Molecular Epidemiology of p53 Protein Mutations in Workers Exposed to Vinyl Chloride

• Published in: American journal of epidemiology Vol. 147; no. 3; pp. 302 - 308
• Main Authors: Smith, Steven J., Li, Yongliang, Whitley, Ronda, Marion, Marie-Jeanne, Partilo, Steven, Carney, Walter P., Brandt-Rauf, Paul W.
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 01.02.1998
• Subjects: Adult; Aged; Antibodies, Neoplasm - analysis; Biological and medical sciences; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Biomarkers, Tumor - immunology; Carcinogens - adverse effects; Chemical and industrial products toxicology. Toxic occupational diseases; Enzyme-Linked Immunosorbent Assay; epidemiology; France - epidemiology; genes; hemangiosarcoma; Hemangiosarcoma - chemically induced; Hemangiosarcoma - epidemiology; Hemangiosarcoma - genetics; Humans; Incidence; liver neoplasms; Liver Neoplasms - chemically induced; Liver Neoplasms - epidemiology; Liver Neoplasms - genetics; Male; Medical sciences; Middle Aged; molecular; Molecular Epidemiology; Mutation - drug effects; Occupational Diseases - chemically induced; Occupational Diseases - epidemiology; Occupational Diseases - genetics; occupational exposure; Occupational Exposure - adverse effects; p53; protein p53; Retrospective Studies; Toxicology; Tumor Suppressor Protein p53 - drug effects; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - immunology; Various organic compounds; vinyl chloride; Vinyl Chloride - adverse effects; France; Europe; Human; Sarcoma; Toxicity; Liver; p53 Protein; Biological marker; Cardiovascular disease; Hepatic disease; Malignant tumor; Angiosarcoma; Occupational exposure; Carcinogenesis; Epidemiology; Vascular disease; TP53 Gene; Vinyl chloride copolymer; Digestive diseases; Mutation; Professional activity; Molecular biology; Onc gene; Occupational medicine; Public health; Tumor suppressor gene
• ISSN: 0002-9262; 1476-6256
• DOI: 10.1093/oxfordjournals.aje.a009450

The production of mutations in cellular tumor suppressor genes such as p53 is involved in the development of many human cancers. These mutations result in the expression of mutant forms of the encoded p53 protein which can potentially serve as a biomarker for this carcinogenic process. Workers exposed to vinyl chloride who are at risk for the development of the sentinel neoplasm angiosarcoma of the liver represent a model population for the study of such a mutant p53 biomarker, since vinyl chloride is known to cause specific p53 mutations in persons with angiosarcoma of the liver. To determine the relation between vinyl chloride exposure and this p53 biomarker, the authors examined serum samples collected between 1987 and 1992 from a cohort of 225 French vinyl chloride workers and 111 unexposed controls (matched according to age, sex, race, smoking, and alcohol drinking) for the presence of mutant p53 protein, using an enzyme-linked immunosor-bent assay. Stratification of the exposed workers by quartite of vinyl chloride exposure (in estimated ppm-years) yielded a statistically significant trend of increasing odds ratios for p53 biomarker seropositivity with increasing exposure. These results suggest that this serum biomarker for mutant p53 protein is related to vinyl chloride exposure and may be an early indicator of carcinogenic risk in exposed individuals. Am J Epidemiol 1998; 147: 302–8.