Critical Reviews in Oral Biology & Medicine, Vol 11, 92-122, Copyright © 2000 by International & American Associations for Dental Research
Biomarkers and molecular epidemiology and chemoprevention of oral carcinogenesis
J. L. Schwartz
Howard University, College of Dentistry, Department of Oral Maxillofacial Pathology, Washington, DC 20059, USA.
Chemopreventives are chemicals that prevent the formation of cancers such
as oral cancer. They can take the form of nutrients or synthetic molecules,
and their fundamental characteristic is that they do not produce disease
processes that would result in debilitating symptoms. Current evidence
indicates that they function by modifying the oxidative state of
transforming cells. Biomarkers can take the form of genetic and molecular
indicators, which characterize the function of chemopreventives and cancer
processes such as oral carcinogenesis. Biomarkers cannot provide all the
required information for risk assessment or possible activity of the
chemopreventives. Other methods, such as epidemiological analyses and
techniques, must be used to enhance our understanding of the risk for oral
cancer in human populations. One common epidemiologic method, the
questionnaire, helps to determine the use and carcinogenic potential of
tobacco and alcohol during oral carcinogenesis. Genetic and molecular
changes in human patient populations may result in a reduction in the
number and function of tumor suppressor genes. If these changes are to be
assessed, the tissues (e.g., buccal mucosa) must be accessible and
harvested in a reliable and consistent manner for the acquisition of DNA,
mRNA, and protein. Oral tissues provide sufficient quantities of these
molecules and, under stringent conditions, the quality required for the
isolation of these molecular constituents. In conjunction with
epidemiologic techniques, various genotypic polymorphisms, such as
glutathione-S-transferase (GSTM1) or cytochrome P450 (CYP450A1), have
indicated a loss in carcinogen detoxification or the processing of internal
growth control signals. Biomarkers are composed of a large diverse group of
genetic and molecular structures. Some of these biomarkers are indicators
for programmed cell death (PCD), while others describe malignant tumor
growth. Many of these classes of molecules are oxidative-responsive (e.g.,
tumor suppressor p53, Bcl-2, growth factors, immune-derived proteins, and
death-inducing molecules) and induce PCD by triggering a cascade of
cysteine proteases and regulators (e.g., caspases, death receptors). This
pathway results in cell-cycle alterations and DNA fragmentation. It is
hoped that a detailed knowledge of the processes involved in malignant
transformation will better define the biomarker-screening tools for oral
cancer. These tools will enhance our ability to predict the incidence of
cancer, detect early malignant change, and quantitate chemoprevention
during oral carcinogenesis. Chemopreventives such as the retinoids have
already demonstrated their ability to suppress potential malignant changes
in pre-malignant oral leukoplakias and decrease the incidence of second
head-and-neck cancer primaries. It is our hope that this review will
increase investigators' interest in developing new screening and detection
systems for oral cancer.
