US researchers found a type of virus known to cause leukemia and tumors in animals occurred in over a quarter of the malignant prostate cancers they examined; this is the first report of such a finding and raises the question of whether some prostate cancers have a viral cause.

The study that led to this finding was the work of researchers from medical schools attached to the University of Utah in Salt Lake City and Columbia University in New York and is to appear in an early September 2009 issue of the Proceedings of the National Academy of Sciences, PNAS.

Prostate cancer is the second most common cancer among men in the US (skin cancer is the most common), where it is expected to affect about 200,000 men this year.

The virus that the researchers found is a retrovirus called XMRV (Xenotropic murine leukemia virus-related virus), and if further research proves that it leads to prostate cancer, it will create new avenues for developing diagnostic tests and vaccines, said the researchers.

A retrovirus invades host cells and uses their resources to make DNA copies of its RNA code, in effect inserting a DNA copy of its genome into the chromosomes of each invaded cell. This insertion sometimes occurs next to a gene that controls cell growth and disrupts its function, a process that can lead to uncontrolled and rapid cell proliferation, the hallmark of cancer.

A group of retroviruses called gammaretroviruses follows this mechanism and is known to cause cancer in animals although it has not been shown to do so in humans.

In this study, the researchers not only proved that XMRV occurs in malignant prostate cancer cells, they also confirmed that it is a gammaretrovirus.

Senior author Dr Ila R. Singh, who is associate professor of pathology at the University of Utah, said in a press statement that:

“We found that XMRV was present in 27 percent of prostate cancers we examined and that it was associated with more aggressive tumors.”

“We still don’t know that this virus causes cancer in people, but that is an important question we’re going to investigate,” she added.

Singh started the research at Columbia University Medical Center, before she moved to Utah in 2008. She is also a member of the University of Utah’s Huntsman Cancer Institute and associate medical director at ARUP Laboratories.

She is currently looking at whether XMRV causes prostate cancer in the same way that gammaretroviruses cause cancer in animals.

XMRV was first isolated from prostate cancers in 2006 by researchers at the University of California, San Francisco (UCSF), and the Cleveland Clinic. However, that study did not look at non-malignant prostate tissue and neither did it find the virus in malignant cells, so could not link it to prostate cancer directly.

For this study, Singh and colleagues compared more than 200 human prostate cancers with more than 100 human non-cancerous prostate tissue samples. They found XMRV proteins almost exclusively in the the malignant cells, suggesting that the virus is directly linked to tumor formation.

They also showed that unlike previous reports, the risk of being infected by XMRV was not dependent on carrying a certain genetic mutation, but probably extends to the population at large. Previous reports have suggestd that infection by XMRV was linked to a certain genetic mutation carried by 10 per cent of the population but Singh and colleagues found no such link.

The study also raised many questions, such as can XMRV infect women, is it transmitted sexually, how common is it in the general population, and is it present in the tissue of other cancers.

Other cancers, such as cervical cancer, sarcomas (cancers of the connective tissue), and lymphomas (immune system cancers), and cancers of other organs, have viral origins. If XMRV is shown to cause prostate cancer, it opens new routes to prevention, for developing vaccines and reducing infection in people.

Recent research has suggested that many men are treated for prostate cancers that are unlikely to progress to a harmful stage during their lifetime: where perhaps a better strategy might be to watch and wait.

Singh and colleagues suggest that identifying markers like XMRV should help to better identify the faster growing and more aggressive prostate cancers and target them for therapy.

— PNAS

Source: University of Utah Health Sciences.

Written by: Catharine Paddock, PhD