Sleep Behaviors, Genetic Predispositions, and Risk of Esophageal Cancer

Xiaoyan Wang, Ruiyi Tian, Xiaoyu Zong, Myung Sik Jeon, Jingqin Luo, Graham A. Colditz, Jean S. Wang, Konstantinos K. Tsilidis, Yo-El S. Ju, Ramaswamy Govindan, Varun Puri, Yin Cao

Risk factors contributing to more than tenfold increase in esophageal cancer in the last 50 years remain underexplored. We aim to examine the associations of sleep behaviors with esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). We prospectively assessed the associations between sleep behaviors (chronotype, duration, daytime napping, daytime sleepiness, snoring, and insomnia) and EAC and ESCC risk in 393,114 participants in the UK Biobank (2006-2016). Participants with 0, 1, and ≥2 unhealthy behaviors, including sleep <6 or >9 h/day, daytime napping, and usual daytime sleepiness were classified as having a good, intermediate, and poor sleep. For EAC, we also examined interactions with polygenic risk score (PRS). Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We documented 294 incident EAC and 95 ESCC. Sleep >9 h/day (HR=2.05, 95%CI: 1.18, 3.57) and sometimes daytime napping (HR=1.36, 95%CI: 1.06, 1.75) were individually associated with increased EAC risk. Compared with individuals with good sleep, those with intermediate sleep had a 47% (HR=1.47, 95%CI: 1.13, 1.91) increased EAC risk, and those with poor sleep showed a 87% (HR=1.87, 95%CI: 1.24, 2.82) higher risk (Ptrend<0.001). The elevated risks for EAC were similar within strata of PRS (Pinteraction=0.884). Evening chronotype was associated with elevated risk of ESCC diagnosed after 2 years of enrollment (HR=2.79, 95%CI: 1.32, 5.88). Unhealthy sleep behaviors were associated with an increased risk of EAC, independent of genetic risk. Sleep behaviors may serve as modifiable factors for the prevention of EAC.