Two of three studies that assessed risk by duration of employment as a welder showed positive trends.3,4 These studies also showed increased ocular melanoma risk associated with eye burns-a proxy for ...UV exposure-and one reported a positive exposure-response association for cumulative occupational exposure to artificial UV radiation, including welding.3,4 Risks persisted after adjustment for sun exposure, sun bed use, or both.4-6 Welding fumes are produced when metals heated above their melting point vaporise and condense to fine particles (mostly <1 μm in size). In one oropharyngeal aspiration study and one inhalation study in male A/J mice, gas metal arc-stainless steel welding fumes promoted 3-methylcholanthrene-induced lung tumours.13,14 Absorption and excretion of metals (chromium, nickel, and manganese) was shown in people exposed to welding fumes, but data for particle deposition and clearance in welders were scarce. 2 International Agency for Research on Cancer, Chromium, nickel and welding, IARC Monogr Eval Carcinog Risks Hum, Vol. 49, 1990, 1-648 3 CM Vajdic, A Kricker, M Giblin, Artificial ultraviolet radiation and ocular melanoma in Australia, Int J Cancer, Vol. 112, 2004, 896-900 4 P Guenel, L Laforest, D Cyr, Occupational risk factors, ultraviolet radiation, and ocular melanoma: a case-control study in France, Cancer Causes Control, Vol. 12, 2001, 451-459 5 EA Holly, DA Aston, DK Ahn, AH Smith, Intraocular melanoma linked to occupations and chemical exposures, Epidemiology, Vol. 7, 1996, 55-61 6 JM Seddon, ES Gragoudas, RJ Glynn, KM Egan, DM Albert, PH Blitzer, Host factors, UV radiation, and risk of uveal melanoma. A case-control...
Mitochondria are sensitive to environmental toxicants due to their lack of repair capacity. Changes in mitochondrial DNA (mtDNA) content may represent a biologically relevant intermediate outcome in ...mechanisms linking air pollution and fetal growth restriction.
We investigated whether placental mtDNA content is a possible mediator of the association between prenatal nitrogen dioxide (NO2) exposure and birth weight.
We used data from two independent European cohorts: INMA (n = 376; Spain) and ENVIRONAGE (n = 550; Belgium). Relative placental mtDNA content was determined as the ratio of two mitochondrial genes (MT-ND1 and MTF3212/R3319) to two control genes (RPLP0 and ACTB). Effect estimates for individual cohorts and the pooled data set were calculated using multiple linear regression and mixed models. We also performed a mediation analysis.
Pooled estimates indicated that a 10-μg/m3 increment in average NO2 exposure during pregnancy was associated with a 4.9% decrease in placental mtDNA content (95% CI: -9.3, -0.3%) and a 48-g decrease (95% CI: -87, -9 g) in birth weight. However, the association with birth weight was significant for INMA (-66 g; 95% CI: -111, -23 g) but not for ENVIRONAGE (-20 g; 95% CI: -101, 62 g). Placental mtDNA content was associated with significantly higher mean birth weight (pooled analysis, interquartile range increase: 140 g; 95% CI: 43, 237 g). Mediation analysis estimates, which were derived for the INMA cohort only, suggested that 10% (95% CI: 6.6, 13.0 g) of the association between prenatal NO2 and birth weight was mediated by changes in placental mtDNA content.
Our results suggest that mtDNA content can be one of the potential mediators of the association between prenatal air pollution exposure and birth weight.
Clemente DB, Casas M, Vilahur N, Begiristain H, Bustamante M, Carsin AE, Fernández MF, Fierens F, Gyselaers W, Iñiguez C, Janssen BG, Lefebvre W, Llop S, Olea N, Pedersen M, Pieters N, Santa Marina L, Souto A, Tardón A, Vanpoucke C, Vrijheid M, Sunyer J, Nawrot TS. 2016. Prenatal ambient air pollution, placental mitochondrial DNA content, and birth weight in the INMA (Spain) and ENVIRONAGE (Belgium) birth cohorts. Environ Health Perspect 124:659-665; http://dx.doi.org/10.1289/ehp.1408981.
BackgroundAn estimated 110 million workers are exposed to welding fumes worldwide. Welding fumes are classified by the International Agency for Research on Cancer as carcinogenic to humans (group 1), ...based on sufficient evidence of lung cancer from epidemiological studies.ObjectiveTo conduct a meta-analysis of case-control and cohort studies on welding or exposure to welding fumes and risk of lung cancer, accounting for confounding by exposure to asbestos and tobacco smoking.MethodsThe literature was searched comprehensively in PubMed, reference lists of relevant publications and additional databases. Overlapping populations were removed. Meta-relative risks (mRRs) were calculated using random effects models. Publication bias was assessed using funnel plot, Eggers’s test and Begg’s test.ResultsForty-five studies met the inclusion criteria (20 case-control, 25 cohort/nested case-control), which reduced to 37 when overlapping study populations were removed. For ‘ever’ compared with ‘never’ being a welder or exposed to welding fumes, mRRs and 95% CIs were 1.29 (1.20 to 1.39; I2=26.4%; 22 studies) for cohort studies, 1.87 (1.53 to 2.29; I2=44.1%; 15 studies) for case-control studies and 1.17 (1.04 to 1.38; I2=41.2%) for 8 case-control studies that adjusted for smoking and asbestos exposure. The mRRs were 1.32 (95% CI 1.20 to 1.45; I2=6.3%; 15 studies) among ‘shipyard welders’, 1.44 (95% CI 1.07 to 1.95; I2=35.8%; 3 studies) for ‘mild steel welders’ and 1.38 (95% CI 0.89 to 2.13; I2=68.1%; 5 studies) among ‘stainless steel welders’. Increased risks persisted regardless of time period, geographic location, study design, occupational setting, exposure assessment method and histological subtype.ConclusionsThese results support the conclusion that exposure to welding fumes increases the risk of lung cancer, regardless of the type of steel welded, the welding method (arc vs gas welding) and independent of exposure to asbestos or tobacco smoking.
Prenatal exposure to the highly toxic and common pollutant cadmium has been associated with adverse effects on child health and development. However, the underlying biological mechanisms of cadmium ...toxicity remain partially unsolved. Epigenetic disruption due to early cadmium exposure has gained attention as a plausible mode of action, since epigenetic signatures respond to environmental stimuli and the fetus undergoes drastic epigenomic rearrangements during embryogenesis. In the current review, we provide a critical examination of the literature addressing prenatal cadmium exposure and epigenetic effects in human, animal, and in vitro studies. We conducted a PubMed search and obtained eight recent studies addressing this topic, focusing almost exclusively on DNA methylation. These studies provide evidence that cadmium alters epigenetic signatures in the DNA of the placenta and of the newborns, and some studies indicated marked sexual differences for cadmium-related DNA methylation changes. Associations between early cadmium exposure and DNA methylation might reflect interference with de novo DNA methyltransferases. More studies, especially those including environmentally relevant doses, are needed to confirm the toxicoepigenomic effects of prenatal cadmium exposure and how that relates to the observed health effects of cadmium in childhood and later life.
Systematic reviews are powerful tools for drawing causal inference for evidence-based decision-making. Published systematic reviews and meta-analyses of environmental and occupational epidemiology ...studies have increased dramatically in recent years; however, the quality and utility of published reviews are variable. Most methodologies were adapted from clinical epidemiology and have not been adequately modified to evaluate and integrate evidence from observational epidemiology studies assessing environmental and occupational hazards, especially in evaluating the quality of exposure assessments. Although many reviews conduct a systematic and transparent assessment for the potential for bias, they are often deficient in subsequently integrating across a body of evidence. A cohesive review considers the impact of the direction and magnitude of potential biases on the results, systematically evaluates important scientific issues such as study sensitivity and effect modifiers, identifies how different studies complement each other, and assesses other potential sources of heterogeneity. Given these challenges of conducting informative systematic reviews of observational studies, we provide a series of specific recommendations based on practical examples for cohesive evidence integration to reach an overall conclusion on a body of evidence to better support policy making in public health.
We conducted an epigenome-wide association study (EWAS) of DNA methylation in placenta in relation to maternal tobacco smoking during pregnancy and examined whether smoking-induced changes lead to ...low birthweight.
DNA methylation in placenta was measured using the Illumina HumanMethylation450 BeadChip in 179 participants from the INfancia y Medio Ambiente (INMA) birth cohort. Methylation levels across 431 311 CpGs were tested for differential methylation between smokers and non-smokers in pregnancy. We took forward three top-ranking loci for further validation and replication by bisulfite pyrosequencing using data of 248 additional participants of the INMA cohort. We examined the association of methylation at smoking-associated loci with birthweight by applying a mediation analysis and a two-sample Mendelian randomization approach.
Fifty CpGs were differentially methylated in placenta between smokers and non-smokers during pregnancy false discovery rate (FDR) < 0.05. We validated and replicated differential methylation at three top-ranking loci: cg27402634 located between LINC00086 and LEKR1, a gene previously related to birthweight in genome-wide association studies; cg20340720 (WBP1L); and cg25585967 and cg12294026 (TRIO). Dose-response relationships with maternal urine cotinine concentration during pregnancy were confirmed. Differential methylation at cg27402634 explained up to 36% of the lower birthweight in the offspring of smokers (Sobel P-value < 0.05). A two-sample Mendelian randomization analysis provided evidence that decreases in methylation levels at cg27402634 lead to decreases in birthweight.
We identified novel loci differentially methylated in placenta in relation to maternal smoking during pregnancy. Adverse effects of maternal smoking on birthweight of the offspring may be mediated by alterations in the placental methylome.
The placenta is an informative and easily available tissue for many epidemiological studies. We analyzed the extent to which storage delay affects DNA methylation.
Biopsies from two placentas were ...sequentially stored at -80°C after standing at room temperature for 30 min, 1 h, 2 h, 6 h and 24 h. Global DNA methylation was measured by bisulfite pyrosequencing of repetitive elements and the luminometric methylation assay.
Small changes in global DNA methylation in relation to time-to-storage were observed by pyrosequencing, with a coefficient of variation (COV) of 2.49% (placenta 1) and 2.86% (placenta 2), similar to the mean technical variation observed for pyrosequencing (COV: 1.91 and 1.51%, respectively). A luminometric methylation assay yielded more variable results in the two placentas analyzed, both among time points (COV: 9.13 and 10.35%, respectively) and technical replicates (COV: 11.60 and 9.80%, respectively).
Global DNA methylation is stable at room temperature. However, some techniques to measure methylation might be confounded by DNA degradation caused by a delay in storage.
Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks.
In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the ...potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation.
The biomarker total effective xenoestrogen burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retroviruses (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated.
A significant sex interaction was observed for AluYb8 (p-value for interaction <0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p-value<0.001), while no significant effects were found in girls (p-value=0.134).
Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development.
•Few epidemiologic studies have analyzed effects of mixtures of hormonally active compounds.•We measured a biomarker of prenatal cumulative exposure to xenoestrogens.•We examined its relationship with DNA methylation of repetitive elements in placenta.•Higher levels of xenoestrogens were associated with lower AluYb8 methylation in boys.
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