Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/3420638

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Lakeman, I.M.M. (2022)

The path to individualised breast cancer screening

Doctoral Thesis
The main objective of work presented in this thesis was to explore the clinical utility of the Polygenic Risk Score (PRS) based on breast cancer associated common low risk variants, which explain ~18% of the familial relative risk, for individual breast cancer risk prediction. It did so by generating knowledge about the PRS in the Dutch general population and in clinic-based breast cancer families, as well as in a large international population of BRCA1/2 pathogenic variant carriers. We have validated the association of the PRS with breast cancer for women in both the Dutch population and breast cancer families and showed a better risk-discrimination by adding the PRS to family-based risk prediction. Secondly, we have shown that addition of the PRS to family-based risk prediction has an impact on screening recommendations for many non-carriers and carriers of a pathogenic variant in a moderate breast cancer gene. The results will support implementation of comprehensive risk...Show moreThe main objective of work presented in this thesis was to explore the clinical utility of the Polygenic Risk Score (PRS) based on breast cancer associated common low risk variants, which explain ~18% of the familial relative risk, for individual breast cancer risk prediction. It did so by generating knowledge about the PRS in the Dutch general population and in clinic-based breast cancer families, as well as in a large international population of BRCA1/2 pathogenic variant carriers. We have validated the association of the PRS with breast cancer for women in both the Dutch population and breast cancer families and showed a better risk-discrimination by adding the PRS to family-based risk prediction. Secondly, we have shown that addition of the PRS to family-based risk prediction has an impact on screening recommendations for many non-carriers and carriers of a pathogenic variant in a moderate breast cancer gene. The results will support implementation of comprehensive risk prediction in the clinic, and may help women to make more informed choices about their optimal clinical management.
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Clinical genetics
Breast cancer
Breast cancer screening
Polygenic Risk Score
Risk prediction
Genetic epidemiology
All authors
Lakeman, I.M.M.
Supervisor
Devilee, P.; Asperen, C.J. van
Co-supervisor
Rodriguez-Girondo, M.
Committee
Schmidt, M.K.; Uitterlinden, A.G.; Schmutzler, R.; Adank, M.A.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2022-06-14

Funding

Sponsorship
Dutch Cancer Society (KWF), grant UL2014-7473