PURPOSE: About 65% of childhood survivors who were exposed to chemotherapeutic agents during treatment suffer from multiple late adverse effects. Even though both males and females were treated with chemotherapy during their cancer, the distinction between them is not always taken into consideration in an exercise oncology context. This study aims to assess cardiorespiratory fitness and moderate to vigorous physical activity (MVPA) of survivors in comparison to healthy participants. Genetic associations with cardiorespiratory fitness levels were reported to provide a better understanding of how physiological parameters differ in both males and females, and to find out whether gender and genetic parameters have an impact on their cardiorespiratory fitness.
METHODS: Germline variants in a selected set of genes were analyzed for an association with cardiorespiratory fitness. Whole-exome sequencing in survivors (N=239) was performed. Cardiorespiratory fitness and MVPA data were compared between childhood ALL survivors (N=221) and healthy participants (N=825). Additional analyses were performed to study the physiological differences between males and females.
RESULTS: We found that female survivors (27.7±6.7mL·kg^-1·min^-1) were more affected than males (36.8±7.1mL·kg^-1·min^-1) by low cardiorespiratory fitness. For a clinically equivalent level of MVPA, cardiorespiratory fitness was significantly lower in female survivors (27.7±6.7mL·kg^-1·min^-1), compared to healthy females (37.0±7.6mL·kg^-1·min^-1). Female survivors' physical deconditioning seems to increase with age. Female survivors have significant genetic associations between their cardiorespiratory fitness and their trainability genes (LEPR, IGFBPI and ENO3 genes) that play an important role in the functioning of their skeletal and cardiac muscles.
CONCLUSIONS: Female survivors are at higher risk than males to have an impairment in their cardiorespiratory fitness and represent at-risk patients in regard to their genetic dispositions. The promotion of physical activity needs to be encouraged through the care system with the involvement of health care professionals in pediatric oncology. An evidence-based medicine approach is essential to help females to improve their cardiorespiratory fitness through physical activity.