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. 2022 Mar;129(3):325-336.
doi: 10.1111/bju.15535. Epub 2021 Aug 15.

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

Sarah Benafif  1 , Holly Ni Raghallaigh  1 , Eva McGrowder  1 , Edward J Saunders  1 , Mark N Brook  1 , Sibel Saya  1   2 , Reshma Rageevakumar  1 , Sarah Wakerell  1 , Denzil James  1 , Anthony Chamberlain  1 , Natalie Taylor  3 , Matthew Hogben  3 , Barbara Benton  3 , Lucia D'Mello  3 , Kathryn Myhill  3 , Christos Mikropoulos  4 , Hywel Bowen-Perkins  5 , Imran Rafi  6 , Michelle Ferris  7 , Andre Beattie  8 , Shophia Kuganolipava  9 , Tamsin Sevenoaks  10 , Juliet Bower  11 , Pardeep Kumar  3 , Steven Hazell  3 , Nandita M deSouza  12 , Antonis Antoniou  13 , Elizabeth Bancroft  1   3 , Zsofia Kote-Jarai  1 , Rosalind Eeles  1   3
Affiliations

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

Sarah Benafif et al. BJU Int. 2022 Mar.

Abstract

Objectives: 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 methods: Healthy 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.

Results: Invitation 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.

Conclusion: The 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. Patient Summary What is the paper about? Very few prostate cancer screening programmes currently exist anywhere in the world. Our pilot study investigated if men in the UK would find it acceptable to have a genetic test based on a saliva sample to examine their risk of prostate cancer development. This test would guide whether men are offered prostate cancer screening tests. What does it mean for patients? We found that the study design was acceptable: 26% of men invited to take part agreed to have the test. The majority of men who were found to have an increased genetic risk of prostate cancer underwent further tests offered (prostate MRI scan and biopsy). We have now expanded the study to enrol 5000 men. The BARCODE1 study will be important in examining whether this approach could be used for large-scale population prostate cancer screening.

Keywords: GWAS; SNPs; precision medicine; prostate cancer; screening.

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Conflict of interest statement

Prof. Rosalind Eeles reports grants from European Research Council funding the submitted work. Prof Eeles reports personal fees from AstraZeneca UK Limited for her role as a member of an external Expert Committee as part of the Prostate Cancer Diagnosis Advisory Panel, and University of Chicago for an invited lecture, both of which are outside the submitted work. Dr Sarah Benafif, Dr Elizabeth Bancroft, Mrs Sarah Wakerell, Mrs Natalie Taylor, Mr Edward Saunders, Dr Holly Ni Raghallaigh, Ms Kathryn Myhill, Dr Eva McGrowder, Dr Zsofia Kote‐Jarai, Mr Denzil James, Mr Matthew Hogben, Mrs Lucia D’Mello, Mrs Barbara Benton, Dr Mark Brook, Mr Anthony Chamberlain, Mrs Reshma Rageevakuma and Dr Sibel Saya report funding for the submitted work from a European Research Council grant for this study. Dr Imran Rafi, Dr Tamsin Sevenoaks, Dr Andre Beattie, Dr Hywel Bowen‐Perkins, Dr Juliet Bower, Dr Shophia Kuganolipava report funding of research costs for the submitted work from The Institute of Cancer Research and from National Institute for Health Research: Clinical Research Network. Dr Michelle Ferris reports funding of research costs for the submitted work from The Institute of Cancer Research and from National Institute for Health Research: Clinical Research Network. Dr Ferris reports financial activities outside the submitted work related to the Befriend Your Boobs project for which she also has a patent, as well as a research grant from Noclor. Prof Antonis Antoniou is listed as creator of the BOADICEA algorithm that has been licensed by Cambridge Enterprise (outside the submitted work). The following authors have no conflict of interest to disclose: Dr Steve Hazell, Dr Christos Mikropoulos, Mr Pardeep Kumar, Prof Nandita De Souza.

Figures

Fig. 1
Fig. 1
BARCODE1 study outline.
Fig. 2
Fig. 2
BARCODE1 pilot study recruitment. Percentages relate to the proportion of invitations to the study. *Saliva samples from four participants were received after 15 April 2018, which was the cut‐off date for DNA extraction in the pilot study. These participants will have DNA extracted and analysed in the main BARCODE1 study. One saliva sample did not yield sufficient DNA at extraction and a new saliva sample was requested. This participant will also be added to the main BARCODE1 study.
Fig. 3
Fig. 3
PRS distribution in BARCODE1 Pilot. (A) The dashed line denotes the 90th centile PRS value (11.15). (B) Boxplot of the PRS distribution in BARCODE1 pilot displaying minimum and maximum values of PRS in whole study cohort as well as outliers. The dashed line denotes the 90th centile PRS value (11.15).
See this image and copyright information in PMC

Comment in

References

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