Is There a Link Between Esophageal Risk and Sleep Habits?

Too much or too little sleep, daytime naps, and other sleep patterns may increase the risk of developing esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), suggest researchers at the Washington University School of Medicine in St. Louis, Missouri.

In their prospective study, the team found that individuals who slept more than 9 hours a night had double the risk of getting EAC after 2 or more years (hazard ratio, 2.06) compared to a person sleeping a “standard” 7 hours a night.

Conversely, people who slept fewer than 6 hours were 21% more likely to be diagnosed with EAC and 63% more likely to get ESCC after 2 years.

The research team, led by Yin Cao MD, an associate professor of surgery, mined UK Biobank data between 2006–2016 for the sleep habits of 393,114 people, then followed them for up to 10 years to see how many developed esophageal cancer. During this time, 294 people developed EAC, and 95 were diagnosed with ESCC.

The study was published in Cancer, Epidemiology Biomarkers and Prevention on May 16.

Cao said that she and her team decided to conduct the study because they were intrigued by evidence suggesting a link between shorter sleep duration with ESCC and Barrett esophagus, the precursor of EAC. “Yet other sleep behaviours [had] not been comprehensively evaluated,” Cao said.

The team also assessed daytime sleep behavior. They found that taking daytime naps or experiencing sleepiness did not bode well down the road with regard to esophageal cancer, depending on the type of cancer. Individuals who “sometimes” took daytime naps were at 39% increased risk of EAC, and those who “usually” experienced sleepiness during the day had twice the risk of ESCC after 2 years.

Chronotype, a person’s natural rhythm of daytime sleepiness, also appeared to play a role. For example, being an “evening person” increased the risk of EAC by 32% and almost tripled the risk of ESCC compared to being a “morning person.”

Neither snoring nor insomnia affected the risk of either type of esophageal cancer.

Cao was surprised that both short and long sleep duration, napping, and daytime sleepiness turned out to be risk factors for esophageal cancer.

The mechanisms underlying these associations are “likely complex,” she said, adding that different aspects of sleep behavior might be driving cancer through differing routes.

“Disruption of circadian physiology could result in gastroesophageal reflux disease (GERD), the most important risk factor for EAC, via altering the expression of circadian-clock genes in esophagus tissue or reducing the expression of melatonin,” said Cao. “Both excess sleep and sleep deprivation might relate to immune dysfunction, which might lead to an increased susceptibility to esophageal cancer.”

In an interview, when asked whether other, simpler explanations were possible, Cao acknowledged that other associations were a potential source of confusion. For example, obesity is known to affect both quality of sleep and cancer risk. Cao said in their analyses, the team adjusted for a myriad of likely confounders, such as sex, smoking status, and shift-work status, in addition to body mass index and the Townsend Deprivation Index, a poverty measure.

Another factor that could have muddied the results was reverse causation, the possibility that already-present esophageal cancer was causing fatigue and poor sleep patterns instead of the other way around. For this reason, Cao’s team conducted a separate analysis that excluded patients who were diagnosed with esophageal cancer during the first 2 years of follow-up. (Data from this separate analysis, available in the supplementary tables, were used for the current article.)

Cao concluded that her team’s data “may serve as modifying risk factors for esophageal adenoma carcinoma” but that “additional validation and mechanistic studies are needed.”

The study was supported by a National Institutes of Health grant. Cao has received personal fees from Geneoscopy outside the published work.

Cancer Epidemiol Biomarkers Prev. Published online May 16, 2023. Abstract

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