Editor’s Note: As you will see in this article, it has now been shown scientifically that Trichlorethylene causes changes to chromosome 3 which can lead to kidney cancer. This includes changes to the VHL gene.

In people who have inherited the VHL gene, there is already a "germline" (inherited) mutation in one copy of the VHL gene. These chemicals can cause "somatic" mutations (during one's lifetime) to the second copy, causing tumors to form. In people who have not inherited a germline mutation, both copies of the VHL gene can be altered, causing kidney cancer tumors to form.

Thus people with VHL are encouraged not to work in areas where they will be exposed to these chemicals. This constitutes a requirement for modification of the workplace under the Americans with Disabilities Act.

If you think you may have been exposed to TRI (also called TR3), contact the company where you worked at the time. All industries are required by U.S. law to have available the MSDS papers (Material Safety Data Sheets) for any and every chemical used by them, available to all employees exposed to them. If they give you trouble, the Environmental Protection Agency (EPA) should be able to assist. There are similar laws in other nations.

The development of renal cell carcinoma (RCC) has been associated with both genetic and environmental 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 trichloroethylene (TRI), an industrially important solvent, for RCC generally. We investigated whether TRI exposure produces 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.

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 microdissected from paraffin-embedded tissue. DNA was isolated from these samples, and somatic VHL mutations were identified by polymerase chain reaction analysis, single-strand conformation polymorphism analysis, DNA sequencing, and restriction enzyme digestion. Control samples included RCC DNA from 107 patients without known TRI exposure and lymphocyte DNA from 97 healthy subjects.

RCCs of TRI-exposed patients showed somatic VHL mutations in 33 (75%) of 44 cases. The mutations were frequently multiple and accompanied by loss of heterozygosity, and there was an association between the number of mutations and the severity of TRI exposure. We observed a specific mutational hot spot at VHL nucleotide 454 in the RCCs of 13 (39%) of the patients, and this mutation was present in adjacent kidney tissue in four of these patients. The nucleotide 454 mutation was neither detected in any of the RCCs from patients without TRI exposure nor in any of the healthy subjects.

Our results suggest that RCC in patients with high, cumulative TRI exposure is associated with a unique mutation pattern in the VHL gene.

Excerpted from Journal of the National Cancer Institute (May 19, 1999) 91:854.

For more information on trichlorethylene, please see http://www.nsc.org/EHC/ew/chems/trichlor.htm

Family Feedback

After we circulated this information in the online discussion vhlfa@egroups.com, one member posted this reply: "When I showed my husband the message about trichlorethylene, he immediately went out to his company truck and brought in a can of cleaner that is used to clean electrical cables (he works for a utility company). The first ingredient was trichlorethylene. We wonder how significant that has been to his health. He seems to have such a severe manifestation of kidney tumors, 30 removed in 1998 alone! Thanks for the information!"

As printed in the VHL Family Forum 8:1, March 2000. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.