Impact of chemotherapy for breast cancer on leukocyte DNA methylation landscape and cognitive function: a prospective study

Abstract 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-chemo...

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Main Authors: Song Yao, Qiang Hu, Sarah Kerns, Li Yan, Adedayo A. Onitilo, Jamal Misleh, Kelley Young, Lianlian Lei, Javier Bautista, Mostafa Mohamed, Supriya G. Mohile, Christine B. Ambrosone, Song Liu, Michelle C. Janelsins
Format: Article
Language:English
Published: BMC 2019-03-01
Series:Clinical Epigenetics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13148-019-0641-1
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spelling doaj-688c0ba8a21f4a47893ef35afcf29e1d2020-11-25T00:11:31ZengBMCClinical Epigenetics1868-70751868-70832019-03-0111111010.1186/s13148-019-0641-1Impact of chemotherapy for breast cancer on leukocyte DNA methylation landscape and cognitive function: a prospective studySong Yao0Qiang Hu1Sarah Kerns2Li Yan3Adedayo A. Onitilo4Jamal Misleh5Kelley Young6Lianlian Lei7Javier Bautista8Mostafa Mohamed9Supriya G. Mohile10Christine B. Ambrosone11Song Liu12Michelle C. Janelsins13Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer CenterDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer CenterDepartment of Radiation Oncology, University of RochesterDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer CenterWisconsin NCORPDelaware NCORPKansas City NCORPDepartment of Public Health Sciences, University of RochesterDepartment of Surgery, Cancer Control, University of RochesterDepartment of Medicine, University of RochesterDepartment of Medicine, University of RochesterDepartment of Cancer Prevention and Control, Roswell Park Comprehensive Cancer CenterDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer CenterDepartment of Surgery, Cancer Control, University of RochesterAbstract 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.http://link.springer.com/article/10.1186/s13148-019-0641-1DNA methylationChemotherapyBreast cancerCognitive function
collection DOAJ
language English
format Article
sources DOAJ
author Song Yao
Qiang Hu
Sarah Kerns
Li Yan
Adedayo A. Onitilo
Jamal Misleh
Kelley Young
Lianlian Lei
Javier Bautista
Mostafa Mohamed
Supriya G. Mohile
Christine B. Ambrosone
Song Liu
Michelle C. Janelsins
spellingShingle Song Yao
Qiang Hu
Sarah Kerns
Li Yan
Adedayo A. Onitilo
Jamal Misleh
Kelley Young
Lianlian Lei
Javier Bautista
Mostafa Mohamed
Supriya G. Mohile
Christine B. Ambrosone
Song Liu
Michelle C. Janelsins
Impact of chemotherapy for breast cancer on leukocyte DNA methylation landscape and cognitive function: a prospective study
Clinical Epigenetics
DNA methylation
Chemotherapy
Breast cancer
Cognitive function
author_facet Song Yao
Qiang Hu
Sarah Kerns
Li Yan
Adedayo A. Onitilo
Jamal Misleh
Kelley Young
Lianlian Lei
Javier Bautista
Mostafa Mohamed
Supriya G. Mohile
Christine B. Ambrosone
Song Liu
Michelle C. Janelsins
author_sort Song Yao
title Impact of chemotherapy for breast cancer on leukocyte DNA methylation landscape and cognitive function: a prospective study
title_short Impact of chemotherapy for breast cancer on leukocyte DNA methylation landscape and cognitive function: a prospective study
title_full Impact of chemotherapy for breast cancer on leukocyte DNA methylation landscape and cognitive function: a prospective study
title_fullStr Impact of chemotherapy for breast cancer on leukocyte DNA methylation landscape and cognitive function: a prospective study
title_full_unstemmed Impact of chemotherapy for breast cancer on leukocyte DNA methylation landscape and cognitive function: a prospective study
title_sort impact of chemotherapy for breast cancer on leukocyte dna methylation landscape and cognitive function: a prospective study
publisher BMC
series Clinical Epigenetics
issn 1868-7075
1868-7083
publishDate 2019-03-01
description Abstract 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.
topic DNA methylation
Chemotherapy
Breast cancer
Cognitive function
url http://link.springer.com/article/10.1186/s13148-019-0641-1
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