Scientists have uncovered the functionality of a genetic variant in the prostate specific antigen (PSA) gene to improve the current diagnostic test to help distinguish aggressive from non-aggressive prostate cancers.

The study, published in Nature Communications, reveals the functionality of the genetic variant in the prostate specific antigen – PSA.

The current PSA test cannot distinguish between non-aggressive and aggressive, deadly prostate cancer.

However, the multinational team has uncovered in tests on mice that the variant is associated with both reduced prostate cancer risk and an aggressive type of this cancer. The insights could help develop point-of-care diagnostics and improved treatments.

First author on the QUT-led study, Brisbane’s Translational Research Institute-based Dr Srilakshmi Srinivasan, from QUT’s School of Biomedical Sciences, said the researchers studied the role of a particular prostate cancer genetic variation or SNP.

“Through comprehensive lab and mice tests we found that this SNP, although associated with reduced prostate cancer risk, is also associated with an aggressive type of this cancer,” Dr Srinivasan said.

“This SNP contributes to reduced serum prostate-specific antigen (PSA) levels that may lead to detection bias during PSA screening leading to delayed diagnosis and treatment.”

Dr Srinivasan said the findings gave some insight into anomalies associated with current diagnostics and treatments for what is the second most common cancer in men world-wide.

“The PSA test has long been used as the basis of non-invasive diagnostic and prognostic prostate cancer tests, and it has saved lives,” she said.

“However, the PSA test cannot identify aggressive versus non-aggressive types of cancer which means some tumours with high PSA in the blood can lead to over-diagnoses with over-treatment.

“This means often men undergo painful procedures such as biopsies for accurate diagnoses which affects their quality of life and incurs extra health system costs.

“Furthermore, because the PSA test is unable to identify aggressive cancers, tumours which exhibit low levels of PSA in the blood can get missed during early screening, leading to highly aggressive disease with high mortality.”

Professor Jyotsna Batra, who led the study, said the research team was now using the information that men with genetic variations in the gene which codes for PSA could be predisposed to aggressive prostate cancer to develop tools that could be used by GPs to identify high-risk patients, but with low blood PSA levels.

“Findings from this study may lead to developing a novel and simple point-of-care (POC) device,” Professor Batra said.

“It is an important step forward in an era of personalised treatment because it can provide an individualised diagnostic assessment that can be a guide for more appropriate clinical care.”

QUT Distinguished Professor Emeritus Judith Clements, who co-led the research with Professor Batra, from QUT’s School of Biomedical Sciences, said: “Our findings may enable better prognostic prediction and, by distinguishing the more aggressive cancers, identify a high-risk group that need early treatment.”

This project is part of Professor Batra’s research focus on unravelling the genetic intricacies of hereditary disorders using bioinformatics and experimental approaches.

The QUT team comprises Professor Batra, Dr Srinivasan, Dr Achala Fernando, Emeritus Distinguished Professor Clements, Associate Professor Nathalie Bock, Adjunct Professor Ian Vela, Adjunct Professor Rupert C Ecker, Adjunct Professor Nigel Brown.

More than 60 researchers from around the world contributed to the study.

The study, A PSA SNP associated with cellular function and clinical outcome in men with prostate cancer, was published in Nature Communications.

Source: Queensland University of Technology