MALIGNAN MESOTHELIOMA IN NORTH AMERICAN

Incidence
In the United States
In 1890 Biggs reported a case of ‘endothelioma’ of the pleura. This report may have
been the first recognised case of malignant mesothelioma in North America. Since then
the incidence of mesothelioma in North America and the world has steadily climbed.
Studies of the incidence of mesothelioma in North America have been hampered
by a paucity of data. Before 1988, the United States did not even have a specific code for
mesothelioma, so many cases were misclassified on death certificates as lung cancers or
abdominal cancers. In the United States, the best estimates of mesothelioma incidence
are derived from the Surveillance, Epidemiology and End Results (SEER) Program of
the National Cancer Institute. The SEER database2 includes about 9.5 per cent of the
United States population. It covers 10 regional areas, in five states (Connecticut, Iowa,
New Mexico, Utah and Hawaii), and five major urban areas – San Francisco–Oakland,
New Orleans, Seattle, Atlanta, and Detroit. Although the SEER regions are reasonably
representative of the United States population in terms of demographic and epidemiological
factors, the programme may not accurately reflect the country as a whole. It
includes some shipbuilding areas, but large urban areas where asbestos was used in
manufacturing and construction are underrepresented. The database is organised by
case; each case is identified by age, sex, race, date of diagnosis and cancer type. The data
for mesothelioma are published only intermittently. However, this database provides
the most comprehensive national incidence data available for this disease.
In 1997 Price analysed the SEER data for mesothelioma. He divided the data into
five-year age groups in each diagnosis year. He found a consistently higher rate of mesothelioma
in men than in women. The rate for women remained relatively constant over
the years. On the other hand, the rate for men increased until 1992, when it peaked at 1.9per 100 000 people. Since then the incidence rate in men has been slowly decreasing
 This trend is presumably due to occupational asbestos exposure, which was
highest during the years 1930–60. The highest lifetime risk was for the 1925–30 birth
cohort – a group that would have been at work in shipyards, manufacturing and construction
during the years 1930–60. In recent years in the United States, the incidence has been
approximately 2000–3000 cases per year, or 11.4 cases per million men and 2.8 cases per
million women. The mortality rate in people with prolonged heavy exposure to asbestos
varies from 2 to 10 per cent in different studies, and the latency period between initial
exposure and manifestation of disease is usually 20–50 years. From 1987 to 1996 an average
of 520 people died per year in the United States of malignant mesothelioma

Data from the United States Department of Health and Human Services5 show that
states with the highest incidence of mesothelioma are all coastal or Great Lakes States.
Florida has displaced New York as the State with the highest number of deaths per year
from mesothelioma. In 1996, 78 people died of mesothelioma in Florida. The states with
the highest age-adjusted mortality rates were Washington and Oregon, probably due to
the presence of shipyards. The most frequently recorded occupation on death certificates
of people with mesothelioma in the United States was homemaker (10.6 per cent of all
deaths), followed by managers and administrators, plumbers, pipefitters and steamfitters,
production supervisors, labourers, electricians, farmers, carpenters and machinists. The
most common industry was construction, followed by ship building and railroads. Other
areas with significant mesothelioma incidence were schools and government.

In Canada
In Canada several large epidemiological studies have provided data for estimates
of the incidence of mesothelioma. Morrison and colleagues in 19846 looked at all cases
of pleural mesothelioma diagnosed in British Columbia from 1973 through 1980 and

reported to the National Cancer Incidence Reporting System (NCIRS) of Statistics
Canada. They identified 64 cases (54 men and 10 women). Almost all cases were clustered
in Cowichan Valley, Capital and Greater Vancouver counties. They noted an
overall increasing incidence with age. Among men, but not women, they found an
increasing incidence over time, and correlated this with a relatively high level of shipbuilding
and ship repair activity in Vancouver and Victoria thirty to forty years before
the study. Similar increased rates of mesothelioma have been observed in shipbuilding
centers in the United States and Great Britain. The authors also compared the incidence
of mesothelioma obtained from NCIRS data to that obtained by looking at death
records. They found that only 60 percent of the cases were identified by looking at
mortality data – so death records are therefore a poor substitute for incidence records,
since mesothelioma is often not recorded as the cause of death.
In 1985 Churg and colleagues7 surveyed all pathologists in British Columbia, in an
attempt to identify all cases of mesothelioma diagnosed in 1982. Occupational histories
were obtained when possible, the pathology slides were reviewed, and when tissue was
available the lung was analysed for asbestos content. They identified 19 cases (17 men
and 2 women) of confirmed mesothelioma; obtained occupational histories for 16, and
analysed lung tissue fibre content in 7. The calculated incidence per year based on their
data was 17 cases per million men and 1.9 cases per million women over age 15. Compared
with data from 1966–1975, this was a marked increase in the incidence rate for
men, but no obvious increase for women – similar to the observations by Price in the
United States. Fourteen of fifteen men had a history of occupational asbestos exposure,
mostly in shipyards, or in construction or insulation work. In the six men whose lung
tissue was analysed, the pulmonary content of chrysotile asbestos was within the range
of the general population, but the values for amosite and crocidolite were elevated on
average 300-fold compared to a reference population. No commercial amphibole was
found in the lungs of the one woman analysed. They concluded that the cases in women
may not have been associated with asbestos, and may represent the background nonasbestos
associated mesothelioma rate in the general population.

Causes of malignant mesothelioma
Asbestos
The adverse effects of asbestos were first observed in the early 1900s and the relationship
to mesothelioma was suggested in the 1940s. One of the earliest reports linking
mesothelioma to occupational asbestos exposure came out of the medical clinic at an
asbestos mine in Canada. At a scientific meeting in 1952 Cartier,10 then in charge of the
industrial medical clinic at Thetford Mines, Quebec, reported eight cases of respiratory
cancer, two of which he described as pleural tumors. He declared that two such rare
cancers in a small series of only eight cases suggested an occupational origin. By 1960
the scientific community generally recognised asbestos as a cause of mesothelioma.
However, the issue was far from settled. In a national survey of mesothelioma in
Canada from 1960 to 1968, McDonald and colleagues11 found a history of asbestos
contact in a relatively small proportion of cases – mostly in insulation and allied trades
rather than in the asbestos-producing industry. They surveyed pathologists across the
country to find all cases of mesothelioma after 1959. They found 165 cases (111 pleural,
47 peritoneal, 3 both and 4 pericardial). Updates in subsequent years showed a
slightly increased association with asbestos exposure, but still lower than expected.
When pathologists reviewed the cases12 the diagnosis was confirmed in only about 50
per cent of the cases, among whom the incidence of asbestos exposure was also higher.
A follow-up analysis added a chrysotile mining industry cohort and two small groups of
employees in gas mask factories to the survey data. They found 254 fatal cases of
mesothelioma (181 men, 73 women) in Quebec from 1960 to 1978. They were able to
obtain occupational and residential histories for the majority, and found that only
about 40 per cent of the male cases and 5.4 per cent of the female cases were attributable
to occupational asbestos exposure (asbestos manufacture, production, insulation,
heating trades, shipyards, and construction). Six people probably had household exposure.
The intervals between first employment and death from mesothelioma were
longer for miners and millers than for manufacturing workers. All the miners and
millers had pleural mesothelioma, while the factory workers included 8 with peritoneal
mesothelioma. The incidence did not clearly increase over this time period.

In 1994 Spirtas and colleagues15 published a study aimed at defining the attributable
risk of asbestos exposure in the United States. They used the Los Angeles County
Cancer Surveillance Program, the New York State Cancer Registry (excluding New York
City), and 39 large Veterans Administration hospitals to identify people diagnosed with
mesothelioma from 1975 to 1980. They identified 208 cases of pathologically confirmed
mesothelioma. Controls were 533 people who had died of other causes. They interviewed
immediate family members to obtain asbestos exposure history. Among men the attributable
risk for asbestos exposure was 88 per cent, among women it was 23 per cent
(although the confidence interval was very wide at 3–72%). The increasing incidence of
mesothelioma in the United States is primarily due to the increased incidence among
men, thus probably reflecting more occupational exposure.
Most patients with mesothelioma do have a history of exposure to asbestos, although
it may have been brief and remote in time. The variability in percentages of
cases with identifiable asbestos exposure may be related to several factors: incomplete
history taking, unknown or hidden occupational exposures, or environmental exposure.

Other possible causes
Although it is clear that asbestos causes mesothelioma, other factors also play a role.
It is not clear why only a relatively small proportion of people exposed to asbestos
develop mesothelioma, or why anywhere from 20 to 60 per cent of people with mesothelioma
in different studies lack a known history of asbestos exposure. There
may be as-yet unidentified cofactors that act as co-carcinogens with asbestos in the
induction of mesothelioma.
Evidence that not all cases of mesothelioma are caused by asbestos is threefold.
First, we have evidence that a background rate of mesothelioma does exist.18 Historically,
primary malignant tumours of the pleura were recognised by pathologists at autopsy
in the late nineteenth century, before the industrial use of asbestos could have
been responsible, and without any link to occupation. Epidemiological evidence from
mortality statistics for mesothelioma over the past 50 years in the United States and
Canada also support a background rate of mesothelioma. Many studies have shown that

disease incidence has increased much more rapidly in men than in women, reflecting
occupational asbestos exposure among the men. The rate among women has remained
relatively stable, indicating that it may be the background rate of mesothelioma. Backward
extrapolation suggests that before the diverging pattern began, mortality was about
1–2 per million population in both sexes. This possibility is supported by data from regions
with low mesothelioma mortality where both male and female rates are at about
this level, and by data for California, after exclusion of occupationally related cases.
However, it is also possible that waterborne or airborne fibres originating from naturally
occurring asbestos deposits are the cause of this background rate of mesothelioma.
Second, since the latency period after asbestos exposure is normally at least 14
years, the occurrence of malignant mesothelioma in childhood may be evidence of a
genetic predisposition, or an environmental exposure which may cause mesothelioma
in some cases. In a Canadian survey, from 1960 to 1980, four fatal cases in children
were found through systematic inquiry of all pathologists – a rate of about 0.7 per 10
million per annum. A similar figure can be derived from the 13 cases identified by
Grundy and Miller from death certificates in the United States from 1965 to 1968.
And data from the SEER programme in the United States (1973–84) reveal an incidence
among children of about 0.5 per 10 million per year.
Third, lung burden analyses provide some evidence that not all cases are caused
by asbestos. In several studies in both the United States and Canada, a certain number
of cases could not be attributed to either amphibole or chrysotile fibres. Various
other agents have been suggested as additional causes of mesothelioma. A report from
India suggested that organic fibres may cause mesothelioma in sugar cane workers.
Reports of cases of mesothelioma in sugar cane workers in southern Louisiana provided
some support for this hypothesis. After the harvest, the cane is burned off and
long, thin, respirable silica fibres form, a process that might also occur after forest
fires and other circumstances. Theoretically, these fibres could cause mesothelioma in
much the same way that asbestos fibres do.

United States and Canadian asbestos use and
production
Historically, Canada has been one of the largest asbestos miners, and the United States
has been one of the largest asbestos consumers. In 1877 extensive chrysotile asbestos
deposits were discovered in eastern Quebec. These areas were developed in the 1880s,
and soon half of all the world’s asbestos was mined in Canada. A small amount was
also mined in the United States. The asbestos industry grew rapidly in the 1930s and
1940s and the use of asbestos in North America was at its peak from the 1950s through
1970. In 1970 the United States used almost a quarter of the asbestos produced throughout
the world

In contrast to other areas of the world, the United States used predominantly
the serpentine chrysotile type asbestos. Approximately 95 per cent of United States
consumption has been chrysotile. Currently it accounts for more than 99 per cent of
United States asbestos consumption.The United States imported 165 000 tons of
chrysotile in 1935 and 650 000 tons in 1962. Crocidolite was used much less, and much
later. Less than 500 tons of crocidolite were imported in 1935, and only 20 000 tons by
1962. In 1997, it was reported that 238 tons were imported, but it has been estimated
that only 5 tons were used. Small amounts of amosite have also been used in the
United States, averaging about 16 000 tons per year in the 1960s.
Starting in 1970, United States consumption of asbestos declined precipitously,
largely as a result of mounting evidence of its toxicity. During the early 1970s the
number of asbestos lawsuits increased dramatically. World production of asbestos has
declined in the 1990s to approximately 2.7 million tons per year – about 50 per cent of
the peak production in 1973. Canada is now the second largest miner of asbestos, after
Russia. In the United States, consumption of asbestos in 1997 was only 21 000 metric
tons

Occupational exposures and the fibre-type debate
Over the years investigators have looked at the incidence of mesothelioma in different
cohorts of workers in North America, attempting to answer several questions about
asbestos and mesothelioma. Initially studies were aimed merely at documenting the

relationship between asbestos and mesothelioma. Subsequently, debate became heated
over whether different types of asbestos fibres were more or less carcinogenic than
others – particularly whether the serpentine type (chrysotile) was as carcinogenic as
the amphiboles (crocidolite, amosite and tremolite). North America was the perfect
forum for this debate, since the mines and mills in Canada seemed to provide a means
to study workers exposed only to chrysotile, and in the United States chrysotile has
been the predominant exposure. Mossman, Gee, McDonald and Wagner, who favored
crocidolite as the sole cause of mesothelioma, squared off against Selikoff, Smith, Cullen
and others, who believed that all forms of asbestos were a threat


Insulators
Asbestos has been used as an insulation material since 1866. In the United States and
Canada, until the early 1940s, the only asbestos used was chrysotile, almost exclusively
from the Canadian mines. During the 1930s the United States began to use small quantities
of amosite asbestos imported from South Africa. Amosite was mixed with chrysotile
in making insulation blocks. The insulators likely had heavy though intermittent
exposure. Exposures were especially high in shipyards where they ripped out and replaced
old asbestos insulation in the confines of boiler rooms and submarine hulls.
The insulators have been a well-organised group. The first insulation workers’
union was formed in New York City in 1883 – the “Salamander Association of Boiler and
Pipe Felters” (the name came from a story about Marco Polo, who was shown some
inflammable cloth while traveling through Siberia, and was told that it was made from
salamander’s wool). In 1910 the Salamander Association merged with other independent
locals in the United States and Canada and became the International Association
of Heat and Frost Insulators and Asbestos Workers. The union rolls thus provided the
ideal cohort to study the relationship between asbestos and mesothelioma.

Miners and millers
The miners and millers of chrysotile asbestos in Canada seemed to be the perfect
group in which to pursue these questions, as they were thought to represent a group
exposed to only one type of fibre. However, the situation was not so simple. Canada
and Russia have produced most of the world’s asbestos. Chrysotile asbestos was first
mined in 1878 in the Eastern Townships region of Quebec, and is now the overwhelming
type mined in Canada. The two main mining areas are now the towns of Asbestos
and Thetford. Most of the mines were open pit mines, where 13-metre (40-foot) holes
were drilled in asbestos-containing ore deposits, and were then blasted with explosives.
Workers loaded the loose ore onto trucks and then transported it to a crushing
machine. Moisture was removed by heating the crushed ore in huge dryers. During
milling the ore went through stages of screening and vacuum separation in which
loose asbestos fibre was lifted from the rock. Conveyor belts, chutes, and vacuumexhaust
pipes transported the ore and fibre through the mills. Most employees worked
in the mills, cleaning up spilled asbestos fibre, feeding asbestos into storage bins, and
maintaining equipment. Before 1970, only total dust counts were made – asbestos
fibre concentrations were not measured separately. Virtually all jobs in this industry
were very dusty. In the 1970s asbestos fibre concentrations were measured, and it was
found that average asbestos-fibre concentrations were significant, especially in the
drying and crushing operation, and greatly exceeded the asbestos standard of 5 fibres
per cubic centimetre (5 f/cm3) of air then in effect in the United States

The shipyards
Currently the highest age adjusted incidence of mesothelioma in the United States is in
Washington and Oregon, probably due to the shipbuilding industry. Asbestos exposure
in shipyards frequently involves massive exposures of short duration in enclosed spaces,
as opposed to the chronic exposure in mining and manufacturing processes. Thus, shipyard
workers represent a group where the effects of short-term intense exposure might
be seen. Asbestos has been used to insulate the steam pipes and boilers of ships since the
turn of the century. The asbestos may be woven in a mattress of cloth and wrapped
around piping, applied as a cement-like material, or sprayed as fireproofing. Not only
the insulators were exposed – bystander exposure in this situation was probably significant,
since the work was done in the enclosed spaces of ship boiler rooms.
Shipyard worker populations fluctuate greatly. In 1918 there were 318 500 shipyard
workers in the United States, compared to 75 000 during the 1920s and 1930s. With
the approach of World War II, the shipyards underwent a tremendous expansion and
shipbuilding became the largest manufacturing industry in the United States for a time.
By the end of 1943, 1 722 500 people were employed in shipyards. In some yards between

10 and 20 per cent of these workers were women. Turnover was very high, so it has been
estimated that about 4.5 million people were employed in shipyards during World War
II. After the war the number of shipyard workers rapidly decreased.
Since no dust counts were taken, no one really knows what levels of asbestos
fibre existed. They were likely very high at times. In 1975 the use of asbestos in shipbuilding
and ship repair was largely abandoned. However, ship repair remained a problem
because asbestos previously used as insulation on steam pipes and boilers had to
be ripped out and replaced during renovation and repair work.

Factory workers
Authors on both sides of the fibre-type debate have investigated factory workers in
various industries. In some workplaces, measurements of dust exposure were made,
and both the exact fibre type and degree of exposure could be evaluated. Thus these
factories proved to be optimal forums to continue the debates over fibre type versus
fibre size versus amount of exposure.
In 1967, Enterline and Kendrik conducted a study of the effect of asbestos exposure
on factory workers. They recorded the causes of deaths among 21 755 white men aged 15 to
65 who worked in several different asbestos-products plants in the United States at some
time during the period 1948 to 1951, identified from social security tax returns filed with the
United States Bureau of Internal Revenue for the first quarters of 1948, 1949, 1950 and
1951. Deaths were identified from death claims filed with the social security administration
through 1963, and death certificates were reviewed. A cohort of 6281 cotton textile workers
was used as a control group for the asbestos textile workers. Among 1853 death certificates
examined, only one listed mesothelioma. Although respiratory cancer rates were increased
overall, mortality was actually lower than for the general population. At most the follow-up
was only 17 years, so the full effect of asbestos exposure had probably not yet been seen.

Construction industry
In the past, the construction industry accounted for an estimated 70–80 per cent of
total United States consumption of asbestos fibre, and an enormous number of workers
in various construction trades have been exposed to varying amounts of asbestos.
From 1958 to 1973, until the Environmental Protection Agency abolished the practice,
asbestos fireproofing material was sprayed in more than half the multistoried buildings
constructed in the United States. About 25 per cent of the sprayed material would
fail to adhere, and was released into the air. All workers on the site during and after
the spraying were exposed. Thirty per cent of the water distribution pipe sold in the
United States in 1974 was asbestos cement.
A mortality study of the members of the union of plumbers and pipefitters in the
United States found significant excesses in proportional mortality ratios for malignancies,
including 7 deaths due to mesothelioma.72 Two studies of sheet-metal workers in New York
City found significantly increased mortality, and mesothelioma was recorded on death
certificates in 9 out of 716 total deaths (1.3 per cent).73,74 Studies in construction workers
are difficult since specific exposures often are not known, and workers change jobs frequently.
Epidemiological studies, however, consistently show that construction workers
are one of the groups most at risk for asbestos-related disease and mesothelioma.
Miscellaneous exposed groups
Several other groups in North America have been studied to determine the effects of asbestos
exposure. Railroad machinists were exposed to significant amounts of mostly chrysotile
asbestos, especially during the application and removal of asbestos insulation on the boilers
of steam locomotives. The last steam engine repairs took place in the late 1950s. In 1988
Mancuso75 published a study investigating the risk of mesothelioma among railroad machinists.
His cohort was railroad machinists employed by a company before 1935, and still
alive in 1945. He analysed the data for 181 people hired from1920 to 1929. By 1986, 156 were
identified as dead. There were 41 cancer deaths, 14 with mesothelioma. The relative risk was
1 mesothelioma in every 13 machinists hired. Similarly, in 1986 Schenker et al.76 completed
a case-control analysis of mesothelioma among United States railroad employees. The United
States Railroad Retirement Board notified investigators of all deaths among male railroad
workers occurring in 1981–82. They reported 15 059 deaths during the study year. Twenty
cases of mesothelioma were identified. More cases occurred among the workers in asbestosexposed
job categories. The latency period was 30 years or more.
In the jewellery industry, asbestos has been used to make

Non-occupational exposure
Several studies have documented that non-occupational exposure to asbestos is also
associated with mesothelioma. Given that chrysotile is thought to be less carcinogenic
than the amphiboles, the question was then raised as to whether the low levels of
exposure seen with non-occupational situations can cause mesothelioma or other asbestos-
related diseases.
Researchers at Mt Sinai Hospital in New York City studied the health experience
of 679 household contacts of the 1664 workers employed at the Paterson, New
Jersey, factory between 1941 and 1954. They discovered 5 cases of mesothelioma in
family members of factory workers. Asbestos dust was also found in the homes of former
Paterson factory workers 20 years after the factory was shut down. There was some
indication that both the occurrence of mesothelioma and the length of the latent period
were dose related.
The impact of neighbourhood asbestos exposure has also been investigated in
relation to the Paterson factory. In 1979, Hammond and Selikoff traced 2447 men
who were living within 800 metres of the factory in 1942, and compared them to residents
of a neighbourhood a few kilometres away. They found that dust samples collected
from houses located near the asbestos factory contained appreciable amounts
of asbestos fibre even many years after the factory closed. So far, however, they have
not reported any increased mortality.
In 1996, Berry published a study of the incidence of mesothelioma in Somerville
County, New Jersey, the location of the Manville asbestos plant. This plant produced
multiple asbestos products, primarily (95 per cent) using chrysotile asbestos. A previous
study in 1987 indicated that the rate of mesothelioma was significantly higher in Somerset
County than in the rest of New Jersey. Berry expanded on this study. He used the New
Jersey State Cancer Registry to identify cases of mesothelioma from 1979 through 1990,
and compared the incidence rates in Manville, Somerset County excluding Manville,
and the rest of New Jersey. He then excluded all who worked at the Manville plant.