Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer
Introduction
Prostate cancer is the most frequent cancer of men in North America and Europe. Well known factors contributing to the risk of prostate cancer are age, androgens, environmental and genetic factors.1 Sporadic (non-familial) prostate cancer is the most common form of prostate cancer (80–90%) and its incidence increases with age. Familial prostate cancer, which accounts for 10–20% of all prostate cancer cases, occurs much earlier in life and is defined as prostate cancer occurring in individuals with three or more first degree relatives who had prostate cancer.
Recent work emphasizes that prostate cancer is frequently associated with chronic prostatic inflammation. A lesion called proliferative inflammatory atrophy is often found in the premalignant stages of the disease.1 Viral infections may be triggers for the inflammatory process. However, epidemiological studies designed to detect links between specific viral infections and prostate cancer have been inconclusive.2, 3, 4, 5, 6, 7, 8, 9
Recently, a new gammaretrovirus, xenotropic murine leukemia virus-related gammaretrovirus (XMRV), was discovered in prostatic tissue from patients with familial prostate cancer;10 specifically in patients homozygous for a missense mutation in the RNase L gene, R462Q. Fluorescence in situ hybridization revealed that prostatic stroma cells were infected at low frequency (0.5–1.2%).
RNase L, an endoribonuclease of the antiviral defense pathway, was one of the first prostate cancer susceptibility genes recognized. The missense mutation R462Q has been linked to hereditary prostate cancer 11, 12, 13 and has been implicated in up to 13% of all prostate cancer cases in some studies.11 Not all studies have confirmed this finding, perhaps because of differences in population genetics or environmental factors.14, 15, 16
In the present study, we analyzed 105 RNA samples from the prostate tissue of 87 sporadic prostate cancer patients and also biopsy samples from 70 healthy men without prostate cancer for the presence of XMRV.
Section snippets
Tissue sampling and RNA isolation
We studied histological tumor-free prostate biopsies from 87 patients (Group A; samples 41–127) with confirmed cancer undergoing radical prostatectomy at the Urology Department of the University Hospital Hamburg-Eppendorf, and from 70 control donors (Group B). Group B samples 1–40 were from men defined as healthy according to the following parameters: serum PSA <1 ng/ml; no family history of prostate cancer; normal transrectal ultrasound or negative digital rectal examination. Group B samples
Low frequency of XMRV in sporadic prostate cancer
The gammaretrovirus XMRV was originally identified in RNase L-deficient prostate cancer tissue of patients with familial prostate cancer. In the absence of epidemiological data for XMRV, the present study was initiated to extend the search for XMRV-specific sequences to include patients with sporadic prostate cancer independent of the RNase L status. Only one sample of 105 obtained from the sporadic prostate cancer patients was positive for XMRV (0.95%) by RT-PCR. Additionally, XMRV sequences
Discussion
XMRV, a novel gammaretrovirus, was recently identified in familial prostate cancer samples using a pan-viral microarray.10 Our earlier studies suggested that functional mutations in RNase L might be important for the acquisition of XMRV. Almost all XMRV-positive prostate cancer cases described so far carry a mutation within RNase L (R462Q), resulting in reduced RNase L activity.10
However, the current study found only a low prevalence of XMRV in non-familial prostate tissue of men in Northern
Conflict of interest
The authors declare they have no competing interest.
Acknowledgement
The study was supported by the Wilhelm Sander Stiftung, grant 2005/166.1
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Thirty years of research on infection and prostate cancer: No conclusive evidence for a link. A systematic review
2013, Urologic Oncology: Seminars and Original InvestigationsLack of evidence for a role of xenotropic murine leukemia virus-related virus in the pathogenesis of prostate cancer and/or chronic fatigue syndrome
2012, Virus ResearchCitation Excerpt :Although 76 of the samples (12.9%) exhibited the “susceptibility” QQ genotype, which is consistent with the frequency in the literature, no XMRV-specific sequences were detected in either the RNA or DNA from the prostate tumor samples. Fischer et al. (2008) employed nested RT-PCR to test 105 German patients with sporadic PCa and found only 1 individual positive for XMRV; however, this individual did not exhibit the QQ RNase L genotype. D’Arcy et al. (2008) failed to detect any XMRV link in Irish PCa patients with the R462Q mutation.
A survey on human T-cell lymphotropic virus type 1 (HTLV-1) and xenotropic murine leukemia virus-related virus (XMRV) coinfection in Tehran, Iran
2018, Journal of Pharmacy and Bioallied Sciences