Dataset Information

Parental occupational exposure to diesel engine exhaust in relation to childhood leukaemia and central nervous system cancers: a register-based nested case-control study in Denmark 1968-2016.

ABSTRACT: OBJECTIVES:Using nationwide register data, we investigated the association between maternal and paternal perinatal employment in industries with exposure to diesel engine exhaust and risk of leukaemia and central nervous system (CNS) cancers, including certain subtypes. METHODS:Children aged?19 years and diagnosed with childhood cancer from 1968 to 2016 were identified in the Danish Cancer Registry and 25 randomly selected cancer-free controls per case were matched by age and sex. Parents were identified in the Danish Civil Registration System and employment histories were retrieved from a nationwide mandatory pension fund. The probability of exposure to diesel engine exhaust was assessed using a validated job exposure matrix. Conditional logistic regression was used for estimation of ORs, including their 95% CIs. RESULTS:Maternal employment in industries with diesel engine exhaust exposure was associated with an increased risk of CNS cancers (OR 1.31, 95%?CI 0.99 to 1.74) and of astrocytoma (OR 1.49, 95%?CI 1.04 to 2.14) in offspring. The highest OR for these cancers were seen for mothers with highest probability of exposure to diesel engine exhaust. For fathers, ORs for cancers under study were close to one. No increased risks of leukaemias were found for either mothers or fathers employed in diesel industries. CONCLUSIONS:Risks were increased for CNS and astrocytoma for maternal employment in industries with diesel engine exhaust.

SUBMITTER: Volk J

PROVIDER: S-EPMC7012305 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Parental occupational exposure to diesel engine exhaust in relation to childhood leukaemia and central nervous system cancers: a register-based nested case-control study in Denmark 1968-2016.

Volk Julie J Heck Julia E JE Schmiegelow Kjeld K Hansen Johnni J

Occupational and environmental medicine 20191101 11

<h4>Objectives</h4>Using nationwide register data, we investigated the association between maternal and paternal perinatal employment in industries with exposure to diesel engine exhaust and risk of leukaemia and central nervous system (CNS) cancers, including certain subtypes.<h4>Methods</h4>Children aged≤19 years and diagnosed with childhood cancer from 1968 to 2016 were identified in the Danish Cancer Registry and 25 randomly selected cancer-free controls per case were matched by age and sex. ...[more]

PMID: 31611302

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Project description:BackgroundMost studies of the association between diesel exhaust exposure and lung cancer suggest a modest, but consistent, increased risk. However, to our knowledge, no study to date has had quantitative data on historical diesel exposure coupled with adequate sample size to evaluate the exposure-response relationship between diesel exhaust and lung cancer. Our purpose was to evaluate the relationship between quantitative estimates of exposure to diesel exhaust and lung cancer mortality after adjustment for smoking and other potential confounders.MethodsWe conducted a nested case-control study in a cohort of 12 315 workers in eight non-metal mining facilities, which included 198 lung cancer deaths and 562 incidence density-sampled control subjects. For each case subject, we selected up to four control subjects, individually matched on mining facility, sex, race/ethnicity, and birth year (within 5 years), from all workers who were alive before the day the case subject died. We estimated diesel exhaust exposure, represented by respirable elemental carbon (REC), by job and year, for each subject, based on an extensive retrospective exposure assessment at each mining facility. We conducted both categorical and continuous regression analyses adjusted for cigarette smoking and other potential confounding variables (eg, history of employment in high-risk occupations for lung cancer and a history of respiratory disease) to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Analyses were both unlagged and lagged to exclude recent exposure such as that occurring in the 15 years directly before the date of death (case subjects)/reference date (control subjects). All statistical tests were two-sided.ResultsWe observed statistically significant increasing trends in lung cancer risk with increasing cumulative REC and average REC intensity. Cumulative REC, lagged 15 years, yielded a statistically significant positive gradient in lung cancer risk overall (P (trend) = .001); among heavily exposed workers (ie, above the median of the top quartile [REC ≥ 1005 μg/m(3)-y]), risk was approximately three times greater (OR = 3.20, 95% CI = 1.33 to 7.69) than that among workers in the lowest quartile of exposure. Among never smokers, odd ratios were 1.0, 1.47 (95% CI = 0.29 to 7.50), and 7.30 (95% CI = 1.46 to 36.57) for workers with 15-year lagged cumulative REC tertiles of less than 8, 8 to less than 304, and 304 μg/m(3)-y or more, respectively. We also observed an interaction between smoking and 15-year lagged cumulative REC (P (interaction) = .086) such that the effect of each of these exposures was attenuated in the presence of high levels of the other.ConclusionOur findings provide further evidence that diesel exhaust exposure may cause lung cancer in humans and may represent a potential public health burden.

Project description:BackgroundDiesel engine exhaust (DEE) exposure causes lung cancer, but the molecular mechanisms by which this occurs are not well understood.ObjectivesTo assess transcriptomic alterations in nasal epithelium of DEE-exposed factory workers to better understand the cellular and molecular effects of DEE.MethodsNasal epithelial brushings were obtained from 41 diesel engine factory workers exposed to relatively high levels of DEE (17.2-105.4 μg/m3), and 38 unexposed workers from factories without DEE exposure. mRNA was profiled for gene expression using Affymetrix microarrays. Linear modeling was used to identify differentially expressed genes associated with DEE exposure and interaction effects with current smoking status. Pathway enrichment among differentially expressed genes was assessed using EnrichR. Gene Set Enrichment Analysis (GSEA) was used to compare gene expression patterns between datasets.Results225 genes had expression associated with DEE exposure after adjusting for smoking status (FDR q < 0.25) and were enriched for genes in pathways related to oxidative stress response, cell cycle pathways such as MAPK/ERK, protein modification, and transmembrane transport. Genes up-regulated in DEE-exposed individuals were enriched among the genes most up-regulated by cigarette smoking in a previously reported bronchial airway smoking dataset. We also found that the DEE signature was enriched among the genes most altered in two previous studies of the effects of acute DEE on PBMC gene expression. An exposure-response relationship was demonstrated between air levels of elemental carbon and the first principal component of the DEE signature.ConclusionsA gene expression signature was identified for workers occupationally exposed to DEE that was altered in an exposure-dependent manner and had some overlap with the effects of smoking and the effects of acute DEE exposure. This is the first study of gene expression in nasal epithelial cells of workers heavily exposed to DEE and provides new insights into the molecular alterations that occur with DEE exposure.

Dataset Information

Parental occupational exposure to diesel engine exhaust in relation to childhood leukaemia and central nervous system cancers: a register-based nested case-control study in Denmark 1968-2016.

Publications

Parental occupational exposure to diesel engine exhaust in relation to childhood leukaemia and central nervous system cancers: a register-based nested case-control study in Denmark 1968-2016.

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