Pre-diagnosis blood DNA methylation profiling of twin pairs discordant for breast cancer points to the importance of environmental risk factors

Autor: Hannes Frederik Bode, Liang He, Jacob V. B. Hjelmborg, Jaakko Kaprio, Miina Ollikainen
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Clinical Epigenetics, Vol 16, Iss 1, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 1868-7083
DOI: 10.1186/s13148-024-01767-y
Popis: Abstract Background Assessment of breast cancer (BC) risk generally relies on mammography, family history, reproductive history, and genotyping of major mutations. However, assessing the impact of environmental factors, such as lifestyle, health-related behavior, or external exposures, is still challenging. DNA methylation (DNAm), capturing both genetic and environmental effects, presents a promising opportunity. Previous studies have identified associations and predicted the risk of BC using DNAm in blood; however, these studies did not distinguish between genetic and environmental contributions to these DNAm sites. In this study, associations between DNAm and BC are assessed using paired twin models, which control for shared genetic and environmental effects, allowing testing for associations between DNAm and non-shared environmental exposures and behavior. Results Pre-diagnosis blood samples of 32 monozygotic (MZ) and 76 dizygotic (DZ) female twin pairs discordant for BC were collected at the mean age of 56.0 years, with the mean age at diagnosis 66.8 years and censoring 75.2 years. We identified 212 CpGs (p
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