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Disturbed Sleep-Wake Rhythm Promotes the Development of Lung Cancer

Lung cancer
According to the Robert Koch Institute's Center for Cancer Registry Data, around 23,655 women and 32,922 men were diagnosed with malignant lung tumors in Germany in 2022 Photo: Getty Images

January 28, 2025, 4:57 pm | Read time: 5 minutes

The change from day to night influences sleep. What many people don’t know: If the circadian rhythm is disturbed – for example, through shift work – this can promote the development of lung cancer. For example, mice that were exposed to irregular light conditions developed significantly more lung tumors.

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Lung cancer is one of the most common forms of cancer in Germany. Around 56,600 people were diagnosed with the disease in 2022. At just under 33,000, the number of men affected is significantly higher than that of women.1 It is well known that tobacco should be avoided as a preventative measure.2 In addition to other known factors such as increased exposure to particulate matter, a family history, age or pre-existing lung disease, circadian rhythm disorders may also play a role in the development of lung cancer. In 2022, a US study investigated the link between lung cancer and this relatively unknown risk factor.

Overview

Disruption of the Circadian Rhythm Is the Cause of Many Diseases

The circadian rhythm refers to the sleep-wake phases. This alternation is also known as the biological or internal clock. If this rhythm is disturbed, for example, due to shift work, this can have serious consequences for health. As the renowned chronobiologist and professor at the Salk Institute in California explained in the past in an interview with FITBOOK, conditions such as sleep disorders, diabetes, high blood pressure, fatty liver, cardiovascular disease, and mental illness are linked to this.

Disturbed Sleep-Wake Rhythm and the Development of Cancer

Researchers discovered a link between circadian rhythm disorders and cancer back in the 1980s. Studies on animals suggested that the resulting melatonin deficiency could promote the development of cancer. One of the first epidemiological studies to show the link between breast cancer – the most common cancer in women – and night shift work was presented many years ago by Danish researcher Johnni Hansen. He found an increased risk of breast cancer in women who work nights. This was thought to be due to reduced melatonin production at night.3 Long-term studies later showed that circadian disruption can also increase the risk of prostate cancer.

With the discovery of circadian genes in the 2000s, it was discovered that they not only regulate the sleep-wake rhythm but are also directly involved in the regulation of cell cycles and DNA repair. Studies have also shown that mutations in these genes can promote tumor formation. For example, a study by Ayesha Shafi and Karen Knudsen from 2019.4 Apparently, as we have now seen, disruption of the circadian rhythm, for example, through shift work or irregular sleep, throws fundamental cellular processes out of balance.

Why the Research Focused Specifically on Lung Cancer

The lungs are also subject to such circadian rhythms. Lung function usually improves throughout the day (= more daylight). In 2022, researchers from the Scripps Research Institute in California and the University of Rochester investigated the question of whether a disrupted circadian rhythm also promotes the development of lung cancer. FITBOOK took a closer look at the study and its results, which were published in Science Advantages at the time.5

In order to answer the question of whether a disrupted circadian rhythm promotes the development of lung cancer in particular, the research team exposed mice that had a gene mutation that is particularly common in lung cancer to a chronic circadian disruption.

The mice had a mutation on the so-called KRAS gene. The name KRAS comes from the fact that the disease was first identified as carcinogenic in the Kirsten rat sarcoma virus. Mutations of the KRAS gene account for 25 to 30 percent of mutations in malignant lung tumors and worsen the prognosis. 6

In order to disrupt their circadian rhythm, the researchers kept the mice under different light conditions. Some of the mice were kept under light conditions that mimicked those of the biological clock. For them, it was alternately 12 hours of light and 12 hours of darkness. The mice in the other group were kept under disturbed lighting conditions, similar to those experienced by people working shifts.

Findings of the Study: Disturbed Circadian Rhythm Risk Factor for Lung Cancer

In fact, the mice from the group whose circadian rhythm had been deliberately disturbed developed more lung tumors than the other animals. On closer examination of the genes, the researchers also discovered that the regulation of the HSF-1 gene was disrupted in the sicker animals. The heat shock factor protein 1 is considered a biomarker for cancer.7

The authors of the study suspect that the increased HSF-1 signaling they discovered indicates a molecular link between a disruption of the circadian rhythm and an increased risk of cancer.

Chronotherapy in Cancer Treatment

The findings of the study lead to two conclusions. On the one hand, it shows that in addition to smoking and other factors (family history, existing lung diseases, particulate matter), a disturbed sleep-wake rhythm can also be a risk factor for lung cancer. On the other hand, the findings can help to optimize cancer therapies. Current research is also focusing on this. It has been found that the effectiveness of treatments such as immunotherapy and radiotherapy varies depending on the time of day.

More on the topic

Influence of Sleep Disorders on Lung Cancer Risk in Women

Because shift work can also increase sleep disorders, a 2021 study also investigated a possible associated risk of lung cancer in women. The results showed that both short and long sleep durations are associated with an increased risk of lung cancer. In addition, factors such as many years of night work and current smoking status increased this risk.8

This article is a machine translation of the original German version of FITBOOK and has been reviewed for accuracy and quality by a native speaker. For feedback, please contact us at info@fitbook.de.

Topics Krebs Schlaf

Sources

  1. Center for Cancer Registry Data: Lung cancer (bronchial carcinoma) 2022, accessed on 22.01.2025 ↩︎
  2. Furrukh M. (2013). Tobacco Smoking and Lung Cancer. Sultan Qaboos University Medical Journal. ↩︎
  3. Springer Nature. Risk of Breast Cancer After Night- and Shift Work: Current Evidence and Ongoing Studies in Denmark. (2006, accessed 22.01.2025) ↩︎
  4. Shafi A.A., Knudsen K.E. (2019). Cancer and the Circadian Clock. Cancer Research. ↩︎
  5. Pariollaud M., Ibrahim L.H., Irzizarry E. et al. (2022). Circadian disruption enhances HSF1 signaling and tumorigenesis in Kras-driven lung cancer. Science Advances. ↩︎
  6. German Cancer Center. Lung cancer: first KRAS inhibitor approved. ↩︎
  7. Carpenter R.L., Gökmen-Polar Y. (2019). HSF1 as a Cancer Biomarker and Therapeutic Target. Current Cancer Drug Targets. ↩︎
  8. Cordina-Duveger E., Uchai S., Tvardik N. et al (2022): Sleep Traits, Night Shift Work and Lung Cancer Risk among Women: Results from a Population-Based Case-Control Study in France (The WELCA Study). MDPI. ↩︎
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