New findings complicate recent evidence for a viral link to prostate cancer. Recent studies have found the virus, called xenotropic murine leukemia virus-related virus (XMRV), in a disproportionate number of cancer tissue samples in men with prostate cancer, but the latest report, published today (October 16) in Retrovirology, detected no sign of XMRV in tissue samples from almost 600 prostate cancer patients.

Prostate cancer cells Image: Wikipedia

"The association [of XMRV] to prostate cancer will require many large screening studies done on various populations across the world," Joseph DeRisi, a biochemist and biophysicist at the University of California, San Francisco, who was not involved in the study, said in an email. "This would be one of many, and I don't expect everyone to get the same results."

Prostate cancer is one of the leading causes of cancer deaths in men, but researchers have a limited understanding of what triggers it. In 2006, DeRisi and his colleagues were the first to identify XMRV infection as a potential risk factor, showing that the virus was present in up to 40% of the prostate tumor samples they studied. Last month, a study in PNAS reported that viral DNA or proteins were present in more than a quarter of 334 prostate cancer tissue samples they studied. XMRV is similar to viruses already known to cause cancer in animals, and these results led some to postulate that prostate cancer, like cervical cancer, may be a sexually transmitted disease.

In the present study, researchers at the Robert Koch Institute and the medical school Charité - Universitätsmedizin Berlin in Germany collected tissue samples from 589 German prostate cancer patients between 2000 and 2006. They screened the patients' DNA and RNA for signs of XMRV using real-time PCR, a method for detecting and amplifying a specific sequence in a DNA or RNA sample, and also used assays to look for antibodies specific for XMRV. The study authors found that none of the tumor samples contained XMRV, and assays showed no XMRV antibodies in the blood.

There are several other studies that have failed to find XMRV in prostate tumor samples. "Our results are in agreement with another study investigating the prevalence of the virus in German prostate cancer patients," Oliver Hohn of the Robert Koch Institute, the current study's first author, wrote in an email. In the 2008 study he referred to, XMRV was detected in only one of 105 prostate tumor samples. "Knowing these data, our results were not too surprising," Hohn said. In addition, he noted, researchers from Ireland reported at the 2008 European Association of Urology conference in Milan that they also found no XMRV in prostate cancer patients.

"It is possible that the methods used may have missed detecting XMRV," said Robert Silverman, a cancer researcher at the Lerner Research Institute in Ohio and an author on last month's PNAS study. Silverman said that the PCR methods used in this paper are significantly less sensitive than the ones he has used in patient samples. Hohn, however, said that he and his team developed specific and highly sensitive PCR assays to detect the viral genome.

Another explanation for the discrepancy between studies, noted Hohn, is that XMRV may be more prevalent in the US than in Germany. DeRisi agreed. "If this is a real infection, I highly doubt it would have globally uniform distribution," said DeRisi, who is also a Howard Hughes Medical Institute investigator. "So not finding it in Germany may imply that this could be geographically restricted or be transmitted in a way that is not occurring there."


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When cancer is just the beginning
[October 2008]