Virus may offer clue to some prostate cancers

May 1, 2007

A virus that is known to cause leukemia in mice, xenotropic murine leukemia-related virus (XMRV), also may be responsible for prostate cancer in humans.

Key Points

Discovery of XMRV was first reported 1 year ago at the Prostate Cancer Symposium by Eric A. Klein, MD, head of the section of urologic oncology, Cleveland Clinic Glickman Urological Institute. At this year's symposium, Dr. Klein gave a status report in which he said that study of the virus is evolving in an interesting fashion.

"It started with an observation that there was a gene on the long arm of chromosome 1 that was associated with the likelihood of getting prostate cancer," he explained. "When fully mapped, that gene turned out to be part of our innate defenses against viruses. So if you get a common cold, this gene, HPC1, gets turned on. The normal function of this gene is to help rid the body of the virus."

Many of the major cancers, such as stomach cancer, are often triggered by an infection.

Further, according to Dr. Klein, epidemiologic evidence suggests that men with a history of prostate infection through prostatitis, sexually transmitted infection, or exposure to herpes are at increased risk of developing prostate cancer.

Tracking down XMRV

Dr. Klein, Robert H. Silverman, PhD, and colleagues Don Ganem, PhD, and Joseph DiRisi, PhD, at the University of California, San Francisco, used a unique discovery tool, the ViroChip, to link viruses and prostate cancer. ViroChip contains little pieces of DNA from each of 1,000 known viruses that infect plants, animals, or humans. Researchers took prostate tissue from men with prostate cancer, hybridized it to the chip, and found XMRV, a retrovirus similar to other retroviruses and closely related to a virus that causes leukemia in mice, suggesting that it, too, might cause cancer. In order to cause disease, retroviruses must integrate into host DNA.

"Our latest findings show in several patients that the XMRV virus does integrate into host DNA, into various different chromosomes and, in one case, near a gene that can affect the expression of the androgen receptor in men, which is the receptor that mediates the effects of testosterone and serves as fuel for prostate cancer," Dr. Klein said.

While it has not been proven yet that XMRV causes prostate cancer, indications are that XMRV is present in about half of the men who have a specific variant in the HPC1 gene, which makes a protein called RNase L. Allelic mutations or variations in RNase L have been implicated in familial susceptibility to prostate cancer. Dr. Silverman, Dr. Klein, and colleagues are now working on the biology to understand exactly what the virus does and how it might cause cancer.

"The clinical applicability is important, and there are several implications," he said. "One is that if you have the virus, you may be at higher risk of getting prostate cancer and may need to be screened more frequently. Second, if you have the virus and cancer, there might be new drugs that help fight the effects of the virus. If we can prove that XMRV causes prostate cancer, our ultimate goal is to develop a vaccine to prevent susceptible men from getting XMRV and prostate cancer to begin with."

Jack Schalken, PhD, professor of experimental urology at Radboud University, Nijmegen Medical Center in the Netherlands, said he was excited by Dr. Klein's finding that a retrovirus may be associated with prostate cancer.

"He is now much further [than a year ago] and indicates at what level the retrovirus might interact with the prostate stromal cells," Dr. Schalken said. "That, by itself, might result in the transformation of the epithelial cells."