CANCER RISK FACTORS

CANCER RISK FACTORS

MAJOR MODIFIABLE RISK FACTORS

OTHER MODIFIABLE RISK FACTORS

CANCER RISK FACTORS

NON - M0DIFIABLE RISK FACTORS

OTHER RISK FACTORS

 MAJOR MODIFIABLE RISK FACTORS

TOBACCO USE

UNHEALTHY DIET

INFECTIOUS AGENTS

ULTRAVIOLET RADIATION

PHYSICAL INACTIVITY
 TOBACCO
The Major Etiologic and Risk Factor of the Development of
Cancer and Nonneoplastic diseases

Totok Utoro
Department of Pathology
Gdjah Mada University School of Medicine
 Tobacco
3000 chemicals are present in tobacco smoke, 60 of which
recognize as carcinogen : nitrosamines and polycyclic
aromatic hydrocarbons

Become carcinogen when activated by specific enzymes

found in many tissues in the body

The compounds can become part of DNA

(deoxyribonucleic acid) molecules and possible interfere
with the normal growth of cells
 Tobacco

Tobacco use is the environmental exposure

most widely known to be associated with an
increase risk of cancer as well as several
nonmalignant diseases.
The associated cancer :
Lung Pancreas
Larynx Kidney
Pharynx Cervix ( uteine )
Esophagus Breast
Bladder
CANCER AND TOBACCO
CANCER AND TOBACCO
Absorption
&
Distribution
of
Toxicants
 SMOKING
Is the largest single preventable cause of death
in the USA (440,000 premature deaths per year)
Direct health cost: tens of billions of dollars a
year ($157 billion)
Estimates have incriminated tobacco in:
- 11-30% of cancer deaths
- 17-30% of cardiovascular deaths
- 30% of deaths from lung diseases (other than cancer)
- 20-30% of the incidence of low-birth-weight infants
 SMOKING
The major diseases responsible for the excess mortality
in cigarette smokers are (in order of frequency):
- coronary heart disease
- cancer of the lung
- COPD (chronic bronchitis and emphysema)

Beginning in the World War I, annual cigarette

consumption increased in men, followed by women
reaching a peak of 4336 cigarettes per capita in 1963
declined to less than 3000 in 1995
 SMOKING
Early exposure to carcinogens in tobacco smoke may
increase risk of developing lung cancer among
children and adolescents smoking continues to be a
major public health problem

Smoking may interacts with other environmental and

occupational exposures in additive or synergistic fashion
(cigarette smokers exposed to asbestos increase in
risk of lung cancer)
 Absorption at Portals of Entry

The inhaled agents of cigarette smoke may act

directly on the:
Mucous membranes
May be swallowed in saliva
May be absorbed into the bloodstream from the
abundant alveolar capillary bed
The mainstream of the cigarette smoke

Particulate phase
Tar: is the total particulate phase without water and
nicotine
- 0.3 3.3 particles per milliliter of mainstream smoke
- more than 4000 constituents including 43 known
carcinogens
Carcinogenic metals: As, Ni, Cd, Cr
Potential promoters: acetaldehyde, phenol
Irritants: nitrogen dioxide, formaldehyde
Nicotine
Gas phase
Carbon monoxide
 Carbon monoxide
Colorless, odorless gas produced during incmplete
combustion of fossil fuels or tobacco
It has 200 times higher affinity for Hb than O2 does
Exposure CO decreases the delivery of O2 to peripheral
tissue
Binds to other heme-comtaining protein such as
myoglobin and cytochrome oxidase
 Nicotine
Important constituent of cigarette smoke
Nicotine is responsible for tobacco addiction
Alkaloid that readily crosses the blood-brain
barrier stimulate nicotine receptor
pharmacologic effects associated with tobacco
use (most likely mediated by catecholamines):
- increased heart rate & blood pressure
- increased coronary artey blood flow
- increased contractility and cardiac output
- increased mobilization of fatty acids
 Organ Specific Carcinogens in
Tobacco Smoke
Lung, larynx Polycyclic aromatic hydrocarbon
4-(Methylnitrosoamino)-1-(3-pyridyl)-1-butanone
(NNK)
Polonium 210
Esophagus N-Nitrosonornicotine (NNN)

Pancreas NNK (?)

Bladder 4-Aminobiphenyl, 2-naphthylamine

Oral cavity Polycyclic aromatic hydrocarbon, NNK, NNN

(smoking)
Oral cavity NNK, NNN, Polonium 210
(snuff)
The risk of dying in smokers and nonsmokers
 Cardiovascular Disease is a
Major Complication of Smoking

Cigarette smoking is recognized as a major independent

risk factor for myocardial infarction, and acts
synergistically with other risk factors such as high blood
pressure and elevated blood cholesterol levels

Atherosclerosis of coronary arteries and the aorta is

more severe and extensive among cigarette smokers
than among nonsmokers, and the effect is dose related
The risk of myocardial infarction in
cigarette smokers
Cancer of the Lung is Largely a
Disease of Cigarette Smokers

More than 85% of deaths from cancer of the lung are

attributed to cigarette smoking, the single most common
cancer in both men and women in the USA today
 Diseases associated
with cigarette smoking
Death rate from lung cancer among smokers &
non-smokers
Dose dependent relationship between cigarette smoking
and the risk of lung cancer
Dose dependent relationship between cigarette smoking
and the risk of pancreatic cancer
 Xenobiotic metabolism

Phase I reaction :
1. Aromatic Hydroxilation and Epoxidation
2. Oxidation by FMO System
3. Peroxidase-Dependent Cooxidation
4. Reduction of NADPH-Cytochrome P-450 Reductase

Phase II Reactions :
1. Activation by Glucuronidation
2. Biomethylation
3. Activation by Cytochrome P-450 and Detoxification by
Glutathion Conjugation
 Xenobiotic metabolism
Phase I reaction :

1. Aromatic Hydroxilation and Epoxidation (benzo(a)pyrene

covalent binding to DNA lung & skin cancer)
2. Oxidation by FMO (flavin-containing monooxygenase)
System (Nicotine Nicotine-1-N-oxide)
3. Peroxidase-Dependent Cooxidation (2-Naphthylamine
self coupling)
4. Reduction of NADPH-Cytochrome P-450 Reductase
(Paraquat)
 Xenobiotic metabolism

Phase II Reactions :

1. Activation by Glucuronidation (2-Naphthylamine N-

Hydroxy- 2-Naphthylamine Bladder cancer)
2. Biomethylation (inorganic mercury dimethyl mercury)
3. Activation by Cytochrome P-450 and Detoxification by
Glutathion Conjugation(Vinyl chloride covalent binding to
macromolecules cancers?)
 Death per Year Attributable to
Cigarette Smoking in the US
Cause of Death No.of Death No.of Death
(Men) (Women)
Cancer 102,812 54,664
Cardiovasc.disease 90,906 57,699
Respiratory disease 53,713 44,429
Residential fires 589 377
Perinatal death 598 407
Lung cancer & heart 15,517 22,536
disease attributable to
passive smoking
Total 264,135 80,112
Lung cancer
Lung cancer
(squamous cell carcinoma)
Lung cancer
(small cell carcinoma)
 Smokers Develop
Nonneoplastic Diseases
Chronic bronchitis & emphysema are primarily dose-
related disease of smokers
Peptic ulcer disease has 70% greater prevalence in male
cigarette smokers than nonsmokers
Osteoporosis: women who smoke > I pack at the
time of menopause exhibit 5-15% deficit in bone density
enough to increase the risk of bone practure
Thyroid disease Graves disease
Occular disease macular degeneration & cataract
The association between cigarette smoking and
pulmonary emphysema
EMPHYSEMA
Smoking Impairs Female
Reproductive Function
REPRODUCTIVE AND HORMONAL FACTORS
Effect of smoking on birth weight
Effect of smoking on the incidence of abruptio placentae
Effect of smoking on the incidence of placenta previa
Effect of smoking on the incidence of
the premature rupture of membrane
 Passive Smoking is defined as
Exposure of Nonsmokers to Smoke
Produced by Tobacco Smokers

Risk associated with exposure to sidestream

smoke also called Environmental Tobacco
Smoke (ETS)
Especially hazardous to infants and young
children (sudden infant death syndrome,
increased incidence of respiratory and ear
infection, exacerbation of asthma)
 Non-neoplastic Diseases Associated
with Cigarette Smoking (on the right)

Diseases Associated
with
Cigarette Smoking

Cancers incidences are known to

be increased in cigarette smokers
 RESUME
Cardiovascular Disease is a Major Complication
of Smoking
Cancer of the Lung is Largely a Disease of
Cigarette Smokers
Smokers Develop Nonneoplastic Diseases
Smoking Impairs Female Reproductive Function
Passive Smoking is defined as Exposure of
Nonsmokers to Smoke Produced by Tobacco
Smokers
Other risk factors
 OTHER MODIFIABLE RISK FACTORS

ALCOHOL USE

OCCUPATIONAL EXPOSURES

SOCIOECONOMIC STATUS

ENVIRONMENTAL POLLUTION

OBESITY

FOOD CONTAMINANTS

IONIZING RADIATION
 ALCOHOL USE
Heavy alcohol use causes cancers of the oral cavity,
oesophagus, liver and upper respiratory tract. The cancer risk
is greatly increased by concurrent smoking. Alcohol use also
increases the risk of breast cancer.

OCCUPATIONAL EXPOSURES
Certain substances encountered of work are carcinogens,
including asbestos, arsenic, benzene, silica and second-hand
tobacco smoke. Lung cancer is the most common occupational
cancer.

SOCIOECONOMIC STATUS
Some cancers occur more often in people with a higher socio-
economic status ( SES ); others are more common in lower-SES
populations. SES is most likely a marker for lifestyle and other
risk factors described in this section.
 INFECTIOUS AGENTS
Infectious agents account for 18% of cancers worldwide.
Human papillomavirus, hepatitis B virus, and the helicobacter
pylori bacterium account for the largest number of cancers
due to infections.

ULTRAVIOLET RADIATION
Sunlight is the major source of UV radiation, which causes
several types of skin cancers, the most common malignancy
in humans

PHYSICAL INACTIVITY
A sedentary lifestyle increases the risk of colon cancers,
and may increase the risk for other types of cancer. Its
effects are closely related to an individuals nutrition
Occupational Exposures
 ENVIRONMENTAL POLLUTION
Pollution of air, water and soil account for between 1% and
4% of all cancers in developed nations.

OBESITY
Obesity is an important risk factor for endometrial, kidney,
gallbladder and breast cancers.

FOOD CONTAMINANTS
Certain food contaminants are carcinogenic, including those
that occur naturally ( eg aflatoxins ) and those that are
manufactured ( eg pesticides )

IONIZING RADIATION
For most, the greatest exposure to ionizing radiation comes
from medical X rays. But we are all exposed to small
amounts of naturally occurring radiation.
 NON MODIFIABLE RISK FACTORS

AGEING

ETHNICITY OR RACE

HEREDITY

SEX
 AGEING
The risk of most types of cancer increases with age. The
highest cancer rates occur among the elderly.

ETHNICITY OR RACE
The risk of many types of cancer varies between racial
and ethnic populations. Some of these differences are
attributable to genetic differences, but most are due to
differences in lifestyle and exposures to cancer causing
agents.

HEREDITY
Inherited cancer genes may cause 4% of all cancers.
Other genes affect our susceptibility to cancer risk factors.

SEX
Certain cancers occur in only one sex due to different
anatomy, eg prostate, uterus. Others occur in both sexes,
but at markedly different rates, eg bladder, breast.
 Genetic makeup
Children with primary immunodefficiency
disorders have an extremely high rate of
lymphoid malignancies.
The incidence of acute leukemia is
4 30 times higher in person with Down
Syndrome> normal.
Translocation of chromosomes 8 and 14 is
associated with Burkitts lymphoma.
 PROPORTION OF CANCERS
CAUSED BY MAJOR RISK FACTORS
 ENVIRONMENTAL POLLUTION
Pollution of air, water and soil account for between 1% and
4% of all cancers in developed nations.

OBESITY
Obesity is an important risk factor for endometrial, kidney,
gallbladder and breast cancers.

FOOD CONTAMINANTS
Certain food contaminants are carcinogenic, including those
that occur naturally ( eg aflatoxins ) and those that are
manufactured ( eg pesticides )

IONIZING RADIATION
For most, the greatest exposure to ionizing radiation comes
from medical X rays. But we are all exposed to small
amounts of naturally occurring radiation.
INFECTION AS A CAUSE OF CANCER
ULTRAVIOLET RADIATION
SEX DIFFERENCES
New cancers cases by sex
2002
THANK YOU