RESUMO
The developmental period in utero is a critical window for environmental exposure. Epigenetic fetal programming via DNA methylation is a pathway through which metal exposure influences the risk of developing diseases later in life. Genetic damage repair can be modified by alterations in DNA methylation, which, in turn, may modulate gene expression due to metal exposure. We investigated the impact of prenatal metal exposure on global and gene-specific DNA methylation and mRNA expression in 181 umbilical cord blood samples from newborns in Mexico City. Global (LINE1) and promoter methylation of DNA-repair (OGG1 and PARP1) and antioxidant (Nrf2) genes was evaluated by pyrosequencing. Prenatal metal exposure (As, Cu, Hg, Mn, Mo, Pb, Se, and Zn) was determined by ICP-MS analysis of maternal urine samples. Multiple regression analyses revealed that DNA methylation of LINE1, Nrf2, OGG1, and PARP1 was associated with potentially toxic (As, Hg, Mn, Mo, and Pb) and essential (Cu, Se, and Zn) elements, and with their interactions. We also evaluated the association between gene expression (mRNA levels quantified by p-PCR) and DNA methylation. An increase in OGG1 methylation at all sites and at CpG2, CpG3, and CpG4 sites was associated with reduced mRNA levels; likewise, methylation at the CpG5, CpG8, and CpG11 sites of PARP1 was associated with reduced mRNA expression. In contrast, methylation at the PARP1 CpG7 site was positively associated with its mRNA levels. No associations between Nrf2 expression and CpG site methylation were observed. Our data suggest that DNA methylation can be inï¬uenced by prenatal metal exposure, which may contribute to alterations in the expression of repair genes, and therefore, result in a lower capacity for DNA damage repair in newborns.
Assuntos
Antioxidantes/metabolismo , Metilação de DNA/efeitos dos fármacos , Reparo do DNA/genética , Metais Pesados/farmacologia , População Urbana , Adolescente , Adulto , Dano ao DNA , DNA Glicosilases/genética , Feminino , Humanos , Recém-Nascido , Metais Pesados/administração & dosagem , México , Fator 2 Relacionado a NF-E2/genética , Poli(ADP-Ribose) Polimerase-1/genética , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , Adulto JovemRESUMO
OBJECTIVE: To evaluate the independent and joint effects of dietary folate, vitamin B(12) consumption and methylenetetrahydrofolate reductase (MTHFR) polymorphisms (677C>T and 1298A>C) on the circulating folate and homocysteine (Hcy) levels among Mexican women of reproductive age. DESIGN: A cross-sectional, population-based study. SUBJECTS: The first 130 healthy non-pregnant women (aged 16-34 years) who agreed to participate in a reproductive cohort in Morelos, Mexico. MAIN OUTCOME MEASUREMENTS: Dietary intakes of vitamin B(12) and folate were estimated using a semiquantitative food frequency questionnaire. MTHFR 677C>T and 1298A>C polymorphisms were ascertained using the PCR-based method. Serum levels of Hcy and folate were determined using high-performance liquid chromatography and radioimmunoassay, respectively. RESULTS: Genotype frequencies for the MTHFR 677C>T polymorphism were 21.5% (CC), 52.3% (CT) and 26.2% (TT) among Mexican women. Of the population, 22% had the MTHFR 1298AC genotype, while no individual carried the 1298CC genotype. We observed an increased level of Hcy among carriers of the 677TT genotype, compared to carriers of the 677CC genotype. The highest level of Hcy was observed among MTHFR 677TT carriers with low B(12) intake (<2.0 microg/day), which resulted with a significant interaction (P=0.01). CONCLUSION: Vitamin B(12) is an important determinant of Hcy levels in Mexico. Supplementation of folic acid with vitamin B(12) may be preferable when the MTHFR 677T variant allele is prevalent.
Assuntos
Ácido Fólico/administração & dosagem , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Vitamina B 12/administração & dosagem , Adolescente , Adulto , Alelos , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Estudos Transversais , Feminino , Frequência do Gene , Genótipo , Humanos , México , Reação em Cadeia da Polimerase , Radioimunoensaio , Inquéritos e QuestionáriosRESUMO
Information on the association between exposure to beta-hexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB) or polychlorinated biphenyls (PCBs) and the incidence of breast cancer is inconclusive. However, exposure to such compounds is a public health concern in Mexico and is subject to recent regulation. Serum levels of beta-HCH, HCB and PCBs were analysed in 95 histologically confirmed breast cancer cases and 95 hospital controls, 20-79 years of age, from Mexico City, enrolled between March 1994 and April 1996. After adjusting for established risk factors, there was no evidence of a relationship between beta-HCH, HCB and PCBs and breast cancer risk (OR for beta-HCH tertile 3 versus tertile 1: 1.05 95% CI 0.46-2.40; OR for HCB tertile 3 versus tertile 1: 0.46 95% CI 0.20-1.07; OR for PCBs 1.31 95% CI 0.33-5.21 for the high category of exposure). This study lends no support to the case for a role for beta-HCH, HCB or PCBs in breast cancer aetiology.
Assuntos
Neoplasias da Mama/sangue , Exposição Ambiental , Hexaclorobenzeno/sangue , Hexaclorocicloexano/sangue , Bifenilos Policlorados/sangue , Adulto , Idoso , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Razão de Chances , RiscoRESUMO
OBJECTIVE: To evaluate the modes of detection of breast malignancies in Mexico City and to estimate the number of patients diagnosed in advanced stages. MATERIAL AND METHODS: This cross-sectional study was conducted between 1994 and 1996, among 256 women with a histological diagnosis of breast cancer, at three tertiary level public hospitals in Mexico City. Personal interviews were conducted to collect data on reproductive characteristics, clinical history, and breast cancer modes of detection. Data analysis consisted of percentages, odds ratios, and 95% confidence intervals. RESULTS: Ninety percent of women sought medical care after identifying a breast lump by themselves. Only 10% of patients had a stage-I tumor; all 27 cases first identified by a physician were in stage II-B and higher. CONCLUSIONS: An increasing trend of breast cancer mortality in Mexico City will persist, unless a greater proportion of tumors in situ is detected; this would require enhancing breast cancer screening programs and conducting an intense educational intervention among women at risk.
Assuntos
Neoplasias da Mama/epidemiologia , Programas de Rastreamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Estudos Transversais , Feminino , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
For almost 50 years, millions of Mexicans have been directly and/or indirectly exposed to (1,1,1-trichloro-2,2-bis[p-chlorophenyl]ethane) (p,p'DDT). The potential related health outcomes of this exposure are of international concern. The objective of the study was to determine the effect of breast-feeding on serum levels of 1,1-dichloro-2; 2'-bis(p-chlorophenyl)ethylene (p,p'DDE) and p,p'DDT in women of childbearing age who were residents of the state of Morelos, Mexico. In March 1999, we examined a sample of 24 women, ages 21 to 36 years, who came with their children to the outpatient facility of a county Health Center in the state of Morelos. The geometric mean for p,p'DDE was 21.8 ng/ml+/-2.58 (GSD) and 2.9 ng/ml+/-2.84 for p,p'DDT. For each month of breast-feeding we observed similar significant decreases for both p,p'DDE (beta=-0.0403 per log concentration unit, P=0.001) and p,p'DDT (beta=-0.0309, P=0.03) serum levels, adjusted by mothers' age and number of children. The adjusted half-life estimate for p,p'DDE serum levels was 17 months. It was concluded that breast-feeding leads to rapid removal of p,p'DDT from the body (<2 year half-life) compared to nonlactational elimination rates (<5 year half-life). In this population, serum p,p'DDE levels were similar to those found 20 years ago in the United States.
Assuntos
Aleitamento Materno , DDT/sangue , Diclorodifenil Dicloroetileno/sangue , Inseticidas/sangue , Lactação/metabolismo , Adulto , Exposição Ambiental , Feminino , Humanos , Cinética , Lactação/sangue , México , Leite Humano/química , Paridade , Projetos PilotoRESUMO
A pilot study was conducted in Morelos, Mexico in March 1999 to assess the body burden of lead in 24 Mexican women of childbearing age. Lead levels were measured in whole blood and at three bone sites: two primarily trabecular (calcaneus and patella) and one primarily cortical (tibia). Demographic and reproductive characteristics of the women and potential sources of lead exposure were gathered by a direct interview. An inverse relationship was noted between months of lactation and age-adjusted calcaneus lead level (P = 0.001). No association was observed between age-adjusted patella or tibia lead level and months of lactation (P = 0.15). Blood lead levels were positively associated with the use of lead-glazed ceramics (P = 0.01). Bone and blood lead levels were observed to be 77% higher in these rural Mexican women than in urban New York City women. This pilot study provides further limited evidence for the hypothesis that lead mobilization occurs during lactation.
Assuntos
Lactação/metabolismo , Chumbo/metabolismo , Adulto , Análise de Variância , Carga Corporal (Radioterapia) , Osso e Ossos/química , Estudos Transversais , Feminino , Humanos , México , Projetos Piloto , Análise de Regressão , População Rural , Inquéritos e Questionários , Estados UnidosRESUMO
We analyzed the intake of selected foods that contain phytoestrogens in relation to breast cancer (BC) risk using data from a hospital-based case-control study performed in Mexico City from 1994 to 1995. A total of 198 women with BC, aged 21-79 years, were individually age matched to an identical number of women with no breast disease. By a direct interview, information on socioeconomic characteristics and diet was obtained. A semiquantitative questionnaire was used to estimate the frequency of consumption of 95 foods. The effect of selected foods that contain phytoestrogens on BC risk was estimated using logistic regression models. The adjusted odds ratio for the consumption of more than one slice of onion per day and BC was 0.27 (95% confidence interval = 0.16-0.47), with a statistically significant trend (p < 0.001). This protective effect remained after adjustment for known risk factors of BC. Among premenopausal women, there was also a protective and significant effect due to the intake of lettuce and spinach and nonsignificant protective effects for the consumption of apples and herbal tea. Additional studies aimed at evaluating the potential protective effect of particular phytoestrogens on BC risk are needed.
Assuntos
Neoplasias da Mama/epidemiologia , Dieta , Estrogênios não Esteroides/administração & dosagem , Isoflavonas , Plantas Comestíveis , Adulto , Idoso , Anticarcinógenos/administração & dosagem , Anticarcinógenos/análise , Neoplasias da Mama/prevenção & controle , Estudos de Casos e Controles , Registros de Dieta , Estrogênios não Esteroides/análise , Feminino , Análise de Alimentos , Humanos , Entrevistas como Assunto , Modelos Logísticos , México/epidemiologia , Pessoa de Meia-Idade , Fitoestrógenos , Preparações de Plantas , Plantas Comestíveis/química , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
The objective of this study was to determine the risk of preterm birth in relation to umbilical cord blood lead levels (UCL) among primiparous and multiparous women. A case-cohort study was performed in Mexico City during 1995. A total of 459 full-term births was compared with 161 preterm births (before 37 gestational weeks). Mothers were interviewed before the delivery about their reproductive histories and other related factors of preterm birth. Lead was determined by atomic absorption spectrophotometry. Lead levels were higher in primiparous women who had a preterm birth than in primiparous women with a full-term birth (9.77+/-2.0 microgram/dl vs 8.24+/-2.15 microgram/dl); this difference was marginally significant. After adjusting for other known preterm birth risk factors, the frequency of preterm birth was almost three times higher among women who had UCL levels greater or equal to 5.1 microgram/dl compared to those who had UCL levels lower than 5.1 microgram/dl. This difference was not observed among multiparous women. Our results suggest that intrauterine lead exposure may be associated with preterm birth in first deliveries but not in subsequent ones.
Assuntos
Chumbo/efeitos adversos , Troca Materno-Fetal , Trabalho de Parto Prematuro/etiologia , Adolescente , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Sangue Fetal/química , Humanos , Exposição Materna , México/epidemiologia , Pessoa de Meia-Idade , Paridade , Gravidez , Medição de RiscoRESUMO
To document the levels and the determinants of dichloro-dyphenyl-trichloroethane (DDT) metabolites in maternal milk, we conducted a cohort study of 50 adult females who lived in Mexico City. We measured social and dietary characteristics via interview. Levels of DDT metabolites were determined by gas-liquid chromatography. The mean values (lipid milk basis) were 0.162 ppm p,p'-DDT; 0.138 ppm o,p'-DDT; and 0.594 ppm 2,2(bis)p-chlorophyenyl-1-1-dichloroethylene (DDE). The main determinants of DDT metabolites were maternal age, lifetime lactation, history of living in an agricultural area, and consumption of salted meat and fish. We estimated that 6.0% of the breast-fed babies had daily intakes of DDT above the level of 0.005 mg/kg d recommended by the World Health Organization/Food and Agriculture Organization of the United Nations (WHO/FAO). Health-outcomes research among children is needed, and investigators should design or adjust current surveillance programs.