RESUMO
Epidemiological studies on associations between breast cancer (BC) and organochlorine pesticides (OCP) are inconclusive. The majority of studies have evaluated the effect of single compounds without considering multiple OCP exposures and immunophenotypes of BC. We aimed to evaluate the association between BC immunophenotypes and serum OCP mixtures, and identify the main contributors within mixtures. We included 767 histopathologically confirmed incident BC cases and 908 controls from a population-based case-control study conducted from 2007 to 2011 in Northern Mexico. We obtained direct information about sociodemographic, lifestyle and reproductive characteristics. We collected data from clinical records about hormonal receptors (HR) and epidermal growth factor receptor 2 (HER2) expressions. Immunophenotypes were determined as HR+/HER2-, HER2+ or HR-/HER2-. We quantified OCP and metabolites by gas chromatography using an electron capture micro detector. We used Weighted Quantile Sum regression to assess the association of BC and exposure to multiple OCP, and their contribution within the mixture. We found a positive adjusted association between BC and an OCP mixture (OR: 3.48, 95%CI: 2.58, 4.69), whose primary contribution arose from the isomers of hexachlorocyclohexane and endosulfan, as well as endosulfan sulfate. We also identified a mixture negatively associated (OR: 0.13, 95%CI: 0.08, 0.20), characterized by p,p'-DDT and chlordane metabolites. All these associations remained regardless BC immunophenotypes. This is the first epidemiological report that identified serum OCP mixtures associated with BC immunophenotypes. Due to OCP ubiquity, biomagnification, and continuous exposure, they constitute a global problem of persistent exposure that might be related to BC risk.
Assuntos
Neoplasias da Mama , Hidrocarbonetos Clorados , Praguicidas , Humanos , Hidrocarbonetos Clorados/sangue , Feminino , Praguicidas/sangue , México , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto , Exposição Ambiental/estatística & dados numéricos , Imunofenotipagem , Poluentes Ambientais/sangue , Idoso , DDT/sangueRESUMO
Objective: The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case-control cohort. Methods: We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4'-DDT and 4,4'-DDE) were measured in the serum by liquid or gas chromatography-mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants' levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods. Results: The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10-3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41-0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants' mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180. Conclusion: Our study suggests, for the first time in a case-control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants' mixture, likely due to a potential reverse causality.
Assuntos
Ácidos Alcanossulfônicos , Disruptores Endócrinos , Fluorocarbonos , Poluentes Orgânicos Persistentes , Bifenilos Policlorados , Neoplasias da Glândula Tireoide , Humanos , Estudos de Casos e Controles , Fluorocarbonos/sangue , Fluorocarbonos/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Disruptores Endócrinos/sangue , Disruptores Endócrinos/efeitos adversos , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/induzido quimicamente , Neoplasias da Glândula Tireoide/genética , Bifenilos Policlorados/sangue , Bifenilos Policlorados/efeitos adversos , Ácidos Alcanossulfônicos/sangue , Adulto , Poluentes Orgânicos Persistentes/efeitos adversos , Poluentes Orgânicos Persistentes/sangue , Idoso , Diclorodifenil Dicloroetileno/sangue , Ácidos Decanoicos/sangue , Ácidos Decanoicos/efeitos adversos , DDT/sangue , DDT/efeitos adversos , Itália/epidemiologia , Caprilatos/sangue , Caprilatos/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/genética , Ácidos Graxos/sangue , Ácidos Sulfônicos/sangue , Mutação , Exposição Ambiental/efeitos adversosRESUMO
The blood levels of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) have been thoroughly investigated in Greek children from the Rhea birth cohort study. This investigation aimed to assess exposure levels, explore their possible relationship with children's age and sex, and indicate potential sources of exposure. Exposure patterns and common sources of PCBs and OCPs were analyzed using bivariate and multivariate statistics. A total of 947 blood samples from study participants were analyzed for OCP and PCB exposure, with 375 samples collected at 4 years old, 239 at 6.5 years old, and 333 at 11 years old. Elevated levels of DDE were observed in 6.5-year-old children compared to corresponding levels in other European countries. Higher levels of DDE were found in 4-year-old children, with the lowest concentrations in the 11-year-old group. The DDT/DDE ratio was consistently less than 1 among all the examined subjects. These results indicate exposure to DDT and DDE both in utero and through breastfeeding and dietary intake. For the entire cohort population, the highest concentration was determined for PCB 28, followed by PCBs 138, 153, and 180. The sum of the six indicator PCBs implied low exposure levels for the majority of the cohort population. Spearman correlations revealed strong associations between PCBs and OCPs, while principal component analysis identified two different groupings of exposure. DDE exhibited a correlation with a series of PCBs (153, 156, 163, 180), indicating a combined OCP-PCB source, and an anticorrelation with others (52, 28, 101), implying a separate and competing source.
Assuntos
DDT , Diclorodifenil Dicloroetileno , Exposição Ambiental , Poluentes Ambientais , Hidrocarbonetos Clorados , Praguicidas , Bifenilos Policlorados , Humanos , Bifenilos Policlorados/sangue , Criança , Feminino , Grécia , Hidrocarbonetos Clorados/sangue , Masculino , Pré-Escolar , Praguicidas/sangue , DDT/sangue , Diclorodifenil Dicloroetileno/sangue , Poluentes Ambientais/sangue , Exposição Ambiental/estatística & dados numéricos , Exposição Ambiental/análise , Coorte de Nascimento , Estudos de Coortes , Dieta/estatística & dados numéricosRESUMO
Breast cancer (BC) is becoming one of the most prevalent non-infectious disease in low and middle income countries. The steady rise of BC incidence may be related to the different risk factors. Among many, rampant presence of environmental pollutants might be one of the risk factors. Therefore, the aim of this study is to investigate exposure to organochlorine pesticides as a risk factor to breast cancer. A case-control study design was employed among breast cancer patients and non-breast cancer individuals (controls). Blood samples were collected from 100 study participants (50 cases and 50 controls) followed by serum separation, extraction and cleanup using standard analytical procdures. The findings revealed that ten organochlorine pesticides were detected in the serum of the study participants. From the detected organochlorine pesticides, heptachlor was observed at higher concentration for breast cancer patients (6.90±4.37 µg/L) and controls (9.15±3.84 µg/L). Mean serum level of p,p'-DDE, p,p'-DDT, heptachlor, gamma-chlordane, endosulfan, and dibutyl-chlorendate were significantly higher in the serum of breast cancer patients than the controls. From the studied pesticides, p,p'-DDT and gamma-chlordane are significant predictors for BC, while, others are equivocal. A unit increment of the concentration of p,p'-DDT (AOR; 2.03, 95% CI: 1.041-3.969) increased the odds of developing breast cancer by two, while for gamma-chlordane (AOR;3.12, 95% CI; 1.186-8.203) by three. Our study results suggesting that, organochlorines are a risk factors for breast cancer in Ethiopia. Decreasing exposure to such organochlorines might have a significant public health relevance in reducing non-communicable chronic illnesses. Besides, continues monitoring of persistent organic pollutants using body biomarkers is important for disease prevention and device mitigation measures.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/epidemiologia , Hidrocarbonetos Clorados/sangue , Praguicidas/sangue , Adulto , Neoplasias da Mama/sangue , Neoplasias da Mama/induzido quimicamente , Estudos de Casos e Controles , Clordano/efeitos adversos , Clordano/sangue , DDT/efeitos adversos , DDT/sangue , Diclorodifenil Dicloroetileno/efeitos adversos , Diclorodifenil Dicloroetileno/sangue , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/sangue , Etiópia/epidemiologia , Feminino , Heptacloro/efeitos adversos , Heptacloro/sangue , Humanos , Hidrocarbonetos Clorados/efeitos adversos , Pessoa de Meia-Idade , Praguicidas/efeitos adversosRESUMO
BACKGROUND: Serum DDTs during or just after pregnancy were associated with breast cancer in mothers (F0), and with breast cancer, mammographic density, and obesity in adult daughters (F1) in the Child Health and Development Studies multi-generational cohort in prior publications. Here, we investigate F0 perinatal serum DDT associations with granddaughters'(F2) measured obesity at a median age of 26 and self-reported age at menarche. METHODS: F2 weight, height and waist circumference were measured by trained examiners. o,p'-DDT, p,p'-DDT and p,p'-DDE were measured in archived F0 perinatal serum. F0 DDT associations with F2 outcomes, accounting for F1 characteristics, were estimated in log-linear models adjusted for F0 and F1 body mass index (BMI), race, and menarche timing (N = 258 triads for obesity; N = 235 triads for early menarche). Interactions between F0 BMI and DDTs were estimated. RESULTS: F0 o,p'-DDT was associated with F2 obesity [Odds ratio (OR), 2.6; 95% confidence interval (CI), 1.3-6.7; tertile 3 vs. 1), among normal weight F0 (70%), but not among overweight and obese F0 (P interaction = 0.03), independent of other DDTs. F0 o,p'-DDT was also associated with F2 early menarche (OR, 2.1; 95% CI, 1.1-3.9, tertile 3 vs. 1) and this association was not modified by F0 BMI. CONCLUSIONS: Ancestral exposure to environmental chemicals, banned decades ago, may influence the development of earlier menarche and obesity, which are established risk factors for breast cancer and cardiometabolic diseases. IMPACT: Discovery of actionable biomarkers of response to ancestral environmental exposures in young women may provide opportunities for breast cancer prevention.See related commentary by Fenton and Boyles, p. 1459.
Assuntos
DDT/sangue , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/sangue , Exposição Materna/efeitos adversos , Menarca , Obesidade/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Adulto , Biomarcadores/sangue , DDT/toxicidade , Poluentes Ambientais/toxicidade , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Gravidez , Fatores de RiscoRESUMO
BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs) may affect child neurobehavior; however, exposures to mixtures of POPs have rarely been examined. METHODS: We estimated associations of prenatal serum concentrations of 17 POPs, namely 5 polybrominated diphenyl ethers (PBDEs), 6 polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyltrichloroethane (DDT), and 4 per- and polyfluoroalkyl substances (PFAS), with Wide Range Achievement Test-4 reading composite scores at age 8 years in 161 children from a pregnancy and birth cohort (Health Outcomes and Measures of the Environment [HOME] Study, 2003-present) in Cincinnati, OH. We applied 6 statistical methods: least absolute shrinkage and selection operator (LASSO), elastic net (ENET), Sparse Principal Component Analysis (SPCA), Weighted Quantile Sum (WQS) regression, Bayesian Kernel Machine Regression (BKMR), and Bayesian Additive Regression Trees (BART), to estimate covariate-adjusted associations with individual and their mixtures in multi-pollutant models. RESULTS: Both LASSO and ENET models indicated inverse associations with reading scores for BDE-153 and BDE-28, and positive associations for CB-118, CB-180, perfluoroctanoate (PFOA), and perfluorononanoate (PFNA). The SPCA identified inverse associations for BDE-153 and BDE-100 and positive associations for perfluorooctane sulfonate (PFOS), PFOA, and PFNA, as parts of different principal component scores. The WQS regression showed the highest weights for BDE-100 (0.35) and BDE-28 (0.16) in the inverse association model and for PFNA (0.29) and CB-180 (0.21) in the positive association model. The BKMR model identified BDE-100 and BDE-153 for inverse associations and CB-118, CB-153, CB-180, PFOA, and PFNA for positive associations. The BART method found dose-response functions similar to the BKMR model. No interactions between POPs were identified. CONCLUSIONS: Despite some inconsistency among biomarkers, these analyses revealed inverse associations between prenatal PBDE concentrations and children's reading scores. Positive associations of PCB congeners and PFAS with reading skills were also found.
Assuntos
Exposição Materna , Poluentes Orgânicos Persistentes , Efeitos Tardios da Exposição Pré-Natal , Leitura , Adulto , Criança , DDT/sangue , Diclorodifenil Dicloroetileno/sangue , Feminino , Fluorocarbonos/sangue , Éteres Difenil Halogenados/sangue , Humanos , Poluentes Orgânicos Persistentes/sangue , Bifenilos Policlorados/sangue , Gravidez/sangueRESUMO
We tested the hypothesis that maternal perinatal serum levels of poly and perfluoroalkyl substances (PFASs) predict risk for breast cancer in daughters in a 54-year follow-up of 9300 daughters born 1959-1967 in the Child Health and Development Studies pregnancy cohort. Total cholesterol and PFASs were measured in archived maternal perinatal serum for 102 daughter breast cancer cases diagnosed by age 52, and 310 controls matched on birth year and blood draw trimester. High maternal N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA), a precursor of perfluorooctane sulfonic acid (PFOS), in combination with high maternal total cholesterol predicted a 3.6-fold increased risk of breast cancer (pinteraction<0.05). Conversely, maternal PFOS was associated with decreased daughters' breast cancer risk. Predictions were robust to alternative modeling and independent of other maternal factors. Future generations continue to be exposed to ubiquitous, persistent PFASs. These findings are relevant to breast cancer prevention if confirmed experimentally and where possible, in additional epidemiology studies of internal doses of PFASs and other chemical mixtures especially during vulnerable windows in early life.
Assuntos
Neoplasias da Mama/epidemiologia , Poluentes Ambientais/sangue , Ácidos Graxos/sangue , Fluorocarbonos/sangue , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Ácidos Sulfônicos/sangue , Adulto , California/epidemiologia , Estudos de Casos e Controles , Colesterol/sangue , Estudos de Coortes , DDT/sangue , Diclorodifenil Dicloroetileno/sangue , Feminino , Humanos , Troca Materno-Fetal , Gravidez , Triglicerídeos/sangue , Adulto JovemRESUMO
Studies measuring dichlorodiphenyltrichloroethane (DDT) exposure during key windows of susceptibility including the intrauterine period suggest that DDT exposure is associated with breast cancer risk. We hypothesized that prenatal DDT exposure is associated with DNA methylation. Using prospective data from 316 daughters in the Child Health and Development Study, we examined the association between prenatal exposure to DDTs and DNA methylation in blood collected in midlife (mean age: 49 years). To identify differentially methylated regions (DMRs) associated with markers of DDTs (p,p'-DDT and the primary metabolite of p,p'-DDT, p,p'-DDE, and o,p'-DDT, the primary constituents of technical DDT), we measured methylation in 30 genes important to breast cancer. We observed DDT DMRs in three genes, CCDC85A, CYP1A1 and ZFPM2, each of which has been previously implicated in pubertal development and breast cancer susceptibility. These findings suggest prenatal DDT exposure may have life-long consequence through alteration in genes relevant to breast cancer.
Assuntos
Neoplasias da Mama/epidemiologia , DDT/sangue , Metilação de DNA , Poluentes Ambientais/sangue , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , Neoplasias da Mama/genética , California/epidemiologia , Criança , Desenvolvimento Infantil , Saúde da Criança , Citocromo P-450 CYP1A1/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Troca Materno-Fetal , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , Fatores de Transcrição/genéticaRESUMO
The advancement of high-resolution metabolomics (HRM) and metabolome-wide-association study (MWAS) enables the readout of environmental effects in human specimens. We used HRM to understand DDT-induced alterations of in utero environment and potential health effects. Endogenous metabolites were measured in 397 maternal perinatal serum samples collected during 1959-1967 in the Child Health and Development Studies (CHDS) and in 16 maternal postnatal serum samples of mice treated with or without DDT. MWAS was performed to assess associations between metabolites and p,p'-DDT, o,p'-DDT and p,p'-DDE levels, followed by pathway analysis. Distinct metabolic profiles were found with p,p'-DDT and p,p'-DDE. Amino acids such arginine had a strong association with p,p'-DDT and o,p'-DDT in both women and mice, whereas lipids and acyl-carnitine intermediates were found exclusively associated with p,p'-DDE in CHDS women indicating mitochondrial impairment. It suggests that the role of serine and fatty acid metabolism on the causal disease pathway should be examined.
Assuntos
DDT/sangue , Diclorodifenil Dicloroetileno/sangue , Poluentes Ambientais/sangue , Metaboloma , Adulto , Aminoácidos/metabolismo , Animais , California , Estudos de Coortes , Ácidos Graxos/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos , Exposição Materna , Troca Materno-Fetal , Camundongos Endogâmicos C57BL , Período Pós-Parto , Gravidez , Ureia/metabolismoRESUMO
The aim of the study was to assess temporal trends in health risks related to most common persistent contaminants, including polychlorinated biphenyls (PCBs), dichloro-diphenyl-trichloroethanes (DDTs), lead (Pb), as well as mercury (Hg) among indigenous peoples living in coastal areas of Chukotka in Arctic Russia. This is examined in relation to exposure pathways and a range of social and behavioral factors capable of modifying the exposure to these contaminants, including place of residence, income, traditional subsistence, alcohol consumption, and awareness of risk prevention. The primary exposure pathway for PCBs is shown to be the intake of traditional foods, which explained as much as 90% of the total health risk calculated employing established risk guidelines. Nearly 50% of past DDT-related health risks also appear to have been contributed by contaminated indoor surfaces involving commonly used DDT-containing insecticides. Individuals who practiced traditional activities are shown to have experienced a 4.4-fold higher risk of exposure to PCBs and a 1.3-fold higher risk for DDTs, Pb, and Hg. Low income, high consumption of marine mammal fat, alcohol consumption, and lack of awareness of health risk prevention are attributed to a further 2- to 6-fold increase in the risk of PCBs exposure. Low socioeconomic status enhances the health risks associated with exposure to the persistent contaminants examined.
Assuntos
DDT/sangue , Exposição Ambiental , Poluentes Ambientais/sangue , Inseticidas/sangue , Chumbo/sangue , Mercúrio/sangue , Bifenilos Policlorados/sangue , Adolescente , Adulto , Idoso , Animais , Regiões Árticas , Humanos , Povos Indígenas , Masculino , Pessoa de Meia-Idade , Medição de Risco , Federação Russa , Adulto JovemRESUMO
Organochlorine pesticides (OCPs) are toxic chemicals that persist in human tissue. Short and long term exposure to OCPs have been shown to have adverse effects on human health. This motivates studies into the concentrations of pesticides in humans. However these studies typically emphasise the analysis of the main effects of age group, gender and time of sample collection. The interactions between main effects can distinguish variation in OCP concentration such as the difference in concentrations between genders of the same age group as well as age groups over time. These are less studied but may be equally or more important in understanding effects of OCPs in a population. The aim of this study was to identify interactions relevant to understanding OCP concentrations and utilise them appropriately in models. We propose a two stage analysis comprising of boosted regression trees (BRTs) and hierarchical modelling to study OCP concentrations. BRTs are used to discover influential interactions between age group, gender and time of sampling. Hierarchical models are then employed to test and infer the effect of the interactions on OCP concentrations. Results of our analysis show that the best fitting model of an interaction effect varied between OCPs. The interaction between age group and gender was most influential for hexachlorobenzene (HCB) concentrations. There was strong evidence of an interaction effect between age group and time for ß-hexachlorocyclohexane (ß-HCH) concentrations in >60 year olds as well as an interaction effect between age group and gender for HCB concentrations for adults aged >45 years. This study highlights the need to consider appropriate interaction effects in the analysis of OCP concentrations and provides further insight into the interplay of main effects on OCP concentration trends.
Assuntos
Hidrocarbonetos Clorados/sangue , Praguicidas/sangue , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , DDT/sangue , Diclorodifenil Dicloroetileno/sangue , Monitoramento Ambiental/métodos , Monitoramento Ambiental/estatística & dados numéricos , Poluentes Ambientais/sangue , Feminino , Hexaclorobenzeno/sangue , Hexaclorocicloexano/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores Sexuais , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Previous epidemiological studies, largely conducted in high-income countries and cross-sectional, have suggested a relatively strong association between exposure to dichlorodiphenyldichloroethylene (DDE), a metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), and type 2 diabetes. DDT is widely used in India and the prevalence of type 2 diabetes there is increasing, but the association between these factors has not been explored to date. OBJECTIVE: The objective was to estimate the association of the p,p' isomer of DDE with incident type 2 diabetes in India. METHODS: A nested case-control study was conducted in a representative prospective cohort of adults from two cities in India. Participants were enrolled in 2010-11 (nâ¯=â¯12,271) and followed for annual assessment of chronic diseases including type 2 diabetes. Baseline plasma samples from incident cases of diabetes (nâ¯=â¯193) and sex-city-matched controls (nâ¯=â¯323) were selected for analysis of p,p-DDE. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. RESULTS: At baseline, cases had higher p,p-DDE concentrations: geometric mean (95% CI) 330 (273-399) ng/g lipid compared to 223 (189-262) ng/g lipid among controls. Delhi participants had higher p,p-DDE concentrations: 579 (521-643) ng/g lipid compared to 122 (102-145) ng/g lipid in Chennai. In unadjusted models, being in the highest versus lowest quartile of p,p-DDE was associated with a more than doubling of the odds of diabetes: unadjusted OR (95% CI), 2.30 (1.19, 4.43). However, this effect was no longer significant after adjustment for age: adjusted (95% CI), 0.97 (0.46, 2.06). DISCUSSION: Results suggest that levels of p,p'-DDE in Delhi are exceptionally high, but we did not observe a significant association between p,p-DDE and incident type 2 diabetes. As this is the first study to evaluate this association in India, more studies are needed to inform our understanding of the association in this context, including potential routes of exposure.
Assuntos
DDT/toxicidade , Diabetes Mellitus Tipo 2/induzido quimicamente , Diclorodifenil Dicloroetileno/sangue , Praguicidas/toxicidade , Adulto , Estudos de Casos e Controles , Estudos de Coortes , DDT/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diclorodifenil Dicloroetileno/efeitos adversos , Feminino , Humanos , Incidência , Índia/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Praguicidas/sangue , Estudos ProspectivosRESUMO
Breast cancer is a multifactorial disease and its etiology is linked to multiple risk factors. There are shreds of controversial evidence that exposure to organochlorine pesticides (OCPs) are important in the etiology of breast cancer. The present study aimed to determine the circulating levels of OCPs in patients with breast tumors in Southeastern of Iran. This case-control study included 27 patients with malignant breast tumors (MBT), 31 patients with benign breast tumors (BBT), and 27 healthy women as a control group. Serum OCPs levels, including α-hexachlorocyclohexane (α-HCH), ß-HCH, γ-HCH, 2,4-dichlorodiphenyltrichloroethane (2,4-DDT), 4,4-DDT, 2,4-dichlorodiphenyldichloroethylene (2,4-DDE), and 4,4-DDE, were measured using gas chromatography. Our data revealed significantly higher concentrations of 2,4-DDT in MBT and BBT groups compared with control ones (P < 0.001 for both comparisons). Patients with breast cancer suffered significantly higher accumulation levels of 4,4-DDE compared with control subjects (P = 0.04). Significant correlations were found among organochlorine compounds with each other in both patients' groups. There was a significant positive correlation between body mass index and serum levels of 2,4-DDT in BBT group (r = 0.407, P = 0.02). The present findings suggest that the serum levels of 4,4-DDE and 2,4-DDT are associated with an increase in the risk of breast cancer in Southeastern women of Iran.
Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/induzido quimicamente , Hidrocarbonetos Clorados/sangue , Praguicidas/sangue , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Cromatografia Gasosa , DDT/sangue , DDT/toxicidade , Diclorodifenil Dicloroetileno/sangue , Diclorodifenil Dicloroetileno/toxicidade , Feminino , Hexaclorocicloexano/sangue , Hexaclorocicloexano/toxicidade , Humanos , Hidrocarbonetos Clorados/toxicidade , Irã (Geográfico) , Pessoa de Meia-Idade , Praguicidas/toxicidade , Fatores de RiscoRESUMO
Indoor Residual Spraying (IRS), the application of insecticides on the inside walls of dwellings, is used by 84 countries for malaria control. Although effective in preventing malaria, this practice results in elevated insecticide exposure to >100 million people, most of whom are Africans. Pyrethroid insecticides and dichlorodiphenyl trichloroethane (DDT) are currently used for IRS. Animal and in vitro studies suggest that pyrethroids and DDT interfere with thyroid hormone homeostasis but human studies are inconsistent and no prior study has investigated this question in a population residing in an area where IRS is conducted. Our objective was thus to evaluate whether prenatal exposure to pyrethroids, DDT or DDT's breakdown product dichlorodiphenyl dichloroethylene (DDE) is associated with altered thyroid hormone levels among neonates from Limpopo, South Africa, where pyrethroids and DDT are used annually to control malaria. We measured serum DDT/E and urinary pyrethroid metabolite concentrations in maternal peripartum samples from 717 women participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), a birth cohort study conducted in Limpopo's Vhembe district. We measured total thyroxine (T4) and thyroid-stimulating hormone (TSH) in dried blood spots collected via heel stick. We found that all pyrethroid metabolites were positively associated with TSH; trans-DCCA and 3-PBA showed the strongest associations with a 12.3% (95%CIâ¯=â¯3.0, 22.3) and 14.0% (95%CIâ¯=â¯0.5, 30.2) change for each 10-fold increase in biomarker concentration, respectively. These associations were substantially stronger among children from households below the South African food poverty line. DDT and DDE were associated with lower total T4 among boys only (ßâ¯=â¯-0.27⯵g/dL per 10-fold increase; 95%CIâ¯=â¯-0.47, -0.04). Results suggest that prenatal exposure to DDT, DDE and pyrethroid insecticides is associated with changes in neonatal thyroid hormones consistent with hypothyroidism/hypothyroxinemia and that sex and poverty modify associations. Further research is needed to confirm these findings and examine whether they have implications for child development.
Assuntos
DDT/toxicidade , Inseticidas/toxicidade , Exposição Materna , Pobreza , Piretrinas/toxicidade , Hormônios Tireóideos/sangue , Tireotropina/sangue , Adulto , População Negra , Criança , Estudos de Coortes , DDT/sangue , Diclorodifenil Dicloroetileno/sangue , Diclorodifenil Dicloroetileno/toxicidade , Exposição Ambiental , Feminino , Humanos , Recém-Nascido , Inseticidas/sangue , Malária/prevenção & controle , Masculino , Período Periparto , Gravidez , Fatores Sexuais , África do SulRESUMO
Prospective studies indicate that the exposure to organochlorine pesticides (OCPs) during fetal life, infancy, and early childhood may be associated with features of neurodevelopmental disorders in children. However, few studies have investigated the concentrations of serum OCPs in children with categorically diagnosed neurodevelopmental disorders. The aim of this study was to assess the concentrations and detection rates of dichlorodiphenyltrichloroethane (DDT) metabolites, hexachlorocyclohexane (HCH) isomers, cyclodienes, and methoxychlor in serum samples of children with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and specific learning disorder (SLD), all of normal intelligence, compared to typically developing controls (TD). In total, 114 schoolchildren, aged 6-13 years old, were assessed and distributed into four groups: ASD (n = 39), ADHD (n = 21), SLD (n = 32), and TD (n = 18). Each clinical group was compared to the TD group. Concentrations of serum OCPs were determined by gas chromatography and are presented as ng/g lipid. Concentrations of ß-HCH, the sum of HCH isomers, and o,p'-DDD were significantly higher in ASD children: ASD vs. TD (mean ± SD): 10.5 ± 7.7 vs. 6.1 ± 4.0, (p = 0.049); 12.0 ± 10.3 vs. 6.6 ± 4.0, (p = 0.025); 7.4 ± 6.5 vs. 2.8 ± 2.3, (p = 0.0019), respectively. The detection rates of p,p'-DDT, at least one substance from DDTs detected, and the cyclodiene heptachlor epoxide, were significantly lower in the ASD group: ASD vs. TD: 12.8% vs. 38.9%, (p = 0.037); 69.2% vs. 94.4%, (p = 0.044); 10.3% vs. 38.9%, (p = 0.026), respectively. No significant differences between the ADHD or SLD groups and the TD group were observed. We demonstrated higher serum concentrations and lower detection rates of selected OCPs in ASD than TD children. Our results add to potential neurodevelopmental concerns surrounding OCPs and provide evidence of specificity in the relations between HCHs and ASD.
Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/sangue , Transtornos do Neurodesenvolvimento/epidemiologia , Praguicidas/sangue , Adolescente , Transtorno do Espectro Autista/epidemiologia , Criança , China , DDT/análise , DDT/sangue , Exposição Ambiental/estatística & dados numéricos , Monitoramento Ambiental/métodos , Grécia/epidemiologia , Hexaclorocicloexano/sangue , Humanos , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/sangue , Praguicidas/análise , Estudos ProspectivosRESUMO
The aim of the present work was to apply a validated methodology for the detection of organochlorine pesticides in Didelphis virginiana (Virginia opossum) serum samples collected in Yucatan, Mexico. Recent studies performed to investigate the presence of Organochlorines (OCLs) in water, human blood and milk, and animal tissues from Yucatan have shown that the OCLs concentrations are high and can be associated with potential human health risk. Since opossum is considered an important synanthropic species in Yucatan, 40 opossum serum samples were analyzed by gas chromatography with electron capture detector. The most common OCLs found in opossum sera were lindanes, chlordanes, drines, and endosulfan. Heptachlor, heptachlor epoxide, and lindanes were found at the highest concentrations, while dichlorodiphenyl trichloroethane and its metabolites were found at the lowest concentrations in the samples. The good linearity, precision, and accuracy obtained in the evaluated parameters in the extraction and chromatographic methods support its application for the monitoring of OCLs pesticides in populations of opossums and other wild species in Yucatan.
Assuntos
Didelphis/sangue , Monitoramento Ambiental , Hidrocarbonetos Clorados/sangue , Praguicidas/sangue , Animais , Cromatografia Gasosa , DDT/sangue , Endossulfano/sangue , Heptacloro/sangue , Hidrocarbonetos Clorados/química , México , Praguicidas/químicaRESUMO
Although experimental evidence indicates that certain organochlorine insecticides are hepatocarcinogens, epidemiologic evidence for most of these chemicals is very limited. We estimated associations, using prospectively collected sera, between organochlorine insecticide concentrations and cancer registry-identified primary liver cancer in two cohorts, one from the United States and one from Norway. In nested case-control studies, we used sera collected in the 1960s-1980s from 136 cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the population-based Norwegian Janus cohort. We measured concentrations of nine organochlorine insecticides/metabolites and markers of hepatitis B and C in sera. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for tertiles of lipid-corrected organochlorines were calculated for each cohort using conditional logistic regression. Among MHC participants with sera from the 1960s, there was a suggestive exposure-response trend for trans-nonachlor (second and third tertile of analyte ORs = 1.63 and 1.95, respectively; p-trend = 0.08) and a nonsignificantly elevated risk for the highest tertile of oxychlordane (OR = 1.87). Among Janus participants with sera from the 1970s, we observed an apparent trend for p,p'-DDT (second and third tertile ORs = 1.70 and 2.14, respectively; p-trend = 0.15). We observed little consistency in patterns of association between the cohorts. We found limited evidence that exposure to p,p'-DDT and chlordane-related oxychlordane and trans-nonachlor may be associated with increased risk of primary liver cancer. However, the modest strength of these associations and their lack of concordance between cohorts necessitate caution in their interpretation.
Assuntos
Hidrocarbonetos Clorados/sangue , Inseticidas/sangue , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Clordano/efeitos adversos , Clordano/análogos & derivados , Clordano/sangue , DDT/efeitos adversos , DDT/sangue , Feminino , Humanos , Hidrocarbonetos Clorados/efeitos adversos , Inseticidas/efeitos adversos , Neoplasias Hepáticas/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Razão de Chances , Estudos Prospectivos , Sistema de Registros , Medição de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Epidemiologic studies suggest an increased risk of leukemia among individuals occupationally exposed to some organochlorine (OC) compounds. Associations between serum OC pesticide and polychlorinated biphenyl (PCB) levels and risk of acute myeloid leukemia (AML), the most common subtype of acute leukemia in adult populations, have not been evaluated prospectively in the general population. OBJECTIVE: We evaluated the risk of AML in relation to pre-diagnostic serum levels of OC pesticides and PCBs in a case-control study nested within the Janus Serum Bank Cohort. METHODS: Janus is a large population-based cohort containing biologic samples collected beginning in the early 1970s from ~318,000 individuals in Norway. Serum levels of 11 OC pesticides or their metabolites and 34 PCB congeners were measured in 56 AML cases and 288 controls. Conditional logistic regression was conducted to evaluate associations between lipid-adjusted serum OC levels and risk of AML. RESULTS: Higher serum levels of total chlordane/heptachlor metabolites were associated with AML risk (3rd vs. 1st tertile odds ratio (OR)â¯=â¯2.26, 95% confidence interval (CI)â¯=â¯0.91-5.63; ptrendâ¯=â¯0.11). Significant exposure-response associations were observed for levels of heptachlor epoxide (3rd vs. 1st tertile ORâ¯=â¯2.85, 95% CIâ¯=â¯1.05-7.73; ptrendâ¯=â¯0.02) and dieldrin (3rd vs. 1st tertile ORâ¯=â¯2.71, 95% CIâ¯=â¯1.07-6.83; ptrendâ¯=â¯0.03). No significant exposure-response associations with AML risk were observed for total DDT or individual isomers and derivatives. Higher serum levels of p,p'-DDT showed a non-significant increase in risk, but the exposure-response became attenuated when co-adjusting for heptachlor epoxide or dieldrin levels. Serum PCB levels were not significantly associated with AML risk. CONCLUSIONS: Our data suggest that higher serum levels of dieldrin and metabolites derived from chlordane/heptachlor are associated with risk of AML in the general Norwegian population, based on samples collected on average ~17â¯years before diagnosis. Further research in populations with historically high or recent exposure to DDT is warranted to assess the association with AML risk with body burden of specific DDT isomers and derivatives.
Assuntos
Poluentes Ambientais/sangue , Hidrocarbonetos Clorados/sangue , Leucemia Mieloide Aguda/induzido quimicamente , Praguicidas/sangue , Bifenilos Policlorados/sangue , Adulto , Estudos de Casos e Controles , Clordano/sangue , Estudos de Coortes , DDT/sangue , DDT/toxicidade , Poluentes Ambientais/toxicidade , Feminino , Humanos , Hidrocarbonetos Clorados/toxicidade , Leucemia Mieloide Aguda/diagnóstico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Noruega , Razão de Chances , Praguicidas/toxicidade , Bifenilos Policlorados/toxicidade , Medição de Risco , Adulto JovemRESUMO
OBJECTIVES: To examine plasma levels of dichlorodiphenyldichloroethene (DDE) and dichlorodiphenyltrichloroethane (DDT) in association with survival among women with breast cancer who participated in a population-based case-control study. METHODS: Participants included 456 white and 292 black women from the Carolina Breast Cancer Study Phase I who were diagnosed with primary invasive breast cancer from 1993 to 1996, and who had available DDE/DDT and lipid measurements from blood samples obtained on average 4.1â¯months after diagnosis. Using the National Death Index, we identified 392 deaths (210 from breast cancer) over a median follow-up of 20.6â¯years. We used Cox regression to estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and breast cancer-specific 5-year mortality, and 20-year mortality conditional on 5-year survival, for lipid-standardized DDE and DDT levels. Associations stratified by race and estrogen receptor (ER) status were also examined. RESULTS: The highest versus lowest DDE tertile and the highest vs non-detectable DDT quantile were associated with HRs of 1.95 (95% CIâ¯=â¯1.31-2.92) and 1.64 (95% CIâ¯=â¯1.10-2.44), respectively, for 20-year conditional all-cause mortality. DDE levels above versus below the median were associated with a HR of 1.69 (95% CIâ¯=â¯1.06-2.68) for 20-year conditional breast cancer-specific mortality among women overall, and HRs were 2.36 (95% CIâ¯=â¯1.03-5.42) among black women and 1.57 (95% CIâ¯=â¯0.86-2.89) among white women (PInteractionâ¯=â¯0.42), and 3.24 (95% CIâ¯=â¯1.38-7.58) among women with ER- tumors and 1.29 (95% CIâ¯=â¯0.73-2.28) among women with ER+ tumors (PInteractionâ¯=â¯0.03). CONCLUSION: Exposure to DDE/DDT may adversely impact overall and breast cancer-specific survival. DDE exposure may contribute to the racial disparities in breast cancer survival.
Assuntos
Neoplasias da Mama/sangue , DDT/sangue , Diclorodifenil Dicloroetileno/sangue , Praguicidas/sangue , Negro ou Afro-Americano , Neoplasias da Mama/etiologia , Neoplasias da Mama/mortalidade , Sobreviventes de Câncer , Estudos de Casos e Controles , DDT/toxicidade , Diclorodifenil Dicloroetileno/toxicidade , Feminino , Humanos , Pessoa de Meia-Idade , North Carolina , Praguicidas/toxicidade , Modelos de Riscos Proporcionais , Análise de Sobrevida , População BrancaRESUMO
BACKGROUND: In a previous Child Health and Development Studies report, p, p'-DDT was associated with a fivefold increased risk of premenopausal (before age 50 years) breast cancer for women first exposed before puberty. Here we extend our observation to breast cancer diagnosed during early postmenopause (ages 50-54 years) to determine whether age at diagnosis modifies the interaction of DDT with age at exposure. METHODS: We conducted a second prospective, nested case-control study in the Child Health and Development Studies (153 incident breast cancer cases diagnosed at ages 50-54 years and 432 controls matched to cases on birth year). These were analyzed separately and pooled with our previous study (129 breast cancer cases diagnosed at ages 31-49 years and 129 controls matched on birth year). Blood samples were obtained during pregnancy (median age, 26 years), 1-3 days after delivery from 1959 to 1967 in Oakland, California. Serum was assayed for p, p'-DDT, o, p'-DDT, and p, p'-DDE. Odds ratios (ORs) below are given for doubling of serum p, p'-DDT. All statistical tests were two-sided. RESULTS: For early postmenopausal breast cancer, p, p'-DDT was associated with risk for all women (ORDDT 50-54 = 1.99, 95% CI = 1.48 to 2.67). This association was accounted for by women first exposed to DDT after infancy (ORDDT 50-54 for first exposure after infancy = 2.83, 95% CI = 1.96 to 4.10 vs ORDDT 50-54 for first exposure during infancy = 0.56, 95% CI = 0.26 to 1.19; Pinteraction DDT x age at first exposure = .01). In contrast, for premenopausal breast cancer, p, p'-DDT was associated with risk among women first exposed during infancy through puberty, but not after (ORDDT<50 for first exposure during infancy = 3.70, 95% CI = 1.22 to 11.26, Pinteraction DDT x age at first exposure x age at diagnosis = .03). CONCLUSIONS: p, p'-DDT was associated with breast cancer through age 54 years. Risk depended on timing of first exposure and diagnosis age, suggesting susceptibility windows and an induction period beginning in early life. DDT appears to be an endocrine disruptor with responsive breast targets from in utero to menopause.