Abstract
BackgroundWe 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).MethodsCases 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.ResultsIn 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.ConclusionThis study does not confirm the association between the number and type of VHL gene mutations and exposure to TCE previously described.
Highlights
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)
Germline mutations of VHL gene are responsible for VHL disease, a rare dominantly inherited cancer syndrome predisposing to a number of highly vascularized tumors including multiple clear-cell RCC whereas somatic mutation or methylation of VHL gene is a frequent event in sporadic clear-cell RCC [4,5]
For subjects in that case control study, a specific pattern of mutations in the VHL gene has been reported in RCC cases with former prolonged and high-level exposures to trichloroethylene [9]
Summary
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). Main histological subtypes of renal epithelial tumours include clear-cell RCC (75%), papillary RCC (10–15%), chromophobe RCC (5%) and oncocytomas (5%). Inactivation of the VHL tumour suppressor gene is thought to result both in development of tumors in the von Hippel-Lindau (VHL) disease (MIM #19330) and in sporadic clear-cell RCC [4]. A number of epidemiological studies have investigated the association between exposure to trichloroethylene and renal cell cancer but the results have been inconsistent [6]. For subjects in that case control study, a specific pattern of mutations in the VHL gene has been reported in RCC cases with former prolonged and high-level exposures to trichloroethylene [9]. Another study carried out in Germany to evaluate the phenotype and the genotype of renal tumours in occupationally TCE-exposed patients revealed no unique phenotype, genotype or mutation pattern in the VHL gene of renal tumours after TCE exposure [10]
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