Risk of lung cancer associated with quantitative beryllium exposure metrics within an occupational cohort

Abstract

Objectives Beryllium has been identified as a human carcinogen on the basis of animal and epidemiological studies. The authors recently reported updated associations between lung cancer and beryllium exposure in a large, pooled occupational cohort. The authors conducted the present study to evaluate the shape of exposureeresponse associations between different exposure metrics and lung cancer in this cohort, considering potential confounders (race, plant, professional and short-term work status, and exposure to other lung carcinogens). Methods The authors conducted Cox proportional hazards regression analyses of lung cancer risk with cumulative, mean and maximum 'daily weighted average' (DWA) exposure among 5436 workers, using age-based risk sets. Different exposureeresponse curves were fitted to the exposure metrics, including categorical, power, restricted cubic spline and piecewise log-linear fits. Results The authors found significant positive associations between lung cancer and mean (p<0.0001) and maximum (p<0.0001) exposure, adjusting for age, birth cohort and plant, and for cumulative (p¼0.0017) beryllium exposure, adjusting for these factors plus short-term work status and exposure to asbestos. The best-fitting models were generally categorical or piecewise log-linear, with the steepest increase in lung cancer risk between 0 and 10 mg/m 3 for both mean and maximum DWA exposure and between 0 and 200 mg/m 3 -days for cumulative DWA exposure. The estimated mean DWA beryllium exposure associated with 10 À3 excess lifetime risk based on the piecewise log-linear model is 0.033 mg/m 3 . Conclusion This study provides evidence that lung cancer risk is elevated at levels near the current US Occupational Safety and Health Administration beryllium exposure limit of 2.0 mg/m 3 DWA for workers.Beryllium exposure has long been associated with an immune-mediated, granulomatous lung disease termed chronic beryllium disease. 1 Toxicological and epidemiological studies have more recently led the International Agency for Research on Cancer to designate beryllium as a human carcinogen. Epidemiological evidence for the carcinogenicity of beryllium derives largely from studies within a pooled cohort of male workers 4 5 at seven US beryllium processing plants, and a nested casee control study of lung cancer at one of the plants. 6 7 We recently reported updated associations between cumulative and maximum beryllium exposure and several diseases of a priori interest (including lung cancer), within a three-plant subcohort having detailed beryllium exposure data. 5Although smoking data were available for only a subset (25%) of cohort members, the positive exposureeresponse associations observed in that study showed little evidence of confounding by smoking, as measured by indirect methods.The present study was conducted to evaluate the association of mean, maximum and cumulative beryllium exposure with lung cancer mortality, considering potential confounders, including age, race, birth cohort, exposure to other lung ca...

Is beryllium-induced lung cancer caused only by soluble forms and high exposure levels?

“…We used the same cohort definitions, cohort entry, mortality follow-up (1940–2005), exposure estimates and statistical methods as in the previous analysis,6 conducting Cox proportional hazards regression of underlying-cause lung cancer deaths (International Classification of Diseases (ICD)-6 and ICD-7 codes 162.0, 162.1, 162.8, 163; ICD-8 and ICD-9 code 162 and ICD-10 codes C33–C34) in age-based full risk sets within the pooled plants 6 and 7. We classified exposure into tertiles of the case distribution (with cutpoints at 0.88 and 1.55 µg/m 3 for mean exposure and 723 and 4211 µg/m 3 -days for cumulative exposure) for categorical analyses.…”

“…We classified exposure into tertiles of the case distribution (with cutpoints at 0.88 and 1.55 µg/m 3 for mean exposure and 723 and 4211 µg/m 3 -days for cumulative exposure) for categorical analyses. We used categorical and power (log–log) models to evaluate exposure–response patterns for mean and cumulative beryllium exposures in the two-plant cohort, comparing findings with published estimates from the full pooled cohort 6. The power model form was selected as it well describes the exposure–response shape within the full cohort 6.…”

“…Since the IARC evaluation, new studies have evaluated cancer risk with extended follow-up in seven of these historical cohorts, including three with quantitative exposure–response evaluation 5 6. One of these studies6 was used recently by the US Occupational Safety and Health Administration (OSHA) in a quantitative risk assessment for lung cancer, as part of the establishment of a more protective permissible exposure limit for workers exposed to beryllium 7…”

Câncer relacionado ao trabalho: uma revisão sistemática

“…O câncer de pulmão também tem sido associado à exposição ocupacional a metais pesados como níquel, cádmio, cromo hexavalente e berílio 37,38 . Um aumento no risco de morte por câncer de pulmão foi observado em um estudo do tipo coorte realizado nos EUA com trabalhadores da indústria de sapatos expostos a solventes como o tolueno 39 .…”

Health hazard evaluation report: evaluation of employee health concern and suspected contamination at an office complex.

“…This is a blood test that measures sensitivity to beryllium and is very specific to determine if a person has an allergic reaction to beryllium. Exposure to beryllium also slightly increases the risk for lung cancer [Schubauer-Berigan 2010].…”