Critical genes as early warning signs: example of vinyl chloride.

We have analysed liver angiosarcomas from individuals having been occupationally exposed to vinyl chloride (VC) to identify, in cancer-related genes, lesions which could be VC-specific. Two genetic alterations have been identified: the first one is a GGC --> GAT (Gly --> Asp, Asp13p21) mutation at codon 13 in the Ki-ras gene, found in five out of six tumors. The second one is an AT --> TA transversion in the p53 gene resulting in missense mutations at different codons and was found in three out of six tumors. By analysing both the tumors and sera from the same patients, we have shown that the Asp13p21 and mutant p53 proteins could be detected reliably in the serum. We thereafter analysed 225 serum samples, selected from a cohort of about 900 VC-exposed workers, for the presence of the two mutant proteins and p53 antibodies. A statistical analysis supports a strong dose-response relationship between the serum markers positivity and the VC-exposure. A follow-up of this cohort should now allow us to assert the predictive value of these markers.