Trichloroethylene exposure and somatic mutations of the VHL gene in patients with Renal Cell Carcinoma

Barbara Charbotel (1) , Sophie Gad (2) , Delphine Caïola (3) , Christophe Béroud (4, 5) , Joëlle Févotte (1) , Alain Bergeret (1) , Sophie Ferlicot (6) , Stéphane Richard (2)

1 UMRESTTE - Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement
2 U753 - Cytokines et Immunologie des Tumeurs Humaines
3 Laboratoire de Génétique Oncologique [Villejuif]
4 LGMR - Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques
5 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
6 Service d'Anatomo-Pathologie

Background We investigated the association between exposure to trichloroethylene (TCE) and mutations in the von Hippel-Lindau (VHL) gene and the subsequent risk for renal cell carcinoma (RCC). Methods Cases were recruited from a case-control study previously carried out in France that suggested an association between exposures to high levels of TCE and increased risk of RCC. From 87 cases of RCC recruited for the epidemiological study, 69 were included in the present study. All samples were evaluated by a pathologist in order to identify the histological subtype and then be able to focus on clear cell RCC. The majority of the tumour samples were fixed either in formalin or Bouin's solutions. The majority of the tumours were of the clear cell RCC subtype (48 including 2 cystic RCC). Mutation screening of the 3 VHL coding exons was carried out. A descriptive analysis was performed to compare exposed and non exposed cases of clear cell RCC in terms of prevalence of mutations in both groups. Results In the 48 cases of RCC, four VHL mutations were detected: within exon 1 (c.332G>A, p.Ser111Asn), at the exon 2 splice site (c.463+1G>C and c.463+2T>C) and within exon 3 (c.506T>C, p.Leu169Pro). No difference was observed regarding the frequency of mutations in exposed versus unexposed groups: among the clear cell RCC, 25 had been exposed to TCE and 23 had no history of occupational exposure to TCE. Two patients with a mutation were identified in each group. Conclusion This study does not confirm the association between the number and type of VHL gene mutations and exposure to TCE previously described.

Mots clés: Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma; Renal Cell Carcinoma Tumour; Exposed Case; Renal Cell Carcinoma Case

Domaines: Génétique humaine

Barbara Charbotel, Sophie Gad, Delphine Caïola, Christophe Béroud, Joëlle Févotte, et al.. Trichloroethylene exposure and somatic mutations of the VHL gene in patients with Renal Cell Carcinoma. Journal of Occupational Medicine and Toxicology, 2007, 2 (1), pp.13. ⟨10.1186/1745-6673-2-13⟩. ⟨hal-01681863⟩