Lung cancer risk after exposure to polycyclic aromatic hydrocarbons: a review and meta-analysis

Environmental Health Perspectives, June 15, 2004 by Ben Armstrong, Emma Hutchinson, John Unwin, Tony Fletcher

Typical polycyclic aromatic hydrocarbon mixtures are established lung carcinogens, but the quantitative exposure-response relationship is less dear. To clarify this relationship we conducted a review and meta-analysis of published reports of occupational epidemiologic studies. Thirty-nine cohorts were included. The average estimated unit relative risk (URR) at 100 [micro]g/[m.sup.3] years benzo[a]pyrene was 1.20 [95% confidence interval (CI), 1.11-1.29] and was not sensitive to particular studies or analytic methods. However, the URR varied by industry. The estimated means in coke ovens, gasworks, and aluminum production works were similar (1.15-1.17). Average URRs in other industries were higher but imprecisely estimated, with those for asphalt (17.5; CI, 4.21-72.78) and chimney sweeps (16.2; CI, 1.64-160.7) significantly higher than the three above. There was no statistically significant variation of URRs within industry or in relation to study design (including whether adjusted for smoking), or source of exposure information. Limited information on total dust exposure did not suggest that dust exposure was an important confounder or modified the effect. These results provide a more secure basis for risk assessment than was previously available. Key words: cancer, lung, meta-analysis, PAH, polycyclics, review. Environ Health Perspect 112:970-978 (2004). doi: 10.1289/ehp.6895 available via http://dx.doLorg/[Online 7 April 2004]

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Airborne polycyclic aromatic hydrocarbons (PAHs), which are emitted when organic matter is burned, are ubiquitous in the occupational and general environment. It has long been known that several PAHs can produce cancers in experimental animals, and epidemiologic studies of exposed workers, especially in coke ovens and aluminum smelters, have shown clear excesses of lung cancer and highly suggestive excesses of bladder cancer [Boffetta et al. 1997; International Agency for Research on Cancer (IARC) 1984, 1985, 1987; Mastrangelo et al. 1996; Negri and La Vecchia 2001]. The animal experiments have included some using airborne exposure and have been mixtures and individual compounds, including particularly benzo[a]pyrene (BaP). Although the existence of a cancer risk is beyond reasonable doubt, considerable uncertainty exists as to the exposure-response relationship, and hence as to the risks posed at today's levels in the workplace and general environment. Information on this relationship is clearly important for setting of occupational and environmental standards.

Estimating exposure-response relationships by extrapolation from animal studies is possible [Collins et al. 1991; U.S. Environmental Protection Agency (U.S. EPA) 1984], but the limitation of this approach, particularly species differences, makes sole reliance on it problematic. Data from a large cohort of coke oven workers in the United States, which has been followed since the 1960s (Costantino et al. 1995; Lloyd 1971), have been used to estimate risk per unit residential exposure [Nisbet and LaGoy 1992; World Health Organization (WHO) 1987]. However, many other studies provide information that has not yet been systematically used to quantitatively assess risk.

The fact that PAHs comprise a mixture, several components of which are animal carcinogens, adds to the complexity of the task. One issue is whether a single index of exposure, such as BaP or total benzene soluble matter (BSM) or cyclohexane soluble matter (CSM) is adequate to determine risk. If such an index is used, risk per unit exposure may differ between studies (and unstudied exposures) because of differences in the ratio of this index to the total carcinogenic potential of the mixture. It is possible that such variation, if present, can be adequately described by classifying exposures in broad categories (e.g., by source). However, this approach remains untested.

We conducted a review and meta-analysis that aimed to use all relevant published evidence from epidemiologic studies to obtain an estimate or estimates of the relationship of PAH exposure with lung and bladder cancer and to identify sources of variation in this relationship. Here we report the results for lung cancer.

Methods

The methods summarized here are described at greater length in a technical report on this work (Armstrong et al. 2002).

Literature Search

We sought all potentially informative peer-reviewed publications reporting epidemiologic studies on the occupational PAH-lung cancer exposure-response relationship. Specifically, we searched the following online electronic databases: MEDLINE (http://www.nlm.nih.gov/databases/databases_medline.html); EMBASE (http://www.embase.com/); OLDMEDLINE (http://www.nlm.nih.gov/databases/databases_oldmedline.html); NIOSHTIC-2 (http://www2.cdc.gov/nioshtic2/niosh2.htm); and CancerLit (http://www.cancer.gov/search/cancer_literature/). We searched publication dates 1958-February 2001) by text phrases and supplemented these publications with articles cited in the studies we obtained.