Download Lung Cancer


Most frequently diagnosed cancer
worldwide
› About 1.35 million new cases diagnosed
worldwide each year

Leading cause of cancer deaths in the
United States

Incidence and
mortality rates
begin to
increase
between the
ages of 45 and
54 and rise
progressively
until age 75

Median age at
diagnosis=70.07

Median age at
death=71.07

Males have a greater lifetime risk of lung
cancer than females (7.81% vs. 5.8%)
› Greater disparity in developing countries
where cigarette use by females is low

AfricanAmericans
have the
highest
incidence
and
mortality,
Hispanics
have the
lowest

Patterns of mortality tend to cluster with
in areas with high prevalence of
cigarette smoking
› In the US, highest rates in Kentucky, lowest in
Utah
› Number of cases highest in California, lowest
in Alaska
› Worldwide, most cases are seen in the
developed countries of North America,
Western Europe, and Australia/New Zealand

Current overall 5 year survival rate is 11%
› Impacted by age, tumor stage, histological
subtype, and treatment

Developed countries have higher survival
rates than developing countries (13% vs.
9%)

Improvements in diagnostic and
therapeutic technologies have contributed
to an increase in survival
› 1 year survival 37% in 1975, 42% in 2000

Higher incidence and mortality rates are
reported among men from lower SES
groups

Cigarette smoking is the most important risk
factor for lung cancer
› Causes approximately 90% of male and 75-80%
of female lung cancer deaths

By the early 1950s, case control studies in
the US and Great Britain clearly showed an
association between smoking and lung
cancer

In 1964, the US Surgeon General released a
report on the causal relationship

United Kingdom
› Cumulative risk of death from lung cancer
rose from 6% in 1950 to 16% in 1990 in male
cigarette smokers

Relative risk of lung cancer after smoking
cessation begins to decrease after 5
years but never reaches the risk of a nonsmoker

More than 80 carcinogens in cigarette
smoke according to the International
Agency for Research on Cancer (IARC)
› Polycyclic aromatic hydrocarbons (PAHs)
are a well documented lung carcinogen
› NNK has been shown to induce lung
carcinoma

History of respiratory diseases such as
asthma, bronchitis, emphysema, hay fever,
or pneumonia may modify risk

When combined with smoking, there is a
complementary cycle of injury and repair
that may increase risk

Respiratory diseases may result in chronic
immune stimulation that causes random
pro-oncogenic mutations that increase risk

Relationship is still speculative

Animal models have indicated that
dietary fat can promote chemically
induced pulmonary tumors
› Relationship may be confounded by the
association between smoking status and diet

Rates of lung cancer are highest in
countries with greatest fat consumption
after controlling for smoking

Lowered risk associated with consumption
of fresh vegetables and fruits
› Case-control and cohort studies
› Risk in those with highest intake was about one-
half of those with lowest intake

Beneficial micronutrients in fruits and
vegetables
›
›
›
›
Carotenoids
Isothiocyanates
Folate
Selenium

Difficult to assess association between
alcohol and lung cancer due to
confounding by smoking status
› Conflicting results of cohort and case-control
studies

IARC categorized several occupational
agents as known carcinogens
› Radon
 Well established lung carcinogen, responsible for 6.5%
of lung cancer deaths in the United Kingdom in 1998
› Asbestos
 SMR for lung cancer= 1.65, dose dependent risk
› Arsenic
› Bischloromthyl ether
› Chromium
› Nickel
› Polycyclic aromatic compounds
› Vinyl chloride

Only a fraction of long-term smokers will
develop lung cancer
› Likely impacted by genetic susceptibility

Familial aggregation
› Studies have reported an excess of lung
cancer mortality in relatives of lung cancer
patients
Polymorphisms in genes encoding for
enzymes responsible for detoxification of
carcinogens affect the internal dose of
tobacco carcinogens that lung tissue is
exposed to
 Many different polymorphisms

› Cytochrome P-450

Defective repair of genetic damage is an
important determinant of susceptibility to
lung cancer
› Hypersensitivity to carcinogenic exposure

Many studies have demonstrated that
cancer cases have a significant
decrease in DNA repair capacity
compared to controls
Genes Involved in Methyl Metabolism
 Cell Cycle Control


Prevent smoking

Screening
› Early detection improves resectability and survival
› Methods
 Low-dose spiral CT
 Combination of chest X-rays and sputum cytology
› May only be cost-effective in high-risk populations

Correlating biomarkers from surrogate
tissues with molecular changes in lung
tissue
› Markers should be readily accessible (blood)
› Provide non-invasive evaluation of risk,
physiologic and pathophysicological states

Chemoprevention and chemotherapy
Cancer Epidemiology, 3rd ed. 2006.
Oxford University Press
 Centers for Disease Control
 American Cancer Society
