DNA methylation age in paired tumor and adjacent normal breast tissue in Chinese women with breast cancer.

Autor: Koka H; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA., Bodelon C; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA., Horvath S; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.; San Diego Institute of Science, Alto Labs, San Diego, CA, USA., Lee PMY; The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong., Prince of Wales Hospital, Sha Tin, N.T., Hong Kong SAR, China., Wang D; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Song L; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Zhang T; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA., Hurson AN; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA., Guida JL; Division of Cancer Control and Population Sciences, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA., Zhu B; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA., Bailey-Whyte M; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.; School of Medicine, University of Limerick, Limerick, Ireland., Wang F; The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong., Prince of Wales Hospital, Sha Tin, N.T., Hong Kong SAR, China., Wu C; Department of Pathology, North District Hospital, Hong Kong, China., Tsang KH; Department of Pathology, Yan Chai Hospital, Hong Kong, China., Tsoi YK; Department of Surgery, North District Hospital, Hong Kong, China., Chan WC; Department of Surgery, North District Hospital, Hong Kong, China., Law SH; Department of Surgery, North District Hospital, Hong Kong, China., Hung RKW; Department of Surgery, North District Hospital, Hong Kong, China., Tse GM; Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China., Yuen KK; Department of Pathology, North District Hospital, Hong Kong, China., Karlins E; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Jones K; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Vogt A; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Zhu B; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Hutchinson A; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Hicks B; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Garcia-Closas M; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA., Chanock S; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA., Barnholtz-Sloan J; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.; Center for Biomedical Informatics and Information Technology, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA., Tse LA; The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong., Prince of Wales Hospital, Sha Tin, N.T., Hong Kong SAR, China. shelly@cuhk.edu.hk., Yang XR; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA. royang@mail.nih.gov.
Jazyk: angličtina
Zdroj: Clinical epigenetics [Clin Epigenetics] 2023 Mar 30; Vol. 15 (1), pp. 55. Date of Electronic Publication: 2023 Mar 30.
DOI: 10.1186/s13148-023-01465-1
Abstrakt: Background: Few 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.
Methods: We 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.
Results: DNAm 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.
Conclusions: Our 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.
(© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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