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Could infections cause prostate cancer?

Cancer can’t be ‘caught’ from another person. But infections caused by viruses and bacteria can trigger certain forms of the disease. For example, human papillomavirus (HPV) can cause cervical cancer and several other types, hepatitis B and hepatitis C can cause liver cancer, and the bacterium Helicobacter pylori is the major cause of stomach cancer.

But could prostate cancer join that list? Two papers, released this week, have suggested that two different infections – a virus and a parasite – could be involved in some cases of prostate cancer.

Is a virus involved?

In 2002, US researchers had noted that men with prostate cancer often also carry faulty copies of a gene called RNaseL that defends the body from viral infection.

This prompted another team of researchers, led by Robert Schlaberg, to scan tumour samples taken from 86 patients for DNA from almost 5,000 viruses. In 2006, they published the results – they had found a virus called xenotropic murine-like retrovirus, or XMRV, in the cell samples from prostate cancer patients.

In fact, their exhaustive search had found XMRV in 45 per cent of men with two faulty copies of the RNaseL gene, but in just 1.5 per cent of men with normal versions. XMRV is one of the retroviruses, a family that includes HIV (which itself causes a type of cancer called Kaposi’s sarcoma).

It was an exciting discovery, suggesting that a small proportion of prostate cancers could be caused by a virus. But it wasn’t conclusive – for a start, the researchers didn’t look at XMRV infection rates in normal people or prostate cancer patients.

So this left a big question. Does XMRV contribute to prostate cancer, or does it merely show up in prostate cancer cells because they can’t clear the infections? In other words, does it cause the disease, or is it just along for the ride?

New evidence

Last week, Schlaberg’s group published some new evidence to strengthen their case. Their latest paper, published in Proceedings of the National Academy of Sciences, shows that the virus can indeed infect human prostate cells and reproduce efficiently in them. The researchers found that the virus works in a remarkably similar to way to the Moloney mouse leukaemia virus (MoMLV) that causes leukaemia in mice.

The researchers compared tissues taken from the prostates of 101 healthy men and 233 men with prostate cancer. They found XMRV DNA in 6 per cent of prostate cancers but just 2 per cent of the healthy tissues. Likewise, they found proteins produced by the virus in 23 per cent of tumours but just 4 per cent of the healthy tissues. All in all, cancerous prostate tissue was five times more likely to test positive for XMRV than healthy tissue.

They also found tentative evidence that more advanced prostate cancers were more likely to test positive for XMRV, although this conclusion was based on a very small number of tumours.

But when the researchers looked at the relationship between the RNaseL gene and XMRV, their results didn’t match previous data. In this study, the results showed faulty RNaseL genes didn’t increase the likelihood of XMRV infection – contradicting the previous findings that suggested men with faulty copies of the gene were more likely to be infected. This new data suggests that many more prostate cancers could be caused by XMRV – not just the minority that have faulty RNaseL genes.

Overall, the picture’s not clear yet. As study author Ila Singh says, ‘We still don’t know that this virus causes cancer in people, but that is an important question we’re going to investigate.’

The next step is to do larger studies to find out more about the relationship between XMRV and prostate cancer, and to see whether the virus affects the outcome for men with the disease.

Parasites?

The second recent paper to suggest that an infection could cause prostate cancer looks at a different sort of infectious agent – a parasite called Trichomonas vaginalis.

T. vaginalis is the most common sexually transmitted infection in the world, infecting an estimated 174 million people each year. Some studies have suggested that it can infect the prostate and make the gland inflamed. Inflammation can help some tumours to grow, and so the theory is that by causing inflammation, T. vaginalis could also be promoting the development of cancer.

The new study, carried out by researchers at the Harvard School of Public Health and Brigham and Women’s Hospital in the USA, aimed to find out more about this theory. They compared blood samples from men with prostate cancer to those from men without the disease, testing each one for parasite antibodies, which indicate infection.

They found that 25 per cent of the blood samples from men with prostate cancer showed signs of infection, compared to 21 per cent of samples from healthy men. This is only a small difference that isn’t statistically significant, meaning it could have been caused by chance.

But their other results were more intriguing. The researchers found that samples from men with advanced prostate cancer were more likely to contain parasite antibodies. The same was true of samples from men whose prostate cancer had spread or caused death.

In fact, men with advanced disease were twice as likely to be infected compared to healthy men, and samples from men whose cancer had spread or caused death were over two and a half times as likely to show infection.

So what’s going on here? Once again we don’t yet have the full picture, and we have to ask the same questions about T. vaginalis as are posed by XMRV. Is the infection really causing the disease, or does the cause-effect relationship work the other way? Prostate cancer may create an environment in which T. vaginalis can flourish, meaning that it’s the cancer helping to increase the levels of infection rather than the other way round.

Another question is whether the infection could in fact be linked to something else that’s contributing to prostate cancer. For example, men with one sexually transmitted disease may be more likely to have others too, which may affect their prostate cancer risk.

But men with prostate cancer shouldn’t be worried that their disease might have been caused by a virus or an STI. We don’t know enough yet to make this conclusion, and that’s why further research is needed.

These two new papers raise more questions than they answer, but this is one of the aims of scientific research. Knowing which questions to investigate is a vital part of the process, and the scientists involved can now plan future work based on their results.

The fact remains that we still know very little about the causes of prostate cancer. Research like this helps to explore every avenue and find out more about possible risk factors for a disease that’s a huge health problem worldwide.

Nell


References:

Casey, G. et al. (2002). RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer cases Nature Genetics, 32 (4), 581-583 DOI: 10.1038/ng1021
Urisman, A. et al. (2006). Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant PLoS Pathogens, 2 (3) DOI: 10.1371/journal.ppat.0020025

Stark, J. et al. (2009). Prospective Study of Trichomonas vaginalis Infection and Prostate Cancer Incidence and Mortality: Physicians’ Health Study JNCI Journal of the National Cancer Institute DOI: 10.1093/jnci/djp306

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Comments

nick November 10, 2010

hi nell,

i spoke with the author and with my dr basically if left untreated it may get to the prostate and cause damage via an oxidative effect which may lead to constant inflamation, she said it is rare and that they suspect inflamation can lead to to proste cancer. my dr said there is no proof and if people beleive inflamation as a causation factor then its up to them, authors just want their PHD’s and so get involved with this type of research to obtain it, its all rubbish

nick November 6, 2010

hi nell,

ive been a bit confused regarding t vaginalis, are they claiming that even a treated case can still leave the prostate in an inflamed, damaged or vulnerable state for the future? ive been treated and i never had symptoms and wouldnt know if it affected my prostate. there has been a few interpretations of this here is a couple of titles for you to see on google:Trichomonas Vaginalis Infection Linked to Aggressive Prostate Cancer….and this one:Prostate cancer linked to sexually transmitted disease – CNN. surely the prostate if has had some sort of inflamation or damage does repair itself? please let me know what you understand about all of this it has worried me.

many thanks

nick

HIFU September 18, 2009

PCa needs to be more scrutinized along with the treatment options. Theres too much data out there to ignore but only a select number of treatments are available. In the US, treatments take years to get approved while other countries use them regularly. Patients should explore all options available.

Nell Barrie September 18, 2009

Hi Anne.
Thanks for your comment – this article is not meant to imply that STIs are the ONLY cause of prostate cancer. The research we wrote about found that having these infections MAY increase the risk of cancer (and this link isn’t yet confirmed), in the same way as any risk factor. There’s not meant to be any implication that ALL cases of prostate cancer are linked to infections, or even that every man with an infection will develop prostate cancer.
Hope that clears things up! Sorry for any confusion.

Nell

Anne Rowbotham September 17, 2009

You are definitely on the wrong track here. Advanced prostate cancer may be linked to sexually transmitted diseases – no way…. My husband was completely faithful married 38 years he was my only partner and I his! I believe it is genetic.

Mike September 17, 2009

eventually, they’ll probably figure out all cancer is caused by one virus or another.