MOLECULAR EPIDEMIOLOGY OF P53 PROTEIN MUTATIONS IN WORKERS EXPOSED TOVINYL-CHLORIDE

The production of mutations in cellular tumor suppressor genes such as p53 is involved in the development of many human cancers. These mutat ions result in the expression of mutant forms of the encoded p53 prote in which can potentially serve as a biomarker for this carcinogenic pr ocess. Workers exposed to vinyl chloride who are at risk for the devel opment of the sentinel neoplasm angiosarcoma of the liver represent a model population for the study of such a mutant p53 biomarker, since v inyl chloride is known to cause specific p53 mutations in persons with angiosarcoma of the liver. To determine the relation between vinyl ch loride exposure and this p53 biomarker, the authors examined serum sam ples 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 immunosorbent assay. Stratificati on of the exposed workers by quartile of vinyl chloride exposure (in e stimated ppm-years) yielded a statistically significant trend of incre asing odds ratios for p53 biomarker seropositivity with increasing exp osure. These results suggest that this serum biomarker for mutant p53 protein is related to vinyl chloride exposure and may be an early indi cator of carcinogenic risk in exposed individuals.