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Genetic Variants in Circadian Rhythm Genes and Self-Reported Sleep Quality in Women with Breast Cancer.

ABSTRACT: Introduction:Women diagnosed with breast cancer (BC) are at increased risk of sleep deficiency. Approximately 30-60% of these women report poor sleep during and following surgery, chemotherapy, radiation therapy, and anti-estrogen therapy. The purpose of this study was to examine the relationship between genetic variation in circadian rhythm genes and self-reported sleep quality in women with BC. Methods:This cross-sectional study recruited women with a first diagnosis of breast cancer at five sites in Nebraska and South Dakota. Sixty women were included in the study. Twenty-six circadian genes were selected for exome sequencing using the Nextera Rapid Capture Expanded Exome kit. 414 variants had a minor allele frequency of ?5% and were included in the exploratory analysis. The association between Pittsburgh Sleep Quality Index (PSQI) score and genetic variants was determined by two-sample t-test or ANOVA. Results:Twenty-five variants were associated with the PSQI score at p < 0.10, of which 19 were significant at p<0.05, although the associations did not reach statistical significance after adjustment for multiple comparisons. Variants associated with PSQI were from genes CSNK1D & E, SKP1, BHLHE40 & 41, NPAS2, ARNTL, MYRIP, KLHL30, TIMELESS, FBXL3, CUL1, PER1&2, RORB. Two genetic variants were synonymous or missense variants in the BHLHE40 and TIMELESS genes, respectively. Conclusions:These exploratory results demonstrate an association of genetic variants in circadian rhythm pathways with self-reported sleep in women with BC. Testing this association is warranted in a larger replication population.

SUBMITTER: LeVan TD

PROVIDER: S-EPMC6611482 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Genetic Variants in Circadian Rhythm Genes and Self-Reported Sleep Quality in Women with Breast Cancer.

LeVan Tricia D TD Xiao Peng P Kumar Gaurav G Kupzyk Kevin K Qiu Fang F Klinkebiel David D Eudy James J Cowan Kenneth K Berger Ann M AM

Journal of circadian rhythms 20190701

<h4>Introduction</h4>Women diagnosed with breast cancer (BC) are at increased risk of sleep deficiency. Approximately 30-60% of these women report poor sleep during and following surgery, chemotherapy, radiation therapy, and anti-estrogen therapy. The purpose of this study was to examine the relationship between genetic variation in circadian rhythm genes and self-reported sleep quality in women with BC.<h4>Methods</h4>This cross-sectional study recruited women with a first diagnosis of breast c ...[more]

PMID: 31303884

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Project description:BackgroundIndividuals with typical circadian rhythm sleep-wake disorders (CRSWDs) have a habitual sleep timing that is desynchronized from social time schedules. However, it is possible to willfully force synchronisation against circadian-driven sleepiness, which causes other sleep problems. This pathology is distinguishable from typical CRSWDs and is referred to here as latent CRSWD (LCRSWD). Conventional diagnostic methods for typical CRSWDs are insufficient for detecting LCRSWD because sufferers have an apparently normal habitual sleep timing.MethodsWe first evaluated the reliability of circadian phase estimation based on clock gene expression using hair follicles collected at three time points without sleep interruption. Next, to identify detection criteria for LCRSWD, we compared circadian and sleep parameters according to estimated circadian phases, at the group and individual level, between subjects with low and high Pittsburgh Sleep Quality Index (PSQI) scores. To validate the reliability of identified detection criteria, we investigated whether the same subjects could be reproducibly identified at a later date and whether circadian amelioration resulted in sleep improvement.FindingsWe successfully validated the reliability of circadian phase estimation at three time points and identified potential detection criteria for individuals with LCRSWD attributed to delayed circadian-driven sleepiness. In particular, a criterion based on the interval between the times of the estimated circadian phase of clock gene expression and getting out of bed on work or school days was promising. We also successfully confirmed the reproducibility of candidate screening and sleep improvement by circadian amelioration, supporting the reliability of the detection criteria.InterpretationAlthough several limitations remain, our present study demonstrates a promising prototype of a detection method for LCRSWD attributed to delayed circadian-driven sleepiness. More extensive trials are needed to further validate this method.FundingThis study was supported mainly by JSPS, Japan.

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Genetic Variants in Circadian Rhythm Genes and Self-Reported Sleep Quality in Women with Breast Cancer.

Publications

Genetic Variants in Circadian Rhythm Genes and Self-Reported Sleep Quality in Women with Breast Cancer.

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