Abstract 438P
Background
Given that CRF is characterized by a lack of energy, it is postulated that mitochondrial dysfunction may contribute to its etiology. Using mitochondrial DNA (mtDNA) copy number and displacement-loop (D-loop) mutation status, this study aims to evaluate mtDNA content between fatigue subclasses, over the course of chemotherapy.
Methods
In a prospective cohort study, early-stage breast patients’ fatigue levels were assessed using the validated Multi-Dimensional Fatigue Symptom Inventory–Short Form (MFSI-SF) and their blood was drawn before, during and after treatment. Relative mtDNA copy number was determined via real-time quantitative polymerase chain reaction while mitochondrial genome was sequenced directly for D-loop mutations at nucleotide positions 303, 489 and 514. Subclasses of extent of fatigue was derived using latent class analysis, based on magnitude of change in sub-domain scores after treatment, with respect to baseline. Clinically relevant factors that differentiate the identified subclasses were then compared between the fatigued groups.
Results
A total of 133 patients (mean age ± SD: 51.2 ± 8.8 years, median mtDNA: 71.0) were classified into two fatigue subclasses: mild fatigue (75.2%) and fatigued group (24.8%) respectively. Based on mtDNA trajectory, patients who are predisposed to CRF started off with lower baseline values and experienced slower recovery. Median mtDNA content was reduced over 12 weeks after initiation of chemotherapy (p < 0.001) and was reported to be consistently lower in fatigued group (T2: 48.0 vs 56.0; T3: 61.4 vs 66.0) although the difference was not found to be statistically significant. The proportion of patients with D-loop mutation status was comparable between fatigued group and mild fatigue (303: 81.8% vs 73.0%, 489: 45.5% vs 47.0% and 514: 45.5% vs 53.0%). However, no association was reported between mtDNA levels over time or D-loop mutation with CRF status.
Conclusions
mtDNA content and D-loop mutation status do not sufficiently differentiate fatigue subclasses, suggesting that future research may be needed to study the differential expression of mitochondrial dysfunction-related genes and the pathways they may perturb.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
National University of Singapore.
Funding
National Medical Research Council.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
97P - The role of adjuvant chemotherapy according to the status of surgical margin in rectal cancer
Presenter: Jong Hoon Lee
Session: Poster display session
Resources:
Abstract
98P - Influence of DPYD*9, DPYD*6 and GSTP1 ile105val genetic polymorphisms on capecitabine and oxaliplatin (CAPOX) associated toxicities in colorectal cancer patients
Presenter: Ashok Varma
Session: Poster display session
Resources:
Abstract
99P - Patient-derived tumour model by new culture method leading to the precision medicine
Presenter: Norikatsu Miyoshi
Session: Poster display session
Resources:
Abstract
100P - Clinical impact and carcinogenic mechanism of NCAPG overexpression in colon cancer
Presenter: Kai-Yuan Lin
Session: Poster display session
Resources:
Abstract
101P - Combined cellular immunotherapy and chemotherapy improves clinical outcome and displays safety in the treatment of patients with colorectal cancer
Presenter: Chang Wang
Session: Poster display session
Resources:
Abstract
102P - Clinical features of anorectal cancer in patients with Crohn’s disease: Japanese single center study
Presenter: Kazuhiro Watanabe
Session: Poster display session
Resources:
Abstract
103P - Contrast-enhanced CT-based textural parameters as potential prognostic factors of survival for colorectal cancer patients receiving targeted therapy
Presenter: Yanfei Yang
Session: Poster display session
Resources:
Abstract
104P - Prognostic significance of tumour location to the oncologic outcome of colon cancer
Presenter: Sare Hosseini
Session: Poster display session
Resources:
Abstract
105P - Detection and clinical significance of circulating tumour cells in patients with rectal cancer
Presenter: Shuohui Dong
Session: Poster display session
Resources:
Abstract
106P - The risk of malignization incidence in patients with polyps and polyposis of the colon and rectum
Presenter: Yakov Ten
Session: Poster display session
Resources:
Abstract