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Review
. 2023 Dec 5;22(2):163-180.
doi: 10.1007/s41105-023-00500-1. eCollection 2024 Apr.

A review for the impacts of circadian disturbance on urological cancers

Tao Li #  1   2 , Yiting Jiang #  3 , Yunjin Bai #  4 , Kehua Jiang  2 , Guangshi Du  5 , Peng Chen  1 , Chao Luo  1 , Lei Li  6 , Jun Qiao  1 , Jun Shen  1
Affiliations
Review

A review for the impacts of circadian disturbance on urological cancers

Tao Li et al. Sleep Biol Rhythms. .

Abstract

Circadian rhythm is an internal timing system and harmonizes a variety of cellular, behavioral, and physiological processes to daily environment. Circadian disturbance caused by altered life style or disrupted sleep patterns inevitably contributes to various disorders. As the rapidly increased cancer occurrences and subsequent tremendous financial burdens, more researches focus on reducing the morbidity rather than treating it. Recently, many epidemiologic studies demonstrated that circadian disturbance was tightly related to the occurrence and development of cancers. For urinary system, numerous clinical researches observed the incidence and progress of prostate cancer were influenced by nightshift work, sleep duration, chronotypes, light exposure, and meal timing, this was also proved by many genetic and fundamental findings. Although the epidemiological studies regarding the relationship between circadian disturbance and kidney/bladder cancers were relative limited, some basic researches still claimed circadian disruption was closely correlated to these two cancers. The role of circadian chemotherapy on cancers of prostate, kidney, and bladder were also explored, however, it has not been regularly recommended considering the limited evidence and poor standard protocols. Finally, the researches for the impacts of circadian disturbance on cancers of adrenal gland, penis, testis were not found at present. In general, a better understanding the relationship between circadian disturbance and urological cancers might help to provide more scientific work schedules and rational lifestyles which finally saving health resource by reducing urological tumorigenesis, however, the underlying mechanisms are complex which need further exploration.

Keywords: Circadian disturbance; Circadian rhythm; Circadian sleep disorder; Epidemiological and fundamental evidence; Urological cancer.

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Conflict of interest statement

Conflict of interestEthical approval is not applicable for this review, the authors have no relevant financial or nonfinancial interests to disclose.

Figures

Fig. 1
Fig. 1
Misaligned environmental factors contribute to diseases through disturbing circadian clock. As the global industrialization and technological advances, rising rates of numerous diseases have coincided with altered lifestyles and work patterns. Nowadays, artificial lights or luminescent screens have been extensively popularized due to elevated work program, increased social pressure, and gradually personal habits with entertainment technological communication platforms. The prolonged nightshift work, jetlag, circadian sleep disorders, and long distance travel across multiple time zones are more frequent. All these factors sharply alter the daily sleep/wake cycle and slowly disturb internal circadian clock
Fig. 2
Fig. 2
Circadian disturbance can damage homeostasis, promote oxidative stress, induce inflammatory responses, and accelerate coagulatory process, which contribute to numerous diseases including. T2DM, hypertension, hyperlipemia, obesity, atherosclerosis, and cancers.
Fig. 3
Fig. 3
Molecular mechanism of circadian clock. After Zeitgebers of light, temperature, eating/drinking, physical activity, and social cues are perceived and transmitted to SCN, the central circadian clock system synchronizes with geophysical time and feedbacks to the downstream brain regions and peripheral organs by nervous system and hormone release. Briefly, CLOCK and BMAL1 form positive transcription factor of a heterodimer complex to promote rhythmic transcriptions of PER, CRY, and clock-controlled genes (CCGs) by integrating with E-box enhancers. PER and CRY accumulate in cytoplasm through the day and then translocate back to nucleus to reduce CLOCK/BMAL1 activity by forming a heterodimer complex. PER/CRY complex is also subsequently disassembled and resolved after CLOCK/BMAL1 concentration is declined. The remained free PER in cytoplasm is phosphorylated by casein kinase Iε (CKIε), and subsequently being ubiquitinated and degraded. Moreover, nuclear receptors of orphan nuclear receptor (REV-ERBα) and retinoic acid related orphan receptor alpha (RORα) can also regulate CLOCK/BMAL1 complex, while REV-ERBα is phosphorylated by glycogen synthase kinase-3β (GSK3β) to transcriptionally repress BMAL1 but RORα induces it
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