The cause of prostate cancer, which infects one in six U.S. men in their lifetimes, has long eluded researchers. A new study presents a convincing argument that prostate cancer, like some other cancers, including cervical cancer, lymphoma and sarcomas, might be linked to a virus.
Researchers, reporting in a study that will be published online tomorrow in the Proceedings of the National Academy of Sciences, found that the retrovirus xenotropic murine leukemia virus-related virus (XMRV) was present in about a quarter of cancerous prostate cells—and just 6 percent of control cells, which suggests a possible relationship. Additionally, "the virus is more likely to be present the more aggressive the prostate cancer is," says Ila Singh, a co-author of the study and an associate professor in pathology at the University of Utah in Salt Lake City.
The link between viruses and some cancers has been accepted for decades, and according to Joseph DeRisi, a professor of biochemistry and biophysics at the University of California, San Francisco and an investigator at the Howard Hughes Medical Institute—and who wasn't involved in the report—some 15 percent of cancers are now known to be linked to viruses. Previous research in DeRisi's lab had described the presence of XMRV in prostate cancers a few years ago, but small sample sizes and lack of a non-cancerous control group prevented definitive correlation.
For such a common cancer—one that kills 3 percent of men worldwide—this is the first viral link to be found. "It's the only viral candidate for prostate cancer," says Singh.
The virus is a gammaretrovirus, which has been known to cause cancer in some animals, including rodents, cats and monkeys, but had not previously been found in humans. Retroviruses can integrate onto the chromosomes of a host, and if they happen to land on a cellular gene that controls growth, it can become overactive, "and you get a tumor," explains Singh.
Singh and her team also determined that the virus is not linked to a genetic mutation, as had previously been assumed—a finding that means all men are susceptible.
To find the viral link, the researchers built on the previous findings of XMRV in prostate cancer and tested 233 samples of prostate cancer cells and 101 benign control sample cells. "We have shown that the virus is actually present," Singh says. Her team's next step is to figure out whether this correlation is in fact causation.
"I think that's going to take a long time and a lot of work to resolve," DeRisi says. He notes that news of the findings is intriguing, and says that the result "raises the possibility of a more causal role."
Researchers are still unsure of the mechanisms at work in XMRV and how men might get it in the first place. Discovering how the virus is transmitted might help Singh and others better understand how it goes to work in the prostate cells. "What is really important to know," says DeRisi, is "whether XMRV is something all people are exposed to."
Finding the route of transmission might also pave the way for preventative measures. If it turns out to be sexually transmitted, protective measures might help decrease its prevalence. But as a more sure-fire method, would a simple vaccine, akin to that being used to ward off human papillomavirus (HPV) be possible if the virus is established as a cause of the cancer? "We hope that we could do something like that," Singh says.
If the virus does indeed turn out to be the culprit, at least behind the most aggressive forms of prostate cancer, the discovery might not mean much for men who have already been diagnosed. "It means a lot more, probably, for prevention," Singh says. However, she notes, "If you could diagnose the virus before the person has cancer, that may be something." Future testing technologies could also be useful for screening donated blood, which is already tested for lymphoma and leukemia-causing agents.
In the meantime, Singh's team is not abandoning the rest of the body. The virus is "absolutely worth looking for" in other places, she says. The team is studying breast cancer and hundreds of other cancers to see if this same virus might be at work. Given its discovery in the prostate, researchers are keen to see if it is encouraged in the presence of hormones like testosterone.
Despite the broad hunt for the virus and its origins, Singh and her team are especially focused on "experiments that will bring us closer to proving that the virus is a cause—or not." And that alone might keep the researchers busy, with thousands of integration sites to sequence and a growing mass of questions still unanswered.