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Lung Cancer Mortality and Styrene Exposure in the Reinforced-Plastics Boatbuilding Industry: Evaluation of Healthy Worker Survivor Bias.

ABSTRACT: The evidence for styrene's being a human lung carcinogen has been inconclusive. Occupational cohorts within the reinforced-plastics industry are an ideal population in which to study this association because of their relatively high levels of exposure to styrene and lack of concomitant exposures to other known carcinogens. However, healthy worker survivor bias (HWSB), where healthier workers stay employed longer and thus have higher exposure potential, is a likely source of confounding bias for exposure-response associations, in part due to styrene's acute effects. Through December 31, 2016, we studied a cohort of 5,163 boatbuilders exposed to styrene in Washington State who were employed between 1959 and 1978; prior regression analyses had demonstrated little evidence for an exposure-response relationship between styrene exposure and lung cancer mortality. Based on estimates of necessary components of HWSB, we found evidence for a potentially large HWSB. Using g-estimation of a structural nested model to account for HWSB, we estimated that 1 year of styrene exposure at more than 30 parts per million accelerated time to lung cancer death by 2.29 years (95% confidence interval: 1.53, 2.94). Our results suggest possibly strong HWSB in our small cohort and indicate that large, influential studies of styrene-exposed workers may suffer from similar biases, warranting a reassessment of the evidence of long-term health effects of styrene exposure.

SUBMITTER: Bertke SJ

PROVIDER: S-EPMC8628256 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Cancer mortality update with an exposure response analysis among styrene-exposed workers in the reinforced plastics boatbuilding industry.

Project description:BackgroundThere is sparse and inconsistent evidence of an association between styrene exposure and cancer.MethodsThis study examines mortality patterns in a previously studied cohort of 5201 workers employed in two Washington boat-building facilities, extending follow-up 5 years. Standardized mortality ratios (SMR) were calculated using state rates as referent. Cox regression calculated rate ratios (RR) per year employed in styrene-exposed exposed jobs.ResultsNo excess deaths from lymphohematopoietic cancers (LHCs) were observed (SMR: 0.99, 95%CI: 0.74-1.30) when compared to the referent population; however, the relative risk increased with duration of employment in internal analyses. Conversely, lung cancer mortality was significantly elevated (SMR: 1.24, 95%CI: 1.08-1.41), but there was no evidence of a dose-response relationship.ConclusionWe found evidence that occupational exposure to styrene was associated with increased LHC risk, while no such association was observed for lung cancer.

| S-EPMC8590871 | biostudies-literature

Assessing the component associations of the healthy worker survivor bias: occupational asbestos exposure and lung cancer mortality.

Project description:BackgroundThe healthy worker survivor bias is well-recognized in occupational epidemiology. Three component associations are necessary for this bias to occur: i) prior exposure and employment status; ii) employment status and subsequent exposure; and iii) employment status and mortality. Together, these associations result in time-varying confounding affected by prior exposure. We illustrate how these associations can be assessed using standard regression methods.MethodsWe use data from 2975 asbestos textile factory workers hired between January 1940 and December 1965 and followed for lung cancer mortality through December 2001.ResultsAt entry, median age was 24 years, with 42% female and 19% non-Caucasian. Over follow-up, 21% and 17% of person-years were classified as at work and exposed to any asbestos, respectively. For a 100 fiber-year/mL increase in cumulative asbestos, the covariate-adjusted hazard of leaving work decreased by 52% (95% confidence interval [CI], 46-58). The association between employment status and subsequent asbestos exposure was strong due to nonpositivity: 88.3% of person-years at work (95% CI, 87.0-89.5) were classified as exposed to any asbestos; no person-years were classified as exposed to asbestos after leaving work. Finally, leaving active employment was associated with a 48% (95% CI, 9-71) decrease in the covariate-adjusted hazard of lung cancer mortality.ConclusionsWe found strong associations for the components of the healthy worker survivor bias in these data. Standard methods, which fail to properly account for time-varying confounding affected by prior exposure, may provide biased estimates of the effect of asbestos on lung cancer mortality under these conditions.

| S-EPMC3773512 | biostudies-literature

Healthy worker survivor bias in the Colorado Plateau uranium miners cohort.

Project description:Cohort mortality studies of underground miners have been used to estimate the number of lung cancer deaths attributable to radon exposure. However, previous studies of the radon-lung cancer association among underground miners may have been subject to healthy worker survivor bias, a type of time-varying confounding by employment status. We examined radon-mortality associations in a study of 4,124 male uranium miners from the Colorado Plateau who were followed from 1950 through 2005. We estimated the time ratio (relative change in median survival time) per 100 working level months (radon exposure averaging 130,000 mega-electron volts of potential ? energy per liter of air, per working month) using G-estimation of structural nested models. After controlling for healthy worker survivor bias, the time ratio for lung cancer per 100 working level months was 1.168 (95% confidence interval: 1.152, 1.174). In an unadjusted model, the estimate was 1.102 (95% confidence interval: 1.099, 1.112)-39% lower. Controlling for this bias, we estimated that among 617 lung cancer deaths, 6,071 person-years of life were lost due to occupational radon exposure during follow-up. Our analysis suggests that healthy worker survivor bias in miner cohort studies can be substantial, warranting reexamination of current estimates of radon's estimated impact on lung cancer mortality.

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Estimating the effect of cumulative occupational asbestos exposure on time to lung cancer mortality: using structural nested failure-time models to account for healthy-worker survivor bias.

Project description:BackgroundPrevious estimates of the effect of occupational asbestos on lung cancer mortality have been obtained by using methods that are subject to the healthy-worker survivor bias. G-estimation of a structural nested model provides consistent exposure effect estimates under this bias.MethodsWe estimated the effect of cumulative asbestos exposure on lung cancer mortality in a cohort comprising 2564 textile factory workers who were followed from January 1940 to December 2001.ResultsAt entry, median age was 23 years, with 42% of the cohort being women and 20% nonwhite. During the follow-up period, 15% of person-years were classified as occurring while employed and 13% as occupationally exposed to asbestos. For a 100 fiber-year/ml increase in cumulative asbestos, a Weibull model adjusting for sex, race, birth year, baseline exposure, and age at study entry yielded a survival time ratio of 0.88 (95% confidence interval = 0.83 to 0.93). Further adjustment for work status yielded no practical change. The corresponding survival time ratio obtained using g-estimation of a structural nested model was 0.57 (0.33 to 0.96).ConclusionsAccounting for the healthy-worker survivor bias resulted in a 35% stronger effect estimate. However, this estimate was considerably less precise. When healthy-worker survivor bias is suspected, methods that account for it should be used.

| S-EPMC4457343 | biostudies-literature

A structural approach to address the healthy-worker survivor effect in occupational cohorts: an application in the trucking industry cohort.

Project description:Occupational cohort studies are often challenged by the Healthy Worker Survivor Effect, which may bias standard methods of analysis. G-estimation of structural failure time models is an approach for reducing this type of bias. Accelerated failure time models have recently been applied in an occupational cohort but cumulative failure time models have not.We used g-estimation of a cumulative failure time model to assess the effect of working as a long-haul driver on ischaemic heart disease mortality in a cohort of 30 448 men employed in the unionised US trucking industry in 1985. Exposure was defined by job title and based on work records. We also applied g-estimation of an accelerated failure time model as a sensitivity analysis and approximated HRs from both models to compare them.The risk ratio (RR) obtained from the cumulative failure time model, comparing the observed risk under no intervention to the risk had nobody ever been exposed as a long-haul driver, was 1.09 (95% CI 1.02 to 1.16). The RR comparing the risk had everyone been exposed as long-haul driver for 8 years to the risk had nobody ever been exposed was 1.20 (95% CI 1.04 to 1.46). After HR approximations, accelerated failure time model results were similar.The cumulative failure time model can effectively control time-varying confounding by Healthy Worker Survivor Effect, and provides an easily interpretable effect estimate. RRs estimated from the cumulative failure time model indicate an elevated ischaemic heart disease mortality risk for long-haul drivers in the US trucking industry.

| S-EPMC4051133 | biostudies-literature

Risk of cancer in workers exposed to styrene at eight British companies making glass-reinforced plastics.

Project description:ObjectivesTo provide further information on the risks of lymphohaematopoietic (LH) and other cancers associated with styrene.MethodsWe extended follow-up to December 2012 for 7970 workers at eight companies in England which used styrene in the manufacture of glass-reinforced plastics. Mortality was compared with that for England and Wales by the person-years method, and summarised by SMRs with 95% CIs. A supplementary nested case-control analysis compared styrene exposures, lagged by 5 years, in 122 incident or fatal cases of LH cancer and 1138 matched controls.ResultsA total of 3121 cohort members had died (2022 since the last follow-up). No elevation of mortality was observed for LH cancer, either in the full cohort (62 deaths, SMR 0.90, 95% CI 0.69 to 1.15), or in those with more than background exposure to styrene (38 deaths, SMR 0.82, 95% CI 0.58 to 1.14). Nor did the case-control analysis suggest any association with LH cancer. In comparison with background exposure, the OR for non-Hodgkin's lymphoma/chronic lymphocytic leukaemia in workers with high exposure (estimated 8-h time-weighted average of 40-100 ppm) for ≥1 year was 0.54 (95% CI 0.23 to 1.27). Mortality from lung cancer was significantly elevated, and risk increased progressively across exposure categories, with an SMR of 1.44 (95% CI 1.10 to 1.86) in workers highly exposed for ≥1 year.ConclusionsWe found no evidence that styrene causes LH cancer. An association with lung cancer is not consistently supported by other studies. It may have been confounded by smoking, but would be worth checking further.

| S-EPMC4548714 | biostudies-literature

Healthy worker survivor analysis in an occupational cohort study of Dutch agricultural workers.

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Exposure-response assessment of cancer mortality in styrene-exposed boatbuilders.

Project description:ObjectivesTo improve exposure estimates and reexamine exposure-response relationships between cumulative styrene exposure and cancer mortality in a previously studied cohort of US boatbuilders exposed between 1959 and 1978 and followed through 2016.MethodsCumulative styrene exposure was estimated from work assignments and air-sampling data. Exposure-response relationships between styrene and select cancers were examined in Cox proportional hazards models matched on attained age, sex, race, birth cohort and employment duration. Models adjusted for socioeconomic status (SES). Exposures were lagged 10 years or by a period maximising the likelihood. HRs included 95% profile-likelihood CIs. Actuarial methods were used to estimate the styrene exposure corresponding to 10-4 extra lifetime risk.ResultsThe cohort (n= 5163) contributed 201 951 person-years. Exposures were right-skewed, with mean and median of 31 and 5.7 ppm-years, respectively. Positive, monotonic exposure-response associations were evident for leukaemia (HR at 50 ppm-years styrene = 1.46; 95% CI 1.04 to 1.97) and bladder cancer (HR at 50 ppm-years styrene =1.64; 95% CI 1.14 to 2.33). There was no evidence of confounding by SES. A working lifetime exposure to 0.05 ppm styrene corresponded to one extra leukaemia death per 10 000 workers.ConclusionsThe study contributes evidence of exposure-response associations between cumulative styrene exposure and cancer. Simple risk projections at current exposure levels indicate a need for formal risk assessment. Future recommendations on worker protection would benefit from additional research clarifying cancer risks from styrene exposure.

| S-EPMC7494518 | biostudies-literature

Quantitative and Semiquantitative Health Risk Assessment of Occupational Exposure to Styrene in a Petrochemical Industry.

Project description:BackgroundStyrene is one of the aromatic compounds used in acetonitrile-butadiene-styrene (ABS) producing petrochemicals, which has an impact on health of workers. Therefore, this study aimed to investigate the health risks of styrene emitted from the petrochemical industry in Iran.MethodsAir samples were collected based on NIOSH 1501 method. The samples were analyzed by the Varian-cp3800 gas chromatograph. Finally, risk levels of styrene's health effects on employees were assessed by the quantitative method of the U.S. Environmental Protection Agency (U.S. EPA) and the semiquantitative way by the Singapore Occupational Safety and Health Association.ResultsBased on the results, the employees had the highest average exposure to styrene vapors (4.06 ×10-1mg.(kg-day)-1 ) in the polybutadiene latex (PBL) unit. Therefore, the most top predictors of cancer and non-cancer risk were 2.3 ×10-4 and 7.26 ×10-1 , respectively. Given that the lowest average exposure (1.5 ×10-2mg.(kg-day)-1 ) was in the dryer unit, the prediction showed a moderate risk of cancer (0.8 ×10-6 ) and non-cancer (2.3 ×10-3 ) for the employees. The EPA method also predicted that there would be a definite cancer risk in 16% and a probable risk in 76% of exposures. However, according to the semiquantitative approach, the rate of risk was at the "low" level for all staff. The results showed that there was a significant difference (p < 0.05) between the units in exposure and health risk of styrene (p < 0.05).ConclusionGiven the high risk of styrene's health effects, appropriate control measures are required to reduce the exposure level.

| S-EPMC8430436 | biostudies-literature

Recycling of Wastes Plastics and Tires from Automotive Industry.

Project description:Waste tires (granulate) and selected plastics from the automotive industry were evaluated by using the tertiary (pyrolysis) and quaternary (calorimetry) recovering. Pyrolysis is proving to be an environmentally friendly alternative to incineration and inefficient landfilling. Currently, the main challenges for pyrolysis of plastic waste are unavailability and inconsistent quality of feedstock, inefficient and hence costly sorting, and last but not least insufficient regulations around plastic waste management. Waste plastics and tire materials were characterized by TG/DTG analysis, Py-GC/MS analysis and calorimetry. TG analysis of the investigated materials gives the typical decomposition curves of synthetic polymers. The tested samples had the highest rate of weight loss process in the temperature range from 375 °C to 480 °C. Analytical pyrolysis of the tested polymers provided information on a wide variety of organic compounds that were released upon thermal loading of these materials without access to oxygen. Analytical pyrolysis offers valuable information on the spectrum of degradation products and their potential uses. Based on the results of calorimetry, it can be stated that the determined calorific value of selected plastic and rubber materials was ranging from 26.261 to 45.245 MJ/kg depending on the ash content and its composition.

| S-EPMC8271936 | biostudies-literature

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