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1.
Epidemiology ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31577632

RESUMO

BACKGROUND: N-nitroso compounds are hypothesized human bladder carcinogens. We investigated ingestion of N-nitroso compound precursors nitrate and nitrite from drinking water and diet and bladder cancer in the New England Bladder Cancer Study. METHODS: Using historical nitrate measurements for public water supplies and measured and modeled values for private wells, as well as self-reported water intake, we estimated average nitrate concentrations (mg/L NO3-N ) and average daily nitrate intake (mg/day) from 1970 to diagnosis/reference date (987 cases and 1180 controls). We estimated overall and source-specific dietary nitrate and nitrite intakes using a food frequency questionnaire (1037 cases and 1225 controls). We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). We evaluated interactions with factors that may affect N-nitroso compound formation (i.e., red meat, vitamin C, smoking), and water intake. RESULTS: Average drinking water nitrate concentration above the 95 percentile (>2.07 mg/L) compared with the lowest quartile (≤0.21 mg/L) was associated with bladder cancer (OR=1.5, 95% CI: 0.97-2.3; p-trend=0.01); the association was similar for average daily drinking water nitrate intake. We observed positive associations for dietary nitrate and nitrite intakes from processed meat (highest vs. lowest quintile OR for nitrate=1.4, 95% CI: 1.0-2.0; p-trend=0.04; OR for nitrite=1.5, 95% CI: 1.0-2.1; p-trend=0.04, respectively), but not other dietary sources. We observed positive interactions between drinking water nitrate and red meat (p-interaction 0.05) and processed red meat (0.07). CONCLUSIONS: Our results suggest the importance of both drinking water and dietary nitrate sources as risk factors for bladder cancer.

2.
Comput Biol Med ; 114: 103417, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31521894

RESUMO

Examining the effects of exogenous exposures on complex metabolic processes poses the unique challenge of identifying interactions among a large number of metabolites. Recent progress in the quantification of the metabolome through mass spectrometry (MS) and nuclear magnetic resonance (NMR) has given rise to high-dimensional biomedical data of specific metabolites that can be leveraged to study their effects in humans. These metabolic interactions can be evaluated using probabilistic graphical models (PGMs), which define conditional dependence and independence between components within and between heterogeneous biomedical datasets. This method allows for the detection and recovery of valuable but latent information that cannot be easily detected by other currently existing methods. Here, we develop a PGM method, referred to as an "Integrated Gaussian Graphical Model (IGGM)", to incorporate exposure concentrations of seven trace elements-arsenic (As), lead (Pb), mercury (Hg), cadmium (Cd), zinc (Zn), selenium (Se) and copper (Cu-into metabolic networks. We first conducted a simulation study demonstrating that the integration of trace elements into metabolomics data can improve the accuracy of detecting latent interactions of metabolites impacted by exposure in the network. We tested parameters such as sample size and the number of neighboring metabolites of a chosen trace element for their impact on the accuracy of detecting metabolite interactions. We then applied this method to measurements of cord blood plasma metabolites and placental trace elements collected from newborns in the New Hampshire Birth Cohort Study (NHBCS). We found that our approach can identify latent interactions among metabolites that are related to trace element concentrations. Application to similarly structured data may contribute to our understanding of the complex interplay between exposure-related metabolic interactions that are important for human health.

3.
Environ Res ; 179(Pt A): 108733, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31561054

RESUMO

BACKGROUND: Exposure to cadmium may contribute to the risk of gestational diabetes mellitus (GDM) and glucose intolerance during pregnancy. METHODS: We examined 917 women enrolled from 2009 to 2017 in the New Hampshire Birth Cohort Study. Lifestyle, diet, demographic factors and pregnancy outcomes were collected by questionnaire and medical record review. Cadmium concentrations were measured in urine samples collected at 24-28 weeks gestation. Women were classified as normal (n = 815), glucose intolerant (n = 86), or GDM (n = 16) based on clinical data (i.e., glucose challenge test, oral glucose challenge test). We calculated odds ratios (OR) and 95% confidence intervals (CI), adjusting for potential confounders, using multinomial logistic regression to examine disease severity (normal, glucose intolerant, GDM) and logistic regression to examine the combined outcome of gestational hyperglycemia. RESULTS: Little to no association was observed for glucose intolerance (OR = 1.11, 95%CI 0.85-1.45) or GDM (OR = 0.86, 95% CI 0.51-1.44) with a doubling of urinary cadmium as compared to normal women. The combined outcome of gestational hyperglycemia yielded similar results (OR = 1.07, 95% CI 0.84-1.35). However, when stratified by pre-pregnancy body mass index (BMI), there was a slight association with the combined outcome in normal weight women (OR = 1.32, 95% CI 0.88-1.98) and no association in the overweight or obese women. This positive association remained in restricted analyses of only women with no exposure to smoking during pregnancy and those who had never smoked. CONCLUSIONS: Cadmium exposure was suggestively associated with increased risk of gestational hyperglycemia among women not already at increased risk of GDM due to being overweight or obese; however, associations of cadmium with gestational hyperglycemia were not statistically significant.

4.
Epigenetics ; : 1-16, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31462129

RESUMO

Copper is an essential trace nutrient and an enzymatic cofactor necessary for diverse physiological and biological processes. Copper metabolism is uniquely controlled in the placenta and changes to copper metabolism have been linked with adverse birth outcomes. We investigated associations between patterns of DNA methylation (DNAm; measured at >485 k CpG sites) and copper concentration measured from placentae in two independent mother-infant cohorts: the New Hampshire Birth Cohort Study (NHBCS, n = 306) and the Rhode Island Child Health Study (RICHS, n = 141). We identified nine copper-associated differentially methylated regions (DMRs; adjusted P < 0.05) and 15 suggestive CpGs (raw P < 1e-5). One of the most robust variably methylated CpGs associated with the expression of the antioxidant, GSTP1. Our most robust DMR negatively associates with the expression of the zinc-finger gene, ZNF197 (FDR = 4.5e-11). Genes co-expressed with ZNF197, a transcription factor, are enriched for genes that associate with birth weight in RICHS (OR = 2.9, P = 2.6e-6, N = 194), genes that are near a ZNF197 consensus binding motif (OR = 1.34, P = 0.01, N = 194), and for those classified in GO biological processes growth hormone secretion (P = 3.4e-4), multicellular organism growth (P = 3.8e-4), and molecular functions related to lipid biosynthesis (P = 1.9e-4). Further, putative transcriptional targets for ZNF197 include genes involved in copper metabolism and placentation. Our results suggest that copper metabolism is tied to DNAm in the placenta and that copper-associated patterns in DNAm may mediate normal placentation and foetal development.

5.
Occup Environ Med ; 76(9): 680-687, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31308155

RESUMO

OBJECTIVES: The validity of surrogate measures of retrospective occupational exposure in population-based epidemiological studies has rarely been evaluated. Using toenail samples as bioindicators of exposure, we assessed whether work tasks and expert assessments of occupational metal exposure obtained from personal interviews were associated with lead and manganese concentrations. METHODS: We selected 609 controls from a case-control study of bladder cancer in New England who had held a job for ≥1 year 8-24 months prior to toenail collection. We evaluated associations between toenail metal concentrations and five tasks extracted from occupational questionnaires (grinding, painting, soldering, welding, working near engines) using linear regression models. For 139 subjects, we also evaluated associations between the toenail concentrations and exposure estimates from three experts. RESULTS: We observed a 1.9-fold increase (95% CI 1.4 to 2.5) in toenail lead concentrations with painting and 1.4-fold increase (95% CI 1.1 to 1.7) in manganese concentrations with working around engines and handling fuel. We observed significant trends with increasing frequency of both activities. For lead, significant trends were observed with the ratings from all three experts. Their average ratings showed the strongest association, with subjects rated as possibly or probably exposed to lead having concentrations that were 2.0 and 2.5 times higher, respectively, than in unexposed subjects (ptrend <0.001). Expert estimates were only weakly associated with manganese toenail concentrations. CONCLUSIONS: Our findings support the ability of experts to identify broad contrasts in previous occupational exposure to lead. The stronger associations with task frequency and expert assessments support using refined exposure characterisation whenever possible.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31253828

RESUMO

BACKGROUND: Residential wood stove use has become more prevalent in high-income countries, but only limited data exist on indoor exposure to PM2.5 and its components. METHODS: From 2014 to 2016, we collected 7-day indoor air samples in 137 homes of pregnant women in Northern New England, using a micro-environmental monitor. We examined associations of wood stove use with PM2.5 mass and its components [black carbon (BC), organic and elemental carbon and their fractions, and trace elements], adjusted for sampling season, community wood stove use, and indoor activities. We examined impact of stove age, EPA-certification, and wood moisture on indoor pollutants. RESULTS: Median (IQR) household PM2.5 was 6.65 (5.02) µg/m3 and BC was 0.23 (0.20) µg/m3. Thirty percent of homes used a wood stove during monitoring. In homes with versus without a stove, PM2.5 was 20.6% higher [although 95% confidence intervals (-10.6, 62.6) included the null] and BC was 61.5% higher (95% CI: 11.6, 133.6). Elemental carbon (total and fractions 3 and 4), potassium, calcium, and chloride were also higher in homes with a stove. Older stoves, non-EPA-certified stoves, and wet or mixed (versus dry) wood were associated with higher pollutant concentrations, especially BC. CONCLUSIONS: Homes with wood stoves, particularly those that were older and non-EPA-certified or burning wet wood had higher concentrations of indoor air combustion-related pollutants.

7.
J Bacteriol ; 201(16)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31209076

RESUMO

Previous work from our group indicated an association between the gastrointestinal microbiota of infants with cystic fibrosis (CF) and airway disease in this population. Here we report that stool microbiota of infants with CF demonstrates an altered but largely unchanging within-individual bacterial diversity (alpha diversity) over the first year of life, in contrast to the infants without CF (control cohort), which showed the expected increase in alpha diversity over the first year. The beta diversity, or between-sample diversity, of these two cohorts was significantly different over the first year of life and was statistically significantly associated with airway exacerbations, confirming our earlier findings. Compared with control infants, infants with CF had reduced levels of Bacteroides, a bacterial genus associated with immune modulation, as early as 6 weeks of life, and this significant reduction of Bacteroides spp. in the cohort with CF persisted over the entire first year of life. Only two other genera were significantly different across the first year of life: Roseburia was significantly reduced and Veillonella was significantly increased. Other genera showed differences between the two cohorts but only at selected time points. In vitro studies demonstrated that exposure of the apical face of polarized intestinal cell lines to Bacteroides species supernatants significantly reduced production of interleukin 8 (IL-8), suggesting a mechanism whereby changes in the intestinal microbiota could impact inflammation in CF. This work further establishes an association between gastrointestinal microbiota, inflammation, and airway disease in infants with CF and presents a potential opportunity for therapeutic interventions beginning in early life.IMPORTANCE There is growing evidence for a link between gastrointestinal bacterial communities and airway disease progression in CF. We demonstrate that infants with CF ≤1 year of age show a distinct stool microbiota versus that of control infants of a comparable age. We detected associations between the gut microbiome and airway exacerbation events in the cohort of infants with CF, and in vitro studies provided one possible mechanism for this observation. These data clarify that current therapeutics do not establish in infants with CF a gastrointestinal microbiota like that in healthy infants, and we suggest that interventions that direct the gastrointestinal microbiota closer to a healthy state may provide systemic benefits to these patients during a critical window of immune programming that might have implications for lifelong health.

8.
Environ Res ; 174: 135-142, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31075694

RESUMO

Early-life exposure to inorganic arsenic (iAs) may adversely impact health later in life. To date, evidence of iAs adverse effects on children's neurodevelopment comes mainly from populations highly exposed to contaminated water with conflicting results. Little is known about those effects among populations with low iAs exposure from food intake. We investigated the cross-sectional association between exposure to iAs and neurodevelopment scores among children living in Spain whose main route of exposure was diet. Arsenic species concentrations in urine from 400 children was determined, and the sum of urinary iAs, dimethylarsinic acid, and monomethylarsonic acid was used to estimate iAs exposure. The McCarthy Scales of Children's Abilities was used to assess children's neuropsychological development at about 4-5 years of age. The median (interquartile range) of children's sum of urinary iAs, MMA, and DMA was 4.85 (2.74-7.54) µg/L, and in adjusted linear regression analyses the natural logarithm transformed concentrations showed an inverse association with children's motor functions (ß, [95% confidence interval]; global scores (-2.29, [-3.95, -0.63])), gross scores (-1.92, [-3.52, -0.31]) and fine scores (-1.54, [-3.06, -0.03]). In stratified analyses by sex, negative associations were observed with the scores in the quantitative index (-2.59, [-5.36, 0.17]) and working memory function (-2.56, [-5.36, 0.24]) only in boys. Our study suggests that relatively low iAs exposure may impair children's neuropsychological development and that sex-related differences may be present in susceptibility to iAs related effects; however, our findings should be interpreted with caution given the possibility of residual confounding.

9.
Environ Health Perspect ; 127(5): 57005, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31082282

RESUMO

BACKGROUND: Prenatal cadmium (Cd) exposure has been recognized to restrict growth, and male and female fetuses may have differential susceptibility to the developmental toxicity of Cd. Imprinted genes, which exhibit monoallelic expression based on parent of origin, are highly expressed in placental tissues. The function of these genes is particularly critical to fetal growth and development, and some are expressed in sex-specific patterns. OBJECTIVES: We aimed to examine whether prenatal Cd associates with the expression of imprinted placental genes, overall or in fetal sex-specific patterns, across two independent epidemiologic studies. METHODS: We tested for Cd­sex interactions in association with gene expression, then regressed the placental expression levels of 74 putative imprinted genes on placental log-Cd concentrations while adjusting for maternal age, sex, smoking history, and educational attainment. These models were performed within study- and sex-specific strata in the New Hampshire Birth Cohort Study (NHBCS; [Formula: see text]) and the Rhode Island Child Health Study (RICHS; [Formula: see text]). We then used fixed-effects models to estimate the sex-specific and overall associations across strata and then examine heterogeneity in the associations by fetal sex. RESULTS: We observed that higher Cd concentrations were associated with higher expression of distal-less homeobox 5 (DLX5) ([Formula: see text]), and lower expression of h19 imprinted maternally expressed transcript (H19) ([Formula: see text]) and necdin, MAGE family member (NDN) ([Formula: see text]) across study and sex-specific strata, while three other genes [carboxypeptidase A4 (CPA4), growth factor receptor bound protein 10 (GRB10), and integrin-linked kinase (ILK)] were significantly associated with Cd concentrations, but only among female placenta ([Formula: see text]). Additionally, the expression of DLX5, H19, and NDN, the most statistically significant Cd-associated genes, were also associated with standardized birth weight z-scores. DISCUSSION: The differential regulation of a set of imprinted genes, particularly DLX5, H19, and NDN, in association with prenatal Cd exposure may be involved in overall developmental toxicity, and some imprinted genes may respond to Cd exposure in a manner that is specific to infant gender. https://doi.org/10.1289/EHP4264.

10.
Nat Commun ; 10(1): 1893, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015461

RESUMO

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10-7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10-74) and BMI in pregnancy (3/914, p = 1.13x10-3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.


Assuntos
Peso ao Nascer/genética , DNA/metabolismo , Epigênese Genética , Genoma Humano , Adolescente , Adulto , Índice de Massa Corporal , Criança , Ilhas de CpG , DNA/genética , Metilação de DNA , Feminino , Desenvolvimento Fetal/genética , Feto , Ácido Fólico/sangue , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fumar/efeitos adversos , Fumar/sangue , Fumar/genética
11.
Environ Health ; 18(1): 18, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30819207

RESUMO

BACKGROUND: Prenatal exposure to arsenic has been linked to a range of adverse health conditions in later life. Such fetal origins of disease are frequently the result of environmental effects on the epigenome, leading to long-term alterations in gene expression. Several studies have demonstrated effects of prenatal arsenic exposure on DNA methylation; however the impact of arsenic on the generation and decoding of post-translational histone modifications (PTHMs) is less well characterized, and has not been studied in the context of prenatal human exposures. METHODS: In the current study, we examined the effect of exposure to low-to-moderate levels of arsenic in a US birth cohort, on the expression of 138 genes encoding key epigenetic regulators in the fetal portion of the placenta. Our candidate genes included readers, writers and erasers of PTHMs, and chromatin remodelers. RESULTS: Arsenic exposure was associated with the expression of 27 of the 138 epigenetic genes analyzed. When the cohort was stratified by fetal sex, arsenic exposure was associated with the expression of 40 genes in male fetal placenta, and only 3 non-overlapping genes in female fetal placenta. In particular, we identified an inverse relationship between arsenic exposure and expression of the gene encoding the histone methyltransferase, PRDM6 (p < 0.001). Mutation of PRDM6 has been linked to the congenital heart defect, patent ductus arteriosus. CONCLUSIONS: Our findings suggest that prenatal arsenic exposure may have sex-specific effects on the fetal epigenome, which could plausibly contribute to its subsequent health impacts.


Assuntos
Arsênico/urina , Poluentes Ambientais/urina , Epigênese Genética , Placenta/metabolismo , Caracteres Sexuais , Transcriptoma , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Troca Materno-Fetal , Gravidez , Segundo Trimestre da Gravidez/urina
12.
Environ Int ; 126: 533-542, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30851484

RESUMO

The quality of the intrauterine environment, in which the placenta plays a critical role, affects birth outcomes and lifelong health. The effect of metal contaminants on the growth and functioning of the placenta have not been widely reported but may provide insights into how metal exposures lead to these outcomes. We examined relationships between placental concentrations of cadmium (Cd), arsenic (As), mercury (Hg) and lead (Pb) and measures of placental growth and functioning (placental weight, placental efficiency (the log ratio of placental weight and birth weight), chorionic disc area and disc eccentricity) as part of the New Hampshire Birth Cohort Study (N = 1159). We additionally examined whether these associations were modified by placental concentrations of essential elements zinc (Zn) and selenium (Se). Associations were evaluated using generalized linear models. Multivariable-adjusted differences in placental weight were - 7.81 g (95% CI: -15.42, -2.48) with every ng/g increase in the Cd concentration of placenta (p-Value = 0.0009). Greater decrements in placental weight and efficiency associated with placental Cd were observed for females. For placentae with below median Zn and Se concentrations, decrements in placental weight were - 8.81 g (95% CI: -16.85, -0.76) and - 13.20 g (95% CI: -20.70, -5.70) respectively. The Cd concentration of placenta was also associated with reductions in placental efficiency both overall, and in Zn- and Se-stratified models. No appreciable differences were observed with other elements (As, Hg or Pb) and with other placental measures (chorionic disc area and disc eccentricity). In structural equation models, placental weight was a mediator in the relation between placental Cd concentration and reduced birth weight. Our findings suggest a role of interacting essential and contaminant elements on birth weight that may be mediated by changes in the growth and function of the placenta.

14.
Environ Res ; 171: 523-529, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30743244

RESUMO

BACKGROUND: Mechanistic studies support the potential for mercury (Hg) to alter immunity, including via in utero exposure. As yet, there are few prospective studies of in utero Hg exposure and subsequent immune-related outcomes, especially in infancy. OBJECTIVES: We investigated the association of biomarkers of prenatal Hg exposure and maternal silver-mercury dental amalgams with the occurrence of infant allergy, respiratory infection, and respiratory symptoms in the first year of life. METHODS: The New Hampshire Birth Cohort Study (NHBCS) ascertained information on infant allergies, infections and symptoms through telephone interviews at 4, 8 and 12 months postpartum and measured total Hg in maternal toenails collected at ~28-30 weeks gestation. Information on maternal fish consumption and presence of dental amalgams was obtained from a questionnaire administered at study enrollment at 24-28 weeks. A total of 1321 NHBCS mother-infant pairs had at least one Hg exposure measure (toenail Hg or information on dental amalgams) and information on dietary fish intake. Generalized linear models and generalized estimating equation models with Poisson regression adjusted for potential confounders (maternal age, level of education, parity, smoking, alternative Healthy Eating Index-2010, infant sex, gestational age, feeding mode, and day care attendance) were used to assess the association between infant outcomes and prenatal toenail Hg levels. We subsetted this analysis on mothers who consumed fish (n = 706) as a measure of in utero methylmercury (MeHg) exposure. Associations between infant outcomes and dental amalgams as a measure of in utero inorganic Hg exposure were assessed among mothers who did not consume fish (n = 218). RESULTS: Among women who ate fish during pregnancy, higher maternal toenail Hg concentrations were associated with an increased risk of lower respiratory infections and respiratory symptoms requiring a doctor visit among infants age 9-12 months (relative risk (RR) 1.4 (95% CI: 1.1, 1.9) and 1.2 (95% CI: 1.0, 1.4) respectively), whereas a reduced risk of lower respiratory infections was observed among infants 0-4 months of age (RR = 0.7 (95% CI: 0.5, 1.0). We found little to no evidence of associations of toenail Hg with upper respiratory infections, allergy or eczema at any age to one year. Among infants of mothers who did not consume fish, we found an elevated risk of upper respiratory infections requiring a doctor visit in relation to having dental amalgams during pregnancy (RR = 1.5 (95% CI: 1.1, 2.1)). Overall, weaker associations were observed with lower respiratory infections, respiratory symptoms, and medically confirmed allergies, and there was no association with eczema. CONCLUSIONS: Our analyses of a US birth cohort, along with prior mechanistic work, raise the possibility that gestational Hg exposure through fish/seafood consumption and dental amalgams may alter respiratory infections and respiratory symptoms in infants.

15.
Int J Obes (Lond) ; 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30765892

RESUMO

BACKGROUND: Mother-to-newborn transmission of obesity-associated microbiota may be modified by birth mode (vaginal vs. Cesarean delivery). Prospective data to test this hypothesis are still sparse. OBJECTIVE: To examine prospective associations of maternal pre-pregnancy BMI and gestational weight gain with the infant gut microbiome by birth-mode strata. SUBJECTS/METHODS: In 335 mother-infant pairs in the New Hampshire Birth Cohort, we ascertained data from questionnaires and medical records, and generated microbiome data from 6-week-old infants' stool using Illumina 16s rRNA gene sequencing (V4-V5 region). Analyses were stratified by birth mode and conducted before and after adjusting for potential confounders, which included maternal age, education, parity, and Mediterranean diet score. RESULTS: Among 335 mothers, 56% had normal pre-pregnancy BMI ( < 25, referent), 27% were overweight (BMI 25-30), and 18% obese (BMI > 30). Among the 312 mothers with weight gain data, 10% had inadequate weight gain, 30% adequate (referent), and 60% excess. Birth mode modified associations of pre-pregnancy BMI with several genera, including the most abundant genus, Bacteroides (P for interaction = 0.05). In the vaginal-delivery group, maternal overweight or obesity was associated with higher infant gut microbiome diversity and higher relative abundance of 15 operational taxonomic units (OTUs), including overrepresentation of Bacteroides fragilis, Escherichia coli, Veillonella dispar, and OTUs in the genera Staphylococcus and Enterococcus. In the Cesarean-delivered group, there were no significant associations of pre-pregnancy BMI with infant microbiome (alpha) diversity or OTUs. Gestational weight gain was not associated with differential relative abundance of infant gut microbial OTUs or with measures of microbial diversity in infants delivered vaginally or by Cesarean section. CONCLUSIONS: Among vaginally-delivered infants, maternal overweight and obesity was associated with altered infant gut microbiome composition and higher diversity. These associations were not observed in Cesarean-delivered infants, whose microbiome development differs from vaginally-delivered infants. Our study provides additional evidence of birth-mode dependent associations of maternal body weight status with the infant gut microbiota. The role of these associations in mediating the intergenerational cycle of obesity warrants further examination.

16.
Cancer Epidemiol Biomarkers Prev ; 28(4): 782-788, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30700445

RESUMO

BACKGROUND: The high rate of non-muscle-invasive bladder cancer recurrence is a major challenge in patient management. miRNAs functionally regulate tumor cell proliferation and invasion, and have strong potential as biomarkers because they are robust to degradation. The objective of this project was to identify reproducible prognostic miRNAs in resected non-muscle-invasive bladder tumor tissue that are predictive of the recurrent tumor phenotype. METHODS: We utilized patients diagnosed with primary non-muscle-invasive bladder cancer in three independent cohorts for a biomarker discovery/validation approach. Baseline tumor tissue from patients with the clinically challenging, non-muscle-invasive primary low stage (Ta), high grade, and T1 tumors (tumors extending into the lamina propria) comprised the discovery cohort (n = 38). We isolated the tumor tissue RNA and assessed a panel of approximately 800 miRNAs. RESULTS: miR-26b-5p was the top-ranking prognostic tumor tissue miRNA, with a time-to-recurrence HR 0.043 for levels above versus below median, (P adj = 0.0003). miR-26b-5p was related to a dose-response reduction in tumor recurrence, and levels above the median were also associated with reduced time-to-progression (P adj = 0.02). We used two independent longitudinal cohorts that included both low-grade and high-grade Ta and T1 tumors for validation and found a consistent relationship between miR-26b-5p and recurrence and progression. CONCLUSIONS: Our results suggest that miR-26b-5p levels may be prognostic for non-muscle-invasive bladder cancer recurrence, and can feasibly be assessed in baseline tumor tissue from a wide variety of clinical settings. IMPACT: Early identification of those non-muscle-invasive bladder tumor patients with refractory phenotypes would enable individualized treatment and surveillance.

17.
Environ Int ; 123: 459-466, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30622071

RESUMO

Swimming in pools during pregnancy may expose the fetus to water disinfection by-products (DBP). As yet, our understanding of the impacts on DBPs on the fetus is uncertain. Individuals with public water systems are typically exposed to DBPs through drinking, showering and bathing, whereas among those on private water systems, swimming in pools may be the primary exposure source. We analyzed the effects of maternal swimming on birth outcomes and cord blood epigenetic changes in the New Hampshire Birth Cohort Study, a cohort of pregnant women with households on private water systems. Information about swimming in pools during pregnancy was obtained from 1033 women via questionnaires. Swimming pool use and duration were modeled using linear regression with newborn weight, length, and head circumference (z-scores) and genome wide cord blood DNA methylation as the outcomes and with adjustment for potential confounders. Overall 19.7% of women reported swimming in a pool during pregnancy. Among swimmers, duration of swimming was inversely related to head circumference (-0.02 z-score per 10% increase in duration, P = 0.004). No associations were observed with birth weight, length or DNA methylation modifications. Our findings suggest swimming pool exposure may impact the developing fetus although longer-term studies are needed.


Assuntos
Metilação de DNA , Sangue Fetal/química , Recém-Nascido , Exposição Materna/efeitos adversos , Piscinas , Adulto , Peso ao Nascer , Estudos de Coortes , Desinfecção , Feminino , Humanos , Masculino , Gravidez , Natação , Poços de Água
18.
Epidemiology ; 30(3): 458-465, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30601243

RESUMO

BACKGROUND: Few studies have modeled smoking histories by combining smoking intensity and duration to show what profile of smoking behavior is associated with highest risk of bladder cancer. This study aims to provide insight into the association between smoking exposure history and bladder cancer risk by modeling both smoking intensity and duration in a pooled analysis. METHODS: We used data from 15 case-control studies included in the bladder cancer epidemiology and nutritional determinants study, including a total of 6,874 cases and 17,727 controls. To jointly interpret the effects of intensity and duration of smoking, we modeled excess odds ratios per pack-year by intensity continuously to estimate the risk difference between smokers with long duration/low intensity and short duration/high intensity. RESULTS: The pattern observed from the pooled excess odds ratios model indicated that for a fixed number of pack-years, smoking for a longer duration at lower intensity was more deleterious for bladder cancer risk than smoking more cigarettes/day for a shorter duration. We observed similar patterns within individual study samples. CONCLUSIONS: This pooled analysis shows that long duration/low intensity smoking is associated with a greater increase in bladder cancer risk than short duration/high intensity smoking within equal pack-year categories, thus confirming studies in other smoking-related cancers and demonstrating that reducing exposure history to a single metric such as pack-years was too restrictive.


Assuntos
Modelos Biológicos , Fumar/epidemiologia , Fumar/psicologia , Neoplasias da Bexiga Urinária/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Fatores de Risco , Fatores de Tempo
19.
Am J Epidemiol ; 188(4): 646-655, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30608527

RESUMO

Several metals have carcinogenic properties, but their associations with breast cancer are not established. We studied cadmium, a metalloestrogen, and 9 other metals-arsenic, cobalt, chromium, copper, mercury, molybdenum, lead, tin, and vanadium--in relation to young-onset breast cancer (diagnosis age <50 years), which tends to be more aggressive than and have a different risk profile from later-onset disease. Recent metal exposure was measured by assessing element concentrations, via inductively coupled plasma mass spectrometry, in toenail clippings of 1,217 disease-discordant sister pairs in the US-based Sister (2003-2009) and Two Sister (2008-2010) studies. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. After correcting for differential calendar time of sample collection, no statistically significant associations were observed between any metals and breast cancer. Vanadium had the largest odds ratio (for fourth vs. first quartile, odds ratio = 1.36, 95% confidence interval: 0.84, 2.21; P for trend = 0.17). Cadmium was associated with a small increase in risk, with no evidence of a dose-response relationship (for fourth vs. first quartile, odds ratio = 1.15, 95% confidence interval: 0.82, 1.60; P for trend = 0.67). Positive associations between urinary cadmium concentrations and breast cancer have been reported in case-control studies, but we observed no such association between young-onset breast cancer and toenail concentrations of any assessed metals.

20.
Epidemiology ; 30(1): 112-119, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30256233

RESUMO

BACKGROUND: Exposure to trace elements may affect health, including breast cancer risk. Trace element levels in toenails are potentially useful biomarkers of exposure, but their reliability is not established. We assessed the reproducibility of toenail element concentrations over time and whether concentrations change following a breast cancer diagnosis. METHODS: We assessed trace element levels in toenails collected at two time points from 221 women (111 with and 110 without an intervening breast cancer diagnosis). We measured levels of arsenic, cadmium, chromium, cobalt, copper, iron, mercury, manganese, molybdenum, nickel, lead, antimony, selenium, tin, vanadium, and zinc using inductively coupled plasma mass spectrometry in samples collected at baseline and 4-10 years later. We compared trace element concentrations over time using Spearman's rank correlation coefficient (R). We used linear models to examine the magnitude and direction of changes and the influence of a breast cancer diagnosis. RESULTS: Overall, we observed positive correlations (R = 0.18-0.71) between paired samples for all trace elements. However, nickel (R = -0.02) and antimony (R = 0.12) were not correlated among cases. We observed decreases in cadmium, chromium, mercury, manganese, molybdenum, nickel, and lead between baseline and follow-up, but case status was unrelated to these changes. The declines are consistent with decreases over calendar time rather than age time. CONCLUSIONS: Toenail trace element concentrations were correlated over time, but many elements showed systematic decreases by calendar year. Aside from nickel and antimony, postdiagnostic toenail levels correlated with prediagnostic levels, providing support for using postdiagnostic toenail samples in retrospective studies.


Assuntos
Neoplasias da Mama/diagnóstico , Metais/análise , Unhas/química , Oligoelementos/análise , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Irmãos , Estatísticas não Paramétricas , Estados Unidos
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