Addition of a 161-SNP polygenic risk score to family history-based risk prediction: impact on clinical management in non-


Journal

Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R

Informations de publication

Date de publication:
09 2019
Historique:
received: 08 02 2019
revised: 29 03 2019
accepted: 20 04 2019
pubmed: 13 6 2019
medline: 12 6 2020
entrez: 13 6 2019
Statut: ppublish

Résumé

The currently known breast cancer-associated single nucleotide polymorphisms (SNPs) are presently not used to guide clinical management. We explored whether a genetic test that incorporates a SNP-based polygenic risk score (PRS) is clinically meaningful in non- 101 non- The mean sPRS for cases and their unaffected relatives was 0.70 (SD=0.9) and 0.53 (SD=0.9), respectively. A significant association was found between sPRS and breast cancer, HR=1.16, 95% CI 1.03 to 1.28, p=0.026. Addition of the sPRS to risk prediction based on family history alone changed screening recommendations in 11.5%, 14.7% and 19.8 % of the women according to breast screening guidelines from the USA (National Comprehensive Cancer Network), UK (National Institute for Health and Care Excellence and the Netherlands (Netherlands Comprehensive Cancer Organisation), respectively. Our results support the application of the PRS in risk prediction and clinical management of women from genetically unexplained breast cancer families.

Sections du résumé

BACKGROUND
The currently known breast cancer-associated single nucleotide polymorphisms (SNPs) are presently not used to guide clinical management. We explored whether a genetic test that incorporates a SNP-based polygenic risk score (PRS) is clinically meaningful in non-
METHODS
101 non-
RESULTS
The mean sPRS for cases and their unaffected relatives was 0.70 (SD=0.9) and 0.53 (SD=0.9), respectively. A significant association was found between sPRS and breast cancer, HR=1.16, 95% CI 1.03 to 1.28, p=0.026. Addition of the sPRS to risk prediction based on family history alone changed screening recommendations in 11.5%, 14.7% and 19.8 % of the women according to breast screening guidelines from the USA (National Comprehensive Cancer Network), UK (National Institute for Health and Care Excellence and the Netherlands (Netherlands Comprehensive Cancer Organisation), respectively.
CONCLUSION
Our results support the application of the PRS in risk prediction and clinical management of women from genetically unexplained breast cancer families.

Identifiants

pubmed: 31186341
pii: jmedgenet-2019-106072
doi: 10.1136/jmedgenet-2019-106072
doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

581-589

Informations de copyright

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Inge M M Lakeman (IMM)

Department of Human Genetics, Leids Universitair Medisch Centrum, Leiden, The Netherlands.

Florentine S Hilbers (FS)

Department of Human Genetics, Leids Universitair Medisch Centrum, Leiden, The Netherlands.
Breast International Group (BIG), Brussels, Belgium.

Mar Rodríguez-Girondo (M)

Department of Medical Statistics and Bioinformatics, Leids Universitair Medisch Centrum, Leiden, The Netherlands.

Andrew Lee (A)

Public Health and Primary Care, Centre for Cancer Gentic Epidemiology, Cambridge University, Cambridge, UK.

Maaike P G Vreeswijk (MPG)

Department of Human Genetics, Leids Universitair Medisch Centrum, Leiden, The Netherlands.

Antoinette Hollestelle (A)

Department of Medical Oncology, Erasmus MC Kanker Instituut, Rotterdam, The Netherlands.

Caroline Seynaeve (C)

Department of Medical Oncology, Erasmus MC Kanker Instituut, Rotterdam, The Netherlands.

Hanne Meijers-Heijboer (H)

Department of Clinical Genetics, VU medisch centrum, Amsterdam, The Netherlands.

Jan C Oosterwijk (JC)

Department of Genetics, Universitair Medisch Centrum Groningen, Groningen, The Netherlands.

Nicoline Hoogerbrugge (N)

Department of Human Genetics, Universitair Medisch Centrum Sint Radboud, Nijmegen, The Netherlands.

Edith Olah (E)

Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.

Hans F A Vasen (HFA)

Department of Gastroenterology and Hepatology, Leids Universitair Medisch Centrum, Leiden, The Netherlands.

Christi J van Asperen (CJ)

Department of Clinical Genetics, Leids Universitair Medisch Centrum, Leiden, The Netherlands.

Peter Devilee (P)

Department of Human Genetics, Leids Universitair Medisch Centrum, Leiden, The Netherlands p.devilee@lumc.nl.
Department of Pathology, Leids Universitair Medisch Centrum, Leiden, The Netherlands.

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