Timing of meal and sleep and cancer risk: mediation by metabolic dysregulation, inflammation and oxidative stress – TICTOC

Cancer development is multifaceted, involving metabolic dysregulation, oxidative stress, and inflammation. Modern lifestyles, characterized by long working hours and a perceived lack of time, have contributed to unintentional widespread changes in eating patterns, including late-night eating, irregular meal schedules, and breakfast skipping. On the other hand, emerging dietary trends targeting meal timing, particularly intermittent fasting and time-restricted eating (TRE), are gaining popularity, especially in the prevention and management of overweight. Yet their impact on cancer risk remains unclear. Short-term human randomized trials yield inconsistent results, and evidence from long-term observational studies is scarce, as assessing meal timing behaviours in cohorts is often challenging. The links between meal timing, sleep patterns, and cancer risk and the potential underlying mechanisms are poorly understood. Yet, evidence from experimental models suggests an important role of meal timing in the regulation of biological clocks.
In addition, detailed meal timing patterns in the French population were never explored.
We hypothesize that beyond nutritional quality of the diet, there are optimal times and durations for food intake and sleep that can help reduce cancer risk. We posit that the links between meal and sleep timing patterns and cancer occurrence are driven by multiple pathways including metabolic dysregulation, inflammation and oxidative stress, with different mediated proportions for each pathway. This project will describe meal timing habits of the French propulation, thanks to the nationwide survey Esteban, and will study, in the French cohort NutriNet-Santé (n=105,000), how meal timing is associated with the risk of cancers (1200 incident breast, 500 prostate, 350 colorectal, 2250 obesity-related cancer cases). Thanks to repeated 24-hour dietary questionnaires, including precise data on meal timing and composition, a biobank, and a 15-year follow-up, this project will study the role of circadian disruption linked to meal and sleep timing in the development of cancer. We will disentangle the role of metabolic dysregulation (through the metabolic syndrome, leptin and adiponectin), inflammation (CRP, interleukins and TNF) and oxidative stress (isoprostances) in these associations.
This project could ultimately enhance dietary guidelines for cancer prevention by integrating scientifically validated elements on meal/sleep timing patterns. It will improve the understanding of the underlying mechanisms between meal timing and cancer risk, providing patterns and monitoring markers for future interventions to lower cancer risk.