Asbestos Selected Cancers (2006) / Chapter Skim
Currently Skimming:
2 Committee’s Approach to Its Charge and Methods Used in Evaluation
2 Committee’s Approach to Its Charge and Methods Used in Evaluation
Pages 18-48
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 18... ...
There are now wellestablished models for meeting the charge, dating as far back as the landmark 1964 report of the US surgeon general on smoking and health (HEW 1964) , which reached the conclusion that smoking causes lung cancer and other diseases.
|
From page 19... ...
. The association of asbestos with mesothelioma constitutes one of the few examples of a high degree of specificity for a toxic agent and cancer risk, but the committee gave minimal weight to the criterion of specificity because the cancer sites under consideration have multiple causes and more will likely be identified.
|
From page 20... ...
Because the legislation mandating this committee's review requested only a determination of whether asbestos played a causal role in inducing these additional types of cancer, it was the committee's judgment that insertion of an additional category for evidence more weakly supportive of causation would unnecessarily generate another, most probably arbitrary distinction in classifying the evidence below the threshold for causal inference. Therefore, the committee adopted the four-category scheme of the recent US surgeon general's report on smoking and health (HHS 2004)
|
From page 21... ...
For investigating such effect modification, information is needed on both asbestos exposure and smoking; this requirement is met by some studies, most often of a case-control design. A recent evaluation of the evidence concerning effect modification by smoking on the risk of lung cancer associated with asbestos exposure by the International Agency for Research on Cancer (IARC 2004)
|
From page 22... ...
, but much of it exclusively addresses asbestos's role in causing asbestosis, lung cancer, and mesothelioma. Given the committee's circumscribed task of answering the question of whether this known carcinogen plays a causal role in producing pharyngeal, laryngeal, esophageal, stomach, or colorectal cancer ("selected cancers")
|
From page 23... ...
We sought to gather a comprehensive set of citations concerning the asbestos cohorts, but to limit procurement of hard copies to articles most relevant to our mission -- the most recent or comprehensive publications on a given cohort and articles specifically addressing the five selected cancers, asbestos exposure, or distribution of asbestos fibers to tissues. All citations related to a given study population were grouped on a spreadsheet to characterize the cohort and how it had been researched over the years.
|
From page 24... ...
A comprehensive dataset on all asbestos's potential health effects was not being sought, but a wide net was cast by retrieving copies of reports involving the selected cancer sites that might address asbestos exposure specifically and of asbestos-exposed cohorts that might present information on the selected sites of this review along with data on the health outcomes that are now accepted to be asbestos related. The committee limited the epidemiologic results in its evidentiary database to findings of appropriately designed cohort and case-control studies.
|
From page 25... ...
CRITERIA FOR EVIDENCE EVALUATION Fiber Type The committee recognized that there is evidence suggesting that the risk associated with asbestos exposure for development of mesothelioma (and possibly of lung cancer) may vary by fiber type.
|
From page 26... ...
In many epidemiologic studies that have examined the association of asbestos with the cancers of interest in this report, sites have been grouped into various categories to allow statistical analyses of rather sparse data, even when cancers at the subsites have very different etiologies. Optimally, one would consider the evidence concerning these cancers in groupings that reflect generally similar etiology, but extracting what information is available from epidemiologic studies conducted over the last half century under circumstances of evolving understanding of biologic mechanisms and epidemiologic analysis make this objective unattainable.
|
From page 27... ...
COMMITTEE'S APPROACH AND METHODS USED 27 TABLE 2.1 Standard Codes and Nonstandard Groupings Used to Characterize "Accepted" and "Selected" Cancers ICD-9 ICD-O-3 (for mortality) (for incidence)
|
From page 28... ...
Study Designs Epidemiologic designs applied in investigations of environmental and occupational risk factors for cancer are primarily of three types: cohort studies of defined groups (such as worker populations) , case-control studies, and "ecologic" studies that compare rates in geographic regions defined by exposure characteristics.
|
From page 29... ...
The committee does not view either the case-control or cohort design as being intrinsically preferable or stronger than the other, and does not believe one type should be weighted more heavily than the other. Consideration of the results from both types of design permits viewing the realworld outcomes available for observation by epidemiologists from two different perspectives, with studies of samples defined on the basis of exposure (cohort studies)
|
From page 30... ...
In contrast with cohort studies, it is not feasible to assess asbestos exposure quantitatively in casecontrol studies using actual measurement data. The most useful casecontrol studies are those that assign a magnitude or probability of exposure (on an ordinal basis)
|
From page 31... ...
The committee adopted a pragmatic approach in order to assess whether classifying a given study population along even a crude exposure gradient would yield evidence for a dose-response relationship between asbestos exposure and risk. The committee recognized limitations of the data available for this purpose and was not seeking accurate quantitative estimates.
|
From page 32... ...
The validity of mortality as an indicator of cancer incidence also depends on the accuracy of both identification of cause of death and its coding. Undoubtedly, there was some degree of misclassification in the assignment of cause of death in the cohort studies considered.
|
From page 33... ...
Confounding Bias Many occupational cohort studies compare disease rates between a worker cohort and the general population. Although comparisons of this type give some indication of overall patterns of relative disease occurrence
|
From page 34... ...
For example, tobaccosmoking and alcohol-consumption patterns, known risk factors for laryngeal cancer, may be quite different between blue-collar industrial workers who are exposed to asbestos and the general population, which includes people from all socioeconomic classes. Contrasts in laryngeal-cancer incidence between a worker cohort and the general population might thus be confounded if smoking is not taken into account.
|
From page 35... ...
For cohort studies, precision of the estimated effects (and therefore power to test hypotheses) is driven primarily by the expected number of events, which is a function of person-years of follow-up and incidence.
|
From page 36... ...
METHODS USED FOR QUANTITATIVE META-ANALYSIS The units of input for the meta-analysis on each selected cancer site were the most complete risk estimates available on discrete study populations. A single citation could therefore generate more than one datum (such as separate results for men and for women)
|
From page 37... ...
In both the case-control and cohort studies, a subset of studies reported RRs across a gradient of exposure; these were used to summarize the effects of "high" exposure to asbestos. Because the definition of high exposure differed by study, we knowingly summarized RRs over an array of definitions.
|
From page 38... ...
would not be affected by a study's thoroughness in determining exposure gradients. Therefore, unlike what was done for case-control results, the cohort results for "any exposure" were not stratified on how exposure quality was measured in the overall study (in which detailed exposure characterization was most often derived TABLE 2.2 Organization of Summary Plots Used for Cohort Studies Informative for Cancer at Each Site Plot Type of RR Studies Included 1 Any vs none All 2 Most extreme vs none (If more than one Studies reporting RR on a gradient gradient reported, aggregates calculated with smallest and with largest reported RRs)
|
From page 39... ...
We view the resulting summary as being robust to variability in the metrics and scales used to report exposure gradients. Computational Conventions Used for Plot Summaries of Cohort Studies The RR for a cohort study is the ratio of observed to expected events (for example, observed deaths divided by expected deaths)
|
From page 40... ...
Table 2.3 summarizes the organization of plots for the case-control studies at each cancer site. As with the cohort studies, for each of the plots described here, a 95% CI for the weighted average of the RRs is given below the individual study values.
|
From page 41... ...
For other sites, the small number of studies did not permit similar stratification. The second set of plots characterizes extreme exposure vs none with data from those studies that reported exposure effects on a gradient; we used the same approach applied to cohort studies.
|
From page 42... ...
Cohort Studies In a cohort study, the number of observed events (such as observed deaths) can be assumed to follow a Poisson distribution with the mean equal to the expected number of events in the absence of an exposure effect (such as, expected number of deaths)
|
From page 43... ...
j Wj INTEGRATION OF DATA Previous evaluations of specific agents or exposures as contributing to an increased risk of cancer have been conducted by expert panels convened by national and international agencies. The expert panels review, evaluate, and integrate the scientific evidence based on three sources of information: epidemiologic studies of cancer in humans, studies of cancer in experimental animals, and biologic mechanistic data.
|
From page 44... ...
Exposure Data and Epidemiologic Evidence The committee considered the geographic distribution, commercial applications of asbestos fibers, and exposure data from occupational and environmental sources. The quality of exposure data and the demonstration of dose-response relationships in human epidemiologic studies were major considerations in evaluating the studies.
|
From page 45... ...
The committee evaluated the overall strengths and weaknesses of the scientific evidence based on human epidemiologic studies, animal studies, and biologic mechanistic studies. It then integrated all this information before reaching a conclusion regarding the strength of the evidence for a causal association between asbestos exposure and an increased risk of cancer at each site under consideration.
|
From page 46... ...
1994. A meta-analysis of colorectal cancer and asbestos exposure.
|
From page 47... ...
1981. Accuracy of cancer death certificates and its effects on cancer mortality statistics.
|
From page 48... ...
2003. An asbestos job exposure matrix to characterize fiber type, length, and relative exposure intensity.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.