Associations between mitochondrial copy number, exercise capacity, physiologic cost of walking, and cardiac strain in young adult survivors of childhood cancer.

Autor: Berkman AM; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA., Goodenough CG; Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS-735, Memphis, TN, 38105, USA., Durakiewicz P; Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS-735, Memphis, TN, 38105, USA., Howell CR; Division of Preventive Medicine, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Wang Z; Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS-735, Memphis, TN, 38105, USA.; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Easton J; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Mulder HL; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Armstrong GT; Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS-735, Memphis, TN, 38105, USA., Hudson MM; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.; Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS-735, Memphis, TN, 38105, USA., Kundu M; Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Ness KK; Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS-735, Memphis, TN, 38105, USA. Kiri.Ness@stjude.org.
Jazyk: angličtina
Zdroj: Journal of cancer survivorship : research and practice [J Cancer Surviv] 2024 Aug; Vol. 18 (4), pp. 1154-1167. Date of Electronic Publication: 2024 Apr 18.
DOI: 10.1007/s11764-024-01590-7
Abstrakt: Purpose: Childhood cancer survivors are at risk for cardiac dysfunction and impaired physical performance, though underlying cellular mechanisms are not well studied. In this cross-sectional study, we examined the association between peripheral blood mitochondrial DNA copy number (mtDNA-CN, a proxy for mitochondrial function) and markers of performance impairment and cardiac dysfunction.
Methods: Whole-genome sequencing, validated by quantitative polymerase chain reaction, was used to estimate mtDNA-CN in 1720 adult survivors of childhood cancer (48.5% female; mean age = 30.7 years, standard deviation (SD) = 9.0). Multivariable logistic regression was performed to evaluate the associations between mtDNA-CN and exercise intolerance, walking inefficiency, and abnormal global longitudinal strain (GLS), adjusting for treatment exposures, age, sex, and race and ethnicity.
Results: The prevalence of exercise intolerance, walking inefficiency, and abnormal GLS among survivors was 25.7%, 10.7%, and 31.7%, respectively. Each SD increase of mtDNA-CN was associated with decreased odds of abnormal GLS (adjusted odds ratio (OR) = 0.88, p = 0.04) but was not associated with exercise intolerance (OR = 1.02, p = 0.76) or walking inefficiency (OR = 1.06, p = 0.46). Alkylating agent exposure was associated with increased odds of exercise intolerance (OR = 2.25, p < 0.0001), walking inefficiency (OR = 2.37, p < 0.0001), and abnormal GLS (OR = 1.78, p = 0.0002).
Conclusions: Increased mtDNA-CN is associated with decreased odds of abnormal cardiac function in childhood cancer survivors.
Implications for Cancer Survivors: These findings demonstrate a potential role for mtDNA-CN as a biomarker of early cardiac dysfunction in this population.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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