Sleep and circadian disruption

Disruption of circadian rhythms, the roughly 24-hour biological cycles that regulate sleep, metabolism, hormone secretion, and immune function, has been associated with increased cancer risk in observational studies. Night shift work is classified as a Group 2A probable carcinogen by IARC, based on sufficient animal evidence and limited human evidence. The cancer types most studied in relation to circadian disruption include breast cancer, colorectal cancer, and prostate cancer, with the strongest evidence for breast cancer in female night shift workers.

Circadian rhythms are regulated by a core molecular clock network consisting of genes including CLOCK, BMAL1, PER, and CRY. Disruption of these rhythms impairs cell cycle control, the timing of DNA repair processes, and immune surveillance, all of which are relevant to cancer prevention. Nocturnal light exposure suppresses melatonin secretion, and melatonin has direct anti-proliferative effects on cancer cells and indirect effects through immune modulation. Circadian disruption also dysregulates glucocorticoid secretion, which normally follows a diurnal oscillatory rhythm. Research has shown that breast cancer can hijack neuronal circuits to blunt normal diurnal glucocorticoid oscillations, and that restoring these rhythms through time-specific neuromodulation enhanced CD8 T cell anti-tumour function and attenuated tumour growth in mouse models. At the molecular level, a multi-omics study using Mendelian randomisation identified GSTM5 (glutathione S-transferase mu 5), a circadian rhythm-related gene involved in oxidative stress metabolism, as a likely causal protective factor against breast cancer based on rigorous genetic evidence from blood and breast tissue datasets.

A multi-omics and Mendelian randomisation study identified GSTM5 as the sole circadian gene meeting stringent causal criteria in an integrative analysis, providing molecular-level support for a link between circadian biology and breast cancer risk. Animal studies using prolonged light exposure to simulate circadian disruption found impaired ovarian follicular development through NAD metabolic reprogramming, illustrating how chronic circadian disruption can alter the hormonal environment in ways relevant to hormone-sensitive cancers. A narrative review linked nocturnal eating, a circadian-disrupting behaviour, to gut microbiota changes and early-onset digestive cancer risk through chrononutrition pathways. Research in breast cancer survivors found that 24-hour movement behaviours, including achieving restorative sleep, were associated with better quality of life outcomes, highlighting the importance of sleep quality in the survivorship setting.

Night shift workers, including nurses, factory workers, emergency responders, and airline crew who regularly work at night, are the most extensively studied group at elevated cancer risk. Women who have worked long-duration rotating night shifts appear to have modestly elevated breast cancer risk in some but not all cohort studies. People with disrupted sleep due to sleep disorders, social jet lag (inconsistent sleep-wake timing across the week), or chronic late-night eating patterns may also experience chronic circadian misalignment, though the cancer risk implications of these less extreme disruptions are not well established.

The evidence is predominantly observational and mechanistic. The IARC Group 2A classification for night shift work is based on sufficient animal evidence and limited human evidence, meaning the classification reflects probable rather than definitive carcinogenicity. Results from large epidemiological cohort studies on night shift work and cancer have been inconsistent, with some showing modest breast cancer associations and others showing null results. Confounding by other lifestyle factors common among shift workers complicates interpretation. Mechanistic evidence from animal models and molecular studies is growing but has not yet translated into definitive human intervention evidence.

Evidence suggests that chronic circadian disruption, particularly through regular night shift work, may modestly increase cancer risk, with the most studied association being breast cancer in women. The biological mechanisms are plausible and increasingly characterised at a molecular level. For the broader population, the relevance of occasional sleep disruption to long-term cancer risk is uncertain, and this remains an active area of research.