Biomarkers and Molecular Epidemiology and Chemoprevention of Oral Carcinogenesis

Abstract

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 (GSTM 1) or cytochrome P450 (CYP450Al), 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.

Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: Use of fuzzy neural networks

“…Several reports have focused on the identification of useful markers such as molecules involved in the proliferation pathway or in the regulation of apoptosis, which may influence the cell death/cell viability balance toward cell proliferation or cancer. [46][47][48][49][50][51] In our study, different immunohistochemical markers of proliferation and apoptosis (PCNA, MIB-1, survivin) were evaluated in relationship to HR HPV infection by means of TS and FNN system analyses. The finding of an association of HPV infection with any of the markers considered could contribute to our understanding of the immunohistochemical cluster of OSCCs found more likely to be HPV-positive.…”

p53 as a prognostic marker associated with the risk of mortality for oral squamous cell carcinoma

“…For this reason, several studies have been performed on the biological patterns of the tumor, which are closely connected with its behavior (greater or lesser aggressiveness) and can predict the prognosis. Oncogenes expressed at varying percentages and associated modifications of chromosomal sites have been identified in oral tumors (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). The p53 tumor suppressor gene (expressed in 4-50% of cases) is the most studied oncogene detected on chromosome 17, and it is clear that preliminary knowledge of the p53 status may be of great assistance in managing OSCC (14)(15)(16)(17)(18).…”

Proapoptotic, Anti-Cell Proliferative, Anti-Inflammatory And Antiangiogenic Potential Of Carnosic Acid During 7,12 Dimethylbenz[A]Anthracene-Induced Hamster Buccal Pouch Carcinogenesis

“…Tobacco and alcohol consumption, in various forms, are strongly attributed to the pathogenesis of oral cancer (Saba et al, 2011). Despite significant improvements have been made for oral cancer treatment with surgical therapy, radiation therapy and chemotherapy, the overall five year survival rate of oral cancer patients remains at about 50% and has not significantly improved for the last three to four decades (Schwartz, 2000). Oral squamous cell carcinoma (SCC) often has a poor prognosis, owing to local tumour invasion and frequent lymph node metastasis.…”