Association of mitochondrial DNA content in peripheral blood with cancer-related fatigue and chemotherapy-related cognitive impairment in early-stage breast cancer patients: a prospective cohort study.

Autor: Chae JW; Department of Pharmacy, National University of Singapore, Blk S4A Level 3, 18 Science Drive 4, Singapore, 117543, Singapore.; Department of Pharmacy, National Cancer Centre Singapore, Singapore, Singapore.; College of Pharmacy, Chungnam National University, Daejeon, South Korea., Chua PS; Department of Pharmacy, National University of Singapore, Blk S4A Level 3, 18 Science Drive 4, Singapore, 117543, Singapore., Ng T; Department of Pharmacy, National University of Singapore, Blk S4A Level 3, 18 Science Drive 4, Singapore, 117543, Singapore.; Department of Pharmacy, National Cancer Centre Singapore, Singapore, Singapore.; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore., Yeo AHL; Department of Pharmacy, National University of Singapore, Blk S4A Level 3, 18 Science Drive 4, Singapore, 117543, Singapore., Shwe M; Department of Pharmacy, National University of Singapore, Blk S4A Level 3, 18 Science Drive 4, Singapore, 117543, Singapore.; Department of Pharmacy, National Cancer Centre Singapore, Singapore, Singapore., Gan YX; Department of Pharmacy, National University of Singapore, Blk S4A Level 3, 18 Science Drive 4, Singapore, 117543, Singapore.; Department of Pharmacy, National Cancer Centre Singapore, Singapore, Singapore., Dorajoo S; Department of Pharmacy, National University of Singapore, Blk S4A Level 3, 18 Science Drive 4, Singapore, 117543, Singapore., Foo KM; Department of Pharmacy, K.K. Women's and Children's Hospital, Singapore, Singapore., Loh KW; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore., Koo SL; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore., Chay WY; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore., Tan TJY; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore., Beh SY; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore., Lim EH; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore., Lee GE; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore., Dent R; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.; Duke-NUS Graduate Medical School Singapore, Singapore, Singapore., Yap YS; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore., Ng R; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.; Duke-NUS Graduate Medical School Singapore, Singapore, Singapore., Ho HK; Department of Pharmacy, National University of Singapore, Blk S4A Level 3, 18 Science Drive 4, Singapore, 117543, Singapore., Chan A; Department of Pharmacy, National University of Singapore, Blk S4A Level 3, 18 Science Drive 4, Singapore, 117543, Singapore. phaac@nus.edu.sg.; Department of Pharmacy, National Cancer Centre Singapore, Singapore, Singapore. phaac@nus.edu.sg.; Duke-NUS Graduate Medical School Singapore, Singapore, Singapore. phaac@nus.edu.sg.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2018 Apr; Vol. 168 (3), pp. 713-721. Date of Electronic Publication: 2018 Jan 08.
DOI: 10.1007/s10549-017-4640-7
Abstrakt: Purpose: Cancer-related fatigue (CRF) and chemotherapy-related cognitive impairment (CRCI) are reported to be associated with mitochondrial dysfunction. Hence, mitochondrial DNA (mtDNA) content, a biomarker of mitochondrial dysfunction, is hypothesized to correlate with the onset of CRF and CRCI. This study aims to evaluate the association between peripheral blood mtDNA content reduction and severity of CRF and CRCI in patients receiving chemotherapy.
Methods: This was a prospective cohort study. Early-stage breast cancer patients receiving anthracycline- or taxane-based chemotherapy were recruited. CRF was assessed using MFSI-SF, and CRCI was assessed using FACT-Cog and CANTAB at two timepoints: baseline (T1; prior to treatment) and 6 weeks after initiation of treatment (T2). mtDNA content was measured at both timepoints using real-time quantitative polymerase chain reaction. Multiple logistic regression was utilized to evaluate the association between mtDNA reduction and worsening of CRF and CRCI, adjusting for age, anxiety, insomnia, plasma cytokines concentrations, and other clinically important covariates.
Results: A total of 108 patients (age 52.0 ± 9.2 years; 82.4% Chinese; 64.8% receiving anthracycline-based chemotherapy) were recruited. Proportions of patients with worsening of CRF increased from the lower to the upper quartiles of mtDNA reduction (22.2, 33.3, 55.6, and 63.0% in quartiles 1, 2, 3, and 4, respectively, p = 0.001 for trend). Reduction of mtDNA content was significantly greater among those with worsening of CRF and CRCI compared to those without CRF [mean reduction (± SD): 36.5 (46.1) vs. 9.4 (34.5), p < 0.001]. After adjusting for covariates, every 1-unit reduction of the mtDNA content was associated with a 4% increased risk for worsening of CRF (95% CI, 1-6%; p = 0.009).
Conclusions: This is the first study to show that the reduction of mtDNA content in peripheral blood is associated with the onset of CRF in patients receiving chemotherapy. Further validation studies are required to confirm the findings.
Databáze: MEDLINE
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