Inhalation of tobacco smoke

The association between cigarette smoking and lung
cancer is strong and well established (e.g. [3,5,6,37–
42]). The incidence of lung cancer is correlated with
the cumulative amount and duration of cigarettes
smoked in a dose–response relationship [7,38,43]
and smoking cessation results in decreased risk of
the disease, with the amount of decrease being re-
lated to time elapsed since the individual stopped
smoking [7,44]. Lung cancer rates and smoking
rates are also highly correlated in different geo-
graphic regions [45]. In 1991, Shopland et al. [46]
showed that the relative risk of lung cancer formale
smokers versus nonsmokers is 22.36 and that for fe-
male smokers versus female nonsmokers is 11.94.
They also estimated that 90% of lung cancers in
men and 78% in women were directly attributable
to tobacco smoking. Kondo et al. [47] showed a
significant (p < 0.001) dose–response relationship
between number of cigarettes smoked and the fre-
quency of p53 mutations in tumors of lung cancer
patients, suggesting that somatic p53mutationsmay
be caused in some way by exposure to a carcino-
gen/mutagen in tobacco smoke or itsmetabolites. A
review by Anberg and Samet [30] discusses this evi-
dence of the role of cigarette smoking in lung cancer
causation inmore detail. None of the evidence given
below for genetic susceptibility loci should be con-
strued as suggesting that cigarette smoking is not
the main cause of lung cancer.