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Molly L Kile

Oregon State University, School of Biological and Population Health, Faculty Member

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Papers by Molly L Kile

Description of exposure profiles for seven environmental chemicals in a US population using recursive partition mixture modeling (RPMM)

Journal of Exposure Science and Environmental Epidemiology, Dec 21, 2017

Biomonitoring studies have shown that humans are exposed to numerous environmental chemicals. Pre... more Biomonitoring studies have shown that humans are exposed to numerous environmental chemicals. Previous work provides limited insights into the dynamic relationship between different chemicals within a population. The objective of this study is to develop an analytical method identifying exposure profiles of seven common environmental chemicals and determine how exposure profiles differ by sociodemographic groups and National Health and Nutrition Examination Survey (NHANES) 2003-2012 cycle year. We used recursive partition mixture modeling (RPMM) to define classes of the population with similar exposure profiles of lead, cadmium, 2,4-dichlorophenol, 2,5-dichlorophenol, bisphenol A (BPA), triclosan, and benzophenone-3 in individuals aged ≥6 years. Additionally, quasibinomial logistic regression was used to examine the association between each class and selected demographic characteristics. Eight exposure profiles were identified. Individuals who clustered together and had the highest chemical exposures were more likely to be older, to be Non-Hispanic Black (NHB) or Other Hispanic (OH), more likely to live below the poverty line, more likely to be male, and more likely to have participated in the earlier NHANES cycle (2003)(2004). The developed method described the dynamic relationship between chemicals and shows that this relationship is different for subpopulations based on their sociodemographic characteristics.

Influence Of Prenatal Mercury And Arsenic Exposure In Utero On Dna Methylation In Umbilical Cord Blood

ISEE Conference Abstracts, 2015

Background: Mercury and arsenic are known developmental toxicants. Prenatal exposures are associa... more

Fecal Colonization With Multidrug-Resistant E. coli Among Healthy Infants in Rural Bangladesh

Frontiers in Microbiology, 2019

Third generation cephalosporins (3GC) are one of the main choices for treatment of infections cau... more Third generation cephalosporins (3GC) are one of the main choices for treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Due to their overuse, an increasing trend of resistance to 3GC has been observed in developing countries. Here, we describe fecal colonization of 3GC-resistant (3GCr) Escherichia coli in healthy infants (1-12 months old) living in rural areas of Bangladesh. We found that stool samples of 82% of infants (n = 100) were positive for 3GCr E. coli with a mean ± standard deviation of 6.21 ± 1.32 log 10 CFU/g wet weight of stool. 3GCr E. coli encompasses an average one third (33%) of the total E. coli of stool. Almost 77% (n = 63) of these 3GCr E. coli were MDR (or resistant to ≥3 classes of antibiotics). Around 90% (n = 74) of 3GCr E. coli were extended spectrum beta-lactamase (ESBL)-producing in which bla CTX-M-group-1 was the predominant (96%, n = 71) ESBL-gene followed by bla TEM (41%, n = 30) and bla OXA-1 (11%, n = 8). A significant proportion (26.5%, n = 22) of 3GCr E. coli was pathogenic, comprising two types, enteroaggregative (EAEC, n = 19) and enteropathogenic (EPEC, n = 3). Colonization of 3GCr E. coli in infant guts was not associated with demographic characteristics such as age, sex, mode of delivery, maternal and infant antibiotic use, disease morbidity, and feeding practices. The high rate of colonization of 3GCr E. coli in infants' guts is a serious public health concern which needs immediate attention and warrants further studies to explore the cause.

A cross sectional study of urinary phthalates, phenols and perchlorate on thyroid hormones in US adults using structural equation models (NHANES 2007–2008)

Environmental Research, 2018

Background: Biomonitoring data shows that people are exposed to phthalates, phenols and perchlora... more Background: Biomonitoring data shows that people are exposed to phthalates, phenols and perchlorates. Many of these compounds are endocrine disrupting compounds that affect thyroid hormone levels. Yet the effect of these compounds on thyroid hormone levels are often evaluated individually rather than as a mixture. Our objective was to examine the association between 11 urinary endocrine disrupting compounds and thyroid hormones using structural equation models. Methods: Using data from the National Health and Nutrition and Examination Survey 2007-2008, we fit a latent variable utilizing urinary measurements of 9 compounds in females (perchlorate, bisphenol A, benzophenone-3, mono-2ethyl5carboxypentyl phthalate, mono-n-butyl phthalate, mono-(3-carboxypropyl) phthalate, mono(2ethyl5hydroxyhexyl) phthalate, monobenzyl phthalate, and mono-isobutyl phthalate) and 8 compounds in males (without benzophenone-3). The association of the latent variable with serum thyroid hormones (Total T3, Total T4, and Thyroid Stimulating Hormones) was assessed in females (N=710) and males (N=850) over the age of 12 controlling for age, race, and urinary creatinine. In males, urinary endocrine disrupting compound levels were negatively associated with thyroxine (β: -0.19, 95% Confidence Interval (95% CI): -0.31, -0.05). In females, urinary endocrine disrupting compound levels were positively associated with triiodothyronine serum concentrations (β: 0.09, 95% CI: -0.03, 0.21) however this association was not statistically significant. This cross-sectional analysis provides additional evidence that environmental exposure to phthalates and phenols is associated with endocrine-related processes. Furthermore, these results suggested sex-specific differences in exposure to endocrine disrupting mixtures, and the exposure-response between endocrine disrupting mixtures and thyroid hormone levels.

A Case Study Describing a Community-Engaged Approach for Evaluating Polycyclic Aromatic Hydrocarbon Exposure in a Native American Community

International Journal of Environmental Research and Public Health, 2019

In 2015, the Swinomish Indian Tribal Community (SITC) was impacted by an air toxic release from o... more In 2015, the Swinomish Indian Tribal Community (SITC) was impacted by an air toxic release from one of two nearby oil refineries. This experience motivated SITC members to learn more about their exposure to air toxics. On the invitation of SITC, this community-based study measured personal exposure to polycyclic aromatic hydrocarbons (PAHs) and conducted interviews with the volunteers to evaluate perceptions of the data and experience of participating. Non-smoking SITC members were recruited in March 2016 (N = 10) and January 2017 (N = 22) with seven volunteers participating both times. Volunteers wore a wristband passive sampler for 7 days and completed daily activity diaries. Wristbands were analyzed for 62 PAHs using gas chromatography mass spectrometry. Wilcoxon exact tests determined if the sum total PAHs (ΣPAH) differed by activity, proximity to the refineries, and time. Aggregated results were shared during community meetings, and volunteers received individual reports. Volun...

Arsenic exposure and intestinal microbiota in children from Sirajdikhan, Bangladesh

PloS one, 2017

Arsenic has antimicrobial properties at high doses yet few studies have examined its effect on gu... more Arsenic has antimicrobial properties at high doses yet few studies have examined its effect on gut microbiota. This warrants investigation since arsenic exposure increases the risk of many diseases in which gut microbiota have been shown to play a role. We examined the association between arsenic exposure from drinking water and the composition of intestinal microbiota in children exposed to low and high arsenic levels during prenatal development and early life. 16S rRNA gene sequencing revealed that children with high arsenic exposure had a higher abundance of Proteobacteria in their stool compared to matched controls with low arsenic exposure. Furthermore, whole metagenome shotgun sequencing identified 332 bacterial SEED functions that were enriched in the high exposure group. A separate model showed that these genes, which included genes involved in virulence and multidrug resistance, were positively correlated with arsenic concentration within the group of children in the high a...

Validation of a Dish-Based Semiquantitative Food Questionnaire in Rural Bangladesh

Nutrients, 2017

A locally validated tool was needed to evaluate long-term dietary intake in rural Bangladesh. We ... more A locally validated tool was needed to evaluate long-term dietary intake in rural Bangladesh. We assessed the validity of a 42-item dish-based semi-quantitative food frequency questionnaire (FFQ) using two 3-day food diaries (FDs). We selected a random subset of 47 families (190 participants) from a longitudinal arsenic biomonitoring study in Bangladesh to administer the FFQ. Two 3-day FDs were completed by the female head of the households and we used an adult male equivalent method to estimate the FD for the other participants. Food and nutrient intakes measured by FFQ and FD were compared using Pearson's and Spearman's correlation, paired t-test, percent difference, cross-classification, weighted Kappa, and Bland-Altman analysis. Results showed good validity for total energy intake (paired t-test, p < 0.05; percent difference <10%), with no presence of proportional bias (Bland-Altman correlation, p > 0.05). After energy-adjustment and de-attenuation for within-person variation, macronutrient intakes had excellent correlations ranging from 0.55 to 0.70. Validity for micronutrients was mixed. High intraclass correlation coefficients (ICCs) were found for most nutrients between the two seasons, except vitamin A. This dish-based FFQ provided adequate validity to assess and rank long-term dietary intake in rural Bangladesh for most food groups and nutrients, and should be useful for studying dietary-disease relationships.

Communicating Results of a Dietary Exposure Study Following Consumption of Traditionally Smoked Salmon

Environmental Justice, 2016

One expectation of community-based participatory research (CBPR) is participant access to study r... more One expectation of community-based participatory research (CBPR) is participant access to study results. However, reporting experimental data produced by studies involving biological measurements in the absence of clinical relevance can be challenging to scientists and participants. We applied best practices in data sharing to report the results of a study designed to explore polycyclic aromatic hydrocarbons absorption, metabolism, and excretion following consumption of traditionally smoked salmon by members of the Confederated Tribes of the Umatilla Indian Reservation (CTUIR). A dietary exposure study was developed, in which nine Tribal members consumed 50 g of traditionally smoked salmon and provided repeated urine samples over 24 hours. During recruitment, participants requested access to their data following analysis. Disclosing data is an important element of CBPR and must be treated with the same rigor as that given to the data analysis. The field of data disclosure is relatively new, but when handled correctly can improve education within the community, reduce distrust, and enhance environmental health literacy. Using the results from this study, we suggest mechanisms for sharing data with a Tribal community.

Neurodevelopmental outcomes among 2- to 3-year-old children in Bangladesh with elevated blood lead and exposure to arsenic and manganese in drinking water

Environmental health : a global access science source, Jan 12, 2016

The people of Bangladesh are currently exposed to high concentrations of arsenic and manganese in... more The people of Bangladesh are currently exposed to high concentrations of arsenic and manganese in drinking water, as well as elevated lead in many regions. The objective of this study was to investigate associations between environmental exposure to these contaminants and neurodevelopmental outcomes among Bangladeshi children. We evaluated data from 524 children, members of an ongoing prospective birth cohort established to study the effects of prenatal and early childhood arsenic exposure in the Sirajdikhan and Pabna Districts of Bangladesh. Water was collected from the family's primary drinking source during the first trimester of pregnancy and at ages 1, 12 and 20-40 months. At age 20-40 months, blood lead was measured and neurodevelopmental outcomes were assessed using a translated, culturally-adapted version of the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Median blood lead concentrations were higher in Sirajdikhan than Pabna (7.6 vs. <LO...

A cross sectional study of anemia and iron deficiency as risk factors for arsenic-induced skin lesions in Bangladeshi women

BMC Public Health, 2016

Background: In the Ganges Delta, chronic arsenic poisoning is a health concern affecting millions... more Background: In the Ganges Delta, chronic arsenic poisoning is a health concern affecting millions of people who rely on groundwater as their potable water source. The prevalence of anemia is also high in this region, particularly among women. Moreover, arsenic is known to affect heme synthesis and erythrocytes and the risk of arsenic-induced skin lesions appears to differ by sex. Methods: We conducted a case-control study in 147 arsenic-exposed Bangladeshi women to assess the association between anemia and arsenic-induced skin lesions. Results: We observed that the odds of arsenic-related skin lesions were approximately three times higher among women who were anemic (hemoglobin < 120 g/L) compared to women with normal hemoglobin levels [Odds Ratio (OR) = 3.32, 95 % Confidence Intervals (CI): 1.29, 8.52] after adjusting for arsenic levels in drinking water and other covariates. Furthermore, 75 % of the women with anemia had adequate iron stores (serum ferritin ≥12 μg/L), suggesting that the majority of anemia detected in this population was unrelated to iron depletion. Conclusions: Considering the magnitude of arsenic exposure and prevalence of anemia in Bangladeshi women, additional research is warranted that identifies the causes of anemia so that effective interventions can be implemented while arsenic remediation efforts continue.

Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework

Environmental science & technology, May 13, 2016

Driven by major scientific advances in analytical methods, biomonitoring, computational tools, an... more Driven by major scientific advances in analytical methods, biomonitoring, computational tools, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the "systems approaches" used in the biological sciences is a necessary step in this evolution. Here we propose the Aggregate Exposure Pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the Adverse Outcome Pathway (AOP) concept in the toxicological sciences. Aggregate…

Estimating effects of arsenic exposure during pregnancy on perinatal outcomes in a Bangladeshi cohort

Epidemiology (Cambridge, Mass.), Jan 18, 2015

The relationship between arsenic and birth weight is not well understood. To evaluate the causal ... more The relationship between arsenic and birth weight is not well understood. To evaluate the causal relationship between prenatal arsenic exposure and birth weight considering the potential mediation effects of gestational age and maternal weight gain during pregnancy using structural equation models (SEMs). A prospectively enrolled cohort of pregnant women was recruited in Bangladesh from 2008-2011. Arsenic was measured in personal drinking water at the time of enrollment (gestational age <16 weeks, N=1,140) and in toenails collected ≤1 month postpartum (N=624) using inductively coupled plasma mass spectrometry. SEMs estimated the direct and indirect effects of arsenic on birth weight with gestational age and maternal weight gain considered as mediating variables. Every unit increase in natural log water arsenic was indirectly associated with decreased birth weight (β=-19.17 grams, 95% CI: -24.64, -13.69) after adjusting for other risk factors. This association was mediated entirel...

Pigmentation changes as a result of arsenic exposure

Dermatotoxicology, 2012

A distinct and replicable variant of the squamous cell carcinoma gene inositol polyphosphate‐5‐phosphatase modifies the susceptibility of arsenic‐associated skin lesions in Bangladesh

Cancer, 2015

BACKGROUNDSingle‐nucleotide polymorphisms (SNPs) in inflammation, one‐carbon metabolism, and skin... more BACKGROUNDSingle‐nucleotide polymorphisms (SNPs) in inflammation, one‐carbon metabolism, and skin cancer genes might influence susceptibility to arsenic‐induced skin lesions.METHODSA case‐control study was conducted in Pabna, Bangladesh (2001‐2003), and the drinking‐water arsenic concentration was measured for each participant. A panel of 25 candidate SNPs was analyzed in 540 cases and 400 controls. Logistic regression was used to estimate the association between each SNP and the potential for gene‐environment interactions in the skin lesion risk, with adjustments for relevant covariates. Replication testing was conducted in an independent Bangladesh population with 488 cases and 2,794 controls.RESULTSIn the discovery population, genetic variants in the one‐carbon metabolism genes phosphatidylethanolamine N‐methyltransferase (rs2278952, P for interaction = .004; rs897453, P for interaction = .05) and dihydrofolate reductase (rs1650697, P for interaction = .02), the inflammation gene...

Correlation of Global and Gene-Specific DNA Methylation in Maternal-Infant Pairs

PLoS ONE, 2010

The inheritance of DNA methylation patterns is a popular theory to explain the influence of paren... more The inheritance of DNA methylation patterns is a popular theory to explain the influence of parental genetic and environmental factors on the phenotype of their offspring but few studies have examined this relationship in humans. Using 120 paired maternal-umbilical cord blood samples randomly selected from a prospective birth cohort in Bangladesh, we quantified DNA methylation by pyrosequencing seven CpG positions in the promoter region of p16, four CpG positions in the promoter region of p53, LINE-1 and Alu. Positive correlations were observed between maternal and umbilical cord blood at p16, LINE-1, and Alu but not p53. Multiple linear regression models observed a significant association between maternal and umbilical cord blood at LINE-1 and Alu (LINE-1: b = 0.63, p,0.0001; Alu: b = 0.28, p = 0.009). After adjusting for multiple comparisons, maternal methylation of p16 at position 4 significantly predicted methylation at the same position in umbilical cord blood (b = 0.43, p = ,0.0001). These models explained 48%, 5% and 16% of the observed variability in umbilical cord %5mC for LINE-1, Alu and p16 at position 4, respectively. These results suggest that DNA methylation in maternal blood was correlated with her offspring at LINE-1, Alu, and p16 but not p53. Additional studies are needed to confirm whether these observed associations were due to the inheritance of epigenetic events or the shared environment between mother and fetus. Future studies should also use a multi-generational family-based design that would quantify both maternal and paternal contributions to DNA methylation in offspring across more than one generation.

Genetic Susceptible Locus in NOTCH2 Interacts with Arsenic in Drinking Water on Risk of Type 2 Diabetes

PLoS ONE, 2013

Background: Chronic exposure to arsenic in drinking water is associated with increased risk of ty... more Background: Chronic exposure to arsenic in drinking water is associated with increased risk of type 2 diabetes mellitus (T2DM) but the underlying molecular mechanism remains unclear. Objectives: This study evaluated the interaction between single nucleotide polymorphisms (SNPs) in genes associated with diabetes and arsenic exposure in drinking water on the risk of developing T2DM. In 2009-2011, we conducted a follow up study of 957 Bangladeshi adults who participated in a case-control study of arsenic-induced skin lesions in 2001-2003. Logistic regression models were used to evaluate the association between 38 SNPs in 18 genes and risk of T2DM measured at follow up. T2DM was defined as having a blood hemoglobin A1C level greater than or equal to 6.5% at follow-up. Arsenic exposure was characterized by drinking water samples collected from participants' tubewells. False discovery rates were applied in the analysis to control for multiple comparisons. Results: Median arsenic levels in 2001-2003 were higher among diabetic participants compared with non-diabetic ones (71.6 mg/L vs. 12.5 mg/L, p-value ,0.001). Three SNPs in ADAMTS9 were nominally associated with increased risk of T2DM (rs17070905, Odds Ratio (OR) = 2.30, 95% confidence interval (CI) 1.17-4.50; rs17070967, OR = 2.02, 95%CI 1.00-4.06; rs6766801, OR = 2.33, 95%CI 1.18-4.60), but these associations did not reach the statistical significance after adjusting for multiple comparisons. A significant interaction between arsenic and NOTCH2 (rs699780) was observed which significantly increased the risk of T2DM (p for interaction = 0.003; q-value = 0.021). Further restricted analysis among participants exposed to water arsenic of less than 148 mg/L showed consistent results for interaction between the NOTCH2 variant and arsenic exposure on T2DM (p for interaction = 0.048; q-value = 0.004). Conclusions: These findings suggest that genetic variation in NOTCH2 increased susceptibility to T2DM among people exposed to inorganic arsenic. Additionally, genetic variants in ADAMTS9 may increase the risk of T2DM.

Association between total ingested arsenic and toenail arsenic concentrations

Journal of Environmental Science and Health, Part A, 2007

The association between arsenic exposure from drinking water and toenail arsenic concentrations a... more The association between arsenic exposure from drinking water and toenail arsenic concentrations appears to be non-linear at low exposure levels. To investigate whether this observation is a result exposure misclassification, a dietary exposure assessment was conducted in a cohort of 47 women concurrently enrolled in a prospective longitudinal biomonitoring study in Pabna, Bangladesh. Arsenic intake was evaluated using a duplicate diet study design which collected food and water samples for a total of 6 days. Total inorganic arsenic was measured in 24-hour composite food samples (N = 282) using inductively coupled plasma-mass spectrometry coupled with a dynamic reaction cell (ICP-DRC-MS). Average annual tubewell arsenic concentrations and toenail arsenic concentrations were computed for each participant using biomonitoring data from the prospective study. Separate multivariate regression models evaluated the association between drinking water, total dietary intake, and total dietary dose with toenail arsenic, a biomarker of internal dose. In these models, dietary intakes were adjusted using the residual method to provide estimate that was independent of water arsenic concentrations. Median daily arsenic intake from food and drinking water was 48.3 µg/day and 4.2 µg/day. Taking into consideration participant's body weight, the median daily arsenic dose was 1.0 µg/kg-day from food and 0.1 µg/kg-day from drinking water although drinking water exposure was highly skewed and was the dominant exposure route for the upper 25th percentile of the distribution. The regression model that used total daily arsenic intake from food (β = 0.46; 95%CI: 0.18-0.73) and drinking water (95%CI: 0.26-0.38) explained the most variability in toenail arsenic concentrations (R 2 a = 0.71). The effect estimates for food and drinking water are similar suggesting that both sources have a similar contribution to internal dose.

Environmental Arsenic Exposure and Diabetes

JAMA, 2008

Type 2 diabetes mellitus emerged as a pandemic in the later half of the 20th century. In the Unit... more Type 2 diabetes mellitus emerged as a pandemic in the later half of the 20th century. In the United States alone, diabetes affects an estimated 7.8% of the US population (24 million individuals) and its prevalence is projected to almost double in the next 25 years. The complications associated with diabetes including cardiovascular disease, retinopathy, nephropathy, neuropathy, and lower limb amputation profoundly affect the quality of life and contribute to the high morbidity and mortality associated with this disease. Diabetes is ranked as the seventh leading cause of death in the United States in 2006 2 ; the economic costs of diabetes are also high. Approximately $1 of every $10 in US health care expenditures can be attributed to the direct costs associated with diabetes. When indirect costs to caregivers are included, it is estimated that the annual cost of diabetes in the United States is $174 billion. Characterized by a combination of deficient insulin secretion and a diminished response to insulin at the target tissue, which can progress to hyperglycemia, the risk of type 2 diabetes increases with age, obesity, and sedentary lifestyle. Clinical trials have shown that lifestyle modification including weight reduction and increased physical activity can reduce the prevalence of type 2 diabetes by as much as 58%, 5 and now these 2 behavioral issues have become the cornerstone of diabetes prevention programs. Yet the etiology of type 2 diabetes remains poorly understood and the role of environmental pollutants, specifically arsenic, in diabetogenesis has received little attention by the medical community. This is somewhat surprising because arsenic exposure has been linked to type 2 diabetes since 1950 when a case report documented a patient developing type 2 diabetes after receiving intravenous arsenical treatment for sexually transmitted diseases. However, research efforts on the role of arsenic in diabetogenesis did not intensify until populationbased epidemiologic studies published in the 1990s from Taiwan 7-9 and Bangladesh 10 demonstrated that chronic exposure to high levels of arsenic from drinking water is associated with a higher prevalence of type 2 diabetes. While the findings of these studies were consistent and indicated a dose-response relationship between chronic arsenic exposure and type 2 diabetes, these populations were considered somewhat unique. A proportion of the populations from Taiwan and Bangladesh

The Dose-response Relationship Between Urinary Arsenic Metabolites and Skin Lesions Using a Pathway Approach

Epidemiology, 2011

Abstracts published in EPIDEMIOLOGY have been reviewed by the societies at whose meetings the abs... more

Age and Gender Modifies Dose-response Relationship Between Tubewell Arsenic Exposure and Toenail Arsenic Concentration

Epidemiology, 2011

Abstracts published in EPIDEMIOLOGY have been reviewed by the societies at whose meetings the abs... more