world cancer report - iarc

ventive options, and may be relevant to
the prevention of other environmentallyinduced
cancer.
Mainstream smoke (the material inhaled
by smokers) is an aerosol including
approximately 4,000 specific chemicals
and containing 10 10 particles per ml. The
particulate matter (tar) is made up of
some 3,500 compounds, the most abundant
being nicotine (0.1-2.0 mg per cigarette)
and also including most of the polycyclic
aromatic hydrocarbons occurring in
the smoke [14]. Another class of carcinogens
represented in tobacco smoke is
N-nitroso compounds, particularly including
the nitroso derivatives of nicotine and
nornicotine [15]. Chemicals such as aromatic
amines, benzene and heavy metals,
independently established as carcinogenic
for humans, are present in tobacco
smoke (Table 2.2). Use of smokeless
tobacco results in exposure to tobaccorelated
nitroso compounds, but not to
polycyclic aromatic hydrocarbons, which
are products of combustion.
Cancer causation by tobacco smoke is not
attributable to any one chemical component,
or any one class of chemicals present,
but to an overall effect of the complex
mixture of chemicals in smoke.
Mechanistic inferences which can be
made from epidemiological studies,
together with relevant experimental data,
indicate a scenario compatible with “multistage
carcinogenesis” as understood at
the cellular and molecular level
(Multistage carcinogenesis, p84) [16].
Epidemiological studies indicate that for
cancers of the lung, bladder and head and
neck (data for other cancers are inadequate
for such evaluation), the various
carcinogens in tobacco smoke exert an
effect on both early and late steps in the
process of carcinogenesis. Evidence for
early effects comes from the higher risk
associated with early age at starting
smoking and with increasing time since
beginning smoking, while the continued
elevated risk, albeit at decreasing levels
over time, following quitting smoking is a
strong argument for late effects.
Most chemical carcinogens in tobacco
smoke require metabolic activation in
order to exert a carcinogenic effect [17].
Fig. 2.8 Estimated prevalence of smoking among adults by region, in the early 1990s.
Fig. 2.9 A model describing stages of the tobacco epidemic based on data from developed countries.
Note the time lag between increase in consumption and the manifestation of lung cancer
The requisite enzymes are present in lung
and other “target” organs. Individual risk
may be affected by the activity and levels
of enzymes such as glutathione-S-transferase,
cytochrome P450 and N-acetyl
transferases. In the course of metabolism,
reactive forms of polycyclic aromatic
hydrocarbons, nitrosamines and aromatic
amines are generated and become covalently
bound to DNA in relevant tissues.
Such DNA adducts, and the products of
their repair, have been detected in tissues,
bodily fluids and urine from smokers and
from persons exposed to environmental
tobacco smoke.
The molecular genetics of tobacco smokeinduced
lung and other cancers are being
progressively elucidated. An increasing
number of genes are implicated as being
relevant to a carcinogenic outcome [18].
The degree of current understanding is
exemplified by studies of the pattern of
mutation in the p53 gene. When comparison
is made of particular mutation frequencies
in lung cancers from smokers
and non-smokers, differences are evident.
Using relevant experimental systems,
mutations evident in smokers are attributable,
at least in part, to the miscoding
caused by the binding of some polycyclic
aromatic hydrocarbons to DNA [19].
Tobacco 27