Incidence of cancer DR. AYSER HAMEED - PowerPoint Presentation

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Incidence of cancer

DR. AYSER HAMEED

LEC.3

Incidence 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.

Etiology 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.

All 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

.

Benzene ………………… Leukemia, lymphoma.

Cadmium ………………… carcinoma of prostate

.

Chromium ………………… carcinoma of lung.

Nickle

…………………….. tumors of Nose, lung.

Vinyl chloride …………….. liver malignancy.

Other 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.

III. 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

.

e.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

.

Characteristics 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.

Acquired 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

.

5.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.

Molecular 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.

2.

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).

III.

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.

Carcinogenesis:

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

.

Genetic 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

.

Mechanisms 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.

Step- 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)

.

Two 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

)

Step- 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).

2. 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.