BARCODE 1: A pilot study investigating the use of genetic profiling to identify men in the general population with the highest risk of prostate cancer to invite for targeted screening.

Abstract

1505 Background: Genetic profiling could be used to target population screening for prostate cancer (PrCa). Approximately 170 single nucleotide polymorphisms (SNPs) have been identified that associate with PrCa development. Although these confer a low to moderate risk of PrCa, the risk is cumulative with increasing number of risk alleles. BARCODE1 is the first study to prospectively investigate the use of a genetic profile in PrCa screening in the UK general population. Methods: A custom Eurek Genomics (EG) SNP assay was developed. Healthy males aged 55-69 were invited to participate via their General Practitioners (GPs). Saliva samples were collected via mailed collection kits. After DNA extraction, genotyping was conducted using the EG assay and a polygenic risk score (PRS) was calculated for each participant. The PRS was calculated using the sum of the weighted alleles for 130 risk loci. Men in the top 10% of the genetic risk profile were invited for prostate MRI and biopsy at the Royal Marsden Hospital (RMH) in London. Results: Invitation letters were sent to 1434 men; overall uptake was 26% (range 13%-47%). 87% of responders were eligible for study entry. DNA was extracted from 303 samples and genotyped. Data were available for 285 men following QC. Mean PRS was 10.33 with a standard deviation of 0.64; twenty-five participants with a PRS above the 90th centile were identified for screening with MRI and prostate biopsy. Of these men (after exclusions due to medical comorbidity/invitations declined) 9 out of 20 had an abnormal MRI (45%) and 18 men underwent biopsy with 7 diagnoses of PrCa (38.8%). All cancers were low-risk with a mean PSA of 1.8 and were managed with Active Surveillance (AS). There were two adverse events following biopsy, both simple lower urinary tract infections managed with oral antibiotics. Average duration of follow-up is 4.5 months (range 1-11). Conclusions: Successful completion of recruitment has shown this community study to be feasible, with an average uptake of 26%. Approximately 70 GP sites have been identified to allow a transition to the full BARCODE-1 study which will recruit 5000 men. The use of genetic profiles to guide PrCa screening is attractive; it requires a one-off test utilising germline DNA which can be assessed for risk loci which are constant, unlike PSA which fluctuates. The results of the BARCODE1 study will be important in defining the role of genetic profiling in targeted PrCa population screening.