Combination of genetic mutation and viral infection may cause prostate cancer

Significant recent interest in the literature (JAMA 2006;295:1503, Lancet, epub) and by patients has arisen in response to a presentation given by Dr. Eric Klein of the Cleveland Clinic at the 2006 Prostate Cancer Symposium in San Francisco, February 24, 2006.

Dr. Klein presented their work on a potential viral etiology for prostate cancer (CaP).

The ideas originated from thinking that CaP might be linked to an infectious etiology in some patients. The Human Prostate Cancer 1 gene (HPC1) encodes an antiviral protein called RNaseL that is activated by viral infection. Alterations or mutations in RNaseL may increase the susceptibility for CaP. In particular, men homozygous for the SNP R462Q were hypothesized to more likely be associated with a viral cause for CaP.

CaP tissue was isolated from 86 radical prostatectomy specimens and mRNA extracted. Corresponding cDNA was examined for the presence of viral sequences. This was performed using a DNA microarray representing more that 5,000 conserved viral sequences. Localization of viruses in tissue was performed with immunohistochemistry and fluorescence in situ hybridization.

In 20 men who were homozygous for RNaseL, 45% had viral sequences found, compared to 1.5% of 66 controls with one or no RNaseL mutations. Especially fascinating was that viral cloning demonstrated that in all cases, the same 1 virus was identified. This virus, named XMRV is related to the xenotropic murine leukemia viruses, which are know to cause cancer in mice.

The localization studies found the virus in the stromal cells adjacent to tumor tissue, suggesting a paracrine effect. The researchers found the virus in the LNCaP cell line and it was replication competent. These exciting data provide new insight into etiologies for CaP in genetically predisposed men.

By Christopher P. Evans, MD
JAMA 2006;295:1503