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Mesothelioma and Lung Cancer Among Motor Vehicle Mechanics a Meta-analysis.txt
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Mesothelioma and Lung Cancer Among Motor Vehicle Mechanics a Meta-analysis.txt
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<div class="article fulltext-view" itemprop="articleBody"><span class="highwire-journal-article-marker-start"></span><h1 id="article-title-1" itemprop="headline">Mesothelioma and Lung Cancer Among Motor Vehicle Mechanics: a Meta-analysis</h1>
<div class="contributors">
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<li class="contributor" id="contrib-1" itemprop="author" itemscope="itemscope"
itemtype="http://schema.org/Person"><span class="name" itemprop="name"><a class="name-search"
href="/search?author1=MICHAEL+GOODMAN&sortspec=date&submit=Submit">MICHAEL GOODMAN</a></span><a id="xref-target-1-1" class="xref-other" href="#target-1">1</a><a id="xref-fn-1-1" class="xref-fn" href="#fn-1">*</a>,
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<li class="contributor" id="contrib-2" itemprop="author" itemscope="itemscope"
itemtype="http://schema.org/Person"><span class="name" itemprop="name"><a class="name-search"
href="/search?author1=M.+JANE+TETA&sortspec=date&submit=Submit">M. JANE TETA</a></span><a id="xref-target-2-1" class="xref-other" href="#target-2">2</a>,
</li>
<li class="contributor" id="contrib-3" itemprop="author" itemscope="itemscope"
itemtype="http://schema.org/Person"><span class="name" itemprop="name"><a class="name-search"
href="/search?author1=PATRICK+A.+HESSEL&sortspec=date&submit=Submit">PATRICK A. HESSEL</a></span><a id="xref-target-3-1" class="xref-other" href="#target-3">3</a>,
</li>
<li class="contributor" id="contrib-4" itemprop="author" itemscope="itemscope"
itemtype="http://schema.org/Person"><span class="name" itemprop="name"><a class="name-search"
href="/search?author1=DAVID+H.+GARABRANT&sortspec=date&submit=Submit">DAVID H. GARABRANT</a></span><a id="xref-target-4-1" class="xref-other" href="#target-4">4</a>,
</li>
<li class="contributor" id="contrib-5" itemprop="author" itemscope="itemscope"
itemtype="http://schema.org/Person"><span class="name" itemprop="name"><a class="name-search"
href="/search?author1=VALERIE+A.+CRAVEN&sortspec=date&submit=Submit">VALERIE A. CRAVEN</a></span><a id="xref-target-5-1" class="xref-other" href="#target-5">5</a>,
</li>
<li class="contributor" id="contrib-6" itemprop="author" itemscope="itemscope"
itemtype="http://schema.org/Person"><span class="name" itemprop="name"><a class="name-search"
href="/search?author1=CAROLYN+G.+SCRAFFORD&sortspec=date&submit=Submit">CAROLYN G. SCRAFFORD</a></span><a id="xref-target-6-1" class="xref-other" href="#target-6">6</a> and
</li>
<li class="last" id="contrib-7"><span class="name"><a class="name-search"
href="/search?author1=MICHAEL+A.+KELSH&sortspec=date&submit=Submit">MICHAEL A. KELSH</a></span><a id="xref-target-7-1" class="xref-other" href="#target-7">7</a></li>
</ol>
<ol class="affiliation-list">
<li class="aff"><a id="aff-1" name="aff-1"></a><address> <a id="CHDIBHIE"></a><sup>1</sup>Emory University Rollins School of Public Health, 1518 Clifton Road NE, Atlanta, GA 30322, USA; <a id="CHDCDCJH"></a><sup>2</sup>Exponent Health Group, 1730 Rhode Island Avenue NW, Suite 1100, Washington, DC 20036, USA; <a id="CHDFIHFD"></a><sup>3</sup>Exponent Health Group, 2 North Riverside Plaza, Suite 1400, Chicago, IL 60606, USA; <a id="CHDBIEBJ"></a><sup>4</sup>University of Michigan School of Public Health, 1420 Washington Heights, Room 6529, Ann Arbor, MI 48109-2029, USA; <a id="CHDHCCHG"></a><sup>5</sup>Exponent Health Risk Group, 631 First Street, Santa Rosa, CA 95404, USA; <a id="CHDDCBDI"></a><sup>6</sup>Exponent Food and Chemicals Group, 1730 Rhode Island Avenue NW, Suite 1100, Washington, DC 20036, USA; <a id="CHDJGJBI"></a><sup>7</sup>Exponent Health Group, 149 Commonwealth Drive, Menlo Park, CA 94025, USA
</address>
</li>
</ol>
<ul class="history-list"></ul>
</div>
<div class="section abstract" id="abstract-1" itemprop="description">
<div class="section-nav">
<div class="nav-placeholder"> </div><a href="#notes-1" title="Next Section" class="next-section-link"><span>Next Section</span></a></div>
<h2>Abstract</h2>
<p id="p-1">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 (meta-RRs) 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 characterization 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.
</p>
</div>
<h3 class="kwd-header">Key words</h3>
<ul class="kwd-group KWD">
<li class="kwd"><span><a class="kwd-search"
href="/search?fulltext=asbestos;+brakes;+epidemiology;+lung+cancer;+mesothelioma;+meta-analysis;+motor+vehicle+mechanics&sortspec=date&submit=Submit&andorexactfulltext=phrase">asbestos; brakes; epidemiology; lung cancer; mesothelioma; meta-analysis; motor vehicle mechanics</a></span></li>
</ul>
<div class="section notes" id="notes-1">
<div class="section-nav"><a href="#abstract-1" title="Abstract" class="prev-section-link"><span>Previous Section</span></a><a href="#sec-1" title="INTRODUCTION" class="next-section-link"><span>Next Section</span></a></div>
<p id="p-2">Received 26 August 2003; in final form 13 November 2003; published online on 17 May 2004</p>
</div>
<div class="section" id="sec-1">
<div class="section-nav"><a href="#notes-1" title="Previous Section" class="prev-section-link"><span>Previous Section</span></a><a href="#sec-2" title="METHODS" class="next-section-link"><span>Next Section</span></a></div>
<h2>INTRODUCTION</h2>
<p id="p-3">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 dose–response
relationship between chrysotile asbestos and mesothelioma and the role of amphibole contaminants in that relationship (<a id="xref-ref-32-1" class="xref-bibr" href="#ref-32">Hodgson and Darnton, 2000</a>). 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 asbestos-containing brakes. (In North America,
automobile 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.
</p>
<p id="p-4"> Some authors (<a id="xref-ref-43-1" class="xref-bibr" href="#ref-43">Lorimer <em>et al.</em>, 1976</a>), regulatory agencies (<a id="xref-ref-24-1" class="xref-bibr" href="#ref-24">EPA, 1986c</a>) and trade organizations (<a id="xref-ref-81-1" class="xref-bibr" href="#ref-81">World Trade Organization, 2000</a>) 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 exposures can occur during brake
work and cases of mesothelioma have been reported among workers who had done brake repair (<a id="xref-ref-22-1" class="xref-bibr" href="#ref-22">EPA, 1986a</a>,b,c).
</p>
<p id="p-5"> When the EPA conducted its evaluation (<a id="xref-ref-23-1" class="xref-bibr" href="#ref-23">EPA, 1986b</a>,c) the epidemiological information on mesothelioma among vehicle mechanics was limited to only three studies (<a id="xref-ref-47-1" class="xref-bibr" href="#ref-47">McDonald and McDonald, 1980</a>; <a id="xref-ref-71-1" class="xref-bibr" href="#ref-71">Teta <em>et al.</em>, 1983</a>; <a id="xref-ref-66-1" class="xref-bibr" href="#ref-66">Spirtas <em>et al.</em>, 1985</a>). However, in more recent years a number of additional 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.
</p>
<p id="p-6"> We conducted a systematic review of the epidemiological 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 (<a id="xref-ref-80-1" class="xref-bibr" href="#ref-80">Wong, 2001</a>). 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 addition, we expanded the scope of our review beyond mesothelioma
to include studies of lung cancer.
</p>
<p id="p-7"> This issue is of growing scientific, public health and societal importance (<a id="xref-ref-63-1" class="xref-bibr" href="#ref-63">Schneider and Smith, 2000</a>; <a id="xref-ref-72-1" class="xref-bibr" href="#ref-72">Truby, 2002</a>). Large numbers of people have been exposed to brake dust over the last several decades (<a id="xref-ref-43-2" class="xref-bibr" href="#ref-43">Lorimer <em>et al.</em>, 1976</a>; <a id="xref-ref-52-1" class="xref-bibr" href="#ref-52">Nicholson <em>et al.</em>, 1984</a>; <a id="xref-ref-36-1" class="xref-bibr" href="#ref-36">Huncharek, 1990</a>) and an increased risk of asbestos-related cancers among these workers could translate into a substantial burden of disease.
</p>
</div>
<div class="section" id="sec-2">
<div class="section-nav"><a href="#sec-1" title="INTRODUCTION" class="prev-section-link"><span>Previous Section</span></a><a href="#sec-6" title="RESULTS" class="next-section-link"><span>Next Section</span></a></div>
<h2>METHODS</h2>
<h3>Study selection</h3>
<p id="p-8"> 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 translated into English. Reference lists of identified articles were examined to locate additional studies.
</p>
<p id="p-9"> Internet and literature searches were also conducted to identify relevant studies that were not published in the peer-reviewed
literature. Of particular 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.
</p>
<p id="p-10"> In order to be included in the review, studies were required to meet all of the following criteria:</p>
<p>
</p>
<ul class="list-unord" id="list-1">
<li id="list-item-1">
<p id="p-12">outcomes of interest included mesothelioma and/or lung cancer;</p>
</li>
<li id="list-item-2">
<p id="p-13">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;
</p>
</li>
<li id="list-item-3">
<p id="p-14">the exposed population was involved in motor vehicle repair, excluding general mechanics.</p>
</li>
</ul>
<p>
</p>
<p id="p-15"> 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.
</p>
<h3>Review of the literature</h3>
<p id="p-16"> 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 methodological strength
and penalizing with a negative score (–1) for each evident shortcoming. The quality scoring was conducted according to the
following criteria.
</p>
<p>
</p>
<ul class="list-unord" id="list-2">
<li id="list-item-4">
<p id="p-18">Overall study design: proportionate mortality/incidence ratio (PMR/PIR) studies or death certificate-based standardized mortality
odds ratio (SMOR) studies = –1; else (cohort or case–control studies) = 0.
</p>
</li>
<li id="list-item-5">
<p id="p-19">Asbestos exposure: non-specific = 0 (e.g. ‘car mechanic’); specific = 1 [e.g. ‘brake repairmen’ or industrial hygiene (IH)
based].
</p>
</li>
<li id="list-item-6">
<p id="p-20">Age adjustment: no = –1; yes = 0.</p>
</li>
<li id="list-item-7">
<p id="p-21">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 at-risk occupations); possible but not clearly evident = 0; unlikely/addressed
= 1 (e.g. studies that accounted for other known at-risk occupations in the analysis).
</p>
</li>
<li id="list-item-8">
<p id="p-22">Exposure–response analysis: no = 0; yes = 1.</p>
</li>
<li id="list-item-9">
<p id="p-23">Analysis by latency: no = 0; yes = 1.</p>
</li>
<li id="list-item-10">
<p id="p-24">For case–control studies: response rate <80% or not reported = –1; >90% = 1; else = 0.</p>
</li>
<li id="list-item-11">
<p id="p-25">For cohort studies: follow-up: <10 years = –1; >20 years = 1; else = 0.</p>
</li>
<li id="list-item-12">
<p id="p-26">Reporting bias: likely = –1 (e.g. interview-based case–control studies with clear differences in terms of sources of information
between cases and controls); possible but not clearly evident = 0; unlikely/addressed = 1 (e.g. in case–control studies using
recorded occupational histories).
</p>
</li>
<li id="list-item-13">
<p id="p-27">Selection bias: likely = –1 (e.g. due to reliance on referral of cases to a clinic or using inappropriate controls); possible
but not clearly evident = 0 (e.g. in hospital-based case–control studies); unlikely/addressed = 1 (e.g. in cohort studies
or population-based case–control studies).
</p>
</li>
</ul>
<p>
</p>
<p id="p-28"> In addition to the above criteria, mesothelioma studies were evaluated based on whether or not the diagnoses were confirmed
by a pathology review (i.e. +1 if yes, 0 if no). Lung cancer studies were also evaluated based on their ability to adjust
results for smoking habit. Studies that did not control for smoking received a negative score (–1), studies that adequately
controlled for both smoking status (current, former or never) and intensity (duration and/or number of cigarettes per day)
received a positive score (+1) and studies that had only partial control for smoking (e.g. using only ever–never categories,
only pack-years or using blue collar/internal reference groups) were neither penalized nor rewarded.
</p>
<p id="p-29"> The scoring was used as a formal approach to classify all studies into three tiers. Tier III included studies that had an
overall negative score (i.e. less than 0) and were considered unreliable. These studies were only mentioned for completeness
and were not included in the meta-analysis. Those studies that had scores of zero or above were divided into two approximately
equal groups. Studies with the higher (above median) total score were included in Tier I and considered most informative.
Tier II included the remaining studies that received a total score of ≥0 but were considered less useful due to methodological
shortcomings.
</p>
<h3>Statistical analysis</h3>
<p id="p-30"> We calculated a meta relative risk (meta-RR) for Tiers I and II separately, followed by stratified analyses of both tiers
combined, based on study design or exposure characterization and, for lung cancer studies, based on adequate adjustment for
smoking. The necessary input from each study included (i) an RR estimate and (ii) the associated measure of variance, which
usually can be derived from the 95% confidence interval (95% CI).
</p>
<p id="p-31"> When case–control studies did not report the results in terms of RRs but did provide information necessary to reconstruct
the two-by-two tables, the odds ratios (ORs) and 95% CIs were calculated using Epi Info software (<a id="xref-ref-12-1" class="xref-bibr" href="#ref-12">CDC, 2001</a>). Some cohort studies did not report 95% CIs, but did provide information on the numbers of observed and expected cases.
In those instances, 95% CIs were calculated based on the Poisson distribution, as recommended by <a id="xref-ref-8-1" class="xref-bibr" href="#ref-8">Breslow and Day (1987</a>).
</p>
<p id="p-32"> In one study (<a id="xref-ref-51-1" class="xref-bibr" href="#ref-51">Morabia <em>et al.</em>, 1992</a>), the information needed to calculate 95% CIs was not provided. However, we were able to calculate the standard deviation
based on the information that there were 39 exposed controls (1.2% of all controls) and the statistical power to detect an
OR of 1.5 was 0.41, as reported by the authors.
</p>
<p id="p-33"> There are two general approaches for combining the data in a meta-analysis: a fixed effects model or a random effects model.
The fixed effects method assumes no heterogeneity among studies and attributes all observed variations among results to sampling
error alone (<a id="xref-ref-69-1" class="xref-bibr" href="#ref-69">Sutton <em>et al.</em>, 1998</a>). The random effects model assumes that the study-specific effect sizes arise from a random distribution of effect sizes
with a certain mean and variance.
</p>
<p id="p-34"> All analyses involved a test for heterogeneity. However, the interpretation of the test for heterogeneity is problematic
because of the wide variation in study designs, study populations and reference groups. Therefore, we used both the fixed
and random effects models for each analysis. Where the variability among studies was negligible (high level of homogeneity),
the random effects model reduced to a fixed effects model (<a id="xref-ref-69-2" class="xref-bibr" href="#ref-69">Sutton <em>et al.</em>, 1998</a>). The details of calculations for both models are provided in the Appendix.
</p>
</div>
<div class="section" id="sec-6">
<div class="section-nav"><a href="#sec-2" title="METHODS" class="prev-section-link"><span>Previous Section</span></a><a href="#sec-33" title="DISCUSSION" class="next-section-link"><span>Next Section</span></a></div>
<h2>RESULTS</h2>
<h3>Mesothelioma</h3>
<h4>Overview of the literature</h4>
<p id="p-35">Relative risk estimates could not be calculated for three cohort studies of motor vehicle mechanics (two from Sweden and one
from Denmark) that provided information on mesothelioma (<a id="xref-ref-37-1" class="xref-bibr" href="#ref-37">Jarvholm and Brisman, 1988</a>; <a id="xref-ref-30-1" class="xref-bibr" href="#ref-30">Hansen, 1989</a>; <a id="xref-ref-29-1" class="xref-bibr" href="#ref-29">Gustavsson <em>et al.</em>, 1990</a>). For this reason, these studies could not be included in the meta-analysis. These three cohort studies combined reported
three observed cases of mesothelioma and one case of ‘pleural cancer’. All three mesothelioma cases had other potential occupational
asbestos exposures. For the remaining case of pleural cancer, information regarding other exposures was not provided.
</p>
<p id="p-36"> There were 11 studies that reported (or permitted calculations of) the relative risk estimates for mesothelioma. These studies
underwent formal evaluation and scoring. The results of scoring for each study are presented in Table <a id="xref-table-wrap-1-1" class="xref-table" href="#T1">1</a>. Four studies were included in Tier III (<a id="xref-ref-13-1" class="xref-bibr" href="#ref-13">Coggon <em>et al.</em>, 1995</a>; <a id="xref-ref-33-1" class="xref-bibr" href="#ref-33">Hodgson <em>et al.</em>, 1997</a>; <a id="xref-ref-49-1" class="xref-bibr" href="#ref-49">Milham and Ossiander, 2001</a>; NIOSH, personal communication, 2002). Of the seven remaining studies, four studies with scores between 3 and 5 were included
in Tier I (Table <a id="xref-table-wrap-2-1" class="xref-table" href="#T2">2</a>A) and three studies with scores between 0 and 2 were included in Tier II (Table <a id="xref-table-wrap-2-2" class="xref-table" href="#T2">2</a>B). 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.
</p>
<div class="table pos-float" id="T1">
<div class="table-inline">
<div class="callout"><span>View this table:</span><ul class="callout-links">
<li><a href="309/T1.expansion.html">In this window</a></li>
<li><a class="in-nw" href="309/T1.expansion.html">In a new window</a></li>
</ul>
</div>
</div>
<div class="table-caption"><span class="table-label">
<strong>Table 1.</strong>
</span>
<p id="p-98" class="first-child"> Quality scores of studies evaluating the association between mesothelioma risk and employment as a motor vehicle mechanic</p>
<div class="sb-div caption-clear"></div>
</div>
</div>
<div class="table pos-float" id="T2">
<div class="table-inline">
<div class="callout"><span>View this table:</span><ul class="callout-links">
<li><a href="309/T2.expansion.html">In this window</a></li>
<li><a class="in-nw" href="309/T2.expansion.html">In a new window</a></li>
</ul>
</div>
</div>
<div class="table-caption"><span class="table-label">
<strong>Table 2.</strong>
</span>
<p id="p-100" class="first-child"> Summary of mesothelioma studies and corresponding RR estimates included in the meta-analysis</p>
<div class="sb-div caption-clear"></div>
</div>
</div>
<h4>Tier I</h4>
<h5>McDonald and McDonald (1980)</h5>
<p id="p-37"> The study here compared histologically confirmed mesothelioma cases to matched controls who had pulmonary metastases from
non-pulmonary malignancies. Occupational 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).
</p>
<p id="p-38"> 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
representative 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 participant’s occupational history
helped decrease potential confounding by other asbestos exposures. However, the occupational category defined as ‘garage’
is insufficiently specific.
</p>
<h5>Teta <em>et al.</em> (1983)
</h5>
<p id="p-39"> 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).
</p>
<p id="p-40"> Unlike other case–control studies, <a id="xref-ref-71-2" class="xref-bibr" href="#ref-71">Teta <em>et al.</em> (1983</a>) relied on objective historical employment information rather than subjective reports from interviews. 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.
</p>
<h5>National Cancer Institute study (Spirtas <em>et al.</em>, 1994, 1985; Hessel <em>et al</em>., 2004, in press)
</h5>
<p id="p-41"> The 1994 report of a case–control study by the National Cancer Institute (NCI) identified mesothelioma cases in the Los Angeles
County Cancer Surveillance Program, the New York State Cancer Registry (excluding New York City) and 39 Veterans Administration
hospitals. A pathology review was conducted in most cases. Controls included patients who died of causes other than cancer,
respiratory disease, suicide or violence. The authors did not calculate ORs by occupational category because of multiple confounding
exposures, preferring to discuss attributable risk of asbestos exposure in general. Among subjects engaged in ‘brake lining
installation or repair’, 33% also had shipbuilding or shipyard work and 55% had performed insulation work.
</p>
<p id="p-42"> In an earlier analysis of the same data, but with cases and controls matched for age, the authors did calculate the ORs for
different occupational groups (<a id="xref-ref-66-2" class="xref-bibr" href="#ref-66">Spirtas <em>et al.</em>, 1985</a>). Brake lining installation or repair had an OR of 1.0 (95% CI 0.6–1.6).
</p>
<p id="p-43"> A re-analysis of these data (<a id="xref-ref-31-1" class="xref-bibr" href="#ref-31">Hessel <em>et al.</em>, 2004</a>, in press) for the occupational category ‘brake installation or repair’ yielded an OR of 1.04 (95% CI 0.46–2.22). After adjusting
for any of eight occupations with potential asbestos exposure, the OR was 0.82 (95% CI 0.36–1.80). When cases and controls
with a history of employment in any of the eight occupations were removed from the analysis, the OR for occupational brake
installation and repair was 0.62 (95% CI 0.01–4.71). These NCI data have several important features: (i) exposure was defined
as brake installation and repair, (ii) confounding by other occupational exposures could be addressed, (iii) information on
duration of employment allowed an exposure–response analysis and (iv) and the majority of the mesotheliomas underwent pathology
review. A limitation of this data set is the relatively low (<80%) response rate.
</p>
<h5>Teschke <em>et al.</em> (1997)
</h5>
<p id="p-44"> Teschke and colleagues compared pathology-confirmed mesothelioma cases from the British Columbia Cancer Agency data to matched
controls selected among provincial voters. Occupational and exposure histories were obtained, whenever possible, directly
from cases and controls. The OR for ‘vehicle mechanics’ considered as an <em>a priori</em> suspect occupational group was 0.8 (95% CI 0.2–2.3). The OR for the category ‘brake lining installation or repair’ was 0.3
(95% CI 0.0–1.4). After removing cases and controls with at-risk occupational asbestos exposures, the OR for ‘vehicle mechanics’
was 0.4 (95% CI 0.0–3.2). The results did not change after 20 years of latency. The authors also reported that, after removal
of at-risk exposures, ‘brake installation and repair did not appear to be associated with mesothelioma’.
</p>
<p id="p-45"> Although fairly small in size, this study is strong methodologically because it considered other asbestos exposures, specified
exposure as ‘brake lining installation or repair’, relied on histologically confirmed diagnoses of mesothelioma and frequency
matched next-of-kin interviews among cases and controls. Unlike other studies, the analyses in <a id="xref-ref-70-1" class="xref-bibr" href="#ref-70">Teschke <em>et al.</em> (1997</a>) considered latency.
</p>
<h4>Tier II studies</h4>
<h5>Olsen and Jensen (1987) and Hansen (personal communication, 2003)</h5>
<p id="p-46"> In 1987, Olsen and Jensen published a proportionate incidence ratio (PIR) surveillance study that linked cases from the Danish
Cancer Registry with occupational histories (<a id="xref-ref-54-1" class="xref-bibr" href="#ref-54">Olsen and Jensen, 1987</a>). There were no cases of mesothelioma (pleural or peritoneal) for the occupational category ‘repair of motor vehicles and
motorcycles’ and for the industry category ‘garage’.
</p>
<p id="p-47"> We contacted the authors of this study and learned that the data had been updated in a case–control study (Hansen, personal
communication, 2003). For the category ‘repair of motor vehicles and motorcycles’ the OR was 0.8 (95% CI 0.4–1.5), based on
10 cases. The weaknesses of this study are lack of histological confirmation of mesothelioma diagnosis and inability to obtain
a complete work history. Its strengths include analysis by latency and a relatively large sample size.
</p>
<h5>Woitowitz and Rödelsperger (1994)</h5>
<p id="p-48"> This German case–control study compared occupational histories of 324 pathology confirmed mesothelioma with two groups of
controls: 315 hospital controls selected among patients who underwent lung resection and 182 population controls. Sixteen
cases, 16 hospital controls and 12 population controls were listed as ‘motor vehicle repair workers’. Calculations based on
these data produced an OR of 0.97 (95% CI 0.45–2.12) using hospital controls and 0.74 (95% CI 0.32–1.75) using population
controls. For people definitely engaged in brake service, the OR was 0.75 (95% CI 0.25–2.23) using hospital controls and 1.32
(95% CI 0.30–6.51) using population controls. When the two types of controls were combined, the OR was 0.87 (95% CI 0.43–1.70)
for motor vehicle mechanics and 0.89 (95% CI 0.31–2.47) for persons definitely engaged in brake servicing. (These calculations
use updated numbers provided by the authors, Prof. H.-J. Woitowitz and Dr K. Rödelsperger, of Justus-Liebig University, Germany.)
</p>
<p id="p-49"> The strengths of this study are its ability to examine the association with brake repair, its high response rate and the
pathology review of cases. The most important shortcomings include the lack of adjustment for age and an inadequate description
of subject selection.
</p>
<h5>Agudo <em>et al.</em> (2000)
</h5>
<p id="p-50"> This hospital-based case–control study compared pathology-confirmed cases of mesothelioma to population/hospital controls
selected using a two-step procedure (<a id="xref-ref-1-1" class="xref-bibr" href="#ref-1">Agudo and Gonzalez, 1999</a>). The authors reported that there were three cases and 14 controls in the category ‘mechanics, motor vehicle’. The non-exposed
category included 51 cases and 148 controls that had never worked in any of the at-risk occupations. Based on this information,
the crude OR for ‘mechanics, motor vehicle’ was 0.62 (95% CI 0.11–2.36). The comparison of motor vehicle mechanics who may
have had other potential asbestos exposure to persons without any exposure is problematical. However, the result indicates
that substantial confounding by other exposures in this study population is unlikely. Because 44% of cases and less than 1%
of controls had next of kin interviews, information bias needs to be considered. The study’s high response rate, novel methods
of control selection and confirmation of diagnosis by pathology review are among its strengths.
</p>
<h4>Meta-analysis</h4>
<p id="p-51"> The results of the meta-analysis for mesothelioma are presented in Table <a id="xref-table-wrap-4-1" class="xref-table" href="#T4">4</a>. 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. The meta-RR estimates for Tier I and Tier II studies were 0.92 (95% CI 0.55–1.56)
and 0.81 (95% CI 0.52–1.28), respectively.
</p>
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<div class="table-caption"><span class="table-label">
<strong>Table 3.</strong>
</span>
<p id="p-102" class="first-child"> Summary of mesothelioma studies and corresponding RR estimates not included in the meta-analysis</p>
<div class="sb-div caption-clear"></div>
</div>
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<div class="table-caption"><span class="table-label">
<strong>Table 4.</strong>
</span>
<p id="p-105" class="first-child"> Meta-analysis results for mesothelioma</p>
<div class="sb-div caption-clear"></div>
</div>
</div>
<p id="p-52"> Analysis limited to studies evaluating the association between mesothelioma and brake repair, as opposed to motor vehicle
repair, resulted in a meta-RR of 0.86 (95% CI 0.48–1.56). Inclusion of only those studies that considered other asbestos exposures
resulted in a meta-RR of 0.80 (95% CI 0.46–1.40).
</p>
<h3>Lung cancer</h3>
<h4>Overview of the literature</h4>
<p id="p-53"> Twenty-nine studies were identified initially. Of these, seven were eliminated because they did not meet the three initial
inclusion criteria or they presented data that overlapped with other studies. The remaining 22 studies were evaluated and
scored (Table <a id="xref-table-wrap-5-1" class="xref-table" href="#T5">5</a>). Thirteen studies were further excluded from the meta-analysis because they had an overall negative score. Nine studies
remained, of which four (scores of 3 or 4) were included in Tier I (Table <a id="xref-table-wrap-6-1" class="xref-table" href="#T6">6</a>A) and five (scores 0–2) were included in Tier II (Table <a id="xref-table-wrap-6-2" class="xref-table" href="#T6">6</a>B). Tier I included two cohort studies (<a id="xref-ref-29-2" class="xref-bibr" href="#ref-29">Gustavsson <em>et al.</em>, 1990</a>; <a id="xref-ref-34-1" class="xref-bibr" href="#ref-34">Hrubec <em>et al.</em>, 1992</a>) and two case–control studies (<a id="xref-ref-42-1" class="xref-bibr" href="#ref-42">Lerchen <em>et al.</em>, 1987</a>; <a id="xref-ref-6-1" class="xref-bibr" href="#ref-6">Benhamou <em>et al.</em>, 1988</a>). Tier II included two cohort studies (<a id="xref-ref-37-2" class="xref-bibr" href="#ref-37">Jarvholm and Brisman, 1988</a>; <a id="xref-ref-30-2" class="xref-bibr" href="#ref-30">Hansen, 1989</a>) and three case–control studies (<a id="xref-ref-75-1" class="xref-bibr" href="#ref-75">Williams <em>et al.</em>, 1977</a>; <a id="xref-ref-73-1" class="xref-bibr" href="#ref-73">Vineis <em>et al.</em>, 1988</a>; Morabia <em>et al.</em>, 1992). Only six studies adequately controlled for smoking; of these, three were included in Tier I. Despite adequate control
for smoking, three studies (<a id="xref-ref-75-2" class="xref-bibr" href="#ref-75">Williams <em>et al.</em>, 1977</a>; <a id="xref-ref-73-2" class="xref-bibr" href="#ref-73">Vineis <em>et al.</em>, 1988</a>; Morabia <em>et al.</em>, 1992) were included in Tier II due to other limitations. The earliest of the studies included in the meta-analysis was published
in 1977 (<a id="xref-ref-75-3" class="xref-bibr" href="#ref-75">Williams <em>et al.</em>, 1977</a>) and the most recent were published in 1992 (<a id="xref-ref-34-2" class="xref-bibr" href="#ref-34">Hrubec <em>et al.</em>, 1992</a>; <a id="xref-ref-51-2" class="xref-bibr" href="#ref-51">Morabia <em>et al.</em>, 1992</a>). Notably, none of the Tier I or II studies was published in the last 10 yr. Three of the four cohort studies included in
the meta-analysis were published in Europe: two in Sweden (<a id="xref-ref-37-3" class="xref-bibr" href="#ref-37">Jarvholm and Brisman, 1988</a>; <a id="xref-ref-29-3" class="xref-bibr" href="#ref-29">Gustavsson <em>et al.</em>, 1990</a>) and one in Denmark (<a id="xref-ref-30-3" class="xref-bibr" href="#ref-30">Hansen, 1989</a>). The fourth cohort study was published in the USA (<a id="xref-ref-34-3" class="xref-bibr" href="#ref-34">Hrubec <em>et al.</em>, 1992</a>, 1995) and presented in two reports, one evaluating cancer risk by occupation and one evaluating cancer risk by industry.
All but one (<a id="xref-ref-6-2" class="xref-bibr" href="#ref-6">Benhamou <em>et al.</em>, 1988</a>) of the case–control studies were conducted in the USA.
</p>
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<div class="table-caption"><span class="table-label">
<strong>Table 5.</strong>
</span>
<p id="p-109" class="first-child"> Quality scores of studies evaluating the association between lung cancer risk and employment as a motor vehicle mechanic</p>
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</div>
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<strong>Table 6.</strong>
</span>
<p id="p-111" class="first-child"> Summary of lung cancer studies and corresponding RR estimates included in the meta-analysis</p>
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<strong>Table 7.</strong>
</span>
<p id="p-116" class="first-child"> Summary of lung cancer studies and corresponding RR estimates not included in the meta-analysis</p>
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<div class="table-caption"><span class="table-label">
<strong>Table 8.</strong>
</span>
<p id="p-122" class="first-child"> Meta-analysis results for lung cancer</p>
<div class="sb-div caption-clear"></div>
</div>
</div>
<h4>Tier I</h4>
<h5>Lerchen <em>et al.</em> (1987)
</h5>
<p id="p-54"> This case–control study compared lung cancer patients from the New Mexico tumor registry to matched controls selected either
through random digit dialing or from the Health Care Financing Administration records. The information for roughly half of
all cases and 2% of controls was available from the next of kin interviews. Smoking variables used for adjustment included
smoking status (current, former or never), number of cigarettes/day and smoking duration. The non-exposed group included subjects
never employed in the industry or occupation of interest. For auto mechanics the adjusted OR was 0.9 (95% CI 0.5–1.9).
</p>
<p id="p-55"> The strengths of this study are the population-based design and adequate adjustment for smoking. Conscious of the disparity
in next of kin interviews, the authors evaluated the number of jobs reported for cases and controls by interview method. Surrogate
interviews generally identified fewer jobs, but the difference between cases and controls was small.
</p>
<h5>Benhamou <em>et al.</em> (1988)
</h5>
<p id="p-56"> In this French case–control study lung cancer cases were matched to controls selected from hospital patients with diseases
not related to tobacco exposure. All subjects had completed a questionnaire that included a full occupational history. The
non-exposed group consisted of people who had never been engaged in the particular occupation under study. Smoking variables
included smoking status, age when started smoking, cigarettes per day and duration of smoking. Analyses for ‘motor vehicle
mechanics’ yielded an adjusted OR of 1.06 (95% CI 0.73–1.54). The major strengths of this study are its very detailed adjustment
for smoking and an apparently high response rate (<a id="xref-ref-44-1" class="xref-bibr" href="#ref-44">Lubin <em>et al.</em>, 1984</a>; <a id="xref-ref-5-1" class="xref-bibr" href="#ref-5">Benhamou <em>et al.</em>, 1985</a>). However, the use of hospital-based controls could be considered a limitation.
</p>
<h5>Gustavsson <em>et al. </em>(1990)
</h5>
<p id="p-57"> Gustavsson and colleagues followed a cohort of workers who were employed in one of five Stockholm bus garages between 1945
and 1970. Exposure to asbestos was estimated by industrial hygienists based on personal sampling results. Observed mortality
for the period from 1952 to 1986 was compared with mortality of the general and the ‘occupationally active’ population of
Stockholm. The SMRs for lung cancer were 1.22 (95% CI 0.71–1.96) using occupationally active population rates and 1.15 (95%
CI 0.67–1.84) using general population rates. The lung cancer SMRs by asbestos exposure index (exposure intensity × duration
in years) were 0.86 for index 0–20, 1.97 for 20–40 and 1.18 for >40.
</p>
<p id="p-58"> 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’.
</p>
<p id="p-59"> 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).
</p>
<p id="p-60"> 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 dose–response analyses.
</p>
<h5>Hrubec <em>et al.</em> (1992, 1995)
</h5>
<p id="p-61"> 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’.
</p>
<p id="p-62"> 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’.
</p>
<h4>Tier II</h4>
<h5>Williams <em>et al.</em> (1977)
</h5>
<p id="p-63"> Using the data from the Third National Cancer Survey, Williams <em>et al</em>. 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
non-exposed category consisted of persons in any other known job. For the industry category ‘car repair services’ 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 weakness was the poor response rate and the use of all other cancers
as controls.
</p>
<h5>Jarvholm and Brisman (1988)</h5>