IMPORTANT NEWS ANNOUNCEMENT National Kidney Cancer Association 1234 Sherman Avenue Evanston, Illinois 60202 708-332-1051 Gene for Kidney Cancer Isolated: How You Can Help A research team headed by scientists at the National Cancer Institute (NCI) has identified the gene responsible for the most common type of kidney cancer. The finding is reported in the May 1994 issue of Nature Genetics. The cancer, called sporadic (non-familial) clear cell carcinoma, accounts for about 23,500 newly diagnosed cases of kidney cancer each year, or about 85 percent of all cases of the disease. Currently, there are an estimated 75,000 kidney cancer patients in the U.S. "With identification of this kidney cancer gene, it will be possible to develop new methods to improve the diagnosis and treatment of the disease and potentially to find way to prevent it," said W. Marston Linehan, M.D., of NCI's "The finding also will make it possible to develop a blood or urine test to detect kidney cancer early when it is most treatable." When detected in its earliest stages, the five-year relative survival rate for kidney cancer is 86 percent. If detected after it has spread to distant organs, the survival rate is 10 to 20 percent at the end of two years. In the United States, about 8,400 people will die this year of clear cell carcinoma of the kidney. The damage or mutated gene responsible for sporadic clear cell carcinoma of the kidney is a tumor suppressor gene located on the short arm of chromosome 3. The protein produced by the gene appears to restrain normal growth. The researchers found that this gene is mutated and inactivated in 57 percent of tumors from patients with sporadic, non-familial kidney cancer. "The disease appears to fit the two-hit model for development of cancer, where both copies of the critical gene are damaged or mutated," said co-investigator Berton Zbar, M.D., chief of NCI's Laboratory of Immunobiology. There are two copies of every gene in most cells. One normal copy of a gene is sufficient to prevent development of cancer. If both copies are damaged or mutated, (the two-hit model) cancer may develop. The researchers also found that the kidney cancer gene is affected early in the development of the disease. This finding is important, Dr. Linehan explained, because its early presence makes it possible to consider development of treatments to halt or reverse the progression of disease in its early stages. The gene responsible for sporadic clear cell carcinoma in the same gene that was identified last year as the cause of the inherited cancer syndrome called von Hippel-Lindau (VHL) disease. This research was conducted by Dr. Zbar and Michael Lerman, M.D., Ph.D., of NCI's Laboratory of Immunobiology, in collaboration with Dr. Linehan and colleagues. People who have VHL disease are predisposed to develop multiple tumors, including cancers of the kidney, eye, brain, spinal cord, and adrenal glands. Isolation of the VHL gene is now leading to improved identification of carriers of the gene in affected families to better manage care. NKCA Involvement Last fall, after the VHL gene was identified, the National Kidney Cancer Association asked patients to participate in the NCI's research. All patients and family members of patients were asked to contact the NKCA if: (a) more than one person in the family had kidney cancer, including deceased family members; or (b) if at least one member of the family had kidney cancer and at least one other family member had contracted or died of tumors of the eye, brain, spinal cord, ear, or adrenal gland. Over 20 families contacted the NKCA. Each family was asked to provide some medical information which the NKCA passed on to Dr. Linehan at the NCI. Afterwards, he sent the NKCA the following note via electronic mail: "The family information you sent has been a home run. This morning we already identified one family with three affected members and another with four." Marston Sometimes, a small amount of assistance at a critical time can lead to important progress in research. Dr. Linehan has again asked the NKCA for assistance in identifying families with kidney cancer. Patients Wanted Kidney cancer patients or family members of patients should call the Association at 708-332-1051. The NKCA will provide a family medical history questionnaire and information on participating in the NCI's research. The NKCA will also provide free information on kidney cancer and the genetics of kidney cancer to callers. When the questionnaires are returned to the NKCA, they are screened and sent to the NCI in batches. This saves the NCI the effort of dealing with individual callers and NCI scientists are not tied up answering questions about kidney cancer. Once the questionnaires are received by the NCI, Dr. Linehan will call those patients and families which seem to be most relevant to the research. If a detailed study is made of a particular family, it usually sufficient for every family member to get a simple blood test from his or her local doctor. The blood is shipped to the appropriate NCI laboratory by the doctor. (Due to AIDS and other blood transmitted diseases, it is important for all blood samples to be properly packed and handled.) Families which have the familial kidney cancer gene should be extra vigilant so any new cases are diagnosed and treated early. Besides helping themselves, families which agree to participate in research will be helping scientists develop diagnostic tests and new treatments for all forms of kidney cancer. Nurses, Social Workers and Doctors Can Help Too If you know any kidney cancer patients, call them and give them the National Kidney Cancer Association phone number, 708-332-1051. Urge them to contact the NKCA. You'll be performing a valuable service. Supporting research. Helping patients get more information about their disease. Perhaps even saving a life.