Could infections cause prostate cancer?

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:

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