The Circadian Clock in Cancer Development and Therapy - Progress in Molecular Biology and Translational Science - page 224

The best-studied circadian output pathways include the autonomic ner-
vous system (ANS) and the neuroendocrine system (NES) that control all
aspects of mammalian physiology as well as the peripheral clocks via cellular
signaling. The rhythmic activities of these systems provide a mechanism for
the central clock to control peripheral tissues directly and indirectly via
peripheral clocks. 24,29-33
Dramatic changes in lifestyles since the industrial revolution due to
increased use of artificial lighting, night-shift working schedules, or rapid
long-distance transmeridian traveling have led to frequent disruptions of
endogenous circadian homeostasis in modern societies. These changes in
lifestyle are coupled with a significant increase in the risk of diseases in all
aspects of human health, including cancer.
2. CIRCADIAN DYSFUNCTION PROMOTES CANCER
DEVELOPMENT IN HUMANS
2.1. Circadian disruption is an independent cancer risk
factor for humans
Recent epidemiology studies have linked circadian disruption to increased
susceptibility to cancer development in all key organ systems in humans.
The cancers observed from these studies included breast, ovarian, lung,
pancreatic, prostate, colorectal and endometrial cancers, non-Hodgkin's
lymphoma (NHL), osteosarcoma, acute myeloid leukemia (AML), head
and neck squamous cell carcinoma, and hepatocellular carcinoma. 34-49
Circadian dysfunction-induced cancer risk increases with the number of
years, the frequency of rotating work schedules, and the number of hours
per week working at night among human night-shift workers. 45,46,50-52
Together, these findings suggest that loss of circadian homeostasis could
be an independent cancer risk factor for humans. 53 Due to the prevalence
of night-shift work schedules in modern societies, the World Health Orga-
nization's International Agency for Research on Cancer (IARC) listed
“shift work that involves circadian disruption” as a probable carcinogen
in 2007.
2.2. Circadian disruption is associated with poor prognosis
and early mortality of cancer patients
Loss of circadian homeostasis not only promotes cancer development but is
also associated with poor performance with regard to anticancer treatments