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Objective: The objective of this study was to examine the presence of mutant-p53 protein (p53Ag) and antibodies to p53 protein (p53Ab) in a population of workers exposed to vinyl chloride (VC)., Method: We have investigated the presence of two cancer markers in the plasma of 151 subjects exposed to varying concentrations of VC (4-2823 ppm). The investigation took place in two sessions: in 1999, the analysis was limited to p53Ab, and in 2000, the analysis was repeated and extended to include also the mutant-p53Ag. The available information on the subjects in this study includes age, total years of employment in the VC polymerization industry, exposure concentration, results of abdominal ultrasonogram, hepatitis status, smoking and alcohol drinking status, and clinical records. Logistic regression analyses were performed to calculate the association between prevalence of positivity for p53Ab or mutant-p53Ag and cumulative VC exposure concentration after adjustment for confounding factors. t test and chi analyses were performed to test significant differences among groups., Results: Three (1.9%) of the 151 workers exposed to VC resulted seropositive for the mutant-p53Ag and five (3.3%) for the p53Ab. All seropositive subjects are distributed in the highest exposure classes (>1000 ppm). No seropositivity was found among controls. The stratified relationship between seropositivity and exposure appeared statistically significant (chi = 23.65 for mutant-p53Ag and 30.35 for p53Ab)., Conclusions: revealing its presence in subjects having a history of VC exposure greater than 1000 ppm. On the basis of this study, and the clinical experience of the authors, the presence of a minimum threshold for the carcinogenic effects of VC is hypothesized.