Eve Bourgkard

Lung Cancer and Exposure to Metals: The Epidemiological Evidence

Exposure to metallic compounds is ubiquitous, with its widespread use in industry and its presence, mostly in trace amounts, in the environment. This paper reviews the epidemiologic evidence of the relation between lung cancer and exposure to metallic compounds by building on and updating the corresponding International Agency for Research on Cancer (IARC) assessments. Given that most of the well-identified human populations with given metal exposure are in occupational settings, this review is mostly based on results in occupational epidemiology. The epidemiological evidence is shortly reviewed for accepted carcinogens: chromium, nickel, beryllium, cadmium, arsenic, and silicon, highlighting what is still unclear. We then review in more detail metals for which the evidence is less clear: lead, titanium, iron, and cobalt. There is scarce evidence for the human carcinogenicity of titanium. Exposure to titanium dioxide is associated with lung cancer excesses in one large study, but this excess may be due to confounders. The evidence for lead is contradictory. The lung cancer risk is presented as a function of a post hoc exposure ranking but no dose-response relationship is found. A weak but consistent lung cancer excess in many populations exposed to iron oxides but it is not possible to state on causality. Finally the evidence in the hard metal industry is presented, which suggests a possible carcinogenic effect of cobalt in presence of tungsten carbide. A short discussion presents the limitations of epidemiology in assessing the carcinogenicity of metals.

Effects of Talc Dust on Respiratory Health: Results of a Longitudinal Survey of 378 French and Austrian Talc Workers

Objectives: The aim of this longitudinal study was to investigate the effects on respiratory health of talc dust, free of asbestiform fibres, at or below airborne concentrations of 2 mg/m3. Methods: The respiratory health and dust exposure of all workers with at least 5 years of employment at two talc producing facilities in France and Austria were surveyed between 1988 and 2003. Standard forced expiratory volumes and standard chest x rays were obtained on repeated occasions and recorded using strict quality control procedures. Of a target population of 430 subjects, 378 (88%) were examined at least twice. A quantitative exposure matrix was set up based on 4602 personal exposure measurements of respirable dust and qualitative descriptions of the industrial processes and individual protection devices. Results: The mean duration of follow-up was 14.5 years with a mean estimated talc dust concentration during follow-up of 1.46 mg/m3. The prevalence of small radiological opacities and lung function parameters were significantly related to cumulative exposure at inclusion but not to exposure during the study period. Overall, the forced expiratory volume in 1 s decreased by 66 ml per 100 years.mg/m3, which is less than that reported for other types of mineral dusts. Conclusions: Although early exposure levels to talc as assessed at inclusion were associated with decreased lung function and an increased prevalence of small radiological opacities, there was no evidence of detrimental effects of talc exposure, as assessed within the study period, on lung function and small radiological opacities.

The 2-phase case-control design: an efficient way to use expert-time.

OBJECTIVES The objective of this paper is to show the benefits of using a 2-phase case-control (2PCC) design in identifying dose-response relationships between cumulative occupational exposure as assessed by experts and lung cancer incidence in an actual study. METHODS A population-based case-control study including 246 cases and 531 controls was conducted in an area with high lung cancer rates in Northeast France. Detailed occupational and personal risk factors were obtained in face-to-face interviews. Cumulative expert-based exposure scores were obtained from a subset of 215 cases and 269 controls stratified on smoking and a prior algorithmic exposure score for asbestos, crystalline silica, and polycyclic aromatic hydrocarbons (PAH) in the framework of a 2PCC design. This subset deliberately under-sampled large strata among controls but not among cases. Logistic regression models adapted to 2PCC studies were applied and corresponding computations of attributable fractions and their confidence intervals developed. RESULTS Based on this 2PCC design, statistically significant dose-response relationships were obtained for asbestos, crystalline silica, PAH, and diesel motor exhaust. Simulations within this study showed that 2PCC studies were always more powerful than random samples. CONCLUSION The 2PCC design may be the design of choice when resources allow only a limited number of subjects with a full expert-based exposure assessment.

0111 Mortality study among Paris sewage workers

Objectives To describe the mortality of sewage workers from Paris (France). Method The cohort of 1594 Paris sewage workers since 1970 was set up in 2010 and followed-up on mortality from 1970 to 2010. Vital status and causes of death were determined by matching with national databases. Standardised Mortality Ratios (SMRs) were computed using local death rates by causes of death and 10-year employment duration classes. Data are currently analysed using relative survival techniques. This study was approved by the national ethic comity. Results Statistically significant mortality excess was observed for all causes (SMR=1.34, 778 cases) and for cancer (SMR=1.49, 337 cases). SMRs were also statistically greater than 1 for malignant (SMR=1.74, 22 cases) and non-malignant (SMR=1.77, 43 cases) liver diseases, lung cancer (SMR=1.59, 97 cases), oesophagus cancer (SMR=2.35, 28 cases), all alcohol-related diseases (SMR=1.78, 128 cases), and suicide (SMR=3.64, 22 cases). Greater than 1 but not statistically significant SMRs were observed for infectious diseases and respiratory infectious diseases. The mortality from several diseases (all causes, all cancer, oesophagus cancer, lung cancer, chronic liver diseases, all alcohol-related diseases, and infectious diseases) increased with employment duration as a sewer worker. Except for lung cancer, the SMR for smoking-related diseases was not statistically greater than 1. Results of survival analysis are in progress. Conclusions The increase mortality observed for lung cancer and infectious diseases with employment duration suggests possible occupational health effect among sewer workers. Conclusions will be completed from the survival analysis.

Bladder cancer and occupational exposure to metalworking fluid mist: a counter-matched case–control study in French steel-producing factories

Objectives To assess the relationship between occupational exposure to metalworking fluids (MWFs) in the steel-producing industry and bladder cancer incidence. Methods A nested case–control study on bladder cancer was set up in a cohort of workers from six French steel-producing factories. Three controls were randomly selected for each incident bladder cancer case diagnosed from 2006 to 2012. Controls were matched to cases on age at diagnosis and counter-matched on a surrogate measure of exposure to MWFs derived from a job-exposure matrix. Cases (n=84) and controls (n=251) were face-to-face interviewed. Experts assessed occupational exposure to MWFs (straight, soluble and synthetic) using questionnaires and reports from factory visits. Occupational exposures were based on three metrics: duration, frequency-weighted duration and cumulative exposure index. Conditional multiple logistic regressions were used to determine ORs and 95% CIs, taking non-occupational and occupational exposure into account. Results In the 25 years before diagnosis, ORs increased significantly with duration of exposure to straight MWFs (OR=1.13 (1.02–1.25)) and increased with frequency-weighted duration of exposure to straight MWFs (OR=1.44 (0.97–2.14)). These results remained valid after adjusting for duration of smoking, average number of cigarettes smoked per day, time since smoking cessation and exposure to polycyclic aromatic hydrocarbons (PAHs). ORs also increased with soluble MWFs but not significantly. No significant association was found with older exposures to MWFs or with exposure to synthetic MWFs. Conclusion The increased risk of bladder cancer observed among workers exposed to straight MWFs and to a lesser extent to soluble MWFs may be explained by the presence of carcinogens (such as PAH) in mineral oils component of straight and soluble oils. Prevention therefore remains necessary in sectors using MWFs.

0072 Oil mist, from exposure determinants to early effect markers: an integrative study design

The present project focuses on the effects of occupational exposure to oil mists on a panel of exposure and effect biomarkers in an epidemiological study. The assumption is that different health outcomes are caused by reactive particles causing oxidative stress leading to lung inflammation and ultimately cancer or asthma. Ninety workers from France and Switzerland (30 controls, 30 exposed to straight cutting oil and 30 to soluble cutting oil) will be followed over two days after a non-exposed period of at least two days. The exposure assessment is based on measurements of particles, metals, aldehydes, amines, the intrinsic oxidative potential of aerosols and the cutting oil. Furthermore, exposure biomarkers are measured in exhaled breath condensate (EBC)- metals, ions (nitrite, nitrate...) and urine –metals, metabolites of PAHs- . Finally, exposure determinants will be collected to guide future efforts in exposure prevention. Effect biomarkers of oxidative stress (malondialdéhyde, 8-isoprostane, 8-hydroxy-2’-deoxyguanosine) in EBC and urine will be repeatedly measured as well as exhaled nitric oxide (FeNO), an inflammation marker. Genotoxic effects will be assessed using the buccal micronucleus cytome assay. Finally, the possible chronic effects of oil mist exposure on respiratory health will be explored by standard questionnaires. This integrative project will gain insights in the exposure determinants that drive the physiopathological effects, thus allowing an efficient prevention strategy to be developed.

O22-1 Bladder cancer and occupational exposure to metalworking fluid mist: a nested case-control study in french steel-producing factories

Objective To assess possible relationships between occupational exposure to metalworking fluid (MWF) mist and bladder cancer risk. Methods A nested case-control study was conducted within a cohort of workers from 6 steel-producing factories. Cases were diagnosed with bladder cancer in 2006–2012. Three controls per case were randomly selected from the cohort, matched to cases by age at diagnostic and counter-matched according to 4 strata of surrogate measure of exposure to MWF mists, assessed using a job-exposure matrix. Cases (n = 84) and controls (n = 251) provided information during personal interviews on occupational history, including the type of MWF used (straight oils, soluble oils, synthetic fluids), and smoking habits. Experts estimated intensity, frequency and probability of exposure to each MWF mist. Conditional logistic regression, adapted to counter-matching, was used to calculate Odds-Ratios (OR) and 95% confidence intervals (95% CI), taking into account the 3 types of MWF mist, and adjusting for smoking and other occupational factors. Results A statistically significant OR for bladder cancer was observed for workers exposed to MWF mist, for over 20 years during occupational history (OR 3.32, 95% CI: 1.48–7.46). ORs were statistically significant for workers ever exposed to straight oils (OR 2.14, 95% CI: 1.05–4.36), for over 20 years during occupational history (OR 5.49, 95% CI: 1.75–17.2). ORs statistically not greater than 1 were observed for workers ever exposed to soluble oils (OR 1.46, 95% CI: 0.71–3.02), for over 20 years during occupational history (OR 2.43, 95% CI: 0.88–6.70). OR was not statistically significant for workers ever exposed to synthetic fluids (OR 1.2, 95% CI: 0.31–3.30). Dose-response relationships were observed with cumulative exposure to MWF mist and straight oils in the last 20 years before diagnosis. Conclusion This study highlighted association between recent exposure to straight oils and bladder cancer risk, but did not detect any relationship concerning soluble oils or synthetic fluids.