British researchers have shown that incorporating a genetic risk score (GRS) for prostate cancer into routine clinical care could help identify patients at greatest risk for the disease who should be prioritized for screening.
The risk score developed by a University of Exeter team could also help men at very low risk of cancer avoid invasive tests, which in turn would reduce patient harm and demand for secondary care services.
You study results are published in the British Journal of Cancer.
lead author dr Harry Green, Research Associate at the University of Exeter Medical School, said: “Our study is the first to show that genetic risks are taken into account in GPs [general practitioner’s] Risk assessment of the symptoms of patients with possible prostate cancer could lead to faster referral of those most at risk.”
The study included data from 6,777 men without a history of prostate cancer registered in the UK Biobank – a biomedical database containing detailed genetic and health information from half a million people – and their GPs on lower urinary tract symptoms (LUTS), such as nocturia, common urination or bad stream.
All of these symptoms are common in men over the age of 50 and are often present at the time of prostate cancer diagnosis. However, they are also associated with the occurrence of benign prostate enlargement and increase with age, complicating attempts to accurately diagnose tumors.
Of the men included in the study, 3.5% had a prostate cancer diagnosis within 2 years of seeing their GP with LUTS.
When the researchers applied a genetic risk score to the cohort based on the 269 known risk variants for prostate cancer, they found that the risk of prostate cancer more than doubled with each increase in the standard deviation.
Put another way, men who scored in the lowest 20% of the observed range had a less than 1% chance of developing cancer within 2 years, while men who scored in the highest 20% of the range had an 8% chance 8% had. a significant difference.
Green and colleagues point out that UK guidelines recommend that anyone with a 3% or more chance of developing cancer should be followed up, but there are suggestions to lower that threshold to 2%.
At the reduced threshold, investigators estimated that at least 40% of the cohort with LUTS could avoid referrals. With GPs in the UK making around 800,000 referrals for suspected prostate cancer each year, including genetic cancer risk in GP triage could mean that 320,000 men could safely avoid a referral and uncomfortable exam, while expediting the remaining 160,000 for a faster exam could.
The team calculated that the accuracy of the GRS alone was 70.3%, but when combined with age, this increased to 77.2%. In comparison, the reported diagnostic accuracy of PSA (prostate-specific antigen) tests – the current screening tool for men with LUTS – is around 72%.
The study authors assume that the combination of GRS with PSA could further improve the accuracy.
“We need more research to find out how PSA and genetic testing would interact and what would be the consequences for PSA if genetic testing were introduced,” said the study’s lead researcher, Dr. Sarah Bailey, senior research fellow at the University of Exeter Medical School, said Inside Precision Medicine.
She added that the team is now looking for more funding to expand the study to include PSA and genetics together in primary care.
Further research is also needed to examine how the GRS works in men of non-European background, as the current study only included white European men.
“In theory, a genetic risk score should do just as well in men of other ethnicities, but more research is needed to ensure that this is the case and that non-European men are not disadvantaged by the genetic testing,” Bailey noted.
At present, genetic sequencing is not available in primary care in the UK, but the researchers say current trends suggest it will become part of routine practice in the future.
Bailey hopes the GRS could be used routinely and “patients at greatest risk of prostate cancer could be quickly followed up for evaluation in primary care, perhaps without having to wait for a PSA test – they could be referred directly if they experience any symptoms.” of the lower urinary tract.”