HISTOLOGICAL VARIABILITY

The relative risk of smoking for the development of the different
histologies for lung cancer has been confirmed many times. 22–26
Figure 2.12 demonstrates these changes in the United States.
However, there is considerable variation between the different
histological types of lung cancer over time between genders and
between countries. Figure 2.13 illustrate the various proportion
of squamous cell versus adenocarcinoma lung cancer in several
countries in Asia and Europe. 27 This has been attributed to several
factors, including genetic susceptibility, but is more likely to
be the result of differences in the smoke chemistry of the cigarettes
smoked, which has changed substantially over time. 28
Although smoking patterns vary greatly worldwide, men
started smoking before women and smoked the cigarettes
of earlier times, whereas women predominantly smoked the
cigarettes of several decades later. 29 These latter cigarettes,
particularly in many Western countries, are lower in tar, more
likely to have ventilated filters, less polycyclic hydrocarbons,
and more tobacco-specific nitrosamines. 29–31 It is therefore
not surprising that women are more likely to develop adenocarcinoma
than the predominantly squamous carcinoma seen
previously in men. The histologic swing to adenocarcinoma
seen in men in recent decades is consistent with this concept as
they too smoke more of the lower tar and filtered cigarettes. It
has also has been demonstrated that nitrosamines vary considerably
around the world, even though they may have a common
manufacturer. 32
The occurrence of adenocarcinoma among Asian women,
many of whom do not smoke yet have a relatively high rate of
lung cancer, requires an alternative explanation.
The literature suggests that the increased risk for lung
cancer in Chinese women has been related to indoor air pollution
from cooking with oil, especially rapeseed oil, 33,34 biomass
fuel, and secondhand smoke. 35,36 Chinese women, and
Asian women in general, have low smoking rates; however,
in most areas they are increasing. Undoubtedly, these raising
rates of cigarette smoking will increase the rates of tobaccorelated
lung cancers. However, how it will impact the ratios of
squamous cell to adenocarcinoma will need to be assessed over
time. Presently, there has already been a shift in the rates from
predominance of squamous cell to adenocarcinoma in Japan,
Israel, and countries in Europe where the prevalence of male
smoking is still high. 37–40 As discussed previously, this shift in
histologies is probably related to the changing cigarette in the
various environments in addition to the increasing prevalence
of smoking-related cancer in women. These trends should be
followed closely—in addition to following how the cigarette
is changing over time in each of these environments. This is a
daunting task.
What might be easier would be to decrease the number of
people smoking, and therefore, more rapidly decrease the deaths
from lung cancer. This decrease can be obtained from tobacco
control efforts. 41 Figure 2.14 demonstrates the 6% decrease in
lung cancer incidence observed in California caused by the efforts
in decreasing initiation and increased cessation through
tobacco control efforts since 1988. 42 Peto et al.43 have concluded
that people who stop smoking in middle age can avoid
90% of their tobacco-attributable risk for lung cancer. In the
United States, the data suggested that the decline in smoking
over the past 50 years, accounted for 40% of the decline in overall
male cancer deaths and prevented 146,000 male lung cancer
deaths in the time period from 1991 to 2003. 44 Certainly, initiatives
of tobacco control, screening, and improved treatment
modalities should be pursued simultaneously. Even with strong
tobacco control policies, we will need the research to see how
best to identify and treat those that continue to be diagnosed
with lung cancer—tobacco related or otherwise.