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Air pollution: another cause of lung cancer

Tuesday, 03 September 2013

Lung cancer is one of the most common cancers and has a poor prognosis. Active smoking is the main cause, but occupational exposures, residential radon, and environ mental tobacco smoke are also established risk factors.

Furthermore, lower socioeconomic position has been associated with a higher risk for lung cancer. Ambient air pollution, specifically particulate matter with absorbed polycyclic aromatic hydrocarbons and other genotoxic chemicals, is suspected to increase the risk for lung cancer. Results of several epidemiological studies have shown higher risks for lung cancer in association with various measures of air pollution and suggested an association mainly in nonsmokers and neversmokers and in individuals with low fruit consumption. In developed countries, overall lung cancer incidence rates have stabilised during the past few decades, but major shifts have been recorded in the frequencies of different histological types of lung cancer, with substantial relative increases in adenocarcinomas and decreases in squamous cell carcinomas. Changes in tobacco blends and ambient air pollution might have contributed to these shifts.

Within the European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to analyse data from 17 European cohort studies with a wide range of exposure levels to investigate the following hypotheses: that ambient air pollution at the residence (specifically particulate matter) is associated with risk for lung cancer; that the association between air pollution and risk for lung cancer is stronger for nonsmokers and people with low fruit intake; and that the association with air pollution is stronger for adenocarcinomas and squamouscell carcinomas than for all lung cancers combined.

In The Lancet Oncology, Ole Raaschou-Nielsen and colleagues present the findings from individual data from 17 European cohorts and show that exposure to particulate matter air pollution increased the risk of lung cancer—particularly adenocarcinoma—with a suggestion of an effect even below the current European Union air pollution limit values (40 μg/m3 for particulate matter with an aerodynamic diameter <10 μm [PM10] and 25 μg/m3 for particulate matter with a diameter <2·5 μm [PM2·5]).

The design of their study is sophisticated and overcame several limitations of previous air pollution studies. Earlier studies examined the effect of air pollution on lung cancer by assessing geographical correlations (ie, between air pollution concentration data in communities and aggregate data on lung cancer), but they suffered from exposure misclassification and confounding (mainly by tobacco smoking). Subsequently, researchers tried to reduce these systematic errors by shifting to individual studies (case-control or cohort studies) with area-level exposure assessment or more precise individual-level exposure assessment. Raaschou-Nielsen and colleagues’ took the next step by combining effect estimates from 17 cohorts with standardised protocols and undertaking a meta- analysis, which increased the number of participants, who came from a wide range of European regions, and reduced the possibility of sampling and publication bias. This study also benefited from a high follow-up rate and adjustment of potential confounders, including a set of smoking variables. This study, therefore, should have reduced much of the systemic and random errors reported previously.

Even in the well known companion textbook for medical doctors, air pollution is not listed as a cause of lung cancer. Although smoking is undoubtedly a strong risk factor, evidence for an association between air pollution exposure and lung cancer is also accumulating. Although the lung cancer risk associated with air pollution (eg, HR 1·22 [95% CI 1·03–1·45] per 10 μg/m3 increase in PM10 in this study) is much lower than that associated with smoking (relative risk [RR] 23·3 for currently smoking men and RR 12·7 for currently smoking women), everybody is exposed to air pollution. Thus, the public health effect is quite large.

For example, WHO estimated that smoking caused 5·1 million deaths and 71% of lung cancer worldwide in 2004, whereas air pollution caused 1·2 million deaths and 8% of lung cancer worldwide in the same year.

Absence of safe thresholds is reported for health effects caused by both short-term exposure and long- term exposure to PM2·5. Even in Raaschou-Nielsen and colleagues study, raised point estimates were still reported below 10 μg/m3 of PM2·5 (a current WHO air quality guideline for yearly PM2·5 exposure). Moreover, the investigators noted that the association between air pollution and lung cancer did not deviate statistically significantly from linearity. These findings clearly support a possibility that “public health benefits will result from any reduction of PM2·5 concentrations whether or not the current levels are above or below the limit values”, as summarised by WHO. Indeed, accountability studies that examined potential benefits of air pollution interventions (eg, planned actions such as reduction of fuel sulphur or regulation of vehicles and unplanned actions such as plant closures due to strikes) consistently showed that interventions reduced air pollution concentrations and improved health outcomes.

So far, air pollution studies that have examined an association with lung cancer have mainly been done in Europe and North America, although several studies have emerged from other continents in recent years that also show associations between air pollutants and lung cancer risk. However, an attempt such as Raaschou-Nielsen and colleagues’ (ie, a meta-analysis of cohorts) has not been reported outside of Europe; future collaborative studies in other continents will thus provide further insights into the risk of lung cancer caused by air pollution exposure. Moreover, Raaschou-Nielsen and colleagues identified a relation between air pollution and the histological subtype of adenocarcinoma in particular; however, in a previousstudy by the same investigat or of three Danish cohorts, a stronger association with squamous-cell carcinoma and small-cell carcinoma was reported than with adenocarcinoma. In view of the shift in frequency of lung cancer types (ie, from squamous-cell carcinoma to adenocarcinoma) and the different frequency distributions of types of lung cancer throughout the world, future assessments of the association between air pollution and specific types of lung cancer are warranted.

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


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