Air pollution and myocardial infarction; effect modification by sociodemographic and environmental factors. A cohort study from Denmark.

Air pollution is associated with increased risk of myocardial infarction (MI), but it is unresolved to what extent the association is modified by factors such as socioeconomic status, comorbidities, financial stress, residential green space, or road traffic noise. We formed a cohort of all (n = 1,964,702) Danes, aged 50-85 years, with 65,311 cases of MI during the followed-up period 2005-2017. For all participants we established residential five-year running average exposure to particulate matter <2.5 µm (PM2.5), ultrafine particles (UFP, <0.1 µm), elemental carbon (EC) and nitrogen dioxide (NO2). We evaluated risk in population strata, using Aalen additive hazards models to estimate absolute risk and Cox proportional hazards models to estimate relative risk of MI with 95% confidence intervals (CI). PM2.5 and the other pollutant were associated with MI. Lower education and lower income were associated with higher absolute risks of MI from air pollution, whereas no clear effect modification was apparent for relative risk estimates. For example, 5 µg/m3 higher PM2.5 was associated with HR for MI of 1.16 (95% CI: 1.10-1.22) among those with only mandatory education and 1.13 (95% CI: 1.03-1.24) among those with long education. The corresponding rate differences per 100,000 person years were 243 (95% CI: 216-271) and 358 (95% CI: 338-379), respectively. Higher level of comorbidity was consistently across all four pollutants associated with both higher absolute and relative risk of MI. In conclusion, people with comorbid conditions or of lower SES appeared more vulnerable to long-term exposure to air pollution and more cases of MI may be prevented by focused interventions in these groups.

Long-term exposure to traffic noise and risk of incident colon cancer: A pooled study of eleven Nordic cohorts.

Background Colon cancer incidence is rising globally, and factors pertaining to urbanization have been proposed involved in this development. Traffic noise may increase colon cancer risk by causing sleep disturbance and stress, thereby inducing known colon cancer risk-factors, e.g. obesity, diabetes, physical inactivity, and alcohol consumption, but few studies have examined this. Objectives The objective of this study was to investigate the association between traffic noise and colon cancer (all, proximal, distal) in a pooled population of 11 Nordic cohorts, totaling 155,203 persons. Methods We identified residential address history and estimated road, railway, and aircraft noise, as well as air pollution, for all addresses, using similar exposure models across cohorts. Colon cancer cases were identified through national registries. We analyzed data using Cox Proportional Hazards Models, adjusting main models for harmonized sociodemographic and lifestyle data. Results During follow-up (median 18.8 years), 2757 colon cancer cases developed. We found a hazard ratio (HR) of 1.05 (95% confidence interval (CI): 0.99-1.10) per 10-dB higher 5-year mean time-weighted road traffic noise. In sub-type analyses, the association seemed confined to distal colon cancer: HR 1.06 (95% CI: 0.98-1.14). Railway and aircraft noise was not associated with colon cancer, albeit there was some indication in sub-type analyses that railway noise may also be associated with distal colon cancer. In interaction-analyses, the association between road traffic noise and colon cancer was strongest among obese persons and those with high NO2-exposure. Discussion A prominent study strength is the large population with harmonized data across eleven cohorts, and the complete address-history during follow-up. However, each cohort estimated noise independently, and only at the most exposed façade, which may introduce exposure misclassification. Despite this, the results of this pooled study suggest that traffic noise may be a risk factor for colon cancer, especially of distal origin.

Long-term Air Pollution Exposure and Pneumonia-related Mortality in a Large Pooled European Cohort.

Rationale: Ambient air pollution exposure has been linked to mortality from chronic cardiorespiratory diseases, while evidence on respiratory infections remains more limited. Objectives: We examined the association between long-term exposure to air pollution and pneumonia-related mortality in adults in a pool of eight European cohorts. Methods: Within the multicenter project ELAPSE (Effects of Low-Level Air Pollution: A Study in Europe), we pooled data from eight cohorts among six European countries. Annual mean residential concentrations in 2010 for fine particulate matter, nitrogen dioxide (NO2), black carbon (BC), and ozone were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and pneumonia, influenza, and acute lower respiratory infections (ALRI) mortality. Measurements and Main Results: Of 325,367 participants, 712 died from pneumonia and influenza combined, 682 from pneumonia, and 695 from ALRI during a mean follow-up of 19.5 years. NO2 and BC were associated with 10-12% increases in pneumonia and influenza combined mortality, but 95% confidence intervals included unity (hazard ratios, 1.12 [0.99-1.26] per 10 µg/m3 for NO2; 1.10 [0.97-1.24] per 0.5 10-5m-1 for BC). Associations with pneumonia and ALRI mortality were almost identical. We detected effect modification suggesting stronger associations with NO2 or BC in overweight, employed, or currently smoking participants compared with normal weight, unemployed, or nonsmoking participants. Conclusions: Long-term exposure to combustion-related air pollutants NO2 and BC may be associated with mortality from lower respiratory infections, but larger studies are needed to estimate these associations more precisely.

Underlying pathways of social inequality in tooth loss: the mediating role of sugary beverages and diabetes.

BACKGROUND: Previous studies show social inequality in tooth loss, but the underlying pathways are not well understood. The aim was to investigate the mediated proportion of sugary beverages (SBs) and diabetes and the association between educational level and tooth loss, and to investigate whether the indirect effect of SBs and diabetes varied between educational groups in relation to tooth loss. METHODS: Data from 47,109 Danish men and women aged 50 years or older included in the Danish Diet, Cancer and Health Study was combined with data from Danish registers. Using natural effect models, SBs and diabetes were considered as mediators, and tooth loss was defined as having <15 teeth present. RESULTS: In total, 10,648 participants had tooth loss. The analyses showed that 3% (95% confidence interval 2-4%) of the social inequality in tooth loss was mediated through SBs and diabetes. The mediated proportion was mainly due to differential exposure to SBs and diabetes among lower educational groups. CONCLUSIONS: The findings show that SBs and diabetes to a minor degree contribute to tooth-loss inequalities. The explanation indicates that individuals in lower educational groups have higher consumption of SBs and more often suffer from diabetes than higher educational groups.

Air pollution at the residence of Danish adults, by socio-demographic characteristics, morbidity, and address level characteristics.

BACKGROUND: Exposure to outdoor air pollution is associated with adverse health effects. Previous studies have indicated higher levels of air pollution in socially deprived areas. AIM: To investigate associations between air pollution and socio-demographic variables, comorbidity, stress, and green space at the residence in Denmark. METHODS: We included 2,237,346 persons living in Denmark, aged 35 years or older in 2017. We used the high resolution, multi-scale DEHM/UBM/AirGIS air pollution modelling system to calculate mean concentrations of air pollution with PM2.5, elemental carbon, ultrafine particles and NO2 at residences held the preceding five years. We used nationwide registries to retrieve information about socio-demographic indicators at the individual and neighborhood levels. We used general linear regression models to analyze associations between socio-demographic indicators and air pollution at the residence. RESULTS: Individuals with high SES (income, higher white-collar worker and high educational level) and of non-Danish origin were exposed to higher levels of air pollution than individuals of low SES and of Danish origin, respectively. We found comparable levels of air pollution according to sex, stress events and morbidity. For neighborhood level SES indicators, we found high air pollution levels in neighborhoods with low SES measured as proportion of social housing, sole providers, low income and unemployment. In contrast, we found higher air pollution levels in neighborhoods with higher educational level and a low proportion of manual labor. People living in an apartment and/or with little green space had higher air pollution levels. CONCLUSION: In Denmark, high levels of residential air pollution were associated with higher individual SES and non-Danish origin. For neighborhood-level indicators of SES, no consistent pattern was observed. These results highlight the need for analyzing many different socio-demographic indicators to understand the complex associations between SES and exposure to air pollution.

Exposure to transportation noise and risk for cardiovascular disease in a nationwide cohort study from Denmark.

BACKGROUND: Transportation noise increases the risk of ischemic heart disease (IHD), but few studies have investigated subtypes of IHD, such as myocardial infarction (MI), angina pectoris, or heart failure. We aimed to study whether exposure to road, railway and aircraft noise increased risk for ischemic heart disease (IHD), IHD subtypes, and heart failure in the entire adult Danish population, investigating exposures at both maximum exposed and silent façades of each residence. METHODS: We modelled road, railway, and aircraft noise at the most and least exposed façades for the period 1995-2017 for all addresses in Denmark and calculated 10-year time-weighted running means for 2.5 million individuals age ≥50 years, of whom 122,523 developed IHD and 79,358 developed heart failure during follow-up (2005-2017). Data were analyzed using Cox proportional hazards models, adjusted for individual and area-level sociodemographic covariates and air pollution. RESULTS: We found road traffic noise at the most exposed façade (Lden) to be associated with higher risk of IHD, myocardial infarction (MI), angina pectoris, and heart failure, with hazard ratios (HRs) (95% confidence intervals (CI)) of 1.052 (1.044-1.059), 1.041 (1.032-1.051), 1.095 (1.071-1.119), and 1.039 (1.033-1.045) per 10 dB higher 10-year mean exposure, respectively. These associations followed a near-linear exposure-response relationship and were robust to adjustment for air pollution with PM2.5. Railway noise at the least exposed façade was associated with heart failure (HR 1.28; 95% CI: 1.004-1.053), but not the other outcomes. Exposure to aircraft noise (>45 dB) seemed associated with increased risk for MI and heart failure. CONCLUSIONS: We found road traffic noise and potentially railway and aircraft noise to increase risk of various major cardiovascular outcomes, highlighting the importance of preventive actions towards transportation noise.

Long-term exposure to transportation noise and risk for atrial fibrillation: A Danish nationwide cohort study.

BACKGROUND: Epidemiological studies have linked transportation noise and cardiovascular diseases, however, atrial fibrillation (AF) has received limited attention. We aimed to investigate the association between transportation noise and AF risk. METHODS: Over the period 1990-2017 we estimated road and railway noise (Lden) at the most and least exposed façades for all residential addresses across Denmark. We estimated time-weighted mean noise exposure for 3.6 million individuals age ≥35 years. Of these, 269,756 incident cases of AF were identified with a mean follow-up of 13.0 years. Analyses were conducted using Cox proportional hazards models with adjustment for individual and area-level sociodemographic covariates and long-term residential air pollution. RESULTS: A 10 dB higher 10-year mean road traffic noise at the most and least exposed façades were associated with incidence rate ratios (IRR) and 95% confidence intervals (CI) for AF of 1.006 (1.001-1.011) and 1.013 (1.007-1.019), respectively. After further adjustment for PM2.5, the IRRs (CIs) were 1.000 (0.995-1.005) and 1.007 (1.000-1.013), respectively. For railway noise, the IRRs per 10 dB increase in 10-year mean exposure were 1.017 (1.007-1.026) and 1.035 (1.021-1.050) for the most and least exposed façades, respectively, and were slightly attenuated when adjusted for PM2.5. Aircraft noise between 55 and 60 dB and ≥60 dB were associated with IRRs of 1.055 (0.996-1.116) and 1.036 (0.931-1.154), respectively, when compared to <45 dB. CONCLUSION: Transportation noise seems to be associated with a small increase in AF risk, especially for exposure at the least exposed façade.

Long-term exposure to air pollution and liver cancer incidence in six European cohorts.

Particulate matter air pollution and diesel engine exhaust have been classified as carcinogenic for lung cancer, yet few studies have explored associations with liver cancer. We used six European adult cohorts which were recruited between 1985 and 2005, pooled within the "Effects of low-level air pollution: A study in Europe" (ELAPSE) project, and followed for the incidence of liver cancer until 2011 to 2015. The annual average exposure to nitrogen dioxide (NO2 ), particulate matter with diameter <2.5 µm (PM2.5 ), black carbon (BC), warm-season ozone (O3 ), and eight elemental components of PM2.5 (copper, iron, zinc, sulfur, nickel, vanadium, silicon, and potassium) were estimated by European-wide hybrid land-use regression models at participants' residential addresses. We analyzed the association between air pollution and liver cancer incidence by Cox proportional hazards models adjusting for potential confounders. Of 330 064 cancer-free adults at baseline, 512 developed liver cancer during a mean follow-up of 18.1 years. We observed positive linear associations between NO2 (hazard ratio, 95% confidence interval: 1.17, 1.02-1.35 per 10 µg/m3 ), PM2.5 (1.12, 0.92-1.36 per 5 µg/m3 ), and BC (1.15, 1.00-1.33 per 0.5 10-5 /m) and liver cancer incidence. Associations with NO2 and BC persisted in two-pollutant models with PM2.5 . Most components of PM2.5 were associated with the risk of liver cancer, with the strongest associations for sulfur and vanadium, which were robust to adjustment for PM2.5 or NO2 . Our study suggests that ambient air pollution may increase the risk of liver cancer, even at concentrations below current EU standards.

Long-term exposure to low-level air pollution and incidence of asthma: the ELAPSE project.

BACKGROUND: Long-term exposure to ambient air pollution has been linked to childhood-onset asthma, although evidence is still insufficient. Within the multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we examined the associations of long-term exposures to particulate matter with a diameter <2.5 µm (PM2.5), nitrogen dioxide (NO2) and black carbon (BC) with asthma incidence in adults. METHODS: We pooled data from three cohorts in Denmark and Sweden with information on asthma hospital diagnoses. The average concentrations of air pollutants in 2010 were modelled by hybrid land-use regression models at participants' baseline residential addresses. Associations of air pollution exposures with asthma incidence were explored with Cox proportional hazard models, adjusting for potential confounders. RESULTS: Of 98 326 participants, 1965 developed asthma during a mean follow-up of 16.6 years. We observed associations in fully adjusted models with hazard ratios of 1.22 (95% CI 1.04-1.43) per 5 µg·m-3 for PM2.5, 1.17 (95% CI 1.10-1.25) per 10 µg·m-3 for NO2 and 1.15 (95% CI 1.08-1.23) per 0.5×10-5 m-1 for BC. Hazard ratios were larger in cohort subsets with exposure levels below the European Union and US limit values and possibly World Health Organization guidelines for PM2.5 and NO2. NO2 and BC estimates remained unchanged in two-pollutant models with PM2.5, whereas PM2.5 estimates were attenuated to unity. The concentration-response curves showed no evidence of a threshold. CONCLUSIONS: Long-term exposure to air pollution, especially from fossil fuel combustion sources such as motorised traffic, was associated with adult-onset asthma, even at levels below the current limit values.

Education and incident type 2 diabetes: quantifying the impact of differential exposure and susceptibility to being overweight or obese.

AIMS/HYPOTHESIS: Educational inequality in type 2 diabetes incidence is evident in many high-income countries. Previous studies have shown that differential exposure to being overweight/obese across educational groups may partly explain this inequality. Whether differential susceptibility to being overweight/obese across educational groups contributes to this inequality has been investigated less frequently, even though it is a plausible mechanism. The two mechanisms may even be highly intertwined. In this longitudinal cohort study, we investigated the simultaneous contribution of differential exposure and differential susceptibility to being overweight/obese to educational inequality in type 2 diabetes incidence. METHODS: The study population comprised 53,159 Danish men and women aged 50-64 years at baseline who were followed for a mean of 14.7 years. We estimated rate differences of type 2 diabetes by education level per 100,000 person-years. Using counterfactual mediation analysis, these rate differences were decomposed into proportions attributable to differential exposure, differential susceptibility and all other pathways, respectively. We compared this approach with conventional approaches to mediation and interaction analysis. RESULTS: Compared with a high level of education, a low education level was associated with 454 (95% CI 398, 510) additional cases of type 2 diabetes, and a medium education level with 316 (CI 268, 363) additional cases. Differential exposure to being overweight/obese accounted for 37% (CI 31%, 45%) of the additional cases among those with a low education level and 29% (CI 24%, 36%) of the additional cases among those with a medium education level. Differential susceptibility accounted for 9% (CI 4%, 14%) and 6% (CI 3%, 10%) of the additional cases among those with a low and medium education level, respectively. Compared with the counterfactual approach, the conventional approaches suggested stronger effects of both mechanisms. CONCLUSIONS/INTERPRETATION: Differential exposure and susceptibility to being overweight/obese are both important mechanisms in the association between education and type 2 diabetes incidence.

Long-term exposure to air pollution and risk of non-Hodgkin lymphoma in Denmark: A population-based case-control study.

There is limited evidence regarding a possible association between exposure to ambient air pollutants and the risk of non-Hodgkin lymphoma (NHL). Previous epidemiological studies have relied on crude estimations for air pollution exposure and/or small numbers of NHL cases. The objective of our study was to analyze this association based on air pollution modeled at the address level and NHL cases identified from the nationwide Danish Cancer Registry. We identified 20,874 incident NHL cases diagnosed between 1989 and 2014 and randomly selected 41,749 controls matched on age and gender among the entire Danish population. We used conditional logistic regression to estimate odds ratios (ORs) and adjusted for individual and neighborhood level sociodemographic variables. There was no association between exposure to PM2.5 , BC, O3 , SO2 or NO2 and overall risk of NHL but several air pollutants were associated with higher risk of follicular lymphoma, but statistically insignificant, for example, PM2.5 (OR = 1.15 per 5 µg/m3 ; 95% CI: 0.98-1.34) and lower risk for diffuse large B-cell lymphoma (OR = 0.92 per 5 µg/m3 ; 95% CI: 0.82-1.03). In this population-based study, we did not observe any convincing evidence of a higher overall risk for NHL with higher exposure to ambient air pollutants.

Development of Europe-Wide Models for Particle Elemental Composition Using Supervised Linear Regression and Random Forest.

We developed Europe-wide models of long-term exposure to eight elements (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) in particulate matter with diameter <2.5 µm (PM2.5) using standardized measurements for one-year periods between October 2008 and April 2011 in 19 study areas across Europe, with supervised linear regression (SLR) and random forest (RF) algorithms. Potential predictor variables were obtained from satellites, chemical transport models, land-use, traffic, and industrial point source databases to represent different sources. Overall model performance across Europe was moderate to good for all elements with hold-out-validation R-squared ranging from 0.41 to 0.90. RF consistently outperformed SLR. Models explained within-area variation much less than the overall variation, with similar performance for RF and SLR. Maps proved a useful additional model evaluation tool. Models differed substantially between elements regarding major predictor variables, broadly reflecting known sources. Agreement between the two algorithm predictions was generally high at the overall European level and varied substantially at the national level. Applying the two models in epidemiological studies could lead to different associations with health. If both between- and within-area exposure variability are exploited, RF may be preferred. If only within-area variability is used, both methods should be interpreted equally.

Long-term residential road traffic noise and mortality in a Danish cohort.

Transportation noise is a growing public health concern worldwide and epidemiological evidence has linked road traffic noise with mortality. However, incongruent effect estimates have been reported between incidence and mortality studies. Therefore, the present study aimed to investigate whether long-term exposure to residential road traffic noise at the most and least exposed façades was associated with all-cause, cardiovascular disease (CVD), ischemic heart disease (IHD), stroke, respiratory, or cancer mortality in a Danish cohort study. In a cohort of 52,758 individuals from Copenhagen and Aarhus, we estimated road traffic noise at the most and least exposed façades, as well as ambient air pollution, at all present and historical residential addresses from 1987 to 2016. Using the Danish cause of death register we identified cause-specific mortality. Analyses were conducted using Cox proportional hazards models. Ten-year time-weighted mean road traffic noise exposure at the most exposed façade was associated with an 8% higher risk for all-cause mortality per interquartile range (IQR; 10.4 dB) higher exposure level (95% CI: 1.05-1.11). Higher risks were also observed for CVD (HR = 1.13, 95% CI: 1.06-1.19) and stroke (HR = 1.11, 95% CI: 0.99-1.25) mortality. Road traffic noise at the least exposed façade (per IQR; 8.4 dB) was associated with CVD (HR = 1.09, 95% CI: 1.03-1.15), IHD (HR = 1.10, 95% CI: 1.01-1.21) and stroke (HR = 1.06, 95% CI: 0.95-1.19) mortality. Results were robust to adjustment for PM2.5 and NO2. In conclusion, this study adds to the body of evidence linking exposure to road traffic noise with higher risk of mortality.

Ambient benzene at the residence and risk for subtypes of childhood leukemia, lymphoma and CNS tumor.

Exposure to benzene increases the risk for acute myeloid leukemia and possibly other types of cancer in adults. For children, only limited evidence about benzene and cancer exists. A few studies have indicated that benzene may increase risk for some subtypes of childhood cancer but not for others. We aimed to investigate if outdoor levels of benzene at the residence increase the risk for subtypes of leukemia, lymphoma and CNS tumor in children. We identified 1,989 children diagnosed with leukemia, lymphoma or CNS tumor during 1968-1991 in the Danish Cancer Registry and randomly selected 5,506 control children from the Danish population, matched on sex, age and calendar time. We traced residential history of all children from 9 months before birth to time of diagnosis, calculated outdoor benzene concentration at all addresses and summarized cumulative exposure over fetal and childhood periods separately. We used conditional logistic regression for the statistical analyses. Benzene exposure during childhood above the 90th percentile was associated with relative risks for acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) of 1.0 (95% confidence intervals (CI): 0.6-1.7) and 1.9 (95% CI: 0.3-11.1), respectively, when compared with exposure levels below the median. For CNS tumors, there was a tendency of lower risk for ependymoma and higher risk for medulloblastoma in association with higher exposure. In conclusion, benzene was associated with higher risk for childhood AML, but not ALL, which is consistent with the few previous studies.

Smoking and risk of coronary heart disease in younger, middle-aged, and older adults.

OBJECTIVES: We investigated associations of smoking and coronary heart disease (CHD) by age. METHODS: Data came from the Pooling Project on Diet and Coronary Heart Disease (8 prospective studies, 1974-1996; n = 192,067 women and 74,720 men, aged 40-89 years). RESULTS: During follow-up, 4326 cases of CHD were reported. Relative to never smokers, CHD risk among current smokers was highest in the youngest and lowest in the oldest participants. For example, among women aged 40 to 49 years the hazard ratio was 8.5 (95% confidence interval [CI] = 5.0, 14) and 3.1 (95% CI = 2.0, 4.9) among those aged 70 years or older. The largest absolute risk differences between current smokers and never smokers were observed among the oldest participants. Finally, the majority of CHD cases among smokers were attributable to smoking. For example, attributable proportions of CHD by age group were 88% (40-49 years), 81% (50-59 years), 71% for (60-69 years), and 68% (≥ 70 years) among women who smoked. CONCLUSIONS: Among smokers, the majority of CHD cases are attributable to smoking in all age groups. Smoking prevention is important, irrespective of age.

Concomitant exposure to air pollution, green space and noise, and risk of myocardial infarction: a cohort study from Denmark.

AIMS: The three correlated environmental exposures (air pollution, road traffic noise, and green space) have all been associated with the risk of myocardial infarction (MI). The present study aimed to analyse their independent and cumulative association with MI. METHODS AND RESULTS: In a cohort of all Danes aged 50 or older in the period 2005-17, 5-year time-weighted average exposure to fine particles (PM2.5), ultrafine particles, elemental carbon, nitrogen dioxide (NO2), and road traffic noise at the most and least exposed façades of residence was estimated. Green space around residences was estimated from land use maps. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence interval (CI), and cumulative risk indices (CRIs) were calculated. All expressed per interquartile range. Models were adjusted for both individual and neighbourhood-level socio-demographic covariates. The cohort included 1 964 702 persons. During follow-up, 71 285 developed MI. In single-exposure models, all exposures were associated with an increased risk of MI. In multi-pollutant analyses, an independent association with risk of MI was observed for PM2.5 (HR: 1.026; 95% CI: 1.002-1.050), noise at most exposed façade (HR: 1.024; 95% CI: 1.012-1.035), and lack of green space within 150 m of residence (HR: 1.018; 95% CI: 1.010-1.027). All three factors contributed significantly to the CRI (1.089; 95% CI: 1.076-1.101). CONCLUSION: In a nationwide cohort study, air pollution, noise, and lack of green space were all independently associated with an increased risk of MI. The air pollutant PM2.5 was closest associated with MI risk.

The present study aimed to analyse their independent and cumulative association of the three correlated environmental exposures: air pollution, road traffic noise, and green space with MI. Air pollution, noise, and lack of green space were all independently associated with MI.Risk estimates for air pollution, noise, and lack of green space were similar, indicating that all may be equally relevant targets for regulatory measures.

Blood Leukocyte AHRR Methylation and Risk of Non-smoking-associated Cancer: A Case-cohort Study of Non-Hodgkin Lymphoma.

Aryl-hydrocarbon receptor repressor (AHRR) hypomethylation in peripheral blood is tightly linked with tobacco smoking and lung cancer. Here, we investigated AHRR methylation in non-Hodgkin lymphoma (NHL), a non-smoking-associated cancer. In a case-cohort study within the population-based Danish Diet, Cancer and Health cohort, we measured AHRR (cg23576855) methylation in prediagnostic blood from 161 participants who developed NHL within 13.4 years of follow-up (median: 8.5 years), with a comparison group of 164 randomly chosen participants. We measured DNA-methylation levels using bisulfite pyrosequencing and estimated incidence rate ratios (IRR) using Cox proportional hazards models with adjustment for baseline age, sex, educational level, smoking status, body mass index, alcohol intake, physical activity, and diet score. Global DNA-methylation levels were assessed by long interspersed nucleotide element 1 (LINE-1) analysis. Overall, the IRR for AHRR hypomethylation (lowest vs. other quartiles) was 2.52 [95% confidence interval (CI), 1.24-5.15]. When stratified according to time between blood draw and diagnosis, low AHRR methylation levels were associated with a future diagnosis of NHL [IRR: 4.50 (95% CI, 1.62-12.50) at 0-<5 years, 7.04 (95% CI, 2.36-21.02) at 5-<10 years, and 0.56 (95% CI, 0.21-1.45) at ≥10 years]. There was no association between global DNA-methylation levels and risk of NHL. Our results show that AHRR hypomethylation in blood leukocytes is associated with a higher risk of NHL in a time-dependent manner, suggesting that it occurs as a response to tumor development. Significance: Our population-based study demonstrated that lower AHRR methylation levels in peripheral blood leukocytes were associated with an increased risk of NHL. This association was independent of tobacco smoking, sex, and lifestyle characteristics, but was highly dependent on time to diagnosis. These findings highlight the potential of AHRR methylation as a biomarker for NHL risk, effective up to 10 years after blood draw.

PM2.5 air pollution components and mortality in Denmark.

BACKGROUND: Ambient fine particulate matter (PM2.5) causes millions of deaths every year worldwide. Identification of the most harmful types of PM2.5 would facilitate efficient prevention strategies. OBJECTIVES: The aim of this study was to investigate associations between components of PM2.5 and mortality in a nation-wide Danish population. METHODS: Our study base was Danes born 1921-1985 and aged 30-85 years, who were followed up for mortality from 1991 to 2015. We included 678,465 natural cause mortality cases and selected five age, sex and calendar time matched controls to each case from the study base. We retrieved the address history of the study population from Danish registries and assessed five-year average concentrations of eight PM2.5 components using deterministic Chemistry-Transport Models air pollution models. We estimated mortality rate ratios (MRRs) by conditional logistic regression and adjusted for socio-demographical factors at individual and neighborhood level. RESULTS: Single pollutant models showed the strongest associations between natural cause mortality and an interquartile increase in sulfate particles (SO4--) (MRR: 1.123; 95 % CI: 1.100-1.147 per 1.5 µg/m3) and secondary organic aerosol (SOA) (MRR: 1.054; 95 % CI: 1.048-1.061 per 0.050 µg/m3). Two-pollutant models showed robust associations between SO4-- and SOA and natural cause mortality. Elemental carbon and mineral dust showed robust associations with higher respiratory and lung cancer mortality. CONCLUSION: This nation-wide study found robust associations between natural cause mortality and SO4-- particles and SOA, which is in line with the results of previous studies. Elemental carbon and mineral dust showed robust associations with higher respiratory and lung cancer mortality.

Concomitant exposure to air pollution, green space, and noise and risk of stroke: a cohort study from Denmark.

Background: Air pollution, road traffic noise, and green space are correlated factors, associated with risk of stroke. We investigated their independent relationship with stroke in multi-exposure analyses and estimated their cumulative stroke burden. Methods: For all persons, ≥50 years of age and living in Denmark from 2005 to 2017, we established complete address histories and estimated running 5-year mean exposure to fine particles (PM2.5), ultrafine particles, elemental carbon, nitrogen dioxide (NO2), and road traffic noise at the most, and least exposed façade. For air pollutants, we estimated total, and non-traffic contributions. Green space around the residence was estimated from land use maps. Hazard ratios (HR) and 95% confidence limits (CL) were estimated with Cox proportional hazards models and used to calculate cumulative risk indices (CRI). We adjusted for the individual and sociodemographic covariates available in our dataset (which did not include information about individual life styles and medical conditions). Findings: The cohort accumulated 18,344,976 years of follow-up and 94,256 cases of stroke. All exposures were associated with risk of stroke in single pollutant models. In multi-pollutant analyses, only PM2.5 (HR: 1.058, 95% CI: 1.040-1.075) and noise at most exposed façade (HR: 1.033, 95% CI: 1.024-1.042) were independently associated with a higher risk of stroke. Both noise and air pollution contributed substantially to the CRI (1.103, 95% CI: 1.092-1.114) in the model with noise, green space, and total PM2.5 concentrations. Interpretation: Environmental exposure to air pollution and noise were both independently associated with risk of stroke. Funding: Health Effects Institute (HEI) (Assistance Award No. R-82811201).

Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort: An ELAPSE study.

BACKGROUND: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. METHODS: Within the project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. RESULTS: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01-1.55), NO2 (1.13; 0.95-1.34 per 10 µg/m3), and BC (1.12; 0.94-1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58-0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95-1.62) or BC (1.28; 0.96-1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5. CONCLUSION: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality.