A recent study, titled “Lung cancer incidence decreases with elevation: evidence for oxygen as an inhaled carcinogen” and published in the journal PeerJ, has found that some features of oxygen metabolism may promote lung cancer development.
This conclusion resulted from the observation that people living at higher altitudes have a lower incidence of lung cancer but not other non-respiratory cancers, suggesting the carcinogenic agent is incorporated through inhalation.
Oxygen is a very reactive agent, and upon cellular consumption results in reactive oxygen species (ROS), that are responsible for cellular damage and genetic mutations.
At higher altitudes, lower pressures result in less inhaled oxygen. For example, within different U.S counties, there is a 34.9% decrease in oxygen from Imperial County, California (-11 m) to San Juan County, Colorado (3473 m).
Researchers Kamen P. Simeonov and Daniel S. Himmelstein, from the University of Pennsylvania and the University of California, respectively, compared the rates of cancer incidence across different counties in different elevations within Western U.S., observing that lung cancer incidence was inversely proportional to elevation increase. However, these results do not directly prove that oxygen inhalation is a direct cause of lung cancer development, since there are many variables in higher elevations that can influence this trend.
As such, the team devised a model that considered such demographic variables, including smoking and education. Nonetheless, even after accounting for these factors, the association between high altitudes and lower lung cancer risk was still verified.
The team preformed the same analysis for non-respiratory cancers, including breast, prostate and colorectal cancers. However, the association between these cancers and low oxygen levels was weak or non-existent.
“(…) We reason that an exposure affecting only a portion of the population must confer a very large risk to produce the strong association observed”, the authors state in their study.“Follow-up biological and experimental analyses will be critical to understanding the causal factor and potential mechanisms underlying the observed elevation association. If future research confirms oxygen-driven tumorigenesis in the human lung, the present study will join the substantial list of ecological analyses that spurred new insights into cancer etiology”, they conclude.