The Association of Mitochondrial Copy Number with Sarcopenia in Adult Survivors of Childhood Cancer
Menée à partir de données portant sur 1 762 adultes ayant survécu à un cancer pédiatrique, cette étude transversale analyse l'association entre le nombre de copies de gènes de l'ADN mitochondrial mesuré dans les leucocytes du sang périphérique et la présence d'une sarcopénie
Background : Adult 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. Methods : Among 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. Results : The prevalence of sarcopenia was 27.0%, higher among females than males (31.5% vs. 22.9%; P < 0.001) and associated with age at diagnosis; 51.7% of survivors with sarcopenia were diagnosed ages 4-13 years (p = 0.01). Sarcopenia was most prevalent (39.0%) among central nervous system tumor survivors. Cranial radiation (OR = 1.84; 95% CI = 1.32-2.59) and alkylating agents (OR = 1.34; 95% CI = 1.04-1.72) increased, while glucocorticoids decreased odds (OR = 0.72; 95% CI = 0.56-0.93) of sarcopenia. mtDNAcn decreased with age (
β=-0.81; P
= 0.002), was higher among females (
β
= 9.23; P = 0.01) and among survivors with a C allele at mt.204 (
β=-17.9; P
= 0.02). In adjusted models, every standard deviation decrease in mtDNAcn increased the odds of sarcopenia 20% (OR = 1.20; 95% CI = 1.07-1.34). Conclusions : While 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.