Abstract
The level of atmospheric oxygen, a driver of free radical damage and tumorigenesis, decreases sharply with rising elevation. To understand whether ambient oxygen plays a role in human carcinogenesis, we characterized age-adjusted cancer incidence (compiled by the National Cancer Institute from 2005 to 2009) across counties of the elevation-varying Western United States and compared trends displayed by respiratory cancer (lung) and non-respiratory cancers (breast, colorectal, and prostate). To adjust for important demographic and cancer-risk factors, 8–12 covariates were considered for each cancer. We produced regression models that captured known risks. Models demonstrated that elevation is strongly, negatively associated with lung cancer incidence (p < 10−16), but not with the incidence of non-respiratory cancers. For every 1,000 m rise in elevation, lung cancer incidence decreased by 7.23 99% CI [5.18–9.29] cases per 100,000 individuals, equivalent to 12.7% of the mean incidence, 56.8. As a predictor of lung cancer incidence, elevation was second only to smoking prevalence in terms of significance and effect size. Furthermore, no evidence of ecological fallacy or of confounding arising from evaluated factors was detected: the lung cancer association was robust to varying regression models, county stratification, and population subgrouping; additionally seven environmental correlates of elevation, such as exposure to sunlight and fine particulate matter, could not capture the association. Overall, our findings suggest the presence of an inhaled carcinogen inherently and inversely tied to elevation, offering epidemiological support for oxygen-driven tumorigenesis. Finally, highlighting the need to consider elevation in studies of lung cancer, we demonstrated that previously reported inverse lung cancer associations with radon and UVB became insignificant after accounting for elevation.
Highlights
At present, four types of cancer—prostate, breast, lung, and colorectal—exceed 100,000 new cases per year in the United States
Population subgroupings We evaluated the association between elevation and lung cancer incidence measured for the following population subgroups: under 65 years old, 65 or older, males, and females
Negative association between elevation & lung cancer incidence Performing best subset regression for each cancer, we found a highly significant, strong negative association between elevation and lung cancer incidence with a standardized coefficient of −0.35 99% CI [−0.46, −0.25] (p < 10−16, one-tailed t-test) (Table 2)
Summary
Four types of cancer—prostate, breast, lung, and colorectal—exceed 100,000 new cases per year in the United States. Of these cancers, lung cancer carries the worst prognosis and will claim an estimated 159,260 lives in 2014 (Siegel et al, 2014). Additional characterized risk factors include genetic susceptibility as well as environmental exposure to carcinogens such as radon, asbestos, and fine-particulate matter (Subramanian & Govindan, 2007). This multifactorial etiology for lung cancer could include long-term exposure to an inhaled carcinogen
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