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


CONCLUSIONS
This study does not confirm the association between the number and type of VHL gene mutations and exposure to TCE previously described.
Charbotel
Barbara
B
UMRESTTE, Université Lyon 1, Université de Lyon, Domaine Rockefeller, Lyon, F-69373, France.|Hospices Civils de Lyon, Service des maladies professionnelles, Centre Hospitalier Lyon Sud, F-69495 Pierre Bénite, France.
Gad
Sophie
S
Laboratoire de Génétique Oncologique EPHE, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre 94275 Le Kremlin-Bicêtre Cedex, France.|CNRS FRE-2939, Institut de Cancérologie Gustave Roussy (IGR), 94805 Villejuif, France.
Caïola
Delphine
D
Laboratoire de Génétique Oncologique EPHE, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre 94275 Le Kremlin-Bicêtre Cedex, France.|CNRS FRE-2939, Institut de Cancérologie Gustave Roussy (IGR), 94805 Villejuif, France.
Béroud
Christophe
C
Laboratoire de Génétique Moléculaire, CHU de Montpellier, Institut Universitaire de Recherche Clinique (IURC), INSERM, U 827, Montpellier, F-34000 France.
Fevotte
Joelle
J
UMRESTTE, Université Lyon 1, Université de Lyon, Domaine Rockefeller, Lyon, F-69373, France.
Bergeret
Alain
A
UMRESTTE, Université Lyon 1, Université de Lyon, Domaine Rockefeller, Lyon, F-69373, France.|Hospices Civils de Lyon, Service des maladies professionnelles, Centre Hospitalier Lyon Sud, F-69495 Pierre Bénite, France.
Ferlicot
Sophie
S
Laboratoire d'Anatomie Pathologique, CHU de Bicêtre, 94275 Le Kremlin-Bicêtre Cedex, France.
Richard
Stéphane
S
Laboratoire de Génétique Oncologique EPHE, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre 94275 Le Kremlin-Bicêtre Cedex, France.|CNRS FRE-2939, Institut de Cancérologie Gustave Roussy (IGR), 94805 Villejuif, France.