Epidemiologists have long been puzzled by a strange pattern in their data: People living at higher altitudes appear less likely to get lung cancer.
Associations like these can be notoriously misleading. There is, for instance, a strong correlation between per-capita cheese consumption and the number of people strangled accidentally by their bedsheets. Slice and dice the profusion of data, and there is no end to the coincidences that can arise. Some were recently collected in a book called “Spurious Correlations.” Year by year, it turns out, the number of letters making up the winning word for the Scripps National Spelling Bee closely tracks the number of people killed by venomous spiders.
These are probably not important clues about the nature of reality. But the evidence for an inverse relationship between lung cancer and elevation has been much harder to dismiss.
A paper published last year in the journal PeerJ plumbed the question to new depths and arrived at an intriguing explanation. The higher you live, the thinner the air, so maybe oxygen is a cause of lung cancer.
Oxygen cannot compete with cigarettes, of course, but the study suggests that if everyone in the United States moved to the alpine heights of San Juan County, Colo. (population: 700), there would be 65,496 fewer cases of lung cancer each year.
This idea didn’t appear out of the blue. A connection between lung cancer and altitude was proposed as early as 1982. Five years later, other researchers suggested that oxygen might be the reason.
But the authors of the PeerJ paper — two doctoral students at the University of Pennsylvania and the University of California, San Francisco — have made the strongest case yet. At the University of Pennsylvania Medical School, the paper won last year’s Abramson Cancer Center prize for basic research. And in July it was chosen as one of PeerJ’s best papers on cancer biology.
Skeptics were quick to strike back, though not very effectively. A would-be debunking on the Cancer Research UK website was quickly followed by a debunking of the debunking.
All of the usual caveats apply. Studies like this, which compare whole populations, can be used only to suggest possibilities to be explored in future research. But the hypothesis is not as crazy as it may sound. Oxygen is what energizes the cells of our bodies. Like any fuel, it inevitably spews out waste — a corrosive exhaust of substances called “free radicals,” or “reactive oxygen species,” that can mutate DNA and nudge a cell closer to malignancy.
That is not a good reason to consume antioxidant pills. While the logic may seem sound, there is no convincing evidence that these supplements add to nature’s already formidable means of repairing oxidative damage — and they may even disrupt some delicate biological balance, increasing cancer risk and speeding tumor growth.
But there is no question that oxidation, so crucial to life, rusts our cells and can edge them closer to becoming cancerous.
In examining the possibility that breathing itself significantly increases the risk of lung cancer, the authors of the paper, Kamen P. Simeonov and Daniel S. Himmelstein, began by eliminating confounding variables. Maybe younger, healthier people tend to live at higher altitudes, with older and weaker ones, including smokers, retreating to lower lands. That could create the illusion of a protective altitude effect, but one that has nothing to do with oxygen.
The authors also took into account factors like income, education and race, which affect access to medical care. To reduce distortions caused by noisy data, the researchers excluded counties with large numbers of recent immigrants, who might have acquired cancer-causing mutations elsewhere. Also ruled out were places with a large number of Native Americans, whose cancer rates often go underreported.
Beyond the human variables were geophysical ones. Air at higher altitudes may be less polluted by carcinogens. And since sunlight exposure is more intense, maybe the increase in vitamin D helps stave off lung cancer — an idea previously suggested. Differences in precipitation and temperature might also have some effect.
These data, too, were added to the scales, along with the influence of radon gas and ultraviolet rays, which is greater at higher elevations. The frequency of obesity and diabetes, which are risks for many cancers, was adjusted for, along with alcohol use, meat consumption and other factors.
After an examination of all these numbers for the residents of 260 counties in the Western United States, situated from sea level to nearly 11,400 feet, one pattern stood out: a correlation between the concentration of oxygen in the air and the incidence of lung cancer. For each 1,000-meter rise in elevation, there were 7.23 fewer lung cancer cases per 100,000 people. (The study found no similar correlations for breast, colon and prostate cancer.)
That is not a good reason to inhale less deeply at sea level or to flee to the mountains. Wherever you live, smoking accounts for as much as 90 percent of lung cancer. Radon is considered a distant second cause. But the PeerJ study complicates things.
For various reasons, radon levels are generally higher at higher altitudes, while lung cancer rates are lower. Does that mean radon is not so dangerous after all? Or are its bad effects offset by the healthy deficit of carcinogenic oxygen?
Or maybe radon, like thinner air, protects against lung cancer. According to a long-debated hypothesis called hormesis, the earth’s low levels of natural radiation actually might reduce cancer risk.
However this all shakes out, the study is a reminder that not all carcinogens are manufactured by chemical plants. And not all of them can be avoided. You can quit smoking and mitigate the radon in your basement. But you can’t mitigate oxygen.