Trichloroethylene exposure and specific somatic mutations in patients with renal cell carcinoma

Background: The development of renal cell carcinoma (RCC) has been associated with both genetic and environ-mental factors—with mutations in the von Hippel–Lindau (VHL) tumor suppressor gene for clear-cell RCC specifically and with long-term exposure to high doses of trichloroethyl-ene (TRI), an industrially important solvent, for RCC generally. We investigated whether TRI exposure pro-duces RCC through a specific mutational effect on the VHL gene by analyzing VHL sequences in the RCCs of patients exposed to high, cumulative doses of TRI. Methods: The level of exposure for each of 44 patients with RCC who had known industrial exposure to TRI was classified according to the duration, frequency, and mode of exposure. Samples of normal and cancerous tissues were microdis-sected from paraffin-embedded tissue. DNA was isolate