Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer

https://doi.org/10.1016/j.jcv.2008.04.016Get rights and content

Abstract

Background

We previously identified a novel exogenous gammaretrovirus (xenotropic murine leukemia virus-related gammaretrovirus (XMRV)) using a pan-viral microarray. XMRV is the first MLV-related virus found in human infection. Forty percent (8/20) of familial prostate cancer patients homozygous for a mutation in RNase L (R462Q) were positive for XMRV, while the virus was rarely (1/66) detected in familial prostate cancer patients heterozygous for R462Q or carrying the wild type allele.

Objectives

To determine the presence of XMRV in non-familial prostate cancer samples.

Study design

RNA from prostate tissue was analyzed for XMRV using nested RT-PCR. In all samples, RNase L (R462Q) genotyping was performed using an allele-specific PCR.

Results

XMRV-specific sequences were detected in one of 105 tissue samples from non-familial prostate cancer patients and from one of 70 tissue samples from men without prostate cancer. The two XMRV-positive patients were wild type or heterozygous for the R462Q mutation and thus carried at least one fully functional RNase L allele.

Conclusions

XMRV was rarely detected in non-familial prostate cancer samples from Northern European patients. The homozygous mutation R462Q (QQ) was significantly underrepresented (<6%) in this cohort when compared to other studies (11–17%).

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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