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* From the MCP Hahnemann School of Medicine, Allegheny University of the Health Sciences, Philadelphia, PA.
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Abstract |
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 TOP Abstract IntroductionCohort Studies With Relevant...Lung Cancer Risk in...Association Between Asbestosis...Exposure-Response Relationship...DiscussionReferences |
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Key Words: asbestos • asbestosis • cohort studies • lung cancer • relative and attributable risk
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Introduction |
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TOPAbstractIntroductionCohort Studies With Relevant...Lung Cancer Risk in...Association Between Asbestosis...Exposure-Response Relationship...DiscussionReferences |
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In 1955, Doll2
published an important cohort study showing that the risk of lung cancer was substantially
elevated among asbestos textile workers in London. The cohort consisted
of 113 men exposed for 
20 years. Follow-up from 1922 to 1953
revealed 11 deaths from lung cancer compared with 0.8 expected based on
lung cancer mortality rates in England and Wales. All 11 cases were
confirmed by autopsy and all had asbestosis.
Most subsequent cohort studies have not included specific information on the relationship of asbestosis to the increased risk of lung cancer. Consequently, some investigators have espoused the concept that increased lung cancer risk can occur in the absence of asbestosis. Much debate has resulted over the hypothesis that excess lung cancer risk occurs only among those workers who develop asbestosis, some favoring the hypothesis3 ,4 ,5 ,6 and some opposing it.7 ,8 ,9 In this debate, there also has been a difference of opinion as to whether the issue is one of causation or one in which asbestosis should be considered a marker that predicts an increased risk of lung cancer and implies attributability.
This review will focus on the cohort studies that provide evidence bearing on the hypothesis. The restriction to cohort studies is based on the principle that risk can be measured only by the incidence or mortality rate. The literature reviewed was limited to articles published through January 1997.
Case-control studies were not considered because there are only a few and they are prone to more opportunities for bias than are cohort studies. They usually do not meet the requirement of two important assumptions inherent in the method: the cases should be representative of all cases of the disease under investigation and the controls should be representative of the population that gave rise to the cases. An example of this problem is a recent case-control study dealing with the issue at hand. Wilkinson et al10 studied a series of 271 patients with confirmed lung cancer admitted to a London chest disease hospital and 678 control subjects in the same hospital with other respiratory disease or cardiac disease. Such hospital-based series are not representative samples of lung cancer cases or the population giving rise to the cases. Other substantial flaws in this study were described by Jones et al6 in a thorough review of the literature bearing on the hypothesis being considered herein. Consequently, the conclusion by the authors that asbestos is associated with lung cancer even in the absence of radiologic evidence of pulmonary fibrosis is not warranted. Autopsy-based studies are subject to similar bias.
While observational cohort studies have some inherent potential for methodologic flaws, they represent the best available current technique for estimating risk of disease. Bias can be a problem, but the major concern is the control of potential confounders. Age and era are generally taken into account but smoking, the most common cause of lung cancer, has been evaluated in only a few studies and in a less than satisfactory way.
It has been suggested that asbestosis is an outcome independent of lung cancer in the response to exposure and that both diseases are associated only because both are dose related to exposure. This interpretation of the available data is speculative until it can be confirmed by valid investigation. In any case, the hypothesis considered herein implies only that asbestosis is a marker for increased risk of lung cancer.
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Cohort Studies With Relevant Data |
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TOPAbstractIntroductionCohort Studies With Relevant...Lung Cancer Risk in...Association Between Asbestosis...Exposure-Response Relationship...DiscussionReferences |
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Thus, there was a substantially elevated risk of lung cancer in the group with chest radiograph abnormalities other than small opacities. This may be due to the fact that Liddell and McDonald15 did not allocate individuals with abnormal radiographs to mutually exclusive categories. All these categories showed some elevation of risk and this may be due to contamination from two of the categories. First, 47 workers had large opacities; these are not characteristic of people exposed to asbestos and at least some of the large opacities represented lung cancer since the relative risk of lung cancer was very high, 20.7. Second, 218 workers had films classified under "additional symbols" in the International Labor Organization (ILO) form for classification of chest radiographs for dust diseases of the lung; this is a miscellaneous category likely to include obvious or suspected lung cancer.
Furthermore, the interval between termination and death from lung
cancer varied markedly. Only 41% had an interval of < 5 years, in
29% it was 10 years, and in 17% it was 20 years. Becklake et
al16
reported a study of 277 Quebec miners and millers
followed from a survey, which occurred in 1967 and 1968 and was
followed-up in 1974. Chest radiographs were evaluated independently by
three readers. Of those with no parenchymal abnormality in the first
radiograph, 17 to 38% were read as showing parenchymal abnormality in
1974 (interreader variation). Consequently, in the mortality
study,15
there was ample opportunity for the workers to
develop parenchymal disease prior to death from lung cancer.
In 1991, Hughes and Weill17
published the results of a
cohort study in which 642 men employed in two asbestos cement plants
were followed up from 1969, when chest radiographs were taken, through
1983. The analysis was controlled for age, cigarette smoking, and
asbestos exposure. Mortality was examined 20 years after hire. The
radiograph assessment was made independently by three experienced
readers who were blind to the exposure history. They used the 1971 ILO
classification. The median reading was used in the analysis.
Their findings are presented in Table 5
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The only group with a statistically significant increase in the risk of
lung cancer was composed of 77 workers with small irregular opacities
(SIOs) in a profusion of 1/0: SMR of 4.29.
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Lung Cancer Risk in Cohorts With No Deaths due to Asbestosis |
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TOPAbstractIntroductionCohort Studies With Relevant...Lung Cancer Risk in...Association Between Asbestosis...Exposure-Response Relationship...DiscussionReferences |
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SMRs ranged from 0.79 to 1.37 (Table 8 ). The only SMR that was statistically significantly elevated above 1.00 was reported by McDonald et al20 in 1984. This dealt with a chrysotile friction products plant. I excluded short-term workers with < 1 year of employment because the authors were puzzled by "the fact that the only subcohort with SMRs clearly above expectation comprises men employed for less than one year." The SMR for this group was 1.80, higher than any other subcohort stratified by duration of employment. This phenomenon has been noted by others.25 Furthermore, there was no gradient of the SMRs in the remaining subcohorts nor was there a dose-response trend with increasing cumulative dust exposure.
The summary SMR for all seven cohorts (Table 8 ) was exactly 1.00. This finding implies that if the asbestos exposure was not sufficient to cause any deaths from asbestosis, there is no increased risk of lung cancer. A further implication is that there is an exposure threshold for asbestos-related lung cancer as discussed by Browne,26 a point that will be considered later in this review.
There are also cohort studies of people who have pleural plaques but no asbestosis with regard to lung cancer risk. In 1993, I reviewed six such studies.27 Two of them reported overlapping data from the same shipbuilding city, Barrow in England. These two were seriously flawed because the authors could not obtain permission to carry out a cohort study of all employees with pleural plaques. None of the remaining four studies had a statistically significant increase in the SMRs for lung cancer. The summary SMR for these four studies was 1.01 (95% CI, 0.75 to 1.33).
In 1994, Hillerdal28 reported an additional study of people with only pleural plaques. The cohort was derived from periodic chest radiographic surveys of a Swedish community with a population of about 250,000. The surveys were done in 1970 to 1985 and follow-up was maintained to the end of 1991. The participation rate was 70% in the age group of 40 to 69 years. Unfortunately, the authors included in the cohort of 1,596 men a group of 246 (15.4%) men in whom plaques were discovered by accident during "investigation for some other reason" so there was a potential source of bias. After excluding those men who developed radiographic evidence of asbestosis, the SMR was 1.4 (95% CI, 1.04 to 1.97) after adjustment for smoking habits. In the age group 40 to 69 years, the relative risk (RR) was 1.29 (95% CI, 0.88 to 1.68), not statistically significant. In view of the potential bias mentioned above, interpretation of the relative risk is uncertain.
Tola et al29 studied cancer incidence in 12,693 shipyard and machine shop male workers who were employed at least 1 year during the period 1945 to 1960 in Finland. Almost all shipyards were first built in 1945. Follow-up was carried out through the national cancer registry for 1953 to 1981 and 99.7% of the workers were traced. In a group of 4,582 shipyard welders and platers, none was diagnosed as having asbestosis. Indirect evidence indicated that asbestos exposure had not been high in Finnish shipyards. The standardized incidence ratios were not statistically significantly elevated for lung cancer among workers in these jobs: 1.15 (95% CI, 0.76 to 1.67) for welders and 1.16 (95% CI, 0.95 to 1.41) for platers.
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Association Between Asbestosis Rates and Excess (or Deficit) Lung Cancer Rates |
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TOPAbstractIntroductionCohort Studies With Relevant...Lung Cancer Risk in...Association Between Asbestosis...Exposure-Response Relationship...DiscussionReferences |
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The analysis was restricted to the latest report on each cohort with the requirement that at least 90% of members be traced. When there were data by sex and occupation, each group was tabulated as a separate cohort, eg, men, women, construction work, mining, etc. All studies used mortality as the outcome measure except for the incidence study by Tola et al.29 In the mortality studies, asbestosis was the underlying cause of death. In the incidence study by Tola et al,29 the authors stated that there were no diagnoses of asbestosis. There was a total of 38 cohorts analyzed in 30 reports.18 ,19 ,20 ,21 ,22 ,23 ,24 ,29 ,30 ,31 ,32 ,33 ,34 ,35 ,36 ,37 ,38 ,39 ,40 ,41 ,42 ,43 ,44 ,45 ,46 ,47 ,48 ,49 ,50 ,51
Table 9 shows the data for the 38 cohorts. The first eight are those in which there were no deaths from or diagnosis of asbestosis and they are listed alphabetically by last name of the first author. The remaining cohort studies are also listed alphabetically by last name of the first author. It should be noted that the article by Peto et al21 is listed with those cohorts having deaths from asbestosis in Table 9 while a subcohort of workers employed < 10 years appears in Tables 6 –8 because there were no deaths from asbestosis in the subcohort. In addition, the male and female cohorts studied by Gardner et al22 were studied separately in Table 9 but combined in Tables 6 –8 .
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Figure 1 is a scattergraph of data for each cohort recorded in Table 9 . The cumulative excess (or deficit) lung cancer rate is regressed on cumulative asbestosis rate for all 38 cohorts. The linear correlation coefficient was 0.74 and this was statistically highly significant. The intercept was not statistically significantly different from a zero excess lung cancer rate.
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The study by Newhouse et al45
is of particular interest
because there were six subcohorts numbering 512 to 1,369 workers (Table 10 ).
Four subcohorts of male factory workers were stratified
semiquantitatively by degree (light and severe) and duration (
2
years and > 2 years) of asbestos exposure. It should be noted that
the small excess lung cancer death rate in the male factory workers
with light/moderate exposure for 2 years is not statistically
significantly different from no excess (see third footnote). The other
two categories consisted of laggers and female factory workers without
information on degree and duration of exposure. Figure 2
is a scattergraph of cumulative excess lung cancer death rate plotted
against cumulative asbestosis death rate for the six groups. The four
male factory subcohorts are represented, from left to right, by the
first three points and the last one. For these four points, the linear
correlation coefficient is 0.99. The points for the laggers and female
factory workers (fourth and fifth points) were close to the regression
line for all six sets of data; the correlation coefficient was 0.98,
statistically highly significant, and the intercept was not
significantly different from a zero excess lung cancer rate.
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Exposure-Response Relationship for Lung Cancer |
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TOPAbstractIntroductionCohort Studies With Relevant...Lung Cancer Risk in...Association Between Asbestosis...Exposure-Response Relationship...DiscussionReferences |
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Steenland et al54 have pointed out that in recent years there has been increasing study of internal markers (biomarkers) as indexes of internal dose of disease-causing agents. Not everyone who is exposed to a carcinogen develops cancer attributable to the carcinogen. An internal marker may be a better predictor of cancer risk than a measure of external exposure. Steenland et al54 noted the well-known observation that cohorts of asbestotics usually have higher lung cancer risks than cohorts of asbestos-exposed workers for which there is no stratification by the presence or absence of asbestosis. They reviewed some of the relevant literature and concluded that the presence or absence of asbestosis is a better predictor of lung cancer risk than the level of asbestos exposure.
In the previous section of this review, analysis of the cohort literature showed a strong association between asbestosis and lung cancer on a group basis in 38 cohorts. To compare the strength of the association between external exposure to asbestos and lung cancer risk, the literature is much more limited.
Lash et al55 recently published a meta-analysis of the relation between cumulative asbestos exposure and the relative risk of lung cancer in 15 cohorts. They found substantial heterogeneity in the exposure-response relationship. Sources of heterogeneity included not only exposure measurement but also industry category, smoking habits (where available), and standardization procedures.
The cumulative exposure units used in the various cohorts were based by the original authors on dust counts in million particles per cubic foot (mppcf) in some reports and on fiber counts (f/mL) in other reports. Lash et al55 used three conversion factors to convert mppcf to f/mL; the conversion factors differed by type of industry.
For the purpose of plotting exposure-response curves, I limited the cohorts in the review by Lash et al55 to eight that provided data on at least five exposure strata in the latest publication available. There were seven articles for the eight cohorts.20 ,21 ,38 ,40 ,56 ,57 ,58
For a textile plant in Charleston, SC, Lash et al55 used a 1994 report by Dement et al. so I used this one also in this analysis; in Table 9 I used a 1994 article by Brown et al33 presenting essentially the same data. For the Quebec miner and miller cohort, Lash et al55 used two nonoverlapping reports by McDonald et al.18 ,41 I also used these in Table 9 that I prepared before publication of the latest comprehensive report on this cohort by Liddell et al.58 The latter article was used for analysis in this section. Thus, the seven reports utilized in this section include my references 20, 21, 38, 40, and 56 to 58, as noted above.
Three articles used by Lash et al55 were excluded for the following reasons: Henderson and Enterline59 dealt only with retirees and two reports by Seidman et al49 ,60 on an amosite factory cohort relied on estimates of exposure from another amosite factory owned by the same company but established elsewhere in the United States after the factory reported on was closed.
The eight cohorts included in this analysis provided 42 pairs of data. Lung cancer SMR was plotted against cumulative asbestos exposure in fiber/mL-years provided by Lash et al.55 The resulting scattergraph is not shown here. There was no correlation between the two variables. The correlation coefficient was 0.036 (p > 0.80).
The individual exposure-response curves are shown in Figures 3 ,4 ,5 . Figure 3 shows the curves for four cohorts of workers engaged in manufacture of asbestos cement and friction products. In two plants reported by Hughes et al,38 plant 1 showed no exposure-response relationship while in plant 2 the curve indicated a small elevation of risk. The cohort reported by A. D. McDonald et al20 showed no exposure-response relationship. In sharp contrast, the cohort reported by Finkelstein56 showed a curve with a very strange shape. This deserves further comment.
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Figure 4 shows the exposure-response curves for three asbestos textile plants.21 ,40 ,57 All curves indicate an exposure-response relationship but there is substantial variation in the slopes. The SMR for the South Carolina plant57 reached a height of 8.33 at a median cumulative exposure of 215 f/mL-years in contrast to 4.16 at 168 f/mL-years at the Pennsylvania plant and 2.22 at 259 f/mL-years at the London plant.
Figure 5 shows the lung cancer SMR curve for the 1997 report on the Quebec miner and miller cohort.58 It should be noted that the exposure levels are much higher for this cohort than for the other seven cohorts: the maximum SMR was only 2.97 at a cumulative exposure of 4,200 f/mL-years. This curve is of particular interest because the cohort was one of the largest reported in the literature. Of special note is the observation that the lung cancer SMRs at the three lowest cumulative exposure levels are low and irregular: 1.13 at 45 f/mL-years, 1.38 at 195 f/mL-years, and 1.21 at 450 f/mL-years. For these three strata combined, the SMR was 1.21. Liddell et al58 said that this small elevation in the low exposure range was probably due to cigarette smoking.
Smoking habits were collected for cohort members who were alive in
1976. Dr. Liddell kindly supplied the age distribution of the cohort in
that year and the percent distribution by smoking habit in each age
group (personal communication, May 1997). The prevalence of current
cigarette smoking was 66.2% in the age group 56 to 65 years and 46.5%
in the age group 66 years. Somewhat similar data were obtained for
Quebec men in 1975,61
giving prevalences of 55.8% for age
group 45 to 64 and 37.4% for age group 65 years. These figures
were used to calculate the ratio of observed to expected prevalences in
the Quebec cohort: 1.21, identical to the SMR of 1.21 described above
and thus confirming the opinion of Liddell et al58
that
cigarette smoking accounts for the small increase in lung cancer risk
in the first three exposure categories.
This observation supports the concept of a threshold for lung cancer risk, especially since 72% of the 587 lung cancer deaths occurred at these low cumulative asbestos exposure levels.
The exposure-response curve for the asbestosis mortality rate was plotted in Figure 5 in terms of the number per 100,000 person-years. The curve rises very smoothly from the very lowest to the highest exposure category, suggesting that there is a much lower threshold, if any, for asbestosis deaths than for lung cancer deaths. The rates rise from 12 to 399 per 100,000 person-years. Above a median exposure of 450 f/mL-years, the curves for lung cancer and asbestosis are almost identical. The two curves are based on disease measures that are not the same for lung cancer as for asbestosis. Nevertheless, the correlation is remarkable.
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Discussion |
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TOPAbstractIntroductionCohort Studies With Relevant...Lung Cancer Risk in...Association Between Asbestosis...Exposure-Response Relationship...DiscussionReferences |
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The literature also contributes support for the hypothesis in two other lines of investigation: animal research and epidemiologic studies of lung cancer risk in other diseases characterized by diffuse pulmonary fibrosis.
To my knowledge, there is only one animal study that provides direct evidence on the issue: an extensive investigation by Wagner et al.62 They exposed rats to various types of asbestos by inhalation. Animals are ordinarily exposed to asbestos in high concentrations, but Wagner et al62 varied the duration of exposure. One group of 201 rats was exposed for only 1 day and examined after survival for at least 600 days. Forty-four (22%) developed asbestosis and 11 (25%) of these 44 were found to have pulmonary tumors. The remaining rats without asbestosis had a tumor rate of 3.8% (6 of 157). A group of 126 control rats who survived at least 300 days had a tumor rate of 5.6%. While the data supplied specified different criteria for minimal survival time, the mean survival time was identical in exposed and control rats: 784 days in the 201 exposed rats and a total of 154 unexposed rats.
Among the 17 tumors in the exposed rats, 3 were adenocarcinomas and 14 were adenomas. The International Agency for Research on Cancer has established the principle that benign tumors are the result of exposure to carcinogens when they occur with malignant tumors of the same cell type in the same organ.63 In the Wagner et al62 study, exposures of 1 day produced three adenocarcinomas (their Table 7 ). In addition, there were two rats with mesothelioma.
An increased risk of lung cancer has been observed in humans with other diseases manifesting diffuse pulmonary fibrosis. Restricting the literature to cohort studies with estimates of RR for lung cancer leaves only a few reports to consider.
In 1980, Turner-Warwick et al.64 reported on 205 cases of cryptogenic fibrosing alveolitis seen at the Brompton Hospital in London between 1955 and 1973. These were followed-up for 4 to 21 years and 20 (9.8%) died from lung cancer; all but 2 of the 20 were smokers. The expected number of lung cancer cases was calculated from general population death rates by age and sex. The RR was 14.1, statistically highly significant. Four of the lung cancers were suspected by chest radiograph at the time of first hospital attendance (prevalence cases) while the rest were incidence cases; subtracting the prevalence cases gives an RR of 11.3, still statistically highly significant.
Two cohort studies reported in 1985 showed increased lung cancer risk among patients with systemic sclerosis (scleroderma). Peters-Golden et al65 followed-up 71 patients, diagnosed in 1972 to 1979 at a Baltimore hospital, until 1982 to 1983 and found 3 cases of lung cancer. The expected number was derived from the Surveillance, Epidemiology, and End Results (SEER) cancer registry rates for 1973 to 1977.66 The RR was 16.5, statistically highly significant. Two were nonsmokers. Two had radiographic evidence of pulmonary fibrosis and the other, a nonsmoker, had restrictive disease by pulmonary function testing.
Roumm and Medsger67 followed-up 262 patients diagnosed at the University of Pittsburgh in 1971 to 1982 and living in the Pittsburgh standard metropolitan statistical area (SMSA). The mean duration of follow-up was 4.3 years and this institution ascertained approximately 80% of the cases in the SMSA. Expected numbers of lung cancer were calculated from the Third National Cancer Survey (1975) adjusted by age and sex to the SMSA population. There was a 23% loss to follow-up but the lost ones were similar to those with complete follow-up. There was a statistically significant RR for lung cancer of 4.4 based on four cases; all were smokers and had pulmonary fibrosis by radiograph.
While the numbers of lung cancers in these two studies are small, the RRs are high and consistent with the findings at the Brompton Hospital.64 The possibility of selection bias, however, cannot be ruled out in hospital-based cohorts.
The disparity between asbestosis and cumulative asbestos exposure as predictors of excess lung cancer risk is striking. The poor consistency of fiber counts as predictors in various cohort studies may be due to a number of uncertainties. The fiber counts were generally derived from area samples rather than from individual personal samples. Conversion factors used to estimate historical fiber counts from total dust counts prior to the 1970s are of questionable validity. Variation in fiber dimensions, geometry, chemistry, integrity, and durability makes fiber counts problematic in the causation of disease as the only measure of exposure in different industrial environments. For these reasons, there is doubt about the relationship between exposure measurements and the effective dose actually delivered to the target tissues. In addition, variation in host factors and other environmental exposures may be confounding in the exposure-response relationship.
Another problem lies in the use of cumulative exposure estimates. Such estimates are derived from combining measures of intensity and duration of exposure. In the exposure-response curves shown in Figures 3 ,4 ,5 for the individual cohorts, some of the curves do show increase in lung cancer SMRs with increasing cumulative exposure. However, McDonald et al41 pointed out that "It has become increasingly evident that the linear relations that have been found between SMRs and cumulative exposure are an oversimplification." They indicated that there is a need to assess "the separate and combined effects of duration and intensity of exposure to asbestos, with appropriate allowance for a number of time related variables, and with due regard to cigarette smoking."
In particular, it should be recognized that duration of exposure overlaps the latency period of asbestos-related disease and this may create artificial linearity in the exposure-response relationship. Vacek and McDonald68 used multivariate RR models, which do not assume that exposure intensity and duration have equal effects on risk, to study lung cancer data from a cohort of vermiculite miners exposed to tremolite. The exposure-response pattern was S-shaped and differed substantially from the pattern using a cumulative exposure index.
It is well established that lung cancer among asbestos-exposed workers is unusual in the absence of cigarette smoking and that the exposure to both agents has a more than additive effect on the risk of lung cancer.69 This may be partially explained by increased retention of asbestos fibers in the airways of smokers.70 Cigarette smoking provides an additional link between asbestosis and lung cancer. There is evidence that smoking alone causes pulmonary interstitial fibrosis at a microscopic level and some evidence that this may be discernible as SIOs radiographically.71 The latter idea has been disputed with the suggestion that the SIOs associated with smoking may represent other pathologic findings such as bronchiolar wall thickening or an appearance created by emphysematous changes. The lack of adequate radiographic-pathologic studies makes interpretation of the radiographic changes uncertain.71 ,72 ,73 ,74 In any case, the SIOs in smokers are generally of minimal degree, largely limited to profusions of 0/1 and 1/0.73
However, there is more general agreement in the literature that smokers exposed to asbestos are at higher risk of developing radiographic evidence of asbestosis than are nonsmokers.74 ,75 Thus, smoking is a factor in determining which asbestos-exposed individuals are diagnosed as having asbestosis and therefore is an effect modifier of the relationship between asbestosis and lung cancer risk.
However, there are more basic mechanisms that link the two diseases together. These have been elucidated by tissue, cellular, and molecular investigations.76 ,77 ,78 Although the validity of extrapolation from such experimental research to explain human disease is uncertain, pathogenetic models may be constructed to improve our understanding.
Recent investigations indicate that inflammation is linked to neoplasia through several mechanisms after exposure to asbestos. Partial ingestion of long fibers by macrophages activates these cells to release substances such as lymphokines, growth factors, active oxidants, and proteases. Some of these may be genotoxic and others may cause cell proliferation.79 The latter increase opportunities for errors to occur during DNA replication, leading to malignant change and limiting repair of DNA damage induced by mutagens. Tissue culture studies have shown that bronchial epithelial cells ingest asbestos fibers. Asbestos fibers may adsorb polycyclic aromatic hydrocarbons (eg, those in cigarette smoke) and thus induce the aryl hydrocarbon hydroxylase system to produce metabolites that can interact with DNA. In addition, asbestos causes chromosomal abnormalities in mammalian cell systems.
Mossman78 has suggested two caveats concerning the interpretation of the above experimental results: (1) there is a lack of dose-response studies, and (2) comparative studies using both positive and negative controls are limited. Nevertheless, the results suggest a close link between bronchial cancer and the preceding inflammatory reaction to asbestos. This link is consistent with the hypothesis that lung cancer risk is elevated only in humans exposed to asbestos when there is asbestosis. That the increased risk is limited to those with radiologic evidence of asbestosis is supported by the available good epidemiologic evidence summarized in this review. More studies of greater magnitude are desirable, including cohorts with serial chest radiographic surveillance and histologic confirmation if possible.
The importance of the issue is both academic and medicolegal. Assuming that the resources available for the compensation of asbestos-exposed workers with lung cancer are limited, fairness would be enhanced by diverting funds from those with no increased risk of lung cancer to those who are at increased risk. The RR for lung cancer is so variable in the cohort studies reported that the attributable risk ranges from zero to a substantial proportion of the workers. A reliable marker for increased risk is therefore needed and asbestosis seems to satisfy this need.
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Footnotes |
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Correspondence to: William Weiss, MD, 3912 Netherfield Rd, Philadelphia, PA 19129-1014
Abbreviations: CI = confidence interval; f/mL = fibers per milliliter; mppcf = million particles (dust) per cubic foot; RR = relative risk; SIO = small irregular opacities; SMR = standardized mortality (or morbidity) ratio; SMSA = standard metropolitan statistical area
Received for publication December 23, 1997. Accepted for publication August 5, 1998.
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TOPAbstractIntroductionCohort Studies With Relevant...Lung Cancer Risk in...Association Between Asbestosis...Exposure-Response Relationship...DiscussionReferences |
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