ArticleClinical epigenetics2023
DNA methylation age in paired tumor and adjacent normal breast tissue in Chinese women with breast cancer.
Article in Clinical epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 9 citations in OpenAlex.
- Article
- Senescent obesity signature in breast cancer: a paradigm of reverse cardio-oncology.European heart journal · 2026Review
- Methylation profiling of normal tissue adjacent to breast tumors reveals two distinct groups with divergent tumor microenvironment features.NPJ breast cancer · 2026Article
- Can DNA Methylation in Peritumoral and Contralateral Breast Tissue Predict Recurrence or Second Breast Cancers?Current issues in molecular biology · 2026Article
- Unravelling the genetics and epigenetics of the ageing tumour microenvironment in cancer.Nature reviews. Cancer · 2025Review
- Epigenetic age and accelerated aging phenotypes: a tumor biomarker for predicting colorectal cancer.Aging · 2025Article
- Genetic determinants of proteomic aging.npj aging · 2025Article
- Functionally enriched epigenetic clocks reveal tissue-specific discordant aging patterns in individuals with cancer.Communications medicine · 2025Article
- Biological Aging in Combination with Lifestyle Factors in the Blood-Based Methylome: A Biomarker for Colorectal Cancer Susceptibility in African American Women.Aging and disease · 2025Article
- Epigenetic Inhibitors Differentially Impact TGF-β1 Signaling Cascades in COPD Airway Smooth Muscle Cells.Cells · 2024Article
- Article
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Authors and funding
31 authors at 10 institutions in 3 countries.
Funding
Abstract
backgroundFew studies have examined epigenetic age acceleration (AA), the difference between DNA methylation (DNAm) predicted age and chronological age, in relation to somatic genomic features in paired cancer and normal tissue, with less work done in non-European populations. In this study, we aimed to examine DNAm age and its associations with breast cancer risk factors, subtypes, somatic genomic profiles including mutation and copy number alterations and other aging markers in breast tissue of Chinese breast cancer (BC) patients from Hong Kong.
methodsWe performed genome-wide DNA methylation profiling of 196 tumor and 188 paired adjacent normal tissue collected from Chinese BC patients in Hong Kong (HKBC) using Illumina MethylationEPIC array. The DNAm age was calculated using Horvath's pan-tissue clock model. Somatic genomic features were based on data from RNA sequencing (RNASeq), whole-exome sequencing (WES), and whole-genome sequencing (WGS). Pearson's correlation (r), Kruskal-Wallis test, and regression models were used to estimate associations of DNAm AA with somatic features and breast cancer risk factors.
resultsDNAm age showed a stronger correlation with chronological age in normal (Pearson r = 0.78, P < 2.2e-16) than in tumor tissue (Pearson r = 0.31, P = 7.8e-06). Although overall DNAm age or AA did not vary significantly by tissue within the same individual, luminal A tumors exhibited increased DNAm AA (P = 0.004) while HER2-enriched/basal-like tumors exhibited markedly lower DNAm AA (P = < .0001) compared with paired normal tissue. Consistent with the subtype association, tumor DNAm AA was positively correlated with ESR1 (Pearson r = 0.39, P = 6.3e-06) and PGR (Pearson r = 0.36, P = 2.4e-05) gene expression. In line with this, we found that increasing DNAm AA was associated with higher body mass index (P = 0.039) and earlier age at menarche (P = 0.035), factors that are related to cumulative exposure to estrogen. In contrast, variables indicating extensive genomic instability, such as TP53 somatic mutations, high tumor mutation/copy number alteration burden, and homologous repair deficiency were associated with lower DNAm AA.
conclusionsOur findings provide additional insights into the complexity of breast tissue aging that is associated with the interaction of hormonal, genomic, and epigenetic mechanisms in an East Asian population.
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