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Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway.
Ho, Peh Joo; Khng, Alexis Jiaying; Tan, Benita Kiat-Tee; Lim, Geok Hoon; Tan, Su-Ming; Tan, Veronique Kiak Mien; Tan, Ryan Shea Ying Cong; Lim, Elaine Hsuen; Iau, Philip Tsau-Choong; Chew, Ying Jia; Lim, Yi Ying; Hartman, Mikael; Tan, Ern Yu; Li, Jingmei.
Afiliación
  • Ho PJ; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore.
  • Khng AJ; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Republic of Singapore.
  • Tan BK; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Republic of Singapore.
  • Lim GH; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore.
  • Tan SM; Department of Breast Surgery, Singapore General Hospital, Singapore, Republic of Singapore.
  • Tan VKM; Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore.
  • Tan RSYC; Department of General Surgery, Sengkang General Hospital, Singapore, Republic of Singapore.
  • Lim EH; KK Breast Department, KK Women's and Children's Hospital, Singapore, 229899, Republic of Singapore.
  • Iau PT; Division of Breast Surgery, Changi General Hospital, Singapore, Republic of Singapore.
  • Chew YJ; Department of Breast Surgery, Singapore General Hospital, Singapore, Republic of Singapore.
  • Lim YY; Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore.
  • Hartman M; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore.
  • Tan EY; Oncology Academic Programme, Duke-NUS Medical School, Singapore, Republic of Singapore.
  • Li J; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore.
Breast Cancer Res ; 25(1): 136, 2023 11 06.
Article en En | MEDLINE | ID: mdl-37932858
BACKGROUND: Exposure to cytotoxic chemotherapy treatment may alter DNA methylation (DNAm) in breast cancer patients. METHODS: We performed DNAm analysis in 125 breast cancer patients with blood drawn before and after chemotherapy, using the Illumina MethylationEPIC array. DNAm changes of 588,798 individual CpGs (including 41,207 promoter regions) were evaluated using linear regression models adjusted for monocyte proportion. Gene set enrichment analyses (GSEA) were conducted to identify key Gene Ontology (GO) biological processes or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with chemotherapy. Results were validated in a separate cohort of breast cancer patients who were treated (n = 1273) and not treated (n = 872) by chemotherapy (1808 blood, 337 saliva). RESULTS: A total of 141 differentially methylated CpGs and 11 promoters were significantly associated with chemotherapy after multiple testing corrections in both the paired sample and single time point analyses. GSEA of promoter regions (pre-ranked by test statistics) identified six suppressed biological processes (p < 4.67e-8) related to sensory perception and detection of chemical stimuli, including smell perception (GO:0007606, GO:0007608, GO:0009593, GO:0050906, GO:0050907, and GO:0050911). The same six biological processes were significantly suppressed in the validation dataset (p < 9.02e-14). The KEGG pathway olfactory transduction (hsa04740) was also found to be significantly suppressed (ppaired-samples = 1.72e-9, psingle-timepoint-blood = 2.03e-15 and psingle-timepoint-saliva = 7.52e-56). CONCLUSION: The enrichment of imprinted genes within biological processes and pathways suggests a biological mechanism by which chemotherapy could affect the perception of smell.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Metilación de ADN Límite: Female / Humans Idioma: En Revista: Breast Cancer Res Asunto de la revista: NEOPLASIAS Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Metilación de ADN Límite: Female / Humans Idioma: En Revista: Breast Cancer Res Asunto de la revista: NEOPLASIAS Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido