Air pollution has been shown to significantly impact human health including cancer. Gastric and upper aerodigestive tract (UADT) cancers are common and increased risk has been associated with smoking ...and occupational exposures. However, the association with air pollution remains unclear. We pooled European subcohorts (N = 287,576 participants for gastric and N = 297,406 for UADT analyses) and investigated the association between residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone in the warm season (O3w) with gastric and UADT cancer. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area‐level. During 5,305,133 and 5,434,843 person‐years, 872 gastric and 1139 UADT incident cancer cases were observed, respectively. For gastric cancer, we found no association with PM2.5, NO2 and BC while for UADT the hazard ratios (95% confidence interval) were 1.15 (95% CI: 1.00–1.33) per 5 μg/m3 increase in PM2.5, 1.19 (1.08–1.30) per 10 μg/m3 increase in NO2, 1.14 (1.04–1.26) per 0.5 × 10−5 m−1 increase in BC and 0.81 (0.72–0.92) per 10 μg/m3 increase in O3w. We found no association between long‐term ambient air pollution exposure and incidence of gastric cancer, while for long‐term exposure to PM2.5, NO2 and BC increased incidence of UADT cancer was observed.
What's new?
Exposure to long‐term ambient air pollution increases mortality and cancer incidence. However, most evidence exists for high exposure levels and lung cancer. In this large European study focusing on air pollution levels even below current EU standards, long‐term exposure to fine particles, nitrogen dioxide and black carbon increased the incidence of upper aerodigestive tract cancers, while no association was found with gastric cancer. These results indicate that ambient air pollution may increase the risk of upper aerodigestive tract cancers, and support the need for aligning current EU air pollution levels with the new WHO Air Quality Guidelines.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Previous studies have explored the relationships of air pollution and metabolic profiles with lung function. However, the metabolites linking air pollution and lung function and the associated ...mechanisms have not been reviewed from a life-course perspective. Here, we provide a narrative review summarising recent evidence on the associations of metabolic profiles with air pollution exposure and lung function in children and adults. Twenty-six studies identified through a systematic PubMed search were included with 10 studies analysing air pollution-related metabolic profiles and 16 studies analysing lung function-related metabolic profiles. A wide range of metabolites were associated with short- and long-term exposure, partly overlapping with those linked to lung function in the general population and with respiratory diseases such as asthma and COPD. The existing studies show that metabolomics offers the potential to identify biomarkers linked to both environmental exposures and respiratory outcomes, but many studies suffer from small sample sizes, cross-sectional designs, a preponderance on adult lung function, heterogeneity in exposure assessment, lack of confounding control and omics integration. The ongoing EXposome Powered tools for healthy living in urbAN Settings (EXPANSE) project aims to address some of these shortcomings by combining biospecimens from large European cohorts and harmonised air pollution exposure and exposome data.
The exposome constitutes a promising framework to improve understanding of the effects of environmental exposures on health by explicitly considering multiple testing and avoiding selective ...reporting. However, exposome studies are challenged by the simultaneous consideration of many correlated exposures.
We compared the performances of linear regression-based statistical methods in assessing exposome-health associations.
In a simulation study, we generated 237 exposure covariates with a realistic correlation structure and with a health outcome linearly related to 0 to 25 of these covariates. Statistical methods were compared primarily in terms of false discovery proportion (FDP) and sensitivity.
On average over all simulation settings, the elastic net and sparse partial least-squares regression showed a sensitivity of 76% and an FDP of 44%; Graphical Unit Evolutionary Stochastic Search (GUESS) and the deletion/substitution/addition (DSA) algorithm revealed a sensitivity of 81% and an FDP of 34%. The environment-wide association study (EWAS) underperformed these methods in terms of FDP (average FDP, 86%) despite a higher sensitivity. Performances decreased considerably when assuming an exposome exposure matrix with high levels of correlation between covariates.
Correlation between exposures is a challenge for exposome research, and the statistical methods investigated in this study were limited in their ability to efficiently differentiate true predictors from correlated covariates in a realistic exposome context. Although GUESS and DSA provided a marginally better balance between sensitivity and FDP, they did not outperform the other multivariate methods across all scenarios and properties examined, and computational complexity and flexibility should also be considered when choosing between these methods. Citation: Agier L, Portengen L, Chadeau-Hyam M, Basagaña X, Giorgis-Allemand L, Siroux V, Robinson O, Vlaanderen J, González JR, Nieuwenhuijsen MJ, Vineis P, Vrijheid M, Slama R, Vermeulen R. 2016. A systematic comparison of linear regression-based statistical methods to assess exposome-health associations. Environ Health Perspect 124:1848-1856; http://dx.doi.org/10.1289/EHP172.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
To investigate whether exposure to particulates and combustion products may explain the association between certain occupations and amyotrophic lateral sclerosis (ALS) risk in a large, multicentre, ...population-based, case-control study, based on full job histories, using job-exposure matrices, with detailed information on possible confounders.
Population-based patients with ALS and controls were recruited from five registries in the Netherlands, Ireland and Italy. Demographics and data regarding educational level, smoking, alcohol habits and lifetime occupational history were obtained using a validated questionnaire. Using job-exposure matrices, we assessed occupational exposure to silica, asbestos, organic dust, contact with animals or fresh animal products, endotoxins, polycyclic aromatic hydrocarbons and diesel motor exhaust. Multivariate logistic regression models adjusting for confounding factors were used to determine the association between these exposures and ALS risk.
We included 1557 patients and 2922 controls. Associations were positive for all seven occupational exposures (ORs ranging from 1.13 to 1.73 for high vs never exposed), and significant on the continuous scale for silica, organic dust and diesel motor exhaust (p values for trend ≤0.03). Additional analyses, adding an exposure (one at a time) to the model in the single exposure analysis, revealed a stable OR for silica. We found similar results when patients with a
mutation were excluded.
In a large, multicentre study, using harmonised methodology to objectively quantify occupational exposure to particulates and combustion products, we found an association between ALS risk and exposure to silica, independent of the other occupational exposures studied.
•Residential pre-natal exposure to pesticides can result in adverse birth outcomes.•We explored associations between 139 pesticides and several birth outcomes.•We found indications of such ...associations for five pesticides.•Fluroxypyr-meptyl, glufosinate-ammonium, linuron, vinclozolin and picoxystrobin.•Confirmatory investigations on these and/or similar compounds is warrented.
Maternal occupational exposure to pesticides has been linked to adverse birth outcomes but associations with residential pesticide exposures are inconclusive.
To explore associations between residential exposure to specific pesticides and birth outcomes using individual level exposure and pregnancy/birth data.
From all 2009–2013 singleton births in the Dutch birth registry, we selected mothers > 16 years old living in non-urban areas, who had complete address history and changed addresses at most once during pregnancy (N = 339,947). We estimated amount (kg) of 139 active ingredients (AI) used within buffers of 50, 100, 250 and 500 m around each mother's home during pregnancy. We used generalized linear models to investigate associations between 12 AIs with evidence of reproductive toxicity and gestational age (GA), birth weight (BW), perinatal mortality, child́s sex, prematurity, low birth weight (LBW), small for gestational age (SGA) and large for gestational age (LGA), adjusting for individual and area-level confounders. For the remainder 127 AIs, we used minimax concave penalty with a stability selection step to identify those that could be related to birth outcomes.
Regression analyses showed that maternal residential exposure to fluroxypyr-meptyl was associated with longer GA, glufosinate-ammonium with higher risk of LBW, linuron with higher BW and higher odds of LGA, thiacloprid with lower odds of perinatal mortality and vinclozolin with longer GA. Variable selection analysis revealed that picoxystrobin was associated with higher odds of LGA. We found no evidence of associations with other AIs. Sensitivity and additional analysis supported these results except for thiacloprid.
In this exploratory study, pregnant women residing near crops where fluroxypyr-meptyl, glufosinate-ammonium, linuron, vinclozolin and picoxystrobin were applied had higher risk for certain potentially adverse birth outcomes. Our findings provide leads for confirmatory investigations on these compounds and/or compounds with similar modes of action.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•We included spatially-varying relationships in our Europe-wide models.•We built spatially- and temporally-varying models to estimate annual air pollution.•Spatially-varying linear regression was ...more robust than a machine learning method.
Previous European land-use regression (LUR) models assumed fixed linear relationships between air pollution concentrations and predictors such as traffic and land use. We evaluated whether including spatially-varying relationships could improve European LUR models by using geographically weighted regression (GWR) and random forest (RF). We built separate LUR models for each year from 2000 to 2019 for NO2, O3, PM2.5 and PM10 using annual average monitoring observations across Europe. Potential predictors included satellite retrievals, chemical transport model estimates and land-use variables. Supervised linear regression (SLR) was used to select predictors, and then GWR estimated the potentially spatially-varying coefficients. We developed multi-year models using geographically and temporally weighted regression (GTWR). Five-fold cross-validation per year showed that GWR and GTWR explained similar spatial variations in annual average concentrations (average R2 = NO2: 0.66; O3: 0.58; PM10: 0.62; PM2.5: 0.77), which are better than SLR (average R2 = NO2: 0.61; O3: 0.46; PM10: 0.51; PM2.5: 0.75) and RF (average R2 = NO2: 0.64; O3: 0.53; PM10: 0.56; PM2.5: 0.67). The GTWR predictions and a previously-used method of back-extrapolating 2010 model predictions using CTM were overall highly correlated (R2 > 0.8) for all pollutants. Including spatially-varying relationships using GWR modestly improved European air pollution annual LUR models, allowing time-varying exposure-health risk models.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Only a small number of risk factors for pancreatic ductal adenocarcinoma (PDAC) has been established. Several studies identified a role of epigenetics and of deregulation of DNA methylation. DNA ...methylation is variable across a lifetime and in different tissues; nevertheless, its levels can be regulated by genetic variants like methylation quantitative trait loci (mQTLs), which can be used as a surrogate.
We scanned the whole genome for mQTLs and performed an association study in 14 705 PDAC cases and 246 921 controls. The methylation data were obtained from whole blood and pancreatic cancer tissue through online databases. We used the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium genome-wide association study (GWAS) data as discovery phase and the Pancreatic Disease Research consortium, the FinnGen project and the Japan Pancreatic Cancer Research consortium GWAS as replication phase.
The C allele of 15q26.1-rs12905855 showed an association with a decreased risk of PDAC (OR=0.90, 95% CI 0.87 to 0.94, p=4.93×10
in the overall meta-analysis), reaching genome-level statistical significance. 15q26.1-rs12905855 decreases the methylation of a 'C-phosphate-G' (CpG) site located in the promoter region of the
antisense (
) gene which, when expressed, decreases the expression of the RCC1 domain-containing (
) gene (part of a histone demethylase complex). Thus, it is possible that the rs12905855 C-allele has a protective role in PDAC development through an increase of
gene expression, made possible by the inactivity of
.
We identified a novel PDAC risk locus which modulates cancer risk by controlling gene expression through DNA methylation.
COVID-19 is characterised by a dysregulated immune response, that involves signalling lipids acting as mediators of the inflammatory process along the innate and adaptive phases. To promote ...understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS platforms to analyse over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). The second publication in a series reports the results of quantitative LC-MS/MS profiling of 63 small lipids including oxylipins, free fatty acids, and endocannabinoids. Compared to samples taken from ward patients, intensive care unit (ICU) patients had 2−4-fold lower levels of arachidonic acid (AA) and its cyclooxygenase-derived prostanoids, as well as lipoxygenase derivatives, exhibiting negative correlations with inflammation markers. The same derivatives showed 2−5-fold increases in recovering ward patients, in paired comparison to early hospitalisation. In contrast, ICU patients showed elevated levels of oxylipins derived from poly-unsaturated fatty acids (PUFA) by non-enzymatic peroxidation or activity of soluble epoxide hydrolase (sEH), and these oxylipins positively correlated with markers of macrophage activation. The deficiency in AA enzymatic products and the lack of elevated intermediates of pro-resolving mediating lipids may result from the preference of alternative metabolic conversions rather than diminished stores of PUFA precursors. Supporting this, ICU patients showed 2-to-11-fold higher levels of linoleic acid (LA) and the corresponding fatty acyl glycerols of AA and LA, all strongly correlated with multiple markers of excessive immune response. Our results suggest that the altered oxylipin metabolism disrupts the expected shift from innate immune response to resolution of inflammation.
Introduction: Studies found that higher risk appraisal of radiofrequency electromagnetic fields is associated with reporting more non-specific symptoms such as headache and back pain. There is ...limited data available on the longitudinal nature of such associations and what aspects of risk appraisal and characteristics of subjects are relevant.
Objective: To examine cross-sectional and longitudinal associations between risk appraisal measures and non-specific symptoms, and assess the role of subject characteristics (sex, age, education, trait negative affect) in a general population cohort.
This study was nested in the Dutch general population AMIGO cohort that was established in 2011/2012, when participants were 31–65 years old. We studied a sample of participants (n = 1720) who filled in two follow-up questionnaires in 2013 and 2014, including questions about perceived exposure, perceived risk, and health concerns as indicators of risk appraisal of base stations, and non-specific symptoms.
Perceived exposure, perceived risk, and health concerns, respectively, were associated with higher symptom scores in cross-sectional and longitudinal analyses. Only health concerns (not perceived exposure and perceived risk) temporally preceded high symptom scores and vice versa. Female sex, younger age, higher education, and higher trait negative affect were associated with higher risk appraisal of mobile phone base stations.
The findings in this study strengthen the evidence base for cross-sectional and longitudinal associations between higher risk appraisal and non-specific symptoms in the general population. However, the directionality of potential causal relations in non-sensitive general population samples should be examined further in future studies, providing information to the benefit of risk communication strategies.
•We studied longitudinal associations in a general population cohort.•Risk appraisal of base stations was associated with higher symptom scores.•The results indicate the presence of bidirectional longitudinal associations.•Female sex, younger age, higher education, were associated with high risk appraisal.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been ...hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow‐up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist‐to‐hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.
What's new?
Obesity can change the body's hormone balance, and encourage the onset of cancer. Here, the authors investigated the relationship between obesity, hormones, and esophageal and gastric cancers. Using data from the EPIC cohort, they obtained information about anthropometric and reproductive factors for 476,160 participants. Excess fat around the waist, they found, was associated with esophageal adenocarcinoma and gastric cardia cancer, in women and men. In women, bearing children, as well as younger age at first pregnancy, had an inverse association with certain cancers. Ovariectomy was positively associated with gastric non‐cardia cancer, suggesting involvement of hormone pathways in these malignancies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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