Impact of chemotherapy for breast cancer on leukocyte DNA methylation landscape and cognitive function: a prospective study. Clin Epigenetics 2019 Mar 12;11(1):45
Date
03/15/2019Pubmed ID
30867049Pubmed Central ID
PMC6416954DOI
10.1186/s13148-019-0641-1Scopus ID
2-s2.0-85062824329 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
BACKGROUND: Little is known about the effects of chemotherapeutic drugs on DNA methylation status of leukocytes, which may be predictive of treatment benefits and toxicities. Based on a prospective national study, we characterize the changes in leukocyte DNA methylome from pre- to post-chemotherapy (approximately 4 months apart) in 93 patients treated for early stage breast cancer and 48 matched non-cancer controls. We further examined significant methylation changes with perceived cognitive impairment, a clinically significant problem related to cancer and chemotherapy.
RESULTS: Approximately 4.2% of the CpG sites measured using the Illumina 450K methylation array underwent significant changes after chemotherapy (p < 1e-7), in comparison to a stable DNA methylome in controls. Post-chemotherapy, the estimated relative proportions of B cells and CD4+ T cells were decreased by a median of 100% and 39%, respectively, whereas the proportion of monocytes was increased by a median of 91%. After controlling for leukocyte composition, 568 CpGs from 460 genes were still significantly altered following chemotherapy. With additional adjustment for chemotherapy regimen, cumulative infusions, growth factors, and steroids, changes in four CpGs remained significant, including cg16936953 in VMP1/MIR21, cg01252023 in CORO1B, cg11859398 in SDK1, and cg19956914 in SUMF2. The most significant CpG, cg16936953, was also associated with cognitive decline in breast cancer patients.
CONCLUSIONS: Chemotherapy profoundly alters the composition and DNA methylation landscape of leukocytes in breast cancer patients. Our results shed light on the epigenetic response of circulating immune cell populations to cytotoxic chemotherapeutic drugs and provide possible epigenetic links to the degeneration of cognitive function associated with chemotherapy.
Author List
Yao S, Hu Q, Kerns S, Yan L, Onitilo AA, Misleh J, Young K, Lei L, Bautista J, Mohamed M, Mohile SG, Ambrosone CB, Liu S, Janelsins MCAuthor
Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antineoplastic AgentsBreast Neoplasms
Cognition
CpG Islands
DNA Methylation
Epigenesis, Genetic
Female
Humans
Leukocytes
Neoplasm Staging
Prospective Studies
Treatment Outcome
