Gene p53 mutations, protein p53, and anti-p53 antibodies as biomarkers of cancer process.
The finding that gene mutations and changes in their expression form the basis of cancer processes, has prompted molecular epidemiologists to use biomarkers for detecting damaged genes or proteins synthesized under their control in easily available cellular material or systemic liquids. Mutations in the suppressor gen p53 are thought to be essential for cancer development. This gen is one of the most important regulators of transcription, cellular cycle, DNA repair and apoptosis detected till now. Inactivation of gene p53 leads to uncontrolled cell divisions, and further to transformation of normal cells into the carcinous ones. Observations that mutations in gene p53 appear under conditions of occupational and environmental exposures to chemical and physical carcinogens, such as vinyl chloride, radon, or aflatoxin B1, have proved to be of enormous importance for the occupational and environmental health. Changes in expression of gene p53, and also its mutations, cause variations of cellular protein p53 concentration. Higher cellular protein p53 levels are associated with increased protein transfer to the extracellular liquid and to blood. It has been observed that increased blood serum protein p53 concentrations may have a prognostic value in early diagnosis of lung cancer. The results of a number of studies confirm that accumulation of a mutated form of protein p53, and presumably also large quantities of wild forms of that protein in the cells, may be a factor that triggers the production of anti-p53 antibodies. Statistical analysis showed that anti-p53 antibodies can be regarded as a specific biomarker of cancer process. The prevalence of anti-p53 antibodies correlated with the degree of cancer malignancy. The increased incidence of anti-p53 antibodies was also associated with higher frequency of mutations in gene p53. There are some reports confirming that anti-p53 antibodies emerging in blood serum in the subclinical phase of cancer development may be associated with the occupational exposure to the carcinogenic agents.
Lutz
Waldemar
W
Department of Immunotoxicology, Nofer Institute of Occupational Medicine, Lódź, Poland. lutz@imp.lodz.pl
Nowakowska-Swirta
Ewa
E
D000906:Antibodies / Q000276:immunology*; D014408:Biomarkers, Tumor; D016158:Genes, p53; D006801:Humans; D017720:Molecular Epidemiology; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D011044:Poland; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
D000906:Antibodies; D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53