Data suggest viral, genetic roles in prostate cancer

San Francisco--A never-before-seen virus associated with prostate cancer suggests that infection may play a role in the development of the disease in genetically susceptible individuals. The new virus, XMRV, is 25 times more likely to be present in prostate cancer patients with a specific genetic mutation than it is in the general male population, researchers reported at the American Society of Clinical Oncology 2006 Prostate Cancer Symposium here.

"Epidemiologic data suggest that men with a history of STIs or prostatitis are at higher risk for prostate cancer," said Eric A. Klein, MD, head of urologic oncology at the Cleveland Clinic's Glickman Urologic Institute. "Further, certain variants in genes which are important in infection and inflammation, such as HPC1, TLR4, and MSR1, also predispose some men to prostate cancer. Where there is no proof that XMRV causes prostate cancer, its presence in prostate tissue may indicate that infectious agents have a role in this disease."

Genetic component

RNaseL, previously discovered by Cleveland Clinic researcher Robert H. Silverman, PhD, is activated by a viral infection, Dr. Silverman said. The protein degrades viral and cellular RNA, blocking viral replication and killing the infected cell, thereby limiting viral spread.

Pinpointing the source

The research group determined the RNaseL status from blood samples of 86 radical prostatectomy patients. Matched prostate tissue samples from the same patients were forwarded to UCSF researcher Joe DeRisi, PhD, to be checked for evidence of viral infection. Dr. DeRisi is the creator of the ViroChip, which was used to identify the SARS virus in 2003. The ViroChip is a 70-mer DNA microarray that can simultaneously detect the known universe of plant, animal, and human virus species: about 950 entities, Dr. Klein told Urology Times.

Dr. DeRisi found a previously unknown virus in nine of 20 samples (45%) from patients who carried two mutant forms of RNaseL. The virus was found in one of 52 samples (1.9%) from patients with two normal copies of RNaseL, and in none of the samples from 14 patients who had one mutant copy and one normal copy of RNaseL.

Further lab work identified the unknown virus as XMRV, a novel virus that shows 94% nucleotide homology with murine leukemia virus DG-75.

"We assume that this virus jumped from mouse to humans at some time in the distant past, but that is not yet proven," Dr. Klein said. "It appears that humans are the natural host for this virus. It is both replication-capable and infectious."

Exploring a possible connection

Epidemiologic data already indicate a possible infectious component to prostate cancer.