Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

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



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-85062824329 (requires institutional sign-in at Scopus site)   26 Citations


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 MC


Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antineoplastic Agents
Breast Neoplasms
CpG Islands
DNA Methylation
Epigenesis, Genetic
Neoplasm Staging
Prospective Studies
Treatment Outcome