Case-control study of pleural mesothelioma in workers

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE (2009)
Case–Control Study of Pleural Mesothelioma
in Workers With Social Security in Mexico
Guadalupe Aguilar-Madrid, MD, MSc, PhD,1 Eduardo Robles-Pérez, MD, MSc,2
Cuauhtémoc Arturo Juárez-Pérez, MD, MSc,1 Isabel Alvarado-Cabrero, MD,3
Flavio Gerardo Rico-Méndez, MD,4 and Kelly-Garcı́a Javier, MD3
Background Environmental and occupational exposure to asbestos in Mexico in the past
has been a cause of deaths and health damages. Its magnitude is unknown to date. Our
objective was to identify the proportion of cases of malignant pleural mesothelioma
(MPM) that can be attributed to and occupational exposure to asbestos.
Methods We carried out a case–control study of MPM in 472 workers insured by the
Mexican Institute of Social Security, all Valley of Mexico residents, with 119 incident cases
and 353 controls. Cases were histologically confirmed. Participants were questioned
concerning their occupational history and sociodemographic data. Assignment to one of the
four exposures was performed qualitatively by an expert hygienist. Odds ratios (ORs) and
attributable risks (ARs) were calculated using a non-conditional logistic regression model.
Results A total of 80.6% of cases and 31.5% of controls had occupational exposure to
asbestos. ORs were adjusted for age and gender and by exposure category, and exhibited an
increase with probability of exposure as follows: 3.7(95% CI 1.3–10.4) for the likely
category and 14.3(95% CI 8–26) for the certain category; AR in the group occupationally
exposed to asbestos was 83.2%, and the population AR was 44%.
Conclusions Our results show that the relationship between industrial uses of all forms of
asbestos is generating an increase in mesothelioma-related diseases and deaths among
Mexican workers. As a public health policy, Mexico should prohibit the use of asbestos in
all production processes with the aim of controlling the epidemic and preventing the
occurrence of new cases of MPM. Am. J. Ind. Med. 2009. ß 2009 Wiley-Liss, Inc.
KEY WORDS: pleural mesothelioma; Insured workers; case –controls; social
security; Mexico
INTRODUCTION
Exposure to asbestos is well identified as an occupational risk, as is its carcinogeniceffect on lungs, pleura, and
1
Unidad de Investigacio¤ n en Salud en el Trabajo, Instituto Mexicano del Seguro Social
(Occupational Health Research Unit,Mexican Institute of Social Security - IMSS), Mexico City,
Mexico
2
Coordinacio¤ n de Salud en el Trabajo (Coordination of Occupational Health), IMSS, Mexico
City, Mexico
3
Unidad Me¤ dica de Alta Especialidad, Hospital de Oncologi¤a, Centro Me¤dico Nacional
Siglo XXI (High Specialization Medical Unit, Oncology Hospital, Siglo XXI National Medical
Center - CMN-SXXI) (Servicio deTora¤ x y Jefatura de Patologi¤a del IMSS^Thorax Clinic and
Pathology Department, IMSS) Mexico City, Mexico
4
Hospital General Gaudencio Gonza¤ lez Garza, Centro Me¤dico La Raza (Gaudencio
Gonza¤lez Garza General Hospital, La Raza Medical Center), IMSS, Mexico City, Mexico
Contract grant sponsor:Irving J. Selikoff International Scholar of the Mount Sinai School of
Medicine; Contract grant number: D43TW000640; Contract grant sponsor: Mount Sinai
2009 Wiley-Liss, Inc.
peritoneum [Selikoff et al., 1965; Mossman and Gee, 1989]
Malignant pleural mesothelioma (MPM) in industrialized
countries is caused predominantly by exposure to asbestos
fibers [Selikoff, 1979; Rösler et al., 1994]. The International
School of Medicine and Queens College, City University of NewYork; Contract grant sponsor:
Fondo de Fomento a la Investigacio¤n (FOFOI); Contract grant number: 2004-001; Contract
grant sponsor: Consejo Nacional de Ciencia yTecnologi¤a-Me¤xico (CONACyT-Salud); Contract
grant number: 2002-C01-8426.
*Correspondence to: Guadalupe Aguilar-Madrid, Unidad de Investigacio¤ n en Salud en el
Trabajo, Instituto Mexicano del Seguro Social, Centro Me¤ dico Nacional Siglo XXI, Av.
Cuauhte¤moc No. 330, Edif. C, 1er piso, Col. Doctores, 62508 Me¤ xico, D.F., Mexico.
E-mail: [email protected], [email protected]
Accepted 26 September 2009
DOI 10.1002/ajim.20780. Published online in Wiley InterScience
(www.interscience.wiley.com)
2
Aguilar-Madrid et al.
Agency for Research on Cancer [IARC, 1977] has considered asbestos a carcinogenic since 1977, as has the International Program on Chemical Safety [1998] since 1998.
Diverse studies have demonstrated the negative impact of
exposure to the fiber on workers’ health [Selikoff et al., 1965;
McDonald et al., 1984; Yano et al., 2001].
In Mexico, chrysotile—or white asbestos—is the type of
fiber most frequently utilized in the industry and represents
the most important exposure source for Mexican workers.
Mexico has imported asbestos since 1932, but it was not until
the 1970s that the most industries employing these fibers
were installed in the country [Gavira et al., 1990; AguilarMadrid et al., 2003].
Ample international scientific evidence has emphatically demonstrated that all asbestos forms are carcinogenic,
that they cause pleural mesothelioma, that there is no safe
asbestos-exposure level, and the World Health Organization
[WHO 2006] have requested its ban. Despite all this
evidence, the proportion of MPM cases that can be attributed
to environmental and occupational exposure remains
unknown in Mexico; this has thus contributed to the lack of
recognition of this exposure as an occupational risk. As a
result, its medical care costs and pensions for workers and
their families are absorbed by Social Security and the
national health system.
Despite the well-known health effects of asbestos
exposure, there exists an international policy spearheaded
by Canada to continue revitalizing the ‘‘safe’’ use of
chrysotile, which implies a clear transfer of dangerous
industries to less-industrialized countries such as Mexico,
which possess a weak and inefficient judicial framework for
worker protection. This will have damaging effects on health
and an important impact in Mexico; similar to what has
occurred since the 1970s in more industrialized countries,
such as France, which has an incidence of 1,000–2,000 cases
annually [Huré, 2006].
The aim of the present study was to determine the
proportion of cases of MPM that are attributable to occupational exposure to asbestos in Mexican workers insured by
the Mexican Institute of Social Security.
METHODS
We carried out a case–control study of malignant pleural
mesothelioma (MPM) incidence in Mexican insured workers
at two concentration hospitals of this cancer type at different
Instituto Mexicano del Seguro Social (Mexican Institute of
Social Security IMSS) hospitals are located in the Valley of
Mexico. One of these was ‘‘La Raza’’ General Hospital
(Pulmonary and another the Oncology Hospital at the ‘‘Siglo
XII’’ National Medical Center (Thorax Service); the latter is
the referral center for four Mexican States including the
Distrito Federal and the States of Mexico, Morelos, and
Hidalgo, where all workers with MPM are referred to for
medical care. The study period was from May 2004 to April
20, 2006. The research protocol was approved by the IMSS
National Research Commission’s Ethics Committee. Study
participants signed informed consent and physicians from the
participating hospitals were invited to collaborate in the
study.
The IMSS is the Mexican Institute of Social Security.
It insures more than 12,000,000 workers, who represent
30% of the country’s economically active population
(45 million). The IMSS is divided into four regions of
Mexico (North, West, Central, and South); each of these
regions has a highly specialized Medical Center that includes
an Oncology Hospital, which serves as the referral center for
cancer cases.
The hospitals participating in this study were from the
Central region of Mexico, with 3,706,755 active insured
workers and 71,681 retirees. The cases and controls in this
study were selected from this population and the data were
obtained from records of the Sistema Nacional de Derechohabientes [SINDO, National System of Policyholders] and
the Sistema de Información de Trabajadores Pensionados de
Cesantı́a, Edad Avanzada y Vejez IMSS [Information System
of Retired Workers].
The cases were recruited from insured workers who were
referred for medical care due to suspected diagnosis of MPM
at any of the previously mentioned hospitals. Diagnosis of
mesothelioma was confirmed by Oncologists and the Head of
the Ward at the CMN-SXXI Oncology Hospital based on
clinical review of the data (clinical history, X-ray films,
computed tomography [CT] scans of the thorax and
laboratory tests) and in the immunohistopathology study
report.
In the study, we only included cases in which MPM was
confirmed by immunohistopathology study carried out by
two pathologists who were certified by the Mexican Council
of Pathology. The participation rate of cases was 99.1%; only
one worker declined to participate, due to his extremely
serious condition.
Controls were selected at a proportion of three cases per
control, with an age range of 5 years, with similar gender
proportions, same insurance type (active workers and
retirees), and same city of residence as well. These controls
were randomly selected from the IMSS insured-worker
population database and from the same Central region of the
SINDO from which the cases originated. A database of 500
eligible workers was constructed: 250 were active workers
and 250 were retired. The controls selected were referred to
Unidades de Medicina Familiar (UMFs, Family Medicine
Units), where they received medical care; by means of
telephone calls and telegrams were sent to their homes and
were invited to participate in the study. We included as
controls insured workers who agreed to sign an informed
consent letter and the questionnaire application. The
Case–Control Study of Pleural Mesothelioma
participation rate was 59% for active workers and 83.2% for
retired workers. Reasons for non-participation included
the following: the person was not found at the address
given; the individual worked in other States or outside of
Mexico. For retired workers, non-participation was due to
their living at other domiciles where someone was in charge
of their care.
Data Collection
A standardized questionnaire was applied face to face to
the workers by previously trained female interviewers whose
background was social work; the questionnaire had been
pilot tested in a healthy worker population. The instrument
was designed to collect data on personal identification;
socioeconomic aspects; worker employment history detailing initiation and termination dates for each of their jobs; type
of industries; occupation in the company within the formal or
informal economy; substances and raw materials utilized,
intermediate and final products; a detailed description of their
activities; and work site safety and hygiene conditions. Based
on these data, insured workers were grouped according to the
International Standard Industrial Code (ISIC) third review;
for workplace, we used the 5-digit International Standard
Classification of Occupations-88 (ISCO) of the International
Labour Organization (ILO).
In addition, we gathered data on para-occupational
exposures, that is, the occupational history of the father or
another family member, as well as information regarding
likely environmental asbestos exposure, such as years of
residence near asbestos industries. Furthermore, we
requested information on smoking and calculated the
smoking index as follows: number of cigarettes smoked
daily multiplied by years of duration of the smoking habit
divided by 20 (the number of cigarettes in a pack); this result
was expressed in the number of cigarette packs smoked
annually [Villalba and Martı́nez, 2004].
Assignment to Occupational Asbestos
Exposure Category
For this assignment, we utilized the ISIC revision 3.0,
and occupational post, large-group headings, main subgroups, and primary groups from the ISCO-88.
Qualitative Exposure Categories
A database was constructed according to work history
information and a detailed description of worker tasks. An
industrial hygiene expert was blinded to the condition of each
participant as case or control, thus ensuring that the data were
coded blindly by workplace, economic activity, and time
of initiation and termination of each employment. The
hygienist had the work history data, as well as a list of the
3
asbestos-importing industries in Mexico and those that
manufactured asbestos in diverse forms (we possessed
information on the 1887 companies located in Mexico that
import asbestos) [Aguilar-Madrid et al., 2003]. The list was
supplied by the Secretarı́a de Fomento Industrial (SECOFI,
The Ministry of Industrial Promotion). Additionally, the
hygienist had access to information from the international
literature on different economic activities and workplaces
known to involve asbestos exposure [Hammad et al., 1979;
Thomas et al., 1982; Dement et al., 1983; Ohlson and
Hogstedt, 1985; Peto et al., 1985; Gardner et al., 1986;
Hughes et al., 1987; Ribak et al., 1989; Albin et al., 1990;
Neuberger and Kundi, 1990; Chrostowski et al., 1991;
Maltoni et al., 1994; Finkelstein, 1996; Burdorf and Swuste,
1999; Sali and Boffetta, 2000] that allowed us to estimate
asbestos exposure in four categories, as follows: certain,
when the worker mentioned direct or indirect occupational
exposure to asbestos; likely, when the worker had been
employed at companies known to have a high risk of
asbestos, but the worker mentioned not being aware of it (for
example: manufacturing asbestos cement products, manufacturing brake lining or clutch plates, transporting asbestos,
insulation asbestos, worker in a power station) ; possible,
when the worker was employed in industries known to have
an asbestos exposure risk, but the worker did not report
these as known and non-exposed (examples: working with
furnaces, wearing heat protective clothing, construction site
work, working in the plastic industry or rubber industry,
working with sugar-cane). This classification is similar to
that used by Rees in South Africa [Rees et al., 1999].
Statistical Analysis
Exploratory data analysis was performed using STATA
9.0 SE statistical software package. We conducted a
distribution analysis of continuous variables, analysis of
variance between case and control groups, and calculated
odds ratios (ORs) per group, as well as differences of
proportions and of means between the groups. Based on nonconditional logistic regression model in which crude ORs
were calculated and adjusted to take into account potential
confounders and interactions. Also we performed analysis of
residuals to determine goodness of fit and predictive value.
Finally, based on the model, attributable risk (AR) was
estimated in exposed workers and for the population at large
based on formulas used by Szklo and Nieto [1999] and
Coughlin et al. [1996] for regression models in case–control
studies.
RESULTS
The study comprised 472 workers, of whom 119 were
incident cases and 353 healthy controls; 86.2% (407) were
males and 13.8% (65) females. Their mean age was
4
Aguilar-Madrid et al.
64.8 years, with a standard deviation (SD) of 11.7 years, and a
range of 39–89 years; the mean age by gender was 61 years
(SD 14.4 years) and 55.6 years (SD 12.5 years) in males
and females, respectively, with a statistically significant
difference.
A total of 58% (69) cases and 58.9% (208) controls were
retirees; the mean age was 46 years (SD 9 years) in active
workers and 70 years (SD 6 years) in retirees. Cases were
from the same populational source from which controls were
selected; 63% (75) of cases and 51% (180) of controls were
from the State of Mexico (Table I).
A total of 8.4% (10) cases and 30% (106) controls were
smokers at the time. The mean smoking index was 12.5 and
12.8 packs of cigarettes per year, respectively. With respect to
education, 6% (7) cases and 2.5% (9) controls were illiterate;
the proportions of elementary (primary) education were
45.7% (49) cases and 45.7% (149) controls, 54% did not
finish their studies, indicating a low level of schooling in
workers participating in the study. Of the exposure categories
69% (82) were in the certain category, as were 21.5% (76) of
controls, with a statistically significant difference. Duration
of exposure to asbestos >13 years was 61% (59) in cases and
38.7% in controls, with a statistically significant difference
(Table I). A 50% of cases had a monthly income of
1.5 minimum wages, while controls earned 2.0 salaries
per month, with a significant difference (Table II).
The overall proportion of certain, likely, and possible
occupational asbestos exposure in some workplaces with
exposure of asbestos during the worker’s entire work-life was
80.6% (96) in cases and 31.5% (111) controls, which was
statistically significant (Table I).
The occupational seniority means in asbestos exposurerelated workplace were significantly different between cases
(20 years) and controls (14.6 years). The mean number of
workplaces with asbestos exposure was two for both groups
(Table II).
The 119 cases of mesothelioma confirmed by histologic
tests were analyzed by the Oncology Hospital’s Chair of the
Pathology Service at the CMN-XXI. A random sample of 33
cases was selected with their respective slides, and a second
reading was performed by a Pathologist from the Instituto
Nacional de Enfermedades Respiratorias (INER, National
Institute of Respiratory Diseases) of the Secretarı́a de Salud
de México (SSA, Mexican Ministry of Health). Agreement
was determined for diagnosis of mesothelioma and mesothelioma type (malignant epithelial, sarcomatoid, malignant
desiduoid). The Kappa test result was 82.2%, which
according to Altam [1991] and Byrt [1996] is a very good
agreement assessment, as referred by Szklo and Nieto
[1999].
Table III shows the distribution of work periods of cases
and controls according to work-life initiation date and
exposure categories, in which the greatest proportion of the
certain exposure category is observed after 1961–1980, the
TABLE I. Frequency Differences Between Mesothelioma Cases and
Controls in IMSS-Insured Workers (2004^2006)
Case
Variable
N
Gender**
119
Males
106
Females
13
Insurance type**
Active workers
50
Retired workers
69
Marital status**
Single
13
Married
80
Widowed
6
Divorced
8
Common law marriage
7
Smoking
Currently smoker
10
Never smoked
38
Smoker in the past
71
Age categories (years)*
31^49
21
50^64
41
65^71
33
72
24
Instruction**
Illiterate
7
Elementary
49
Middle school
19
Technical
7
High school
9
Undergraduate
21
Master
2
Place of residence**
Distrito Federal
44
State of Mexico
75
Occupational exposure categories*
No exposure
23
Possible exposure
8
Likely exposure
6
Certain exposure
82
Time of exposure*
13 years
37
>13 years
59
Control
%
N
%
89
11
353
301
52
85.2
14.7
42
58
145
208
41
58.9
11.4
70.1
5.3
7
6.2
35
245
30
10
18
10.3
72.4
9
3
5.3
8.4
32
59.6
106
12
124
30
35
35
17.6
34.5
27.7
20.2
101
80
87
85
28.5
22.5
25
24
6
45.7
17.7
6.5
8.4
19.6
1.8
9
149
64
25
34
48
6
2.5
45.7
19.6
7.6
10.4
14.7
1.8
37
63
173
180
49
51
19.3
6.7
5
69
242
14
21
76
68.5
4
6
21.5
38.5
61.5
68
43
61.3
38.7
Instituto Mexicano del Seguro Social (Mexican Institute of Social Security).
*Pearson w2, <0.001.
**Pearson w2 >0.001.
Case–Control Study of Pleural Mesothelioma
5
TABLE II. Comparison Between Cases and Controls IMSS-Insured Workers (2004^2006)
Case
Control
Variable
N
Mean
SD
Range
N
Mean
SD
Range
Age (years)**
Active workers
Retired
Monthly income in USD*
Smoking index (packs of cigarettes per year)**
Occupational seniority with exposure to asbestos (years)*
Possible
Likely
Certain
Number of workplaces with exposure to asbestos**
119
50
69
111
81
96
8
6
82
96
61.1
51
69
243
12.5
20
12
28.5
20
2
11.6
7.3
7.3
263
18.7
13
12
12.6
12.6
1
33^84
33^66
49^89
30^1,364
0.1^100.6
1^55
1^40
13^55
1.5^49
1^6
353
145
208
30
230
111
14
21
76
111
60
44
70
291
12.8
14.6
12.8
11.3
16
2
15
9
6
315
18.3
13.6
14.3
13.5
13.5
1
31^85
31^65
61^85
32^2727
0.1^102.6
0.5^52
0.5^44
0.5^36.5
0.5^52
1^6
MPM, malignant pleural mesothelioma; SD, standard deviation. $10 Mexican pesos ¼ roughly $1US dollar (USD).
*P < 0.05.
**P > 0.05.
period of greatest asbestos industry installation activity in
Mexico [Gavira et al., 1990; Aguilar-Madrid et al., 2003].
There were a total of 42 work positions distributed
among 27 economic activities that were considered to
involve an asbestos exposure risk (Table IV). The greatest
proportion of cases included individuals who worked in the
manufacture of other non-metallic mineral products 15.6%
(15), such as occupations involving the manufacture of
products with asbestos (water tanks and asbestos-cement
sheets, brakes, and clutches), mainly manufacturing industry
laborers 12.5% (12), followed by construction industry
workers such as bricklayers and building maintenance
handymen, occupations that were well known for their high
risk of exposure to asbestos (Table IV).
Table V shows crude and adjusted ORs for certain, likely
and possible strata that were calculated through a nonconditional logistic regression model, adjusted by gender and
age as continuous variables. The adjusted ORs (aOR) for
each exposure category, with 95% confidence intervals were
as follows: the certain exposure category had an aOR ¼ 14.3
(95% CI 8–26), while the likely exposure category had an
OR ¼ 3.7 (95% CI 1.3–10.4), and the possible category an
OR of 7.7 (95% CI 2.8–21.2)
The model clearly showed an increase in the risk of
developing pleural mesothelioma with greater accuracy of
asbestos-exposure data. Furthermore, we carried out the
analysis of the residuals of the model, applying goodness-offit tests and testing the assumptions of the generalized linear
models
Based on non-conditional logistic regression model
data, 76.27% of cases and controls were correctly classified;
in addition, the model data allowed us to calculate the
proportion of asbestos exposures among cases (52.9%) and
controls (15.8%), and obtain the overall model OR ¼ 6 (95%
TABLE III. Distribution of Job Periods AmongWorkers, According to Exposure Category and Decade of Initiation (Mexico, Case^Control Study, 2004^2006)
Prior to1960
Probability of
exposure
Cases
Certain
Likely
Possible
Total (96)
Controls
Certain
Likely
Possible
Total (111)
1961^1970
1971^1980
1981^1990
1991^2006
N
%
N
%
N
%
N
%
N
%
32
3
2
37
86.5
8
5.5
24
1
2
27
89
3.7
7.4
19
1
1
21
90
4.7
4.7
4
1
1
6
66.6
16.6
16.6
3
60
2
5
40
37
9
5
51
72.5
17.6
9.8
14
3
2
19
73.6
15.7
10.5
7
1
3
11
63.4
9
27.3
10
6
1
17
59
35
6
8
2
3
13
61.5
15.4
33.1
6
Aguilar-Madrid et al.
TABLE IV. Most Frequent Industrial Activities and Occupations by Initiation of Occupational Life
Cases
Economic activity (two-digit ISIC. Revision 3.0)
26-Manufacture of other non-metallic mineral products
45-Construction
50-Sale, maintenance andrepairofmotor vehicles and motorcycles; retail sale of automotivefuel
27-Manufacture of basic metals
28-Manufacture of fabricated metal products, except machinery and equipment
36-Manufacture of furniture; manufacturing n.e.c.
40-Electricity, gas, steam and hot water supply
15-Manufacture of food products and beverages
25-Manufacture of rubber and plastics products
Other industries
Occupation (five-digit ISCO 88)
71229 Bricklayer, stonemason
71249 Carpenter
72128 Setter operator, soldering
72318 Mechanic, automobile
72338 Mechanic Industrial machinery
81217 Furnace-operator, converting/steel
91619 Collector, garbage
93139 Handyman building maintenance
93229 Laborer, manufacturing
Other professions
Total
Controls
N
%
N
%
15
13
8
7
7
6
5
5
4
26
15.6
13.6
8.3
7.3
7.3
6.3
5.2
5.2
4.2
27
8
26
5
8
15
3
7
3
3
33
7.3
23.4
4.5
7.2
13.5
2.7
6.3
2.7
2.7
29.7
4
5
9
1
9
9
4
6
12
37
96
4.1
5.2
9.4
1
9.4
9.4
4.2
6.3
12.5
38.5
7
0
13
4
20
14
1
11
8
33
111
6.3
11.7
3.6
18
12.6
0.9
10
7.2
29.7
ISCO, International Standardized Classification of Occupations; ISIC International Standard Industrial Classification of All Economic Activities.
CI, 3.6–9.6). These data allowed us to calculate the
attributable risk (AR) in exposed workers and for the
population with the formula described by Szklo and Nieto
[1999] and Coughlin et al. [1996], as follows: AR in exposed
workers (ARE) ¼ OR–1/OR ¼ 6–1/6 ¼ 0.8323 ¼ 83.2%,
with a 95% CI (72.7–89.6). The population AR (ARP) was
calculated as: (proportion of exposure in cases proportion
of exposure in controls)/1 proportion of exposure in
controls ¼ (0.5294 0.1586)/1 0.1586 ¼ 0.4406 ¼ 44%.
DISCUSSION
TABLE V. Crude and Adjusted Odds Ratios in Cases and Controls of Malignant Pleural Mesothelioma in the Non-Conditional Logistic Regression Model
Exposure categories
Not exposed
Possible
Likely
Certain
Gender
Age
Crude OR
Adjusted OR
(95% CI)a
(95% CI)a
1
6 (2.2^15.8)
3 (1.1^8.1)
11.3 (6.6^19.2)
1
7.7 (2.8^21.2)
3.7 (1.3^10.4)
14.3 (8^26)
2.5 (1.1^5.6)
1.01 (0.99^1.02)
OR, odds ratio; 95% CI, 95% confidence interval.
a
Age- and gender-adjusted in the non-conditional logistic regression model.
Comparison of our results with those of other international studies of MPM cases and controls and occupational
asbestos exposure is not easy, due to different instruments,
methods, and criteria for estimating and evaluating occupational exposure retrospectively. Nonetheless, results of case–
control MPM studies and asbestos exposure are very similar
to ours, such as seeing in Table VI. Also, our findings show
that the pattern of this relationship observed in the more
industrialized countries during the 1970s is being repeated at
present in Mexico.
The results of the present study depend on the estimation
of asbestos exposure by the expert hygienist, who could
introduce bias as a result of nondifferential misclassification.
The hygienist was blinded with regard to disease classification of the subject; thus the direction of a nondifferential
Case–Control Study of Pleural Mesothelioma
7
TABLE VI. Odds Ratios in Diverse Case^Control Studies of Pleural Mesothelioma
References
Agudo et al. [2000], Spain
Spirtas et al. [1994], US
Iwatsubo et al. [1998], Paris, France
Tuomi et al. [1991], Finland
Aguilar-Madrid Currents data, Mexico
N
132 cases
257 controls
208 cases
533 controls
405 cases
387 controls
51cases
51controls
119 cases
353 controls
Exposure categories
Certain
High probability and high intensity of exposure
OR (95% CI)
13.2 (6.4^27.3)
27.1 (9.28^79.3)
Certain
13.9
Certain
Certain
Likely
Certain
Likely
3.6 (2.4^5.3)
17.7 (3.4^253)
3 (0.9^10.6)
14.3 (8^26)
3.7 (1.3^10.4)
OR, odds ratio; 95% CI, 95% confidence interval.
misclassification bias always dilutes the strength of the
association may not hold in certain situations involving more
than two exposure categories [Szklo and Nieto, 1999]. We
were only able to get a hold of one hygienist, as only
approximately eight certified hygienists exist in Mexico.
Only one of them collaborated with us in this research
project, which obviously constitutes a limitation in this study.
However, the absence of an increase in risk in the likely
and possible categories shows it was difficult to assign with
accuracy the exposure in these intermediate categories, thus
this increases the likelihood of misclassification. Nonetheless, one advantage of this classification is that it recovers and
takes into account work history information of companies,
workplace, and years of exposure. Also, because the
employment history depends on the precision of the
information provided by the worker it is considered that
the validity is acceptable, because the study comprised
incident cases of MPM. This permitted us to apply the
questionnaire at the time of the worker’s first request for
medical care due to suspicion of tumor; thus, worker cases
were unaware of the association between asbestos exposure
and presence of mesothelioma. This allowed controlling a
probable bias in over-reporting of exposure in the cases; we
observed a very low schooling level in workers with MPM.
This unfortunately means that their knowledge regarding
the health risk for asbestos exposure is very limited; it is
precisely under this premise that dangerous industries such as
asbestos have been installed in Mexico.
Retrospective evaluation of exposure is one of the
principal problems in case–control studies. Some authors
have constructed exposure matrixes by workplaces [Kauppinen et al., 1998]. In these, information on the exposure levels
of certain chemical substances or fibers is known, and
exposure frequency and intensity can be described. In
addition, Teschke et al. [2002] mention that one of the best
strategies for estimating occupational exposure lies in adding
environmental measurement data. One limitation of this
study is the likely underestimation of risk, due to the fact that
in Mexico environmental asbestos monitoring remains
unreliable, unavailable, and unpublished. Thus, we utilized
information from studies published in international journals
that clearly identify industries with asbestos exposure risks.
Reliance on monitoring for air-borne exposure to asbestos is
fraught with hazard as it is often not representative of true
working conditions. But this is particularly true for malignant
mesothelioma, where very low levels can result in disease.
The high AR among exposed workers in this study
(83.2%) indicates that this percentage of pleural mesothelioma can be attributed to occupational exposure to asbestos
probably chrysotile, the variant most imported to Mexico,
from Canada [Aguilar-Madrid et al., 2003]. Spirtas et al.
[1994] reported similar results in a case–control study in 208
cases and 533 controls on MPM-associated to deaths from
1975 to 1980 in New York of State Health Department
Cancer Registry, but also from the Los Angeles County
Cancer Surveillance Program and 39 large Veterans Administration Hospitals; they obtained an AR among males due to
asbestos exposure of 88% (95% CI 76–95). Also, Gennaro
et al. [2000] in a study of mortality among oil-refinery
maintenance workers in Italy and Canada, revealed that 96–
100% of deaths due to mesothelioma and 42–49% of lung
cancers were attributable to exposure to asbestos.
Our results show a clear relationship between industrial
use of all types of asbestos and MPM, and in Mexico the
major type of asbestos is chrysotile imported from Canada
[Aguilar-Madrid et al., 2003], confirming that asbestos is a
carcinogenic agent that has been recognized as such by IARC
since 1977. As an addition to the case–control study, we did a
follow-up of the survival of the 119 cases of MPM examined
and confirmed by immunohistopathology; 34.7% (24) of
these individuals had died by March 2006; of these, only in
29% (7) of cases was malignant pleural mesothelioma the
cause of death annotated on the decease certificate. This
generates an underreporting in the official mortality data by
8
Aguilar-Madrid et al.
mesothelioma in Mexico by approximately 71%. From this
point of view, the trend shown in Figure 1 could be more
pronounced: instead of 170 cases officially reported in the
country (there should be 500 cases reported annually), only
four cases are being recorded as occupational illness for
social security [SUI-ST-5, 2000–2006]. Also, in this study
the cost of medical attention for each mesothelioma case
during the first year or treatment was estimated at $90,625
pesos (8,238 dollars), with a minimum value of $5,531 pesos
(503 dollars and maximum 368,236 pesos (3,3476 dollars).
This means that for every 500 mesothelioma cases estimated
by us in 2005, the mean yearly cost for medical care in
the health sector, at 2005 costs, was $45,312,500 pesos
(4,119,318 dollars). Thus cost is fully covered by the health
system, not by the companies that created the risk, because
these diseases are not recognized as work related illness.
The social and economic impact of these diseases and
asbestos-related deaths should be absorbed by the industries
that have generated the damage and not by the health
institutions, as it occurs at present. According to Hure [2004],
‘‘. . . the utilization of asbestos can punish the economy of
countries during more than 30 years, leaving to future
generations the responsibility to indemnify the victims and
the financial burden of medical care for the victims’’. LaDou
[2004] reported that migration of asbestos industry to
developing countries increasingly bear the cost of its adverse
effects, including the cost that should be borne by the
asbestos industry.
The increase in the number of cases of MPM is
generating disease and death among Mexican workers. The
transfer of this dangerous industry to Mexico with the
consent of the health and labor authorities (Fig. 1), has also
been encouraged by international organizations [COP3,
2006]. In this issue, Summers Lawrence [1991] proposed
that the World Bank must support the migration of dirty and
toxic-waste industries to developing countries due to the
logical economic reasons concerned with certain comparative advantages of these countries, including low wages;
large spaces where there is still much room for contamination
and the low incidence of cancer in the poor countries
[Galeano, 1998].
However, reality shows us that Canada has faithfully
applied the recommendations of Summers and comprises a
deplorable example of the manner in which dangerous
industries are being deliberately exported to Mexico and less
industrialized countries. According to records from 1994 to
2003, exports of the mineral asbestos from Canada to Mexico
represented $114,713,210 million USD in 1991–2000,
ranking in 5th place with 7.8% of the total world exports of
Canada. Other countries purchasing from Canada included
Japan (25%), Thailand (21.2%), India (18.6%), Indonesia
(8%), Korea (7.7%), the U.S. (3.5%), and Algeria (3.4%). By
continuing this Mexican policy of importing this risk, cases
of pleural mesothelioma will continue to increase nationwide
[Trade Data Asbestos Canada 2004] (Fig. 1).
The ILO [2006] has calculated that worldwide, premature death occurs in 100,000–140,000 persons as a result of
asbestos-associated cancers. Additionally, the exact number
of persons who have been exposed to the fiber is unknown.
However, a WHO estimation notes that even if exposure is
FIGURE 1. Malignant pleural mesothelioma-associatedmortality by gender.Mexico,1979^2005.
Case–Control Study of Pleural Mesothelioma
eliminated soon, there will be 5–10 million additional deaths
caused by asbestos [WHO, 2006].
On May 5, 2006 the WHO cited the following: (1) all
types of asbestos cause asbestosis, mesothelioma, and cancer
of the lung; (2) there is no safe level of exposure to asbestos;
(3) there are safe substitutes, and (4) exposure of workers and
other users of asbestos-containing products is extremely
difficult to control. In June 2006 at its 95th Reunion, the ILO
adopted a resolution stating the following: (a) ban and
suspension of all forms of asbestos and of materials that
contain asbestos constitute the most efficient means of
protecting workers from asbestos exposure and for preventing future asbestos-related diseases and deaths, and (b) the
Asbestos Agreement of 1986, number 16, should not be put
forth to justify or support the continuation of the use of
asbestos, and (c) requests that the Administrative Council
promote the elimination of use of all forms of asbestos and of
materials containing asbestos in all of the Member States.
Despite these declarations, the Mexican State has not
banned asbestos use and the asbestos-exporting countries
headed by Canada (followed by Russia and China) blocked
the efforts of the United Nations (UN) to include chrysotile
asbestos in the list of substances. This is having a very clear
impact on the life of the Mexican population [COP,
Communication of Progress, 2006]. Regrettably, at this
meeting Mexico declared that ‘‘. . . we support this decision,’’
although it also declared that ‘‘. . . we support the noninclusion of chrysotile, because for Mexico it could be
difficult to carry out this, despite the Mexican Health
Ministry’s possessing knowledge of the tendency of the
increase (23–170) in cases of malignant pleural mesothelioma (Fig. 1). This increase is similar to that reported in
European countries, the U.S., and China [Karjalainen et al.,
1997; Albin et al., 1999; Goodman et al., 1999; Banaei et al.,
2000; Pinheiro et al., 2004; Hodgson et al., 2005]. According
to Nicholson et al. [1982], it has been estimated that for every
pleural mesothelioma-associated death there are 2.3 (95%
CI, 2–2.7) asbestos exposure-related deaths due to lung
cancer.
Application of ban asbestos in Mexico as a precautionary principle [Gee and Greenberg, 2002] of the Declaration of Rio on the Environment and Development should not
only be a call to reason for the health and work authorities. In
addition, it should be a call for them to comply with their
obligation and commitment to safeguard the population, and
their liability to guarantee the constitutional right to health
and life of the Mexican population. Also, there should be a
measure to halt the impunity with which the national and
transnational asbestos companies operate in Mexico.
9
exposure in categories was utilized for demonstrating that the
relationship between asbestos exposure and MPM is similar
to that reported by studies internationals.
Based on our findings, we propose that the Mexican
Government must ban the use and commercialization of all
forms of asbestos so as to prevent the epidemic clearly
shown using national mortality data and as an urgent measure
to protect the life of future generations. Moreover, an
epidemiologic surveillance program of these workers, as well
as of the communities near this type of industry should be
developed. Thirdly, financial expenses of medical expenses
and pensions should be imposed upon asbestos manufacturers and importers in Mexico. We also show that the low
educational level of the workers promotes to put them in this
kind of risk because their scarce knowledge about this issue.
Thus the Government should implement a national information campaign for the population on preventing and
controlling exposure linked to the presence of asbestos in
buildings, industrial equipment, sheet constructions, homes,
drinking water, automobiles, and other products, taking into
account that at present there is the technical possibility of
substituting asbestos for the prevention for the mesothelioma
epidemic in Mexico, which will continue to increase at least
during the next 50 years if its use is not banned at once.
ACKNOWLEDGMENTS
We are grateful to the active workers and retirees who
participated in this study for their valuable cooperation,
especially those who died prematurely without knowing the
reason why, without punishment of the guilty, to those who
died inexorably and who even so offered us their information,
and to their forsaken families, to the directors, service heads,
and medical Oncologists, Pneumologists, Pathologists, and
nurses at the participating hospitals, especially to social
workers Amparo Gómez M and Irais I Pastelı́n-Ramı́rez for
their great dedication in administering the surveys, and to
Dr. Vı́ctor Hugo Borja-Aburto, Dr. Benedetto Terracini and
Dr. Luis Haro for their support and comments.
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