DNA methylation at quantitative trait loci (mQTLs) varies with cell type and nonheritable factors and may improve breast cancer risk assessment.
Journal
NPJ precision oncology
ISSN: 2397-768X
Titre abrégé: NPJ Precis Oncol
Pays: England
ID NLM: 101708166
Informations de publication
Date de publication:
27 Sep 2023
27 Sep 2023
Historique:
received:
27
03
2023
accepted:
13
09
2023
medline:
28
9
2023
pubmed:
28
9
2023
entrez:
27
9
2023
Statut:
epublish
Résumé
To individualise breast cancer (BC) prevention, markers to follow a person's changing environment and health extending beyond static genetic risk scores are required. Here, we analysed cervical and breast DNA methylation (n = 1848) and single nucleotide polymorphisms (n = 1442) and demonstrate that a linear combination of methylation levels at 104 BC-associated methylation quantitative trait loci (mQTL) CpGs, termed the WID™-qtBC index, can identify women with breast cancer in hormone-sensitive tissues (AUC = 0.71 [95% CI: 0.65-0.77] in cervical samples). Women in the highest combined risk group (high polygenic risk score and WID™-qtBC) had a 9.6-fold increased risk for BC [95% CI: 4.7-21] compared to the low-risk group and tended to present at more advanced stages. Importantly, the WID™-qtBC is influenced by non-genetic BC risk factors, including age and body mass index, and can be modified by a preventive pharmacological intervention, indicating an interaction between genome and environment recorded at the level of the epigenome. Our findings indicate that methylation levels at mQTLs in relevant surrogate tissues could enable integration of heritable and non-heritable factors for improved disease risk stratification.
Identifiants
pubmed: 37758816
doi: 10.1038/s41698-023-00452-2
pii: 10.1038/s41698-023-00452-2
pmc: PMC10533818
doi:
Types de publication
Journal Article
Langues
eng
Pagination
99Subventions
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : 742432
Organisme : Cancerfonden (Swedish Cancer Society)
ID : 22 2093 Pj
Informations de copyright
© 2023. Nature Publishing Group UK.
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