Description: Objectives Casale Monferrato (north west Italy) is an area with an exceptionally high incidence of mesothelioma caused by asbestos contamination at work and in the general environment from the asbestos-cement Eternit plant that was operational until 1986. The purpose of this study was to quantify the association between pleural malignant mesothelioma (PMM) and asbestos cumulative exposure using individual assessment of environmental and domestic exposure, as well as of occupational exposure. Methods This population-based case-control study included cases of PMM diagnosed between January 2001 and June 2006 among residents in the Casale Monferrato Local Health Authority. Population controls were randomly sampled, matched by age and sex to cases. Cumulative exposure was estimated to account for the lifelong exposure history. Analyses were conducted using unconditional logistic regression models adjusting for gender, age at diagnosis and type of interview (direct or proxy respondents). Results 200 PMM cases of 223 eligible cases (89.7%) and 348 (63%) of 552 eligible controls accepted to be interviewed. ORs increased with cumulative exposure index (p〈0.0001) from 4.4 (CI 95% 1.7 to 11.3) (〈1 f/mL-years) to 62.1 (CI 95% 22.2 to 173.2) (≥10 f/mL-years). Among subjects never occupationally exposed, corresponding ORs were 3.8 (CI 95% 1.3 to 11.1) and 23.3 (CI 95% 2.9 to 186.9) (reference: background level of asbestos exposure). ORs of about 2, statistically significant, were observed for domestic exposure and for living in houses near buildings with large asbestos cement parts. Conclusions Risk of PMM increased with cumulative asbestos exposure and also in analyses limited to subjects non-occupationally exposed. Our results also provide indication of risk associated with common sources of environmental exposure and are highly relevant for the evaluation of residual risk after the cessation of asbestos industrial use.

Description: Sir, The criticisms by Boffetta 1 give us the opportunity to provide more details on the methods and results of our study. 2 First, the proportion of proxy respondents among controls was 7.2% (table 1) and not 93% as erroneously indicated by Boffetta. As expected, the exposure–response trend was steeper for direct interviews that provided more detailed information (see online supplementary table S3). Casale Monferrato inhabitants are aware of asbestos-related cancer risks. However, this applies to the entire community, not only to cases, therefore it is an unproven assumption that local awareness explains our study results because of participation and recall biases. On the contrary, if exposed controls selectively entered the study because of their motivation, our findings would be biased towards the null. After study publication, we investigated demographic and social characteristics of respondents and non-respondents, observing no differences (paper in preparation). Our findings are neither...

Description: Marsh and Benson 1 commented on our paper and the associated correspondence with Boffetta highlighting two issues. 2–4 First, they questioned our exposure–response analyses because we had not always used the same reference categories. We repeated all secondary analyses reported in our online supplementary tables S1 and S2 by using the same reference as in our main analysis ( table 1 ). Risk estimates by exposure category are consistent with our main analysis results (see table 2 of our paper), confirming the exposure–response trend for pleural malignant mesothelioma irrespective of the route of exposure (occupation or environment). Owing to space constraints, we are only showing our new results for occupational and environmental exposures, but all other findings were similar, including those stratified by probability of exposure (definite, probable, possible). Second, Marsh and Benson commented on the external consistency of our results,...