Discussion

Previous studies demonstrating an increased risk of lung cancer in painters have allowed IARC to classify occupation as a painter as carcinogenic to humans (Group 1) (IARC 1989, in press). This meta-analysis supports the IARC Group 1 classification by demonstrating a 35% increased risk of lung cancer in painters after adjusting for smoking (meta-RR = 1.35; 95% CI, 1.211.51; I 2 = 41.2%, p = 0.01). This association was stronger for population-based casecontrol studies (meta-OR, 1.34; 95% CI, 1.181.51; I 2 = 25.9%, p = 0.16) or studies that adjusted for other potentially confounding occupational exposures (meta-RR = 1.57; 95% CI, 1.212.04; I 2 = 0%, p = 0.68). Furthermore, exposureresponse analyses suggested that the risk increased with duration of employment. Although paint composition or the painting environment could have differed by major geographic region, the results did not vary much when stratified by region (North America, Europe, Asia, and South America). This is the first meta-analysis that demonstrates a relative increase in incidence/mortality from lung cancer in persons occupationally exposed as painters when restricted to never-smokers (and also nonsmokers), as well as demonstrating a statistically significant, positive durationresponse relationship.

It is important to note that the interpretation of a meta-SMR (or meta-SIR) for the cohort and record linkage studies is difficult because different reference populations were used in each study for the calculation of expected cases or deaths (Rothman et al. 2008). Although the cohort studies of painters could assess possibly higher exposures from longer periods of follow-up, exposure assessment in many of the record linkage studies was often crude: Occupation as a painter was usually assessed at a single time point in a census and then linked to death registries. Although there can be relatively poor correspondence between occupation recorded on death certificates and in census records (Dubrow and Wegman 1984; Enterline and McKiever 1963; Guralnick 1963; OPCS 1971, 1978) and there is a chance of false-positive results due to multiple testing of occupations in record linkage studies, the SMRs were remarkably consistent between individual studies, generally ranging between 1.10 and 2.57. This also suggested that the significant results were not likely due to chance. Thus, the approach to combine the cohort and record linkage study SMRs for calculating a meta-SMR seemed to be justified.

In casecontrol studies, painters may only form a small proportion of the study population, but the full occupational history and additional information on lifestyle factors allowed several studies to adjust for tobacco smoking and some for other occupational carcinogens. An increased lung cancer risk associated with painting was consistently demonstrated in the casecontrol studies, suggesting that occupation as a painter is a risk factor for lung cancer. Population-based casecontrol studies may be less subject to selection biases than hospital-based casecontrol studies (Rothman et al. 2008) because there is generally no concern about the appropriate source population if indeed the general population is represented. However, if response rates are low in population controls, this could result in a lack of comparability with cases and therefore be prone to selection biases. A subanalysis comparing the meta-OR of hospital-based and population-based casecontrol studies showed similar results.

Estimates of the PMR may be biased if the population under study does not share the same distribution of mortality as the standard population used to compute the proportions for categories other than the ones studied (Rothman et al. 2008). However, the proportionate mortality analyses also showed significantly elevated relative risks for lung cancer in painters within the same range of effect as the analyses overall and in cohort studies, further suggesting that these results remained robust to these biases.

Smoking-adjusted estimates were available for 23 of 29 casecontrol studies and in only 4 of 18 cohort and record linkage studies. The robustness of the summary estimates after adjusting for tobacco use, and the higher relative risk in never-smokers, suggest that residual confounding by tobacco use is unlikely and that occupation as a painter is independently associated with the risk of lung cancer.

In women, the meta-RR was similar for all studies (meta-RR = 2.04; seven studies) (Jahn et al. 1999; Muscat et al. 1998; OPCS 1958, 1971; Pronk et al. 2009; Pukkala 2009; Zeka et al. 2006) and for studies restricted to never-smokers (meta-RR = 2.00; three studies) (Kreuzer et al. 2001; Pronk et al. 2009; Zeka et al. 2006), further strengthening the evidence that the results are not confounded by smoking. However, female painters (and never-smoking females) may not actually have a higher risk of lung cancer compared with male painters (meta-RR = 1.37; 39 studies). The relative risk in women is higher, which may be due to the fact that women have a lower background lung cancer risk than men (Schottenfeld and Fraumeni 2006).

The robustness of the results is also indicated by the presence of a durationresponse relationship, with higher RRs seen for exposure over ≥ 10 years (meta-RR = 1.95) and ≥ 20 years (meta-RR = 2.00) compared with those with < 10 and < 20 years of exposure, respectively (the reference category was no exposure).

Some painters (e.g., in the construction industry) could have been exposed to asbestos. Indeed, a number of studies have shown an increased risk of mesothelioma in painters (Brown et al. 2002; Peto et al. 1995), which is most likely due to occupational asbestos exposure. However, taking into account that the exposureresponse relationship for pleural mesothelioma is very different from that for lung cancer, potential asbestos exposure cannot explain all of the increase in lung cancer. Therefore, other suspected carcinogens to which painters are exposed, such as chlorinated solvents, chromium VI compounds, and cadmium compounds (IARC 1987, 1995, 1999, in press; Straif et al. 2009), may also partially explain the increased risk of lung cancer. Very few studies reported results for specific suspected causative agents. van Loon et al. (1997) reported a positive exposureresponse relationship with paint dust and Siemiatycki et al. (1987) found a suggestive association with mineral spirits, whereas Alexander et al. (1996) did not find an increased risk of lung cancer in a cohort of painters and other employees in the aerospace industry exposed to chromium VI compounds.