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- Herausgeber: John Wiley & Sons
- Kategorie: Fachliteratur
- Serie: At a Glance
- Sprache: Englisch
The market‐leading at a Glance series is popular among healthcare students and newly qualified practitioners for its concise and simple approach and excellent illustrations.
Each bite‐sized chapter is covered in a double‐page spread with clear, easy‐to‐follow diagrams supported by succinct explanatory text.
Covering a wide range of topics, books in the at a Glance series are ideal as introductory texts for teaching, learning and revision, and are useful throughout university and beyond.
Everything you need to know about Oncology… at a Glance!
Discover a comprehensive, newly-revised edition of Oncology at a Glance!
Oncology at a Glance demystifies the complexities of cancer biology and treatment for medical students and junior healthcare practitioners. With updated content including emerging therapies, multidisciplinary team approaches, and palliative care, Oncology at a Glance, Second Edition bridges gaps in the often-fragmented exposure to oncology during clinical training. Real-world case studies and accompanying exercises deepen comprehension, enhance understanding, and support problem-solving in oncology practice.
Ideal for foundational learning or a quick refresher in clinical practice, Oncology at a Glance, Second Edition:
- Consolidates key information into concise sections on individual cancers and broader oncological principles
- Covers foundational cancer biology, investigation, clinical management, and key human issues such as communication and palliative care
- Includes multiple-choice questions, self-assessment exercises, and a companion website with interactive self-testing features
Developed with feedback from medical students to ensure relevance and clarity, Oncology at a Glance, Second Edition remains a must-have for undergraduate medical students, nursing students, junior doctors, and allied health professionals.
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Seitenzahl: 463
Veröffentlichungsjahr: 2025
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Table of Contents
Cover
Table of Contents
Title Page
Copyright Page
About the Authors
Preface
Abbreviations
Part 1: Scientific foundation of oncology
1 The global burden of cancer
The global burden of cancer
Developed and developing countries
Challenges
2 The nomenclature of cancer
Tumour nomenclature
Tumour grade
Cytology
Cytogenetic analysis
Tumour stage
Performance status
3 Environmental determinants of cancer
Environmental factors
Radiation
Chemicals
Infections
Hormones
Nutrition and lifestyle
4 The hallmarks of cancer 1
The 10 hallmarks of cancer
1. Sustaining proliferative signalling
5 The hallmarks of cancer 2
2. Resisting cell death
3. Evading growth suppressors
Tumour microenvironment
6 The hallmarks of cancer 3
4. Inducing angiogenesis
5. Activating invasion and metastasis
7 The hallmarks of cancer 4
6. Enabling replicative immortality
7. Genome instability and mutation
8 The hallmarks of cancer 5
8. Reprogramming energy metabolism
9. Tumour‐promoting inflammation
10. Evading immune destruction
9 Cancer genetics and inherited cancer
Principles of cancer genetics
How genes cause cancer
Oncogenes
Tumour suppressor genes
Multistep carcinogenesis
Inherited cancer syndromes
Mainstreaming of cancer genetics
Part 2: Clinical aspects of oncology
10 Communicating with cancer patients
Communicating with cancer patients
The doctor–patient relationship
Breaking bad news
Dealing with the emotional patient
Communicating with younger patients
11 Presenting problems in a patient with cancer
Presenting features of cancer
Local effects
Metastatic effects
12 Paraneoplastic syndromes
Ectopic hormone production
Neurological manifestations
Cutaneous manifestations
Haematological manifestations
Gastrointestinal manifestations
Renal manifestations
Other paraneoplastic syndromes
13 Metabolic emergencies in cancer patients
Hypercalcaemia
Syndrome of inappropriate antidiuresis
Hypomagnesaemia
Tumour lysis syndrome
14 Oncological emergencies
Neutropenic sepsis
Superior vena cava obstruction
Spinal cord compression
15 Investigation and management of metastatic disease
Brain metastases
Lung metastases
Liver metastases
Bone metastases
Malignant pleural effusion
Malignant ascites
Other sites
16 Tumour markers
Serum proteins
Clinical usefulness
17 Screening for cancer
Successful screening
Breast cancer screening
Colorectal cancer screening
Gastric cancer screening
Prostate cancer screening
Cervical cancer screening
Ovarian cancer screening
Lung cancer screening
The Future
18 Imaging in oncology
Plain film imaging
Ultrasound
Computerised tomography
Magnetic resonance imaging
Radioisotope imaging
Positron emission tomography
19 Principles of staging
The TNM staging system
Number staging systems
Cellular classification
Other considerations
20 Approach to treatment and response assessment
Treatment goals
Treatment approach
Assessment of toxicity
Evaluation of treatment
21 Principles of surgical oncology
Surgical oncology
Prevention
Evaluation of primary disease
Treatment
Palliative procedures
22 Pharmacology of anticancer agents
An introduction to chemotherapy
Growth fractions and doubling time
Tumour growth
Drug resistance
Class of anticancer agents
23 Principles of immunotherapy
Immune checkpoint inhibition
Cellular immunotherapy
Cancer vaccines
24 Principles of radiotherapy
How radiotherapy works
Types of radiation treatment
25 Adverse effects of treatment
Treatment toxicity
Specific toxicities
Late adverse effects
26 Adverse effects of immunotherapy and biological therapy
Immune check point inhibitors
Presenting symptoms
Management of ICPi toxicity
Pseudoprogression
Other biological agents
27 Management of nausea
Pathophysiology
Oncology practice
Approach to treatment
Patients with advanced disease
28 Analgesia
Pain assessment
Treatment
Opioid analgesia
29 Clinical trials in cancer patients
Asking a research question
Phase I clinical trials
Phase II clinical trials
Phase III clinical trials
Meta‐analysis
30 Role of multidisciplinary teams
Multidisciplinary team meetings
Role of the team
Benefit of MDT meetings
Combined clinics
Recruitment into clinical trials
Educational opportunities
31 End‐of‐life care
Physical symptoms
Psychological issues
Managing the terminal phase
Part 3: Specific cancers
32 Carcinoma of unknown primary
Epidemiology
Aetiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
33 Breast cancer
Epidemiology
Aetiology and pathophysiology
Clinical presentation
Treatment
Screening
34 Lung cancer
Epidemiology
Aetiology
Pathophysiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
35 Mesothelioma
Epidemiology
Aetiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
36 Oesophageal cancer
Epidemiology
Aetiology and pathophysiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
37 Gastric cancer
Epidemiology
Aetiology
Pathophysiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
38 Colorectal cancer
Epidemiology
Aetiology
Pathophysiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
Screening
39 Pancreatic cancer
Epidemiology
Aetiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
40 Hepatobiliary cancer
Epidemiology
Aetiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
41 Ovarian cancer
Epidemiology
Aetiology
Pathophysiology
Clinical presentation
Investigation and staging
Treatment
Complications
Prognosis
42 Endometrial cancer
Epidemiology
Aetiology
Clinical presentation
Investigations and staging
Treatment
Complications
Prognosis
43 Cervical cancer
Epidemiology
Aetiology
Clinical presentation
Investigations and staging
Screening
Treatment
Prognosis
44 Germ cell tumours
Epidemiology
Aetiology
Pathophysiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
45 Prostate cancer
Epidemiology
Aetiology and pathophysiology
Clinical presentation
Investigations and staging
Treatment
Screening
Prognosis
46 Bladder and renal cancer
Epidemiology
Aetiology
Pathophysiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
47 Head and neck cancer
Epidemiology
Aetiology
Pathophysiology
Clinical examination
Investigations and staging
Treatment
Prognosis
48 Thyroid cancer
Epidemiology
Aetiology
Pathophysiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
49 Bone cancer and sarcoma
Epidemiology
Aetiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
50 Skin cancer
Epidemiology
Aetiology
Non‐melanoma skin cancer
Melanoma
51 Cancers of the central nervous system
Epidemiology
Aetiology
Clinical presentation
Investigations and staging
Treatment
Complications
Prognosis
52 Neuroendocrine tumours
Argentaffin and hormone secretion
Carcinoid tumours
Gastroenteropancreatic NETs
Serum tumour markers
53 Leukaemia
Epidemiology and pathogenesis
Clinical presentation
Investigations and classification
Treatment
Prognosis
54 Hodgkin lymphoma
Epidemiology
Aetiology
Pathophysiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
55 Non‐Hodgkin lymphoma
Epidemiology
Aetiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
56 Myeloma
Epidemiology
Aetiology
Clinical presentation
Investigations and staging
Treatment
Prognosis
57 Childhood cancers
Paediatric oncology
Teenager and young adult oncology
Aetiology
Haematological cancers
Embryonal tumours
Central nervous system cancer
Germ cell tumours
Soft‐tissue sarcoma and bone tumours
Carcinoma and melanoma
58 Oncology as a career
Oncology in the United Kingdom
Life as an oncologist
Becoming an oncologist in the United Kingdom
Case studies and questions
Answers to case studies
Glossary
Index
End User License Agreement
List of Tables
Chapter 2
Table 2.1 Nomenclature of tumours
Table 2.2 Eastern Cooperative Oncology Group (ECOG) performance status scal...
Table 2.3 Karnofsky performance status score
Chapter 3
Table 3.1 Environmental influence on carcinogenesis
Table 3.2 Effects of hormone manipulation on cancer risk
Chapter 4
Table 4.1 The 10 hallmarks of cancer and corresponding therapeutic approach...
Chapter 9
Table 9.1 Inherited cancer predisposition syndrome or primary site of cance...
Chapter 10
Table 10.1 Outline of communication skill attributes
Table 10.2 Overcoming barriers to communication
Chapter 11
Table 11.1 Local features of malignant disease
Chapter 12
Table 12.1 Ectopic hormone production by tumours
Chapter 14
Table 14.1 Comparison of features of cord, conus and cauda compression
Chapter 16
Table 16.1 Examples of serum tumour markers
Chapter 17
Table 17.1 World Health Organisation considerations for successful screenin...
Table 17.2 Utility of a screening test
Table 17.3 Factors to consider when assessing a screening programme
Chapter 18
Table 18.1 Interventional radiology approaches in oncology practice
Chapter 19
Table 19.1 Aims of cancer staging
Table 19.2 Example other staging systems in use
Table 19.3 TNM clinical classification
Table 19.4 pTNM pathological classification
Chapter 20
Table 20.1 Response criteria for evaluation of target lesions
Chapter 21
Table 21.1 Basic rules of surgical oncology
Table 21.2 Common procedures in surgical oncology
Table 21.3 Important characteristics in describing a lump
Chapter 22
Table 22.1 Examples of common chemotherapy agents
Chapter 27
Table 27.1 Types of nausea and vomiting in patients with cancer
Chapter 28
Table 28.1 Exploring the history and characteristics of pain
Table 28.2 Adjuvant therapies used as co‐analgesia approaches
Chapter 29
Table 29.1 Purpose and typical endpoints of anti‐cancer therapy clinical tr...
Chapter 30
Table 30.1 Problems encountered in multidisciplinary meetings
Chapter 32
Table 32.1 Common sites of involvement
Table 32.2 Approach to patients
Table 32.3 Light microscopy can classify CUP
Table 32.4 Immunohistochemistry can identify
Chapter 33
Table 33.1 Biological treatments for breast cancer
Chapter 34
Table 34.1 Biological treatments for lung cancer
Chapter 38
Table 38.1 Biological treatments for colorectal cancer
Chapter 40
Table 40.1 Biological treatments for hepatobiliary cancers
Chapter 42
Table 42.1 Risk factors for endometrial cancer
Chapter 44
Table 44.1 Risk factors for testicular GCT
Table 44.2 Summary of the WHO classification of ovarian GCT
Chapter 45
Table 45.1 Prognosis of prostate cancer
Chapter 46
Table 46.1 Risk factors for developing bladder cancer
Chapter 49
Table 49.1 Clinical features of soft‐tissue sarcomas
Chapter 50
Table 50.1 The ABCDE rule for examining suspicious naevi
Table 50.2 Clinicopathological features of common forms of melanoma
Table 50.3 British Association of Dermatologists guidelines for the excisio...
Table 50.4 Standard treatment options for melanoma
Table 50.5 Prognostic factors in malignant melanoma
Chapter 51
Table 51.1 Types of cancer of the central nervous system
Chapter 57
Table 57.1 Distribution of childhood cancers by gender
List of Illustrations
Chapter 1
Figure 1.1 Age‐standardised mortality rate (world) per 100 000 (both sexes i...
Chapter 4
Figure 4.1 Regulation of the cell cycle
Figure 4.2 The ErbB family and ligands
Chapter 5
Figure 5.1 The complex tumour microenvironment and therapeutic strategies
Chapter 6
Figure 6.1 Mechanism of tumour angiogenesis
Figure 6.2 Activating invasion and metastasis
Chapter 7
Figure 7.1 Multistep tumour progression as a series of clonal expansions and...
Figure 7.2 PARP‐1 repair of single‐strand DNA breaks.
Chapter 8
Figure 8.1 Contribution of inflammatory cells to cancer development
Chapter 11
Figure 11.1 Clinical examination of a patient suspected of having cancer
Chapter 13
Figure 13.1 Clinical features of metabolic emergencies in cancer patients
Figure 13.2 Cause of hypomagnesaemia
Figure 13.3 Tumour lysis syndrome
Chapter 14
Figure 14.1 Clinical features of oncological emergencies
Figure 14.2 Approach to neutropenic sepsis
Chapter 15
Figure 15.1 Clinical features of metastatic disease
Chapter 18
Figure 18.1 A chest X‐ray showing multiple lung metastases
Figure 18.2 MR scan showing liver metastasis from ovarian cancer
Figure 18.3 A PET scan showing a positive lymph node in the left axilla. Nor...
Figure 18.4 A repeat PET image following treatment showing resolution of the...
Chapter 20
Figure 20.1 Low‐dose therapy
Figure 20.2 High‐dose therapy
Figure 20.3 Dose dense therapy
Figure 20.4 Alternating therapy
Chapter 21
Figure 21.1 A core biopsy (Dixon (2012) / John Wiley & Sons)
Chapter 23
Figure 23.1 PD‐L1 and PD‐1 blockade in cancer cells
Figure 23.2 CTLA‐4 blockade results in T cell activation
Chapter 24
Figure 24.1 The most common interactions relevant to radiotherapy
Chapter 25
Figure 25.1 Clinical manifestation of anticancer therapy adverse effects
Chapter 26
Figure 26.1 Clinical features of toxicity from immunotherapy and biological ...
Figure 26.2 The temporal relationship of immunotherapy toxicity after starti...
Chapter 27
Figure 27.1 Neural pathways in vomiting
Chapter 28
Figure 28.1 Factors that influence the perception of pain
Figure 28.2 The WHO pain ladder
Chapter 31
Figure 31.1 Aims of end‐of‐life care planning
Chapter 32
Figure 32.1 Clinical features of a carcinoma of unknown primary
Chapter 33
Figure 33.1 Clinical features of breast cancer
Chapter 34
Figure 34.1 Clinical features of lung cancer
Chapter 35
Figure 35.1 Clinical features of mesothelioma
Chapter 36
Figure 36.1 Clinical features of oesophageal cancer
Chapter 37
Figure 37.1 Clinical features of gastric cancer
Chapter 38
Figure 38.1 Clinical features of colorectal cancer
Chapter 39
Figure 39.1 Clinical features of pancreatic cancer
Chapter 40
Figure 40.1 Clinical features of hepatobiliary cancer
Chapter 41
Figure 41.1 Clinical features of ovarian cancer
Chapter 42
Figure 42.1 Clinical features of endometrial cancer
Chapter 43
Figure 43.1 Clinical features of cervical cancer
Chapter 44
Figure 44.1 Clinical features of germ cell cancer
Figure 44.2 Classification of germ cell tumours and typical tumour marker pr...
Chapter 45
Figure 45.1 Clinical features of prostate cancer
Chapter 47
Figure 47.1 Clinical features of head and neck cancer
Chapter 49
Figure 49.1 Clinical features of bone cancer and sarcomas
Chapter 51
Figure 51.1 Clinical features of cancer of the central nervous system
Chapter 52
Figure 52.1 Pituitary neuroendocrine tumours
Chapter 53
Figure 53.1 Clinical features of leukaemia
Chapter 54
Figure 54.1 Clinical features of Hodgkin lymphoma
Chapter 55
Figure 55.1 Clinical features of non‐Hodgkin lymphoma
Chapter 56
Figure 56.1 Clinical features of myeloma
Figure 56.2 Approach to the management of myeloma
Chapter 57
Figure 57.1 Percentage of cases by tumour type and age group
Chapter 58
Figure 58.1 Training pathway for clinical and medical oncology
Figure 58.2 The nine domains of the GMC generic professional capabilities
Case studies and questions
Figure C6.1 A CT of thorax showing a solitary lung nodule in the left lung
Figure C13.1 A peripheral blood film (Reproduced with permission from Mehta ...
Guide
Cover Page
Table of Contents
Title Page
Copyright Page
About the Authors
Preface
Abbreviations
Begin Reading
Case studies and questions
Answers to case studies
Glossary
Index
Wiley End User License Agreement
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Oncologyat a Glance
Second Edition
Graham G. Dark
MBBS, FRCP, FHEA, FACP, FAACE, FEACESenior Lecturer in Cancer EducationConsultant in Medical OncologyDepartment of Medical OncologyNewcastle UniversityFreeman HospitalNewcastle upon TyneNE7 7DNUK
Lindsay Hennah
MBBS, BSc, MRCPSpecialist Registrar in Medical OncologyDepartment of Medical OncologyFreeman HospitalNewcastle upon TyneNE7 7DNUK
This second edition first published 2025© 2025 John Wiley & Sons Ltd
Edition HistoryJohn Wiley & Sons Ltd (1e, 2013).
All rights reserved, including rights for text and data mining and training of artificial intelligence technologies or similar technologies. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.
The right of Graham G. Dark and Lindsay Hennah to be identified as the authors of this work has been asserted in accordance with law.
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Library of Congress Cataloging‐in‐Publication Data applied for
PB ISBN: 9781394292691
Cover Design: WileyCover Image: Courtesy of Dr. Divya Manoharan
About the Authors
Graham G. DarkMBBS, FRCP, FHEA, FACP, FAACE, FEACESenior Lecturer in Cancer EducationConsultant in Medical OncologyDepartment of Medical OncologyNewcastle UniversityFreeman HospitalNewcastle upon TyneNE7 7DNUK
Lindsay HennahMBBS, BSc, MRCPSpecialist Registrar in Medical OncologyDepartment of Medical OncologyFreeman HospitalNewcastle upon TyneNE7 7DNUK
Cover Art Title: Cellular Symphony of Malignancy
Artwork Modality: Apple iPad and Apple Pencil (Digital Artwork)
Artist: Dr. Divya Manoharan BMedSci (Hons), MB ChB (Edin.), MSc, MRCP(UK)
Specialty Resident in Clinical Oncology
Description:
The image was created with layers of cross hatching, soft glow, and paper texture brushes, complemented with double‐stranded helix DNAs in the middle ground with matching range of colours in the background. The foreground has dark blue cells in the lower right corner, depicting cancer cells and symbolising the heinous and malicious nature of these feared cells. There are a few light and bright‐coloured spiked immune cells floating around demonstrating their gatekeeping and combatant nature. The cancer cells are seen secreting tumour‐specific antigens, whilst the immune cells are secreting cytokines. Biological agents and immunotherapy are key systemic anti‐cancer treatments, which have been depicted by numerous circulating antibodies, representing monoclonal antibodies and checkpoint inhibitors. Lastly, there are chemical structures of agents from the six key chemotherapeutic classes; taxanes (Docetaxel), topoisomerase inhibitors (Etoposide), antimetabolites (Gemcitabine), alkylating agents (Ifosfamide), anti‐tumour antibiotics (Epirubicin), and platinums (Oxaliplatin).
Preface
Oncology is a discipline that embraces a number of scientific fields. It is at the cutting edge of technology with regard to developments in therapeutic approaches. It is a stimulating and intellectual challenge to not only deliver the therapies of today but to research and develop the treatments of tomorrow. Research is embedded within the specialties and reflects the origins within academic departments. The delivery of high quality chemotherapy and radiotherapy services is an important political target and there has been considerable financial investment by the government in expanding cancer services in the UK.
For the undergraduate medical student, oncology can be overwhelming and often the exposure to patients with cancer can be quite fragmented in the undergraduate curriculum. Most student rotations will focus on the diagnostic processes as patients with cancer present to general medical and surgical firms, possibly as acute admissions or via outpatients with a variety of presenting symptoms. Other schools will provide specific rotations in the oncology department and this text is to provide the core knowledge to underpin such a learning experience.
The clinical practice of oncology is the application of a foundation of sciences including; anatomy, to interpret radiological imaging; physiology, for the impact of a multisystem disease; pharmacology, to design, deliver and monitor systemic anticancer treatments; molecular biology, for the development of viable targets of therapy and to understand the mechanisms of carcinogenesis, genetic risk and resistance to therapy; cell biology, the process of metastasis, vascular invasion, and microenvironment of the tumour and how this can affect outcome and approaches to therapy; pathology, to recognise the features of a disease that can affect all systems of the body.
Oncology is therefore the clinical application of the knowledge of science that underpins so much of clinical medicine and does so in a very evidence‐based manner. This requires clarity of understanding, a fastidious approach to investigation of the patient to obtain a diagnosis and effective communication with the patient, their family and others within the multidisciplinary team. There are frequent challenges as sometimes the investigations do not produce a definitive answer and yet a clear plan of management is required for the benefit of the patient.
For many, oncology seems like a depressing specialty and yet there is so much reward for those involved in the care of complex patients. The satisfaction of demonstrating clinical improvement after the intellectual challenge of getting the right diagnosis, planning the right treatment, given the context of the patient and their disease, having communicated understanding to the patient to explain what is likely to happen in the future and having had opportunity to address their concerns and fears, is a reward for many clinicians involved in the management of patients with complex problems, especially those with cancer.
The origins of Medical Oncology as a specialty lie in the management of haematological and paediatric malignancies. It began as a small research orientated specialty and clinical research remains an important feature of the specialty. Over the last 20 years, enormous developments have taken place in the medical management of cancer, particularly in the development of therapies for common solid tumours. Today, Medical Oncology is a broad‐based clinical specialty. It ensures that for common cancers, state‐of‐the‐art therapies of established efficacy are delivered on a national basis, within a framework of care, tailored for the patient as an individual. Medical oncologists increasingly see patients at the beginning of their cancer journey for consideration of adjuvant and neoadjuvant therapies. They work as part of a multidisciplinary team and are able to advise on all aspects of oncological treatment including its integration with surgery and radiotherapy as well as having the skills to deliver specialist medical therapy.
Clinical Oncology arose from the discovery of radiation and therapeutic irradiation but most practitioners also deliver chemotherapy. In recent years there have been considerable technological advances in the delivery of radiation treatment with intensity modulation, photon therapy and stereotactic radiotherapy and some consultants focus on delivering specialised radiotherapy only.
New anticancer treatments are constantly in development by clinicians that are working at the interface between the clinic and the scientific foundations of knowledge. There is therefore opportunity for individuals to develop an academic career as a clinician scientist, with an interest in translational research that interfaces the scientific laboratory with the clinic.
This book is aimed at undergraduate students that will encounter patients with cancer throughout their clinical training and junior rotations. In some centres there may be minimal opportunity to study within the oncology departments as clinical experience may be gained with the teams that refer patients to a multidisciplinary team, rather than with the oncologists that deliver the subsequent treatment.
In some medical schools, students will have opportunity to undertake a student selected component (SSC). This is a period that allows personal learning outcomes to be defined and for individual students to explore either the depth or breadth of oncology practice. During one such period an informal discussion about learning resources resulted in the concept and idea of this book. A student focus group was used to identify the topics for inclusion and considerable attention was given to what is important for an undergraduate. Therefore some topics are left out by intention as they were not relevant to such an audience.
We have made considerable effort to ensure that this text remains appropriate for students and delivers the core knowledge required. We are grateful to the student reviewers for their attention to detail and for providing constructive comments that have improved the content and allowed the project to remain focused.
This book is not a detailed reference text about cancer but instead has been written to provide a basic foundation of knowledge to underpin successful clinical training in cancer medicine for undergraduates of medicine and for others working inoncology such as junior doctors and allied health professionals, to provide an understanding of the principles of treatment approaches used for common cancers in oncology practice.
Graham G. DarkLindsay Hennah
Abbreviations
5‐HIAA
5‐hydroxyindoleacetic acid
5‐HT
5‐hydroxytryptamine (serotonin)
5‐HTP
5‐hydroxytryptophan
ACCS
acute common core stem
ACE
angiotensin converting enzyme
ACTH
adrenocorticotrophic hormone
ADH
antidiuretic hormone or vasopressin
ADT
androgen deprivation therapy
AFP
alpha feto‐protein
ALK
anaplastic lymphoma kinase
ALL
acute lymphoblastic leukaemia
AML
acute myeloid leukaemia
AOS
acute oncology service
ARCP
annual review of competency progression
ATG
antithymocyte globulin
aTNM
autopsy classification of stage
ATP
adenosine triphosphate
BCC
basal cell carcinoma
BCG
Bacillus Calmette–Guérin
BEP
bleomycin, etoposide, cisplatin chemotherapy
BMT
bone marrow transplant
BP
blood pressure
BSO
bilateral salpingo‐oophorectomy
CACS
cancer anorexia and cachexia syndrome
CAR T
chimeric antigen receptor T‐cell therapy
CCT
certificate of completed training
CD
cluster of differentiation
CDK
cyclin‐dependent kinase
CEA
carcinoembryonic antigen
CHART
continuous hyperfractionated radiotherapy
CHRPE
congenital hypertrophy of the retinal pigment epithelium
CIN
cervical intraepithelial neoplasia
CINV
chemotherapy‐induced nausea and vomiting
CIS
carcinoma in‐situ
CLL
chronic lymphocytic leukaemia
CML
chronic myeloid leukaemia
CMT
core medical training
CNS
central nervous system
COCP
combined oral contraceptive pill
COX
cyclooxygenase
CR
complete response
CRP
C‐reactive protein
CSF
cerebrospinal fluid
CT
computed tomography
CTC
common toxicity criteria
ctDNA
circulating tumour DNA
CTLA4
cytotoxic T‐lymphocyte antigen 4
cTNM
clinical classification of stage
CTZ
chemoreceptor trigger zone
CUP
carcinoma of unknown primary
CVA
cerebrovascular accident
CXR
chest X‐ray
DCIS
ductal carcinoma in situ
DLT
dose‐limiting toxicity
dMMR
deficient mismatch repair
DNA
deoxyribonucleic acid
DRR
digitally reconstructed radiograph
DVT
deep vein thrombosis
EBV
Epstein‐Barr virus
ECM
extracellular matrix
ECOG
Eastern Cooperative Oncology Group
EGFR
epidermal growth factor receptor
EM
electron microscopy
EMA
epithelial membrane antigen
EMT
epithelial‐mesenchymal transformation
ENT
ear nose and throat
ER
oestrogen receptor/emergency room
ERCP
endoscopic retrograde cholangiopancreatography
ESMO
European Society for Medical Oncology
ESR
erythrocyte sedimentation rate
eV
electron volt
FAP
familial adenomatous polyposis
FBC
full blood count
FDG
fluorodeoxyglucose
FGF
fibroblast growth factor
FIGO
International Federation of Gynaecology and Obstetrics
FISH
fluorescent in‐situ hybridisation
FIT
faecal immunochemical test
FNA
fine needle aspiration
FOB
faecal occult blood
FSH
follicle stimulating hormone
G‐CSF
granulocyte‐colony stimulating factor
GCT
germ cell tumour
GFR
glomerular filtration rate
GI
gastrointestinal
GIST
gastrointestinal stromal tumour
GU
genitourinary
Gy
Gray
HAD
hospital anxiety and depression scale
HBV
hepatitis B virus
HCC
hepatocellular carcinoma
hCG
human chorionic gonadotrophin
HCV
hepatitis C virus
HGF
hepatocyte growth factor
HHV
human herpes virus
HIV
human immunodeficiency virus
HNPCC
hereditary non‐polyposis colorectal cancer
HOA
hypertrophic osteoarthropathy
HPV
human papilloma virus
HRT
hormone replacement therapy
HTLV‐1
human T‐cell lymphotrophic virus‐1
ICP
intracranial pressure
ICPi
immune checkpoint inhibitor
IDA
iron deficiency anaemia
IGF
insulin‐like growth factor
IHC
immunohistochemistry
IL
interleukin
IMRT
intensity modulated radiotherapy
IQ
intelligence quotient
IV
intravenous
IVC
inferior vena cava
JVP
jugular venous pressure
LCIS
lobular carcinoma in situ
LD
longest diameter
LDH
lactate dehydrogenase
LEMS
Lambert–Eaton myasthenic syndrome
LFT
liver function tests
LH
leutenising hormone
LHRH
luteinising hormone releasing hormone
mAb
monoclonal antibody
MALT
mucosa‐associated lymphoid tissue
MAP
mitogen‐activated protein
MDT
multidisciplinary team
MEN
multiple endocrine neoplasia
mIBG
meta‐iodobenzylguanidine
MMF
mycophenolate
MMR
mismatch repair
MR/MRI
magnetic resonance imaging
MRCP
magnetic resonance cholangiopancreatography
MSCC
malignant spinal cord compression
MSU
mid stream urine
MTD
maximum tolerated dose
mTOR
mammalian target of rapamycin
NAFLD
non‐alcoholic fatty liver disease
NER
nucleotide excision repair
NET
neuroendocrine tumour
NHL
non‐Hodgkin lymphoma
NHS
National Health Service
NK‐1
neurokinin‐1
NOS
not otherwise specified
NSAID
non‐steroidal anti‐inflammatory drug
NSCLC
non‐small cell lung cancer
NSE
neurone‐specific enolase
NSGCT
non‐seminomatous germ cell tumour
NTRK
neurotrophic tyrosine receptor kinase
OS
overall survival
PARP
poly (ADP‐ribose) polymerase
PCOS
polycystic ovarian syndrome
PD
progressive disease
PD‐1
programmed cell death 1
PDGF
platelet‐derived growth factor
PD‐L1
programmed cell death ligand 1
PE
pulmonary embolism
PEFR
peak expiratory flow rate
PEG
percutaneous endoscopic gastrostomy
PET
positron emission tomography
PFS
progression‐free survival
PJP
Pneumocystis jirovecii pneumonia
PLAP
placental alkaline phosphatise
PMB
postmenopausal bleeding
pMMR
proficient mismatch repair
PR
progesterone receptor/per rectum/partial response
PS
performance status
PSA
prostate‐specific antigen
PT
prothrombin time
PTH
parathyroid hormone
PTHrP
parathyroid hormone‐related polypeptide
pTNM
pathological classification of stage
PTT
partial thromboplastin time
PV
per vagina
PVC
polyvinyl chloride
RCC
renal cell carcinoma
RECIST
response evaluation criteria in solid tumours
RNA
ribonucleic acid
RR
relative risk
rTNM
recurrent classification of stage
SCC
squamous cell carcinoma
SCF
supraclavicular fossa
SCLC
small cell lung cancer
SCT
stem cell transplant
SD
stable or static disease
SIAD
syndrome of inappropriate antidiuresis
SIRT
selective internal radiotherapy
SPECT
single photon emission computed tomography
SpR
specialist registrar
SVC
superior vena cava
SVCO
superior vena cava obstruction
TACE
trans‐arterial chemoembolisation
TCC
transitional cell cancer
TENS
transcutaneous electrical nerve stimulation
TGF
transforming growth factor
TIL
tumour infiltrating lymphocyte
TKI
tyrosine kinase inhibitor
TLS
tumour lysis syndrome
TNBC
triple negative breast cancer
TNF
tumour necrosis factor
TSH
thyroid stimulating hormone
TSP‐1
thrombospondin‐1
TURBT
transurethral resection of bladder tumour
TURP
transurethral resection of the prostate
TYA
teenager and young adult
U&E
urea and electrolytes
UICC
Union for International Cancer Control
UK
United Kingdom
UMN
upper motor neurone
US
United States
UTI
urinary tract infection
UV
ultraviolet
VAT
video‐assisted thoracoscopy
VEGF
vascular endothelial growth factor
VIP
vasoactive intestinal polypeptide
WHO
World Health Organization
Part 1Scientific foundation of oncology
Chapters
1
The global burden of cancer
2
The nomenclature of cancer
3
Environmental determinants of cancer
4
The hallmarks of cancer 1
5
The hallmarks of cancer 2
6
The hallmarks of cancer 3
7
The hallmarks of cancer 4
8
The hallmarks of cancer 5
9
Cancer genetics and inherited cancer
1The global burden of cancer
Figure 1.1 Age‐standardised mortality rate (world) per 100 000 (both sexes in 2022) (World Health Organization / https://gco.iarc.fr/today/en/dataviz/maps‐heatmap?mode=population&types=1)
The global burden of cancer
Cancer represents a significant economic burden for the global economy and is now the third leading cause of death worldwide. By 2050, it is projected that there will be 35 million new cancer cases and 18 million cancer deaths per year.
The developing world is disproportionately affected by cancer and in 2008 developing nations accounted for 56% of new cancer cases and 75% of cancer deaths (Figure 1.1). These deaths happen in countries with limited or no access to treatment and with low per capita expenditure on healthcare. In recognition of this, the Union for International Cancer Control (UICC) conceived the World Cancer Declaration in 2008, with an update in 2013 showing there is progress in the majority of targets:
World cancer declaration (2013 update)
Strengthen health systems for effective cancer control
Measure cancer burden and impact of cancer plans in all countries
Reduce exposure to cancer risk factors
Universal coverage of HPV and HBV vaccination
Reduce stigma and dispel myths about cancer
Universal access to screening and early detection for cancer
Improve access to services across the cancer care continuum
Universal availability of pain control and distress management
Improve education and training of healthcare professionals
Developed and developing countries
Developing nations often do not have the funding, expertise or infrastructure to deliver effective cancer services. They may have limited or no cancer screening, few facilities and patients may have limited access to treatments and analgesia. The lowest‐income countries have a survival rate of 25% compared to that of 56% in the wealthiest, discrepancies that have worsened following the COVID pandemic. Prevention is therefore a key strategy to reduce cancer deaths as it has the largest potential impact at the least expense.
Tobacco
Tobacco use is the single largest preventable cause of cancer and premature deaths, and an estimated 1.1 billion people in the world currently smoke tobacco. Smoking prevalence is highest among men in Eastern Europe, the former Soviet Union, China and Indonesia, and whilst there have been some improvements with 33.3% of the global population smoking in 2000 versus 24.9% in 2015, the declines have been most significant in high‐income countries with little change in lower‐ to middle‐income countries.
Tobacco contributes to the development of 3 million cancers (lung, oropharynx, larynx, bladder and kidney), which could be prevented by smoking cessation. Lung cancer has been the most common cancer in the world since 1985 and cigarette smoking accounts for more than 20% of all global cancer deaths, 80% of lung cancer cases in men and 50% of lung cancer cases in women worldwide.
Lifestyle
Like tobacco, obesity, physical inactivity and poor nutrition are established causes of several types of cancer. Diet contributes to 3 million cancer deaths per year (gastric, colon, oesophagus, breast, liver, oropharynx and prostate) and diet modification could reduce these by avoiding animal fat and red meat, increasing fibre, fresh fruit and vegetable intake as well as avoiding obesity.
A significant increase in the incidence of obesity (body mass index greater than 30 in adults) has occurred globally since the 1980s. The trend towards overweight and obesity is even greater in children than in adults and has occurred not only in high‐resource countries but also in urban and even rural areas of many low‐ and middle‐income countries. This is attributed to increased availability of calorie‐dense foods and reduced physical activity.
Infections
Chronic infection accounts for 18% of cancers worldwide; the most common including cancers of the cervix, gastric and liver are, in turn, caused by HPV, Helicobacter pylori and hepatitis B and C viruses. These pathogens are more prevalent in developing nations, where the resulting cancers are threefold more prevalent (26% versus 8% in developed nations).
Cervical cancer is the fourth leading cause of cancer mortality in women worldwide, with 80% of cases in developing nations and 99.7% cases caused by HPV. HPV infection rates can be reduced by the use of condoms and a vaccination against HPV has been available since 2010. This has produced a 71% decrease in pre‐cancerous cervical cytology and a 90% reduction in genital wart cases in the United Kingdom in the last decade. Global uptake is varied, with a range of 31% uptake (Kenya) to 81% (Malaysia), with an average reduction in uptake from 65% to 50% during the pandemic.
The incidence and death rates from gastric cancer have steadily declined over the last 50 years, even though it remains one of the leading causes of cancer mortality (65% in developing nations). Chronic or recurrent infection with H. pylori is the main cause of chronic gastritis and peptic ulcers and increases risk for developing gastric lymphoma and cancer of the distal stomach. The exact causes of the worldwide decline in gastric cancer incidence in the past decades are not known but are thought to include improvements in diet, food storage and a decline in H. pylori infection due to a general improvement in sanitary conditions and increasing use of antibiotics.
More than 80% of liver cancer cases occur in developing nations, with more than 55% occurring in China alone. Globally, 75% of all liver cancer cases and 50% of all liver cancer deaths are caused by chronic infection with either HBV or HCV. A safe and effective vaccine against HBV is available and is the most cost‐effective strategy to reduce liver cancer. Over three‐quarters of WHO member states have introduced hepatitis B vaccine into routine infant immunisation schedules, although vaccine delivery is particularly challenging in high‐risk, low‐resource areas of Africa.
Challenges
Prevention with vaccination against certain cancers could reduce the cancer burden with protection against HBV and HPV.
Education is important as low rates of literacy are associated with regions of poverty. Education about cancer could result in earlier diagnosis, better engagement with screening and acceptance of diagnostic and treatment services. Such approaches need to reflect the local cultural requirements.
Access to treatment is resource limited as treatment for cancer relies on surgery, radiotherapy and chemotherapy, all of which remain expensive and often unavailable in developing nations. New targeted therapies will be too expensive and therefore the newest developments in therapy will be unavailable without successful engagement of the pharmaceutical industry to negotiate reimbursement schemes which might make new drugs more affordable and accessible.
Cure the curable: with a greater understanding of the hallmarks of cancer, specific features of cancers can be used as targets for treatment and could be used to reclassify the cancers. Understanding the microenvironment of the cancer cell is vital to delivering successful future therapies, but open access to research findings for all nations should be a key principle for funding research.
Provide palliation whenever it is required as the majority of cancer treatment is not aimed at cure but more to control symptoms of the patient. Access to analgesia is often poor with only 9% of the world’s morphine used in developing nations which have 83% of the world’s population. In some regions of Africa, patients have to walk for more than a day in each direction to and from a pharmacy to receive only 5 days’ supply of medication. There are persisting misconceptions about the use of strong opioids analgesia that have yet to be overcome.
End‐of‐life care is not expensive but requires involvement of the family and other caregivers. It can be improved by access to better training and education and provision of community‐based services that understand the diversity and requirements of the local population.
2The nomenclature of cancer
Table 2.1 Nomenclature of tumours
Originating tissue
Benign tumour
Malignant tumour
Blood vessel
Angioma
Angiosarcoma
Bone
Osteoma
Osteosarcoma
Cartilage
Chondroma
Chondrosarcoma
Fat
Lipoma
Liposarcoma
Fibrous tissue
Fibroma
Fibrosarcoma
Germ cell
Mature teratoma/dermoid cyst
Immature teratoma Seminoma/dysgerminoma
Glandular epithelium
Adenoma
Adenocarcinoma
Granulocyte
Myeloid leukaemia
Liver
Hepatic adenoma
Hepatocellular carcinoma
Marrow lymphocyte
Lymphocytic leukaemia
Node lymphocyte
Lymphoma
Plasma cell
Malignant myeloma
Skin
Papilloma
Squamous cell carcinoma Basal cell carcinoma
Skin melanocyte
Naevus
Malignant melanoma
Smooth muscle
Leiomyoma
Leiomyosarcoma
Squamous epithelium
Squamous papilloma
Squamous cell carcinoma
Striated muscle
Rhabdomyoma
Rhabdomyosarcoma
Transitional epithelium
Transitional papilloma
Transitional cell carcinoma
Table 2.2 Eastern Cooperative Oncology Group (ECOG) performance status scale
Score
Description
0
Fully active, able to carry out normal activities without restriction and without the need for analgesics
1
Restricted in strenuous activity, but ambulatory and able to carry out light work or pursue a sedentary occupation. This group also includes patients who are fully active but only with the aid of analgesics
2
Ambulatory and capable of self‐care but unable to work Up and about for more than 50% of waking hours
3
Capable only of limited self‐care Confined to a bed or chair for more than 50% of waking hours
4
Completely disabled Unable to carry out any self‐care and permanently confined to a bed or chair
Table 2.3 Karnofsky performance status score
Score (%)
Description
100
Normal, no complaints, no evidence of disease
90
Able to carry on normal activity, minor signs or symptoms
80
Normal activity with effort, some signs or symptoms
70
Care for self, unable to carry on normal activity or do active work
60
Requires occasional assistance but able to care for most of needs
50
Requires considerable assistance and frequent medical care
40
Disabled, requires special care and assistance
30
Severely disabled, hospitalisation indicated but death not imminent
20
Very sick, hospitalisation required, active supportive treatment required
10
Moibund, fatal processes progressing rapidly
The diagnosis of cancer is usually made following a histological assessment of a biopsy or resected specimen. The results should be interpreted within the context of the clinical case and discussed at a multidisciplinary meeting involving oncologists and the pathologist. The histopathological features of cancer include abnormal cellular morphology, increased rate of mitosis, multinucleated cells, increased nuclear DNA and nuclear‐cytoplasmic ratio and tissue architecture which is less organised than that of the originating tissue. A histopathology report will outline the gross features (tumour size, lymph node size and number) and microscopic findings (tumour grade, margins, lymphovascular invasion, mitotic rate and immunohistochemistry staining).
Tumours typically invade the basement membrane, but those that have not yet done so are termed in situ tumours. These are non‐invasive but demonstrate all the other features of cancer. They represent a stage in the progression from dysplasia to cancer.
Tumour nomenclature
The suffix ‐oma (Greek, ‘swelling’) is used to denote a benign tumour, although some are not tumours (e.g. granuloma). If the tumour is malignant, the suffix ‐carcinoma (Greek, ‘crab’) is used for epithelial tumours and ‐sarcoma (Greek, ‘flesh’) is used for tumours derived from connective tissue. Table 2.1 outlines the common terms used for benign and malignant tumours arranged by originating tissue.
Prefixes are used to denote the originating tissue of the tumour, e.g. adeno‐ for glandular epithelium, osteo‐ for bone, lipo‐ for fat, angio‐ for vasculature etc. The four main originating tissues are epithelial, connective tissue, lymphoid and haemopoietic tissue and germ cells. Germ cell derivatives use the term terato‐ (Greek, ‘monster’). Other tumours, because of prolonged usage, continue to bear eponyms (e.g. Hodgkin’s disease, Kaposi sarcoma).
Sometimes there is more than one type of cancer tissue present within a single organ (e.g. carcinosarcoma) or within a single type of epithelium (e.g. adenosquamous carcinoma), each with its own special characteristics, prognosis and response to therapy. In some epithelial cancers, the cancer tissue may not fit within a known classification and is often termed carcinoma ‘not otherwise specified’ (NOS).
Tumour grade
Tumours are graded by the degree of differentiation and growth rate, often on a scale of 1–3, where 3 represents the least differentiated, fastest dividing tumours. Tumours that more closely resemble the tissue of origin are graded as well‐differentiated (grade 1), while tumours with a more aggressive growth and high mitotic rates are graded as poorly differentiated (grade 3) cancers. The term anaplastic (Greek, ‘to form backwards’) is used to describe tumours that are so poorly differentiated that they have very few tissue‐specific features and often do not stain well to surface markers.
The grade has prognostic significance with grade 1 tending to have a more favourable prognosis and grade 3 the worst. Formal grading systems exist for a range of cancers but it does remain a subjective assessment, and typically a single cancer can be heterogeneous such that areas differing significantly in differentiation and mitotic activity exist side by side, with a risk of sampling error. Therefore for accurate diagnosis and grading, sufficient tissue and microscopic sections must be sampled so that the most malignant areas are found.
Some cancers are so well differentiated that their malignant cells cannot be distinguished from those of benign tumours or even from normal cells. In such instances, the recognition of abnormal cellular relationships becomes especially important for correct diagnosis.
Cytology
The examination of cells can be useful for a diagnosis in patients that have had a fine‐needle aspiration (FNA) of a palpable mass. Fluid cytology can be performed on ascites, pleural fluid or CSF and can be diagnostic in some cases. However, sampling errors can lead to false‐negative results, whereas active infection or abscess formation may produce false‐positive results. Cytology can examine cells from sputum, urine, cervix, pleural effusions and ascites.
Abnormalities of individual cancer cells may be helpful in diagnosis, particularly increased numbers of mitoses and cytological features relating to the state of tumour cell differentiation. Cytological features of malignancy include altered polarity, tumour cell enlargement, increased nuclear to cytoplasmic ratio, pleomorphism (variation in size and shape) of tumour cells and their nuclei, clumping of nuclear chromatin and distribution of chromatin along the nuclear membrane, enlarged nucleoli, atypical or bizarre mitoses (e.g. tripolar) and tumour giant cells with one or more nuclei.
Additional immunohistochemistry analysis can be used to understand different antigen expression amongst subtypes of each tumour site – e.g. HER2 receptor expression in breast cancer.
Cytogenetic analysis
Some tumours have typical chromosomal changes that can aid diagnosis and these specific abnormalities are usually demonstrated using a karyotype. In karyotype nomenclature, 9q31 designates the chromosome (9), the long arm (q) (rather than short arm (p)), the region distal to the centromere (3) and the band within that region (1). The utilisation of fluorescent in situ hybridisation (FISH) techniques can be useful in specific cancers such as Ewing’s sarcoma and peripheral neuroectodermal tumours, where there is a translocation between chromosome 11 and 22 − t(11; 22)(q24; q12).
Tumour stage
The stage of a cancer is a geographical term that denotes the extent of tumour spread and a uniform classification system is used based upon the size of the primary tumour (T), the presence of involved lymph nodes (N) and distant metastases (M). (See Chapter 19.)
Performance status
One of the most important factors that impacts on the planning of treatment and prognosis is the performance status of the patient. This requires an assessment of their functional capacity, ability to self‐care and mobility. The performance status correlates with prognosis and tolerance of treatment, and a number of different scales are used, the more common being the ECOG (Table 2.2) and Karnofsky scales (Table 2.3).
Patients with performance status 3 or 4 do not tolerate treatment as well and indeed some systemic chemotherapy may shorten their life and therefore requires careful consideration and assessment.
3Environmental determinants of cancer
Table 3.1 Environmental influence on carcinogenesis
Factor
Processes
Cancers associated
Occupational exposure
(see also ultraviolet and radiation)
Dye and rubber manufacturing (aromatic amines)
Bladder cancer
Asbestos mining, construction work, shipbuilding (asbestos)
Lung cancer, Mesothelioma
Hardwood furniture making (hardwood dust)
Nasal cavity adenocarcinoma
Vinyl chloride manufacturing (PVC)
Liver angiosarcoma
Petrochemical industry (benzene)
Acute leukaemia
Chemicals
Chemotherapy (e.g. melphalan, cyclophosphamide)
Acute myeloid leukaemia
Pesticide manufacture and copper refining (arsenic)
Lung cancer, squamous cell skin cancer
Cigarette smoking
Exposure to carcinogens from inhaled smoke
Lung cancer, bladder cancer
Viral infection
Herpesviruses (EBV, HHV‐8)
Burkitt’s lymphoma, nasopharyngeal cancer, Kaposi’s sarcoma
Hepatitis viruses (HBV, HCV)
Hepatocellular carcinoma
Retroviruses (HTLV‐1)
Adult T‐cell leukaemia
Papillomaviruses (HPV)
Cervical cancer, anal cancer
Bacterial infection
Helicobacter pylori
Gastric cancer, gastric mucosa‐associated lymphoid tissue (MALT) lymphomas
Parasitic infection
Liver fluke (Opisthorchis sinensis)
Cholangiocarcinoma
Schistosoma haematobium
Squamous cell bladder cancer
Dietary factors
Low roughage/high fat content diet
Colorectal cancer
High nitrosamine intake
Gastric cancer
Aflatoxin from contamination of
aspergillus flavus
Hepatocellular cancer
Radiation
Ultraviolet (UV) exposure
Basal cell carcinoma, melanoma, non‐melanocytic skin cancer
Nuclear fallout following explosion (e.g. Hiroshima)
Leukaemia, solid tumours
Diagnostic exposure (e.g. CT imaging)
Cholangiocarcinoma (following thorotrast usage)
Occupational exposure (e.g. beryllium and strontium mining)
Lung cancer
Therapeutic radiotherapy
Medullary thyroid cancer, sarcoma
Inflammatory diseases
Ulcerative colitis
Colon cancer
Hormonal
Androgenic anabolic steroids
Hepatocellular carcinoma
Oestrogens
Endometrial cancer, breast cancer
Table 3.2 Effects of hormone manipulation on cancer risk
Combined oral contraceptive
Hormone replacement therapy
Nulliparity and low parity
Ovarian cancer
Reduced risk
Increased risk (small)
Increased risk
Breast cancer
No effect
Increased risk (with long‐term use)
Increased risk
Endometrial cancer
Reduced risk
Increased risk if oestrogen only
Increased risk
Environmental factors
The majority of cancers result from a complex interaction between genetic factors and exposure to environmental carcinogens. Most of these environmental triggers have been identified using epidemiological studies which examine patterns of cancer distribution in patients of different age, sex, social class and geography, with different concomitant illnesses (Table 3.1). Sometimes these give strong pointers to the molecular or cellular causes of the disease, but for many solid cancers, there is evidence of a multifactorial pathogenesis even when there is a known principal cause.
Radiation
The major physical carcinogen is radiation, which is ubiquitous in the environment and may be ionising or non‐ionising. Ionising radiation has very high energy and includes gamma rays from cosmic radiation, isotope decay like alpha particles from radon gas and X‐rays from medical imaging. Non‐ionising radiation has less energy and includes ultraviolet radiation from the sun and radiofrequency radiation from electronic devices.
High‐frequency, high‐energy ionising radiation damages cellular structures and DNA by displacing electrons from atoms resulting in an ion pair. Some tissues such as bone marrow, thyroid and breast tissue are particularly susceptible to the effects of ionising radiation.
Non‐ionising radiation does not yield an ion pair but can still excite electrons resulting in a chemical change to the target tissue. It is UVB that is the most significant in this category, causing distortion of the DNA double helix. This distortion is normally repaired by the nucleotide excision repair (NER) pathway. Patients with xeroderma pigmentosum have defects in this mechanism resulting in UV‐induced skin malignancies. The incidence of cancers is greater in less‐pigmented populations as melanin absorbs UV radiation and acts to shield the dividing cells in the skin. Severe sunburn in youth is a significant risk factor for the subsequent development of malignant melanoma.
Chemicals
Many chemicals can induce cancer and are referred to as carcinogens, which can act upon three distinct steps of initiation, promotion and progression. Initiation requires replication of cells where repair of the chemically induced DNA damage has failed and a single exposure to a carcinogen may be sufficient. Promotion is a reversible process requiring multiple exposures, often with a dose‐response threshold, which produces a selective growth advantage, usually without DNA mutation. Progression is irreversible and involves multiple complex DNA changes, such as chromosomal alterations and morphological cellular changes, which are detectable with microscopy.
Many potent carcinogens are strong electrophiles that can accept electrons such as vinyl chloride, aflatoxin, N‐hydroxylated metabolites of azo dyes and alkyldiazonium ions from nitrosamines.
Smoking
The chemical constituents of tobacco smoke are carcinogens and particularly increase the risk of lung, oropharyngeal, oesophageal and bladder cancers. However, associations exist with all cancers with the exception of endometrial cancer for which smoking appears to be protective. Ninety percent of lung cancers are directly attributable to smoking, and mortality from lung cancer is 30‐fold higher in smokers.
Infections
Infection makes the most significant contribution to the global burden of cancer with approximately 1.5 million associated cases of cancer (15%) per year, typically cervical, stomach, liver, bladder and lymphoma. The association between viral infection and cancer was first demonstrated in 1911 by Peyton Rous studying the development of sarcoma in chickens. Following HIV infection, the weakened immune system cannot respond to other viral carcinogens. In the presence of HIV, those infected with human herpes virus (HHV) 8 will develop Kaposi’s sarcoma and Castleman’s syndrome. The majority of other herpes viruses have been implicated in cancers, most notably Epstein–Barr virus (EBV) in causing Hodgkin lymphoma or Burkitt lymphoma.
The papilloma viruses HPV 16, 18, 31 and 45 are major aetiological factors for the development of cervical cancer and the hepatitis B and C viruses are known causes of hepatocellular carcinoma. The main parasitic infections linked to cancer are malaria associated with Burkitt’s lymphoma and schistosoma associated with various other cancers. Schistosoma japonicum has been linked to colorectal, hepatocellular and lymphoreticular cancers and schistosoma haematobium to bladder cancer. Chronic inflammation is thought to play a central role in both cases. Chronic bacterial infections such as tuberculosis have been linked to an increased risk of developing cancer (Table 3.1).
Hormones
Cancer can be induced by overproduction of endogenous hormones as well as exogenous substances as contained within the combined oral contraceptive pill (COCP) and hormone replacement therapy (HRT) (Table 3.2
