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Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure.

ABSTRACT: From 1958 to 1970, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes, including lung and bladder cancer.We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007 to 2010, and 508 age and gender-matched controls.ORs adjusted for age, sex, and smoking in those only exposed in early life to arsenic water concentrations of ?110, 110 to 800, and >800 ?g/L were 1.00, 1.88 [95% confidence interval (CI), 0.96-3.71], and 5.24 (3.05-9.00; P(trend) < 0.001) for lung cancer, and 1.00, 2.94 (1.29-6.70), and 8.11 (4.31-15.25; P(trend) < 0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (>800 ?g/L) involved exposures that started 49 to 52 years before, and ended 37 to 40 years before the cancer cases were diagnosed.Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early life, even up to 40 years after high exposures ceased. Such findings have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure.Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease.

SUBMITTER: Steinmaus C

PROVIDER: S-EPMC4344186 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure.

Steinmaus Craig C Ferreccio Catterina C Acevedo Johanna J Yuan Yan Y Liaw Jane J Durán Viviana V Cuevas Susana S García José J Meza Rodrigo R Valdés Rodrigo R Valdés Gustavo G Benítez Hugo H VanderLinde Vania V Villagra Vania V Cantor Kenneth P KP Moore Lee E LE Perez Saida G SG Steinmaus Scott S Smith Allan H AH

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20140523 8

<h4>Background</h4>From 1958 to 1970, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes, including lung and bladder cancer.<h4>Methods</h4>We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the ...[more]

PMID: 24859871

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Project description:ImportanceRice-a typical first food and major ingredient in various infant foods-contains inorganic arsenic (As), but the extent of As exposure from these foods has not been well characterized in early childhood.ObjectiveTo determine the types and frequency of rice and rice-containing products consumed by infants in the first year of life and the association with As biomarker concentrations.Design, setting, and participantsIncluded were infants from singleton births of pregnant women enrolled in the New Hampshire Birth Cohort Study from 2011 to 2014 whose parents were interviewed during their first year of life. Enrolled women from selected clinics were aged 18 to 45 years, living in the same residence since their last menstrual period, in households served by a private water system, and had no plans to move during pregnancy. Data on infants' intake of rice and rice products were collected from interviews with their parents at 4, 8, and 12 months' follow-up and from a 3-day food diary at 12 months from March 2013 to August 2014.ExposuresInfants' intake of rice and rice products.Main outcomes and measuresTotal urinary As and the sum of As species measured using inductively coupled mass spectrometry and high-performance liquid chromatography with inductively coupled mass spectrometry. Commonly reported infant rice snacks were tested for As.ResultsWe obtained dietary data on 759 of 951 infants (79.8% participation rate). Of these, 391 infants (51.7%) were male, and the mean (SD) gestational age was 39.4 (1.7) weeks. An estimated 80% were introduced to rice cereal during their first year. At 12 months, 32.6% of infants (42 of 129) were fed rice snacks. Among infants aged 12 months who did not eat fish or seafood, the geometric mean total urinary As concentrations were higher among those who ate infant rice cereal (9.53 µg/L) or rice snacks (4.97 µg/L) compared with those who did not eat rice or rice products (2.85 µg/L; all P < .01). Infant rice snacks contained between 36 and 568 ng/g of As and 5 to 201 ng/g of inorganic As.Conclusions and relevanceOur findings indicate that intake of rice cereal and other rice-containing foods, such as rice snacks, contribute to infants' As exposure and suggest that efforts should be made to reduce As exposure during this critical phase of development.

Project description:BackgroundIn utero arsenic exposure may alter fetal developmental programming by altering DNA methylation, which may result in a higher risk of disease in later life. We evaluated the association between in utero arsenic exposure and DNA methylation (DNAm) in cord blood and its influence in later life.MethodsGenome-wide DNA methylation in cord blood from 64 subjects in the Taiwanese maternal infant and birth cohort was analyzed. Robust regressions were applied to assess the association of DNA methylation with in utero arsenic exposure. Multiple testing was adjusted by controlling false discovery rate (FDR) of 0.05. The DAVID bioinformatics tool was implemented for functional annotation analyses on the detected CpGs. The identified CpGs were further tested in an independent cohort. For the CpGs replicated in the independent cohort, linear mixed models were applied to assess the association of DNA methylation with low-density lipoprotein (LDL) at different ages (2, 5, 8, 11 and 14 years).ResultsIn total, 579 out of 385,183 CpGs were identified after adjusting for multiple testing (FDR = 0.05), of which ~60% were positively associated with arsenic exposure. Functional annotation analysis on these CpGs detected 17 KEGG pathways (FDR = 0.05) including pathways for cardiovascular diseases (CVD) and diabetes mellitus. In the independent cohort, about 46% (252 out of 553 CpGs) of the identified CpGs showed associations consistent with those in the study cohort. In total, 11 CpGs replicated in the independent cohort were in the pathways related to CVD and diabetes mellitus. Via longitudinal analyses, we found at 5 out of the 11 CpGs methylation was associated with LDL over time and interactions between DNA methylation and time were observed at 4 of the 5 CpGs, cg25189764 (coeff = 0.157, p-value = 0.047), cg04986899 (coeff. For interaction [coeff.int] = 0.030, p-value = 0.024), cg04903360 (coeff.int = 0.026, p-value = 0.032), cg08198265 (coeff.int = -0.063, p-value = 0.0021), cg10473311 (coeff.int = -0.021, p-value = 0.027).ConclusionIn utero arsenic exposure was associated with cord blood DNA methylation at various CpGs. The identified CpGs may help determine pathological epigenetic mechanisms linked to in utero arsenic exposure. Five CpGs (cg25189764, cg04986899, cg04903360, cg08198265 and cg10473311) may serve as epigenetic markers for changes in LDL later in life.

Project description:BackgroundWe have previously reported that in utero arsenic exposure is associated with increased length and other anthropometric outcomes at birth in a U.S. cohort. However, it is unknown whether these anthropometric differences persist through early life.ObjectivesWe assessed in utero arsenic exposure in relation to attained anthropometry and growth trajectories through the first year of life.MethodsAmong 760 mother-infant pairs from the New Hampshire Birth Cohort Study, we assessed in utero arsenic exposure using maternal second trimester urinary arsenic and assessed infant growth from medical records.ResultsMedian maternal second trimester total urinary arsenic (tAs; inorganic arsenic + monomethylarsonic acid + dimethylarsinic acid) was 3.96 μg/L (IQR: 2.02, 6.72). In adjusted linear mixed effects models, each doubling of maternal urinary tAs was associated with a 0.05 increase in length WHO Z score (95% CI: 0, 0.09) over the first year of life which corresponds to an approximately 0.12 cm increase in males and 0.13 cm increase in females at 12 months. No associations were observed between urinary tAs and attained weight, weight-for-length, or head circumference. In adjusted piecewise linear mixed effects models, each doubling of urinary tAs was associated with a 0.07 (95% CI: 0.02, 0.12) cm per month decreased length growth rate through 3.5 months with no evidence of an association thereafter. No associations were observed between urinary tAs and infant weight gain or change in weight-for-length and head circumference through one year.ConclusionsOn average, infants exposed to higher in utero arsenic attained modestly longer length during the first year, despite having slower linear growth in the first 3.5 months of life. This suggests that the previously demonstrated arsenic-associated longer length among study infants at birth persists through the first year of life. No other anthropometric associations with in utero arsenic exposure were observed across the full study population.

Dataset Information

Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure.

Publications

Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure.

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