Pre-diagnostic DNA methylation patterns differ according to mammographic breast density amongst women who subsequently develop breast cancer: a case-only study in the EPIC-Florence cohort.

Autor: Caini S; Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Via Cosimo il Vecchio 2, 50141, Florence, Italy., Fiorito G; Laboratory of Biostatistics, Department of Biomedical Sciences, University of Sassari, Sassari, Italy.; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College, London, UK., Palli D; Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Via Cosimo il Vecchio 2, 50141, Florence, Italy. d.palli@ispro.toscana.it., Bendinelli B; Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Via Cosimo il Vecchio 2, 50141, Florence, Italy., Polidoro S; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College, London, UK.; Italian Institute for Genomic Medicine (IIGM), Turin, Italy., Silvestri V; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Ottini L; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Ambrogetti D; Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Via Cosimo il Vecchio 2, 50141, Florence, Italy., Zanna I; Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Via Cosimo il Vecchio 2, 50141, Florence, Italy., Saieva C; Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Via Cosimo il Vecchio 2, 50141, Florence, Italy., Masala G; Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Via Cosimo il Vecchio 2, 50141, Florence, Italy.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2021 Sep; Vol. 189 (2), pp. 435-444. Date of Electronic Publication: 2021 Jun 08.
DOI: 10.1007/s10549-021-06273-w
Abstrakt: Purpose: Mammographic breast density (MBD) is a marker of increased breast cancer (BC) risk, yet much remains to be clarified about the underlying mechanisms. We investigated whether DNA methylation patterns differ between high- vs. low-MBD women who developed BC during an 8.9-year median follow-up in the Florence section of the European Prospective Investigation into Cancer and Nutrition.
Methods: We analysed 96 pairs of women with BC arising on high- vs. low-MBD breasts (BI-RADS category III-IV vs. I). DNA methylation was determined on pre-diagnostic blood samples using the Illumina Infinium MethylationEPIC BeadChip assay. The statistical analysis was conducted by performing an epigenome-wide association study (EWAS), by searching differentially methylated regions (DMRs) in gene promoters (followed by functional enrichment and gene annotation analysis); and through a "candidate pathways" approach focusing on pre-defined inflammation-related pathways.
Results: In EWAS, no single CpG site was differentially methylated between high- and low-MBD women after correction for multiple testing. A total of 140 DMRs were identified, of which 131 were hyper- and 9 hypo-methylated amongst high-MBD women. These DMRs encompassed an annotation cluster of 35 genes coding for proteins implicated in transcription regulation and DNA binding. The "apoptosis signalling" was the only inflammation-related candidate pathway differentially methylated between high- and low-MBD women.
Conclusion: Pre-diagnostic methylation patterns differ between high- vs. low-MBD women who subsequently develop BC, particularly, in genes involved in the regulation of DNA transcription and cell apoptosis. Our study provides novel clues about the mechanisms linking MBD and BC.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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