Coding malignant mesothelioma

The association of malignant mesothelioma (MM) and nonoccupational asbestos exposure is currently debated. Our study investigates environmental and domestic asbestos exposure in the city where the largest Italian asbestos cement (AC) factory was located. This population-based case-control study included pleural MM (histologically diagnosed) incidents in the area in 1987-1993, matched by age and sex to two controls (four if younger than 60). Diagnoses were confirmed by a panel of five pathologists. We interviewed 102 cases and 273 controls in 1993-1995, out of 116 and 330 eligible subjects. Information was checked and completed on the basis of factory and Town Office files. We adjusted analyses for occupational exposure in the AC industry. In the town there were no other relevant industrial sources of asbestos exposure. Twenty-three cases and 20 controls lived with an AC worker [odds ratio (OR) = 4.5; 95% confidence interval (CI), 1.8-11.1)]. The risk was higher for the offspring of AC workers (OR = 7.4; 95% CI, 1.9-28.1). Subjects attending grammar school in Casale also showed an increased risk (OR = 3.3; 95% CI, 1.4-7.7). Living in Casale was associated with a very high risk (after selecting out AC workers: OR = 20.6; 95% CI, 6.2-68.6), with spatial trend with increasing distance from the AC factory. The present work confirms the association of environmental asbestos exposure and pleural MM, controlling for other sources of asbestos exposure, and suggests that environmental exposure caused a greater risk than domestic exposure. Key words: asbestos, asbestos cement, environmental exposure, pleural mesothelioma. Environ Health Perspect 109:915-919 (2001). [Online 23 August 2001]

http://ehpnet1.niehs.nih.gov/docs/2001/109p915-919magnani/abstract.html

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Malignant mesothelioma (MM) is associated with all types of asbestos, with higher risk for amphiboles (1). Beyond the well-known association with occupational exposure (2), an increased risk was found for domestic exposure (3,4) as well as for residence near asbestos factories (3) and mines (5,6). Epidemics of MM also occurred near naturally occurring deposits of asbestiform fibers and their use in whitewash and stucco (7-10).

Evidence relating MM to environmental (nonoccupational) exposure to asbestos, however, was not considered convincing in a recent review (11). Further information is expected from epidemiologic studies in areas where the risk from different sources of asbestos exposure can be disentangled and compared. One of these areas is Casale Monferrato (northwest Italy), a medium-size town where a large Eternit asbestos cement (AC) factory had been active from 1907 to 1985. Our original studies on mortality of workers (12) have been expanded to their wives (13) as well as to estimates of the incidence of MM in the general population (14). Rates were up to 10 times higher than those in other industrial areas of Northern Italy served by a cancer registry.

A case-control study conducted in 1995-1997 in several areas in Italy (including Casale), Spain, and Switzerland was the first to estimate the risks for MM from nonoccupational asbestos exposure (15). Here we present the results of another study in the area of Casale, performed independently of the previous one and based on more individual data than was feasible in the international project. There is no overlapping between the present database and that used in the previous study.

Materials and Methods

The factory and the town. The size of the work force varied over time and never exceeded 1,500 workers. In 1981 the company reported the use of 15,000 tons of asbestos (10% crocidolite) (12). The factory is upwind from the town, at about 1,500 m from the center and 250 m from the closest residential areas. Its products were used largely in Casale. Environmental asbestos concentration was measured only shortly before the factory shutdown and afterward. Estimates reported here are the average of repeated measurements and, if not otherwise specified, are limited to airborne asbestos fibers (AF) with length > 5 [micro]m and diameter > 0.3 [micro]m. Marconi et al. (16) in 1984 reported between 11 AF/L close to the plant and 1 AF/L in the city area farthest away. The Local Health Authority (LHA) in 1990-1991 measured annual averages below 1 AF/L, this concentration being exceeded in 12% of samples (157). Chiappino et al. (18) reported a range of 2.2-7.4 AF/L in the residential areas of Casale--more than in 7 other Italian cities. Amphiboles in the three sets of estimates ranged between 15% and 50% of AF. In Casale average concentration of total (any length) asbestos fibers was 48.4 AF/L and of total amphiboles was 1.5 AF/L, versus, respectively, 0.2-12.1 and 0.0-0.2 AF/L in other industrial cities (18,19). Besides AC production and activities related to it (warehousing and transportation of raw asbestos and final products), no other noticeable sources of asbestos exposure of industrial origin were recorded in Casale (20).

Study design. This is a population-based case-control study that includes cases of pleural MM recorded between 1 January 1987 and 30 June 1993 in residents in the Local Health Authority (LHA) of Casale (48 towns and 100,000 inhabitants, of whom 40,000 live in Casale). Cases were retrospectively identified through periodic surveys of the pathology units of the hospitals serving the study area (14).

Cases were histologically diagnosed and revised by a panel of five pathologists (21,22). Each pathologist independently reviewed the slides and classified each case according to an ordinal scale (definite, probable, possible, improbable, and definitely not MM) (23). Cases were included if all pathologists rated them at least as "possible" and none as "improbable" or "definitely non-MM." Ninety percent of all submitted cases were accepted. Seven cases for which slides could not be traced were included.

Cases and controls were individually matched by sex, birth date ([+ or -] 18 month), vital status, and date of death ([+ or -] 6 months). Controls were randomly selected either from the files of residents in the LHA of Casale (if the corresponding case was alive) or from the mortality files (for deceased cases, no cause of death was excluded). Living status of cases was checked before the sampling of controls. Three cases alive at sampling were matched to alive controls but died before the interview; the original controls were not replaced. To increase power in the younger age classes, the case-control ratio was 1:2 for cases 60 years or older and 1:4 for younger cases.

Trained interviewers conducted the interviews from 1993 to 1995 using a standardized questionnaire. When the index subject had died, the closest relative was interviewed. The questionnaire included sections on demographic characteristics, smoking, radiation treatments, schools attended, lifelong occupational and residential histories, as well as occupations held by spouse, parents, and other cohabitants. Information on residence included the address and a description of each dwelling and its neighborhood environment. Indoor (i.e., domestic) exposure to asbestos was addressed through questions on the use of asbestos material such as ironing table; fire-proof sheets close to heat sources such as cookers, ovens, fireplaces, and stoves; AC material in very close proximity to the house (e.g., garden, courtyard); or AC roofs in the courtyard or very close to the house. Some questions about domestic exposure to asbestos were added after inclusion of the first 24 cases and 80 controls.

Interview data were checked against other sources of information. For example, occupational histories (subjects and relatives) were compared to factory rosters. Cohen's kappa (24) of [greater than or equal to] 0.78 was estimated for work at the AC factory of the index subject (five subjects with discordant information), of the spouse (three subjects discordant), and of parents (seven subjects discordant). For subjects with discordant information, the questionnaire was used. Regarding residential history in Casale, the most precise available information from the questionnaire and the Town Office was used. All addresses of study subjects in Casale were coded as geographic coordinates. Interview, retrieval of information from city files, coding, revision of questionnaires, and the like were conducted blindly in respect to case-control status.

Main data analyses used conditional logistic regression (25,26). O[R.sub.C] (conditional logistic regression) indicates the logistic regression estimate and is computed taking into account the matched sets. Statistical significance is set at 0.05.