Virus Found in 27% of Prostate Cancers, Linked to More Aggressive Tumors

Zosia Chustecka

September 08, 2009

September 8, 2009 — A type of virus known to cause leukemia and sarcomas in animals has been found in malignant human prostate cancer cells, and this infectious agent might be responsible prostate cancer.

Researchers from the University of Utah found evidence of Xenotropic murine leukemia virus-related virus (XMRV) in 27% of the prostate cancer samples that were examined, and the virus was associated with the 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," senior author Ila Singh, MD, PhD, associate professor of pathology at the University of Utah in Salt Lake City, said in a statement.

The finding is reported in the Proceedings of the National Academy of Sciences.

If confirmed, it could lead to the development of new diagnostic tests, therapeutics, and vaccines in a manner that could mirror the developments stemming from the finding that human papillomavirus is responsible for cervical cancer.

Virus Found in Malignant Cells

This is not the first time that this virus has been implicated in prostate cancer. An earlier study (PLoS Pathog. 2006;2:e25) found XMRV in prostate cancer cells, but it did not examine benign prostate tissue, so could not link the virus to prostate cancer, the researchers explain.

Dr. Singh and colleagues examined 334 consecutive prostate-resection specimens, of which 233 samples were prostate cancer and 101 were benign prostate tissue. Using a quantitative PCR assay and immunohistochemistry with an anti-XMRV-specific antiserum, they detected the presence of viral DNA or viral proteins in 27% of prostate cancer samples, compared with 6% of the benign prostate tissue.

The viral proteins were found almost exclusively in malignant prostate cells, suggesting that the XMRV infection is linked directly to the formation of tumors, the researchers note.

Detection of XMRV in 6% of the controls could indicate that the virus causes cancer only after a long induction period, the researchers suggest. Alternatively, these men might have cancer in an unsampled area of the prostate.

But it is also possible that XMRV infection does not always lead to cancer, they acknowledge.

The study confirmed that XMRV is a gammaretrovirus. As a general rule, these retroviruses infect cells and insert viral DNA into the cell's chromosome. Sometimes this insertion is adjacent to a gene that regulates cell growth, which results in a disruption of normal cell growth, leading to more rapid proliferation and eventually cancer. Dr. Singh and colleagues are now carrying out studies to see if this is the pattern of events that occurs when XMRV infects prostate cells.

All Men Could be at Risk

Dr. Singh and colleagues found, in contradiction to the 2006 report, that susceptibility to XMRV infection is not enhanced by a genetic mutation. The previous study had found that men who carried a specific genetic mutation (of the RANSEL gene) were more susceptible to XMRV, suggesting that only these men — who amounted to about 10% of the population — would be at risk.

However, Dr. Singh and colleagues found no connection between XMRV and the RANSEL gene mutation, which suggests that all men could be at risk for infection.

Currently, however, it is not clear whether this virus also affects women, if it is sexually transmitted, or if it is associated with any other cancers apart from prostate cancer.

"We have many questions right now," Dr. Singh said, "and we believe that this merits further investigation."

"A determination that a retrovirus can cause prostate cancer would focus efforts on preventing transmission, antiviral therapy, and vaccine development," the researchers conclude.

This work was supported by a grant from the United States Department of Defense. The researchers have disclosed no relevant financial relationships.

Proc Natl Acad Sci U S A. Published online September 7, 2009.


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