Viral cause for prostate cancer?

 

Prostate cancer is increasingly looking like an infectious disease, a new study shows, and may be sexually transmitted

 

Mounting evidence suggests that prostate cancer is an infectious disease caused by a recently identified virus. The latest report, published today (September 7) in the Proceedings of the National Academy of Sciences, found the virus was associated especially with aggressive prostate cancers and noted that "all individuals may be at risk" for infection.

Human prostate cancer tissue. Brown, granular staining shows malignant epithelial cells that express XMRV proteins Image: R. Schlaberg and H. M. Thaker

The notion that prostate cancer is an infectious disease like cervical cancer would not surprise most cancer experts, said Ila Singh of the University of Utah, the study's senior author. Almost 20% of visceral cancers are now proven infectious diseases, and there is a lot of indirect evidence from epidemiology and genetics that prostate cancer may be one of them.

The suspect is xenotropic murine leukemia-related virus (XMRV), a gammaretrovirus similar to viruses known to cause cancer in animals. Researchers at Columbia University and the University of Utah found the virus in more than a quarter of some 300 prostate cancer tissue samples, especially in malignant cells. That prostate cancer is a viral disease is not yet proven, but this is the third independent confirmation that XMRV infects prostate tissue.

Singh pointed out that clinicians badly need better tools for distinguishing between prostate cancers that are potentially deadly and those that develop so slowly that the affected men die of something else. "We have no idea if this virus is such a marker but it clearly needs to be investigated further," she said.

Research has long hinted that prostate cancer, also like cervical cancer, is a sexually transmitted disease. Eric Klein and colleagues at the Cleveland Clinic in Ohio reported in July that both human semen and one of its major components, acid phosphatase, increase XMRV infectivity for prostate cells 100-fold. They also found the virus in prostatic secretions of men with prostate cancer. "That really strongly suggests that XMRV is sexually transmitted," he said. Klein was part of a group in Cleveland and the University of California, San Francisco, that in 2006 first identified XMRV in prostate tumors. He was not involved in today's paper.

Klein said the July findings suggested a biological mechanism for sexually transmitted XMRV infection. If a man with viral particles in his lower genital tract has intercourse and deposits semen in his partner, acid phosphatase in the semen could increase the virus's ability to infect prostate tissue of the partner's subsequent partners.

Singh cautioned, "We can't really say that it's an STD at this point." Her lab is looking for XMRV in semen and also in women's cervical samples.

Many steps lie ahead for demonstrating conclusively that an infectious agent, in particular XMRV, causes prostate cancer. One approach is to inject lab animals with the virus and follow the results. Researchers have been trying to develop an animal model, but XMRV, although derived from a mouse virus, has since acquired an envelope that prevents it from infecting most strains of lab rodents, according to Singh. Klein's colleagues are working on a monkey model.

Klein and his colleagues showed last year that XMRV integrates into host DNA. So another proof would be to demonstrate that XMRV inserts near a gene that promotes cell growth. "That would be very convincing proof for most people that the retrovirus is involved in causing cancer," said Singh. Her group is working on that possibility with Frederic Bushman, a microbiologist at the University of Pennsylvania.

Establishing an infectious cause for prostate cancer would offer men something they have never had before: potential ways of preventing this common deadly disease. The new paper emphasizes how establishing a viral cause for prostate cancer could affect biomedical research. It would trigger epidemiological studies, vaccine development, and studies on interference with viral replication and antiviral therapies.

Klein noted that the US National Cancer Institute is now encouraging collaboration on XMRV studies among far-flung research groups. Prostate cancer strikes 1 in 6 US men and is the second-most common type of cancer in men, after skin cancer. Except for lung cancer, it also causes the most cancer deaths in men.


Correction (September 23): A previous version of this story incorrectly stated that skin cancer causes more deaths than prostate cancer in men. In fact, lung cancer and prostate cancer, respectively, cause the most cancer deaths in men. The Scientists regrets the error.