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1.
Hum Mol Genet ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600786

RESUMO

We previously identified five SNPs at four susceptibility loci for diffuse large B-cell lymphoma (DLBCL) in individuals of European ancestry through a large genome-wide association study (GWAS). To further elucidate genetic susceptibility to DLBCL, we sought to validate 2 loci at 3q13.33 and 3p24.1 that were suggestive in the original GWAS with additional genotyping. In the meta-analysis (5,662 cases and 9,237 controls) of the four original GWAS discovery scans and three replication studies, the 3q13.33 locus (rs9831894; minor allele frequency [MAF]=0.40) was associated with DLBCL risk (OR=0.83, P=3.62x10-13). rs9831894 is in linkage disequilibrium (LD) with additional variants that are part of a super-enhancer that physically interacts with promoters of CD86 and ILDR1. In the meta-analysis (5,510 cases and 12,817 controls) of the four GWAS discovery scans and four replication studies, the 3p24.1 locus (rs6773363; MAF=0.45) was also associated with DLBCL risk (OR=1.20, P=2.31x10-12). This SNP is 29,426 bp upstream of the nearest gene EOMES and in LD with additional SNPs that are part of a highly lineage-specific and tumor-acquired super-enhancer that shows long-range interaction with AZI2 promoter. These loci provide additional evidence for the role of immune function in the etiology of DLBCL, the most common lymphoma subtype.

2.
Br J Nutr ; : 1-35, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31583990

RESUMO

Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent, and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterize the association between plasma concentrations of 35 polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis the odds and 95% confidence intervals (CI-s) of elevated serum hsCRP (>3 mg/L) were calculated within quartiles and per standard deviation (SD) higher level of plasma polyphenol concentrations. In multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per SD) was associated with 29% lower odds of elevated hsCRP (95% CI: 50%-1%). In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR= 0.66, 95%CI 0.46-0.96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR=0.58, 95%CI 0.39-0.86), 3,4-dihydroxyphenylpropionic acid (OR= 0.63, 95% CI 0.46-0.87), ferulic acid (OR= 0.65, 95%CI 0.44-0.96), and caffeic acid (OR= 0.69, 95%CI 0.51-0.93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR= 0.67, 95%CI 0.48-0.93). This study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies.

3.
Epidemiology ; 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577634

RESUMO

INTRODUCTION: Various established occupational lung carcinogens are also suspected risk factors for laryngeal cancer. However, individual studies are often inadequate in size to investigate this relatively rare outcome. Other limitations include imprecise exposure assessment and inadequate adjustment for confounders. METHODS: This study applied a quantitative job exposure matrix (SYN-JEM) for four established occupational lung carcinogens to five case-control studies within the INHANCE Consortium. We used occupational histories for 2256 laryngeal cancer cases and 7857 controls recruited from 1989-2007. We assigned quantitative exposure levels for asbestos, respirable crystalline silica, chromium-VI, and chromium-VI & nickel combined (to address highly correlated exposures) via SYN-JEM. We assessed effects of occupational exposure on cancer risk for males (asbestos, respirable crystalline silica, chromium-VI, chromium-VI & nickel) and females (asbestos, respirable crystalline silica), adjusting for age, study, tobacco smoking, alcohol consumption, and asbestos exposure where relevant. RESULTS: Among females, odds ratios (ORs) were increased for ever versus never exposed. Among males, p-values for linear trend were <0.05 for estimated cumulative exposure (all agents) and <0.05 for exposure duration (respirable crystalline silica, chromium-VI, and chromium-VI & nickel); strongest associations were for asbestos at >90%ile cumulative exposure (OR=1.3, CI=1.0-1.6), respirable crystalline silica at 30+ years duration (OR=1.4, CI=1.2-1.7) and 75%-90%ile cumulative exposure (OR=1.4, CI=1.1-1.8), chromium-VI at >75%ile cumulative exposure (OR=1.9, CI=1.2-3.0), and chromium-VI & nickel at 20-29 years duration (OR=1.5, CI=1.1-2.2). CONCLUSIONS: These findings support hypotheses of causal links between four lung carcinogens (asbestos, respirable crystalline silica, chromium-VI, and nickel) and laryngeal cancer.

4.
PLoS One ; 14(10): e0223522, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31647846

RESUMO

Shift work induces chronic circadian disturbance, which might result in increased health risks, including cardio-metabolic diseases. Previously, we identified sCD36 as a potential non-circadian biomarker of chronic circadian disturbance in mice. The aim of the current study (n = 232 individuals) was to identify whether sCD36 measured in plasma can be used as a non-circadian marker of chronic circadian disturbance in humans, which would allow its use to measure the effects of interventions and monitoring in large-scale studies. We compared levels of plasma sCD36 of day workers with recent (< 2 years) and experienced (> 5 years) night-shift workers within the Klokwerk study. We detected no differences in sCD36 levels between day workers and recent or experienced night-shift workers, measured during a day or afternoon shift. In addition, sCD36 levels measured directly after a night shift were not different from sCD36 levels measured during day or afternoon shifts, indicating no acute effect of night shifts on sCD36 levels in our study. In summary, our study does not show a relation between night-shift work experience (recent or long-term) and plasma levels of sCD36. Since we do not know if and for which time span night-shift work is associated with changes in sCD36 levels, and our study was relatively small and cross-sectional, further evidence for an association between chronic circadian disruption and this candidate biomarker sCD36 should be gathered from large cohort studies.

5.
JAMA Intern Med ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479109

RESUMO

Importance: Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date. Objective: To examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality. Design, Setting, and Participants: This population-based cohort study involved participants (n = 451 743 of the full cohort) in the European Prospective Investigation into Cancer and Nutrition (EPIC), an ongoing, large multinational cohort of people from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom), with participants recruited between January 1, 1992, and December 31, 2000. Excluded participants were those who reported cancer, heart disease, stroke, or diabetes at baseline; those with implausible dietary intake data; and those with missing soft drink consumption or follow-up information. Data analyses were performed from February 1, 2018, to October 1, 2018. Exposure: Consumption of total, sugar-sweetened, and artificially sweetened soft drinks. Main Outcomes and Measures: Total mortality and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazards regression models adjusted for other mortality risk factors. Results: In total, 521 330 individuals were enrolled. Of this total, 451 743 (86.7%) were included in the study, with a mean (SD) age of 50.8 (9.8) years and with 321 081 women (71.1%). During a mean (range) follow-up of 16.4 (11.1 in Greece to 19.2 in France) years, 41 693 deaths occurred. Higher all-cause mortality was found among participants who consumed 2 or more glasses per day (vs consumers of <1 glass per month) of total soft drinks (hazard ratio [HR], 1.17; 95% CI, 1.11-1.22; P < .001), sugar-sweetened soft drinks (HR, 1.08; 95% CI, 1.01-1.16; P = .004), and artificially sweetened soft drinks (HR, 1.26; 95% CI, 1.16-1.35; P < .001). Positive associations were also observed between artificially sweetened soft drinks and deaths from circulatory diseases (≥2 glasses per day vs <1 glass per month; HR, 1.52; 95% CI, 1.30-1.78; P < .001) and between sugar-sweetened soft drinks and deaths from digestive diseases (≥1 glass per day vs <1 glass per month; HR, 1.59; 95% CI, 1.24-2.05; P < .001). Conclusions and Relevance: This study found that consumption of total, sugar-sweetened, and artificially sweetened soft drinks was positively associated with all-cause deaths in this large European cohort; the results are supportive of public health campaigns aimed at limiting the consumption of soft drinks.

6.
Int J Epidemiol ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31539056

RESUMO

BACKGROUND: Previous results from the Diesel Exhaust in Miners Study (DEMS) demonstrated a positive exposure-response relation between lung cancer and respirable elemental carbon (REC), a key surrogate for diesel exhaust exposure. Two issues have been raised regarding DEMS: (i) the use of historical carbon monoxide (CO) measurements to calibrate models used for estimating historical exposures to REC in the DEMS exposure assessment; and (ii) potential confounding by radon. METHODS: We developed alternative REC estimates using models that did not rely on CO for calibration, but instead relied on estimated use of diesel equipment, mine ventilation rates and changes in diesel engine emission rates over time. These new REC estimates were used to quantify cumulative REC exposure for each subject in the nested case-control study. We conducted conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals for lung cancer. To evaluate the impact of including radon as a potential confounder, we estimated ORs for average REC intensity adjusted for cumulative radon exposure in underground miners. RESULTS: Validation of the new REC exposure estimates indicated that they overestimated historical REC by 200-400%, compared with only 10% for the original estimates. Effect estimates for lung cancer using these alternative REC exposures or adjusting for radon typically changed by <10% when compared with the original estimates. CONCLUSIONS: These results emphasize the robustness of the DEMS findings, support the use of CO for model calibration and confirm that radon did not confound the DEMS estimates of the effect of diesel exposure on lung cancer mortality.

7.
Environ Health Perspect ; 127(9): 97001, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31487206

RESUMO

BACKGROUND: Lung cancer rates among never-smoking women in Xuanwei and Fuyuan in China are among the highest in the world and have been attributed to the domestic use of smoky (bituminous) coal for heating and cooking. However, the key components of coal that drive lung cancer risk have not been identified. OBJECTIVES: We aimed to investigate the relationship between lifelong exposure to the constituents of smoky coal (and other fuel types) and lung cancer. METHODS: Using a population-based case-control study of lung cancer among 1,015 never-smoking female cases and 485 controls, we examined the association between exposure to 43 household air pollutants and lung cancer. Pollutant predictions were derived from a comprehensive exposure assessment study, which included methylated polycyclic aromatic hydrocarbons (PAHs), which have never been directly evaluated in an epidemiological study of any cancer. Hierarchical clustering and penalized regression were applied in order to address high colinearity in exposure variables. RESULTS: The strongest association with lung cancer was for a cluster of 25 PAHs [odds ratio (OR): 2.21; 95% confidence interval (CI): 1.67, 2.87 per 1 standard deviation (SD) change], within which 5-methylchrysene (5-MC), a mutagenic and carcinogenic PAH, had the highest individual observed OR (5.42; 95% CI: 0.94, 27.5). A positive association with nitrogen dioxide ([Formula: see text]) was also observed (OR: 2.06; 95% CI: 1.19, 3.49). By contrast, neither benzo(a)pyrene (BaP) nor fine particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]) were associated with lung cancer in the multipollutant models. CONCLUSIONS: To our knowledge, this is the first study to comprehensively evaluate the association between lung cancer and household air pollution (HAP) constituents estimated over the entire life course. Given the global ubiquity of coal use domestically for indoor cooking and heating and commercially for electric power generation, our study suggests that more extensive monitoring of coal combustion products, including methylated PAHs, may be warranted to more accurately assess health risks and develop prevention strategies from this exposure. https://doi.org/10.1289/EHP4913.

8.
Int J Cancer ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31513294

RESUMO

Although smoking and oxidative stress are known contributors to lung carcinogenesis, their mechanisms of action remain poorly understood. To shed light into these mechanisms, we applied a novel approach using Cys34-adductomics in a lung cancer nested case-control study (n = 212). Adductomics profiles were integrated with DNA-methylation data at established smoking-related CpG sites measured in the same individuals. Our analysis identified 42 Cys34-albumin adducts, of which 2 were significantly differentially abundant in cases and controls: adduct of N-acetylcysteine (NAC, p = 4.15 × 10-3 ) and of cysteinyl-glycine (p = 7.89 × 10-3 ). Blood levels of the former were found associated to the methylation levels at 11 smoking-related CpG sites. We detect, for the first time in prospective blood samples, and irrespective of time to diagnosis, decreased levels of NAC adduct in lung cancer cases. Altogether, our results highlight the potential role of these adducts in the oxidative stress response contributing to lung carcinogenesis years before diagnosis.

9.
Cancer Epidemiol Biomarkers Prev ; 28(9): 1552-1555, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31481495

RESUMO

BACKGROUND: There is a lack of prospective data on the potential association of Fusobacterium nucleatum (F. nucleatum) and colorectal cancer risk. In this study, we assessed whether antibody responses to F. nucleatum are associated with colorectal cancer risk in prediagnostic serum samples in the European Prospective Investigation into Nutrition and Cancer (EPIC) cohort. METHODS: We applied a multiplex serology assay to simultaneously measure antibody responses to 11 F. nucleatum antigens in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: We observed neither a statistically significant colorectal cancer risk association for antibodies to individual F. nucleatum proteins nor for combined positivity to any of the 11 proteins (OR, 0.81; 95% CI, 0.62-1.06). CONCLUSIONS: Antibody responses to F. nucleatum proteins in prediagnostic serum samples from a subset of colorectal cancer cases and matched controls within the EPIC study were not associated with colorectal cancer risk. IMPACT: Our findings in prospectively ascertained serum samples contradict the existing literature on the association of F. nucleatum with colorectal cancer risk. Future prospective studies, specifically detecting F. nucleatum in stool or tissue biopsies, are needed to complement our findings.

10.
Int J Epidemiol ; 2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31377785

RESUMO

BACKGROUND: Lifetime use of bituminous ('smoky') coal is associated with nearly a 100-fold higher risk of lung cancer mortality compared with anthracite ('smokeless') coal use in rural Xuanwei, China, among women. Risk of mortality from ischaemic heart disease (IHD) and stroke for these coal types has not been evaluated. METHODS: A cohort of 16 323 non-smoking women in Xuanwei, who were lifetime users of either smoky or smokeless coal, were followed up from 1976 to 2011. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) to evaluate lifetime use of coal types and stoves in the home in relation to risk of IHD and stroke mortality. RESULTS: Among lifetime users of smokeless coal, higher average exposure intensity (≥4 tons/year vs <2.5 tons/year, HR = 7.9, 95% CI = 3.5-17.8; Ptrend =<0.0001) and cumulative exposure (>64 ton-years vs ≤28 ton-years, HR = 6.5, 95% CI = 1.5-28.3; Ptrend =0.003) during follow-up and over their lifetime was associated with increased IHD mortality, and ventilated stove use dramatically reduced this risk (HR = 0.2, 95% CI 0.1-0.5). Higher cumulative exposure to smoky coal during follow-up showed positive associations with IHD mortality, but the evidence for other metrics was less consistent compared with associations with smokeless coal use. CONCLUSIONS: Higher use of smokeless coal, which is burned throughout China and is generally regarded to be a cleaner fuel type, is associated with IHD mortality. Use of cleaner fuels or stove interventions may be effective in reducing the increasing burden of IHD in developing regions that currently rely on smokeless coal for cooking and heating.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31434759

RESUMO

BACKGROUND: We investigated the association between cigarette smoking and risk of amyotrophic lateral sclerosis (ALS) in a pooled analysis of population-based case-control studies and explored the independent effects of intensity, duration and time-since-quitting. METHODS: ALS cases and controls, matched by age, sex and region, were recruited in the Netherlands, Italy and Ireland (*Euro-MOTOR project). Demographics and detailed lifetime smoking histories were collected through questionnaires. Effects of smoking status, intensity (cigarettes/day), duration (years), pack-years and time-since-quitting (years) on ALS risk were estimated using logistic regression models, adjusting for age, sex, alcohol, education and centre. We further investigated effect modification of the linear effects of pack-years by intensity, duration and time-since-quitting using excess OR (eOR) models. RESULTS: Analyses were performed on 1410 cases and 2616 controls. Pack-years were positively associated with ALS risk; OR=1.26 (95% CI: 1.03 to 1.54) for the highest quartile compared with never smokers. This association appeared to be predominantly driven by smoking duration (ptrend=0.001) rather than intensity (ptrend=0.86), although the trend for duration disappeared after adjustment for time-since-quitting. Time-since-quitting was inversely related to ALS (ptrend<0.0001). The eOR decreased with time-since-quitting smoking, until about 10 years prior to disease onset. High intensity smoking with shorter duration appeared more deleterious than lower intensity for a longer duration. CONCLUSIONS: Our findings provide further support for the association between smoking and ALS. Pack-years alone may be insufficient to capture effects of different smoking patterns. Time-since-quitting appeared to be an important factor, suggesting that smoking may be an early disease trigger.

12.
Int J Cancer ; 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31319002

RESUMO

Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.

13.
Occup Environ Med ; 76(8): 545-553, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31285358

RESUMO

OBJECTIVES: Asbestos is the main risk factor for peritoneal mesothelioma (PeM). However, due to its rarity, PeM has rarely been investigated in community-based studies. We examined the association between asbestos exposure and PeM risk in a general population in Lombardy, Italy. METHODS: From the regional mesothelioma registry, we selected PeM cases diagnosed in 2000-2015. Population controls (matched by area, gender and age) came from two case-control studies in Lombardy on lung cancer (2002-2004) and pleural mesothelioma (2014). Assessment of exposure to asbestos was performed through a quantitative job-exposure matrix (SYN-JEM) and expert evaluation based on a standardised questionnaire. We calculated period-specific and gender-specific OR and 90% CI using conditional logistic regression adjusted for age, province of residence and education. RESULTS: We selected 68 cases and 2116 controls (2000-2007) and 159 cases and 205 controls (2008-2015). The ORs for ever asbestos exposure (expert-based, 2008-2015 only) were 5.78 (90% CI 3.03 to 11.0) in men and 8.00 (2.56 to 25.0) in women; the ORs for definite occupational exposure were 12.3 (5.62 to 26.7) in men and 14.3 (3.16 to 65.0) in women. The ORs for ever versus never occupational asbestos exposure based on SYN-JEM (both periods) were 2.05 (90% CI 1.39 to 3.01) in men and 1.62 (0.79 to 3.27) in women. In men, clear positive associations were found for duration, cumulative exposure (OR 1.33 (1.19 to 1.48) per fibres/mL-years) and latency. CONCLUSIONS: Using two different methods of exposure assessment we provided evidence of a clear association between asbestos exposure and PeM risk in the general population.

14.
Environ Health Perspect ; 127(7): 74501, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31271296

RESUMO

The International Initiative on Spatial Lifecourse Epidemiology (ISLE) convened its first International Symposium on Lifecourse Epidemiology and Spatial Science at the Lorentz Center in Leiden, Netherlands, 16­20 July 2018. Its aim was to further an emerging transdisciplinary field: Spatial Lifecourse Epidemiology. This field draws from a broad perspective of scientific disciplines including lifecourse epidemiology, environmental epidemiology, community health, spatial science, health geography, biostatistics, spatial statistics, environmental science, climate change, exposure science, health economics, evidence-based public health, and landscape ecology. The participants, spanning 30 institutions in 10 countries, sought to identify the key issues and research priorities in spatial lifecourse epidemiology. The results published here are a synthesis of the top 10 list that emerged out of the discussion by a panel of leading experts, reflecting a set of grand challenges for spatial lifecourse epidemiology in the coming years. https://doi.org/10.1289/EHP4868.

15.
Int J Epidemiol ; 2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31302690

RESUMO

BACKGROUND: Mobile phone use and exposure to radiofrequency electromagnetic fields (RF-EMF) from it have been associated with symptoms in some studies, but the studies have shortcomings and their findings are inconsistent. We conducted a prospective cohort study to assess the association between amount of mobile phone use at baseline and frequency of headache, tinnitus or hearing loss at 4-year follow-up. METHODS: The participants had mobile phone subscriptions with major mobile phone network operators in Sweden (n = 21 049) and Finland (n = 3120), gave consent for obtaining their mobile phone call data from operator records at baseline, and filled in both baseline and follow-up questionnaires on symptoms, potential confounders and further characteristics of their mobile phone use. RESULTS: The participants with the highest decile of recorded call-time (average call-time >276 min per week) at baseline showed a weak, suggestive increased frequency of weekly headaches at 4-year follow-up (adjusted odds ratio 1.13, 95% confidence interval 0.95-1.34). There was no obvious gradient of weekly headache with increasing call-time (P trend 0.06). The association of headache with call-time was stronger for the Universal Mobile Telecommunications System (UMTS) network than older Global System for Mobile Telecommunications (GSM) technology, despite the latter involving higher exposure to RF-EMF. Tinnitus and hearing loss showed no association with call-time. CONCLUSIONS: People using mobile phones most extensively for making or receiving calls at baseline reported weekly headaches slightly more frequently at follow-up than other users, but this finding largely disappeared after adjustment for confounders and was not related to call-time in GSM with higher RF-EMF exposure. Tinnitus and hearing loss were not associated with amount of call-time.

16.
Int J Cancer ; 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31342519

RESUMO

Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval [CI] 0.77-1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80-1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55-2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.

17.
Environ Int ; 130: 104934, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31229871

RESUMO

Empirical spatial air pollution models have been applied extensively to assess exposure in epidemiological studies with increasingly sophisticated and complex statistical algorithms beyond ordinary linear regression. However, different algorithms have rarely been compared in terms of their predictive ability. This study compared 16 algorithms to predict annual average fine particle (PM2.5) and nitrogen dioxide (NO2) concentrations across Europe. The evaluated algorithms included linear stepwise regression, regularization techniques and machine learning methods. Air pollution models were developed based on the 2010 routine monitoring data from the AIRBASE dataset maintained by the European Environmental Agency (543 sites for PM2.5 and 2399 sites for NO2), using satellite observations, dispersion model estimates and land use variables as predictors. We compared the models by performing five-fold cross-validation (CV) and by external validation (EV) using annual average concentrations measured at 416 (PM2.5) and 1396 sites (NO2) from the ESCAPE study. We further assessed the correlations between predictions by each pair of algorithms at the ESCAPE sites. For PM2.5, the models performed similarly across algorithms with a mean CV R2 of 0.59 and a mean EV R2 of 0.53. Generalized boosted machine, random forest and bagging performed best (CV R2~0.63; EV R2 0.58-0.61), while backward stepwise linear regression, support vector regression and artificial neural network performed less well (CV R2 0.48-0.57; EV R2 0.39-0.46). Most of the PM2.5 model predictions at ESCAPE sites were highly correlated (R2 > 0.85, with the exception of predictions from the artificial neural network). For NO2, the models performed even more similarly across different algorithms, with CV R2s ranging from 0.57 to 0.62, and EV R2s ranging from 0.49 to 0.51. The predicted concentrations from all algorithms at ESCAPE sites were highly correlated (R2 > 0.9). For both pollutants, biases were low for all models except the artificial neural network. Dispersion model estimates and satellite observations were two of the most important predictors for PM2.5 models whilst dispersion model estimates and traffic variables were most important for NO2 models in all algorithms that allow assessment of the importance of variables. Different statistical algorithms performed similarly when modelling spatial variation in annual average air pollution concentrations using a large number of training sites.

18.
Sci Rep ; 9(1): 8818, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31217483

RESUMO

We aim to investigate to what extent a set of immune markers mediate the association between air pollution and adult-onset asthma. We considered long-term exposure to multiple air pollution markers and a panel of 13 immune markers in peripheral blood samples collected from 140 adult cases and 199 controls using a nested-case control design. We tested associations between air pollutants and immune markers and adult-onset asthma using mixed-effects (logistic) regression models, adjusted for confounding variables. In order to evaluate a possible mediating effect of the full set of immune markers, we modelled the relationship between asthma and air pollution with a partial least square path model. We observed a strong positive association of IL-1RA [OR 1.37; 95% CI (1.09, 1.73)] with adult-onset asthma. Univariate models did not yield any association between air pollution and immune markers. However, mediation analyses indicated that 15% of the effect of air pollution on risk of adult-onset asthma was mediated through the immune system when considering all immune markers as a latent variable (path coefficient (ß) = 0.09; 95% CI: (-0.02, 0.20)). This effect appeared to be stronger for allergic asthma (22%; ß = 0.12; 95% CI: (-0.03, 0.27)) and overweight subjects (27%; ß = 0.19; 95% CI: (-0.004, 0.38)). Our results provides supportive evidence for a mediating effect of the immune system in the association between air pollution and adult-onset asthma.

19.
Environ Health Perspect ; 127(6): 67001, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31157976

RESUMO

BACKGROUND: Exposure to light at night (LAN) can perturb the biological clock and affect sleep and health. Previous epidemiological studies have evaluated LAN levels measured by satellites, but the validity of this measure as a proxy for personal LAN exposure is unclear. In addition, outdoor satellite-measured LAN levels are higher in urban environments, which means that this measure could potentially represent a proxy for other, likely urban, environmental exposures. OBJECTIVES: We evaluated correlations of satellite-assessed LAN with measured bedroom light levels and explored correlations with other environmental exposures, in particular, air pollution, green space, and area-level socioeconomic position (SEP). METHODS: We compared satellite measurements with evening and nighttime bedroom measurements of illuminance (in units of lux) for 256 children, and we evaluated correlations between satellite-based measures and other urban exposures such as air pollution, area-level SEP, and surrounding green space for 3,021 children. RESULTS: Satellite-measured LAN levels (nanowatts per centimeter squared per steradian) were not correlated with measured evening or nighttime lux levels [Spearman correlation coefficients ([Formula: see text]) [Formula: see text] to 0.04]. There was a weak correlation with measurements during the darkest time period if parents and their children reported that outdoor light sometimes or usually influenced indoor light levels ([Formula: see text], [Formula: see text]). In contrast, satellite-measured LAN levels were correlated with air pollution ([Formula: see text] with [Formula: see text], [Formula: see text] with [Formula: see text]), and surrounding green space ([Formula: see text] for green space within [Formula: see text] of the home). A weak correlation with area-level SEP was also observed ([Formula: see text]). CONCLUSIONS: Outdoor satellite-assessed outdoor LAN exposure levels were correlated with urban environmental exposures, but they were not a good proxy for indoor evening or nighttime personal exposure as measured in our study population of 12-y-old children. Studies planning to evaluate potential risks from LAN should consider such modifying factors as curtains and indoor lighting and the use of electronic devices and should include performing indoor or personal measurements to validate any exposure proxies. The moderate-to-strong correlation of outdoor LAN with other environmental exposures should be accounted for in epidemiological investigations. https://doi.org/10.1289/EHP3431.

20.
Epigenetics ; 14(11): 1112-1124, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31241004

RESUMO

Human exposure to trichloroethylene (TCE) is linked to kidney cancer, autoimmune diseases, and probably non-Hodgkin lymphoma. Additionally, TCE exposed mice and cell cultures show altered DNA methylation. To evaluate associations between TCE exposure and DNA methylation in humans, we conducted an epigenome-wide association study (EWAS) in TCE exposed workers using the HumanMethylation450 BeadChip. Across individual CpG probes, genomic regions, and globally (i.e., the 450K methylome), we investigated differences in mean DNA methylation and differences in variability of DNA methylation between 73 control (< 0.005 ppm TCE), 30 lower exposed (< 10 ppm TCE), and 37 higher exposed ( ≥ 10 ppm TCE) subjects' white blood cells. We found that TCE exposure increased methylation variation globally (Kruskal-Wallis p-value = 3.75e-3) and in 25 CpG sites at a genome-wide significance level (Bonferroni p-value < 0.05). We identified a 609 basepair region in the TRIM68 gene promoter that exhibited hypomethylation with increased exposure to TCE (FWER = 1.20e-2). Also, genes that matched to differentially variable CpGs were enriched in the 'focal adhesion' biological pathway (p-value = 2.80e-2). All in all, human exposure to TCE was associated with epigenetic alterations in genes involved in cell-matrix adhesions and interferon subtype expression, which are important in the development of autoimmune diseases; and in genes related to cancer development. These results suggest that DNA methylation may play a role in the pathogenesis of TCE exposure-related diseases and that TCE exposure may contribute to epigenetic drift.

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