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01-04-2018 | Epidemiology

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

Authors: Jung-Woo Chae, Peh Siang Chua, Terence Ng, Angie Hui Ling Yeo, Maung Shwe, Yan Xiang Gan, Sreemanee Dorajoo, Koon Mian Foo, Kiley Wei-Jen Loh, Si-Lin Koo, Wen Yee Chay, Tira Jing Ying Tan, Sok Yuen Beh, Elaine Hsuen Lim, Guek Eng Lee, Rebecca Dent, Yoon Sim Yap, Raymond Ng, Han Kiat Ho, Alexandre Chan

Published in: Breast Cancer Research and Treatment | Issue 3/2018

Abstract

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.

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Title: 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
Authors: Jung-Woo Chae
Peh Siang Chua
Terence Ng
Angie Hui Ling Yeo
Maung Shwe
Yan Xiang Gan
Sreemanee Dorajoo
Koon Mian Foo
Kiley Wei-Jen Loh
Si-Lin Koo
Wen Yee Chay
Tira Jing Ying Tan
Sok Yuen Beh
Elaine Hsuen Lim
Guek Eng Lee
Rebecca Dent
Yoon Sim Yap
Raymond Ng
Han Kiat Ho
Alexandre Chan
Publication date: 01-04-2018
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2018
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-017-4640-7

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Abstract

Purpose

Methods

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Conclusions

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