||5R01CA207020-03 Interpret this number
||University Of California, San Francisco
||Sleep and Cancer: Evaluation of Risk and Insights Into Mechanisms
The CDC recently declared insufficient sleep to be a “public health epidemic,” noting that an estimated 50-70
million US adults have sleep or wakefulness disorders. Although it is well-recognized that insufficient sleep
increases the risk for many chronic conditions, the role of sleep in the development of cancer is unclear. While
epidemiologic studies are sparse, they have yielded some provocative but inconsistent findings. Such
inconsistencies may reflect the complexity of underlying etiologic mechanisms. Sleep plays a fundamental role
in the maintenance of a number of key processes integral to carcinogenesis, including inflammation and
cellular replication and proliferation. Furthermore, there may be individual differences in vulnerability to the
effects of sleep deficiency, depending on chronotype (i.e., whether one’s endogenous biological rhythm of
sleep/wakefulness follows a morning or evening preference). Our objective is to advance the understanding of
how sleep deficiency may influence cancer risk, considering both potential underlying mechanisms and host
vulnerability. The study will capitalize on resources available from the California Teachers Study (CTS) in
which 65,000 women have provided detailed self-reported data on sleep and chronotype, a subset of whom
have also provided blood samples available for the conduct of biomarker assays to quantify physiologic effects.
The specific aims are to: 1.) evaluate cancer risks associated with self-reported sleep deficiency among CTS
participants; 2.) assess the relationship between self-reported sleep deficiency and biomarkers of physiologic
effect for chronic inflammation and telomere length; 3.) evaluate the degree to which cancer risks and the
physiologic responses to sleep deficiency vary by chronotype. In addressing each of these aims, several specific
dimensions of sleep deficiency will be considered, including poor sleep quality, extremes in sleep duration,
fragmented sleep and long sleep latency. Cases of invasive breast and other selected commonly-diagnosed
cancers (colorectal, melanoma, endometrial, non-Hodgkin’s lymphoma, thyroid) will be identified via linkage
to the California Cancer Registry. Biomarker assays will be run on 800 blood samples collected from non-
cancer cases within a year of the sleep and chronotype data. Multiplexed immunometric assays will be used to
quantify levels of circulating biomarkers of inflammation. Quantitative PCR will be used to measure telomere
length. Cox Proportional Hazards and Ordinary Logistic Regression models will be used to estimate risks for
each dimension of sleep deficiency, adjusting for other known risk factors. Multivariable linear models will be
used to characterize the relationship between the biomarkers and specific dimensions of sleep. Initial models
will be expanded, incorporating chronotype to explore potential differences in risk and/or effect by chronotype.
The long-term objective of this project supports the NCI’s mission to reduce the burden of cancer by furthering
our understanding of its etiology and avenues for prevention. Additionally, it supports NIH’s recently identified
priority to advance the understanding of sleep and circadian functions in health and disease.
Chronotype and postmenopausal breast cancer risk among women in the California Teachers Study.
, Goldberg D.
, Von Behren J.
, Clague DeHart J.
, Wang S.
, Reynolds P.
Chronobiology international, 2019 11; 36(11), p. 1504-1514.