- Circadian rhythms are “biological clocks” responsible for coordinating many processes in the body, including the sleep-wake cycle.
- Disrupted circadian rhythms due to shift work or jet lag can negatively affect health and well-being. Some research has even linked circadian rhythm disruption to certain types of cancer.
- Now, new research has found a molecular link between circadian rhythm disruption and lung cancer growth.
- The study findings suggest that disrupted circadian rhythms may enhance a cancer-causing gene that can trigger a specific type of lung cancer.
- Scientists say that this discovery could lead to the development of medications that target this gene.
Circadian rhythms impact health in many ways. These biological processes serve an essential role in sleep patterns, digestion, body temperature, and hormone release.
However, certain factors can affect this delicate system, causing circadian rhythms to be out of sync.
A 2019 study suggests that circadian rhythm regulatory functions could play a role in cancer, including control of cell growth, cell death, DNA repair, and metabolic changes. And according to 2016 research, circadian rhythm disruptions may contribute to lung cancer progression.
Despite this evidence, relatively few studies have examined the relationship between circadian rhythm disruption and lung cancer — until now.
Research led by the Scripps Research Institute in California and co-authored by scientists at the University of Rochester Wilmot Cancer Institute has discovered a link between disrupted circadian rhythms and elevated heat shock factor 1 (HSF1) — a cancer signature gene that may cause lung cancer.
In the study, recently published in Science Advances, the researchers suggest it may be possible to target HSF1 with medications to prevent cancer in people who frequently experience circadian rhythm disruptions.
What are circadian rhythms?
Human circadian rhythms primarily respond to daylight and darkness. These natural processes are also responsible for the body’s sleep-wake cycle.
Moreover, the body’s biological clock — composed of specific proteins that interact with cells — helps regulate circadian rhythms.
Virtually every tissue in the body has a biological clock controlled by a brain structure in the hypothalamus.
This control center has around 20,000 nerve cells that receive and transmit information from the environment — specifically, light cues from daylight.
Circadian rhythm disruptions are also common. Factors affecting circadian rhythm regulatory functions may include:
- light from electronic devices
- jet lag
- shift work
The link between circadian rhythms and cancer
According to the new study, circadian rhythm disruptions may influence the risk of lung adenocarcinoma (LUAD) — a subtype of non-small cell lung cancer.
In humans, Kirsten rat sarcoma (KRAS) is a commonly mutated cancer-causing gene in LUAD.
To investigate how circadian rhythm disruption impacts lung cancer, the research team used genetically engineered mice that model the features of KRAS-driven lung cancer (K-mice). They housed one group of mice in standard lighting conditions consisting of 12 hours of light and 12 hours of darkness for 8 weeks.
In addition, the scientists housed another group in lighting conditions that mimic what humans experience during rotating shift work or chronic jet lag.
After analyzing the data, the team found that the K-mice developed more lung tumors when housed in chronic jet lag conditions compared to standard light conditions.
Moreover, after the scientists analyzed the RNA sequencing and gene expression in the K-mice, they found that interruptions of the circadian clock disrupt the regulation of HSF1 — enhancing its action on lung cells.
The study authors suggest that this enhanced HSF1 signaling indicates a molecular link between circadian rhythm disruption and increased cancer risk.
Although the study used mice and not human participants, the scientists say it could be possible to target HSF1 with medications — potentially preventing cancer in people with ongoing circadian rhythm disruptions.
Why would circadian rhythms increase lung cancer risk?
Despite the links between out-of-sync circadian rhythms and increased cancer risk, the researchers point out that 2019 studies published in the journals Cancer Discovery and PLOS Biology suggest that circadian rhythm disruption does not appear to be a universal characteristic of cancer.
For example, some cancer cells have circadian clocks intact, such as those found in:
- specific types of leukemia
Be that as it may, the study authors note that the lungs are particularly vulnerable to changes in circadian rhythms.
“Disruption of the typical circadian rhythm can lead to dysregulation of other cellular responses,” Dr. Samuel Riney, an oncologist at Methodist Le Bonheur Healthcare in Memphis, TN, told Healthline.
“Sometimes, this dysregulation can activate pathways that increase the risk for developing cancer.”
Reducing the adverse health effects of circadian rhythm disruption
Several factors play a role in the development of lung cancer, but more research on circadian rhythm disruptions in humans is still needed to determine the risk of developing lung cancer.
“This study shows an increased risk of developing lung cancer in a mice model,” Riney noted.
“How this would apply to human subjects is currently unclear. While the World Health Organization has declared disrupted circadian rhythms a likely cause of cancer, the degree of risk remains mostly an unknown.”
As such, Riney suggests those prone to circadian rhythm disruptions, such as shift workers and individuals experiencing frequent jet lag, may wish to consider avoiding other known lung cancer risk factors as a precaution.
Riney indicated these risk factors include:
- inhaled chemicals (i.e., arsenic, beryllium, cadmium, silica, vinyl chloride, nickel compounds, chromium compounds, coal products, mustard gas, and chloromethyl ethers)
- exposure to second-hand smoke, radon, diesel exhaust, and asbestos
“It is always wise to discuss your lung cancer risk with your primary care physician, who can help you identify modifiable risk factors,” he added.
Dr. Shelby Harris, a licensed clinical psychologist and clinical associate professor of neurology and psychiatry at Albert Einstein College of Medicine in the Bronx, NY, told Healthline:
“If you work rotating shifts, consider asking your employer if you can work in a clockwise rotation with shifts (e.g., morning, daytime, evening, nighttime) instead of moving and skipping between daytime, nighttime, afternoon, and so on. Working with the body’s natural clock to stay up a bit later over time is easier than jumping all around with shifts.”
Circadian rhythms are an important factor in health and well-being. Moreover, people who work varying shifts or have frequent jet lag can experience disruptions in their circadian rhythms.
According to the new mouse study, disrupted circadian rhythms may lead to the enhancement of HSF1, a cancer-causing gene — which may increase the risk of certain types of lung cancer.
However, the researchers suggest that eventually, it may be possible to target HSF1 with medications to help prevent cancer in people with frequently disrupted circadian rhythms.
Until more evidence in humans is uncovered, there are actionable steps you can take that may help reduce the potential health risks associated with chronic circadian rhythm disruption.
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