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1.
Mutational Landscape and Environmental Effects in Bladder Cancer.
Hayashi, T, Fujita, K, Hayashi, Y, Hatano, K, Kawashima, A, McConkey, DJ, Nonomura, N
International journal of molecular sciences. 2020;(17)
Abstract
Bladder cancer is the most common cancer of the urinary tract. Although nonmuscle-invasive bladder cancers have a good prognosis, muscle-invasive bladder cancers promote metastases and have a poor prognosis. Comprehensive analyses using RNA sequence of clinical tumor samples in bladder cancer have been reported. These reports implicated the candidate genes and pathways that play important roles in carcinogenesis and/or progression of bladder cancer. Further investigations for the function of each mutation are warranted. There is suggestive evidence for several environmental factors as risk factors of bladder cancer. Environmental factors such as cigarette smoking, exposure to chemicals and gases, bladder inflammation due to microbial and parasitic infections, diet, and nutrition could induce several genetic mutations and alter the tumor microenvironment, such as immune cells and fibroblasts. The detailed mechanism of how these environmental factors induce carcinogenesis and/or progression of bladder cancer remains unclear. To identify the relationship between the mutations and the lifestyle could be useful for prevention and treatment of bladder cancer.
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Arsenic exposure associated T cell proliferation, smoking, and vitamin D in Bangladeshi men and women.
Burchiel, SW, Lauer, FT, Factor-Litvak, P, Liu, X, Islam, T, Eunus, M, Abu Horayara, M, Islam, MT, Rahman, M, Ahmed, A, et al
PloS one. 2020;(6):e0234965
Abstract
There are limited data examining the consequences of environmental exposure to arsenic on the immune system in adults, particularly among smokers. Smoking has been shown to exacerbate or contribute to impaired immune function in men chronically exposed to arsenic. In contrast, vitamin D (VitD) is known to have a positive influence on innate and adaptive immune responses. The effect of circulating VitD on arsenic-associated immune dysfunction is not known. Here we examine the relationship of arsenic exposure and T cell proliferation (TCP), a measure of immune responsiveness, and circulating VitD among adult men and women in Bangladesh. Arsenic exposure was assessed using total urinary arsenic as well as urinary arsenic metabolites all adjusted for urinary creatinine. TCP was measured ex vivo in cryopreserved peripheral blood mononuclear cells from 614 adult participants enrolled in the Bangladesh Health Effects of Arsenic Longitudinal Study; serum VitD was also evaluated. The influence of cigarette smoking on arsenic-induced TCP modulation was assessed only in males as there was an inadequate number of female smokers. These studies show that arsenic suppressed TCP in males. The association was significantly strong in male smokers and to a lesser extent in male non-smokers. Interestingly, we found a strong protective effect of high/sufficient serum VitD levels on TCP among non-smoking males. Furthermore, among male smokers with low serum VitD (⊔20 ng/ml), we found a strong suppression of TCP by arsenic. On the other hand, high VitD (>20 ng/ml) was found to attenuate effects of arsenic on TCP among male-smokers. Overall, we found a strong protective effect of VitD, when serum levels were >20 ng/ml, on arsenic-induced inhibition of TCP in men, irrespective of smoking status. To our knowledge this is the first large study of immune function in healthy adult males and females with a history of chronic arsenic exposure.
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Catalog of exogenous risk factors for bladder carcinogenesis.
Jahrreiss, V, Pradere, B, Laukhtina, E, Mori, K, Shariat, SF
Current opinion in urology. 2020;(3):449-456
Abstract
PURPOSE OF REVIEW The aim of this article is to provide an overview of recent findings regarding the risk factors for bladder cancer. RECENT FINDINGS Most of the available data derive from retrospective analysis. Smoking represents the most common and important risk factor. Occupational, dietary, and environmental exogenic carcinogen exposure, as well as several lifestyle factors, can increase the risk of developing bladder cancer. SUMMARY Bladder cancer is a common malignancy worldwide. Cigarette smoking, exposure to aromatic amines and arsenic are known risk factors for bladder cancer. Evidence on other modifiable risk factors such as carcinogen exposure derived from the diet or environment as well as occupational hazards is still weak. Medical conditions leading to chronic inflammation, altering insulin resistance, negatively modulating the immune system and/or genetic alterations may have a role in bladder cancer carcinogenesis. Further studies are, however, necessary to identify possible exogenic risk factors, as well as their interactions, that partake in the carcinogenesis of bladder cancer.
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Protective Effect of Breastfeeding on the Adverse Health Effects Induced by Air Pollution: Current Evidence and Possible Mechanisms.
Zielinska, MA, Hamulka, J
International journal of environmental research and public health. 2019;(21)
Abstract
Air pollution is a major social, economic, and health problem around the world. Children are particularly susceptible to the negative effects of air pollution due to their immaturity and excessive growth and development. The aims of this narrative review were to: (1) summarize evidence about the protective effects of breastfeeding on the adverse health effects of air pollution exposure, (2) define and describe the potential mechanisms underlying the protective effects of breastfeeding, and (3) examine the potential effects of air pollution on breastmilk composition and lactation. A literature search was conducted using electronic databases. Existing evidence suggests that breastfeeding has a protective effect on adverse outcomes of indoor and outdoor air pollution exposure in respiratory (infections, lung function, asthma symptoms) and immune (allergic, nervous and cardiovascular) systems, as well as under-five mortality in both developing and developed countries. However, some studies reported no protective effect of breastfeeding or even negative effects of breastfeeding for under-five mortality. Several possible mechanisms of the breastfeeding protective effect were proposed, including the beneficial influence of breastfeeding on immune, respiratory, and nervous systems, which are related to the immunomodulatory, anti-inflammatory, anti-oxidant, and neuroprotective properties of breastmilk. Breastmilk components responsible for its protective effect against air pollutants exposure may be long chain polyunsaturated fatty acids (LC PUFA), antioxidant vitamins, carotenoids, flavonoids, immunoglobins, and cytokines, some of which have concentrations that are diet-dependent. However, maternal exposure to air pollution is related to increased breastmilk concentrations of pollutants (e.g., Polycyclic aromatic hydrocarbons (PAHs) or heavy metals in particulate matter (PM)). Nonetheless, environmental studies have confirmed that breastmilk's protective effects outweigh its potential health risk to the infant. Mothers should be encouraged and supported to breastfeed their infants due to its unique health benefits, as well as its limited ecological footprint, which is associated with decreased waste production and the emission of pollutants.
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A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASs) and present understanding of health effects.
Sunderland, EM, Hu, XC, Dassuncao, C, Tokranov, AK, Wagner, CC, Allen, JG
Journal of exposure science & environmental epidemiology. 2019;(2):131-147
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Abstract
Here, we review present understanding of sources and trends in human exposure to poly- and perfluoroalkyl substances (PFASs) and epidemiologic evidence for impacts on cancer, immune function, metabolic outcomes, and neurodevelopment. More than 4000 PFASs have been manufactured by humans and hundreds have been detected in environmental samples. Direct exposures due to use in products can be quickly phased out by shifts in chemical production but exposures driven by PFAS accumulation in the ocean and marine food chains and contamination of groundwater persist over long timescales. Serum concentrations of legacy PFASs in humans are declining globally but total exposures to newer PFASs and precursor compounds have not been well characterized. Human exposures to legacy PFASs from seafood and drinking water are stable or increasing in many regions, suggesting observed declines reflect phase-outs in legacy PFAS use in consumer products. Many regions globally are continuing to discover PFAS contaminated sites from aqueous film forming foam (AFFF) use, particularly next to airports and military bases. Exposures from food packaging and indoor environments are uncertain due to a rapidly changing chemical landscape where legacy PFASs have been replaced by diverse precursors and custom molecules that are difficult to detect. Multiple studies find significant associations between PFAS exposure and adverse immune outcomes in children. Dyslipidemia is the strongest metabolic outcome associated with PFAS exposure. Evidence for cancer is limited to manufacturing locations with extremely high exposures and insufficient data are available to characterize impacts of PFAS exposures on neurodevelopment. Preliminary evidence suggests significant health effects associated with exposures to emerging PFASs. Lessons learned from legacy PFASs indicate that limited data should not be used as a justification to delay risk mitigation actions for replacement PFASs.
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[Air pollution and atopic eczema : Systematic review of findings from environmental epidemiological studies].
Krämer, U, Behrendt, H
Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 2019;(3):169-184
Abstract
BACKGROUND Among the many risk factors for the development of atopic eczema (AE), the influence of air pollution has recently been discussed more often. A systematic review about this topic however is lacking. AIMS Which effects of outdoor air pollution (particles, nitric oxides, sulfur dioxide, ozone or general traffic exhaust emissions) on AE can be demonstrated in a systematic analysis of available environmental epidemiologic studies? METHODS All environmental epidemiologic studies on AE and air pollution found in the literature database PubMed were identified. The most important key figures of these studies were tabulated, the quality of evidence was graded and the studies described. RESULTS A total of 57 studies were identified. Only one of the 15 cross-sectional studies with a large-scale exposure assessment found a significant association between AE and air pollution. In contrast 23 of 30 studies with small-scale exposure assessment found a significant association between AE and traffic related emissions-especially from trucks. Of the 30 studies, 14 were cohort studies (1 adult, 13 birth cohorts). The sole adult cohort found an association with intrinsic AE. In the East Asian cohorts (all published since 2015), an association between maternal exposure to traffic-related pollution and incidence of AE in the offspring was found. This was less clear in cohorts from Europe/US or simply not investigated. In 5/5 panel studies (all from South Korea), symptom severity of AE was found to be significantly and positively related to outdoor air pollution. CONCLUSIONS In a systematic analysis of environmental epidemiologic studies about air pollution and AE rather good evidence was found that, based on small-scale exposure measurements, especially truck traffic emissions increased AE prevalence, while large-scale exposure to larger particles (PM10) or SO2 was without effect. Considering pathophysiologic aspects traffic exhaust emissions seem to affect both skin barrier function and activation of immune responses.
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A systematic literature review and critical appraisal of epidemiological studies on outdoor air pollution and tuberculosis outcomes.
Popovic, I, Soares Magalhaes, RJ, Ge, E, Marks, GB, Dong, GH, Wei, X, Knibbs, LD
Environmental research. 2019;:33-45
Abstract
Ambient air pollution is the leading environmental risk factor for disease globally. Air pollutants can increase the risk of some respiratory infections, but their effects on tuberculosis (TB) are unclear. In this systematic literature review, we aimed to assess epidemiological studies on the association between outdoor air pollutants and TB incidence, hospital admissions and death (collectively referred to here as 'TB outcomes'). We sought to consolidate available evidence on this topic and propose recommendations for future studies. Following PRISMA guidelines, we searched PubMed, Web of Science, Google Scholar, and Scopus with no restrictions imposed on year of publication. A total of 11 epidemiological studies, performed in Asia, Europe and North America, met our inclusion criteria (combined sample size: 215,337 people). We extracted key study characteristics from each eligible publication, including design, exposure assessment, analytical approaches and effect estimates. The studies were assessed for overall quality and risk of bias using standard criteria. The pollutant most frequently associated with statistically significant effects on TB outcomes was fine particulate matter ( < 2.5 µm; PM2.5); 6/11 studies assessed PM2.5, of which 4/6 demonstrated a significant association). There was some evidence of significant associations between PM10 ( < 10 µm), nitrogen dioxide (NO2) and sulfur dioxide (SO2) and TB outcomes, but these associations were inconsistent. The existing epidemiological evidence is limited and shows mixed results. However, it is plausible that exposure to air pollutants, particularly PM2.5, may suppress important immune defence mechanisms, increasing an individual's susceptibility to development of active TB and TB-related mortality. Considering the small number of studies relative to the demonstrably large global health burdens of air pollution and TB, further research is required to corroborate the findings in the current literature. Based on a critical assessment of existing evidence, we conclude with methodological suggestions for future studies.
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Particulate metal exposures induce plasma metabolome changes in a commuter panel study.
Ladva, CN, Golan, R, Liang, D, Greenwald, R, Walker, DI, Uppal, K, Raysoni, AU, Tran, V, Yu, T, Flanders, WD, et al
PloS one. 2018;(9):e0203468
Abstract
INTRODUCTION Advances in liquid chromatography-mass spectrometry (LC-MS) have enabled high-resolution metabolomics (HRM) to emerge as a sensitive tool for measuring environmental exposures and corresponding biological response. Using measurements collected as part of a large, panel-based study of car commuters, the current analysis examines in-vehicle air pollution concentrations, targeted inflammatory biomarker levels, and metabolomic profiles to trace potential metabolic perturbations associated with on-road traffic exposures. METHODS A 60-person panel of adults participated in a crossover study, where each participant conducted a highway commute and randomized to either a side-street commute or clinic exposure session. In addition to in-vehicle exposure characterizations, participants contributed pre- and post-exposure dried blood spots for 2-hr changes in targeted proinflammatory and vascular injury biomarkers and 10-hr changes in the plasma metabolome. Samples were analyzed on a Thermo QExactive MS system in positive and negative electrospray ionization (ESI) mode. Data were processed and analyzed in R using apLCMS, xMSanalyzer, and limma. Features associated with environmental exposures or biological endpoints were identified with a linear mixed effects model and annotated through human metabolic pathway analysis in mummichog. RESULTS HRM detected 10-hr perturbations in 110 features associated with in-vehicle, particulate metal exposures (Al, Pb, and Fe) which reflect changes in arachidonic acid, leukotriene, and tryptophan metabolism. Two-hour changes in proinflammatory biomarkers hs-CRP, IL-6, IL-8, and IL-1β were also associated with 10-hr changes in the plasma metabolome, suggesting diverse amino acid, leukotriene, and antioxidant metabolism effects. A putatively identified metabolite, 20-OH-LTB4, decreased after in-vehicle exposure to particulate metals, suggesting a subclinical immune response. CONCLUSIONS Acute exposures to traffic-related air pollutants are associated with broad inflammatory response, including several traditional markers of inflammation.
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Risk factors and disease mechanisms in myositis.
Miller, FW, Lamb, JA, Schmidt, J, Nagaraju, K
Nature reviews. Rheumatology. 2018;(5):255-268
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Abstract
Autoimmune diseases develop as a result of chronic inflammation owing to interactions between genes and the environment. However, the mechanisms by which autoimmune diseases evolve remain poorly understood. Newly discovered risk factors and pathogenic processes in the various idiopathic inflammatory myopathy (IIM) phenotypes (known collectively as myositis) have illuminated innovative approaches for understanding these diseases. The HLA 8.1 ancestral haplotype is a key risk factor for major IIM phenotypes in some populations, and several genetic variants associated with other autoimmune diseases have been identified as IIM risk factors. Environmental risk factors are less well studied than genetic factors but might include viruses, bacteria, ultraviolet radiation, smoking, occupational and perinatal exposures and a growing list of drugs (including biologic agents) and dietary supplements. Disease mechanisms vary by phenotype, with evidence of shared innate and adaptive immune and metabolic pathways in some phenotypes but unique pathways in others. The heterogeneity and rarity of the IIMs make advancements in diagnosis and treatment cumbersome. Novel approaches, better-defined phenotypes, and international, multidisciplinary consensus have contributed to progress, and it is hoped that these methods will eventually enable therapeutic intervention before the onset or major progression of disease. In the future, preemptive strategies for IIM management might be possible.
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Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis.
Olsson, T, Barcellos, LF, Alfredsson, L
Nature reviews. Neurology. 2017;(1):25-36
Abstract
Genetic predisposition to multiple sclerosis (MS) only explains a fraction of the disease risk; lifestyle and environmental factors are key contributors to the risk of MS. Importantly, these nongenetic factors can influence pathogenetic pathways, and some of them can be modified. Besides established MS-associated risk factors - high latitude, female sex, smoking, low vitamin D levels caused by insufficient sun exposure and/or dietary intake, and Epstein-Barr virus (EBV) infection - strong evidence now supports obesity during adolescence as a factor increasing MS risk. Organic solvents and shift work have also been reported to confer increased risk of the disease, whereas factors such as use of nicotine or alcohol, cytomegalovirus infection and a high coffee consumption are associated with a reduced risk. Certain factors - smoking, EBV infection and obesity - interact with HLA risk genes, pointing at a pathogenetic pathway involving adaptive immunity. All of the described risk factors for MS can influence adaptive and/or innate immunity, which is thought to be the main pathway modulated by MS risk alleles. Unlike genetic risk factors, many environmental and lifestyle factors can be modified, with potential for prevention, particularly for people at the greatest risk, such as relatives of individuals with MS. Here, we review recent data on environmental and lifestyle factors, with a focus on gene-environment interactions.