The Association of Mitochondrial Copy Number with Sarcopenia in Adult Survivors of Childhood Cancer.

Abstract

BACKGROUND\nAdult childhood cancer survivors are at risk for frailty, including low muscle mass and weakness (sarcopenia). Using peripheral blood (PB) mitochondrial DNA copy number (mtDNAcn) as a proxy for functional mitochondria, this study describes cross-sectional associations between mtDNAcn and sarcopenia among survivors.\n\n\nMETHODS\nAmong 1,762 adult childhood cancer survivors (51.6% male; median age = 29.4 [IQR = 23.3-36.8] years), with a median of 20.6 years from diagnosis (IQR = 15.2-28.2), mtDNAcn estimates were derived from whole-genome sequencing. A subset was validated by quantitative polymerase chain reaction and evaluated cross-sectionally using multivariable logistic regression for their association with sarcopenia, defined by race-, age-, and sex-specific low lean muscle mass or weak grip strength. All statistical tests were 2-sided.\n\n\nRESULTS\nThe prevalence of sarcopenia was 27.0%, higher among females than males (31.5% vs. 22.9%; P\u2009<\u20090.001) and associated with age at diagnosis; 51.7% of survivors with sarcopenia were diagnosed ages 4-13 years (p\u2009=\u20090.01). Sarcopenia was most prevalent (39.0%) among central nervous system tumor survivors. Cranial radiation (OR\u2009=\u20091.84; 95% CI\u2009=\u20091.32-2.59) and alkylating agents (OR\u2009=\u20091.34; 95% CI\u2009=\u20091.04-1.72) increased, while glucocorticoids decreased odds (OR\u2009=\u20090.72; 95% CI\u2009=\u20090.56-0.93) of sarcopenia. mtDNAcn decreased with age (β=-0.81; P\u2009=\u20090.002), was higher among females (β\u2009=\u20099.23; P\u2009=\u20090.01) and among survivors with a C allele at mt.204 (β=-17.9; P\u2009=\u20090.02). In adjusted models, every standard deviation decrease in mtDNAcn increased the odds of sarcopenia 20% (OR\u2009=\u20091.20; 95% CI\u2009=\u20091.07-1.34).\n\n\nCONCLUSIONS\nWhile a growing body of evidence supports PB mtDNAcn as a biomarker for adverse health outcomes, this study is the first to report an association between mtDNAcn and sarcopenia among childhood cancer survivors.