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Pollution, Lung Cancer Link Grows Stronger

Long-term exposure even to low-level air pollution may increase the risk of lung cancer, particularly adenocarcinoma, an analysis of 17 European studies suggested.

Ambient air concentrations of particulate matter <10 micrometers and <2.5 micrometers had statistically significant associations with adenocarcinoma of the lung, the most common lung cancer histology. Both types of air pollution were associated with >50% increased risk of lung adenocarcinoma, reported Ole Raaschou-Nielsen, PhD, of the Danish Cancer Society Research Center in Copenhagen, and colleagues.

Concentrations of particulate matter <10 micrometers also had a significant association with any lung cancer, they wrote online in The Lancet Oncology.

"This very large multicenter study shows an association between exposure to particulate matter air pollution and the incidence of lung cancer, in particular adenocarcinoma, in Europe, adding substantially to the weight of the epidemiological evidence," Raaschou-Nielsen's group concluded.

"The cohort-specific analyses consistently identified smoking-related variables as the most important confounders, in accordance with the fact that smoking is the most important risk factor for lung cancer," they noted. "Information about smoking variables was available for all the cohorts, and we would expect only weak confounding, if any, from exposure to environmental tobacco smoke."

Multiple studies have implicated ambient air pollution as a potential cause of lung cancer. Lung cancer incidence has stabilized in recent years in most developed countries, but major shifts in histologic subtypes have occurred, the authors noted.

Specifically, the incidence of adenocarcinoma has increased substantially, accompanied by substantial decline in the incidence of squamous-cell carcinomas. Of note, adenocarcinoma accounts for a majority of lung cancer cases among smokers and nonsmokers.

The European Study of Cohorts for Air Pollution Effects (ESCAPE) maintains data from 17 European cohort studies that have investigated associations between various levels of air pollution and lung cancer. Raaschou-Nielsen and colleagues analyzed ESCAPE data to address three hypotheses:

Ambient air pollution at the residence is associated with lung cancer risk Air pollution has a stronger association with lung cancer among nonsmokers and people with low fruit intake The association is stronger for adenocarcinoma and squamous-cell carcinoma than for all lung cancers combined

The primary outcome was all lung cancer, and key secondary outcomes pertained to adenocarcinomas and squamous-cell carcinomas.

The 17 studies comprised cohorts representing 12 cities and nine countries. Investigators analyzed data for each cohort, and cohort-specific estimated effects were combined by meta-analysis. Exposure estimates were derived from land-use regression models.

The land-use models included particulate matter <10 micrometers, <2.5 micrometers, 2.5 to 10 micrometers, soot, nitrogen oxides, and two traffic indicators.

The overall analysis comprised 312,944 study participants and about 4.1 million person-years at risk. During a mean follow-up of 12.8 years, 2,095 cases of lung cancer were diagnosed. The meta-analyses showed a significant association between lung cancer and particulate matter <10 micrometers, represented by a hazard ratio of 1.22 (95% CI 1.03-1.45 per 10 micrometers/m3). An HR hazard ratio of 1.18 for particulate matter <2.5 micrometers did not achieve significance (95% CI 0.96-1.46 per 5 micrometers/m3).

Analyses of associations between air pollution and adenocarcinoma lung cancer showed significant associations for particulate matter <10 micrometers (HR 1.51, 95% CI 1.10-2.08) and <2.5 micrometers (HR 1.55, 95% CI 1.05-2.29). Associations were strongest for participants who resided at the same address for longer periods of time.

Analyses related to traffic intensity on the nearest street, increased road traffic in proximity to residence, and nitrogen oxide concentrations showed no significant associations with lung cancer.

The author of an invited commentary credited the investigators with designing and performing a study that "is sophisticated and overcame several limitations of previous air pollution studies."

Nonetheless, Takashi Yorifuji, MD, PhD, of Okayama University, and Saori Kashima, PhD, of Hiroshima University, both in Japan, lamented the lack of recognition of air pollution as a contributing factor in lung cancer. For example, the 18th edition (2012) of Harrison's Principles of Internal Medicine excluded air pollution from a list of lung cancer risks.

"Although smoking is undoubtedly a strong risk factor, evidence for an association between air pollution exposure and lung cancer is also accumulating," Yorifuji and Kashima said. "Although the lung cancer risk associated with air pollution is much lower than that associated with smoking, everybody is exposed to air pollution. Thus, the public health effect is quite large."

"At this stage, we might have to add air pollution, even at current concentrations, to the list of causes of lung cancer and recognize that air pollution has large effects on public health, although fortunately, like tobacco smoking, it is a controllable factor," they added.

The study was supported by the European Community's Seventh Framework Program.

The authors reported no conflicts of interest.

Yorifuji and Kashima reported no conflicts of interest.