Sleep apnea linked to about 2 more brain cancer cases per 1,000 people over 15 years

Brain cancer is uncommon, and among more than 114,000 people with obstructive sleep apnea in Denmark it stayed uncommon. Over 15 years, about six in every 1,000 of them were diagnosed with it, against fewer than four in 1,000 members of the general population.

Kristina Laugesen and colleagues at Aarhus University Hospital and Aarhus University report the gap in The American Journal of Medicine, drawing on Danish registries from 1995 to 2021. Most research on sleep apnea and cancer had previously treated cancer as a single outcome. This team looked at each cancer site separately, and then checked the results against a second group of people with overweight or obesity.

Of all the cancer sites, only the brain and spinal cord came out higher, and both stayed higher when people with excess weight were the comparison.

How the Aarhus team tried to separate sleep apnea from excess weight

In obstructive sleep apnea, the most common type, the airway can collapse or become blocked during sleep, and normal breathing starts again with a snort or choking sound. Apnea and excess weight travel together. More than 80% of adult patients with apnea are overweight, and more than half are obese, according to researchers writing in the International Journal of Obesity in 2020. That makes weight the first suspect for almost any disease that turns up more often in people with apnea. The two are so entangled that a 2022 review in the Journal of Clinical Sleep Medicine suggested some of the cancer blamed on excess weight could in fact be due to underlying apnea.

From the registries, Laugesen’s team drew 114,264 people diagnosed with obstructive sleep apnea, 115,497 members of the general population and 113,034 people with overweight or obesity. They weighted the two comparison groups statistically so that sex, age and other illnesses were comparable across the three, which made each resemble the apnea group: about three-quarters male, with a median age of 53.

With more than 110,000 people in each of the three, the researchers could count cancers this uncommon with some precision. The weight comparison also asks a sharper question, namely whether people with apnea differ from people who share one of its biggest risk factors. Weighting has a limit, though, because it can only balance what the registries record. Anything unmeasured that rises alongside both apnea and these cancers would show up in data like these as an apparent effect of apnea. So the study can say with some confidence that brain and spinal cord cancers were diagnosed more often in people with apnea in Denmark. It cannot say apnea is the reason.

How much higher brain and spinal cord cancer ran in people with sleep apnea

In relative terms the brain result sounds large, a 15-year risk about 60% higher compared with the general population. In absolute terms that is about two more cancers of the brain for every 1,000 people with apnea, or roughly one more for every 460.

Spinal cord cancer pointed the same way on a smaller scale, at 1.65 per 1,000 people with apnea against 1.17 per 1,000 in the general population, about 40% higher. That works out to one additional diagnosis for roughly every 2,000 people. Because spinal cord cancers are rarer, the estimate rests on fewer cases and is less certain than the brain figure.

When people with overweight or obesity stood in for the general population, the associations persisted, though the abstract gives no figures for that version of the analysis. That result does more than any single number to narrow the possible explanations, because it suggests excess weight, at least as the registries capture it, does not fully account for the pattern.

Sleep apnea and brain cancer were linked before, in Taiwan’s insurance records

Researchers in Taiwan saw something similar more than a decade earlier. Using the country’s national health insurance claims, they compared 23,055 people newly diagnosed with sleep apnea against patients matched by age and gender. They counted only cancers that appeared from 2 years after the diagnosis onward, a step that helps exclude tumors that may already have been growing. Their 2014 paper in Sleep Medicine reported an excess of primary brain cancers, those that start in the brain, but not of primary spinal cord cancers. The Danish study adds to that earlier finding with nearly five times as many people with apnea, and it picked up a spinal cord signal as well.

For cancer as a whole, the evidence has been far less consistent. Two pooled analyses published three months apart in 2015, drawing on almost the same research, came to the exact opposite conclusions. The 2022 review, which combined 20 studies, found that an apnea diagnosis on its own was not associated with overall cancer, although people with apnea who spent more of the night with low blood oxygen were more likely to develop it.

It also listed cancers of the central nervous system, the brain and spinal cord, among more than a dozen cancer types linked to sleep apnea, though there is substantial disagreement over them. Because different cancer types may behave differently, its authors argued, each needs investigating on its own. Laugesen’s team did exactly this, and its results fit: no rise at other cancer sites, and a narrow one confined to the brain and spinal cord.

The Danish abstract offers no explanation for why apnea would single out those two sites. The main theory for how apnea might promote cancer holds that its intermittent hypoxia and sleep fragmentation, meaning repeated drops in oxygen and broken sleep, feed tumor growth. It has been studied in cell and mouse models of melanoma, a blood cancer called myeloma, and lung, breast, colon, and kidney cancer. None of those is a brain tumor. The abstract reports no oxygen measurements either, so these data neither test that theory nor explain their own result.

Why the Danish results may not hold for undiagnosed sleep apnea

Apnea is common yet underdiagnosed and undertreated, and a registry sees only the people whose apnea was diagnosed. The Danish data cannot tell whether people living with undiagnosed apnea show the same pattern. The authors of the 2022 review also cautioned that studies based in clinics and administrative databases may have introduced selection bias, meaning the people who end up in those records can differ from everyone else in ways that skew a comparison.

The people behind these results were mostly middle-aged men, all of them in Denmark. The full paper is paywalled and this article draws on its abstract. Details such as how severe participants’ apnea was, whether they were treated, which kinds of brain tumor were counted and whether cancers found soon after an apnea diagnosis were set aside could not be checked. Neither could the authors’ own account of the study’s limits.

What the brain cancer link changes for people with sleep apnea

Laugesen and colleagues end on apnea itself: “These findings highlight the importance of effective prevention of obstructive sleep apnea and the need for further research on treatment,” they write.

For people who already have apnea, the study adds no new step to take about brain cancer, and nothing in it points to scanning for tumors. The 2022 review left open whether cancer screening and apnea treatment are beneficial, and it found no randomized trials showing a drop in cancer risk with treatment.

Anyone who is told they snore or gasp for air during sleep already has reason to talk to a healthcare provider. Untreated sleep apnea increases the risk for stroke, heart attack, and other serious problems, according to the National Heart, Lung, and Blood Institute.

Brain cancer may yet join that list, but for now it is a question for researchers rather than a new worry for patients.