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