BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Sleep duration, diet, and obesity have each been identified as modifiable risk factors linked to CRC. However, their joint effect on CRC incidence is underexplored. This study investigated the association between sleep duration and CRC incidence and explored the joint effects of sleep duration, a pro-inflammatory diet, and obesity on CRC incidence in the Multiethnic Cohort (MEC). METHODS: This prospective cohort study analyzed 193,027 participants from Hawaii and California enrolled in the MEC between 1993 and 1996. Sleep duration was self-reported and categorized as short (≤6 h), normal (7-8 h), or long (≥9 h). Diet was self-reported via FFQ and inflammatory potential was assessed using the energy-adjusted Dietary Inflammatory Index (E-DII). CRC cases were identified via cancer registries. Cox proportional hazards models estimated the hazard ratios (HRs) for CRC risk. RESULTS: After 23.8 years of follow-up, 5825 CRC cases were identified. A pro-inflammatory diet combined with suboptimal sleep increased CRC risk by 12% (short sleep duration, aHR: 1.12
95% CI: 1.02-1.24) and 22% (long sleep duration, aHR: 1.22, 95% CI: 1.05-1.43). Furthermore, long sleep duration was associated with a 10% increase in CRC risk (aHR: 1.10
95% CI: 1.01-1.22) compared with normal sleep, while short sleep showed no significant association overall. Obese individuals with short or long sleep had significantly higher CRC risk (short sleep aHR: 1.35
95% CI: 1.21-1.51
long sleep aHR: 1.36
95% CI: 1.14-1.64) compared with non-obese individuals with corresponding sleep durations. CONCLUSIONS: Long sleep duration and a combination of suboptimal sleep duration and a pro-inflammatory dietary pattern or obesity amplifies the risk.