There is no doubt that
hormones have a role in the development of many, perhaps most,
cancers. This is because they are vital in maintaining homeostasis in multicellular organisms in which
cancer appears. The stage or stages at which
hormones are important in the process are not known well, but experiments in animals indicate that hormonal intervention at initiation, promotion, or progression can be important, assuming that such neat division pertains to
cancer development in humans (Schmähl, 1985).
Hormones may affect initiation through control of the levels of activating and detoxifying
enzymes in the liver and other organs, which affect the pharmacokinetics of
carcinogens to which the animal is exposed.
Hormones control the levels of structural or functional components of some organs, for example, the alpha-2 micro-
globulin in the kidney of male rats, which affect the disposition of foreign chemicals.
Hormones have enormous influence on growth and development of animals and must play a part in the well-known heightened susceptibility of young animals (including humans) to the effects of exposure to
carcinogens. Animals exposed in utero to transplacental
carcinogens, or those exposed to single doses as newborns or infants, frequently develop
tumors that appear in animals treated as adults not at all or after exposure to much higher doses. Examples are
nervous system tumors in rodents exposed transplacentally (Ivankovic, 1979) and liver
tumors in rodents treated as infants (Vesselinovitch et al., 1979). It is probable that effects of
hormones on cell proliferation are an important part of these effects. From the studies of hormonal effects on
carcinogenesis in animals we can conclude that alterations in the function of
hormones through inheritance, or through diet, habits, accidents, disease states, or sexual maturity could affect susceptibility of an individual to
carcinogens, thereby increasing or decreasing the probability of developing
cancer. Compounds with antithyroid properties (e.g.,
thiouracil or
ethylene thiourea, a contaminant and by-product of many
thiocarbamates widely used in agriculture and industry) or substances affecting adrenal or pituitary secretions might be implicated as modulators of
tumor development, following the leads suggested by experiments in animals described above.
Castration, aging, or hypersecretion of
sex hormones would also modulate the effects of
carcinogens, as they do in experimental animals. There have been few studies of the effects of other
hormones such as
insulin,
gastrin,
prolactin, and so forth (Griffin et al., 1955), although these vital
hormones vary in distribution even within an individual at different times. An early study (Sugiura and Benedict, 1933) failed to show an effect of treatment with a variety of
hormones on the growth of several transplanted
tumors. One elusive mystery is why
estrogens and
diethylstilbestrol induce kidney
tumors in Syrian hamsters but not mammary
tumors, whereas in rats they give rise to mammary
tumors but not to kidney
tumors. Obviously we need to know much more about biology in order to better understand the intricacies of neoplastic transformation and development of
cancer.