Chronic atrophic gastritis (CAG) is a critical precancerous stage in the development of gastric cancer (GC). Circadian rhythm disruption perturbs the core clock gene network, including circadian locomotor output cycles kaput (CLOCK), brain and muscle ARNT-like 1 (BMAL1), period circadian protein homolog (PER), and cryptochrome (CRY). These alterations contribute to a multi-layered pathological cascade involving DNA damage accumulation, epigenetic remodeling, altered epithelial cell plasticity, cellular senescence, microbiota dysbiosis, tumor microenvironment remodeling, metabolic reprogramming, aberrant angiogenesis, and dysregulated cell death, thereby accelerating CAG to GC progression. However, existing studies have predominantly treated the circadian rhythm as a passive risk factor for disease onset and have yet to elevate it to an actionable interventional target within the full-course management of gastric precancerous lesions. Building on a systematic synthesis of the mechanistic evidence outlined above, this review proposes a predictive, preventive and personalised medicine (PPPM/3PM) three-tier management framework grounded in circadian-based individualised protection. At the predictive level, digital biomarkers (sleep-wake rhythms, light exposure, physical activity, and dietary behavior), multi-omics profiles, and circadian-related molecular signatures are integrated to achieve dynamic risk stratification of CAG populations. At the targeted prevention level, pharmacological agents and natural compounds with circadian-regulating potential are deployed to develop proactive protective strategies tailored to distinct pathological stages and circadian phenotypes. At the personalised treatment level, lifestyle interventions, chronotherapy, nano-carrier-based circadian-synchronised delivery, and dynamic biomarker monitoring are combined to formulate precision intervention regimens informed by individual circadian phenotypes. This framework repositions the circadian rhythm from a latent risk factor to a protectable and therapeutically targetable axis, offering new insights into time-optimised intervention strategies for the inflammation to cancer transition in CAG.
