Discussion
In a large heterogeneous sample of adult survivors of childhood cancer, we found associations between phenotypes of short sleep duration and clinically assessed physical and psychological health outcomes. Short sleep duration with prolonged sleep onset latency increased risk of high/serve burden of chronic health conditions greater than 2-fold. Associations between all phenotypes of short sleep duration and psychological health outcomes ranged from 2 to 3-fold in strength. While we did not observe large differences in the strength of associations between our phenotypes of short sleep duration and health outcomes, short sleep with prolonged SOL or WASO yielded consistent and strong associations to several health outcomes, including pulmonary, endocrine, gastrointestinal, neurologic, anxiety, and depression.
In our sample, 44% of survivors reported a habitual short sleep duration of less than seven hours per night. Among survivors with a short sleep duration, 21-27% also reported a prolonged SOL and/or WASO, and nearly 30% of short sleepers met criteria for a poor sleep efficiency defined as <85%. Overall, 57% of the sample scored above the PSQI clinical cut-off for poor sleep quality. Consistent with previous literature,18,19 these findings underscore the severity and prevalence of sleep disturbances among survivors. Additionally, sleep disturbances30and fatigue are associated with reduced quality of life19, neurocognitive impairment,30and depression19 among cross-sectional studies of childhood cancer survivors. One longitudinal study reported associations between dimensions of self-reported sleep and new onset psychological distress and new onset migraines.18 However, this study relied on self-reported health conditions. The current study utilized clinically-ascertained health conditions and highlights the range in which sleep duration relates to many biological systems (i.e. cardiac, pulmonary, gastrointestinal, and neurologic) and dimensions of psychological health.
There are several physiological pathways through which sleep duration could relate to adverse health conditions or overall poorer physical functioning. For example, sleep and immune functioning are bidirectionally related. Immune activation can alter sleep quality and patterns, while changes in sleep patterns can also impact the body’s inflammatory response.31 Sleep patterns and duration are associated with the release of several hormones that regulate appetite, metabolism, and glucose tolerance.32,33Other physiological processes follow diurnal patterns and may be disrupted by sleep disturbances. For instance, blood pressure often decreases at night (i.e. nocturnal dipping) and lack of decrease (i.e. non-dipping), which is associated with increased risk of cardiovascular disease,33 is more prevalent among individuals with sleep disturbances, such as obstructive sleep apnea and advanced sleep cycles.34 While there are several biological pathways through which sleep patterns and sleep disturbances could affect chronic health conditions, these relationships and their directions have not been fully elucidated. However, the potential causal significance of poor sleep and its associations with adverse health outcomes are reinforced by several prospective studies15-17/reviews14,29.
Understanding associations between sleep duration and chronic health conditions in childhood cancer survivors is important because sleep may serve as a modifiable point of intervention to improve the health of this vulnerable population. In survivorship, excess risk of chronic conditions is driven by treatment exposures; however, intervening on lifestyle factors can improve health outcomes in this population35. Several behavioral sleep interventions in non-cancer samples have been successful in improving sleep quantity and quality36,37 and some provide preliminary support for health improvements38-40 and thus, merit further study among cancer survivors.
The results of our study should be considered within the context of several limitations. Because our analyses were cross-sectional and sleep was measured at only one time point, we cannot assess the temporality of associations between sleep and health outcomes. In addition, chronic health conditions were assessed from the time of cohort participation up to three months after the sleep assessment. Although we acknowledge short sleep duration may have been chronic as well, we were unable to assess this in the current study. While there are several prospective studies identifying sleep preceding chronic health conditions, there is also strong potential for bidirectional associations. Moreover, as we examined a range of health conditions, it is possible that some chronic conditions could cause or contribute to sleep disturbances, while for others, sleep may be the antecedent. Despite our inability to ascertain the directionality of our found associations, sleep is modifiable and may serve as an important component of lifestyle interventions that aim to improve health among survivors. Interventions targeting sleep may be necessary irrespective of whether it is an antecedent or consequent of chronic health conditions.
The present study of long-term survivors of childhood cancer identifies associations between short sleep duration and several physical and psychological health conditions. While short sleep duration alone was consistently associated with several health conditions (e.g. pulmonary, endocrine, gastrointestinal/hepatic), short sleepers with prolonged SOL and/or WASO were associated with two additional health conditions (e.g., cardiac and neurologic conditions). Examining additional sleep disturbances among short sleepers may serve as a sensitive measure between sleep and health outcomes. In addition, SOL and/or WASO may severe as additional points of interventions when targeting sleep extension.
Conflict of interest statement: The authors have declared no conflicts of interest.
Acknowledgements: This work was supported by the National Cancer Institute at the National Institutes of Health (CA195547, M. Hudson and L. Robison, Principal Investigators; CA239689, T. Brinkman and K. Krull, Principal Investigators) and by the National Cancer Institute Training in Pediatric Cancer Care Survivorship award (5T32CA225590, K. Krull, Principal Investigator). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Support to St. Jude Children’s Research Hospital was also provided by the Cancer Center Support (CORE) grant (CA21765, C. Roberts, Principal Investigator) and the American Lebanese Syrian Associated Charities (ALSAC).
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request