PRINCIPLES OF TOXICOLOGY

in lung, colorectal, and breast cancers (among the major cancer types) as well as being a key factor in
many rarer forms of cancer such as nevoid basal cell carcinoma. This area of research may well change
the way in which we view certain chemical exposures, as the risk of cancer may ultimately be shown
to be more a function of an individual’s or groups of individuals’ unique susceptibility to a given
chemical. Such information would not only improve our understanding of the carcinogenic process,
but it may alter chemical exposure regulation by allowing screening tests to eliminate potentially
susceptible persons from future potentially adverse exposures.
For example, El-Zein et al. report that the inheritance of variant polymorphic genes such as CYP2D6
and CYP2E1 for the activation of certain chemicals, and GSTM1 and GSTT1 for the detoxification of
certain chemicals, may predispose smokers with these traits to lung cancer. The importance of
identifying the range of phenotypic expression among specific genes is clearly manifest in the impact
that such changes may frequently make in the ultimate outcome of chemical exposure. In the future,
identifying gene variants have a large impact on epidemiological research, cancer prevention, and the
development of more effective intervention and treatment modalities. In addition, the ability to identify
those genetic traits that influence certain types of cancer might become useful biomarkers that enable
employers to place persons in positions that do not expose them to agents that would otherwise place
them at a greater risk than the normal population.
Because of the cell transformation that occurs in carcinogenesis, there is some “genetic” component
to every cancer. However, the traits referred to as one’s “genetic makeup” are only a portion of
the many factors that might occur in the progression from a healthy cell to an immortal, cancerous one.
The role of environmental factors, as they might impact or augment hereditary or genetic elements of
carcinogenesis are illustrated in Figure 13.11. The “all environmental risks” box in this diagram is
intended to represent the sum of all possible environmental insults; these might come from occupational
exposures, lower-level environmental chemical exposures (indoor air, drinking water, diet), diets and
dietary insufficiency, viruses and other infectious diseases, and important lifestyle factors (e.g.,
inactivity, smoking, drinking, illicit drug use).
Smoking
13.9 CANCER AND OUR ENVIRONMENT 313
The American Cancer Society (ACS) has compiled statistical data for the incidence of cancers in the
U.S. population (Figure 13.12). For six major cancer sites in males in the United States, only lung
cancers, which are far and away associated with tobacco smoking (perhaps 87 percent of all lung cancer
deaths), have shown any demonstrable increase in the last 65+ years. The data for female cancers were
similar. Lung cancer in females, driven by smoking, has now outstripped breast cancer as the leading
cause of cancer death among U.S. women. The ACS stated:
Figure 13.11 Interactions of environmental (lifestyle, diet viral, occupational) exposures and genes.