Circadian rhythms and cancer: potential mechanisms

Humans are incredible omnivorous beasts that can thrive on a great variety of diets, but crumble if you mess with their sleep.

Circadian arrhythmia is thought to be a driving force behind a few types of cancer.  But how, exactly, does seemingly harmless things like artificial light, skipping breakfast, or jet lag actually promote tumorigenesis?  There are many potential mechanisms, and I’d bet different circadian disruptions promote different cancers in different #contexts.

In some cell types, circadian disruptions which dampen amplitude increase proliferation.  This has led to some researchers to believe a robust circadian rhythm per se is tumor-suppressive.  In agreement with this, many tumor suppressors are direct targets of circadian transcription factors.  As was observed in some skin cancers, you may want suppressed proliferation at some times of the day but not others, so the tissue can renew properly.  But you don’t want, for example, skin cells to be proliferating while they’re being exposed to UV light, so this process happens at night (in circadian fashion).

Circadian transcription factors also directly interact with endogenous antioxidant systems.




Cancer clocks out for lunch: disruption of circadian rhythm and metabolic oscillation in cancer (Altman, 2016)





In a mouse model of lung cancer, multiple different circadian disruptions were shown to promote tumor growth and progression, and decrease survival rate (Papagiannakopoulos et al., 2016).  They showed that mimicking jet lag or shift work by shifting the light/dark cycle was just as bad as genetic deletion of Per2 or Bmal1.  Yikes!




Other researchers believe circadian disruptions cause aberrant epigenetic modifications which directly transform normal cells into cancer cells.



Carcinogenic effects of circadian disruption: an epigenetic viewpoint (Salavaty 2015)




Irregular eating patterns like delaying food intake long after light onset, sunrise, in the morning, and eating large meals at night, is a potent way to desynchronize peripheral circadian clocks from the master clock in SCN.

And some of the strongest evidence, imo, is the link between shift work, melatonin, and breast cancer.  I mean, seriously, how many hazard ratios of 3 do you see with food?  Humans are incredible omnivorous beasts that can thrive on a great variety of diets, but crumble if you mess with their sleep.

Books: Circadian Physiology and Circadian Medicine

“Robust circadian function can be achieved through programmed exercise, light exposure, meal timing, sleep scheduling, and administration of drug usage with optimal circadian timing.”



Further reading (to prove I’m not crazy):

Daily timed meals dissociate circadian rhythms in hepatoma and healthy host liver (Davidson et al., 2006)

Circadian disruption in experimental cancer processes (Filipski and Levi, 2009)

Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice (Lee et al., 2010)

The circadian timing system in clinical oncology (Innominato et al., 2014)

Epigenetic drift, epigenetic clocks, and cancer risk (Zheng et al., 2016)

Circadian dysrhythmias, physiological aberrations, and the link to skin cancer (Gutierrez and Arbesman, 2016)

Circadian rhythms: breast cancer and prostate cancer.


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