenotype 201
References 202
Chapter 10: Genotype Phenotype Correlation in Familial Adenomatous Polyposis 208
10.1 Colonic Polyposis 209
10.2 Rectal Cancer Risk 210
10.3 Upper Gastrointestinal Polyps 210
10.4 Desmoid Tumors 211
10.5 Congenital Hypertrophied Pigmented Retinal Epithelium 211
10.6 Osteomas 211
10.7 Thyroid Cancer 211
10.8 Summary 212
References 212
Chapter 11: Surgery for Familial Adenomatous Polyposis 214
11.1 Introduction 215
11.2 Aims of Surgery 215
11.3 Factors Influencing Choice and Timing of Surgery 215
11.3.1 Disease Severity 215
11.3.2 Desmoid Tumors 216
11.4 Surgical Options 216
11.4.1.a Postoperatively 218
11.4.2 IPAA 219
11.4.2.a Type of Pouch 219
11.4.2.b Type of Anastomosis 219
11.4.2.c Diversion or Not 220
Postoperatively 220
11.5 Factors Influencing Choice of Surgery 221
11.5.2 Patient Age and Body Habitus 221
11.5.3 Risk of Desmoids 222
11.5.4 Timing of Surgery 222
11.6 Outcome of Surgery 222
11.7 Reoperative Surgery in Patients with FAP 225
11.8 Summary 226
References 227
Chapter 12: Duodenal Adenomas in Familial Adenomatous Polyposis 229
12.1 Introduction 229
12.2 Epidemiology 230
12.3 Distribution 230
12.4 Aetiology 231
12.4.1 Bile 231
12.4.2 Genetics 231
12.5 Hormones and Pregnancy 232
12.6 Adenoma–Carcinoma Sequence 233
12.7 Natural History 234
12.7.1 Ampulla 235
12.7.2 Non-ampullary Duodenum 235
12.8 Endoscopic Appearances 237
12.9 Management 238
12.9.1 Endoscopic Surveillance 238
12.9.2 Medical 239
12.9.3 Surgical 240
12.9.4 Endoscopic 241
12.9.5 Summary 243
References 243
Chapter 13: FAP-Associated Desmoid Tumours 248
13.1 Introduction 248
13.2 Aetiology 249
13.3 Categorization and Staging 250
13.3.1 DES Classification (Diameter–Expansion–Site for DESmoids) 250
13.3.2 Desmoid Tumour Staging System [15] 251
13.3.3 MRI Appearance as a Predictor of Growth Potential 251
13.4 Treatment 252
13.4.1 Radiotherapy 252
13.4.2 Surgery 253
13.4.3 Systemic Therapy 253
13.4.3.1 Non-cytotoxic Chemotherapy 254
NSAIDs 255
Anti-oestrogens 255
Other Non-cytotoxic Agents 256
Cytotoxic Chemotherapy 256
Take Home Message 258
References 258
Chapter 14: Attenuated Familial Adenomatous Polyposis: Diagnosis, Management, and Future Prognosis 261
14.1 Clinical Presentation 261
14.2 Clinical Management 263
14.3 Molecular Genetics 264
14.4 Genotype–Phenotype Correlations 265
14.5 Deletions 266
14.6 Splicing Mutations 267
14.7 Modifiers 268
14.8 Outliers 269
14.9 Summary 269
14.10 Future Directions 270
References 271
Chapter 15: An Overview of the Lynch Syndrome (Hereditary Non-polyposis Colorectal Cancer) 277
15.1 Introduction 278
15.2 Clinical Features 279
15.2.1 Autosomal Dominant Inheritance 279
15.2.2 Cancers Associated with the Lynch Syndrome 280
15.2.3 Cancer Risk and Geno/Phenotype Correlations 280
15.2.4 Modifier Genes 281
15.2.5 Early Age of Onset 282
15.2.6 Occurrence of Multiple Tumours 283
15.2.7 Features of Colorectal Adenoma and Carcinoma 283
15.2.8 Features of Endometrial Cancer 284
15.2.9 Features of Other Associated Cancers 284
15.2.9.1 Ovarian Cancer 284
15.2.9.2 Gastric Cancers 284
15.2.9.3 Cancer of the Ureter/Pyelum 285
15.2.9.4 Small Bowel 285
15.2.9.5 Brain 285
15.2.9.6 Skin Tumours 286
15.2.10 Features of Individuals with Bi-allelic MMR-Mutations 286
15.3 Clinical Criteria for the Lynch Syndrome 287
15.3.1 Amsterdam Criteria I and II 287
15.3.2 Bethesda and Other Criteria 287
15.3.3 Tests Performances of Amsterdam and Bethesda Criteria 288
15.4 Molecular Genetic Studies 288
15.4.1 Mutation Analysis 288
15.4.2 Microsatellite Instability (MSI) Analysis of Colorectal Tumours 289
15.4.3 The Role of Immunohistochemical Analysis of the Mismatch Repair Proteins 289
15.4.4 Sensitivity of MSI and IHC for Identification of Mutations 290
15.4.5 Diagnostic Approach in Patients Suspected of Lynch Syndrome 291
15.5 Presymptomatic Diagnosis 292
15.6 Surveillance 293
15.6.1 Colorectum 293
15.6.2 Surveillance of the Endometrium/Ovary 294
15.6.3 Surveillance for Other Related Cancers 295
15.7 Treatment 297
15.7.1 Surgical Management of Colorectal Cancer 297
15.7.2 Chemotherapy 297
15.8 Chemoprevention 298
15.9 Conclusions 298
References 299
Chapter 16: Surgical Management in Lynch Syndrome 306
16.1 Introduction 306
16.2 Colon and Rectum 307
16.2.1 Surgery for a Newly Diagnosed Tumor 307
16.2.2 Colon 307
16.2.3 Rectum 308
16.3 Previous Segmental Resection 310
16.4 Mutation Carriers with Adenomas 311
16.5 Gene Mutation Carriers 311
16.6 Patients with Microsatellite Unstable Colorectal Cancer (MSI-H) 311
16.7 Prophylactic Hysterectomy and Salpingoophorectomy 312
16.8 Conclusions 312
References 312
Chapter 17: Extracolonic Tumors 315
17.1 Tumor Spectrum 316
17.2 Lifetime Risk of Cancer 318
17.3 Endometrium 320
17.4 Urinary Tract 322
17.5 Small Bowel 322
17.6 Brain 324
17.7 Stomach 324
17.8 Hepatobiliary Tract and Pancreas 325
17.9 Skin 326
17.10 Breast 326
17.11 Conclusion 332
References 332
Chapter 18: Surveillance 338
18.1 Introduction 338
18.2 Identification of HNPCC 339
18.3 Genetic Testing 340
18.4 Screening Guidelines 342
18.4.1 Colonoscopy Surveillance 342
18.4.2 Surveillance for Gynecological Cancer 344
18.4.3 Surveillance for Other Related Cancers 345
18.5 Alternative Strategies 346
18.5.1 Prophylactic Surgery 346
18.5.2 Chemoprevention 347
18.6 Summary 347
References 347
Chapter 19: MUTYH-Associated Polyposis 351
19.1 MUTYH-Associated Polyposis 351
19.2 MUTYH Mutations in MUTYH-Associated Polyposis 352
19.3 Colorectal Phenotype 354
19.4 Extracolonic Manifestations 356
19.5 Genotype–Phenotype Relationship 358
19.6 Heterozygous MUTYH Mutation Carriers 360
19.7 Genetic Testing and Clinical Management of MUTYH-Associated Polyposis 360
References 361
Chapter 20: Peutz–Jeghers Syndrome 366
20.1 Introduction 366
20.2 Clinical Manifestations 367
20.2.1 Clinical Presentation 367
20.2.2 Gastrointestinal Polyps 367
20.2.3 Gastrointestinal and Nongastrointestinal Neoplasia 368
20.3 Genetic Cause 370
20.4 Management 371
20.4.1 Screening of At-Risk Individuals 371
20.4.2 Surveillance of Affected Individuals 372
20.4.3 Treatment 373
References 374
Chapter 21: Clinical Aspects of Juvenile Polyposis 376
21.1 Historical Perspective 376
21.2 The Current View 379
21.2.1 Definition 379
21.2.2 Subtypes 379
21.2.3 Clinical Diagnosis, Workup, and Testing 380
21.3 The Juvenile Polyp 381
21.4 Genetics and Inheritance 384
21.5 Cancer Predisposition 385
21.5.1 Colorectal 385
21.5.2 Gastric 388
21.5.3 Pancreas 390
21.6 Differential Diagnosis 390
21.6.1 PTEN Hamartoma Tumor Syndromes: Cowden and Bannaya–Riley–Ruvalcaba Syndrome 390
21.6.2 Peutz–Jeghers Syndrome 390
21.6.3 Hereditary Mixed Polyposis Syndrome 391
21.6.4 Familial Adenomatous Polyposis 391
21.7 Associated Anomalies 391
21.8 Management 393
21.8.1 Screening and Surveillance 393
21.8.2 Operative Management for Colonic Disease 393
21.8.2.1 Polypectomy 393
21.8.2.2 Colectomy with Ileorectal Anastomosis 394
21.8.2.3 Total Colectomy with Ileoanal Pull Through 395
21.8.2.4 Operative Management for Gastric Disease 396
21.9 Genetic Counseling 396
References 396
Chapter 22: Hereditary Mixed Polyposis Syndrome and Multiple Adenoma Patients 401
22.1 Introduction 401
22.2 Hereditary Mixed Polyposis Syndrome 402
22.2.1 Clinical Features 402
22.2.2 Genetic Studies in HMPS 403
22.2.2.1 Linkage Analysis 403
22.2.2.2 Loss of Heterozygosity 405
22.2.2.3 Association Study 405
22.2.3 Clinical Management of HMPS 406
22.3 Multiple Adenoma Patients 406
22.3.1 Clinical Features 406
22.3.2 Genetic Studies 407
22.3.3 Clinical Management of Multiple Adenoma Patients 407
References 408
Chapter 23: Hyperplastic Polyposis 410
23.1 Introduction 410
23.2 Definition and Diagnostic Criteria 410
23.3 Hyperplastic Polyposis and Colorectal Cancer 415
23.4 Management of Patients with Hyperplastic Polyposis 416
23.5 Conclusions 417
References 418
Chapter 24: Genetic Counseling Overview 422
References 425
Chapter 25: Across Culture and Health Systems: Europe 427
25.1 Introduction and Background 427
25.1.1 Languages and Religions 429
25.1.2 History 429
25.1.3 Politics 429
25.2 Healthcare Systems in Europe 429
25.2.1 HealthCare Resources 432
25.2.2 Financing 433
25.2.3 Services Provided 433
25.2.4 Access to HealthCare Service 434
25.2.5 Colorectal Cancer Incidence and 5 Year Survival 434
25.2.6 Performance and Overall Goal Attainment 435
25.2.7 Responsiveness 435
25.2.8 Reservations About the Statistical Material 436
25.2.9 Handling of HNPCC in the Health Care System 436
25.3 Summary 438
References 438
Chapter 26: Across Culture and Health Systems: Asia (Hong Kong) 440
26.1 Introduction: Colorectal Cancer in Hong Kong 440
26.2 The Hereditary Gastrointestinal Cancer Registry 441
26.3 Psychosocial Impact of Hereditary Colorectal Cancer in Chinese 443
26.3.1 Influence of Chinese Culture 443
26.3.2 Genetic Testing 445
26.4 Psychosocial Program 446
26.4.1 Psychoeducational Program for Genetic Testing 446
26.4.1.1 Educational Material 446
26.4.1.2 Genetic Counseling 447
26.4.1.3 Pre-testing Genetic Counseling 448
26.4.1.4 Group Psycho-Education for Extended Family 448
26.4.1.5 Procedure for Disclosure of Genetic Testing Result 449
26.4.1.6 Post-testing Genetic Counseling 449
26.4.1.7 Post-disclosure Follow-Up 449
26.4.2 Psychosocial Support Program 449
26.4.2.1 Patient Support Groups 449
26.4.2.2 Ad Hoc Peer and Professional Psychological Support 450
26.4.3 Intervention Based on the Theory of Positive Psychology: Future Direction of Psychological Service 450
26.5 Issues Relating to HCRC in Hong Kong 451
26.5.1 Government Involvement in the Management of HCRC 451
26.5.2 Economics of Genetic Testing 452
26.5.3 Training of Cancer Genetic Counselor 452
26.5.4 Legislation Against Genetic Discrimination 452
References 453
Chapter 27: Across Culture and Health Systems: Asia (Japan) 455
27.1 Health Insurance System of Japan 455
27.2 Genetic Counseling in General 456
27.3 Genetic Counseling for Hereditary Colorectal Cancer 457
27.4 Genetic Counseling as a Medical Professional or Specialty in Japan 458
27.5 Bases for Genetic Counseling for Hereditary Colorectal Cancer 458
27.6 Patients’ Association for Familial Adenomatous Polyposis and Their Family Members 463
References 463
Chapter 28: Across Culture and Health Systems: Africa 464
28.1 Introduction 464
28.2 Aim 466
28.3 Methods 466
28.3.1 Study Design 466
28.3.2 Study Population 467
28.4 Results 467
28.4.1 Demographic Profile 468
28.4.2 Themes Identified 469
28.4.2.1 Service 469
Genetic Service 469
Surveillance Service 471
Understanding of Service 472
28.4.2.2 Disease 473
Awareness of CRC 473
Fear of Cancer 473
Stigmatization of Cancer 473
28.5 Discussion 474
28.6 Conclusion 476
References 477
Chapter 29: Across Culture and Health Systems: Argentina 480
29.1 Overview of the Economic, Social, and Health Situation 481
29.2 Genetic Services in the South America: Collaboration Is Beginning 482
29.3 Cancer Figures 483
29.4 Register History and Characteristics 484
29.5 The First 10 Years of Experience 485
29.6 Results 486
29.6.1 Genetic Counseling 491
29.7 Final Considerations 492
References 493
Chapter 30: Genetic Counselling Across Culture and Health Systems: Australia 495
30.1 Multi-cultural Australia 495
30.2 The Australian Healthcare System 498
30.2.1 Universal Health Cover 498
30.2.2 Public 498
30.2.3 Private 499
30.2.4 Comprehensive Cancer Centres 499
30.3 Population Screening for Colorectal Cancer in Australia 499
30.4 Cancer Registries in Australia 500
30.4.1 Compulsory Registration 500
30.4.2 Special Consideration for Familial Cancer Clinics 501
30.5 Legal Context: Privacy and Confidentiality 502
30.5.1 Family History Information in Clinical Practice 502
30.5.2 Variation to Constraints on Disclosure 503
30.5.3 The Power of Consent 504
30.5.4 Consent and Research 504
30.6 Genetic and Genetic Counselling Services in Australia 505
30.6.1 State Variations 505
30.6.2 Benefits of Centralization 507
30.6.3 Integration with Adult Hospitals 507
30.6.4 Training 508
30.6.5 Research 508
30.7 Clinical Approach to Counselling in Australia 509
30.7.1 Referrals 509
30.7.2 Intake 509
30.7.3 Family History Ascertainment 510
30.7.4 Family Tree Construction and Verification of Diagnoses 510
30.7.5 Multi-disciplinary Meeting 510
30.7.6 The First Consultation 511
30.7.6.1 Checking the Pedigree 511
30.7.6.2 Risk Assessment and Tumour Testing 511
30.7.6.3 Syndromic Information 512
30.7.6.4 Penetrance 512
30.7.6.5 Mode of Inheritance 512
30.7.6.6 Pre-genetic Testing and Mismatch Repair Deficiency 512
30.7.6.7 Mutational Analysis 513
30.7.6.8 Insurance Considerations 513
30.7.6.9 Insurance Considerations 514
30.7.6.10 Consent 514
30.7.6.11 Benefits of Surveillance 515
30.7.6.12 Surveillance Recommendations and Planning 515
30.7.6.13 Primary Prevention Advice 515
30.7.6.14 Research 515
30.7.6.15 The Clinic Correspondence 516
30.7.7 The Second Consultation 516
30.7.8 The Third Consultation: Disclosure of Mutation 516
30.7.9 Disclosure of Family Specific Mutational Information to Other Family Members 517
30.7.10 Surveillance Services 518
30.7.11 Clinical Meetings Supporting Genetic Counselling for Cancer in Australia 519
30.7.11.1 Hospital Meetings 519
30.7.11.2 State-wide Familial Cancer Clinic Meetings 519
30.7.11.3 The Cancer Councils 520
30.7.11.4 Human Genetics Society of Australasia 520
30.7.11.5 Organ and Disease Specialty Meetings 521
30.7.11.6 Research Organisations 521
30.7.11.7 Research 521
Interaction with International Organisations and Expertise 522
APPENDIX30.8 Familial Cancer Centre 523
30.8.1 Consent Form for Genetic Testing 523
30.8.1.1 Genetic Testing 523
30.8.1.2 What are the implications of genetic testing? 523
30.8.1.3 What will be done with the test results? 524
30.8.1.4 What will be done with the sample after testing? 524
30.8.1.5 Research 524
References 525
Chapter 31: Across Culture and Health Systems: Korea 527
31.1 The Korean Polyposis Registry 528
31.2 Korean Hereditary Colorectal Cancer Registry 528
31.3 Korean Hereditary Tumor Registry 528
31.4 Cancer Gene Clinic 529
31.5 The Hereditary Tumor and Genome Research Workshop 529
31.6 Familial Adenomatous Polyposis 529
31.7 Hereditary Nonpolyposis Colorectal Cancer 530
31.8 Founder Mutations in Korean HNPCC 530
31.9 Suspected HNPCC 531
31.10 Gastric Cancer in FAP and HNPCC 531
31.11 Peutz–Jeghers Syndrome/Juvenile Polyposis 532
31.12 MYH-Associated Polyposis 532
31.13 Korean Health Insurance System 533
31.14 Insurance Support in Gene Testing 533
31.15 National Cancer Screening Program 533
31.16 Summary 534
References 534
Chapter 32: Across Culture and Health Systems: America 537
32.1 Introduction 537
32.2 Overview of the American Health Care System 538
32.3 Identification of High-Risk Individuals 540
32.4 Provision of Clinical Cancer Genetic Services 541
32.5 Genetic Discrimination 545
32.6 Summary 546
References 546
Chapter 33: Psychological Impact of Genetic Counseling and Testing for Hereditary Colorectal Cancers 550
33.1 Uptake of Genetic Counseling and Testing for Lynch Syndrome and FAP 551
33.1.1 Genetic Testing for Lynch Syndrome-Associated Mutations 551
33.1.2 Genetic Testing for APC Mutations in FAP 552
33.2 Psychological Effects of Genetic Counseling and Testing for Lynch Syndrome and FAP 554
33.2.1 Lynch Syndrome 554
33.2.2 FAP 555
33.3 Family Communication About Genetic Testing and Inherited Cancer Risk 556
33.4 Adoption of Risk Management Recommendations for Lynch Syndrome and FAP 557
33.4.1 Lynch Syndrome 558
33.4.1.1 Colorectal Cancer Screening 558
33.4.2 Gynecologic Cancer Screening 559
33.4.3 Risk-Reducing Surgery 559
33.4.4 FAP 560
33.4.4.1 Colorectal Screening 560
33.4.4.2 Risk Reducing Surgery 561
33.5 Implications for Clinical Practice and Future Research Directions 561
References 562
Chapter 34: Chemoprevention for Inherited Colorectal Cancer 566
34.1 Introduction 567
34.1.1 Early FAP Trials 569
34.1.2 Nonsteroidal Anti-inflammatory Drugs 570
34.2 Selective COX-2 Inhibitors 571
34.2.1 Clinical Trials of COX-2 Inhibitors 571
34.2.2 Primary Prevention of Adenomas in Children with FAP 572
34.2.3 Combination Chemotherapy 573
34.2.4 The CAPP I Trial 573
34.3 Logistic Challenges in the Conduct of Clinical Trials in FAP 574
34.3.1 Endpoint Measure: Adenoma Reduction 574
34.3.2 Chemoprevention in Hereditary Nonpolyposis Colorectal Cancer 576
34.3.3 CAPP II 577
34.4 Conclusion 578
References 578
Chapter 35: Registries* 582
35.1 Introduction 582
35.2 History 583
35.3 Aim 584
35.4 Roles 584
35.4.1 Clinical Function 584
35.4.2 Education 584
35.4.3 Research 586
35.5 Type of Register 587
35.6 Data Confidentiality 587
35.7 Establishment of a Register 588
35.7.1 Ascertainment of Patients 588
35.7.2 Construction of Pedigrees 588
35.7.3 Identification of Family Members at Risk 589
35.7.4 Screening of Family Members at Risk 590
35.7.5 Treatment of Newly Diagnosed Patients 590
35.7.6 Follow-Up and Evaluation 590
35.8 Research 591
35.9 International Cooperation 591
35.10 Results of the Registries 591
35.11 Future Challenges: Electronic Data Exchange 592
References 593
Index 600

Produkt-Details

• Erscheint lt. Verlag: 10.9.2010
• Reihe/Serie: MD Anderson Solid Tumor Oncology Series
• Reihe/Serie: MD Anderson Solid Tumor Oncology Series
• Zusatzinfo: XVIII, 630 p.
• Verlagsort: New York
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Chirurgie
• Themenwelt: Medizinische Fachgebiete ► Innere Medizin ► Gastroenterologie
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Onkologie
• Schlagworte: Adenomas • Colorectal Cancer • Polyposis • Surgery • surgical oncology • Tumors
• ISBN-10: 1-4419-6603-X / 144196603X
• ISBN-13: 978-1-4419-6603-2 / 9781441966032