Circadian–Biological Rhythm Disruption: An Invisible Cancer Risk?

The Silent Alarm of Our Internal Clock

Through millions of years of evolution, the human body developed a biological clock mechanism: circadian rhythm. This rhythm governs not only sleep but hormones, metabolism, the immune system, and even cellular DNA repair. Modern lifestyles, however—staying awake late, looking at screens filled with blue light, and eating irregularly—disrupt this internal clock. Strong scientific evidence is now emerging that this very disruption may substantially increase cancer risk.

New Publication: The Connection Between Circadian Disruption and Colorectal Cancer

📄In a study published on May 26, 2025 in Nature Immunology , Bridget M. Fortin and colleagues at the University of California examined how sleep disturbances, nighttime light exposure, and irregular eating , as factors that disrupt circadian rhythm, affect the early stages of colorectal cancer development.

They also assessed whether timing treatments such as chemotherapy and immune checkpoint inhibitors (‘chronotherapy’) in alignment with the biological clock could improve efficacy.

What Is Circadian Rhythm, and Why Does It Matter?

Circadian rhythm is governed by the suprachiasmatic nucleus (SCN) in the brain’s hypothalamus and operates in cycles of approximately 24 hours. This system regulates:

• The sleep–wake cycle
• Hormone release (particularly melatonin and cortisol)
• Immune activity
• Metabolic processes
• Cell division and DNA repair throughout the body.

Related topic: Timing Makes a Difference in Immunotherapy: ASCO 2025 and the Lung Cancer Study

Figure 1 explained:

• a) The body’s circadian rhythm is controlled by the master clock in the hypothalamus, the suprachiasmatic nucleus (SCN) . Light signals from the eyes reach this center, aligning the biological clock with environmental light. Through endocrine and autonomic signals, the SCN synchronizes peripheral clocks in organs such as the liver, intestine, and pancreas. Each organ consequently functions according to the time of day; hormone secretion, digestion, and immune responses, for example, are timed accordingly.
• b) At the cellular level, this rhythm is maintained through the transcriptional–translational feedback loop (TTFL) . During daytime, CLOCK and BMAL1 proteins activate specific DNA regions (E-box), initiating the production of clock genes such as PER, CRY, REV-ERB, and ROR. During the night, these proteins accumulate, return to the nucleus, and suppress the CLOCK-BMAL1 complex, stopping gene expression. This genetic cycle repeats approximately every 24 hours and forms the cellular basis of circadian rhythm. Disruption may impair vital processes such as DNA repair, metabolism, and immunity.

Figure 2 explained:

• a) Cell Cycle: The circadian clock rhythmically controls expression of genes regulating cell-cycle phases (G1, S, G2, M). This synchronization ensures that cell growth and division occur at particular times of day. Circadian disruption may allow uncontrolled cell-cycle progression and tumor formation.
• b) DNA Damage and Repair: Clock proteins participate directly in DNA damage responses and repair mechanisms. For example, PER2stabilizes p53 protein to support repair, while CRY2promotes degradation of the MYC proto-oncogene, limiting cell proliferation. By preserving cellular integrity, these pathways play critical roles in preventing cancer development.
• c) Immune System: Immune cells (T cells, macrophages, etc.) are also synchronized with the circadian clock. Cytokine and chemokine release occurs rhythmically at specific times of day. This timed release optimizes immune-cell migration to tissues and infection responses.
• d) Metabolism: Circadian rhythm regulates metabolic processes—particularly energy-related pathways such as glucose metabolism and fat storage . These processes also operate in alignment with meal timing. Eating at appropriate times thus helps metabolic functions work more efficiently. Rhythm disturbances may lead to conditions such as obesity, diabetes, and metabolic syndrome.

The Cancer Connection: When the Clock Malfunctions, So Do Cells

Numerous studies indicate that circadian disruption may contribute to both cancer initiation and progression . It may promote cancer through:

• Reduced expression of core clock genes (BMAL1, PER, CRY, CLOCK)
• Impaired DNA repair mechanisms
• Disrupted rhythmic organization of immune cells
• Mistimed activation of tumor suppressor genes

Figure 3 explained:

• a) Tumor-Suppressing Functions: Circadian clock genes can suppress tumors in certain cancers. For example, reduced BMAL1 expression accelerates colorectal cancer arising in the context of an Apc mutation, while deficiency of BMAL1 and PER2 promotes progression of Kras -driven lung cancer. Similarly, loss of BMAL1 increases accumulation of immunosuppressive MDSC cells, while deficiency of CRY2 worsens development of MYC -driven lymphoma. These findings show that certain clock genes normally suppress tumor development and exert antioncogenic effects.
• b) Tumor-Promoting Functions: Conversely, the absence or suppression of certain clock genes may delay tumor formation and strengthen immune responses. For example, BMAL1 deficiency may reduce skin squamous cell carcinoma development, while deficiency of CRY1 and CRY2 may slow p53 -driven lymphoma development. In addition, in human glioblastomas, BMAL1 and CLOCK suppression causes cancer stem-cell apoptosis, while CLOCK overexpression leads to immunosuppression. These data show that clock genes can also have tumor-promoting (pro-oncogenic) functions in some cancers, so targeting them requires careful planning.

Evidence Linking Circadian Disruption to Cancer

• Since the 1970s, the incidence of early-onset colorectal cancer in individuals aged 15–39 has increased particularly markedly.
• During the same period, exposure to artificial light at night (ALAN – artificial light at night) increased dramatically.
• ALAN suppresses melatonin secretion and disrupts sleep and rhythmic gene expression .
• In a meta-analysis involving more than 170,000 women, high ALAN exposure increased the risk of estrogen receptor-positive breast cancer .
• Time-zone changes (jet lag) may also affect cancer risk by disrupting the circadian system.

Figure 4 explained:

• a) Cancer Initiation (Cancer initiation): Colorectal cancer (CRC) usually begins with a mutation in the APC tumor suppressor gene. In this initial phase, however, circadian clock disruption also plays an important role. In particular, BMAL1 gene deletion (knockout) accelerates this process. Such genetic disruptions of the biological clock may disturb cellular balance and cause cancer to begin earlier.
• b) Cancer Progression (Cancer progression): As cancer progresses, other oncogenic mutations accumulate (for example: KRAS, p53, SMAD4). This process is also influenced by environmental circadian disruption . In particular, conditions such as night-shift work, nighttime light exposure (ALAN) and chronic jet lag can disrupt circadian rhythm and increase cancer burden. Both genetic and environmental circadian clock disruptions may cause colorectal cancer to progress faster and occur at younger ages.

A Particularly Sensitive Organ: The Intestine

The gastrointestinal system is highly sensitive to circadian disruption:

• The intestinal mucosarenews at the same times each day.
• The gut microbiotais sensitive to light and feeding rhythms.
• Irregular mealtimesmay be a potential risk factor for colorectal cancer.

What Can Be Done Going Forward?

1. Preventive Measures:

• Regular sleep and meal schedules
• Specific light and sleep measures for night-shift workers
• Outside daylight hours, avoid eating (a 6–12-hour eating window)
• Regular physical activity

2. The Importance of Treatment Timing:

Chronotherapymeans administering cancer drugs at times aligned with the body’s biological clock. This approach may:

• Improve drug tolerability
• Optimize efficacy
• Particularly with immunotherapies, rhythm-related changes in immune activity may offer benefits

Conclusion: Circadian Health = Cellular Health

Circadian rhythm is about more than sleep patterns; it may also be decisive in cancer prevention and treatment success . Disruption of this system may be a silent culprit behind rising early-onset cancer rates .