Cancer Epidemiology and Carcinogenesis
Cancer Epidemiology and Carcinogenesis
Cancer Epidemiology and Carcinogenesis
AND CARCINOGENESIS
DR MUHAMMAD ALI SOOMRO
DEFINATION:
The study of the prevalence, causes, and
distribution of malignant disease in certain
populations is known as cancer epidemiology.
The goal is to identify the contributing causes
so that preventive measures can be developed
to manage the disease.
Epidemiologic evaluation gives the doctor a
way to quantify the cancer risk, lays out the
rationale for screening methods for high-risk
populations, and assesses the effectiveness of
any preventative measures.
EXAMPLES:
The now well established concept that cigarette
smoking is linked with lung carcinoma arose
from the epidemiological data.
A comparasion of incidence rates of colon cancer
between Europe and Africa, revealed that
consumption of higher quantities of red meat
and lack of fiber in diet led to raised risk of
colon adenocarcinoma.
Certain diseases associated with a raised risk for
developing cancer also provide clues to
pathogenesis of cancer.
CANCER INCIDENCE:
An increase in population has led to risk of
carcinogenesis of variety of carcinomas.
By 2035, it is estimated that there would be 24
million cases of cancer and 14 million deaths by
cancer globally.
With passage of time, cancer mortality has
altered significantly. Among men, 80% decline
in mortality is seen amongst victims of lung,
prostate and colon carcinomas.
CANCER INCIDENCE:
Among women, 60% decline in mortality has
been seen in cases of breast, cervix and
colorectal carcinomas.
This comes in lieu of the fact that a better
understanding and preventive measures have
been taken into account for the purpose of
treatment on prompt grounds.
ENVIRONMENTAL FACTORS:
Environmental factors are dominant cause
behind the carcinogenesis.
Variation with regards to exposure of
environmental pathogens and with respect to
geography are regarded as stem factors behind
carcinogenesis of various cancers and
mortality.
Nearly all these evidences from various regions
have indicated that environmental influence
impact the pathogens in carcinogens.
EXAMPLE:
Mortality from breast carcinoma is higher in
Europe and America than in Asia.
Liver cancer is more lethal in Africans in
contrast to America where it is rare.
IMPORTANT ENVIRONMENTAL
FACTORS:
DIET: variation in dietary habits especially lack of
fiber in diet and obesity is the main reason behind
carcinogenesis of colon carcinoma.
SMOKING: tobacco consumption has lead to
raised risk of carcinomas of esophagus, bladder
and especially lung.
ALCOHOL: Alcohol consumption leads to
cirrhosis and ultimately liver carcinoma.
SEXUAL HISTORY: Multiple sexual contacts with
different partners has lead to increased risk of
cervical carcinoma in women in the west.
IMPORTANT ENVIRONMENTAL
FACTORS:
HORMONAL IMBALANCE: Alteration in
progestrone and estrogen leads to breast
carcinoma risk in women.
Infectious Agents: Agents like parasites,
viruses, bacteriae etc raise the risk of
carcinoma. Example: Schistoma are common
cause of urinary bladder carcinoma.
AGE AND CANCER:
Majority of carcinomas occur between 55 to 75
years age.
Somatic mutations accumulated in genetic
matter with passage of age leads to inactivation
of various genes responsible for healthy cells.
The decline in immune competence that
accompanies aging may also be a factor behind
carcinogenesis.
ACQUIRED CONDITIONS LEADING
TO CANCER:
Conditions like disorders linked with chronic
inflammation, immuno-deficiency and pre-
cursor lesions are well known stem factors
behind various cancers.
Chronic inflammatory disorders often end up
in carcinomas but cases of mesotheliomas and
lymphomas do occur.
Precursor lesions are lesions linked with local
disturbances of epithelial diffrentiation linked
with high risk of carcinogenesis.
ACQUIRED CONDITIONS LEADING
TO CANCER:
Molecular analysis have revealed that precursor
lesions often have some of genetic lesions found
in their associated cancers. Some of the precursor
lesions leading to cancer are as follows:
Squamous metaplasia and dysplasia in lung leading to
bronchogenic carcinoma
Endometrial hyperplasia and dysplasia leads to
endometrial carcinoma.
Leukoplakia of oral cavity, vulva and penis lead to
squamous cell carcinoma in the respective regions.
Villous adenoma leads to colon adenocarcinoma.
INTERACTION OF GENETIC AND
ENVIRONMENTAL FACTORS:
Cancer behaves like an inherited trait in some families
usually due to germ line mutations that affect the
function of a gene that suppresses cancer.
Instances like these involve inherited enzymes like
components of cytochrome 450 that metabolizes pro-
carcinogens to active carcinogens.
Also the environment in which the genes have been
impacting the nature of disease also impact the nature
of disease.
Breast cancer risk is three fold higher in women in
BRCA 1 and 2 mutation born after 1940 than in
women born prior to 1940.
CANCER GENES:
Cancer is a disease caused by mutations that alter
the function of a finite subset of 20,000 or so
human genes. We call them as onco-genes.
Cancer genes can be defined as genes that are
recurrently affected by genetic abberations in
cancers, presumably as they contribute directly
with the malignant behavior of cancer cells.
Causative mutations that give rise to cancer genes
may be acquired by action of environmental
agents such as chemical, radiation or viruses may
occur spontaneously or might be inherited.
CANCER GENES:
Cancer genes fall into 4 categories:
ONCOGENES: Genes that induce a transformed
phenotype when expressed in cells by promoting
increased cell growth. Often arise as mutated versions of
proto-oncogenes.
Most genes translate into transcription factors, pro-
growth signals, and cell survival enhancers.
TUMOR SUPRESSOR GENES: These prevent abnormal
proliferation of cells, and when mutated lead to
neoplastic changes.
There are two suppressors:
GOVERNORS: Serve as important brakes in cell growth
GUARDIANS: Sensing damage in genome.
CANCER GENES:
APOPTOSIS REGULATING GENES: Act by
enhancing cell survival rather than stimulating
proliferation. Genes that promote apoptosis are over
expressed in neoplasia.
GENES REGULATING INTERACTION BETWEEN
TUMOR AND HOST CELLS.
CARCINOGENESIS: A MULTISTEP
PROCESS