New research led by UK scientists has shown that a protein in urine could be a reliable marker for prostate cancer risk, and although there is still a lot of work to be done to move it from the laboratory to the clinic, the finding is raising hopes that an easy and reliable clinical test for prostate cancer is now much closer.

The study, led by scientists from the Cancer Research UK (CRUK) Cambridge Research Institute and The Institute of Cancer Research (ICR), was published online on 13 October in PLoS ONE, an open access scientific journal from the Public Library of Science. Scientists from other research centres in the UK, Australia, Spain and the US were also involved in the study.

Lead author Dr Hayley Whitaker, from CRUK's Cambridge Research Institute, told the press that the protein, microseminoprotein-beta (MSMB), is "easy to detect because it is found in urine and would potentially be a very simple test to carry out on men to identify those most at risk".

Whitaker and colleagues built on earlier genome-wide association studies (GWAS) that had linked a genetic change linked to prostate cancer risk with a significant reduction in MSMB protein.

The protein, which is produced by normal prostate cells and secreted into urine from semen, regulates cell apoptosis or programmed cell death and is linked to an increased risk of developing prostate cancer.

MSMB is the second most abundant protein in semen after prostate specific antigen (PSA), the protein used in the current test for prostate cancer.

The reason that people are getting excited about this research is because unlike PSA, levels of this protein appear to be unaffected by an enlarged prostate or by hormones, thus raising the hope that it will lead to a more reliable test.

There is a lot of uncertainty surrounding the current PSA test, for instance whether to use it for routine prostate cancer screening like the mammography test is used for breast cancer screening, because PSA can go up for reasons other than prostate cancer, and not all prostate cancers raise PSA.

One hope is that a test based on MSMB could be used in conjunction with PSA to help identify men at greater risk of developing prostate cancer.

Co-author Professor Dr Rosalind Eeles, of the ICR and the The Royal Marsden Hospital, said:

"Our studies have shown that men with a small change in their MSMB gene are at a higher risk of prostate cancer, and so we are very excited that there may be a simple test for this genetic change."

"At the moment, PSA testing is the best method we have to detect prostate cancer but it has significant limitations, so there is an urgent need to find new biomarkers such as MSMB that could be used in screening and diagnosis," she added.

Whitaker explained that they "looked in tissue and urine from over 350 men with and without prostate cancer to find out how much MSMB they had".

"We then looked to see who had the genetic change. It was really exciting to find out that the genetic change and the amount of protein were linked," she added.

The earlier GWAS research that the researchers in this study built on had scanned the genomes of thousands of men with and without prostate cancer.

Those studies found a small "single letter" nucleotide variant called rs10993994 was strongly linked to an increased risk of developing cancer. The variant is common and occurs in about 30 to 40 per cent of European men and 70 to 80 per cent of men with African ancestry.

However, it should be stressed that not all men who carry the variant will develop prostate cancer: studies suggest that having one copy of the variant (ie from one parent), confers a 1.3 times higher risk of developing prostate cancer compared with carrying none.

The location of the variant is in a section of DNA that controls the production of MSMB, such that in carriers of the variant (the "high risk allele") MSMB is less active than normal.

Whitaker and colleagues found that men who carried two copies of the high-risk rs10993994 variant had the lowest levels of MSMB protein in their prostate tissue, while those who carried no copies had the highest.

They also found that:

"Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. "

They concluded that the variant they found from the genome studies does have an effect on the prostate and prostate cancer and that their study provides the "first link" between the genetic variant and a "potential test in human tissue and bodily fluids".

"There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring," they added.

Prostate cancer is the most common cancer in men in the UK, where in 2006 more than 35,000 men were diagnosed with the disease and every year over 10,000 die from it.

Funds from the University of Cambridge, CRUK, The Institute of Cancer Research, The Everyman Campaign, the EU, Hutchison Whampoa Limited and The Prostate Cancer Research Foundation helped pay for the study.

"The rs10993994 Risk Allele for Prostate Cancer Results in Clinically Relevant Changes in Microseminoprotein-Beta Expression in Tissue and Urine. ."
Whitaker HC, Kote-Jarai Z, Ross-Adams H, Warren AY, Burge J, et al.
PLoS ONE, 5(10): e13363, Published 13 October 2010.
DOI:10.1371/journal.pone.0013363

Additional sources: Cancer Research UK, NHS Choices.

Written by: Catharine Paddock, PhD