Germline genetic variation in prostate susceptibility does not predict outcomes in the chemoprevention trials PCPT and SELECT

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  • Mahbubl Ahmed, The Institute of Cancer Research, Royal Marsden Hospital, NHS Foundation Trust, 123 Old Brompton Road, London, SW7 3RP, UK. Mahbubl.ahmed@icr.ac.uk.
  • ,
  • Chee Goh, The Institute of Cancer Research, Royal Marsden Hospital, NHS Foundation Trust, 123 Old Brompton Road, London, SW7 3RP, UK.
  • ,
  • Edward Saunders, The Institute of Cancer Research, Royal Marsden Hospital, NHS Foundation Trust, 123 Old Brompton Road, London, SW7 3RP, UK.
  • ,
  • Clara Cieza-Borrella, The Institute of Cancer Research, Royal Marsden Hospital, NHS Foundation Trust, 123 Old Brompton Road, London, SW7 3RP, UK.
  • ,
  • Zsofia Kote-Jarai, The Institute of Cancer Research, Royal Marsden Hospital, NHS Foundation Trust, 123 Old Brompton Road, London, SW7 3RP, UK.
  • ,
  • Fredrick R Schumacher, Department of Epidemiology and Biostatistics, Case Western Reserve University; Seidman Cancer Center, University Hospitals, Cleveland, OH, USA.
  • ,
  • Ros Eeles, The Institute of Cancer Research, Royal Marsden Hospital, NHS Foundation Trust, 123 Old Brompton Road, London, SW7 3RP, UK.
  • ,
  • The PRACTICAL Consortium

BACKGROUND: The development of prostate cancer can be influenced by genetic and environmental factors. Numerous germline SNPs influence prostate cancer susceptibility. The functional pathways in which these SNPs increase prostate cancer susceptibility are unknown. Finasteride is currently not being used routinely as a chemoprevention agent but the long term outcomes of the PCPT trial are awaited. The outcomes of the SELECT trial have not recommended the use of chemoprevention in preventing prostate cancer. This study investigated whether germline risk SNPs could be used to predict outcomes in the PCPT and SELECT trial.

METHODS: Genotyping was performed in European men entered into the PCPT trial (n = 2434) and SELECT (n = 4885). Next generation genotyping was performed using Affymetrix® Eureka™ Genotyping protocols. Logistic regression models were used to test the association of risk scores and the outcomes in the PCPT and SELECT trials.

RESULTS: Of the 100 SNPs, 98 designed successfully and genotyping was validated for samples genotyped on other platforms. A number of SNPs predicted for aggressive disease in both trials. Men with a higher polygenic score are more likely to develop prostate cancer in both trials, but the score did not predict for other outcomes in the trial.

CONCLUSION: Men with a higher polygenic risk score are more likely to develop prostate cancer. There were no interactions of these germline risk SNPs and the chemoprevention agents in the SELECT and PCPT trials.

Original languageEnglish
JournalProstate Cancer and Prostatic Diseases
Volume23
Issue2
Pages (from-to)333-342
Number of pages10
ISSN1365-7852
DOIs
Publication statusPublished - 2020

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