The BARCODE1 Pilot: a feasibility study of using germline single nucleotide polymorphisms to target prostate cancer screening

Abstract

To assess the feasibility and uptake of a community-based prostate cancer (PCa) screening programme selecting men according to their genetic risk of PCa. To assess the uptake of PCa screening investigations by men invited for screening. The uptake of the pilot study would guide the opening of the larger BARCODE1 study recruiting 5000 men. Subjects and MethodsHealthy males aged 55-69 years were invited to participate via their general practitioners (GPs). Saliva samples were collected via mailed collection kits. After DNA extraction, genotyping was conducted using a study specific assay. Genetic risk was based on genotyping 130 germline PCa risk single nucleotide polymorphisms (SNPs). A polygenic risk score (PRS) was calculated for each participant using the sum of weighted alleles for 130 SNPs. Study participants with a PRS lying above the 90th centile value were invited for PCa screening by prostate magnetic resonance imaging (MRI) and biopsy. ResultsInvitation letters were sent to 1434 men. The overall study uptake was 26% (375/1436) and 87% of responders were eligible for study entry. DNA genotyping data were available for 297 men and 25 were invited for screening. After exclusions due to medical comorbidity/invitations declined, 18 of 25 men (72%) underwent MRI and biopsy of the prostate. There were seven diagnoses of PCa (38.9%). All cancers were low-risk and were managed with active surveillance. ConclusionThe BARCODE1 Pilot has shown this community study in the UK to be feasible, with an overall uptake of 26%. The main BARCODE1 study is now open and will recruit 5000 men. The results of BARCODE1 will be important in defining the role of genetic profiling in targeted PCa population screening.

How Well do Polygenic Risk Scores Identify Men at High Risk for Prostate Cancer? Systematic Review and Meta-Analysis

“…Prostate cancer screening with PSA has been shown to decrease PCa mortality in the ERSPC trialhowever, with the disadvantage of overdiagnosis and overtreatment of indolent disease [16]. The potential of more tailored, risk-adapted, or personalized screening utilizing genetic susceptibility or clinical parameters to target screening is of major scientific interest [17,18].…”

Can polygenic risk scores contribute to cost-effective cancer screening? A systematic review

“…51 Future modeling could also consider the effect of possible intervention-generated inequalities, 52 and the effect of knowledge of one's own PRS on anxiety, participation in screening, and other outcomes. 53,54 A further broad area for future research relates to the costing and valuing of polygenic risk data. All studies necessarily lacked robust external data on the per-individual costs of population-level genotyping and on all downstream economic impacts stemming from the use of these data.…”

Principles of molecular testing for hereditary cancer

“…PRS for breast, colorectal and prostate cancers in particular may be informative for population-based screening and prevention. 210,[212][213][214][215][216][217][218][219][220] Polygenic background can modify risks for monogenic cancers, and PRS may therefore have utility for refining cancer risk estimates for patients with monogenic cancer variants. 221 For example, the BOADICEA model for breast cancer risk prediction incorporates PRS along with monogenic variants and other risk factors (eg, age, mammographic density) to generate personalized breast cancer risk estimates.…”

“…PRS may identify a greater proportion of the population at increased risk for cancer than would be identified by traditional genetic testing approaches. PRS for breast, colorectal and prostate cancers in particular may be informative for population‐based screening and prevention 210,212–220 . Polygenic background can modify risks for monogenic cancers, and PRS may therefore have utility for refining cancer risk estimates for patients with monogenic cancer variants 221 .…”