Epidemiology of peritoneal mesothelioma: a review
Epidemiology of peritoneal mesothelioma: a review
P. Boffetta 0
0 International Agency for Research on Cancer , Lyon , France
The epidemiology of peritoneal mesothelioma is complicated by possible geographic and temporal variations in diagnostic practices. The incidence rates in industrialized countries range between 0.5 and three cases per million in men and between 0.2 and two cases per million in women. Exposure to asbestos is the main known cause of peritoneal mesothelioma. Results on peritoneal mesothelioma have been reported for 34 cohorts exposed to asbestos, among which a strong correlation was present between the percentages of deaths from pleural and peritoneal mesothelioma (correlation coefficient 0.8, P < 0.0001). Studies of workers exposed only or predominantly to chrysotile asbestos resulted in a lower proportion of total deaths from peritoneal mesothelioma than studies of workers exposed to amphibole or mixed type of asbestos. Cases of peritoneal mesothelioma have also been reported following exposure to erionite and Thorotrast, providing further evidence of common etiological factors with the pleural form of the disease. The role of other suspected risk factors, such as simian virus 40 infection and genetic predisposition, is unclear at present. Control of asbestos exposure remains the main approach to prevent peritoneal mesothelioma.
The peritoneum is the second most frequent site of origin of
mesothelioma, after the pleura. In developed countries,
malignant mesothelioma (International Classification of Diseases
for Oncology?Morphology codes 9050?9055) is the most
frequent malignant neoplasm of the peritoneum [
of peritoneal mesothelioma are unspecific, the most frequent
being increased abdominal girth, pain and weight loss [
diagnosis occurs late. Treatment includes the combination of
debulking surgery and i.p. chemotherapy. Survival remains poor;
in the USA Surveillance, Epidemiology and End Results (SEER)
cancer registry data median survival is 10 months and relative
5-year survival is 16% [
], however, in selected clinical series
a longer survival (median >50 months) has been reported [
Although asbestos has been known for several decades to cause
peritoneal mesothelioma, in addition to the pleural form of the
], no detailed review of the epidemiological features of
this disease has been published recently.
The descriptive epidemiology of peritoneal mesothelioma is
complicated by temporal and geographic variability in
diagnostic criteria. In addition, low sensitivity and low
specificity of the diagnosis are important concerns, since
mesothelioma of the peritoneum can be misdiagnosed as
a neoplasm originating from other abdominal organs, notably
adenocarcinoma from the ovary, and vice versa [
Furthermore, sensitivity and specificity of the diagnosis may
vary by place and time, thus complicating geographic and
temporal analyses of the occurrence of the disease. Furthermore,
given the strong association between asbestos and
mesothelioma, knowledge of previous exposure might
influence diagnostic accuracy; if this is the case, a diagnosis
of peritoneal mesothelioma would be more frequently made
for a patient with recognized past asbestos exposure than for
a patient with a similar clinical presentation but without
history of asbestos exposure.
The consequences of these potential biases are difficult to
assess. Although it is likely that occurrence of peritoneal
mesothelioma is underestimated in most populations,
overestimation might occur in circumstances of recognized
asbestos exposure. In general, caution should be used in the
interpretation of the available data on the incidence and
mortality from this disease.
Recent international data on the incidence of peritoneal
mesothelioma are available from Eurocim, a collaboration of
European population-based cancer registries [
], and from the
SEER program of the United States [
]. Only sparse data are
available from the other countries. Figure 1 reports the most
recent data from selected nationwide European cancer registries
and the SEER registries; at this level of aggregation,
agestandardized incidence rates among men range from 0.5 to
about three cases per million population. However, higher rates
are reported in smaller areas with widespread past use of
asbestos, such as the harbor city of Genoa, Italy
(agestandardized rate in men in 1995, 5.5 per million). In most
populations, rates among women are in the range 0.2?2 per
million and are lower than in men; although in some countries,
such as Sweden, rates are comparable in the two sexes. A
correlation in incidence rates exists between the two sexes
(correlation coefficient of 1991?1995 rates on the basis of
41 European and nine USA populations covered by cancer
registry, 0.41; P = 0.003).
Figure 2 shows the temporal trend in peritoneal
mesothelioma incidence among men in selected countries [
Rates between 1971 and 1995 remained stable in Sweden and
United States (SEER), while they have increased in countries
such as Denmark and Scotland. The analysis of age-specific
rates provides a deeper insight in the pattern of disease
incidence, but it is feasible only in populations with a large
enough number of cases to provide meaningful results. Figure 3
shows such rates in England during 1971?1995 (men only);
a birth cohort effect is indicated, with the highest rates
experienced by men born between 1920 and 1930. A decline
in the last time periods is apparent among young men,
indicating that the overall incidence might decline in the
future. Age- and time-specific trends in women cannot be
adequately studied because of random variability.
In an analysis of 50 European and USA populations [
incidence rates of peritoneal mesothelioma in men were one
order of magnitude lower than those of pleural mesothelioma.
Rates of peritoneal mesothelioma among men showed only
a modest correlation with that of the pleural form of the disease
(Figure 4). A comparable analysis among women resulted in an
even weaker correlation (correlation coefficient 0.14, P value
0.32). The modest correlation between peritoneal and pleural
mesothelioma rates can be explained by differences in risk
factors (e.g. circumstances of exposure to asbestos), but can also
derive from bias in diagnostic and registration procedures.
exposure to asbestos
Data on the occurrence of peritoneal mesothelioma have been
reported for 34 cohort studies of workers exposed to asbestos
and asbestosis patients. The characteristics and key results of
these cohorts are summarized in Table 1. A formal analysis of
observed versus expected deaths (or cases) was presented in only
few studies, because of difficulties in obtaining reliable reference
rates. In order to provide some comparison between the
cohorts, we used the proportion of peritoneal mesothelioma
deaths over the total number of death as a measure of risk.
This approach ignores differences in the age structure of the
different study populations as well as temporal changes in the
underlying rates. However, it is a relatively good indicator of
the effect of an important determinant of the disease.
No peritoneal mesothelioma deaths were reported in 14 of the
34 studies; only two of these studies, however, comprised >1000
deaths, thus providing a reasonable power to detect a risk [
]. The proportion over total deaths ranged in most of the
remaining studies between 1/1000 and 1/100 (Table 1), with the
1 Gas mask manufacture Cr
2 Gas mask manufacture Ch
3 Gas mask manufacture Cr
4 Textile product manufacture P Ch
5 Cement workers P Ch
6 Cement workers Mixed
7 Friction product manufacture Ch
8 Insulation manufacture Am
9 Railroad repair workers Mixed
10 Textile product manufacture P Ch
11 Cement workers P Ch
12 Shipyard workers Mixed
13 Cement workers Mixed
14 Mixed exposure P Ch
15 Mixed exposure Mixed
16 Various product manufacture Am
17 Cement workers Ch
18 Cement workers P Ch
19 Vermiculite miners Tre-Act
20 Mixed exposure Mixed
21 Crocidolite miners Cr
22 Cement workers P Ch
23 Insulation workers Mixed
24 Shipyard workers P Ch
25 Miners Am, Cr
26 Railroad construction work Mixed
27 Textile product manufacture Ch
28 Miners Antho
29 Cement workers P Ch
30 Asbestosis patients Mixed
31 Cement workers Mixed
32 Various product manufacture Ch
33 Asbestosis patients Mixed
34 Cement workers P Ch
aPeriod of diagnosis.
Fiber type: Ch, pure chrysotile; P Ch, predominantly chrysotile; Cr, crocidolite (pure or predominant); Am, amosite (pure or predominant); Antho,
anthophillite; Tre-Act, tremolite-actinophyllite. Sex: M, males; F, females; MF, males and females; PM, predominantly males. Evidence: DC, death certificate;
CR, cancer registry; BE, best evidence (ad hoc investigation); MR, routine medical records. TD, total deaths; PlMD, pleural mesothelioma deaths; PeMD,
peritoneal mesothelioma deaths; LC SMR, standardized mortality ratio of lung cancer; NA, not available.
exception of cohorts of cement workers from Canada [
insulators from United States [
] and asbestosis patients from
] in which ?4% of total deaths were from peritoneal
mesothelioma. There was a strong correlation between the
percentage of peritoneal mesothelioma deaths and both the
percentage of pleural mesothelioma deaths (Figure 5) and the
standardized mortality ratio of lung cancer (not shown in detail,
correlation coefficient 0.85, P < 0.0001). The latter result
replicates the finding of a previous analysis of a smaller number
of cohort studies [
A higher proportion of studies of cohorts of workers exposed
to chrysotile (either as unique or as predominant fiber type)
reported no peritoneal mesothelioma deaths (nine of 15) as
compared with studies of cohorts of workers to amphiboles or
mixed fibers (four of 17; Table 2, column 3; chi-square test, P
value 0.04). The proportion of mesothelioma deaths over total
4 6 8
% pleural meso.
correlation coefficient 0.80, p<0.0001
deaths was higher in cohorts exposed to amphiboles or mixed
fibers than in cohorts exposed to chrysotile (Table 2), but the
difference was not statistically significant (P value after
aInformation on proportion of PMD available for 30 cohorts (see Table 1 for details), excluding cohorts with no PMD.
Two cohorts (number 19 and 28) excluded from the analysis.
NA, not applicable.
adjustment for geographic region, 0.09). It was not possible to
assess the effect of different types of amphibole fibers. Similar
conclusions were noticed in a previous analysis of a smaller
number of cohorts [
]. No effect of geographic region on the
proportion of mesothelioma deaths over total deaths was
detected [P value, on the basis of four regions (United States,
UK, Western Europe, other countries) and adjusted for asbestos
type, 0.9]. Only four studies were available of women (Table 1),
pre-empting detailed analyses. No difference was found in the
proportion of peritoneal mesothelioma deaths over total deaths
according to diagnostic accuracy (death certificate versus best
evidence, results not shown in detail). An effect of period of
employment was apparent, with the cohorts of workers first
employed before 1950 having a lower proportion of
peritoneal mesothelioma deaths over total deaths than
cohorts of workers employed later (P value after adjustment
for geographic region, 0.005). This finding might reflect
improved diagnostic accuracy during recent decades.
The dose?response relationship between occupational
asbestos exposure and peritoneal mesothelioma risk has been
investigated on the basis of the studies providing information
on quantitative asbestos exposure [
]. The risk of peritoneal
mesothelioma for workers exposed to amphiboles was
proportional to the square of cumulative exposure, while
a similar estimate could not be obtained for chrysotile-exposed
The important role of occupational exposure to asbestos in
causing peritoneal mesothelioma has been confirmed in two
community-based studies. A study from 24 of the United States
] included 657 death certificates with peritoneal cancer (not
specified as to histological type) as underlying cause recorded
during 1984?1992. The occupation listed on the death certificate
of these decedents (typically, the last occupation) was more
frequently a job-entailing exposure to asbestos than the
occupation of controls (deaths from other causes, matched
10 : 1 to cases). In particular, the odds ratio (OR) of peritoneal
cancer was 180 [95% confidence interval (CI) 23, 1375] for
insulation workers and 7.6 (95% CI 2.3, 25) for manufacturers
of nonmetallic mineral products, including asbestos. When the
authors applied a matrix for asbestos exposure on the basis of
the jobs listed on the death certificate, they found a strong
relationship with probability and intensity of exposure.
In a case?control study from Los Angeles and New York,
USA, 20 cases of (or deaths from) peritoneal mesothelioma
among men were compared with death certificate controls [
Interviews were conducted with next of kin. Exposure to
asbestos, either self-reported or derived from occupational
history, was present for 17 of the cases (OR 3.1, 95% CI 0.8, 15).
The fraction of peritoneal mesothelioma attributable to asbestos
exposure in this population was 58% (95% CI 20, 89).
Two studies provided evidence of an increased risk of
peritoneal mesothelioma following nonoccupational exposure
to asbestos. In a study from England, two cases of peritoneal
mesothelioma were reported in women with household
]. No cases were reported among individuals with
neighborhood exposure, while for seven cases, including three in
men, there was no evidence of occupational or environmental
exposure to asbestos. In a study from United States, eight cases
of peritoneal mesothelioma were reported among women
without occupational exposure; household exposure was
reported for seven of them and residential exposure for three,
including the case without household exposure [
]. In the
case?control study from Los Angeles and New York mentioned
above, no cases of peritoneal mesothelioma had residential
exposure to asbestos [
exposure to other mineral fibers
Erionite is a silicate fiber belonging to the family of zeolites [
An increased risk of pleural mesothelioma and lung cancer has
been reported among residents in a contaminated area from
Cappadocia, Turkey, in which no sources of asbestos exposure
were identified [
]. In particular, in a survey of 141 deaths
in four villages, during 1979?1983, 29 deaths from pleural
mesothelioma (20.5%) and four deaths from peritoneal
mesothelioma (3.5%) were identified [
]. In a study of 162
Cappadocian migrants to Sweden, one case of peritoneal
mesothelioma was identified [
There is no evidence of an increased risk of peritoneal
mesothelioma among workers exposed to man-made vitreous
], although the available studies do not have
a sufficient statistical power to detect a small increase in risk.
Three cohorts of patients receiving Thorotrast for radiological
examinations reported results on peritoneal mesothelioma risk
(Table 3). Although a formal estimate of the risk is complicated
by uncertainties in the calculation of expected deaths, these
patients experienced a cumulative incidence of peritoneal
mesothelioma between 0.2% and 0.6%, higher than that of
many cohorts of asbestos-exposed workers listed in Table 1. The
incidence of peritoneal mesothelioma among Thorotrast
patients was comparable with, or even greater than, that of
pleural mesothelioma. The deposition of a-particles in
abdominal organs adjacent to the peritoneum, such as the liver,
spleen and lymph nodes is a plausible explanation of these
findings. The time of appearance of peritoneal mesotheliomas in
the Danish cohort of Thorotrast patients was longer than that of
other cancers whose risk was also increased, such as liver and
lung cancer [
]. An additional three cohorts of Thorotrast
patients have been studied [
], but results for peritoneal
mesothelioma have not been reported. The evidence on the risk
of peritoneal mesothelioma following exposure to other sources
of ionizing radiation is limited to a few case reports, e.g. of
cancer patients who underwent radiotherapy [
other risk factors
A large number of studies detected sequences of the
papovavirus, simian virus 40 (SV40) in samples of pleural
]; however, the causal nature of this
association has been questioned [
], and laboratory
contamination may explain some of the findings [
]. In one
of these studies, 11 German cases of peritoneal mesothelioma
were also included, seven of which were positive for SV40 Tag
A possible role of chronic pancreatitis in peritoneal
mesothelioma has been indicated, but not formally evaluated
]. Genetic factors have been indicated to play a role in pleural
]. Very limited information is available on the
peritoneal form of the disease. In the case?control study from
Los Angeles and New York mentioned above, the mother of an
asbestos-exposed case of peritoneal mesothelioma was reported
to have suffered from the same neoplasm [
]. No studies are
available on other potential risk factors (e.g. nutrition).
The rarity of the peritoneal mesothelioma and its diagnostic
uncertainties limit our understanding of its epidemiological
features. Asbestos is the main known cause of the disease, but
other risk factors are likely to be involved in its etiology and
pathogenesis. Although the evidence is not conclusive, this
review of cohort and case?control studies indicates that the
association between asbestos exposure and peritoneal
mesothelioma is less strong than in the case of pleural
mesothelioma. This might explain the relatively low correlation
between the incidence of the two diseases. The other known risk
factors explain only a very small proportion of cases of
peritoneal mesothelioma. Despite these limitations, control of
exposure to asbestos, in particular at the workplace, remains the
main approach for the prevention of peritoneal mesothelioma.
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