Description: Objectives To evaluate the lungs asbestos fibres concentration in participants with malignant pleural mesothelioma (MPM) who have been occupationally exposed. Methods The lung samples were obtained from pleuropneumonectomies or autopsies of 271 male MPMs. The lung samples were examined through scanning electron microscopy. Retrospective assessment was used to assess for asbestos exposure. This study includes 248 MPMs with an occupational exposure defined as either ‘definite’ or ‘probable’ or ‘possible’. Results The participants had finished working in asbestos exposure conditions more than 20 years ago (on average 26.1±11.0 years). The fibre burden resulted with a geometric mean equal to 2.0 (95% CI 1.6 to 2.4) million fibres per gram of dry lung tissue. The burden was higher among participants employed in asbestos textiles industry and in shipyards with insulation material, if compared with construction workers or non-asbestos textile workers or participants working in chemicals or as auto mechanics. 91.3% of MPMs had a detectable amount of amphibole fibres. A strong lung clearance capability was evident among workers exposed to chrysotile fibres. Owing to that, the 1997 Helsinki Criteria for occupational exposure were reached in 〈35% of cases among participant working in construction, in metallurgical industry, in chemical or textile industry and among those performing brake repair activities. Conclusions The MPM cases are now occurring in Italy in participants who ceased occupational asbestos exposure decades before the analysis. A large majority still shows a residual content of amphibole fibres, but given the lung clearance capability, attribution to occupational exposure cannot rely only on fibres detection.

Description: Background Malignant mesothelioma (MM) has distinct histological subtypes (epithelioid, sarcomatoid and biphasic) with variable behaviour and prognoses. It is well recognised that survival time varies with the histological subtype of MM. It is not known, however, if asbestos exposure characteristics (type of asbestos, degree of exposure) are associated with different histological subtypes. Aim To determine if the pathological MM subtype is associated with the type of asbestos or the attributes of asbestos exposure. Methods Cases of MM for the period 1962 until 2012, their main histological subtype and their most significant source of asbestos exposure were collected from the Western Australian Mesothelioma Registry. Exposure characteristics included, degree of asbestos exposure (including total days exposed, years since first exposure and, for crocidolite only, calculated cumulative exposure), source of exposure (occupational or environmental), form of asbestos handled (raw or processed) and type of asbestos (crocidolite only or mixed fibres). Results Patients with the biphasic subtype were more likely to have occupational exposure (OR 1.83, 1.12 to 2.85) and exposure to raw fibres (OR 1.58, 1.19 to 2.10). However, differences between subtypes in the proportions with these different exposure characteristics were small and unlikely to be biologically relevant. Other indicators of asbestos exposure were not associated with the histological subtype of mesothelioma. Conclusions There was no strong evidence of a consistent role of asbestos exposure indicators in determining the histological subtype of MM.

Description: Background It is of considerable interest to forecast the future burden of mesothelioma mortality. Data on deaths are available, whereas no measure of asbestos exposure is available. Methods We compare two Poisson models: a response-only model with an age-cohort specification and a multinomial model with epidemiologically motivated frequencies. Results The response-only model has 5% higher peak mortality than the dose–response model. The former performs slightly better in out-of-sample comparison. Conclusions Mortality is predicted to peak at about 2100 deaths around 2017 among males in cohorts until 1966 and below 90 years of age. The response-only model is a simple benchmark that forecasts just as well as more complicated models.

Description: Objectives Exposure to asbestos fibres increases the risk of mesothelioma and lung cancer. Although the vast majority of mesothelioma cases are caused by asbestos exposure, the number of asbestos-related lung cancers is less clear. This number cannot be determined directly as lung cancer causes are not clinically distinguishable but may be estimated using varying modelling methods. Methods We applied three different modelling methods to the Dutch population supplemented with uncertainty ranges (UR) due to uncertainty in model input values. The first method estimated asbestos-related lung cancer cases directly from observed and predicted mesothelioma cases in an age-period-cohort analysis. The second method used evidence on the fraction of lung cancer cases attributable (population attributable risk (PAR)) to asbestos exposure. The third method incorporated risk estimates and population exposure estimates to perform a life table analysis. Results The three methods varied substantially in incorporated evidence. Moreover, the estimated number of asbestos-related lung cancer cases in the Netherlands between 2011 and 2030 depended crucially on the actual method applied, as the mesothelioma method predicts 17 500 expected cases (UR 7000–57 000), the PAR method predicts 12 150 cases (UR 6700–19 000), and the life table analysis predicts 6800 cases (UR 6800–33 850). Conclusions The three different methods described resulted in absolute estimates varying by a factor of ~2.5. These results show that accurate estimation of the impact of asbestos exposure on the lung cancer burden remains a challenge.

Description: Objective The objective of the study was to investigate the joint effect of occupational exposure to asbestos, and tobacco and alcohol consumption, on the risk of laryngeal cancer among men. Methods We used data from a large population-based case–control study conducted in France. We estimated two-way and three-way interactions between asbestos exposure (never vs ever exposed), tobacco consumption (〈20 vs ≥20 pack-years) and alcohol consumption (〈5 vs ≥5 drinks per day). The interaction on an additive scale was assessed by estimating the relative excess risk due to interaction (RERI) and the attributable proportion due to interaction, and the interaction on a multiplicative scale was assessed by estimating the multiplicative interaction parameter (). Multiplicative interactions were also assessed using fractional polynomials for alcohol drinking, tobacco smoking and asbestos exposure. Results When compared with light-to-moderate smokers and drinkers never exposed to asbestos, the increase in laryngeal cancer risk was smallest among light-to-moderate drinkers and smokers exposed to asbestos (OR=2.23 (1.08 to 4.60)), and highest among heavy smokers and drinkers ever exposed to asbestos (OR=69.39 (35.54 to 135.5)). We found an additive joint effect between asbestos exposure and alcohol consumption (RERI=4.75 (–4.29 to 11.12)), whereas we observed a more than additive joint effect between asbestos exposure and tobacco consumption (RERI=8.50 (0.71 to 23.81)), as well as between asbestos exposure, and tobacco and alcohol consumption (RERI=26.57 (11.52 to 67.88)). However, our results did not suggest any interaction on a multiplicative scale. Conclusions Our results suggest that asbestos exposure, in combination with tobacco and alcohol exposure, accounted for a substantial number of laryngeal cancer cases. Our findings therefore highlight the need for prevention in activities, such as construction work, where exposure to asbestos-containing materials remains.

Description: Objective The aim of our study was to estimate the incidence of digestive cancers within a cohort of asbestos-exposed workers. Methods Our study was based on a cohort of 2024 participants occupationally exposed to asbestos. The incidence of digestive cancers was calculated from 1 January 1978 to 31 December 2009 and compared with levels among the local general population using Standardised Incidence Ratios (SIRs). Asbestos exposure was assessed using the company’s job-exposure matrix. Results 119 cases of digestive cancer were observed within our cohort, for an expected number of 77 (SIR=1.54 (1.28 to 1.85)). A significantly elevated incidence was observed for peritoneal mesothelioma, particularly in women. Significantly elevated incidences were also observed among men for: all digestive cancers, even when excluding peritoneal mesothelioma (SIR=1.50 (1.23 to 1.82)), oesophageal cancer (SIR=1.67 (1.08 to 2.47)) and liver cancer (SIR=1.85 (1.09 to 2.92)). Concerning colorectal cancer, a significant excess of risk was observed for men with exposure duration above 25 years (SIR=1.75 (1.05 to 2.73)). Conclusions Our results are in favour of a link between long-duration asbestos exposure and colorectal cancer in men. They also suggest a relationship between asbestos exposure and cancer of the oesophagus in men. Finally, our results suggest a possible association with small intestine and liver cancers in men.

Description: Objective To examine the association between employment duration, elongate mineral particle (EMP) exposure, silica exposure and the risk of lung cancer in the taconite mining industry. Methods We conducted a nested case–control study of lung cancer within a cohort of Minnesota taconite iron mining workers employed by any of the mining companies in operation in 1983. Lung cancer cases were identified by vital records and cancer registry data through 2010. Two age-matched controls were selected from risk sets of cohort members alive and lung cancer free at the time of case diagnosis. Calendar time-specific exposure estimates were made for every job and were used to estimate workers’ cumulative exposures. ORs and 95% CIs were estimated using conditional logistic regression. We evaluated total lung cancer risk and risk of histological subtype by total work duration and by cumulative EMP, and silica exposure by quartile of the exposure distribution. Results A total of 1706 cases and 3381 controls were included in the analysis. After adjusting for work in haematite mining, asbestos exposure and sex, the OR for total duration of employment was 0.99 (95% CI 0.96 to 1.01). The ORs for quartile 4 versus 1 of EMP and silica exposure were 0.82 (95% CI 0.57 to 1.19) and 0.97 (95% CI 0.70 to 1.35), respectively. The risk of each histological subtype of lung cancer did not change with increasing exposure. Conclusions This study suggests that the estimated taconite mining exposures do not increase the risk of developing lung cancer.

Description: Objectives Millions of workers worldwide are employed in occupations involving potentiality hazardous exposure to crystalline silica. The diatomaceous earth industry can have particularly high exposures, but there is a lower likelihood of simultaneously occurring confounding exposures. We extended follow-up for diatomaceous earth industry workers previously studied for mortality. Methods The cohort included 2342 white men who were employed for at least 1 year at a diatomaceous earth plant in Lompoc, California beginning in 1942. Workers’ vital status was updated using the National Death Index through 2011, an extension of 19 years from earlier studies. Detailed work history and quantitative air monitoring measurements estimated exposure intensity. Cox proportional hazards modelling estimated HRs and 95% CIs. SMRs were calculated. Results Elevated mortality was observed by quartile of cumulative crystalline silica exposure for lung cancer (HR=2.03, 95% CI 1.07 to 3.85, highest quartile, unlagged) and non-malignant respiratory disease (NMRD) (HR=3.59, 95% CI 1.94 to 6.67, highest quartile, unlagged), although trends were not statistically significant. Associations were attenuated when adjusted for smoking and asbestos exposure. Mortality from NMRD was significantly increased over the entire follow-up compared to the general population (SMR=1.37, 95% CI 1.17 to 1.60). An increase for lung cancer was confined to the earlier follow-up (SMR=1.29, 95% CI 1.01 to 1.61). Conclusions The risk of lung cancer and NMRD mortality remained elevated, although generally non-significant, and exposure-response trends with cumulative crystalline silica persisted on extended follow-up of this cohort. The findings support a generally consistently observed aetiological relation between crystalline silica and lung cancer.

Description: Background Asbestos is a known carcinogen. However, little is known about the differential effects of size-specific asbestos fibres. Previous research has examined the relationship with lung cancer of each fibre group in the absence of others. Attempts to model all fibre groups within a single regression model have failed due to high correlations across fibre size groups. Methods We compare results from frequentist models for individual fibre size groups, and a hierarchical Bayesian model that included all fibre groups to estimate the relationship of size-specific asbestos fibre groups to lung cancer mortality. The hierarchical model assumes partial exchangeability of the effects of size-specific asbestos fibre groups to lung cancer, and is capable of handling the strong correlation of the exposure data. Results When fibre groups are modelled independently with a frequentist model, there appears to be an increase in the dose-response with increasing fibre size. However, when subject to a hierarchical structure, this trend vanishes, and the effects of distinct fibre groups appear largely similar. Conclusions This is the first occasion where distinct asbestos fibre groups have been assessed in a single regression model; however, even the use of a hierarchical modelling structure does not appear to overcome all the statistical fluctuations arising from the high correlations across fibre groups. We believe these results should be compared with other occupational cohorts with similar fibre group information. Finally, results for the smallest fibre group may be suggestive of a carcinogenic potential for nanofibres.

Description: Objectives In attempts to overcome the limitations of self-reported data in occupational health research, job-exposure matrices, which assign exposure by occupation, have emerged as an objective approach for assessing occupational exposures. On the basis of a lung cancer case–control study conducted in the Greater Toronto Area, 1997–2002, assessment of occupational exposure to asbestos was compared using self-reports and a general population job-exposure matrix (DOM-JEM). Methods Cases and frequency matched controls provided life-time job histories and self-reported exposures to potential lung carcinogens including asbestos through a detailed questionnaire. Exposure to asbestos was also assigned to each job by linking occupational histories with DOM-JEM. Agreement in classification of exposed and unexposed jobs according to self-reports and DOM-JEM was evaluated using Cohen's . Risks for lung cancer were estimated using unconditional logistic regression for each exposure assessment approach. Results The prevalence of occupational asbestos exposure was greater when based on DOM-JEM than when based on self-reports. Agreement in classifying exposure to jobs between the two assessment approaches was poor. The risk of lung cancer was not elevated among workers who self-reported asbestos exposure, whereas workers considered exposed on the basis of DOM-JEM were almost twice as likely as unexposed workers to be diagnosed with lung cancer (OR 1.9, 95% CI 1.3 to 2.7). Conclusions It is generally assumed by epidemiologists that self-reported exposure assessments result in inflated risk estimates. In this study, self-reports found no association with a well-established risk factor, whereas a high-quality job-exposure matrix revealed relative risk estimates that are more consistent with previous findings.