Screening of TP53 mutations by DHPLC and sequencing in brain tumours from patients with an occupational exposure to pesticides or organic solvents.

摘要

The aetiology of brain tumours remains unclear. Occupational exposures to pesticides and organic solvents are suspected risk factors. The case-control study CEREPHY (221 cases, 442 controls) carried in the Departement de la Gironde in France revealed a significantly increased risk of brain tumours for subjects most exposed to pesticides. In some cancers, TP53 mutations could reflect exposure to specific carcinogens. These mutations are present in approximately 30% of astrocytic brain tumours. In a pilot study, we explored the hypothesis that pesticide or solvent exposure could raise the frequency of TP53 mutations in brain tumour cells. We investigated TP53 mutations in exons 2-11 by denaturing high performance liquid chromatography (DHPLC) and sequencing, and p53 accumulation by immunohistochemistry in brain tumour of the 30 patients from CEREPHY study with a history of occupational exposure to pesticides (n = 21) and/or organic solvents (n = 14) for whom tumoral tissue was available. Included cases concerned 27% of CEREPHY cases exposed to pesticides and, based on the cumulative index of occupational exposure, they were more exposed to pesticides. There were 12 gliomas, 6 meningiomas, 7 neurinomas, 2 central nervous system lymphomas and 3 tumours of other histological types. We detected TP53 mutations in three tumours, which is similar to the expected number (3.3) calculated from 46 published studies referenced in the IARC TP53 mutations database, taking into account histological types. Considering TP53 mutations previously detected in the laboratory by DHPLC and the frequency of TP53 polymorphisms detected in this sample (similar to published data), the TP53 mutations rate is probably not underestimated. These preliminary results, even if it was on a limited number of tumours, are not in favour of the role of pesticide or organic solvent exposure in the occurrence of TP53 mutations in brain tumours.