The BARCODE1 pilot study targeting men with increased genetic risk of developing prostate cancer: Examining the feasibility of a community-based screening program using polygenic risk score to target screening.

Authors

null

Jana Kathlyn McHugh

Institute of Cancer Research, London, United Kingdom

Jana Kathlyn McHugh , Sarah Benafif , Holly ni Raghallaigh , Elizabeth Bancroft , Zsofia Kote-Jarai , Ros A. Eeles

Organizations

Institute of Cancer Research, London, United Kingdom, The Institute of Cancer Research, Sutton, United Kingdom, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom, Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom

Research Funding

Other
European Research Council Seventh Framework Programme ERC-2013-AdG-339208, National Institute for health Research (NIHR).

Background: A significant proportion of Prostate cancer (PrCa) risk is attributable to heritable risk factors of which only a minority are high risk Mendelian traits. A greater proportion of PrCa is due to the combined effect of multiple low risk variants. There have been approximately 170 single nucleotide polymorphisms (SNPs) identified that are associated with PrCa risk in Europeans. Although each of these confer a low to moderate risk of PrCa, the cumulative risk (polygenic risk score, PRS) of increasing numbers of these risk alleles may confer a substantial relative risk. In PrCa genetic profiling, using PRS, could be used to target population screening to those at highest risk. BARCODE1 is the first study to prospectively review the use of a genetic profile in PrCa screening in the general population in the UK. Methods: Our study invited healthy males aged 55-69 to participate through their Primary Care physicians. Collection kits were mailed to retrieve saliva samples. Genotyping was carried out after DNA extraction using a study specific assay and the PRS was calculated for each participant using the sum of weighted alleles for 130 risk loci. Prostate MRI and Biopsy were then offered to men in the top 10% of the genetic risk profile. Results: 1434 men were invited by letter to participate. The uptake was 26%, of whom 87% of men were eligible for inclusion. Following DNA extraction, genotyping, and quality control checks, data were available for 297 men. 25 participants had PRS in the top 10% and were invited for screening; 19 underwent a prostate MRI, and 18 went on to have a systematic (+/- targeted prostate biopsy. There were 7 diagnoses of PrCa (38.9%). The cancers detected were low-risk and are being managed with Active Surveillance (AS). Results of the first year of follow up will be presented and an update of the main study which aims to recruit 5000 men. Conclusions: The BARCODE1 pilot has shown the feasibility of this population-based study, with an overall uptake of 26% and a cancer incidence of nearly 40%. We have identified approximately 70 Primary care providers who have contributed to the transition to the full BARCODE1 study, which will aim to recruit 5,000 men. The BARCODE1 study results will be important in defining the role of PRS genetic profiling in targeted PrCa population screening. Clinical trial information: IRAS257684.

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Abstract Details

Meeting

2021 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session: Prostate Cancer - Localized Disease

Track

Prostate Cancer - Localized

Sub Track

Prevention, Screening, and Hereditary Cancers

Clinical Trial Registration Number

IRAS257684

Citation

J Clin Oncol 39, 2021 (suppl 6; abstr 227)

DOI

10.1200/JCO.2021.39.6_suppl.227

Abstract #

227

Poster Bd #

Online Only

Abstract Disclosures