CARCINOGENESIS

Hematology-Oncology Division Child Health Dept. University of Sumatera Utara

Normal human cell populate specific areas of the body:function,grow,divide in response to signals (i.e,growth factors) die ( checkpoints cell growth death ) Malignancy : cell develop genetic defects DNA change lose growth pattern resistent to celullar mechanism , ability to acoid programmed cell death , leave their usual sitetravel blood stream, lymphatic system grow in new location
2

Principal genes

Oncogenes Tumor suppressor genes Apoptosis ( programmed cell death )

Oncogenes :genes whose normal function involves promoting the growth and reproduction of cells in regulated When uncontrolled malignant transformation of cell Tumor suppressor genes :normal to stop cell proliferation p53 P53 lost DNA damage not repair mutation malignant transformation
4

 Genesis of malignant tumor : multistep process , involves derangement of multiple genes normal function of cells Most malignancy do not have a clear hereditary genetic basis

Genetic cancer syndromes

Familial Retinoblastoma Li-Fraumeni syndrome Wilms Tumor Neurofibromatosis Type I Familial Adenomatous polyposis Multiple endocrine neoplasia Hereditary nonpolyposis colon cancer
6

Carcinogenesis :multistage process that leads to uncontrolled clonal cell growth evolution of normal cells into malignant cells Stage carcinogenesis: 1.Transformation 2.Growth 3.Local invasion 4.Metastasis

Carcinogen: any subtance when exposed to living tissue potential to lead cancer
1.Radiation : ultraviolet, ionizing 2.Infection agents: virus,bacteria,flatworms 3.Chemical : -direct acting initiators: vinyl chloride -indirect initiators (procarcinogen ) : polycyclic aromatic hydrocarbon 4.Foreign body reaction :asbestos, silica

What are intervals between exposure to a carcinogen and the development of cancer?
from a few years to decade Epidemiologic studies very complicated Smoking related cancers : after 15 years of exposure Asbestos related cancer : 25 40 years Ionizing radiation related skin cancer and leukemia : few years Malignancies of connective tissue , and adenocarcinoma : 15 30 years
9

Exposure in children
Appear more dangerous Carcinogenic interval : shorter Increased overall exposure concentration Increased level of replicating cells

10

How can prevent or minimized carcinogenesis

Minimize exposure to carcinogen Dont smoke Maintain healthy diet : adequate fiber , antioxidant Use sunscreen and limit intense sun exposure Childhood Immunization: avoid viral infection associated with cancer ( Hepatitis B) Hereditary risk cancer : intensive screening Treatment pre-cancerous lesion (e.g.excision) Avoid excessive iatrogenic drug (antineoplastic, estrogen,oral contraceptive,diethylstilbestrol )
11

How can we prevent or minimize carcinogenesis?

Choose cancer free abcestors Minimize exposure to carcinogens Dont smoke Maintain a nutritious diet with antioxidant Use sunscreen and limit intense sun exposure Immunization: avoid viral infection associated with cancer Intensive screening: for hereditary risk Treatment of pre-cancerous lesions Avoid excessive iatrogenic drugs and hormones
12

13