Clocking the damage: circadian rhythm, redox homeostasis and genome integrity in cancer

Circadian rhythms are inherent biological cycles that govern vital physiological processes, aligning with external signals such as light and food consumption. These rhythms, which originated over 2.5 billion years ago as a defense against oxidative stress, are essential for maintaining genomic stability by regulating DNA repair pathways, oxidative stress responses, and cell cycle regulation. Alterations in circadian rhythms are increasingly attributed to modern lifestyle practices, including irregular sleep schedules, prolonged exposure to artificial light, and shift work. These disturbances are closely linked to increased oxidative damage and genomic instability, both of which are essential for the development of cancer. There is growing evidence linking circadian misalignment to cancer, and the International Agency for Research on Cancer (IARC) has categorized shift employment that disturbs circadian rhythms as a potential carcinogen. Sleep deprivation intensifies this imbalance, resulting in heightened DNA damage and compromised repair processes. This disturbance is especially alarming in younger individuals, as chronic circadian misalignment may contribute to increasing prevalence of early-onset cancers, including hormone-related malignancies. This review examines the impact of oxidative stress-induced instability and the function of circadian rhythms in mitigating these effects. It underscores the critical influence of sleep deprivation on circadian misalignment and its associated cancer risk implications. Comprehending these relationships is essential for formulating preventive strategies and enhancing cancer treatments, thereby aligning therapeutic interventions with the body's intrinsic biological clock. Mitigating lifestyle-induced circadian disturbances may be crucial in alleviating the increasing incidence of early-onset malignancies in younger adults.