Cargando…
Potential of polygenic risk scores for improving population estimates of women’s breast cancer genetic risks
PURPOSE: Breast cancer risk has conventionally been assessed using family history (FH) and rare high/moderate penetrance pathogenic variants (PVs), notably in BRCA1/2, and more recently PALB2, CHEK2, and ATM. In addition to these PVs, it is now possible to use increasingly predictive polygenic risk...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553614/ https://www.ncbi.nlm.nih.gov/pubmed/34230637 http://dx.doi.org/10.1038/s41436-021-01258-y |
_version_ | 1784591617536032768 |
---|---|
author | Wolfson, Michael Gribble, Steve Pashayan, Nora Easton, Douglas F. Antoniou, Antonis C. Lee, Andrew van Katwyk, Sasha Simard, Jacques |
author_facet | Wolfson, Michael Gribble, Steve Pashayan, Nora Easton, Douglas F. Antoniou, Antonis C. Lee, Andrew van Katwyk, Sasha Simard, Jacques |
author_sort | Wolfson, Michael |
collection | PubMed |
description | PURPOSE: Breast cancer risk has conventionally been assessed using family history (FH) and rare high/moderate penetrance pathogenic variants (PVs), notably in BRCA1/2, and more recently PALB2, CHEK2, and ATM. In addition to these PVs, it is now possible to use increasingly predictive polygenic risk scores (PRS) as well. The comparative population-level predictive capability of these three different indicators of genetic risk for risk stratification is, however, unknown. METHODS: The Canadian heritable breast cancer risk distribution was estimated using a novel genetic mixing model (GMM). A realistically representative sample of women was synthesized based on empirically observed demographic patterns for appropriately correlated family history, inheritance of rare PVs, PRS, and residual risk from an unknown polygenotype. Risk assessment was simulated using the BOADICEA risk algorithm for 10-year absolute breast cancer incidence, and compared to heritable risks as if the overall polygene, including its measured PRS component, and PV risks were fully known. RESULTS: Generally, the PRS was most predictive for identifying women at high risk, while family history was the weakest. Only the PRS identified any women at low risk of breast cancer. CONCLUSION: PRS information would be the most important advance in enabling effective risk stratification for population-wide breast cancer screening. |
format | Online Article Text |
id | pubmed-8553614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-85536142021-11-04 Potential of polygenic risk scores for improving population estimates of women’s breast cancer genetic risks Wolfson, Michael Gribble, Steve Pashayan, Nora Easton, Douglas F. Antoniou, Antonis C. Lee, Andrew van Katwyk, Sasha Simard, Jacques Genet Med Article PURPOSE: Breast cancer risk has conventionally been assessed using family history (FH) and rare high/moderate penetrance pathogenic variants (PVs), notably in BRCA1/2, and more recently PALB2, CHEK2, and ATM. In addition to these PVs, it is now possible to use increasingly predictive polygenic risk scores (PRS) as well. The comparative population-level predictive capability of these three different indicators of genetic risk for risk stratification is, however, unknown. METHODS: The Canadian heritable breast cancer risk distribution was estimated using a novel genetic mixing model (GMM). A realistically representative sample of women was synthesized based on empirically observed demographic patterns for appropriately correlated family history, inheritance of rare PVs, PRS, and residual risk from an unknown polygenotype. Risk assessment was simulated using the BOADICEA risk algorithm for 10-year absolute breast cancer incidence, and compared to heritable risks as if the overall polygene, including its measured PRS component, and PV risks were fully known. RESULTS: Generally, the PRS was most predictive for identifying women at high risk, while family history was the weakest. Only the PRS identified any women at low risk of breast cancer. CONCLUSION: PRS information would be the most important advance in enabling effective risk stratification for population-wide breast cancer screening. Nature Publishing Group US 2021-07-06 2021 /pmc/articles/PMC8553614/ /pubmed/34230637 http://dx.doi.org/10.1038/s41436-021-01258-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wolfson, Michael Gribble, Steve Pashayan, Nora Easton, Douglas F. Antoniou, Antonis C. Lee, Andrew van Katwyk, Sasha Simard, Jacques Potential of polygenic risk scores for improving population estimates of women’s breast cancer genetic risks |
title | Potential of polygenic risk scores for improving population estimates of women’s breast cancer genetic risks |
title_full | Potential of polygenic risk scores for improving population estimates of women’s breast cancer genetic risks |
title_fullStr | Potential of polygenic risk scores for improving population estimates of women’s breast cancer genetic risks |
title_full_unstemmed | Potential of polygenic risk scores for improving population estimates of women’s breast cancer genetic risks |
title_short | Potential of polygenic risk scores for improving population estimates of women’s breast cancer genetic risks |
title_sort | potential of polygenic risk scores for improving population estimates of women’s breast cancer genetic risks |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553614/ https://www.ncbi.nlm.nih.gov/pubmed/34230637 http://dx.doi.org/10.1038/s41436-021-01258-y |
work_keys_str_mv | AT wolfsonmichael potentialofpolygenicriskscoresforimprovingpopulationestimatesofwomensbreastcancergeneticrisks AT gribblesteve potentialofpolygenicriskscoresforimprovingpopulationestimatesofwomensbreastcancergeneticrisks AT pashayannora potentialofpolygenicriskscoresforimprovingpopulationestimatesofwomensbreastcancergeneticrisks AT eastondouglasf potentialofpolygenicriskscoresforimprovingpopulationestimatesofwomensbreastcancergeneticrisks AT antoniouantonisc potentialofpolygenicriskscoresforimprovingpopulationestimatesofwomensbreastcancergeneticrisks AT leeandrew potentialofpolygenicriskscoresforimprovingpopulationestimatesofwomensbreastcancergeneticrisks AT vankatwyksasha potentialofpolygenicriskscoresforimprovingpopulationestimatesofwomensbreastcancergeneticrisks AT simardjacques potentialofpolygenicriskscoresforimprovingpopulationestimatesofwomensbreastcancergeneticrisks |