IMPORTANCE: Esophageal cancer is among the most lethal type of cancers worldwide. However, risk factors contributing to more than tenfold increase in esophageal cancer in the last 50 years remain underexplored. OBJECTIVE: This study aimed to examine the associations between sleep behaviors and esophageal cancer overall, by histology, and according to genetic predispositions. DESIGN: A prospective cohort study. SETTING: A population-based study. PARTICIPANTS: A total of 410,428 participants aged

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... 37-73 years at enrollment between 2006 and 2010 in the UK Biobank were followed up until March 31st, 2016 for England and Wales and October 31st, 2015 for Scotland. MAIN OUTCOME AND MEASURE: The risk of incident esophageal cancer. RESULTS: During 2,799,342 person-years of follow-up, 410 incident esophageal cancer cases (294 adenocarcinomas) were diagnosed. Evening chronotype, sleep <6 or >9 h/day, daytime napping, and daytime sleepiness were significantly associated with increased risk of esophageal cancer in age-adjusted models and had a Plikelihood ratio test ≤0.20 after multivariable adjustment. Compared with the group without these high-risk behaviors, participants with one high-risk behavior had a 41% (HR=1.41, 95%CI: 1.13, 1.77) increased risk of esophageal cancer, and those with two or more behaviors showed a 79% higher risk (HR=1.79, 95%CI: 1.32, 2.42) (Ptrend<0.001). These associations were largely driven by esophageal adenocarcinoma (Ptrend<0.001) but not squamous cell carcinoma (Ptrend=0.340). The elevated risks for esophageal adenocarcinoma were similar within strata of PRS quintiles (Pinteraction=0.791). CONCLUSION AND RELEVANCE: Unhealthy sleep behaviors were associated with an increased risk of esophageal cancer, primarily adenocarcinoma, independent of genetic risk. Sleep behaviors may serve as modifiable factors for the prevention of esophageal cancer, particularly esophageal adenocarcinomas.