Programme: The Health Report
ABC Australia
Monday April 12, 2010
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http://www.abc.net.au/rn/healthreport/
Virus linked to prostate cancer and chronic fatigue syndrome
"Professor Myra McClure from the Imperial College London talks about the remarkable and incredibly controversial finding of a virus linked to prostate cancer and a tantalising link to chronic fatigue syndrome."
http://www.abc.net.au/rn/healthreport/stories/2010/2867629.htm#transcript
Transcript
This transcript was typed from a recording of the program. The ABC cannot guarantee its complete accuracy because of the possibility of mishearing and occasional difficulty in identifying speakers.
Norman Swan: Welcome to the program. This morning on the Health Report a curable cancer that occurs during pregnancy and which could probably be looked after a lot better. The latest on lung cancer including a possible new treatment and an extraordinary story which is evolving as we speak. It's whether prostate cancer is linked to a viral infection, a very unusual virus and a suggestion by some researchers that this same virus may have something to do with chronic fatigue syndrome.
As you're about to hear it's a research landscape littered with landmines and someone who's been making her way through it with only minor injuries so far, is Myra McClure who's a Professor of Retrovirology at Imperial College London.
Myra McClure: The virus is xenotropic murine leukaemia virus related viruses. We call it XMRV for short.
Norman Swan: XMRV is one of a family of viruses that once upon a time infected mice then weaseled its way into mouse chromosomes to find a permanent home. Having done so the viral genes have been passed down to offspring as part of their inheritance. But this particular virus seems to have broken out of its genetic prison and is infecting humans. Myra McClure again.
Myra McClure: Well it is an entirely new virus in the sense that it's not exactly the same as any other known murine leukaemia virus.
Norman Swan: Why did it come to your attention?
Myra McClure: Well it came to our attention quite late in the day actually because the first paper of the identification of the virus was in 2006 and we didn't get really interested in it until last year 2009 when a second paper came out showing that this virus was connected not just with the familial form of prostate cancer but with all forms of prostate cancer.
Norman Swan: So just go back to this earlier identification, what was being identified here?
Myra McClure: Genome sequences related to the virus were being identified in tissue samples taken from patients with prostate cancer from the tumour they identified this strange murine leukaemia virus.
Norman Swan: So in a sense although it's not HIV, it's done what HIV does which is interpolated itself into the DNA of the human being.
Myra McClure: Absolutely right, all retroviruses have this characteristic that when they infect a cell their genetic material gets integrated into the whole cell genetic material and it's there for life after that.
Norman Swan: So that was the first paper, and then another paper came out.
Myra McClure: Then another paper came out saying that we can find this virus in not just the familial cases, that is where families have got a history of prostate cancer but in sporadic cases and people that just get prostate cancer serendipitously and that became interesting because I think the figure was 23% of all prostate cancer patients were carrying this virus, or evidence of this virus infection.
Norman Swan: 23%?
Myra McClure: Yes that's a lot.
Norman Swan: Compared to, I mean what's the average in terms of men carrying this virus?
Myra McClure: Well this virus hadn't been found anywhere before in any malignancy so this was really the first finding. Nobody had any inclination that there was a virus connected with prostate cancer before this was found. So to find it now in 23% of tissues was quite a finding.
Norman Swan: And have you looked at normal men without prostate cancer?
Myra McClure: Yes they have and the incidence is very much lower, it's about something in the region of 1% and indeed there has been another interesting paper come out recently looking at healthy Japanese blood donors and they find that 1.7% of them are carrying the virus. So this is quite an interesting virus there is a percentage of people who are healthy who have got it but the much higher percentage of men with prostate cancer seem to have it.
Norman Swan: And has anybody found the free virus?
Myra McClure: No, as far as I'm aware this virus has just been found in tissues, I don't think anybody has actually isolated the virus from for example a blood sample yet - no.
Norman Swan: And what did you decide what you wanted to do with it?
Myra McClure: Well we run here as part of our research department a diagnostic service so making the sort of tests that identify viruses is second nature to us and we're interested in retroviruses, all sorts of retroviruses. So we thought well let's see if this virus has now been identified in two different centres in the United States, if it's real it's going to revolutionise the treatment of prostate cancer. So we thought we'll develop a test which will tell us whether or not the archived samples, the samples we've had stored for many years here at St Mary's Hospital are actually showing evidence of the virus. So we had the test ready to do that and that's what we are doing.
Norman Swan: So you had if you like a bio-bank of samples from men with prostate cancer?
Myra McClure: Yes, that's exactly right. The urologist here Dr Anoop Patel had been very foreseeing ten years ago he started setting up this bio-bank when he had patients with cancer who had had a biopsy he sent it to the histopathologist and the histopagthologist here Dr Marjorie Walker kept the tissue in paraffin blocks so they've been here maintained over all these years. And we get a small slice of these and we looked to see if the virus is present.
Norman Swan: And at the time of doing this interview with you you're not allowed to tell me what the results were because you haven't published yet.
Myra McClure: Well I'd rather not because you know there's a huge controversy. This virus has been born into controversy. The Americans say they can find that the first studies said 40% of familial prostate cancer, the second study said 23% of all prostate cancers, then an Irish group and a Swedish group came out and said they may be finding it in the States but we can't find it in our prostate cancers. Then a German group looked at 500 prostate cancer patients and they couldn't find it either. So people were beginning to say well if it is a real virus it's not in Europe but we're actually finding it I have to say.
Norman Swan: And it's not possible it's a contaminant that it's just crept into samples by accident?
Myra McClure: That's always a problem with retroviruses and their association with disease - this time it's not and I'll tell you why, because the people who published the American studies have been very careful to sequence this virus and the sequence and the phylogenetic analysis that is looking at the sequence of one virus compared to another and the eight samples they have are sequences taken from eight different viruses, taken from eight different patients with prostate cancer. All these are slightly different. Now if it were a lab contaminant you would have expected them all to be the same and they're not.
And secondly if it were a lab contaminant it would be exactly the same in sequence as all other known murine leukaemia viruses and it's not - it's different. So it's a real new virus.
Norman Swan: To what extent are retroviruses carcinogenic, cancer causing, because it could just be a traveller with cancer, you could be susceptible because you've got the cancer rather than it having anything to do with the cause?
Myra McClure: Absolutely right and in fact the mechanism as to how this virus causes cancer is not clear because this is a very simple virus, it only has three genes, there is no oncogene there.
Norman Swan: No cancer gene.
Myra McClure: No cancer gene, so there's no cancer causing gene in the virus so it's not doing it in an obvious way. It's possible that it's an indirect effect of the infection. In other words the infection with this virus is causing inflammation and it's the inflammatory response which is maybe playing a role in producing the cancer.
Norman Swan: If it were to be a real effect that it's there and much more commonly in people with prostate cancer what might you speculate is the epidemiology, how it behaves in the community?
Myra McClure: You're asking the very questions that we've just applied for funding to investigate. Nobody knows what the epidemiology is like and that's the very first question that we have to answer. Whose got it, is it just in the States, is it in Europe, what other cancers in fact are associated with this? There are all sorts of questions to be asked not least because if the Japanese study is right and 1.7% of healthy people are carrying this then we're talking about a virus which may or may not have an association with a cancer which is in the general population. And retroviruses are transmitted sexually and they are transmitted via bodily fluids so you would want to know what the epidemiology of this is.
Norman Swan: And accidentally you got involved with chronic fatigue syndrome?
Myra McClure: Completely accidentally, as I say we were set up to look at this virus and its association with prostate cancer when we were approached by people at King's College London who have a cohort of chronic fatigue syndrome patients. Now this is not a disease that we have any expertise in or that we work on here but because they knew we were a retrovirus lab they wrote and asked had we heard of this virus and of course we had, and what did we think of the association with chronic fatigue - well we had no idea.
Norman Swan: And it's exactly the same virus that you were looking at in prostate cancer?
Myra McClure: Exactly the same virus yes. So they asked us would we be willing to test samples that they had stored at King's and of course we said yes. So they sent us DNA that they had stored down over several years from people who had been very sick with chronic fatigue and we tested it with our assay which was highly sensitive, in fact the assay will detect one single copy of this virus and we didn't find any evidence for the infection.
Norman Swan: And you published it to some controversy?
Myra McClure: It's always controversial when you publish findings that are diametrically opposed to findings that have had such a high profile. After all Science is probably one of the best scientific journals in the world.
Norman Swan: And to explain, there is a bit of an industry here suggesting that retroviruses are a cause of chronic fatigue syndrome.
Myra McClure: Well that's what we were afraid of really, I don't suppose we would have rushed out to publish these findings, I mean for us it was just a couple of weeks work, it was not our mainstream interest. But the reason we rushed into print with this and we did, was because we had some evidence through the net and through the grapevine that people were being offered this test, quite expensive, and much, much worse than that that patients were being offered anti-retroviral therapy, the sort of therapy you would give HIV patients. And there's no evidence that these drugs will work effectively against this virus, and you don't want to be giving this sort of therapy which has all sorts of side effects unless you're absolutely sure that (a) the virus is sensitive and (b) that the virus is causing the disease.
Now there has been a Japanese study which has shown, an invitro study, that's just looking at the virus growing in the laboratory in culture to show that only one of the known anti-retroviral drugs works against this invitro and that's AZT. So it's a waste of time giving anything else anyway and we don't even know if it's going to work in vivo, so we wanted to put a stop to that because we felt it wasn't ethical.
Norman Swan: And so based on this particular sample it doesn't look as if there is a cause and effect relationship at all, in fact it's not there at all.
Myra McClure: I can't say that because all we have done is to test 186 chronic fatigue patients, I mean we could be in the same position for example as the Americans are with their prostate cancer. They are the only people who can find an association so far until we publish anything that we might find. So we can't say that because as the American group, Lombardi's group, have pointed out ad nauseam to people we are not testing the same patients as they have.
Norman Swan: The Lombardi group?
Myra McClure: That's the people who published the Science paper showing the association of chronic fatigue with this virus. In fact they say that 68% of chronic fatigue people are carrying this virus. We looked at our patients and didn't find any.
Norman Swan: Myra McClure is Professor of Retrovirology at Imperial College London. And you're listening to the Health Report here on ABC Radio National with me Norman Swan.
References:
Van Kuppeveld FJM et al. Prevalence of xenotropic murine leukaemia virus-related virus in patients with chronic fatigue syndrome in the Netherlands. British Medical Journal 2010;340:c1018
Myra McClure and Simon Wessely. Chronic fatigue syndrome and human retrovirus XMRV. (Editorial) British Medical Journal 2010;340:c1099
Kaye EO et al Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome. PLoS One 2010 Jan 6;5(1):e8519
Lombardi VC et al. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science 2009;326:585-9
