In this case-control study of African Americans and Latino Americans in the San Francisco Bay Area, self-reported duration of occupational exposure to asphalt and tar was associated with a statistically significant increase in lung cancer risk in the overall population. Though the exposed individuals were not divided equally among African Americans (61 subjects) and Latino Americans (19 subjects), the risk estimates associated with exposure duration were almost identical in both subgroups (although not statistically significant when stratified in this way). Statistically significant increases in lung cancer risk were also observed for smoking, automobile exhaust, and asbestos.
Additionally, we found evidence in Latino Americans that CYP1A1 M2 polymorphisms modified the effect of smoking such that lung cancer risks were lower among individuals with CYP1A1 M2 variants than among those who did not carry a variant allele. The effect estimates examining potential modification of exposure to asphalt and tar and automobile exhaust by CYP1A1 were found to be in the same direction as that of smoking, but were not statistically significant. CYP1A1 is induced by PACs (e.g. benzo(a)pyrene) and activates these compounds such that variants of CYP1A1 are more commonly observed to be associated with greater PAH-related lung cancer risk (Guengerich, 1988
; Ishibe et al., 1997
). However, because the inverse interaction of CYP1A1 variants and PAH-associated lung cancer risk was observed previously in this Latino population (Wrensch et al., 2005
), we were interested in investigating other PAH exposures (ie asphalt and tar, automobile exhaust) to see if a similar effect would be observed. The inverse interactions of CYP1A1 variants and PAH-associated lung cancer risk in this Latino population could be due to linkage disequilibrium with an unrecognized lung cancer susceptibility gene. It is possible that the recently admixed genetic structure of the Latino population in northern California may have brought about the unique allelic association that we have observed.
Our findings are consistent with those of previous studies suggesting that occupational exposure to PACs, in particular asphalt and tar and automobile exhaust, may increase risk of lung cancer (Boffetta et al., 2003a
; Boffetta et al., 2003b
; Bosetti et al., 2007
; Garshick et al., 2008
; MacArthur et al., 2009
). Most notably, Boffetta et al (2003b)
conducted a multi-country study of 29,820 male asphalt workers from eight European countries with mortality that was documented from 1953 to 2000. Though the standardized mortality ratio (SMR) of lung cancer among asphalt-exposed workers (SMR: 1.08, 95%CI: 0.99–1.18) was comparable to that of non-exposed workers (SMR: 1.05, 95%CI: 0.92–1.19), the SMR of lung cancer in a sub-cohort of workers who were exposed to asphalt but not coal tar was significantly elevated (SMR: 1.23, 95% CI 1.02–1.48). However, more recently a nested case-control study was conducted using a subset of the same cohort (433 cases and 1,253 controls) to address the limitations of the original study by utilizing improved estimates of exposure to asphalt and confounders such as silica, asbestos, and coal tar (Olsson et al., 2010
). Olsson et al. (2010)
found no consistent evidence of an association asphalt exposure and lung cancer risk and suggested that the previously observed excess mortality may have been largely due to tobacco consumption and possibly to coal tar exposure.
In a previous study of asphalt paving workers, we found that inhalation and dermal exposures to PACs varied by task and that dermal exposure was strongly associated with urinary 1-hydroxypyrene as a biomarker of internal dose, which also varied by task and increased throughout the work week (McClean et al., 2004a
; McClean et al., 2004b
). We also found that PAH-DNA adducts exhibited task-based differences and a weekday trend that were consistent with the investigation of absorbed dose in the same population (McClean et al., 2007b
). The formation of DNA adducts occurs when reactive metabolites bind to sites within the DNA molecule, providing a useful measure of DNA damage that has been found to be associated with both PAH exposure and lung cancer risk (Tang et al., 1995
; Wiencke et al., 1995
To assess occupational exposures, we relied on self-reported years of employment in jobs that involved exposure to asphalt and tar, automobile exhaust, and asbestos. In other words, if a subject reported having exposure to asphalt and tar while employed in a particular job, duration of employment in that job was used as a surrogate measure of duration of exposure. Self-reported exposure and work histories have been shown to yield valid and reproducible data for use in epidemiologic studies (Delclos et al., 2006
; Hobson et al., 2009
; Ikin et al., 2002
). Additionally, self reported ‘ever-never’ exposure to asbestos and self-reported duration of exposure to asbestos were both significantly associated with an elevated lung cancer risk in both Latinos and African Americans, again suggesting that the questionnaire data provided a valid measure of historical exposure.
An assumption of this analysis is that length of employment in an exposed-job provides a reasonable surrogate measure for duration of exposure and would therefore be an improvement over simply relying on the ever-never metric, since all ever-exposed subjects are essentially assumed to have had the same exposure whereas duration of exposure allows for some differentiation. Given that a more biologically relevant metric would likely require information about frequency and intensity of exposure (which was unavailable), the use of the ever-never and exposure duration metrics likely resulted in non-differential misclassification, a type of error which leads to underestimation of the true risk.
A strength of this analysis is the availability of individual data for potential confounders (automobile exhaust, asbestos and smoking) in a population of minority individuals who may historically have had relatively high exposure, which allowed us to address common limitations of previous investigations of asphalt and tar (NIOSH, 2000
; Schulte, 2007
). However, a major limitation of this analysis is that the questionnaire asked about ‘asphalt and tar’ as a single substance, such that it was not possible to disentangle the increased lung cancer risk that may have been attributable to asphalt as compared to that of tar. Tar is derived from coal and contains a higher percentage of PACs than asphalt, which is derived from petroleum. Accordingly, workers exposed to coal tar are more likely to have experienced high exposures to PACs, though the likelihood and intensity of such exposures have varied over time and by sector of the asphalt industry (McClean et al., 2007a
; Mundt et al., 2009
). Of the 80 subjects who reported exposure to asphalt and tar, 22 subjects indicated that they worked in road paving, 16 reported that they worked on roofs, and the remaining 42 provided information that was insufficient for determining the nature of the work (e.g. construction, laborer, missing, etc). Accordingly, the limited job description data did not allow for an assessment of lung cancer risk by industry.
We cannot rule out the potential effect of recall bias, since the lung cancer patients may have been more likely than controls to self-report occupational exposures to substances such as asphalt and tar, automobile exhaust, and asbestos. However, for each job in their work history, subjects were asked for fairly objective information: a job description, year started, year stopped, and whether they were exposed to each of 21 substances (yes/no) while employed in that job. Subjects were not asked to provide subjective estimates of exposure intensity. For the 80 jobs reported to have included exposure to asphalt and tar, 60% of the descriptions were consistent with such exposures (i.e. paving, roofing, and/or specifically mentioned working with asphalt or tar), while another 19% provided less specific descriptions that were still consistent with asphalt and tar exposure (i.e. construction, laborer). Since self-reported exposure to asphalt and tar appear to be consistent with the described work for the majority of the reported job descriptions, the greatest potential for recall bias was likely among the remaining 20% of subjects (10 cases, 6 controls) who provided job descriptions that did not have an obvious connection to asphalt or tar (e.g. maintenance, factory worker, missing).
In conclusion, the results of this case-control study are consistent with the literature suggesting that exposure to asphalt and tar may be associated with an increased risk of lung cancer. However, it was not possible to separate the effects and asphalt and tar in this study. The known relationship between smoking and lung cancer and the increasingly recognized association between automobile exhaust and lung cancer were both observed in our case-control study and provide further evidence that occupational exposure to PAC mixtures increase the risk of lung cancer.