The past four decades of epidemiological research have yielded valuable information on the risks of populations to environmental exposures such as tobacco,
asbestos, and dietary components. Prevention efforts have been focused on large-scale population-based interventions to minimize exposure to such external
carcinogens. While some
cancers are beginning to show a decline from changing environmental exposures,
hormone-related
cancers, such as breast and prostate, are becoming more prevalent. The development of these
cancers appears to be closely related to endogenous exposures to circulating
steroid hormones. Although prevention trials using antihormone agents are proving successful in some instances, the long-term control of these
cancers necessitates a clearer understanding of the metabolism and transport of the relevant
hormone in vivo. The revolution in molecular biology has provided powerful genetic tools for evaluating mechanisms of
cancer causation as well as the potential to better define individual susceptibility. Using tobacco exposure as an example, we and others have demonstrated that polymorphisms in genes controlling aromatic
amine metabolism provide at least a partial explanation for ethnic and individual susceptibility to
bladder cancer. Similar studies have examined genetic polymorphisms in the metabolism of tobacco
smoke and
lung cancer risk, red meat and
colorectal cancer, and
aflatoxin and
liver cancer. Our current studies have pursued a similar paradigm of genetic polymorphism and individual
cancer susceptibility in prostate and breast
carcinogenesis. We are evaluating polymorphisms in the
steroid 5 alpha-reductase type II and
androgen receptor genes in relation to
prostate cancer based on the evidence that intracellular
dihydrotestosterone is the critical "
carcinogen." We are pursuing genetic polymorphisms affecting
estradiol metabolism, including those in the 17 beta-
hydroxysteroid dehydrogenase 2 and
estrogen receptor genes as they relate to susceptibility to
breast cancer. The potential role of a polymorphism in the
cytochrome P450c 17 alpha gene in both breast and
prostate cancers is also being examined.