•Occupational diesel engine exhaust (DEE) exposure alters nasal gene expression.•DEE-associated genes have an exposure-response relationship with elemental carbon levels.•DEE and cigarette smoke (CS) ...exposures up-regulate common genes.•DEE and CS exposure have a synergistic effect on gene expression.
Diesel engine exhaust (DEE) exposure causes lung cancer, but the molecular mechanisms by which this occurs are not well understood.
To assess transcriptomic alterations in nasal epithelium of DEE-exposed factory workers to better understand the cellular and molecular effects of DEE.
Nasal 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.
225 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.
A 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.
The Chinese national pollution census has indicated that the domestic burning of solid fuels is an important contributor to nitrogen dioxide (NO2) and sulfur dioxide (SO2) emissions in China. To ...characterize indoor NO2 and SO2 air concentrations in relation to solid fuel use and stove ventilation in the rural counties of Xuanwei and Fuyuan, in Yunnan Province, China, which have among the highest lung cancer rates in the nation, a total of 163 participants in 30 selected villages were enrolled. Indoor 24‐h NO2 and SO2 samples were collected in each household over two consecutive days. Compared to smoky coal, smokeless coal use was associated with higher NO2 concentrations geometric mean (GM) = 132 μg/m3 for smokeless coal and 111 μg/m3 for smoky coal, P = 0.065 and SO2 limit of detection = 24 μg/m3; percentage detected (%Detect) = 86% for smokeless coal and 40% for smoky coal, P < 0.001. Among smoky coal users, significant variation of NO2 and SO2 air concentrations was observed across different stove designs and smoky coal sources in both counties. Model construction indicated that the measurements of both pollutants were influenced by stove design. This exposure assessment study has identified high levels of NO2 and SO2 as a result of burning solid fuels for cooking and heating.
Bladder cancer has been associated with exposure to chlorination by-products in drinking water, and experimental evidence suggests that exposure also occurs through inhalation and dermal absorption. ...The authors examined whether bladder cancer risk was associated with exposure to trihalomethanes (THMs) through ingestion of water and through inhalation and dermal absorption during showering, bathing, and swimming in pools. Lifetime personal information on water consumption and water-related habits was collected for 1,219 cases and 1,271 controls in a 1998–2001 case-control study in Spain and was linked with THM levels in geographic study areas. Long-term THM exposure was associated with a twofold bladder cancer risk, with an odds ratio of 2.10 (95% confidence interval: 1.09, 4.02) for average household THM levels of >49 versus ≤8 μg/liter. Compared with subjects not drinking chlorinated water, subjects with THM exposure of >35 μg/day through ingestion had an odds ratio of 1.35 (95% confidence interval: 0.92, 1.99). The odds ratio for duration of shower or bath weighted by residential THM level was 1.83 (95% confidence interval: 1.17, 2.87) for the highest compared with the lowest quartile. Swimming in pools was associated with an odds ratio of 1.57 (95% confidence interval: 1.18, 2.09). Bladder cancer risk was associated with long-term exposure to THMs in chlorinated water at levels regularly occurring in industrialized countries.
The aim of this work was to examine the risk of lymphohaematopoietic (LH) cancer according to benzene exposure among offshore workers.
Cancer registry data were used to identify 112 cancer cases ...diagnosed during 1999-2011 in a cohort of 24 917 Norwegian men reporting offshore work between 1965 and 1999. Analyses were conducted according to a stratified case-cohort design with a reference subcohort of 1661 workers. Cox regression was used to estimate hazard ratios with 95% confidence intervals, adjusted for other benzene exposure and smoking.
Most workers were exposed to benzene for <15 years. The upper range values of average intensity and cumulative exposure were estimated to 0.040 p.p.m. and 0.948 p.p.m.-years, respectively. Risks were consistently elevated among exposed workers for all LH cancers combined and for most subgroups, although case numbers were small and yielded imprecise risk estimates. There was evidence of dose-related risk patterns according to cumulative exposure for acute myeloid leukaemia (AML), multiple myeloma (MM) (P trends 0.052 and 0.024, respectively), and suggestively so for chronic lymphocytic leukaemia (CLL) according to average intensity (P trend 0.094).
Our results support an association between cumulative and intensity metrics of low-level benzene exposure and risk for AML, MM, and suggestively for CLL.
Mitochondria are eukaryotic organelles responsible for energy production. Mitochondrial DNA (mtDNA) lack introns and protective histones, have limited DNA repair capacity and compensate for damage by ...increasing the number of mtDNA copies. As a consequence, mitochondria are more susceptible to reactive oxygen species, an important determinant of cancer risk, and it is hypothesized that increased mtDNA copy number may be associated with carcinogenesis. We assessed the association of mtDNA copy number and lung cancer risk in 227 prospectively collected cases and 227 matched controls from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age at randomization, smoking years and number of cigarettes smoked per day. There was suggestion of a dose-dependent relationship between mtDNA copy number and subsequent risk of lung cancer, with a prominent effect observed in the highest mtDNA copy number quartile ORs (95% CI) by quartile: 1.0 (reference), 1.3 (0.7–2.5), 1.1 (0.6–2.2) and 2.4 (1.1–5.1); Ptrend = 0.008. This is the first report, to the best of our knowledge, to suggest that mtDNA copy number may be positively associated with subsequent risk of lung cancer in a prospective cohort study; however, replication is needed in other studies and populations.
Shift work involving disruption of circadian rhythms has been classified as a probable cause of human cancer by the International Agency for Research on Cancer, based on limited epidemiologic ...evidence and abundant experimental evidence. The authors investigated this association in a population-based prospective cohort study of Chinese women. At baseline (1996–2000), information on lifetime occupational history was obtained from 73,049 women. Lifetime night-shift exposure indices were created using a job exposure matrix. During 2002–2004, self-reported data on frequency and duration of night-shift work were collected. Hazard ratios and 95% confidence intervals, adjusted for major breast cancer risk factors, were calculated. During follow-up through 2007, 717 incident cases of breast cancer were diagnosed. Breast cancer risk was not associated with ever working the night shift on the basis of the job exposure matrix (adjusted hazard ratio = 1.0, 95% confidence interval: 0.9, 1.2) or self-reported history of night-shift work (adjusted hazard ratio = 0.9, 95% confidence interval: 0.7, 1.1). Risk was also not associated with frequency, duration, or cumulative amount of night-shift work. There were no indications of effect modification. The lack of an association between night-shift work and breast cancer adds to the inconsistent epidemiologic evidence. It may be premature to consider shift work a cause of cancer.
Formaldehyde (FA) is an economically important industrial chemical to which millions of people worldwide are exposed environmentally and occupationally. Recently, the International Agency for Cancer ...Research concluded that there is sufficient evidence that FA causes leukemia, particularly myeloid leukemia. To evaluate the biological plausibility of this association, we employed a chromosome-wide aneuploidy study approach, which allows the evaluation of aneuploidy and structural chromosome aberrations (SCAs) of all 24 chromosomes simultaneously, to analyze cultured myeloid progenitor cells from 29 workers exposed to relatively high levels of FA and 23 unexposed controls. We found statistically significant increases in the frequencies of monosomy, trisomy, tetrasomy and SCAs of multiple chromosomes in exposed workers compared with controls, with particularly notable effects for monosomy 1 P = 6.02E-06, incidence rate ratio (IRR) = 2.31, monosomy 5 (P = 9.01E-06; IRR = 2.24), monosomy 7 (P = 1.57E-05; IRR = 2.17), trisomy 5 (P = 1.98E-05; IRR = 3.40) and SCAs of chromosome 5 (P = 0.024; IRR = 4.15). The detection of increased levels of monosomy 7 and SCAs of chromosome 5 is particularly relevant as they are frequently observed in acute myeloid leukemia. Our findings provide further evidence that leukemia-related cytogenetic changes can occur in the circulating myeloid progenitor cells of healthy workers exposed to FA, which may be a potential mechanism underlying FA-induced leukemogenesis.
Black carbon (BC) emissions from solid fuel combustion are associated with increased morbidity and mortality and are important drivers of climate change. We studied BC measurements, approximated by ...particulate matter (PM2.5) absorbance, in rural Yunnan province, China, whose residents use a variety of solid fuels for cooking and heating including bituminous and anthracite coal, and wood. Measurements were taken over two consecutive 24‐h periods from 163 households in 30 villages. PM2.5 absorbance (PMabs) was measured using an EEL 043 Smoke Stain Reflectometer. PMabs measurements were higher in wood burning households (16.3 × 10−5/m) than bituminous and anthracite coal households (12 and 5.1 × 10−5/m, respectively). Among bituminous coal users, measurements varied by a factor of two depending on the coal source. Portable stoves (which are lit outdoors and brought indoors for use) were associated with reduced PMabs levels, but no other impact of stove design was observed. Outdoor measurements were positively correlated with and approximately half the level of indoor measurements (r = 0.49, P < 0.01). Measurements of BC (as approximated by PMabs) in this population are modulated by fuel type and source. This provides valuable insight into potential morbidity, mortality, and climate change contributions of domestic usage of solid fuels.
The recent completion of the first draft of the human genome sequence and advances in technologies for genomic analysis are generating tremendous opportunities for epidemiologic studies to evaluate ...the role of genetic variants in human disease. Many methodological issues apply to the investigation of variation in the frequency of allelic variants of human genes, of the possibility that these influence disease risk, and of assessment of the magnitude of the associated risk. Based on a Human Genome Epidemiology workshop, a checklist for reporting and appraising studies of genotype prevalence and studies of gene-disease associations was developed. This focuses on selection of study subjects, analytic validity of genotyping, population stratification, and statistical issues. Use of the checklist should facilitate the integration of evidence from these studies. The relation between the checklist and grading schemes that have been proposed for the evaluation of observational studies is discussed. Although the limitations of grading schemes are recognized, a robust approach is proposed. Other issues in the synthesis of evidence that are particularly relevant to studies of genotype prevalence and gene-disease association are discussed, notably identification of studies, publication bias, criteria for causal inference, and the appropriateness of quantitative synthesis.
The influence of different types and intensities of physical activity on risk for breast cancer is unclear.
In a prospective cohort of 73,049 Chinese women (40-70 years), who had worked outside the ...home, we studied breast cancer risk in relation to specific types of self-reported and work history-related physical activity, including adolescent and adult exercise and household activity and walking and cycling for transportation. Occupational sitting time and physical activity energy expenditure were assigned based on lifetime occupational histories.
In all, 717 incident breast cancer cases were diagnosed. Breast cancer risk was lower for women in the lowest quartile of average occupational sitting time and in the highest quartile of average occupational energy expenditure (adjusted hazard ratio (HR): 0.81 and 0.73, respectively, P ≤ 0.05). Adult exercise at or above the recommended level (8 metabolic equivalent (MET) h per week per year) was associated with lower risk (adjusted HR: 0.73, P<0.05) in post-menopausal women. Analysis of joint effects showed that having both an active job and exercise participation did not confer an additional benefit. Other common daily activities were not associated with lower risk.
These findings suggest that both exercise and occupational activity are associated with lower breast cancer risk, which supports current health promotion campaigns promoting exercise.
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