Issue: May 25, 2012
March 20, 2012
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Diesel exhaust exposure linked to increased risk for lung cancer mortality

Issue: May 25, 2012
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Exposure to heavy diesel exhaust may increase the risk for dying of lung cancer, according to two studies published in the Journal of the National Cancer Institute.

Past studies have indicated a possible correlation between heavy diesel exhaust and the progression of lung cancer — in 1989, the International Agency for Research on Cancer classified diesel exhaust as a probable carcinogen based on limited evidence of carcinogenicity. To establish the relationship between heavy diesel exhaust exposure and increased mortality risk for lung cancer, researchers conducted a cohort study of 12,315 workers in eight underground nonmetal mining facilities, including 198 lung cancer deaths and 562 incidence density–sampled control participants.

For each lung cancer mortality, researchers enrolled approximately four control participants, matched on mining facility, sex, race/ethnicity and birth year (within 5 years), from all workers who were alive before the day the patient died. Researchers estimated diesel exhaust exposure — represented by respirable elemental carbon — for each patient according to job and year, based on extensive exposure assessments at the mining facilities.

According to the studies, researchers observed a statistically significantly increased risk for lung cancer with increasing respirable elemental carbon exposure among underground workers — among heavily exposed workers, lung cancer risk was approximately three times greater (OR=3.2; 95% CI, 1.33-7.69) than that among workers in the lowest quartile of exposure. Evidence of heightened risk was also observed for longer-term workers above ground who were exposed to elevated levels of respirable elemental carbon.

“Because such workers had at least a 50% increased lung cancer risk, our results suggest that the high air concentrations of elemental carbon reported in some urban areas may confer increased risk of lung cancer,” researcher Debra T. Silverman, ScD, said in a press release. “Thus, if the diesel exhaust/lung cancer relation is causal, the public health burden of the carcinogenicity of inhaled diesel exhaust in workers and in populations of urban areas with high levels of diesel exposure may be substantial.”

Notable limitations of this study included the uncertainty in retrospective exposure assessment and information on workers’ hazardous exposures before and after the study job, as well as the fact that certain lifestyle risk factors, such as smoking, were obtained from the patient’s next of kin.

“Our findings are important, not only for miners but also for the 1.4 million American workers and the 3 million European workers exposed to diesel exhaust and for urban populations worldwide,” Silverman said, adding that in past decades, cities such as Mexico City, Estarreja, Portugal, and nine urban centers in China have reported diesel exposure levels comparable to some underground workers in the lower range of diesel exposure found in this study.

Disclosure: The researchers disclosed funding from the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics and the National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies.

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PERSPECTIVE

Greg Otterson, MD
Greg
Otterson

Tobacco use has been established as a lung cancer carcinogen since the 1950s. Additional occupational/environmental exposures have also been established, particularly asbestos and radon. Investigators at the National Cancer Institute and the National Institute for Occupational Safety and Health have recently added to the conversation with two studies based upon the Diesel Exhaust in Miners Study (DEMS), a cohort mortality study and a paired case-control study of lung cancer mortality published in the Journal of the National Cancer Institute.

What are the implications of these studies? Over the last decade, the concept that never-smoking lung cancer is a distinct entity from smoking-related lung cancer has become firmly established by the finding that never-smokers with lung cancer are much more likely to have mutations within the epidermal growth factor receptor or translocations involving ALK or ROS1 (J Clin Oncol. 2012;30:863-870; J Clin Oncol. 2009;27:4247-4253; and J Clin Oncol. 2001;29:2066-2070). The implied assumption is that these cancers have a distinct carcinogen, though what was unclear — asbestos, radon, second-hand smoke may all be less likely in that these carcinogens have clear “synergistic” (or at a minimum, greater than additive) properties with active tobacco use (J Natl Cancer Inst. 1980;65:507-513 and Am J Epidemiol. 2009;169:718-730).

Could diesel exhaust explain never-smoking lung cancer? These studies don’t definitely answer this clinical question, but clearly, there are public health implications regarding the attempt to reduce exposure to respirable carbon. Other non-mine workers have significant exposure to diesel exhaust, and the authors point out that urban centers often have high elemental carbon levels: Los Angeles (4 mcg/m3), urban sites in China (8.3 mcg/m3), Mexico City (5.8 mcg/m3), for example. They postulate that while these are significantly lower than that they found in the eight mines evaluated, a lifetime exposure to these levels may cumulatively cause substantial burdens to individuals and populations.

Greg Otterson, MD
Co-director of Thoracic Oncology, Division of Medical Oncology
Ohio State University Comprehensive Cancer Center
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Columbus, Ohio

Disclosure: Dr. Otterson reported no relevant financial disclosures.