Integrating a Polygenic Risk Score into a clinical setting would impact risk predictions in familial breast cancer.
J Med Genet
; 61(2): 150-154, 2024 Jan 19.
Article
in En
| MEDLINE
| ID: mdl-37580114
ABSTRACT
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, PRS313) into clinical sequencing of women with familial BC in Sweden.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 without and with PRS313.RESULTS:
Women with BC but no pathogenic variants in hereditary BC genes have a higher PRS313 compared with population controls (mean+0.78 SD, p<3e-9). Implementing PRS313 in the clinical risk estimation before their BC diagnosis would have changed the recommended follow-up in 24%-45% of women.CONCLUSIONS:
Our results show the potential impact of incorporating PRS313 directly in the clinical genomic investigation of women with familial BC.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
Language:
En
Journal:
J Med Genet
Year:
2024
Document type:
Article
Affiliation country:
Sweden