Association of Sleep Behaviors with Risk of Esophageal Cancer

Abstract

ABSTRACTIMPORTANCEEsophageal 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.OBJECTIVEThis study aimed to examine the associations between sleep behaviors and esophageal cancer overall, by histology, and according to genetic predispositions.DESIGNA prospective cohort study.SETTINGA population-based study.PARTICIPANTSA total of 410,428 participants aged 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 MEASUREThe risk of incident esophageal cancer.RESULTSDuring 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 aPlikelihood 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 RELEVANCEUnhealthy 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.Key PointsQuestionAre sleep behaviors associated with the risk of esophageal cancer?FindingsIn this prospective cohort study that included 410,428 participants in the UK Biobank, evening chronotype, sleep <6 or >9 h/day, daytime napping, and sleepiness were associated with increased risk of esophageal cancer. A greater number of these unhealthy sleep behaviors was associated with a higher risk of esophageal cancer. The elevated risks were primarily observed for esophageal adenocarcinoma and were independent of genetic risk.MeaningSleep behaviors may serve as modifiable factors for the esophageal cancer prevention, particularly esophageal adenocarcinoma, independent of genetic risk.