Lifetime occupational exposures and chronic obstructive pulmonary disease risk in the UK Biobank cohort.

BACKGROUND AND AIM: Occupational exposures are important, preventable causes of COPD. We previously found an increased risk of COPD among six occupations by analysing lifetime job histories and lung function data in the population-based UK Biobank cohort. We aimed to build on these findings and elucidate the underlying potential causal agents to focus preventive strategies. METHODS: We applied the ALOHA+job exposure matrix (JEM) based on the International Standard Classification of Occupations V.1988 codes, where exposure to 12 selected agents was rated as 0 (no exposure), 1 (low) or 2 (high). COPD was spirometrically defined as FEV1/FVC less than the lower limit of normal. We calculated semiquantitative cumulative exposure estimates for each agent by multiplying the duration of exposure and squared intensity. Prevalence ratio (PR) and 95% CI for COPD were estimated using robust Poisson regression adjusted for centre, sex, age, smoking and coexposure to JEM agents. Only associations confirmed among never-smokers and never-asthmatics were considered reliable. RESULTS: Out of 116 375 participants with complete job histories, 94 514 had acceptable/repeatable spirometry and smoking data and were included in the analysis. Pesticide exposure showed increased risk of COPD for ever exposure (PR=1.13, 95% CI 1.01 to 1.28) and high cumulative exposure (PR=1.32, 95% CI 1.12 to 1.56), with positive exposure-response trends (p trend=0.004), which were confirmed among never-smokers (p trend=0.005) and never-asthmatics (p trend=0.001). CONCLUSION: In a large population-based study, occupational exposure to pesticides was associated with risk of COPD. Focused preventive strategies for workers exposed to pesticides can prevent the associated COPD burden.

Occupational exposure to inhaled pollutants and risk of airflow obstruction: a large UK population-based UK Biobank cohort.

BACKGROUND: Although around 10% to 15% of COPD burden can be attributed to workplace exposures, little is known about the role of different airborne occupational pollutants (AOP). The main aim of the study was to assess the effect size of the relationship between various AOP, their level and duration of exposure with airflow obstruction (AFO). METHODS: A cross-sectional analysis was conducted in 228 614 participants from the UK Biobank study who were assigned occupational exposure using a job exposure matrix blinded to health outcome. Adjusted prevalence ratios (PRs) and 95% CI for the risk of AFO for ever and years of exposure to AOPs were estimated using robust Poisson model. Sensitivity analyses were conducted for never-smokers, non-asthmatic and bi-pollutant model. RESULTS: Of 228 614 participants, 77 027 (33.7%) were exposed to at least one AOP form. 35.5% of the AFO cases were exposed to vapours, gases, dusts or fumes (VGDF) and 28.3% to dusts. High exposure to vapours increased the risk of occupational AFO by 26%. Exposure to dusts (adjusted PR=1.05; 95% CI 1.01 to 1.08), biological dusts (1.05; 1.01 to 1.10) and VGDF (1.04; 1.01 to 1.07) showed a significantly increased risk of AFO, however, statistically not significant following multiple testing. There was no significant increase in risk of AFO by duration (years) of exposure in current job. The results were null when restricted to never-smokers and when a bi-pollutant model was used. However, when data was analysed based on the level of exposure (low, medium and high) compared with no exposure, directionally there was increase in risk for those with high exposure to vapours, gases, fumes, mists and VGDF but statistically significant only for vapours. CONCLUSION: High exposure (in current job) to airborne occupational pollutants was suggestive of higher risk of AFO. Future studies should investigate the relationship between lifetime occupational exposures and COPD.

The occupations at increased risk of COPD: analysis of lifetime job-histories in the population-based UK Biobank Cohort.

Occupational exposures are important, preventable causes of chronic obstructive pulmonary disease (COPD). Identification of COPD high-risk jobs is key to focus preventive strategies, but a definitive job-list is unavailable.We addressed this issue by evaluating the association of lifetime job-histories and lung function data in the population-based UK Biobank cohort, whose unprecedented sample size allowed analyses restricted to never-smokers to rule out the most important confounder, tobacco smoking. COPD was spirometrically defined as forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal. Lifetime job-histories were collected via OSCAR (Occupations Self-Coding Automatic Recording), a new validated online tool that automatically codes jobs into the UK Standard Occupational Classification v.2000. Prevalence ratios for COPD by employment duration in each job compared to lifetime office workers were estimated using robust Poisson regression adjusted for age, sex, centre and smoking. Only associations confirmed among never-smokers and never-asthmatics were considered reliable.From the 116 375 participants with complete job-histories, 94 551 had acceptable/repeatable spirometry data and smoking information and were included in the analysis. Six occupations showed an increased COPD risk among never-smokers and never-asthmatics; most of these also with positive exposure-response trends. Interesting new findings included sculptors, gardeners and warehouse workers.COPD patients, especially never-smokers, should be asked about their job-history for better disease management. Focussed preventive strategies in COPD high-risk jobs are warranted.

Cancers in France in 2015 attributable to occupational exposures.

BACKGROUND: Recent and comprehensive estimates for the number of new cancer cases in France attributable to occupational exposures are lacking. OBJECTIVES: To estimate the number of new cancer cases attributable to occupational exposures, using a newly developed methodology and the most recent data, for a comprehensive set of occupational carcinogens in France in 2015. METHODS: Surveys among employees, the national labor force data, a cohort of agricultural workers, national monitoring of workers exposed to ionizing radiation and job-exposure matrix in France were used. The number and proportion of new cancer cases attributable to established occupational carcinogens (Group 1) was estimated using estimation of lifetime exposure and risk estimates from cohort studies. Cancer data were obtained from the French Cancer Registries Network. RESULTS: In France in 2015, an estimated 7905 new cancer cases, 7336 among men and 569 among women, were attributable to occupational exposures, representing 2.3% of all new cancer cases (3.9% and 0.4% among men and women respectively). Among men and women, lung cancer was impacted the most, followed by mesothelioma and bladder cancer in men, and by mesothelioma and ovary in women. These cancers contributed to 89% of the total cancers attributable to occupational carcinogens in men, and to 80% in women. The main contributing occupational agent was asbestos among men (45%) and women (60%). CONCLUSIONS: Currently, occupational exposures contribute to a substantial burden of cancer in France. Enhanced monitoring and implementation of protective labor policies could potentially prevent a large proportion of these cancers.

Occupational exposures and cancer: a review of agents and relative risk estimates.

OBJECTIVES: The contribution of occupational exposures to the cancer burden can be estimated using population-attributable fractions, which is of great importance for policy making. This paper reviews occupational carcinogens, and presents the most relevant risk relations to cancer in high-income countries using France as an example, to provide a framework for national estimation of cancer burden attributable to occupational exposure. METHODS: Occupational exposures that should be included in cancer burden studies were evaluated using multiple criteria: classified as carcinogenic or probably carcinogenic by the International Agency for Research on Cancer (IARC) Monographs volumes 1-114, being a primary occupational exposure, historical and current presence of the exposure in France and the availability of exposure and risk relation data. Relative risk estimates were obtained from published systematic reviews and from the IARC Monographs. RESULTS: Of the 118 group 1 and 75 group 2A carcinogens, 37 exposures and 73 exposure-cancer site pairs were relevant. Lung cancer was associated with the most occupational carcinogenic exposures (namely, 18), followed by bladder cancer and non-Hodgkin's lymphoma. Ionising radiation was associated with the highest number of cancer sites (namely, 20), followed by asbestos and working in the rubber manufacturing industry. Asbestos, bis(chloromethyl)ether, nickel and wood dust had the strongest effect on cancer, with relative risks above 5. CONCLUSIONS: A large number of occupational exposures continues to impact the burden of cancer in high-income countries such as France. Information on types of exposures, affected jobs, industries and cancer sites affected is key for prioritising policy and prevention initiatives.

Estimating the burden of occupational cancer: assessing bias and uncertainty.

BACKGROUND AND OBJECTIVES: We aimed to estimate credibility intervals for the British occupational cancer burden to account for bias uncertainty, using a method adapted from Greenland's Monte Carlo sensitivity analysis. METHODS: The attributable fraction (AF) methodology used for our cancer burden estimates requires risk estimates and population proportions exposed for each agent/cancer pair. Sources of bias operating on AF estimator components include non-portability of risk estimates, inadequate models, inaccurate data including unknown cancer latency and employment turnover and compromises in using the available estimators. Each source of bias operates on a component of the AF estimator. Independent prior distributions were estimated for each bias, or graphical sensitivity analysis was used to identify plausible distribution ranges for the component variables, with AF recalculated following Monte Carlo repeated sampling from these distributions. The methods are illustrated using the example of lung cancer due to occupational exposure to respirable crystalline silica in men. RESULTS: Results are presented graphically for a hierarchy of biases contributing to an overall credibility interval for lung cancer and respirable crystalline silica exposure. An overall credibility interval of 2.0% to 16.2% was estimated for an AF of 3.9% in men. Choice of relative risk and employment turnover were shown to contribute most to overall estimate uncertainty. Bias from using an incorrect estimator makes a much lower contribution. CONCLUSIONS: The method illustrates the use of credibility intervals to indicate relative contributions of important sources of uncertainty and identifies important data gaps; results depend greatly on the priors chosen.

The future excess fraction of occupational cancer among those exposed to carcinogens at work in Australia in 2012.

BACKGROUND: Studies in other countries have generally found approximately 4% of current cancers to be attributable to past occupational exposures. This study aimed to estimate the future burden of cancer resulting from current occupational exposures in Australia. METHODS: The future excess fraction method was used to estimate the future burden of occupational cancer (2012-2094) among the proportion of the Australian working population who were exposed to occupational carcinogens in 2012. Calculations were conducted for 19 cancer types and 53 cancer-exposure pairings, assuming historical trends and current patterns continued to 2094. RESULTS: The cohort of 14.6 million Australians of working age in 2012 will develop an estimated 4.8 million cancers during their lifetime, of which 68,500 (1.4%) are attributable to occupational exposure in those exposed in 2012. The majority of these will be lung cancers (n=26,000), leukaemias (n=8000), and malignant mesotheliomas (n=7500). CONCLUSIONS: A significant proportion of future cancers will result from occupational exposures. This estimate is lower than previous estimates in the literature; however, our estimate is not directly comparable to past estimates of the occupational cancer burden because they describe different quantities - future cancers in currently exposed versus current cancers due to past exposures. The results of this study allow us to determine which current occupational exposures are most important, and where to target exposure prevention.

The burden of occupationally-related cutaneous malignant melanoma in Britain due to solar radiation.

BACKGROUND: Increasing evidence highlights the association of occupational exposure and cutaneous malignant melanoma (CMM). We estimated the burden of CMM and total skin cancer burden in Britain due to occupational solar radiation exposure. METHODS: Attributable fractions (AF) and numbers were estimated for CMM mortality and incidence using risk estimates from the published literature and national data sources for proportions exposed. We extended existing methods to account for the exposed population age structure. RESULTS: The estimated total AF for CMM is 2.0% (95% CI: 1.4-2.7%), giving 48 (95% CI: 33-64) deaths in (2012) and 241 (95% CI: 168-325) registrations (in 2011) attributable to occupational exposure to solar radiation. Higher exposure and larger numbers exposed led to much higher numbers for men than women. Industries of concern are construction, agriculture, public administration and defence, and land transport. CONCLUSIONS: These results emphasise the urgent need to develop appropriate strategies to reduce this burden.

The future excess fraction model for calculating burden of disease.

BACKGROUND: Estimates of the burden of disease caused by a particular agent are used to assist in making policy and prioritizing actions. Most estimations have employed the attributable fraction approach, which estimates the proportion of disease cases or deaths in a specific year which are attributable to past exposure to a particular agent. While this approach has proven extremely useful in quantifying health effects, it requires historical data on exposures which are not always available. METHODS: We present an alternative method, the future excess fraction method, which is based on the lifetime risk approach, and which requires current rather than historical exposure data. This method estimates the future number of exposure-related disease cases or deaths occurring in the subgroup of the population who were exposed to the particular agent in a specific year. We explain this method and use publically-available data on current asbestos exposure and mesothelioma incidence to demonstrate the use of the method. CONCLUSIONS: Our approach to modelling burden of disease is useful when there are no historical measures of exposure and where future disease rates can be projected on person years at risk.

Occupations associated with COPD risk in the large population-based UK Biobank cohort study.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Exposure to occupational hazards is an important preventable risk factor but the contribution of specific occupations to COPD risk in a general population is uncertain. Our aim was to investigate the association of COPD with occupation in the UK population. METHODS: In 2006-2010, the UK Biobank cohort recruited 502 649 adults aged 40-69 years. COPD cases were identified by prebronchodilator forced expiratory volume in 1 s/forced vital capacity

The proportion of cancer attributable to occupational exposures.

PURPOSE: To review the literature on the estimation of the population attributable fraction (PAF) of cancer due to occupational exposures and to describe challenges in the estimation of this metric. To help illustrate the inherent challenges, we also estimate PAFs for selected cancers diagnosed in the United States in 2010 attributable to work as a painter (causally associated with bladder and lung cancer) and shift work (possibly associated with breast cancer). METHODS: We reviewed and summarized previous reports providing quantitative estimates of PAF for total cancer due to occupational exposures. We calculated PAF estimates for painters and shift work using methodology from a detailed investigation of the occupational cancer burden in Great Britain, with adaptations made for the US population. RESULTS: The estimated occupation-attributable fraction for total cancer generally ranged between 2% and 8% (men, 3%-14%; women, 1%-2%) based on previous reports. We calculated that employment as a painter accounted for a very small proportion of cancers of the bladder and lung diagnosed in the United States in 2010, with PAFs of 0.5% for each site. In contrast, our calculations suggest that the potential impact of shift work on breast cancer (if causal) could be substantial, with a PAF of 5.7%, translating to 11,777 attributable breast cancers. CONCLUSIONS: Continued efforts to estimate the occupational cancer burden will be important as scientific evidence and economic trends evolve. Such projects should consider the challenges involved in PAF estimation, which we summarize in this report.

UK health performance: findings of the Global Burden of Disease Study 2010.

BACKGROUND: The UK has had universal free health care and public health programmes for more than six decades. Several policy initiatives and structural reforms of the health system have been undertaken. Health expenditure has increased substantially since 1990, albeit from relatively low levels compared with other countries. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to examine the patterns of health loss in the UK, the leading preventable risks that explain some of these patterns, and how UK outcomes compare with a set of comparable countries in the European Union and elsewhere in 1990 and 2010. METHODS: We used results of GBD 2010 for 1990 and 2010 for the UK and 18 other comparator nations (the original 15 members of the European Union, Australia, Canada, Norway, and the USA; henceforth EU15+). We present analyses of trends and relative performance for mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE). We present results for 259 diseases and injuries and for 67 risk factors or clusters of risk factors relevant to the UK. We assessed the UK's rank for age-standardised YLLs and DALYs for their leading causes compared with EU15+ in 1990 and 2010. We estimated 95% uncertainty intervals (UIs) for all measures. FINDINGS: For both mortality and disability, overall health has improved substantially in absolute terms in the UK from 1990 to 2010. Life expectancy in the UK increased by 4·2 years (95% UI 4·2-4·3) from 1990 to 2010. However, the UK performed significantly worse than the EU15+ for age-standardised death rates, age-standardised YLL rates, and life expectancy in 1990, and its relative position had worsened by 2010. Although in most age groups, there have been reductions in age-specific mortality, for men aged 30-34 years, mortality rates have hardly changed (reduction of 3·7%, 95% UI 2·7-4·9). In terms of premature mortality, worsening ranks are most notable for men and women aged 20-54 years. For all age groups, the contributions of Alzheimer's disease (increase of 137%, 16-277), cirrhosis (65%, ?15 to 107), and drug use disorders (577%, 71-942) to premature mortality rose from 1990 to 2010. In 2010, compared with EU15+, the UK had significantly lower rates of age-standardised YLLs for road injury, diabetes, liver cancer, and chronic kidney disease, but significantly greater rates for ischaemic heart disease, chronic obstructive pulmonary disease, lower respiratory infections, breast cancer, other cardiovascular and circulatory disorders, oesophageal cancer, preterm birth complications, congenital anomalies, and aortic aneurysm. Because YLDs per person by age and sex have not changed substantially from 1990 to 2010 but age-specific mortality has been falling, the importance of chronic disability is rising. The major causes of YLDs in 2010 were mental and behavioural disorders (including substance abuse; 21·5% [95 UI 17·2-26·3] of YLDs), and musculoskeletal disorders (30·5% [25·5-35·7]). The leading risk factor in the UK was tobacco (11·8% [10·5-13·3] of DALYs), followed by increased blood pressure (9·0 % [7·5-10·5]), and high body-mass index (8·6% [7·4-9·8]). Diet and physical inactivity accounted for 14·3% (95% UI 12·8-15·9) of UK DALYs in 2010. INTERPRETATION: The performance of the UK in terms of premature mortality is persistently and significantly below the mean of EU15+ and requires additional concerted action. Further progress in premature mortality from several major causes, such as cardiovascular diseases and cancers, will probably require improved public health, prevention, early intervention, and treatment activities. The growing burden of disability, particularly from mental disorders, substance use, musculoskeletal disorders, and falls deserves an integrated and strategic response. FUNDING: Bill & Melinda Gates Foundation.

Intervening to reduce the future burden of occupational cancer in britain: what could work?

In Britain, 14 carcinogenic agents and occupational circumstances currently account for 86% of estimated occupation attributable cancer. The future burden associated with these carcinogens has been forecast, using attributable fractions for forecast scenarios representing patterns of past and predicted future exposure, and exposure levels representing the introduction of new occupational exposure limits, increased levels of compliance with these limits and other reductions in worker exposure. Without intervention, occupational attributable cancers are forecast to remain at more than 10,000 by 2060. With modest intervention over 2,600, or with stricter interventions more than 8,200 cancers could be avoided by 2060 although because of long latency no impact will be seen until at least 10 years after intervention. Effective interventions assessed in this study include reducing workplace exposure limits and improving compliance with these limits. Cancers associated with asbestos, diesel engine exhaust, polycyclic aromatic hydrocarbons, work as a painter, radon, and solar radiation are forecast to continue, with construction remaining the prime industry of concern. Although exposure levels to the established carcinogens are falling, workers are remaining exposed at low levels at which there is still a cancer risk, although the aging population also contributes to rising cancer numbers, These forecasts can be used to assess the relative costs to society of different occupational carcinogenic agents, and the relative merits and savings associated with alternative intervention strategies. The methods are adaptable for different data circumstances, other types of interventions and could be extended to environmental carcinogens and other chronic diseases.

Occupational cancer in Britain. Exposure assessment methodology.

To estimate the current occupational cancer burden due to past exposures in Britain, estimates of the number of exposed workers at different levels are required, as well as risk estimates of cancer due to the exposures. This paper describes the methods and results for estimating the historical exposures. All occupational carcinogens or exposure circumstances classified by the International Agency for Research on Cancer as definite or probable human carcinogens and potentially to be found in British workplaces over the past 20-40 years were included in this study. Estimates of the number of people exposed by industrial sector were based predominantly on two sources of data, the CARcinogen EXposure (CAREX) database and the UK Labour Force Survey. Where possible, multiple and overlapping exposures were taken into account. Dose-response risk estimates were generally not available in the epidemiological literature for the cancer-exposure pairs in this study, and none of the sources available for obtaining the numbers exposed provided data by different levels of exposure. Industrial sectors were therefore assigned using expert judgement to 'higher'- and 'lower'-exposure groups based on the similarity of exposure to the population in the key epidemiological studies from which risk estimates had been selected. Estimates of historical exposure prevalence were obtained for 41 carcinogens or occupational circumstances. These include exposures to chemicals and metals, combustion products, other mixtures or groups of chemicals, mineral and biological dusts, physical agents and work patterns, as well as occupations and industries that have been associated with increased risk of cancer, but for which the causative agents are unknown. There were more than half a million workers exposed to each of six carcinogens (radon, solar radiation, crystalline silica, mineral oils, non-arsenical insecticides and 2,3,7,8-tetrachlorodibenzo-p-dioxin); other agents to which a large number of workers are exposed included benzene, diesel engine exhaust and environmental tobacco smoke. The study has highlighted several industrial sectors with large proportions of workers potentially exposed to multiple carcinogens. The relevant available data have been used to generate estimates of the prevalence of past exposure to occupational carcinogens to enable the occupational cancer burden in Britain to be estimated. These data are considered adequate for the present purpose, but new data on the prevalence and intensity of current occupational exposure to carcinogens should be collected to ensure that future policy decisions be based on reliable evidence.

Occupational cancer burden in Great Britain.

A sound knowledge base is required to target resources to reduce workplace exposure to carcinogens. This project aimed to provide an objective estimate of the burden of cancer in Britain due to occupation. This volume presents extensive analyses for all carcinogens and occupational circumstances defined as definite or probable human occupational carcinogens by the International Agency for Research on Cancer. This article outlines the structure of the supplement - two methodological papers (statistical approach and exposure assessment), eight papers presenting the cancer-specific results grouped by broad anatomical site, a paper giving industry sector results and one discussing work-related cancer-prevention strategies. A brief summary of the methods and an overview of the updated overall results are given in this introductory paper. A general discussion of the overall strengths and limitations of the study is also presented. Overall, 8010 (5.3%) total cancer deaths in Britain and 13,598 cancer registrations were attributable to occupation in 2005 and 2004, respectively. The importance of cancer sites such as mesothelioma, sinonasal, lung, nasopharynx, breast, non-melanoma skin cancer, bladder, oesophagus, soft tissue sarcoma and stomach cancers are highlighted, as are carcinogens such as asbestos, mineral oils, solar radiation, silica, diesel engine exhaust, coal tars and pitches, dioxins, environmental tobacco smoke, radon, tetrachloroethylene, arsenic and strong inorganic mists, as well as occupational circumstances such as shift work and occupation as a painter or welder. The methods developed for this project are being adapted by other countries and extended to include social and economic impact evaluation.

Occupational cancer in Britain. Statistical methodology.

An approach using the attributable fraction (AF) has been developed to estimate the current burden of occupational cancer in Britain. The AF combines the relative risk (RR) associated with exposure with the proportion exposed. For each cancer-exposure pairing, the RR is selected from key epidemiological literature such as an industry, or population-based study, meta-analysis or review. The CARcinogen EXposure (CAREX) database provides point estimates for the number of workers exposed to a range of carcinogens; alternative sources are national surveys such as the Labour Force Survey and Census of Employment. The number of workers exposed are split between high and low exposure levels matched to appropriate RRs from the literature. The relevant period for cancer development during which exposure occurred is defined as the risk exposure period (REP). Estimation of the numbers ever exposed over the REP takes into account the changes in the number of people employed in primary and manufacturing industry and service sectors in Britain where appropriate, and adjustment is made for staff turnover over the period and for life expectancy. National estimates of the population ever of working age during the REP are used for the proportion denominator. Strategies have been developed to combine exposure AFs correctly while avoiding double counting and minimising bias. The AFs are applied to national cancer deaths and registrations to obtain occupation-attributable cancer numbers. The methods are adaptable for other diseases and other geographies, and are also adaptable to more sophisticated modelling if better exposure and dose-response data are available.

Toward risk reduction: predicting the future burden of occupational cancer.

Interventions to reduce cancers related to certain occupations should be evidence-based. The authors have developed a method for forecasting the future burden of occupational cancer to inform strategies for risk reduction. They project risk exposure periods, accounting for cancer latencies of up to 50 years, forward in time to estimate attributable fractions for a series of forecast target years given past and projected exposure trends and under targeted reduction scenarios. Adjustment factors for changes in exposed numbers and levels are applied in estimation intervals within the risk-exposure periods. The authors illustrate the methods by using a range of scenarios for reducing lung cancer due to occupational exposure to respirable crystalline silica. Attributable fractions for lung cancer due to respirable crystalline silica could be potentially reduced from 2.07% in 2010 to nearly 0% by 2060, depending on the timing and success of interventions. Focusing on achieving compliance with current exposure standards in small industries can be more effective than setting standards at a lower level. The method can be used to highlight high-risk carcinogens, industries, and occupations. It is adaptable for other countries and other exposure situations in the general environment and can be extended to include socioeconomic impact assessment.