Germline genetic variation in prostate susceptibility does not predict outcomes in the chemoprevention trials PCPT and SELECT.
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ICR Authors
Authors
Ahmed, M
Goh, C
Saunders, E
Cieza-Borrella, C
PRACTICAL consortium,
Kote-Jarai, Z
Schumacher, FR
Eeles, R
Goh, C
Saunders, E
Cieza-Borrella, C
PRACTICAL consortium,
Kote-Jarai, Z
Schumacher, FR
Eeles, R
Document Type
Journal Article
Date
2020-06-01
Date Accepted
2019-06-24
Date Available
Abstract
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.
Citation
Prostate cancer and prostatic diseases, 2020, 23 (2), pp. 333 - 342
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
1365-7852
eISSN
1476-5608
Research Team
Oncogenetics