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...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| 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 |
| _version_ | 1811278609132814336 |
|---|---|
| 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 |
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T00:38:56Z |
| format | Article |
| id | doaj.art-688c0ba8a21f4a47893ef35afcf29e1d |
| institution | Directory Open Access Journal |
| issn | 1868-7075 1868-7083 |
| language | English |
| last_indexed | 2024-04-13T00:38:56Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-688c0ba8a21f4a47893ef35afcf29e1d2022-12-22T03:10:15ZengBMCClinical 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 |
| 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 |
| title | 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_short | 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 |
| topic | DNA methylation Chemotherapy Breast cancer Cognitive function |
| url | http://link.springer.com/article/10.1186/s13148-019-0641-1 |
| work_keys_str_mv | AT songyao impactofchemotherapyforbreastcanceronleukocytednamethylationlandscapeandcognitivefunctionaprospectivestudy AT qianghu impactofchemotherapyforbreastcanceronleukocytednamethylationlandscapeandcognitivefunctionaprospectivestudy AT sarahkerns impactofchemotherapyforbreastcanceronleukocytednamethylationlandscapeandcognitivefunctionaprospectivestudy AT liyan impactofchemotherapyforbreastcanceronleukocytednamethylationlandscapeandcognitivefunctionaprospectivestudy AT adedayoaonitilo impactofchemotherapyforbreastcanceronleukocytednamethylationlandscapeandcognitivefunctionaprospectivestudy AT jamalmisleh impactofchemotherapyforbreastcanceronleukocytednamethylationlandscapeandcognitivefunctionaprospectivestudy AT kelleyyoung impactofchemotherapyforbreastcanceronleukocytednamethylationlandscapeandcognitivefunctionaprospectivestudy AT lianlianlei impactofchemotherapyforbreastcanceronleukocytednamethylationlandscapeandcognitivefunctionaprospectivestudy AT javierbautista impactofchemotherapyforbreastcanceronleukocytednamethylationlandscapeandcognitivefunctionaprospectivestudy AT mostafamohamed impactofchemotherapyforbreastcanceronleukocytednamethylationlandscapeandcognitivefunctionaprospectivestudy AT supriyagmohile impactofchemotherapyforbreastcanceronleukocytednamethylationlandscapeandcognitivefunctionaprospectivestudy AT christinebambrosone impactofchemotherapyforbreastcanceronleukocytednamethylationlandscapeandcognitivefunctionaprospectivestudy AT songliu impactofchemotherapyforbreastcanceronleukocytednamethylationlandscapeandcognitivefunctionaprospectivestudy AT michellecjanelsins impactofchemotherapyforbreastcanceronleukocytednamethylationlandscapeandcognitivefunctionaprospectivestudy |