LEC3 Incidence of cancer In male 30 Carcinoma of prostate 14 Carcinoma of Lung 11 Carcinoma of colon amp rectum In female 31 breast carcinoma 12 carcinoma of lung ID: 930315
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Slide1
Incidence of cancer
DR. AYSER HAMEED
LEC.3
Slide2Incidence of cancer
In male
30% Carcinoma of prostate
.
14% Carcinoma of Lung.
11% Carcinoma of colon & rectum.
In female
31% breast carcinoma
.
12% carcinoma of lung.
12% carcinoma of colon.
6% uterine carcinoma.
Cancer death:
In male
31% carcinoma of lung
.
11% carcinoma of prostate.
In female
25% carcinoma of lung
.
15% carcinoma of breast.
Slide3Etiology of cancer
Many factors may play a role in etiology of cancer:
I. Geographical & environmental factors:
These factors
form about 65% of all cancer etiology, while genetic factor form about 26%- 42% of cancer etiology
.
There is
geographical difference in the death from specific forms of cancer,
e.g. death from carcinoma of breast is about 4 - 5 times higher in U.S.A than Japan.
e.g. death from carcinoma of stomach in man & women is about 7 times higher in Japan than in U.S.A.
Slide4All these geographical differences are due to environmental rather than genetic causes.
These
environmental factors
can present in workplace (occupational factors), in the
food,………etc.
Examples on occupation factors & associated cancer are:
Arsenic …………… Carcinoma of lung, carcinoma of skin
.
Asbestos ……………….. Carcinoma of lung, mesothelioma
.
Slide5Benzene ………………… Leukemia, lymphoma.
Cadmium ………………… carcinoma of prostate
.
Chromium ………………… carcinoma of lung.
Nickle
…………………….. tumors of Nose, lung.
Vinyl chloride …………….. liver malignancy.
Slide6Other environmental factors that have role in development of cancer:
1. Alcohol consumption.
2. Smoking.
II. Age:
Frequency of cancer increase with Age
(most
death of cancer between 55- 75 years), this is could be due to accumulation of Somatic mutations & change in immunity with increase age.
Cancer cause 10% of all death among children (below 15 years)
Major lethal Cancer in children is leukemia, CNS tumors, lymphoma & soft tissue sarcoma.
Slide7III. Hereditary factor:
Hereditary forms of cancers can be divided into:-
Inherited cancer syndromes:
These syndromes characterized by:
There is inheritance of a
single mutant gene
(increase the risk of cancer).
Mode of inheritance is
Autosomal dominant
.
Slide8e.g. Familial retinoblastoma.
Multiple endocrine
neoplasia
.
Neurofibromatosis type I & type II.
2. Familial cancer:
Virtually all sporadic cancer can be occur in familial pattern:
e.g.
Carcinoma of colon, carcinoma of breast, CNS tumors
.
Slide9Characteristics of Familial cancer:
1.
Early age of onset
.
2. Tumors
arising in two or more close relatives of patient
.
3.
Multiple or bilateral cancer
.
4.
Mode of transmission is not clear.
3.
Autosomal recessive syndromes of defective DNA repair.
A small group of
autosomal recessive disorders is collectively characterized by DNA instability.
e.g.
X
eroderma
pigmentosa
, Ataxia telangiectasia.
Slide10Acquired pre neoplastic disorders:
1.Chronic skin fistula or long stand unhealed skin woun
d
(e.g. chronic osteomyelitis predisposing to develop
squamous cell carcinoma of skin
).
2.Hyperplasia, Metaplasia & dysplasia:
Like
carcinoma of lung,
develop in dysplastic bronchial tissue of habitual smoker.
3.Chronic atrophic gastritis
can predispose to
carcinoma of stomach
.
4.Chronic ulcerative colitis
, predispose to
carcinoma of colon
.
Slide115.Leukoplakia of oral cavity
,
vulva
(
squamous cell carcinoma
).
6.Villous adenoma of colon
, increase risk of
carcinoma of colon
.
Important note
:
Some of
benign tumors
can predispose to
malignant tumors
, like
adenoma of
colon, when enlarge can undergo malignant transformation.
Slide12Molecular basis of Cancer (Carcinogenesis):
Principles of genetic basis of cancer:
1. Nonlethal genetic damage lies at the heart of carcinogenesis.
This damage
may be acquired
by the action of environmental agents like (chemicals, radiation, viruses), or may be due to genetic cause.
Slide132.
Three classes of normal regulatory genes (control the growth of cancers):
I.
Growth promoting
protooncogenes
,
dominant genes, can transformed cells into malignant cells with single allele is damaged.
II.
Growth inhibiting
cancer suppressor genes (
antioncogenes
)
(recessive genes, can transformed cells into malignant cells only if both alleles of gene are damaged).
Slide14III.
Genes that regulate the apoptosis.
These genes
are targets of non-lethal genetic damage
.
3.
DNA repair gene
, disability of DNA repair genes can predispose to widespread mutation & neoplastic transformation.
Slide15Carcinogenesis:
is a multistep process at both
phenotypic & genetic levels.
Phenotypic level
includes:
I. Excessive growth.
II. Local invasion.
III. Metastasis.
These three criteria are called collectively
Tumor Progression
.
Slide16Genetic level
includes:
Six changes in normal cell physiology, that results in cancer formation
These changes are included:
1. Autonomous growth:
This pattern of growth of cancer is under the control of
Oncogenes
(genes
derived from
Protoncogenes
).
These oncogenes produced
oncoproteins
(growth factors), which result in autonomous growth of cancer
.
Slide17Mechanisms of action of
oncoproteins
:
By following steps:-
Step-I;
The
binding of growth factor
(
Oncoproteins
) to
specific receptors
on cell membrane.
Malignant cells acquire autonomous growth by followings:-
1. Acquiring the ability to synthesize the same growth factors to which they responsive (gene overexpression).
2. Pathological overexpression of normal growth factor receptors,
Her2 receptors
are overexpressed in 25- 30% of breast, lung carcinoma.
Slide18Step- II; Growth factor & receptor complex activate several proteins on inner side of cell membrane
(transient activation under normal state while persistent activation under neoplastic conditions).
Step- III;
Transmission of signals from these proteins
along inner side of cell membrane along the cytoplasm
to the nucleus via secondary messenger.
Step- II & III: this is called (singling pathway)
.
Slide19Two important genes that control this pathway (
Ras
….increase cells proliferation &
ABL…
……inhibit cell proliferation).
Cancer cells acquire autonomous growth is by
mutation in these genes that control the signaling pathway
(
transfer of signal from inner side of cell membrane to nucleus).
So
mutant
Ras
is the most common oncogene abnormalities in human tumors
Mutant
Ras
gene are present in 35% of human cancers (carcinoma of colon, carcinoma of pancreas……
etc
)
Slide20Step- IV;
Activation of transcription inside the nucleus
.
Mutations affect the genes that regulate transcription of DNA may result in autonomous growth of cancers.
e.g.
Myc
gene
is commonly involved in human tumors like in carcinoma of colon, breast, lung)..
Step- V;
Entry of cell into the cell cycle
& result in cell division.
Normal cell cycle is consists of five phases (G
0
,G
1
, S, G
2
, M).
All these phases are under control of proteins (
Cyclins
&
Cyclins
dependent Kinase).
Cyclin
D overexpression is seen in many cancers (breast, esophagus & liver).
Slide212. Insensitivity to inhibitory signals
(
disruption of tumor suppressor genes):
Disruptions of
tumor suppressor genes
make the
cells resistant to inhibition of growth & increase their proliferation.
All tumor suppressor genes are caused inhibition of cell growth by two pathways:
I. stimulate antigrowth signal, causing cells to enter G
0
phase.
II. Prevent the cell to pass from phase G
1
to S phase.