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Genetics and Genomics

Response to: Genetic risk scores may compound rather than solve the issue of prostate cancer overdiagnosis (BJC-LT3342090)

British Journal of Cancer volume 128, pages 487–488 (2023)Cite this article

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We thank the authors Horton et al. [1] for their comments on our recent paper about the potential application of a genetic risk score for prostate cancer detection in primary care settings [2]. We agree that the evidence base is not yet strong enough to support the use of genetic risk scores in clinic, although we would argue that Conti et al.’s GRS for prostate cancer [3] is reasonably, not weakly, predictive with an AUC of 0.703 when applied in our study.

The authors cite a study by Klein et aI. as evidence that ‘PSA is more predictive of prostate cancer metastasis or death than a genetic risk score’ [4]. Klein et al. applied a risk score including 125 SNPs to two screening (asymptomatic) cohorts; the outcome was lifetime distant metastases or death from prostate cancer. In that study, the AUC of a single PSA test was 0.78, and the AUC of the GRS was 0.63. The AUC of GRS alone in our study was 0.703; the difference could be explained by the inclusion of a greater number of SNPs in the Conti score or the differences in study population. Crucially, our study included men with lower urinary tract symptoms and the outcome was prostate cancer within two years; this is different to the screening population.

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References

  1. Rechtman L, Brenner S, Wright M, Ritsick M, Rahman F, Han M, et al. Genetic risk scores may compound rather than solve the issue of prostate cancer overdiagnosis. Br J Cancer. 2022;9:1692–701.

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  2. Green HD, Merriel SWD, Oram RA, Ruth KS, Tyrrell J, Jones SE, et al. Applying a genetic risk score for prostate cancer to men with lower urinary tract symptoms in primary care to predict prostate cancer diagnosis: a cohort study in the UK Biobank. Br J Cancer. 2022;127:1534–9.

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  5. Merriel SWD, Pocock L, Gilbert E, Creavin S, Walter FM, Spencer A, et al. Systematic review and meta-analysis of the diagnostic accuracy of prostate-specific antigen (PSA) for the detection of prostate cancer in symptomatic patients. BMC Med. 2022;20:54.

  6. NICE guideline [NG131]. Overview. Prostate cancer: diagnosis and management. Guidance. NICE; 2019.

  7. National Prostate Cancer Audit. Results of the NPCA Prospective Audit in England and Wales for men diagnosed from 1 April 2019 to 31 March 2020 and the Impact of COVID-19 in England during 2020. London; 2022.

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Authors and Affiliations

  1. Exeter Centre of Excellence for Diabetes Research (EXCEED), University of Exeter Medical School, St Luke’s Campus, University of Exeter, Heavitree Road, Devon, Exeter, EX1 2LU, UK

    Harry D. Green

  2. DISCOVERY Group, University of Exeter Medical School, St Luke’s Campus, University of Exeter, Heavitree Road, Devon, Exeter, EX1 2LU, UK

    Samuel W. D. Merriel & Sarah E. R. Bailey

  3. Institute of Biomedical and Clinical Science, University of Exeter Medical School, St Luke’s Campus, University of Exeter, Heavitree Road, Devon, Exeter, EX1 2LU, UK

    Richard A. Oram & Michael N. Weedon

  4. Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK

    Katherine S. Ruth & Jessica Tyrrell

  5. Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland

    Samuel E. Jones

  6. University of Exeter Medical School, St Luke’s Campus, University of Exeter, Heavitree Road, Devon, Exeter, EX1 2LU, UK

    Chrissie Thirlwell

  7. UCL Cancer Institute, Huntley St, EX1 2LU, London, UK

    Chrissie Thirlwell

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  1. Harry D. Green
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  9. Sarah E. R. Bailey
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SB drafted the response. All authors reviewed before submission.

Corresponding author

Correspondence to Sarah E. R. Bailey.

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Green, H.D., Merriel, S.W.D., Oram, R.A. et al. Response to: Genetic risk scores may compound rather than solve the issue of prostate cancer overdiagnosis (BJC-LT3342090). Br J Cancer 128, 487–488 (2023). https://doi.org/10.1038/s41416-022-02081-1

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