Cancer is predominantly a disease of middle age and elderly. Environment and genetics influence cancer risk. The global cancer burden is estimated at 10 million new cases per year, predicted to rise to 15 million by 2020. Cancer is the second most common cause of death in developed countries. The major cancers vary by sex, with lung cancer most common in men and breast cancer in women. Cancer risk depends on factors like age, sex, geography, occupation, diet, and smoking. Cancer spreads locally, through lymphatics, blood vessels, body cavities, and along epithelial surfaces. Premalignant conditions include changes in benign tumors, intraepithelial neoplasia, and malignancies from chronic inflammation.

2. Cancer and Benign Tumours
Cancer Epidemiology
 Cancer is predominantly a disease of middle age and
elderly.
 The varying incidence of cancer in different population
may indicate the underlying causes of these tumours
 Environment and genetics are important ion determining
cancer risk.
 Smoking and diet are major risk predisposing causes

3. The Global Cancer Burden
 WHO publishes annual cancer mortality statistics for most
of the countries, and is its subsidiary.
 It estimated that that about 10 million new cases
diagnosed each year and cancer accounts 12% of all deaths
worldwide.
 The annual total is predicted to rise to 15 million per year
in 2020 as the population increases and ages. cancer is
predominantly a disease of midle-age and elderly

4.  Taking all forms together, cancer is the second most
common cause of death in developed countries and has
recently overtaken heart disease to become the major killer
in some western word, killing about 25% of some societies.
 The major malignant human cancer is carcinoma
(malignant epithelial tumour), lymphoma (malignant
lymphoid tissue), ranks about tents, and sarcomas
(malignant connective tissue tumour) are rarer still.

5.  In men the commonest tumour is bronchial cancer, following
stomach, colorectal and prostate.
 Carcinoma of the breast is the commonest in the women,
cervical, colorectal and endometrial carcinomas are relatively
common.
 The risk of development of cancer depend on many factors,
among them
 age,
 sex,
 geographical location,
 race,
 occupational history,
 social habits and
 socio-economic class.

6. Age
 Overall, cancer affects middle age and elderly, but
different tumour types have deferent age profiles.
 Some particularly affect children (some lymphoblastic
leukaemia) and adoloscents (osteosarcoma). Hodgkin
lymphoma, a from of lymphoma has a bimodal peak
affecting young adults and then the middle aged to
elderly.
 Carcinomas, commonest cancers tend to affect the
middle age and elderly, incidence increase with age.

7. Geographical variation
 There are striking regional variation in cancer
incidence throughout the world.
 Many of these variations depend on
environmental factors such as carcinogens rather
than genetic factors.
 In Asia and Africa hepatocellular carcinoma is
very common due to high prevalence of HBV
infection and environmental exposure of to
carcinogens such as aflatoxins present in mouldy
granules.

8.  Malignant melanoma in mainly disease of white-
skinned people and specially common in sunny
climates such as Australia.
 Gastric carcinoma is common in former USSR, in
Japan and in china due H. Pylori infection and
environmental factors.
 Breast and colorectal carcinoma is common in
western world.

9. Diet
 In general, diet rich in fruit and
vegetables are associated with lower
risks of many major forms of cancer
including the tumours of lung, stomach,
breast and colon.
 In contrast a diet rich in animal fat is
statistically linked to increased
incidence of cancers of breast, colon,
prostate and endometrium.

10.  The risk of colon carcinoma is directly proportional to
the extent of meat consumption.
 A diet rich in salted fish is associated with high
incidence of gastric and nasopharyngeal carcinoma.
 alcohol consumption is associated breast, colon and
liver cancers and acts synergistic manner with
smoking.

11. Cigarette smoking
 It is generally acknowledged that
cigarette smoking is responsible for at
least a quarter of cancer deaths, specially
from cancers of the lung, larynx, oral
cavity and the lesser extent of urinary
tract.
 There is a direct proportional between
the number of cigarette smoked and the
risk of lung cancer.

12. General Features of Tumours
 A neoplasm, literally is an abnormal mass of tissue,
whose growth is uncoordinated with and exceeds that
of the normal tissue.
 It results from aberrations of the normal mechanisms
which control the cell number; these are cell
production by cell division and cell loss by the process
of apoptosis.

13. Classification of Tumours
 Tumours are divided in to two major groups
according to their behaviour, benign and malignant.
 Benign tumours remain localised at their site of
origin.
 They grow by expansion, pushing normal tissue away,
often with the formation of a capsule of compressed
fibrous tissue.
 Benign tumours usually grow slowly.

14.  Malignant tumours (cancers), grow by infiltrating
in to surrounding normal tissue and have the ability to
spread to distant sites, to metastases, where secondary
deposit takes place.
 The histological appearance of metastases similar to
that of origin tumour.
 While malignant tumour usually grow rapidly, it must
be remembered that not all malignant tumours are not
equally malignant.

16.  Some are highly aggressive and highly metastases
early, for example small cell carcinoma of the
bronchus.
 Others although they are slow growing and although
they are locally infiltrative, they rarely metastasize.
Basal cell carcinoma and adenocarcinoma are good
examples of this.
 The degree of malignancy, described as tumour grade,
usually correlates well with survival

17. Benign Malignant
 Growth pattern Expansion, localized infiltrative locally, spread to
distant sites (metastaize)
 Growth rate Slowly Faster
 Clinical effects Local pressure; horm- Local pressur destruction
ne secretion in appropriate hormone
secretion; distant metatases
 Histology Resembles tissue of many differ from tissue of
origin origin (less differentiated)
 Nuclei Small, regular, uniform Large, pleomorphic
 Mitoses Few, normal Numerous, including
atypical forms
 Treatment Local excision Local excision and
systemic therapy
therapy if metastasepresent

18. Tumour Nomenclature
Epithelial Benign Malignant
 Covering epith. Papilloma Carcinoma
 Glandular epith. Adenoma Adenocarcinoma
Connective tissue
 Smooth muscle Leimyoma liemyosarcoma
 Skeletal muscle Rhabdomyoma Rhabdosarcoma
 Bone forming Osteoma Osteosarcoma
 Cartilage Chondroma Chondrosarcoma

19. Benign Malignant
 Lymphoid No benign Hodkin & non-Hodkin
 Melanocytes Moles Malignant melanoma
 Haemopoietic No benign Leukemia

20. Epithelial Tumours
 Benign tumours may from both covering e.g. squamous
type, forming papillomas, and from glandular epithelium,
e.g. colon or thyroid forming adenomas.
Papillomas
 Papillomas are warty growths in which the proliferating
epithelium is thrown upwards into folds, and does not
invade in to underlying connective tiussue.

21. Adenomas
 Adenomas are benign tumours of glandular epithelium.
 The tumour cells in such tumour glandular structures
mimicking the arrangement of the normal tissue.
 These cells are differentiated and often continue to secrete
the normal product of the gland; thus the cells of adenoma
of colonic adenoma may produce mucin and the thyroid
adenoma thyroglobulin.
 If the glands become distended by secretion they may be
form cysts – resulting in a multiloculated lesion called
cystadenoma which may be found in the ovary or pancreas.

22.  Adenoma of viscera such as the colon tend to grow into
lumen, and often adopt a papillary architecture.
 Some are sessile and are thrown into greatly thickened
papillary folds – so called villous adenoma – whereas others
become pedunculated with stalk of normal mucosa – these
are known a tubular adenomas.
 In most benign tumours, the cytological features closely
resemble those of the normal tissue from which they arise.

23. Malignant Epithelial Tumours
 Carcinoma are the commonest type of malignant tumour
in humans.
 They fall into several subtypes, depending on the form of
differentiation they show.

24.  Squamous carcinomas can arise from pre-existing
squamous epithelium for example skin or larynx, but
some for example of bronchus and cervical
transformation zone, arise sites where there is a
normally glandular epithelium, but where there
squamous metaplasia has been followed by malignant
change.
Squamous carcinoma

25. Adenocarcinoma
 These are tumours showing glandular differentiation.
 They usually arise from glandular epithelium, for example
within the stomach, endometrium or colon and may arise
metaplastic glandular tissue e.g. in the lower third of
esophagus when chronic acid reflux has resulted in
metaplasia.
 Adenocarcinoma may be well differentiated or poorly
differentiated.

26. Transitional Cell Carcinoma
 Transitional cell carcinoma arises from the transitional
epithelium of the urogenital tract.
 It too may show considerable variation;
 well differentiated papillary transitional cell carcinoma
resemble papillomas, and may of the underlying stroma, but
they arenot show any invasion e regarded as malignant for
practical purpose because they have high risk of recurrence,
often in more aggressive from.
 Poorly differentiated cell carcinoma have a more solid
architecture and frequently invade deeply within the wall of
the bladder or ureter.

27. Small Cell Carcinoma
 Small cell carcinoma is tumour which shows
neuroendocrine differentiation in the form of
neurosecretory granules.
 Typically it arises from the bronchus, where is the most
aggressive form of lung cancer, but occasionally other sites
such as the cervix and esophagus.

28.  Other types of carcinoma include HCC, the malignant
tumour of hepatocytes and BCC, a variety of skin
cancer, which is always locally destructive, but seldom
metastasizes.

29. Connective Tissue Tumours
 The connective tissue are fibrous, fat, nerve, muscle,
blood vessels, bone and cartilage.
 Both benign and malignant tumours can be found,
which show differentiation towards one of these forms.
 It is likely that all arise from primitive mesenchymal
stem cell which retain the ability to differentiate in
many directions.

30. Benign Connective Tissue Tumours
 The nomenclature of the tumours is straightforward –
the name consists of a prefix indicating the type of
differentiation, for example lipo (fat), chondro
(cartilage), haemangio (blood vessel), with the suffix –
oma donating a benign tumour.
 Most are slowly growing encapsulated tumours
composed of appropriate differentiated tissue.

31.  The commonest is the leimyoma, a benign tumour
showing smooth muscle differentiation, often
occurring in the uterine muscle.
 Lipomas are also common tumours, usually occurring
in the subcutaneous tissues of adults, typically at the
back of the shoulder.
 They consists a encapsulated mass of mature fat.

32. Malignant Connective Tissue Tumours
 These are known sarcomas.
 They are far less common than carcinomas.
 Most common within the deep soft tissue of the limbs and
trunk although some arise within viscera.
 There are numerous different types.
 Like benign tumours, the nomenclature indicates the form
of differentiation shown: for example leiomyosarcoma is a
malignant tumour showing smooth muscle differentiation.
 Rhabdosarcoma show skeletal muscle differentiation and
are among the commonest tumours of childhood.

33.  Well differentiated contain myosin and actin
myofilaments so well orientated cross-striations
similar to those found in normal skeletal muscle can
be seen.
 In poorly differentiated tumours, the diagnosis is
made on the basis that proteins found in the skeletal
muscle (desmin, myoglobin) or involved in skeletal
muscle differentiations (MyoD1) can be demonstrated
by immunochemistry.

34. Spread of Malignant Tumour
Malignant tumours spread in several ways :-
Local spread
Lymphatic spread
Blood (haematogenous spread)
Transcoelomic spread
Intraepithelial spread

35. Local Spread
 Malignant cells have the ability to insinuate
themselves between adjacent normal cells and invade
the surrounding tissue, e.g. for epithelial tumours the
first step is for tumour cells to breach the basement
membrane, i.e. to proceed from the stage of
intraepithelial neoplasia to that of invasive tumour.

36.  It is at this point that the cells can be said to have
become malignant, tumour cells can easily spread
through loose fibrous tissue and adipose tissue.
 Dense fibrous tissue such as fascia and periosteum
tend to form more barrier, but are eventually also
penetrated.

37. Lymphatic Spread
 This is the principal mode by which carcinomas spread.
The very thin wall of lymphatics are readily penetrated by
tumour tissue, which is carried along in the lymph to the
first lymph node in lymph node chain, the sentinel node.
 Whether this node is involved by tumour is now
recognized to be important in planning the extent of
surgery, for example melanoma or the carcinoma of the
breast

38.  The malignant cells move from lymph node to other in
the lymph chain.
 Ultimately may reach to thoracic duct and enter the
SVC from which further dissemination through the
blood stream may occur.

39. Blood (haematogenous) spread
 Tumour cells also able to invade thin walled veins and grow
along the venous system or embolize in to the blood
stream.
 The site of initial metastasis (first-pass organ) depends on
the venous drainage of the location of the tumour.
 Most of tumour emboli pass through the right heart and
impact in pulmonary capillary bed, whereas many tumours
of splanchnic origin, for example of bowel metastasize by
blood to the liver along the portal vein.

40.  Visceral organs also invade blood vessels which
communicate with the paravertebral venous plexus of
Batson, a complex valveless veins.
 Retrograde flow occurring, for example when intra-
abdominal pressure increases, is responsible for the
metastases to the spine seen for example in prostate
carcinoma.

41.  Tumour emboli from the lungs enter the systemic
circulation and may be widely disseminated to the brain or
elsewhere.
 In contrast to the thin walled veins, the thick walled
arteries are resistant to invasion by tumours.
 It is not only the anatomical features of blood flow which
explain the site of metastases.
 The term ‘seed and soil’ was coined in the nineteenth
century to describe tendency to some cancers to spread
specific sites.

42.  Gastric carcinoma cans spread in a similar fashion, to
involve peritoneal cavity, often seeding in the ovaries.
When these ovarian metastases are bilateral in
premenopausal women they are known as Krukenberg
tumours.

43. Intraepithelial Spread
 This is the process by which tumour cells can infiltrate
between cells of normal epithelium, without invading
the underlying stroma.
 It is best seen in Paget’s disease of the nipple in which
the cells of ductal carcinoma in situ grow in to nipple
skin giving an appearance resembling eczema.

44. Premalignancy
 Three main groups can be considered as
premalignancies:-
 Malignant change in benign tumours
 Intraepithelial malignancy/dysplasia
 Malignancy developing in chronic inflammation

45.  Benign tumours which undergo malignant change,
examples include colonic adenomas which may become
adenocarcinomas (adenoma-carcinoma sequence),
 Intraepithelial premalignant condition is the basis of
understanding carcinomas. In numerous condition it is
possible to identify stage of pre-invasive condition, where
epithelial cells show the cytological features of malignancy
but not yet developed to invade adjacent normal tissues.
 This process has been known as dysplasia, carcinoma in
situ and more recently ‘intraepithelial neoplasia’.

46.  It can effect the epithelia of all types- squamous,
transitional, glandular, detection of early of these
changes can prevent the overt change in to
malignancy.
 This is the basis of cervical screening programmes
in which the abnormal cells from cervical
intraepithelial neoplasia (CIN) can be seen in
cervical smears.

47. Major Sites of Intraepithelial Neoplasia
Site Terminology
Cervix CIN (cervical intraepithelial neoplasia)
Vulva VIN (vulval intraepithelial neoplasia)
Vagina VAIN (vaginal intraepithelial neoplasia)
Prostate PIN (prostatic intraepithelial neoplasia)
Skin Carcinoma
Breast Ductal & lobular carcinoma in situ

48.  Breast screening aims to detect the carcinoma in situ
and also small invasive carcinomas with the hope of
diagnosis before metastases occurred.
 Dysplastic changes can be seen in metaplastic
intestinal epithelium found in the oesophagus in
Barret’s oesophagus, an important precursor of
adenocarcinoma of the oesophagus.

49.  Chronic inflammatory conditions can change in to
malignancy due to increased proliferation and
reparative conditions.
 Examples include longstanding ulcerative colitis in
which there is an increased risk of colonic cancer and
Hashimoto’s thyroiditis in which lymphoma may
develop.
 Hepatocellular carcinoma typically arise livers affected
by cirrhosis.

50. Clinical Effects of Tumours
 Not all tumours are symptomatic.
 Many are found accidentally on X-rays or post-mortem
and all tumours pass through a stage when they are too
small to cause any effects.

51. Benign Tumours
 Despite their name these are not always harmless. As they
remain localized at their site of origin, the effects occur
into three broad categories:-
1. The presence of palpable lump, often painless, but
occasionally causing discomfort.
2. The effects of substance produced by a tumour.
The cells of benign tumour are well differentiated and often
remain the function of the tissue of origin such as the
production of hormones. This usually out with the normal
feedback mechanism and over activity may result, e.g. the
thyroid adenoma may lead to hyperthyroidism.

52. 3- The effect of adjacent tissues due to pressure from
expansion of the tumour. This usually seen particularly
when tumour arises from confined area e.g. within the
cranial cavity.
 The distortion of the uterine cavity by fibroid
(leiomyoma) often results in heavy menstrual bleeding.

53. Malignant Tumours
Direct Effects
 Malignant tumours may cause a palpable mass which often
grows rapidly and compresses adjacent structures such as
nerves with resulting pain.
 Blood loss due to haemorrhage from an ulcerated
carcinoma may be acute or chronic, thus leading to iron
deficiency anaemia.
 Carcinomas cause narrowing (stenosis) or complete
obstruction of hollow viscus

54. Metastatic Effects
 Metastases can cause similar mass effects to primary
tumours, but because they are usually multiple
consequences tend to be more severe.

55. Common Sites of Metastases and their Effects
Site Effects
Lung Haemoptysis, pneumonia, pleural effusion
Bone Pain, fracture, spinal cord compression
Liver Hepatomegaly, jaundice, hepatic failure
Brain Seizures, stroke, raised ICP
Bone marrow Anaemia, leucopoenia, thrombocytopenia

56. Non-metastatic Effects
 This is heterogeneous group of disorders, many due to
release of cytokines, such as interleukin 1 (IL 1) and tumour
necrotizing factor α (TNFα) from tumour cells.
 Patients with advanced cancer are wasted (cachectic) with
weight loss, anorexia and fever.
 Immunosuppression, abnormalities of coagulation, e.g.
thrombophlebitis migrans and neurological disorders, e.g.
neuropathy, cerebellar degeneration and Eaton-Lambert
syndrome, a syndrome resembling myastenia gravis may be
all seen.

57. Inappropriate Hormone Production
 Many tumours produce hormones not only produced
by their tissue of origin. These include ADH, ACTH
typically secreted by small cell carcinoma of the
bronchus.
 Many tumours including squamous carcinoma
produce parathyroid hormone related which has
parathormone-like action and results in humoral
hypercalcaemia of malignancy.

58. Common Cancers and their Effects
Lung Cough, haemoptysis, chest pain,
pneumonia, PE, obstruction of SVC,
metastases to bone, brain,
Breast Lump, early spread to nodes, bone,
lung & liver
Prostate Urinary symptoms, metastases to
bone (spine)
Colon Altered bowel habit, obstruction,
anaemia, metastases to the liver
Pancreas Obstructive jaundice, back pain
esophagus Dysphagia, anaemia, early local
spread and metastaes

59. Pathological Diagnosis of Tumours
 Although clinical, radiological and biochemical
findings all contribute towards the diagnosis of
tumour, the final diagnosis is made in almost all cases
by microscopic examination: a so-called tissue
diagnosis.
 Depending on the procedure used to obtain a sample
for examination, the entire lesion, a large or small
sample, or few cells may be studed.

60. Biopsies for Histopathological Assessment
 These allow assessment both of the appearance of the
tumour cells and their relationship to normal tissues,
i.e. the tissue architecture.
Excisional biopsy
 In this procedure, usually performed for relatively
small tumours, the lesion is removed and submitted
for examination.

61. Incisional Biopsy
 In this procedure, the surgeon exposes the tumour and
removes a wedge of tissue of fairly large and hopefully
representative specimen.
 On the basis of the biopsy result, either immediately
by frozen section or after a day or so, the appropriate
therapy can be instituted.

62. Needle Biopsy
 Many tumours, including deep-seated ones under
radiological control, can be sampled by needle biopsy
in which a thin core of tissue is removed.
 This technique provides small amounts of tissue.
 This may not representative of the entire lesion, i.e
there is potential for sampling error.

63. Cytology
 In recent years there has been a explosion in the use of
cytology, to obtain the cells for study.
 The technique relies largely on interpretation of the
appearance of the individual cells, although the degree
of cohesion of the tumour cells (a feature of epithelial
tumours) can also be assessed.

64.  Cells can be easily found in body fluids, eg. Aspiration
from pleural or peritoneal cavities by needle and
syringe or saliva or sputum.
 Fine needle aspiration of solid tumours is now
routine.
 It does not need anaesthesia and other preparation
and it is simple procedure for superficial lesion. E.g.
Breast lump and deeply located lesion can be sampled
under imaging control.

65. Conventional Diagnosis and Additional
Techniques
 In most cases, for example carcinomas of breast, colon
or lung the diagnosis is made on stained sections
applying the conventional criteria of malignancy.
 Simple histological techniques, for example for the
detection of glycogen, much polysacharides and the
pigments such as melanin help in some cases.

66.  Immunochemistry, using antibodies to cell constituents,
contributes much to the diagnosis of poorly differentiated
tumours and often allows a precise diagnosis to be made on
small needle biopsies.
 Immunostaining has largely superseded electron
microscopy in this regard.

67. Tumour Markers
 These substances are produced by tumour cells, are
detectable in the blood, and are of value in diagnosis
and in monitoring progress following treatment.
 Many are onco-fetal antigens, proteins that are usually
produced by fetal cells but not by normal mature adult
cells.

68. Marker Tumour
α-fetoprotein Teratoma, Hepatocellular carcinoma
hCG Choriocarcinoma; teratoma
PSA Prostatic carcinoma
CA125 Ovarian carcinoma
Carcinoembryonic
antigen
Carcinoma of the gut, lung
Calcitonin Medullary carcinoma of the thyroid
Thyroglobulin Follicular and pupillary carcinoma of thyroid

69. Tumour Staging & Grading
 Once the diagnosis of cancer is made, it is important
to predict the likely behaviour of a tumour, both to
decide the appropriate therapy and to estimate the
patient’s survival.
 The two main factors are the biological nature of the
tumour, the grade and its extent, the stage.

70.  Grade: degree of malignancy of a neoplasm usually
judged from its histological feature (nuclear size and
regularity, mitotic frequency).
 Stage:- a recognized phase in the development
(progression) of disease usually neoplasm.
 Different grading systems have been developed for the
various tumour types.

71.  The parameters are:
- Mitotic activity
- Nuclear pleomprphism
- Degree of differentiation
- Extent of necrosis
 The tumour staging can be assessed in number of
ways.
 The TNM system, developed by the Union of
International Cancer Centre (UICC) is applied in
many tumour types specially carcinomas.

72.  In this scoring system an increasing number is
described to more extensive disease, at the primary
site T, in draining lymph nodes N and distant sites of
metastasis M.
 Other systems include Duke’s staging system for
colonic carcinoma.

73. TNM Staging of Gastric Carcinoma
Stage Explanation
T1 Tumour in Mucosa or submucosa
T2 Tumour penetrates muscularis mucosa
propria
T3 Tumour erodes through serosa
T4 Tumour involved adjacent organs
N0 No nodal metastases
N1 Metastases in 1 – 6 lymph nodes
N2 Metastases 7 – 15 regional lymph nodes
N3 Metastases in more than 15 lymph
nodes
M0 No distant metastases
M1 Distant metastases

74. Carcinogenesis
 Cancer is not a single disease, and different cancers
have different causes.
 In some tumours a single major factor is implicated,
but in most tumours multiple factors are involved.
 The clues or our understanding of the causes of cancer
come from several sources, but it is clear that
environment, genetic predisposition and inter-
individual variability in coping with toxic injuries are
all important.

75. Environmental Factors
Chemical Carcinogens
 Many chemicals have been implicated in causing
cancer in humans.
 Sometimes this is based on strong epidemiological
evidence, for example lung cancer and cigarette
smoking or bladder cancer in aniline dye worker, but it
may also assumed from animal experiments.

76. Chemical Occurrence Tumour
Alkyl ting agents Chemotherapy Leukemia
Asbestos Insulation Mesothelioma
Benzene Solvents Leukemia
Nickel Mining Lung cancer
Nitrosamines Dietary Gastric Carcinoma
Polycyclic
hydrocarbons
Burning of organic
material
Carcinoma
Radon Mining Lung cancer
Vinyl chloride PVC monomer Angiosarcoma of liver

77.  From animal studies it become apparent that
chemicals acted in different ways to cause cancer.
 Some acted directly, while others required metabolic
conversion to an active from.
 Many chemicals are weakly carcinogenic but that
potency is much increased when chemicals are given
in combination or subsequently.

78.  Multistep theory of carcinogens is observed.
 Initiation leads to DNA damaged mutation of cells
followed by promotion where there is clonal expansion
of the abnormal cell eventually giving rise to cancer.
 Some chemicals appear to be initiators and promoters,
so-called complete carcinogens but not all of these
cause DNA damage

79.  Human and rodents have markedly different metabolic
pathways in some respects and may therefore cope with a
potential carcinogen in quite different ways.
 The capacity of human cells to repair damage may be differ.
 Animal experiments tend to rely on constant, relatively
high exposure to one or few agents whereas human context
exposure to potential carcinogens occurs intermittently,
frequently at low dose, and ad complex mixture rather than
single agent.

80. Radiation
 There is evidence that ionizing radiation can induce
cancer.
 Radiation induced cancers were seen in early
radiologists, who used there own hands to calibrate
their equipment.
 Many of the survivors of atomic bombs in Nagasaki &
Hiroshima in 1945 later succumbed to tumours,
especially carcinomas and leukemia.

81.  An increased incidence of thyroid cancer is seen after the
Chernobyl nuclear explosion in 1986.
 Therapeutic irradiation can cause an other cancer after
several years, both carcinomas and sarcomas.
 Ionizing radiation acts by damaging the DNA.
 Both single & double cleavage is seen.
 Breaks in single strand of DNA repaired but, specially in
rapidly growing cells this may be inaccurate leading to
single base mutaion

82.  In contrast, double strand damage leads to chromosomal
rearrangement such as translocation and deletion.
 Ultraviolet radiation is strongly implicated in the aetiology
of skin tumours especially malignant melanoma of which
90% of cases can be attributed to exposure.

83. Viruses and Cancers
 It has been recognized that viruses are responsible for some
cancers.
 Viruses cause the development of cancers in different ways,
some RNA viruses contain gene (viral oncogenesis) – which
are directly responsible for transforming cells to
malignancy.
 The viral RNA genome is copied into DNA by the enzyme
reserve transcriptase and this is then inserted in to the host
genome.
 Viral genes can thus influence the expression of adjacent
cellular genes.

84.  Other viruses e.g. HCV can cause direct tissue injury,
leading to increased proliferation and an increased risk of
mutation.
 The final common pathways of many of these precipitating
factors is mutation of DNA.
 Other such as chronic infection or hormonal stimulation
caused increased cell turnover and may therefore make
mutations more likely.
 Immunosuppression is associated with an increase
particularly of lymphoma, a common complication of
AIDS.

85. Viruses Implicated in Human Cancers
Virus Human tumour
HPV especially types 16 &
18
Cervical carcinoma, Anal carcinoma &
penile carcinoma
Epstein-Barr VIRUS Nasopharyngeal carcinoma
Burkitt’s lymphoma
Hodgkin lymphoma
HBV/HCV HCC
Herpes 8 Kaposi sarcomas

86. Genetic Factors
 Undoubtedly there are individuals with significant genetic
predisposition to various tumours including the common
cancers of breast, lung and colon.
 There are three broad categories of familial cancers.
.

87. Familial Cancer Syndromes
 In this group of disorders the increased risk of
cancer is due to transmission of a single gene
which appears to act in an autosomal dominant
manner, although in fact both copies of the gene
must be inactivated before a tumour develops
 The familial adenomatous polyposis coli is
characterized by the growth of numerous
adenoma in the colon and is inevitable
development of colonic carcinoma in the middle
age.

88.  The responsible gene (APC) - on the long arm of
chromosome 5 - has been identified and its
function as an inhibitor of growth promoting
signal transduction molecules established.
 The normal APC protein binds β-catenin and
promotes its proteolytic destruction; mutations of
APC tend therefore to increase the concentration
of β-catenin, which is important in carcinogens.

89.  In the Li-Fraumeni syndrome family members have an
increased propensity of premature development of a
variety of different tumour types (sarcomas, brain
tumours & breast cancer); for example the early
development of breast cancer and childhood sarcoma,
typically in mother and child.
 It is due to change of P53 gene.

90.  Familial retinoblastoma is characterized by almost
inevitable development, usually bilaterally, of the rare
retinal tumour retinoblastoma.
 This is due to inheritance of one abnormal copy of the
retinoblastoma (Rb) gene.

91. Familial Cancers
 In some families there is a striking increase in the
incidence of a common cancer, for example of breast,
colon or ovary.
 In some cases the responsible gene can be discovered,
for example the BRCA1 (on chromosome 17) and
BRCA2 (on chromosome 13) genes associated with
familial breast carcinoma.

92. Familial Recessive Disorders due to Defects in DNA Repair
 In ataxia-telangiectasia, an autosomal recessive
condition, there is an increased risk of developing
lymphoma or leukemia.
 This related excessive fragility of the chromosomes,
either spontaneously or following radiation.
 The responsible gene (AT) thought to act as a sensor of
DNA damage which activates the p53 gene causing the
cell enter Go until DNA repair is complete.

93.  In its absence, the mutated cell continues to proliferate
increasing the chance of malignancy.
 Hereditary non-polypous colon cancer is an other
disorder due to impaired DNA repair.
 The relevant genes are known as ‘mismatch repair
genes’; they detect point mutations where the
nucleotides on complementary DNA strands do not
match correctly (A:T, C:G) and excise the abnormal
base.

94.  Failure of these mismatch repair genes can be detected by
the accumulation of variable microsatellites, short
sequence which are normally identical in any individual;
microsatellite instability is an indication of mismatch
repair.
 Xeroderma pigmentosum is due to loss of the genes
involved in excision of so-called primidine dimers caused
by ultraviolet damage. It leads to greatly increased risk of
skin cancer.

95.  The topic of oncogenes and tumour suppressor genes can
be difficult and confusing. Is simple terms the cancer is due
to excessive and uncontrolled proliferation or insufficient
loss of cells, i.e. it results from defects in the normal
control mechanism for cell population.
 Normal genes switches on when cell division cell in needed
and which when expressed promote cell division are known
as cellular proto-oncogenes.

96. Thank you for your attention