Dormant virus may drive bladder cancer development

Infection by a common virus during childhood is associated with the development of bladder cancer later in life.

Many bladder cancers contain mutations caused by APOBEC3 enzymes, which normally act to defend the body against viral infections. However, up until now, no virus has been directly associated with bladder cancer. The BK polyomavirus is a common childhood virus which can remain dormant in the kidneys for decades. Researchers from the University of York have found that reactivation of the BK virus can trigger APOBEC3 activity in bladder cells, generating the mutations which lead to bladder cancer.

Dr Simon Baker, lead author of this study and an intermediate research fellow at the University of York, said, 'While more research is needed to confirm a causal link, this research marks a huge shift in our understanding. While we've long known that things like smoking increase cancer risk, this breakthrough means we can now envision a future where we might actually eradicate bladder cancers by stopping the initial virally triggered damage.'

In this study, published in Science, the team exposed bladder cells to the BK virus and analysed the resulting DNA mutations. They also identified the mutational signature associated with APOBEC enzymes. The group found that the mutations found in the bladder cells infected by BK virus matched the pattern of mutations caused by APOBEC enzymes. This suggested that the body's antiviral response to the BK virus, in the form of APOBEC enzymes, resulted in the mutations commonly found in bladder cancer.

Dr David Crosby, chief research officer at Kidney Research UK (who partially funded this research), said, 'These findings move us closer to understanding why some people develop bladder cancer and show how tackling BK virus early could one day stop these cancers from developing at all.'

People who receive a kidney transplant have a threefold higher risk of bladder cancer, since immunosuppressive drugs allow reactivation of the BK virus. However, the virus is usually absent from bladder tumours in the wider population. The researchers also found that APOBEC-associated mutations appeared not only in infected bladder cells, but also in nearby uninfected cells. This could explain why many bladder cancers show no trace of the virus at diagnosis, even if they arise from a BK-virus-triggered antiviral response.

Tim Tavender is one such person who received a kidney transplant and subsequently developed bladder cancer due to BK virus reactivation. He told Kidney Research UK, 'I've seen there is a link between the BK virus and bladder cancer in renal transplant patients who are immunosuppressed. Early screening of people at-risk would be lifesaving. Had I not gone to the doctor when I did, there may not have been an opportunity to treat my bladder cancer before it spread. If that was the case, I might not be here today.'