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Twice a year, as we turn our clocks backward or forward to adjust for daylight savings time, we see headlines everywhere about the implications of the time change on our biological clocks. This year, however, our biological clock got extra attention due to the recent announcement of the 2017 Nobel Prize in Physiology or Medicine. The prize was awarded jointly to three scientists for discovering the mechanisms controlling circadian rhythm. Jeffrey C. Hall, Michael Rosbash, and Michael W Young discovered several genes and proteins that unveiled the inner workings of our biological clock at the cellular level. 

While the idea that we have adapted to the rotation of the earth by developing a natural timepiece is widely accepted, we now understand how the cogs operate together thanks to these Nobel laureates.  Some of the cellular cogs include the period gene, which encodes PER protein, the timeless gene, which encodes TIM protein, and the doubletime gene, which encodes DBT protein.

In perfect “clockwork” fashion, these genes continuously work together to release proteins that synchronize our biological rhythms with the time of day. Their groundbreaking research could potentially shed light on the growing correlation between cancer and circadian disruption.

Shift Work and Cancer

Research has indicated an association between sleep disturbances, such as shift work and jet lag, and the development of certain cancers. In fact, according to the International Agency for Research on Cancer, shift work is now considered a “probable” carcinogenic. It is suggested that the circadian rhythm has a profound effect on healthy cell division. If the genes and proteins representing the cogs in the clock become dysregulated, it can result in pathogenic cellular activity.

Some studies on the relationship between breast cancer and sleep disturbances from shift work point to hypermethylation of certain circadian genes and the shortening of telomeres—both associated risk factors for cancer. These studies unveiled that the cancer risk appears to increase with the intensity and duration of the shift work. So, we can rest easy knowing that an occasional all-nighter is unlikely to significantly increase our cancer risk.

Time Zones and Cancer

The cellular dysregulation may not be limited to sleep disturbances, however, with a new study discovering higher rates of cancer in the Western portion of time zones. 

After evaluating four million cancer patients in 607 United States counties, the findings of this study suggested that disruption to the circadian rhythm of Western time zone residents may increase the rates of specific cancers. These cancers include non-Hodgkin’s lymphoma and prostate cancer in males, breast and corpus uteri cancer in women, and certain stomach, liver, esophageal, colorectal, and liver cancers.

Circadian Clock Cancer Treatment

Luckily, as we work to understand the relationship between cancer and the circadian clock, the information we uncover are milestones along the road to a new frontier of treatment. If we know how the cogs of the timepiece are dysregulated, we can potentially recalibrate them to prohibit cell division within tumors.  

A recent study published in BMC Biology found that when the circadian clock is enhanced, it can prohibit tumor growth. The researchers studied melanoma in mice using the glucocorticoid dexamethasone (DEX) to increase the functionality of the circadian clock. The DEX was administered via timed injections into tumors made primarily of B16 melanoma cells. The results determined that as the circadian clock function was enhanced, it inhibited growth of the tumor. 

Perhaps more exciting is the fact that these scientists could replicate their findings in humans, opening an entirely new field of promising potential cancer treatments. 

Resources:

https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-017-0349-7

https://cancerres.aacrjournals.org/content/77/22_Supplement/A01

https://cebp.aacrjournals.org/content/26/8/1306

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010688/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604437/

https://www.nobelprize.org/nobel_prizes/medicine/laureates/2017/press.html