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Exposure to arsenic at different life-stages and DNA methylation meta-analysis in buccal cells and leukocytes.
Bozack, AK, Boileau, P, Wei, L, Hubbard, AE, Sillé, FCM, Ferreccio, C, Acevedo, J, Hou, L, Ilievski, V, Steinmaus, CM, et al
Environmental health : a global access science source. 2021;(1):79
Abstract
BACKGROUND Arsenic (As) exposure through drinking water is a global public health concern. Epigenetic dysregulation including changes in DNA methylation (DNAm), may be involved in arsenic toxicity. Epigenome-wide association studies (EWAS) of arsenic exposure have been restricted to single populations and comparison across EWAS has been limited by methodological differences. Leveraging data from epidemiological studies conducted in Chile and Bangladesh, we use a harmonized data processing and analysis pipeline and meta-analysis to combine results from four EWAS. METHODS DNAm was measured among adults in Chile with and without prenatal and early-life As exposure in PBMCs and buccal cells (N = 40, 850K array) and among men in Bangladesh with high and low As exposure in PBMCs (N = 32, 850K array; N = 48, 450K array). Linear models were used to identify differentially methylated positions (DMPs) and differentially variable positions (DVPs) adjusting for age, smoking, cell type, and sex in the Chile cohort. Probes common across EWAS were meta-analyzed using METAL, and differentially methylated and variable regions (DMRs and DVRs, respectively) were identified using comb-p. KEGG pathway analysis was used to understand biological functions of DMPs and DVPs. RESULTS In a meta-analysis restricted to PBMCs, we identified one DMP and 23 DVPs associated with arsenic exposure; including buccal cells, we identified 3 DMPs and 19 DVPs (FDR < 0.05). Using meta-analyzed results, we identified 11 DMRs and 11 DVRs in PBMC samples, and 16 DMRs and 19 DVRs in PBMC and buccal cell samples. One region annotated to LRRC27 was identified as a DMR and DVR. Arsenic-associated KEGG pathways included lysosome, autophagy, and mTOR signaling, AMPK signaling, and one carbon pool by folate. CONCLUSIONS Using a two-step process of (1) harmonized data processing and analysis and (2) meta-analysis, we leverage four DNAm datasets from two continents of individuals exposed to high levels of As prenatally and during adulthood to identify DMPs and DVPs associated with arsenic exposure. Our approach suggests that standardizing analytical pipelines can aid in identifying biological meaningful signals.
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Micronucleus assay for monitoring the genotoxic effects of arsenic in human populations: A systematic review of the literature and meta-analysis.
Dong, J, Wang, JQ, Qian, Q, Li, GC, Yang, DQ, Jiang, C
Mutation research. Reviews in mutation research. 2019;:1-10
Abstract
The micronucleus (MN) assay has been used to determine the potential genotoxic effects in human populations exposed to arsenic. Some of these studies found an increase in MN frequency among exposed individuals, but others found no increase or inconclusive results. Thus, the main purpose of this current study was to investigate whether MN can be used as a biomarker for the arsenic exposure, as well as whether or not the different cell types that have been used to monitor MN frequency differ in their sensitivity to upon arsenic exposure. A systematic literature review was conducted followed by a meta-analysis. The review identified 25 useful studies with data from 3232 exposed individuals (15 studies assaying lymphocytes, 16 assaying buccal cells, and 9 assaying urothelial cells), with 18 studies measuring drinking water exposure, 5 measuring occupational exposure, one measuring coal burning, and one measuring dietary exposure. The meta-analysis indicated that the overall estimates of Mean Ratio (MR, defined as the mean value of the response in the exposed group divided by the mean value of the response in the reference group) were 2.95 (95% confidence interval (CI): 2.00 to 4.35), 2.36 (95% CI: 1.77 to 3.15), and 2.82 (95% CI: 1.86 to 4.28) for MN assays conducted with lymphocytes, buccal cells, and urothelial cells in the MN assay, respectively. Subgroup analysis showed that when the exposure method was drinking water, the MN frequencies increased significantly in lymphocytes (MR = 3.59, 95% CI: 2.30 to 5.60), in buccal cells (MR = 2.35, 95% CI: 1.76 to 3.15), and in urothelial cells (MR = 3.16, 95% CI: 2.02 to 4.97). However, when the exposure method was the occupational setting or others, the MN detection using the three types of cells did not find significant differences between groups. Subgroup analysis also showed that lymphocyte MN frequencies increased significantly in both routine-culture MN assays (MR = 2.88, 95% CI: 1.15 to 7.24) and cytokinesis-block MN assays (MR = 2.89, 95% CI: 1.84 to 4.55). The performance of the MN assay with different types of cells was also compared, but no significant differences were found. Therefore, our analysis indicates that MN can be used as an effective biomarker for monitoring arsenic-exposed populations, and that MN assays conducted with lymphocytes, buccal cells, and urothelial cells do not differ in their ability to detect the genetic damage from arsenic.
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Concentrations of arsenic and lead in rice (Oryza sativa L.) in Iran: A systematic review and carcinogenic risk assessment.
Fakhri, Y, Bjørklund, G, Bandpei, AM, Chirumbolo, S, Keramati, H, Hosseini Pouya, R, Asadi, A, Amanidaz, N, Sarafraz, M, Sheikhmohammad, A, et al
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2018;:267-277
Abstract
Exposure to heavy metals such as arsenic (As), lead (Pb), and cadmium (Cd) in either the short or the long term can cause cancers in humans. Dietary intake and consumption of rice (Oryza sativa L.) is increasing in Iran, and several studies on the concentration of heavy metals in rice have been carried out in this country in recent years. In this perspective, the main objective of the present study was to investigate, even via a meta-analysis of the existing literature, the presence of As and Pb in rice from many geographical areas in Iran, as well as to estimate the carcinogenic risk of these heavy metals in rice consumers. The results of the present ten years-spanning systematic review indicate that 21 reports, collecting a total of 2088 samples, were performed between 2008 and October 2017. The minimum and maximum concentration of As was observed in the Golestan area (0.01 ± 0.01 mg/kg d.w) and the Gillan region (3 mg/kg d.w); and Pb in the Shahrekord (0.07 ± 0.02 mg/kg d.w) and Mazandaran (35 mg/kg d.w). The meta-analysis of data showed that pooled concentration of As in the rice was 0.04 (95%CI: 0.02-0.06 mg/kg d.w), which resulted lower than the National Standard (NS) limits. However, the pooled concentration of Pb in the rice was 0.38 (95%CI: 0.25-0.5 mg/kg d.w), i.e., higher than NS limits. The heterogeneity was significant between As (I2 = 63%, P value = .003) and Pb (I2 = 96%, P value < .001) studies. The carcinogenic risk assessment showed that minimum and maximum incremental lifetime cancer risk (ILCR) of As was in the 45-54 (4.53 × 10-2) and 15-24 (5.50 × 10-2) year age groups consumers; and Pb, 45-54 (2.442 × 10-3) and 15-24 (2.96 × 10-3), respectively. The overall carcinogenesis risk of As (4.864 × 10-2) was 18.5 times higher than Pb (2.623 × 10-3). All age groups consumers of rice content of As and Pb are at considerable carcinogenesis risk (ILCR > 10-3). Therefore a decreased level of heavy metals in rice cultivation should be encouraged and performed in next planning.
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A dose-response meta-analysis of chronic arsenic exposure and incident cardiovascular disease.
Moon, KA, Oberoi, S, Barchowsky, A, Chen, Y, Guallar, E, Nachman, KE, Rahman, M, Sohel, N, D'Ippoliti, D, Wade, TJ, et al
International journal of epidemiology. 2017;(6):1924-1939
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Abstract
BACKGROUND Consistent evidence at high levels of water arsenic (≥100 µg/l), and growing evidence at low-moderate levels (<100 µg/l), support a link with cardiovascular disease (CVD). The shape of the dose-response across low-moderate and high levels of arsenic in drinking water is uncertain and critical for risk assessment. METHODS We conducted a systematic review of general population epidemiological studies of arsenic and incident clinical CVD (all CVD, coronary heart disease (CHD) and stroke) with three or more exposure categories. In a dose-response meta-analysis, we estimated the pooled association between log-transformed water arsenic (log-linear) and restricted cubic splines of log-transformed water arsenic (non-linear) and the relative risk of each CVD endpoint. RESULTS Twelve studies (pooled N = 408 945) conducted at high (N = 7) and low-moderate (N = 5) levels of water arsenic met inclusion criteria, and 11 studies were included in the meta-analysis. Compared with 10 µg/l, the estimated pooled relative risks [95% confidence interval (CI)] for 20 µg/l water arsenic, based on a log-linear model, were 1.09 (1.03, 1.14) (N = 2) for CVD incidence, 1.07 (1.01, 1.14) (N = 6) for CVD mortality, 1.11 (1.05, 1.17) (N = 4) for CHD incidence, 1.16 (1.07, 1.26) (N = 6) for CHD mortality, 1.08 (0.99, 1.17) (N = 2) for stroke incidence and 1.06 (0.93, 1.20) (N = 6) for stroke mortality. We found no evidence of non-linearity, although these tests had low statistical power. CONCLUSIONS Although limited by the small number of studies, this analysis supports quantitatively including CVD in inorganic arsenic risk assessment, and strengthens the evidence for an association between arsenic and CVD across low-moderate to high levels.
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A Systematic Review and Meta-Regression Analysis of Lung Cancer Risk and Inorganic Arsenic in Drinking Water.
Lamm, SH, Ferdosi, H, Dissen, EK, Li, J, Ahn, J
International journal of environmental research and public health. 2015;(12):15498-515
Abstract
High levels (> 200 µg/L) of inorganic arsenic in drinking water are known to be a cause of human lung cancer, but the evidence at lower levels is uncertain. We have sought the epidemiological studies that have examined the dose-response relationship between arsenic levels in drinking water and the risk of lung cancer over a range that includes both high and low levels of arsenic. Regression analysis, based on six studies identified from an electronic search, examined the relationship between the log of the relative risk and the log of the arsenic exposure over a range of 1-1000 µg/L. The best-fitting continuous meta-regression model was sought and found to be a no-constant linear-quadratic analysis where both the risk and the exposure had been logarithmically transformed. This yielded both a statistically significant positive coefficient for the quadratic term and a statistically significant negative coefficient for the linear term. Sub-analyses by study design yielded results that were similar for both ecological studies and non-ecological studies. Statistically significant X-intercepts consistently found no increased level of risk at approximately 100-150 µg/L arsenic.
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Arsenic and type 2 diabetes: commentary on association of inorganic arsenic exposure with type 2 diabetes mellitus: a meta-analysis by Wang et al.
Becker, A, Axelrad, D
Journal of epidemiology and community health. 2014;(5):393-5