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Ann. occup. Hyg., Vol. 48, No. 4, pp. 309-326, 2004 2004 British Occupational Hygiene Society Published by Oxford University Press DOI: 10.1093/annhyg/meh022 Downloaded from http://annhyg.oxfordjournals.org by on March 11, 2010 Mesothelioma and Lung Cancer Among Motor Vehicle Mechanics: a Meta-analysis MICHAEL GOODMAN1*, M. JANE TETA2, PATRICK A. HESSEL3, DAVID H. GARABRANT4, VALERIE A. CRAVEN5, CAROLYN G. SCRAFFORD6 and MICHAEL A. KELSH7 1Emory University Rollins School of Public Health, 1518 Clifton Road NE, Atlanta, GA 30322, USA; 2Exponent Health Group, 1730 Rhode Island Avenue NW, Suite 1100, Washington, DC 20036, USA; 3Exponent Health Group, 2 North Riverside Plaza, Suite 1400, Chicago, IL 60606, USA; 4University of Michigan School of Public Health, 1420 Washington Heights, Room 6529, Ann Arbor, MI 48109-2029, USA; 5Exponent Health Risk Group, 631 First Street, Santa Rosa, CA 95404, USA; 6Exponent Food and Chemicals Group, 1730 Rhode Island Avenue NW, Suite 1100, Washington, DC 20036, USA; 7Exponent Health Group, 149 Commonwealth Drive, Menlo Park, CA 94025, USA Received 26 August 2003; in final form 13 November 2003; published online on 17 May 2004 We conducted a systematic review and analysis of the epidemiological literature that examines the risk of lung cancer and mesothelioma among motor vehicle mechanics who may have been engaged in brake repair and, thus, were potentially exposed to asbestos. All relevant studies were classified into three tiers according to their quality. Tier III (lowest quality) studies were cited for completeness, but were not included in the meta-analysis. Meta relative risks (metaRRs) were calculated for mesothelioma and lung cancer using both fixed and random effects models for Tiers I and II, separately, followed by stratified analyses based on study design or exposure characterization (garage workers versus brake workers) and, for lung cancer studies, based on adequate adjustment for smoking. The meta-analysis for Tier I (higher quality) and Tier II (lower quality) studies of mesothelioma yielded RR estimates of 0.92 (95% CI 0.55-1.56) and 0.81 (95% CI 0.52-1.28), respectively. Further stratification according to exposure charac terization did not affect the results. The meta-analysis for lung cancer produced RR estimates of 1.07 (95% CI 0.88-1.31) for Tier I and 1.17 (95% CI 1.01-1.36) for Tier II. When the lung cancer analysis was limited to studies that used adequate control for smoking, the resulting RR estimate was 1.09 (95% CI 0.92-1.28). Based on these findings, we conclude that employment as a motor vehicle mechanic does not increase the risk of developing mesothelioma. Although some studies showed a small increase in risk of lung cancer among motor vehicle mechanics, the data on balance do not support a conclusion that lung cancer risk in this occupational group is related to asbestos exposure. Keywords: asbestos; brakes; epidemiology; lung cancer; mesothelioma; meta-analysis; motor vehicle mechanics INTRODUCTION The causal association between inhaled asbestos fibers and the development of lung cancer is well established. While the causal role of amphibole asbestos in the development of mesothelioma is also clear, there is still disagreement regarding the doseresponse relationship between chrysotile asbestos *Author to whom correspondence should be addressed. Tel: +1 404 727 2734; Fax: +1 404 727 8737; E-mail: mgoodm2@sph.emory.edu and mesothelioma and the role of amphibole contam inants in that relationship (Hodgson and Darnton, 2000). Excess risk of these two cancers has not been found in all settings where there is potential exposure to asbestos. Recent attention has shifted from highly exposed occupational groups such as insulators and shipyard workers to those with asbestos exposures that could be both qualitatively and quantitatively different. One such occupation is motor vehicle repair, where exposure to short chrysotile fibers can occur during installation and repair of asbestoscontaining brakes. (In North America, automobile 309 310 M. Goodman et al. Downloaded from http://annhyg.oxfordjournals.org by on March 11, 2010 brakes typically contained chrysotile asbestos embedded in a solid binder.) The process of brake replacement involves two potential opportunities for release of asbestos fibers: (i) small amounts of chrysotile asbestos (usually less than 1%) that may be present in the brake wear debris and (ii) asbestos that can be released during grinding and beveling of new asbestos brake linings or pads. Some authors (Lorimer et al., 1976), regulatory agencies (EPA, 1986c) and trade organizations (World Trade Organization, 2000) have opined in the past that motor vehicle mechanics are likely to be at increased risk of developing asbestos-related disease, most notably mesothelioma. These opinions have been based primarily on the fact that asbestos expo sures can occur during brake work and cases of mesothelioma have been reported among workers who had done brake repair (EPA, 1986a,b,c). When the EPA conducted its evaluation (EPA, 1986b,c) the epidemiological information on mesothelioma among vehicle mechanics was limited to only three studies (McDonald and McDonald, 1980; Teta et al., 1983; Spirtas et al., 1985). However, in more recent years a number of addi tional epidemiological studies have examined the risk of mesothelioma and/or lung cancer among motor vehicle mechanics or specifically among brake workers. These studies are preferable to case reports and case series in assessing associations between exposure and disease. We conducted a systematic review of the epidemi ological literature examining the relative risks of mesothelioma and lung cancer among workers engaged in motor vehicle repair and, when possible, among workers occupationally exposed to brake dust. A previous review of the literature examined six case-control studies of mesothelioma among garage mechanics (Wong, 2001). However, we felt that these analyses could be enhanced by including additional published and unpublished studies and by including a re-analysis of one of the original data sets. In addi tion, we expanded the scope of our review beyond mesothelioma to include studies of lung cancer. This issue is of growing scientific, public health and societal importance (Schneider and Smith, 2000; Truby, 2002). Large numbers of people have been exposed to brake dust over the last several decades (Lorimer et al., 1976; Nicholson et al., 1984; Huncharek, 1990) and an increased risk of asbestosrelated cancers among these workers could translate into a substantial burden of disease. METHODS Study selection A number of electronic literature databases were searched using a variety of search strategies and multiple combinations of keywords such as `asbestos', `brakes', `mesothelioma', `lung cancer', `cancer', `garage mechanics', `automobile mechanics', `motor mechanics', `mechanics', etc. Copies of the articles were obtained, including those from foreign language journals, which were trans lated into English. Reference lists of identified arti cles were examined to locate additional studies. Internet and literature searches were also conducted to identify relevant studies that were not published in the peer-reviewed literature. Of partic ular interest were government documents and book chapters. When information was missing from published reports, attempts were made to contact the authors to obtain the missing information. In order to be included in the review, studies were required to meet all of the following criteria: outcomes of interest included mesothelioma and/or lung cancer; relative risk estimates and associated variance measures were either reported by the authors or could be calculated based on the data obtained from the authors or reported in the papers; the exposed population was involved in motor vehicle repair, excluding general mechanics. After this initial study selection, the meta-analysis included two steps: (i) a review and quality scoring of each study and (ii) a quantitative analysis of the pooled measures of association from studies that met the inclusion criteria. Review of the literature All potentially relevant studies underwent a formal evaluation and were assigned a quality score according to their methodological strengths and weaknesses. The general approach involved awarding each study a point (+1) for each methodo logical strength and penalizing with a negative score (-1) for each evident shortcoming. The quality scoring was conducted according to the following criteria. Overall study design: proportionate mortality/ incidence ratio (PMR/PIR) studies or death cer tificate-based standardized mortality odds ratio (SMOR) studies = -1; else (cohort or case-con trol studies) = 0. Asbestos exposure: non-specific = 0 (e.g. `car mechanic'); specific = 1 [e.g. `brake repairmen' or industrial hygiene (IH) based]. Age adjustment: no = -1; yes = 0. Confounding by other occupational exposure: likely = -1 (e.g. studies where motor vehicle mechanics with other multiple occupations were compared with persons with no history of any atrisk occupations); possible but not clearly evi dent = 0; unlikely/addressed = 1 (e.g. studies that Downloaded from http://annhyg.oxfordjournals.org by on March 11, 2010 312 M. Goodman et al. There were 11 studies that reported (or permitted calculations of) the relative risk estimates for mesothe lioma. These studies underwent formal evaluation and scoring. The results of scoring for each study are presented in Table 1. Four studies were included in Tier III (Coggon et al., 1995; Hodgson et al., 1997; Milham and Ossiander, 2001; NIOSH, personal communication, 2002). Of the seven remaining studies, four studies with scores between 3 and 5 were included in Tier I (Table 2A) and three studies with scores between 0 and 2 were included in Tier II (Table 2B). All relevant studies were published in English. Two studies were conducted exclusively in the USA, one study was conducted in Canada, one combined US and Canadian data and three took place in Europe (one in Germany, one in Denmark and one in Spain). The years of publication ranged from 1980 to 2004. A more detailed discussion of each Tier I and Tier II study follows. Tier I. McDonald and McDonald (1980). The study here compared histologically confirmed mesothelioma cases to matched controls who had pulmonary metastases from non-pulmonary malignancies. Occupa tional histories obtained through interviews with relatives were ranked according to their potential for asbestos exposure. Of the 156 cases and 156 controls without a recognized increase in mesothelioma risk, the occupation `garage' was reported for 11 cases and 12 controls, from which we calculated an OR of 0.91 (95% CI 0.35-2.34). This study had a large sample size, a high response rate and used pathologists to establish the diagnosis of mesothelioma. The use of non-pulmonary cancers as controls has both advantages and disadvantages. Hospital-based cancer cases may not be representa tive of the general population (i.e. possible selection bias). However, the choice of controls with other cancers may have reduced recall bias. The use of the highest asbestos exposure to characterize each partic ipant's occupational history helped decrease poten tial confounding by other asbestos exposures. However, the occupational category defined as `garage' is insufficiently specific. Teta et al. (1983). After a pathology review, cases from the Connecticut Tumor Registry and from a large Veterans Administration hospital were compared with controls selected from the death certificate files of the Connecticut State Department of Health Services. Occupational histories for cases and controls were obtained from death certificates and from city directories. The OR for subjects employed in `automobile repair and related service' was 0.65 (95% CI 0.08-5.53). Unlike other case-control studies, Teta et al. (1983) relied on objective historical employment information rather than subjective reports from inter views. The choice of population controls, the high response rate and the histological confirmation of the mesothelioma diagnoses have to be considered as methodological strengths. The main shortcomings are non-specific exposure characterization and the inability to eliminate other exposures due to its small size. Table 1. Quality scores of studies evaluating the association between mesothelioma risk and employment as a motor vehicle mechanic Quality criteria Study 1 2 3 4 5 6 7 8 9 10 11 Overall study design: PMR/PIR/SMOR = -1; else = 0 0 0 0 0 0 0 0 -1 -1 -1 -1 Asbestos exposure: non-specific (e.g. `car mechanic') = 0; specific (e.g. brake repairman, or IH-based) = 1 0 1 1 00 0 1 0 0 0 0 Age adjustment: no = -1; yes = 0 0 0 0 -1 0 0 -1 0 0 0 0 Confounding by other occupational exposure: likely = -1; possible = 0; unlikely/addressed = 1 1 11 00 0 00000 Exposure-response analysis: no = 0; yes = 1 0 1 0 00 0 0 0 0 0 0 Analysis by latency: no = 0; yes = 1 0 0 1 00 0 0 0 0 0 0 For case-control studies: response rate: <80% or not reported = -1; >90% = 1; else = 0 1 --1 0 11 1 1 0000 For cohort studies: follow-up <10 yr = -1; >20 yr = 1; else = 0 0 00 00 0 00000 Reporting bias: likely = -1; possible = 0; unlikely/addressed = 1 0 0 1 -1 1 0 00000 Selection bias: likely = -1; possible = 0; unlikely/addressed = 1 0 10 11 0 00000 Diagnosis of mesothelioma by pathology review: no = 0; yes = 1 1 11 11 0 1 0000 Total score 3 4 5 1 4 1 2 -1 -1 -1 -1 1, McDonald and McDonald (1980); 2, Hessel et al. (2004); 3, Teschke et al. (1997); 4, Agudo et al. (2000); 5, Teta et al. (1983); 6, Hansen (personal comunication, 2003); 7, Woitowirz and Rodelsperger (1994); 8, Coggon et al. (1995); 9, Hodgson et al. (1997); 10, Milham and Ossiander (2001); 11, NIOSH (personal comunication, 2002). Mesothelioma and lung cancer among motor vehicle mechanics Table 2. Summary of mesothelioma studies and corresponding RR estimates included in the meta-analysis First author (A) Tier I studies McDonald Teta Hessel Teschke (B) Tier II studies Hansen Woitowitz Year 1980 1983 2004 1997 2003 1994 Design Exposure definition Source of cases Case-control Case-control Case-control Case-control Garage workers Hospital records Automobile repair and related services CT Tumor Registry Brake lining installation or repair NY Cancer Registry, LA County Cancer Surveillance Program, VA Hospitals Other asbestos exposures controlled Vehicle mechanics British Columbia's Cancer Registry Brake lining installation or repair Vehicle mechanics (ever employed in at risk occupations excluded) Case-control Case-control Repair of motor vehicles and motorcycles Motor vehicle repair workers Danish Cancer Registry Not specified Agudo 2000 Definitely engaged in brake service Case-control Mechanics, motor vehicles Hospital records Comparison group RR estimate (95% CI) Non-pulmonary cancers 0.91 (0.35-2.34) Connecticut decedents 0.65 (0.08-5.53) Deaths from causes other than cancer, 1.04 (0.46-2.22) respiratory disease, suicide or violence 0.82 (0.36-1.80) Randomly selected from voters lists 0.8 (0.2-2.3) 0.3 (0.0-1.4) 0.4 (0.0-3.2) All other occupations combined 0.8 (0.4-1.5) Lung resection patients and population 0.87 (0.43-1.70) controls 0.89 (0.31-2.47) Patients with non-asbestos-related conditions 0.62 (0.11-2.36) CI, confidence interval; CT, Connecticut; LA, Los Angeles; NIOSH, National Institute for Occupational Safety and Health; NY, New York; RR, estimate of relative risk; VA, Veterans Administration. 313 010Z 'LL L)3JB|AI uo Aq 6jo'S|BUjnorpjojxo'6AquuB//:djjq luojj pspBO|UMOQ 314 M. Goodman et al. Table 3. Summary of mesothelioma studies and corresponding RR estimates not included in the meta-analysis First author Malker1 Jarvholm Schiffman Hansen Gustavsson Coggon Year 1985 1988 1988 1989 1990 1995 Design Cohort Cohort Case-control Cohort Cohort Proportionate mortality RR estimate 2.4 (P < 0.01) NA (1 case) 0 (no cases, 2 controls) NA (1 case) NA (2 cases) 0.46 95% CI NA NA NA NA NA NA Hodgson Milham NIOSH 1997 2001 2002 Proportionate mortality Proportionate mortality Proportionate mortality 0.4 approximated from figure 0.75 0.81 0.3-0.7 approximated from figure 0.30-1.55 0.45-1.34 Reason for eclusion Exposure defined as `mechanics' Unable to calculate relative risk Exposure defined as `mechanics' Unable to calculate relative risk Unable to calculate relative risk Total score <0; data overlapping with Hodgson et al. (1997) PMR design; total score <0 PMR design; total score <0 PMR design; total score <0 CI, confidence interval; NIOSH, National Institute for Occupational Safety and Health; NA, not available; PMR, proportionate mortality ratio; RR, estimate of relative risk. aOf the 16 mechanics with mesothelioma in this study, only one was likely to be an auto mechanic (Blot, personal communication, 2003). 010Z 'LL L)3JB|AI uo Aq 6jo'S|BUjnorpjojxo'6AquuB//:djjq luojj pspBO|UMOQ Mesothelioma and lung cancer among motor vehicle mechanics Table 5. Quality scores of studies evaluating the association between lung cancer risk and employment as a motor vehicle mechanic Quality criteria Overall study design: PMR/PIR/SMOR = -1; else = 0 Asbestos exposure: non-specific (e.g. `car mechanic') = 0; specific (e.g. brake repairman, or iH-based) = 1 Age adjustment: no = -1; yes = 0 Confounding by other occupational exposure: likely = -1; possible = 0; unlikely/addressed = 1 Exposure-response analysis: no = 0; yes =1 Analysis by latency: no = 0; yes = 1 For case-control studies: response rate: <80% or not reported = -1; >90% = 1; else = 0 For cohort studies: follow-up <10 yr = -1; >20 yr = 1; else = 0 Adjustment for smoking: none = -1, partial/inadequate = 0; adequate/ detailed = 1 Reporting bias: likely = -1; possible = 0; unlikely/addressed = 1 Selection bias: likely = -1; possible = 0; unlikely/addressed = 1 Total score Study 12 00 01 34 00 00 00 00 00 00 01 00 00 00 00 00 -1 1 -1 0 00 -1 0 00 11 -1 4 00 11 01 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 000 0 0 0 0 -1 0 0 0 0 -1 0 -1 -1 -1 -1 000 1 00000000000000 000 000000000000000 0 0 0 -1 0 0 -1 0 0 0 0 0 0 0 0 0 0 0 000 000 1 00000000000 000 000000000000 1 00 0 0 1 -1 -1 -1 -1 0 0 0 0 0 0 -1 1 0 0 0 1 00 111 0 0 0 0 0 0 -1 -1 -1 -1 0 0 0 0 0 1 1 1 0 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 010 1 10 332 000000000000000 0 0 0 -1 0 0 1 1 1 0 0 0 0 0 0 0 0 0 -2 -2 -1 -1 -1 -1 -3 -2 -1 -1 -2 -2 1, Rushton et al. (1983); 2, Gustavsson et al. (1990); 3, Jarvholm and Brisman (1988); 4, Hansen (1989); 5, Hrubec et al. (1992); 6, Lerchen et al. (1987); 7, Benhamou et al. (1988); 8, Vineis et al. (1988); 9, Williams et al. (1977); 10, Morabia et al. (1992); 11, Swanson et al. (1993); 12, Achwartz (1987); 13, Finkelstein (1995); 14, Enterline and McKiever (1963); 15, Menck and Henderson (1976); 16, Leigh (1996); 17, Petersen and Milham (1980); 18, Milne et al. (1983); 19, Dubrow and Wegman (1984); 20, Olsen and Jensen (1987); 21, Milham and Ossiander (2001); 22, NIOSH (personal communication, 2002). 317 010Z 'LL L)3JB|AI uo Aq 6jo'S|BUjnorpjojxo'6AquuB//:djjq luojj pspBO|UMOQ Mesothelioma and lung cancer among motor vehicle mechanics Table 7. Summary of lung cancer studies and corresponding RR estimates not included in the meta-analysis First author Enterline Menck Decoufle Petersen Rushton Milne Dubrow Blair Olsen Schoenberg Schwartz Carstensen Zahm Burns Swanson Year 1963 1976 1977 1980 1983 1983 1984 1985 1987 1987 1987 1988 1989 1991 1993 Design Cohort Cohort Cohort Proportionate mortality Cohort Case-control Case-control Cohort Proportionate incidence Case-control Proportionate mortality Cohort Case-control Case-control Case-control RR estimate 1.28 1.46 1.12 1.23 1.01 (workers in bus garages) 0.92 (bus mechanics)d 1.2 1.38 1.03 1.17 1.4 1.12 1.07 1.3 1.72 (mechanics, motor vehicles) 1.56 (automobile repair) Presented OR by number of years employed 95% CI NR NR NR NR NR NR NR NR NR 0.8-1.63 0.84-2.3 0.82-1.53 0.92-1.22 1.0-1.7 1.15-2.59 0.85-2.87 Presented OR by number of years employed Finkelstein De Stefani Leigh 1995 1996 1996 Case-control Case-control Cohort 0.88 0.6 1.31 0.39-1.85 0.3-1.2 1.08-1.54 Pezzotto Milham NIOSH 1999 2001 2002 Case-control Proportionate mortality Proportionate mortality 1.3 1.15 1.15 0.7-2.4 NR NR Reason for eclusion No control for smoking, follow up 1 yr; total score <0 No control for smoking, follow up 5 yr; total score <0 Exposure defined as `mechanics and repairmen' No control for smoking, follow up 3 yr; total score <0 No control for smoking, follow up <10 yr; total score <0 No control for smoking, does not report response rate; total score <0 No control for smoking; total score <0 Updated in Hrubec et al. (1992) PIR design, no control for smoking; total score <0 Included in a larger study by Vineis et al. (1988) PMR design, no control for smoking; total score <0 Exposure defined as `mechanics and repairmen' Exposure defined as `mechanics, repairers' Updated in Swanson et al. (1993); selection bias due to use of colon or rectum cancer cases as controls, confounding by other occupations, total score <0 Selection bias due to use of colon or rectum cancer cases as controls, confounding by other occupations, poor response rate; inadequate control for smoking; total score <0 No control for smoking; total score <0 Exposure defined as `mechanic' No control for smoking, follow up 3 yr, relative risk related to large occupational group (auto, bus, truck, stationary engine mechanics); total score <0 Exposure defined as `mechanics' PMR design, no control for smoking; total score <0 PMR design, no control for smoking; total score <0 CI, confidence interval; NR, not reported; PIR, proportionate incidence ratio; PMR, proportionate mortality ratio; RR, estimate of relative risk. aAdequately controlled for smoking. bValues used in meta-analysis. c95% CI recalculated, authors only reported 90% CI. dAs reported in Wong (1993, 2001). 319 010Z 'LL L)3JB|AI uo Aq 6jo'S|BUjnorpjojxo'6AquuB//:djjq luojj pspBO|UMOQ 320 M. Goodman et al. Downloaded from http://annhyg.oxfordjournals.org by on March 11, 2010 The standardized incidence ratio for lung cancer compared with the general population rates was 1.61 (95% CI 0.94-2.57). However, in this analysis two cases of mesothelioma and one case of alveolar cell cancer were counted as `lung cancers'. A nested case-control analysis using logistic regression reported the following RRs: index 0-20 = 1.0 (reference); 20-40 = 1.67 (95% CI 0.50-5.60); 40-60 = 1.26 (95% CI 0.32-5.00); >60 = 1.20 (95% CI 0.26-5.64). The limitations of this study are the potential inclusion of workers not involved in motor vehicle repair and the lack of smoking information. However, the use of internal comparisons in the nested case-control analysis potentially attenuated the confounding effect of smoking. A particularly important feature that sets this study apart from other studies is its ability to conduct IH-based doseresponse analyses. Hrubec et al. (1992, 1995). Hrubec and co-workers conducted a cohort study of 248 046 US veterans followed from 1954 through 1980. In addition to occupational history, the cohort members responded to questionnaires providing information on smoking habits. The response rate was 84%. The underlying cause of death was identified for 95% of the decedents. Cause-specific mortality by occupation was adjusted for smoking using information on smoking status and amount of smoking. For cancers of the respiratory system, the smoking-adjusted RR was 1.1 (90% CI 0.89-1.36) in the occupational group `automobile mechanics and repairmen' and 0.9 (90% CI 0.69-1.17) in the industry type `automobile repair services and garages'. This study's strengths included its large sample size, ability to control for smoking (unusual for a cohort study) and a long follow-up period. However, its weakness was the use of the category `respiratory cancer', which is less specific than `lung cancer'. Tier II. Williams et al. (1977). Using the data from the Third National Cancer Survey, Williams et al. conducted inter-cancer case-control analyses for various occupations and industries while controlling for age, sex, race, education, smoking, alcohol use and geographic location. Only 57% of the cases approached for interviews participated. The nonexposed category consisted of persons in any other known job. For the industry category `car repair serv ices' the lung cancer analysis showed an OR of 0.85 (confidence interval not reported). Although this study adequately controlled for tobacco, alcohol and socio-economic status in all analyses, its main weak ness was the poor response rate and the use of all other cancers as controls. Jarvholm and Brisman (1988). These authors used 1960 Swedish census records to identify men employed as `mechanics' in the `car repair' industry. This information was linked to the Swedish Death Register (1961-1973) and the Swedish Cancer Registry (1961-1979). There were 39 deaths from lung cancer versus 23 expected, yielding an SMR of 1.70. Ninety-three lung cancers occurred among car mechanics from 1961 to 1979, while 73.0 were expected, resulting in a standardized incidence ratio (SIR) of 1.27 (95% CI 1.03-1.56). These results are limited by the lack of adjustment for smoking and by the absence of asbestos-specific exposure infor mation. Vineis et al. (1988). Occupational data from five case-control studies from five US states were combined to determine the risk of lung cancer associ ated with different occupations. Cases were identi fied from cancer registries, hospitals or death certificates. Controls for one of the individual studies were population based and matched on vital status; the remaining studies used hospital controls or deceased controls from death certificates. The nonexposed group consisted of people without any history of exposure to established and suspected lung carcinogens. Odds ratios were calculated for everemployment in the selected occupations and were adjusted for age, birth cohort and cigarette use. Ninety-eight cases and 90 controls were ever employed as `automobile brake workers' (OR = 1.2, 95% CI 0.9-1.7). Among the limitations of this study is the lack of a uniform job classification scheme. The comparison of automobile brake workers who may have had other potential asbestos exposure to persons without any exposure potentially biased the results. The combined response rate was <80%. The study's advantages include a relatively large sample size, adequate control for smoking and information specific to brake repair workers. Hansen (1989). A cohort of 21 800 male `auto mechanics' and 52 000 male skilled workers identi fied from the 1970 Danish Census was followed for 10 yr. Deaths were identified through the Danish National Bureau of Statistics. The reference cohort of skilled workers included carpenters, electricians, instrument makers, dairymen, upholsterers and glaziers. There were 41 lung cancer deaths among the motor vehicle mechanics, compared to 40.7 deaths expected based on the reference rates (SMR = 1.01, 95% CI 0.72-1.37). Limitations of the study included short follow-up, inclusion of workers with potential exposure to asbestos (e.g. carpenters and electricians) in the comparison group and lack of control for smoking. However, the latter limitation may have been partially offset by the use of a comparison group of manual workers. Downloaded from http://annhyg.oxfordjournals.org by on March 11, 2010 Mesothelioma and lung cancer among motor vehicle mechanics 321 Morabia et al. (1992). This hospital-based casecontrol study was conducted in nine US metropolitan areas. Cases were matched (age, race, hospital, year of interview and smoking) to two types of controls (cancer and non-cancer). Participants completed standardized, in-person questionnaires. Adjustment for smoking was performed using smoking status and amount of smoking categories. The reference group (non-exposed) consisted of people who were never employed in an occupation with exposure to confirmed or suspected lung carcinogens. For the usual occupation of `mechanics and repairmenautomobile' the adjusted OR was 0.7 (confidence interval not reported). The main strength of this study is adjustment for smoking. The comparison of auto mobile mechanics who may have had other potential asbestos exposure to persons without any history of at-risk exposures is a potential source of bias. Use of hospital controls and the fact that the authors did not report a response rate should also be considered as weaknesses. Meta-analysis. The results of the summary ana lysis for lung cancer are presented in Table 8. All tests for heterogeneity produced non-significant results regardless of stratification, and in all analyses the random effects model reduced to a fixed effects model. Analyses of the Tier I and Tier II studies pro duced meta-RR estimates of 1.07 (95% CI 0.88-1.31) and 1.17 (95% CI 1.01-1.36), respectively. When the analysis was limited to studies that used adequate control for smoking regardless of tier, the resulting meta-RR estimate was 1.09 (95% CI 0.92-1.28). The analysis that was limited to case-control studies (including the nested case-control results from Gustavsson et al., 1990) resulted in a meta-RR esti mate of 1.08 (95%CI 0.87-1.34), while the analysis of the cohort studies produced a meta-RR of 1.16 (95% CI 1.00-1.34). DISCUSSION None of the individual studies that examined risk of mesothelioma among motor vehicle mechanics demonstrated increased risk and, thus, the results of the meta-analysis also showed no increased risk of mesothelioma. It is also noteworthy that the meta analysis results remained virtually the same after the analysis was limited to studies specifically mentioning brake mechanics and did not change after the removal of those with other occupations poten tially involving asbestos exposures. Although the three potentially relevant cohort studies (Jarvholm and Brisman, 1988; Hansen, 1989; Gustavsson et al., 1990) could not calculate the RR, their findings largely support the case-control and PMR/PIR surveillance studies and are consistent with the results of the meta-analysis. There were four cases in a total of ~600 000 person-yr of follow-up. For reference, the reported annual rates of mesothe lioma among males in Denmark and Sweden are 1.47 and 1.1 per 100 000, respectively (Ferguson et al., 1987; Parkin et al., 1997). In a Swedish study of bus garage mechanics Gustavsson et al. (1990) reported two cases of mesothelioma. One of these was not a mechanic but an electrician and both cases `may have been exposed to asbestos during previous employments'. In another Swedish study Jarvholm and Brisman (1988) found `one case of mesothelioma in the cancer register and none in the death register'. The authors noted that the person diagnosed as having mesothelioma also worked in the construction industry and concluded that their data `indicate no increased risk of mesothe lioma in car mechanics ...' (Jarvholm and Brisman, 1988) . The Danish study of garage mechanics also found only one death due to cancer of the pleura (Hansen, 1989) . The author interpreted the finding of a single case of pleural cancer as an indication that exposure to asbestos via brake repair `was not negligible'. Unlike Gustavsson et al. (1990) and Jarvholm and Brisman (1988), Hansen (1989) did not evaluate other sources of asbestos exposure for the individual who developed pleural cancer. The conclusion by Hansen is inconsistent with the results of another record linkage study based on the data from the Danish Cancer Registry and from the Supplementary Pension Fund and the Central Popula tion Registry (Olsen and Jensen, 1987). In this study Table 8. Meta-analysis results for lung cancer Analyses Tier I studies Tier II studies Studies with adequate adjustment for smokinga Case-control studies Cohort studies K Meta-RR 95% CI Q-test 4 1.07 0.88-1.31 0.96 5 1.17 1.01-1.36 0.64 6 1.09 0.92-1.28 0.92 6 1.08 0.87-1.34 0.92 3 1.16 1.00-1.34 0.44 CI, confidence interval; K, number of studies; Q-test, P-value of the test for heterogeneity; RR, estimate of relative risk. aHrubec et al. (1992), Lerchen et al. (1987), Benhamou et al. (1988), Vineis et al. (1988), Williams et al. (1977) and Morabia et al. (1992).