Integrating a Polygenic Risk Score into a clinical setting would impact risk predictions in familial breast cancer.

Genetics, Medical

Journal

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

Informations de publication

Date de publication:
14 Aug 2023
Historique:
received: 02 04 2023
accepted: 28 07 2023
medline: 15 8 2023
pubmed: 15 8 2023
entrez: 14 8 2023
Statut: aheadofprint

Résumé

Low-impact genetic variants identified in population-based genetic studies are not routinely measured as part of clinical genetic testing in familial breast cancer (BC). We studied the consequences of integrating an established Polygenic Risk Score (PRS) (BCAC 313, PRS We developed an add-on sequencing panel to capture 313 risk variants in addition to the clinical screening of hereditary BC genes. Index patients with no pathogenic variant from 87 families, and 1000 population controls, were included in comparative PRS calculations. Including detailed family history, sequencing results and tumour pathology information, we used BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) V.6 to estimate contralateral and lifetime risks Women with BC but no pathogenic variants in hereditary BC genes have a higher PRS Our results show the potential impact of incorporating PRS

Sections du résumé

BACKGROUND BACKGROUND
Low-impact genetic variants identified in population-based genetic studies are not routinely measured as part of clinical genetic testing in familial breast cancer (BC). We studied the consequences of integrating an established Polygenic Risk Score (PRS) (BCAC 313, PRS
METHODS METHODS
We developed an add-on sequencing panel to capture 313 risk variants in addition to the clinical screening of hereditary BC genes. Index patients with no pathogenic variant from 87 families, and 1000 population controls, were included in comparative PRS calculations. Including detailed family history, sequencing results and tumour pathology information, we used BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) V.6 to estimate contralateral and lifetime risks
RESULTS RESULTS
Women with BC but no pathogenic variants in hereditary BC genes have a higher PRS
CONCLUSIONS CONCLUSIONS
Our results show the potential impact of incorporating PRS

Identifiants

pubmed: 37580114
pii: jmg-2023-109311
doi: 10.1136/jmg-2023-109311
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Panagiotis Baliakas (P)

Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Arielle R Munters (AR)

Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Anders Kämpe (A)

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.

Bianca Tesi (B)

Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Department of Clinical Genetics, Karolinska Institutet, Stockholm, Sweden.

Marie-Louise Bondeson (ML)

Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Claes Ladenvall (C)

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Daniel Eriksson (D)

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden daniel.eriksson@igp.uu.se.
Department of Clinical Genetics, Akademiska Sjukhuset, Uppsala, Sweden.

Classifications MeSH