CarcinogenesisCarcinogenesis

Carcinogenesis is mostly due to nonCarcinogenesis is mostly due to non--lethal genetic damagelethal genetic damage

Such genetic damage (or mutation) may Such genetic damage (or mutation) may be acquired by the action of be acquired by the action of environmental agents, such as chemicals, environmental agents, such as chemicals, radiation, or viruses, or it may be radiation, or viruses, or it may be inherited in the germ lineinherited in the germ line

The tumour mass results from clonal The tumour mass results from clonal expansion of a single progenitor cell that expansion of a single progenitor cell that has acquirehas acquiredd the genetic damage the genetic damage (i.e., (i.e., tumors are monoclonal)tumors are monoclonal)

CarcinogenesisCarcinogenesis

Carcinogenesis is a Carcinogenesis is a multistep processmultistep process A malignant tumour has several A malignant tumour has several

phenotypic features, such as excessive phenotypic features, such as excessive growth, local invasiveness, and the growth, local invasiveness, and the ability to form distant metastasesability to form distant metastases

These characteristics are acquired in a These characteristics are acquired in a stepwise fashion stepwise fashion (tumour (tumour progression)progression)

CarcinogenesisCarcinogenesis Three classes of normal regulatory genes are Three classes of normal regulatory genes are

the principal targets of genetic damage:the principal targets of genetic damage:

1.1. Growth-promoting Growth-promoting protprotoncogenesoncogenes

2.2. Tumor suppressor genesTumor suppressor genes

3.3. Genes that regulate apoptosisGenes that regulate apoptosis In addition, a fourth category of genes, In addition, a fourth category of genes, DNA DNA

repair genesrepair genes those regulate repair of those regulate repair of damaged DNA, is important in damaged DNA, is important in

carcinogenesiscarcinogenesis..

OncogenesOncogenes Proto-oncogenes: cellular genes that Proto-oncogenes: cellular genes that

encode protiens promoting normal encode protiens promoting normal cell growth & differentiationcell growth & differentiation

Oncogenes: genes whose products Oncogenes: genes whose products are associated with neoplastic are associated with neoplastic tranformationtranformation

Proto-oncogene Oncogene

ETIOLOGY OF CANCERETIOLOGY OF CANCER::CARCINOGENIC AGENTSCARCINOGENIC AGENTS

Three classes of carcinogenic agents Three classes of carcinogenic agents can be identified:can be identified:

1.1. Chemicals Chemicals

2.2. Radiant energy, andRadiant energy, and

3.3. Microbial agents. Microbial agents.

ETIOLOGY OF CANCERETIOLOGY OF CANCER::CARCINOGENIC AGENTSCARCINOGENIC AGENTS

Chemical CarcinogensChemical Carcinogens Benzo-pyreneBenzo-pyrene produced from cigarette smoking produced from cigarette smoking

and cause lung cancer . and cause lung cancer . Polycyclic hydrocarbonsPolycyclic hydrocarbons produced from boiled produced from boiled

animal fats and are present in smoked meats and animal fats and are present in smoked meats and fish and cause GIT cancer. fish and cause GIT cancer.

Aromatic amines Aromatic amines : produce bladder cancers in : produce bladder cancers in exposed workers of rubber industries. exposed workers of rubber industries.

Azo dyes Azo dyes used to color food (e.g., butter-yellow used to color food (e.g., butter-yellow to make margarine more enticing and scarlet-red to make margarine more enticing and scarlet-red for cherries) and cause GIT cancer.for cherries) and cause GIT cancer.

ETIOLOGY OF CANCERETIOLOGY OF CANCER::CARCINOGENIC AGENTSCARCINOGENIC AGENTS

Chemical CarcinogensChemical Carcinogens Nitrosamines produced Nitrosamines produced formed nitrites that formed nitrites that

have been added to food as preservatives and have been added to food as preservatives and cause cancer stomach. cause cancer stomach.

Aflatoxin Aflatoxin produced by Aspergillus, a mold that produced by Aspergillus, a mold that grows on improperly stored grains and nuts. Food grows on improperly stored grains and nuts. Food contamination lead to contamination lead to hepatocellular hepatocellular carcinomacarcinoma. .

Vinyl chloride, arsenic, nickel, chromium, Vinyl chloride, arsenic, nickel, chromium, insecticides, fungicidesinsecticides, fungicides, all are chemical , all are chemical carcinogens. carcinogens.

ETIOLOGY OF CANCERETIOLOGY OF CANCER::CARCINOGENIC AGENTSCARCINOGENIC AGENTS

Radiation CarcinogenesisRadiation Carcinogenesis Radiation, whatever its source Radiation, whatever its source (UV rays of (UV rays of

sunlight, x-rays, nuclear fission, sunlight, x-rays, nuclear fission, radionuclides) radionuclides) is an established carcinogen. is an established carcinogen.

The effect of ionizing radiation is related to its The effect of ionizing radiation is related to its mutagenic effectsmutagenic effects

Because the latent period of irradiation-Because the latent period of irradiation-associated cancers is extremely longassociated cancers is extremely long

Natural UV radiationNatural UV radiation derived from the sun can derived from the sun can cause skin cancers cause skin cancers (melanomas, squamous (melanomas, squamous cell carcinomas, and basal cell carcinomas)cell carcinomas, and basal cell carcinomas). . At greatest risk are fair-skinned people. At greatest risk are fair-skinned people.

ETIOLOGY OF CANCERETIOLOGY OF CANCER::CARCINOGENIC AGENTSCARCINOGENIC AGENTS

Viral and Microbial CarcinogenesisViral and Microbial Carcinogenesis Human Papillomavirus Human Papillomavirus (HPV) type 16 &18 cause (HPV) type 16 &18 cause

squamous cell cancers of the cervix and anal, squamous cell cancers of the cervix and anal, perianal area, vulva, and penis.perianal area, vulva, and penis.

Epstein-Barr Virus (EBV) Epstein-Barr Virus (EBV) cause Burkitt lymphoma, cause Burkitt lymphoma, primary CNS lymphoma in AIDS patients, and primary CNS lymphoma in AIDS patients, and nasopharyngeal carcinoma.nasopharyngeal carcinoma.

Hepatitis B Virus (HBV) Hepatitis B Virus (HBV) chronic HBV infection chronic HBV infection cause hepatocellular carcinoma.cause hepatocellular carcinoma.

Hepatitis C virus (HCVHepatitis C virus (HCV) also is strongly linked to ) also is strongly linked to hepatocellular carcinomahepatocellular carcinoma

Helecobacter pylori bacteria,Helecobacter pylori bacteria, cause gastric cause gastric carcinoma and gastric lymphoma. carcinoma and gastric lymphoma.

BiopsyBiopsy Fine needle aspirationFine needle aspiration Cytologic smearsCytologic smears ImmunocytochemistryImmunocytochemistry Tumor markersTumor markers Flow cytometryFlow cytometry

Diagnosis of CancerDiagnosis of Cancer