Occupational Benzene Exposure and Lung Cancer Risk: A Pooled Analysis of 14 Case-Control Studies.

Rationale: Benzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer. Objectives: We aimed to examine the relationship between occupational benzene exposure and lung cancer. Methods: Subjects from 14 case-control studies across Europe and Canada were pooled. We used a quantitative job-exposure matrix to estimate benzene exposure. Logistic regression models assessed lung cancer risk across different exposure indices. We adjusted for smoking and five main occupational lung carcinogens and stratified analyses by smoking status and lung cancer subtypes. Measurements and Main Results: Analyses included 28,048 subjects (12,329 cases, 15,719 control subjects). Lung cancer odds ratios ranged from 1.12 (95% confidence interval, 1.03-1.22) to 1.32 (95% confidence interval, 1.18-1.48) (Ptrend = 0.002) for groups with the lowest and highest cumulative occupational exposures, respectively, compared with unexposed subjects. We observed an increasing trend of lung cancer with longer duration of exposure (Ptrend < 0.001) and a decreasing trend with longer time since last exposure (Ptrend = 0.02). These effects were seen for all lung cancer subtypes, regardless of smoking status, and were not influenced by specific occupational groups, exposures, or studies. Conclusions: We found consistent and robust associations between different dimensions of occupational benzene exposure and lung cancer after adjusting for smoking and main occupational lung carcinogens. These associations were observed across different subgroups, including nonsmokers. Our findings support the hypothesis that occupational benzene exposure increases the risk of developing lung cancer. Consequently, there is a need to revisit published epidemiological and molecular data on the pulmonary carcinogenicity of benzene.

The Association of Post-COVID-19-Related Symptoms and Preceding Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Fully Vaccinated Paramedics in Canada.

This study investigated the association between previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and risk of symptoms associated with post-COVID conditions among fully vaccinated paramedics in Canada. We included vaccinated paramedics who provided blood sample and questionnaire data on the same date during the study period. We examined the presence of symptoms associated with post-COVID conditions and depression severity against prior SARS-CoV-2 infection categories. Compared to the "no previous SARS-CoV-2 infection" group, there was no detected association between known prior SARS-CoV-2 infection (odds ratio [OR], 1.42 [95% confidence interval {CI}, 0.96-2.09]), nor unknown prior SARS-CoV-2 infection (OR, 0.54 [95% CI, 0.29-1.00]), and the presence of symptoms associated with post-COVID conditions.

Carpal tunnel syndrome among Manitoba workers: Results from the Manitoba Occupational Disease Surveillance System.

BACKGROUND: Carpal tunnel syndrome (CTS) is associated with occupational high-force repetitive tasks and vibration. This project examines the relationship between CTS and work to: (1) identify jobs and industries with increased CTS risk; (2) explore whether there is a sex difference in the risk of CTS after controlling for occupation; and (3) determine whether any observed relationships persist after excluding Workers Compensation Board (WCB) accepted time-loss CTS claims. METHODS: We linked 95.5% of time-loss WCB claims from 2006 to 2019 to provincial administrative health data. The cohort included 143,001 unique person-occupation combinations. CTS cases were defined as at least two medical claims for (ICD-9 354) within a 12-month period or a surgical claim for CTS from 2 years before the WCB claim to 3 years after. WCB accepted CTS time-loss claims not identified by the medical claims were also included. RESULTS: A total of 4302 individuals (3.0%) met the CTS definition. Analysis revealed that the hazard ratios (HRs) of CTS vary considerably with occupation. Sex-based differences in CTS risks were observed, both in low- and high-risk occupations. In many occupations with increased HR, the HR remained elevated after excluding accepted time-loss WCB cases. CONCLUSIONS: The risk of developing CTS varied with occupation. Job titles with ergonomic risk factors had higher risks than those with lower exposures. This finding remained after eliminating time-loss compensated WCB cases, suggesting that all cases of CTS in high risk jobs are not identified in WCB statistics. Female workers in some job titles had excess CTS cases compared to male workers within the same job title.

Comparison of internal and external reference populations for occupational cancer surveillance in a cohort drawn from a diverse workforce.

OBJECTIVES: Prior analyses of the Occupational Disease Surveillance System (ODSS) have compared cancer rates using internal referent groups. As an exploratory analysis, we sought to estimate cancer risk using general population reference rates to evaluate the impact that the comparison population has on findings from our surveillance program. METHODS: A cohort of approximately 2.3 million workers in Ontario, Canada with an accepted lost-time workers' compensation claim were followed for all cancer diagnoses between 1983 and 2018. Standardized incidence ratios (SIRs) and 95% confidence intervals were calculated for workers in specific occupational groups using (1) all other workers in the ODSS cohort, and (2) the general population of Ontario. RESULTS: SIRs using the general population reference group were generally equal to or modestly lower compared to SIRs using the internal reference group. Within occupation groups, SIRs had a discordant direction of association (increased rate in the internal comparison and decreased in the external comparison) for some cancer sites including urinary, prostate, and colorectal. CONCLUSIONS: Findings emphasize the importance of the choice of reference group when evaluating cancer risks in large occupational surveillance cohorts. Importantly, the magnitude of confounding and the healthy worker hire bias may depend on the occupation group and cancer site of interest.

Prevalent occupational exposures and risk of lung cancer among women: Results from the application of the Canadian Job-Exposure Matrix (CANJEM) to a combined set of ten case-control studies.

BACKGROUND: Worldwide, lung cancer is the second leading cause of cancer death in women. The present study explored associations between occupational exposures that are prevalent among women, and lung cancer. METHODS: Data from 10 case-control studies of lung cancer from Europe, Canada, and New Zealand conducted between 1988 and 2008 were combined. Lifetime occupational history and information on nonoccupational factors including smoking were available for 3040 incident lung cancer cases and 4187 controls. We linked each reported job to the Canadian Job-Exposure Matrix (CANJEM), which provided estimates of probability, intensity, and frequency of exposure to each selected agent in each job. For this analysis, we selected 15 agents (cleaning agents, biocides, cotton dust, synthetic fibers, formaldehyde, cooking fumes, organic solvents, cellulose, polycyclic aromatic hydrocarbons from petroleum, ammonia, metallic dust, alkanes C18+, iron compounds, isopropanol, and calcium carbonate) that had lifetime exposure prevalence of at least 5% in the combined study population. For each agent, we estimated lung cancer risk in each study center for ever-exposure, by duration of exposure, and by cumulative exposure, using separate logistic regression models adjusted for smoking and other covariates. We then estimated the meta-odds ratios using random-effects meta-analysis. RESULTS AND CONCLUSIONS: None of the agents assessed showed consistent and compelling associations with lung cancer among women. The following agents showed elevated odds ratio in some analyses: metallic dust, iron compounds, isopropanol, and organic solvents. Future research into occupational lung cancer risk factors among women should prioritize these agents.

Incidence of cancer among Nordic police officers.

Police work may expose officers to various circumstances that have potential for increasing their risk of cancer, including traffic-related air pollution, night shift work and radiation from radars. In this study, we examined the incidence of cancer among Nordic male and female police officers. We utilize data from the Nordic Occupational Cancer (NOCCA) project, which linked census data on occupations from Finland, Iceland, Norway and Sweden to national cancer registries for the period 1961 to 2005. We report standardized incidence ratios (SIR) and 95% confidence intervals (CI) of selected cancers for each country by sex, age and calendar period. The cohort included 38 523 male and 1998 female police officers. As compared with the general population, male police officers had a 7% (95% CI: 4-9%) excess cancer risk, with elevated SIRs for various cancer sites, including prostate (SIR 1.19, 1.14-1.25), breast (SIR 1.77, 1.05-2.80), colon (SIR 1.22, 1.12-1.32) and skin melanoma (SIR 1.44, 1.28-1.60). Conversely, male police officers had a lower risk of lung cancer than the general population (SIR 0.72, 0.66-0.77). In female police officers, the SIR for cancer overall was 1.15 (0.98-1.34), and there was a slight excess of cancers of the breast (SIR 1.25, 0.97-1.59) and colon (SIR 1.21, 0.55-2.30). In conclusion, cancer incidence among the police officers was slightly higher than in the general population. Notably, SIRs were elevated for cancer sites potentially related to night shift work, namely colon, breast and prostate cancer.

Occupational exposure to nickel and hexavalent chromium and the risk of lung cancer in a pooled analysis of case-control studies (SYNERGY).

There is limited evidence regarding the exposure-effect relationship between lung-cancer risk and hexavalent chromium (Cr(VI)) or nickel. We estimated lung-cancer risks in relation to quantitative indices of occupational exposure to Cr(VI) and nickel and their interaction with smoking habits. We pooled 14 case-control studies from Europe and Canada, including 16 901 lung-cancer cases and 20 965 control subjects. A measurement-based job-exposure-matrix estimated job-year-region specific exposure levels to Cr(VI) and nickel, which were linked to the subjects' occupational histories. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated by unconditional logistic regression, adjusting for study, age group, smoking habits and exposure to other occupational lung carcinogens. Due to their high correlation, we refrained from mutually adjusting for Cr(VI) and nickel independently. In men, ORs for the highest quartile of cumulative exposure to CR(VI) were 1.32 (95% CI 1.19-1.47) and 1.29 (95% CI 1.15-1.45) in relation to nickel. Analogous results among women were: 1.04 (95% CI 0.48-2.24) and 1.29 (95% CI 0.60-2.86), respectively. In men, excess lung-cancer risks due to occupational Cr(VI) and nickel exposure were also observed in each stratum of never, former and current smokers. Joint effects of Cr(VI) and nickel with smoking were in general greater than additive, but not different from multiplicative. In summary, relatively low cumulative levels of occupational exposure to Cr(VI) and nickel were associated with increased ORs for lung cancer, particularly in men. However, we cannot rule out a combined classical measurement and Berkson-type of error structure, which may cause differential bias of risk estimates.

Do patterns of past asbestos use and production reflect current geographic variations of cancer risk?: mesothelioma in Ontario and British Columbia, Canada.

PURPOSE: Canada was a major global asbestos producer and consumer. Geographic patterns of Canadian asbestos use and mesothelioma, a highly fatal cancer linked to asbestos exposure, have not been previously reported. This study summarized key trends in mesothelioma incidence by geography and time in two Canadian provinces, Ontario and British Columbia (BC), and explored how past workforce characteristics and geographic trends in asbestos production and use may shape variations in regional rates of mesothelioma. METHODS: We report trends in mesothelioma incidence (1993-2016) for Ontario and British Columbia using population-based incidence data that were age-standardized to the 2011 Canadian population. Historical records of asbestos production and use were analyzed to geo-locate industrial point sources of asbestos in Ontario and BC. The prevalence of occupations in regions with the highest and lowest rates of mesothelioma in Ontario and BC were calculated using labor force statistics from the 1981 Canadian Census. RESULTS: Regional mesothelioma rates varied in both provinces over time; more census divisions in both Ontario and BC registered mesothelioma rates in the highest quintile of incidences during the period 2009 to 2016 than in any prior period examined. Certain occupations such as construction trades workers were more likely to be overrepresented in regions with high mesothelioma rates. CONCLUSION: This work explored how studying asbestos exposure and mesothelioma incidence at small-scale geographies could direct cancer surveillance and research to more targeted areas. Findings indicated that regional variations in mesothelioma could signal important differences in past occupational and potentially environmental exposures.

Radon and lung cancer in the pooled uranium miners analysis (PUMA): highly exposed early miners and all miners.

OBJECTIVES: Radon is a ubiquitous occupational and environmental lung carcinogen. We aim to quantify the association between radon progeny and lung cancer mortality in the largest and most up-to-date pooled study of uranium miners. METHODS: The pooled uranium miners analysis combines 7 cohorts of male uranium miners with 7754 lung cancer deaths and 4.3 million person-years of follow-up. Vital status and lung cancer deaths were ascertained between 1946 and 2014. The association between cumulative radon exposure in working level months (WLM) and lung cancer was modelled as the excess relative rate (ERR) per 100 WLM using Poisson regression; variation in the association by temporal and exposure factors was examined. We also examined analyses restricted to miners first hired before 1960 and with <100 WLM cumulative exposure. RESULTS: In a model that allows for variation by attained age, time since exposure and annual exposure rate, the ERR/100 WLM was 4.68 (95% CI 2.88 to 6.96) among miners who were less than 55 years of age and were exposed in the prior 5 to <15 years at annual exposure rates of <0.5 WL. This association decreased with older attained age, longer time since exposure and higher annual exposure rate. In analyses restricted to men first hired before 1960, we observed similar patterns of association but a slightly lower estimate of the ERR/100 WLM. CONCLUSIONS: This new large, pooled study confirms and supports a linear exposure-response relationship between cumulative radon exposure and lung cancer mortality which is jointly modified by temporal and exposure factors.

Cancer Risks among Emergency Medical Services Workers in Ontario, Canada.

OBJECTIVES: Emergency medical services workers, such as paramedics, provide important emergency care and may be exposed to potential carcinogens while working. Few studies have examined the risk of cancer among paramedics demonstrating an important knowledge gap in existing literature. This study aimed to investigate cancer risks among paramedics in a large cohort of Ontario workers. METHODS: Paramedics were identified in the Occupational Disease Surveillance System (ODSS) from 1996 to 2019. The ODSS was established by linking lost-time worker's compensation claims to administrative health data, including the Ontario Cancer Registry to identify incident cases of cancer. Cox-proportional hazard models were used to calculate age and sex-adjusted hazard ratios and 95% confidence intervals to estimate the risk of cancer among paramedics compared to all other workers in the ODSS. RESULTS: A total of 7240 paramedics were identified, with just over half of the paramedics identifying as male similar to the overall ODSS cohort. Paramedics had a statistically significant elevated risk of any cancer (HR 1.19, 95% CI 1.06-1.34), and elevated risks for melanoma (HR 2.18, 95% CI 1.46-3.26) and prostate cancer (HR 1.73, 95% CI 1.34-2.22). Paramedics had a statistically significant reduced risk for lung cancer (HR 0.48, 95% CI 0.28-0.83). Findings were similar to cancer risks identified in firefighters and police in the same cohort. CONCLUSIONS: This study contributes valuable findings to understanding cancer risks among paramedics and further supports the existing evidence on the increased risk of cancer among emergency medical services workers. We have observed some similar results for firefighters and police, which may be explained by similar exposures, including vehicle exhaust, shiftwork, and intermittent solar radiation. This can lead to a better understanding of carcinogens and other exposures among paramedics and inform cancer prevention strategies.

Radon exposure and risk of neurodegenerative diseases among male miners in Ontario, Canada: A cohort study.

BACKGROUND: Environmental radon has been examined as a risk factor for neurodegenerative diseases in a small number of previous studies, but the findings have been inconsistent. This study aims to investigate the association between occupational radon exposure and neurodegenerative disease in a cohort of male miners with work experience in multiple ore types in Ontario, Canada. METHODS: Radon exposure (1915-1988) was assessed using two job-exposure matrices (JEM) constructed from using historical records for 34,536 Ontario male miners. Neurodegenerative outcomes were ascertained between 1992 and 2018. Poisson regression models were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI) between cumulative radon exposure in working level months (WLM) and each neurodegenerative outcome. RESULTS: Levels of cumulative radon exposure showed variability among cohort members with a mean of 7.5 WLM (standard deviation 24.4). Miners in uranium mines or underground jobs had higher levels and more variability in exposure than workers in non-uranium work or surface jobs. Compared to the reference group (radon < 1 WLM), increased rates of Alzheimer's (RR 1.23, 95% CI 1.05-1.45) and Parkinson's disease (RR 1.43, 95% CI 1.08-1.89) were observed among workers with >1-5 WLM and >5-10 WLM, respectively, but not among higher exposed workers (>10 WLM). CONCLUSION: This study did not observe a positive monotonic dose-response relationship between cumulative radon exposure and Alzheimer's or Parkinson's disease in Ontario mining workers. There was no association observed with motor neuron disease.

A Higher Antibody Response Is Generated With a 6- to 7-Week (vs Standard) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine Dosing Interval.

The optimal dosing interval for severe acute respiratory syndrome coronavirus 2 vaccines remains controversial. In this prospective study, we compared serology results of paramedics vaccinated with mRNA vaccines at the recommended short (17-28 days) vs long (42-49 days) interval. We found that a long dosing interval resulted in higher spike, receptor binding domain, and spike N terminal domain antibody concentrations.

A Prospective Observational Cohort Comparison of SARS-CoV-2 Seroprevalence Between Paramedics and Matched Blood Donors in Canada During the COVID-19 Pandemic.

STUDY OBJECTIVE: SARS-CoV-2 represents an occupational risk to paramedics, who work in uncontrolled environments. We sought to identify the occupation-specific risk to paramedics by comparing their seroprevalence of SARS-CoV-2 infection-specific antibodies to that of blood donors in Canada. METHODS: In this prospective cohort study, we performed serology testing (Elecsys Anti-SARS-CoV-2 nucleocapsid assay) on samples from paramedics and blood donors (January to July 2021) in Canada. Paramedic samples were compared to blood donor samples through 1:1-matched (based on age, sex, location, date of blood collection, and vaccination status) and raking weighted comparisons. We compared the seroprevalence with a risk difference (and 95% confidence interval [CI]) and performed secondary analyses within subgroups defined by vaccination status. RESULTS: The 1:1 match included 1,627 cases per group; in both groups, 723 (44%) were women, with a median age of 38. The raking weighted comparison included 1,713 paramedic samples and 19,515 blood donor samples, with similar characteristics. In the 1:1 match, the seroprevalence was similar (difference 1.2; 95% CI -0.20 to 2.7) between paramedics (5.2%) and blood donors (3.9%). The raking weighted comparison was consistent (difference 0.97; 95% CI -0.10 to 2.0). The unvaccinated paramedic samples, in comparison to the blood donor samples, demonstrated a higher seroprevalence in the 1:1 (difference 5.9; 95% CI 1.8 to 10) and weighted (difference 6.5; 95% CI 1.8 to 10) comparisons. Among vaccinated cases, the between-group seroprevalence was similar. CONCLUSION: Overall, paramedics demonstrated similar evidence of prior SARS-CoV-2 infection to that of blood donors. However, among unvaccinated individuals, evidence of prior infection was higher among paramedics compared to blood donors.

Comparison of cancer incidence and mortality in the Norwegian Fire Departments Cohort, 1960-2018.

OBJECTIVES: Elevated risk of cancer at several sites has been reported among firefighters, although with mixed findings. The purpose of this study was to calculate standardised incidence ratios (SIRs) and standardised mortality ratios (SMRs) for cancer and compare them to assess whether use of the different measures could be a source of inconsistencies in findings. METHODS: The Norwegian Fire Departments Cohort, comprising 4295 male employees who worked at 15 fire departments across Norway, was linked to health outcome registries for the period 1960-2018. SIRs and SMRs were derived using national reference rates. RESULTS: Overall, we observed elevated incidence of colon cancer (SIR, 95% CI 1.27, 1.01 to 1.58), mesothelioma (2.59, 1.12 to 5.11), prostate cancer (1.18, 1.03 to 1.34) and all sites combined (1.15, 1.08 to 1.23). Smaller, non-significant elevations were found for mortality of colon cancer (SMR, 95% CI 1.20, 0.84 to 1.67) and mesothelioma (1.66, 0.34 to 4.86), while SMR for prostate cancer was at unity. Potential errors were observed in some of the mortality data, notably for mesothelioma cases. Among those who died of cancer, 3.7% (n=14) did not have a prior diagnosis of malignancy at the same site group. CONCLUSIONS: Assessment of incidence or mortality did not greatly influence the interpretation of results. The most prominent differences in SIR and SMR appeared to be due to inconsistencies between sites of cancer diagnosis and cause of death. The difference in SIR and SMR for prostate cancer suggested a detection bias from differential screening practices.

Cancer risk among firefighters and police in the Ontario workforce.

OBJECTIVE: Firefighters and police often work in high-stress, complex environments with known and suspected carcinogenic exposures. We aimed to characterise cancer incidence among firefighters and police. METHODS: The Occupational Disease Surveillance System (ODSS) was used to identify workers employed as firefighters or police in Ontario. A cohort of workers were identified using lost-time workers' compensation claims data and followed for cancer in the Ontario Cancer Registry (1983-2020). Cox proportional hazard models were used to estimate HRs and 95% CIs for primary site-specific cancer diagnoses adjusted for age at start of follow-up, birth year and sex. RESULTS: A total of 13 642 firefighters and 22 595 police were identified in the cohort. Compared with all other workers in the ODSS, firefighters and police had increased risk of prostate cancer (firefighters: HR=1.43, 95% CI 1.31 to 1.57; police: HR=1.47, 95% CI 1.35 to 1.59), colon cancer (firefighters: HR=1.39, 95% CI 1.19 to 1.63; police: HR=1.39, 95% CI 1.21 to 1.60) and skin melanoma (firefighters: HR=2.38, 95% CI 1.99 to 2.84; police: HR=2.27, 95% CI 1.96 to 2.62). Firefighters also had increased risk of cancer of the pancreas, testis and kidney, as well as non-Hodgkin's lymphoma and leukaemia. Police had increased risk of thyroid, bladder and female breast cancer. When compared directly with the police, firefighters had an elevated risk of mesothelioma and testicular cancer. CONCLUSIONS: Firefighters and police demonstrated some similar as well as some unique cancer risks. Findings from this larger worker population may have important implications for workplace and policy-level changes to improve preventative measures and reduce potential exposures to known carcinogenic hazards.

The current burden of non-melanoma skin cancer attributable to ultraviolet radiation and related risk behaviours in Canada.

PURPOSE: Ultraviolet radiation (UVR) is an established cause of non-melanoma skin cancer (NMSC)-basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The aim of this study was to estimate the current burden of BCC and SCC associated with UVR and modifiable UVR behaviours (sunburn, sunbathing, and indoor tanning) in Canada in 2015. METHODS: The current burden of BCC and SCC associated with UVR was estimated by comparing 2015 incidence rates with rates of less exposed body sites (trunk and lower limbs) after adjusting for estimated surface areas. The burden associated with modifiable UVR behaviours was estimated by using prevalence estimates among Caucasians from the Second National Sun Survey, and relative risks that are generalizable to Canadians from conducting meta-analyses of relevant studies. RESULTS: We estimated that 80.5% of BCCs and 83.0% of SCCs were attributable to UVR. Adult sunburn was associated with relative risks of 1.85 (95% CI 1.15-3.00) for BCC and 1.41 (95% CI 0.91-2.18) for SCC, while adult sunbathing was associated with relative risks of 1.82 (95% CI 1.52-2.17) for BCC and 1.14 (95% CI 0.53-2.46) for SCC. We estimated that 18.6% of BCCs and 9.9% of SCCs were attributable to adult sunburn, while 28.1% of BCCs were attributable to adult sunbathing. We estimated that 46.2% of BCCs and 17.3% of SCCs were attributable to modifiable UVR behaviours combined. CONCLUSION: Our results provide quantifiable estimates of the potentially avoidable burden of NMSCs among Canadians. These estimates can be used to motivate prevention efforts in Canada.

Lung cancer risk in painters: results from the SYNERGY pooled case-control study consortium.

OBJECTIVES: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project. METHODS: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens. RESULTS: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0). CONCLUSIONS: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters.

Respirable Crystalline Silica Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Analysis of Case-Control Studies.

Rationale: Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype.Objectives: We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks.Methods: Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed.Measurements and Main Results: Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated (P trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated (P trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes.Conclusions: Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.

Diesel Engine Exhaust Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Exposure-Response Analysis of 14 Case-Control Studies.

Rationale: Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes.Objectives: We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations.Methods: We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men.Measurements and Main Results: Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 µg/m3 were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined.Conclusions: We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.

Metabolic health measurements of shift workers in a national cross-sectional study: Results from the Canadian Health Measures Survey.

BACKGROUND: Shift work exposure may be a concern for a range of health effects, including metabolic health outcomes such as insulin resistance, high body weight, and abdominal obesity. METHODS: We analyzed shift work and indicators of metabolic health (overweight/obesity defined by body mass index, self-reported changes in body mass index (BMI) in previous 1 and 10 years, waist circumference, waist-to-hip ratio, and insulin resistance assessed by the homeostasis model assessment 2 (HOMA-2-IR)) in the cross-sectional Canadian Health Measures Survey (CHMS). We analyzed descriptive characteristics of shift workers (regular night, evening, and rotating shift) and used multivariable linear regression to examine the association between two definitions of shift work exposure and measures of metabolic health, adjusted for age, sex, daily energy expenditure, sleep, and poor dietary quality. RESULTS: 5470 anthropometry (2637 fasting) participants in CHMS Cycles 1 and 2 were included, of whom 16.5% worked regular evening, night, or rotating shifts. Shift workers were younger and slept longer hours than non-shift workers. Bivariate associations showed inverse relationships between shift work and BMI, waist circumference, waist-to-hip ratio, and HOMA-2-IR. In adjusted analyses, BMI was inversely related to shift work, and other metabolic health outcomes showed no significant associations. CONCLUSIONS: Healthy worker effects (including self-selection of exposure) could explain inverse relationships, particularly as the cross-sectional design only allowed assessment of current exposure. Key strengths include the population-based design and measurement of metabolic health indicators. Results underscore the importance of consideration of the health of shift workers following departure from the exposed population.