P-1050 - Maternal exposure to plasticizer compounds is inversely associated with gestational weight gain in women with obesity
Abstract Control Number
1282
Abstract Body
Background/Aims: Phthalates are endocrine disruptors with ubiquitous exposure in pregnant women, but their impact on maternal gestational weight gain (GWG) is unclear. We investigated associations of prenatal exposure with GWG and considered whether associations differed by maternal pre-pregnancy BMI (ppBMI). Methods: In 444 pregnant women from Champaign-Urbana, Illinois, we calculated GWG (kg) from self-reported pre-pregnancy weight and weight at median (range) 34 (29-38) weeks gestation. We quantified 19 phthalate/alternative metabolites in pools of five first-morning cross-pregnancy urines. These reflect exposures to 10 phthalates/alternatives as individual metabolites or molar sums of metabolites from the same phthalate/alternative [e.g. di(2-ethylhexyl) phthalate (SumDEHP), diisononyl phthalate (SumDiNP), di(2-ethylhexyl) terephthalate (SumDEHTP)]. We categorized ppBMI (kg/m2) as under-/normal weight (<25.0), overweight (25.0-29.9), and obese (≥30.0). We used linear regression to assess overall and ppBMI-stratified associations of ln-transformed specific gravity-adjusted biomarker concentrations with GWG, controlling for maternal age, race, ppBMI, parity, smoking status, diet quality, fetal sex, and gestational age at mid-to-late pregnancy weight. Results: These predominately Caucasian/White, college-educated women gained on average 12.1kg through mid-to-late pregnancy and >50% had a normal ppBMI. All women were exposed to measured chemicals, with similar concentrations to U.S. women. Overall, only SumDEHP and SumDEHTP were associated with GWG. Specifically, two-fold increases in SumDEHP and SumDEHTP were associated with 0.8kg lower GWG (95%CI: -1.5, -0.7 and -1.4, -0.2), respectively. However, when stratified by ppBMI, associations were strongest in obese women. Only in obese women, two-fold increases in SumDEHP and SumDiNP were associated with 1.9 and 1.3kg lower GWG, respectively. Similarly, in overweight and obese women, a two-fold increase in SumDEHTP was associated with 1.2 and 1.6kg lower GWG. Conclusions: In obese women, prenatal exposure to phthalates is associated with reduced GWG. Given the importance of appropriate GWG for fetal growth, especially in obese women, these findings should be corroborated in other populations.
P-0434 - Epidemiology of SARS-CoV-2 Antibodies among Firefighters/Paramedicsof a U.S. Fire Department
Abstract Control Number
3280
Abstract Body
Background/Aim: Given the high risk of hazardous biological exposures encountered by first responders during routine patient rescue, it is critically important that fire departments have access to accurate up-to-date information on workforce exposure, infection, and illness to inform the best possible decisions while serving their communities. We estimate the point seroprevalence of SARS-CoV-2 antibodies in a frontline firefighter/paramedic workforce of a South Florida fire department located in the epicenter of a State outbreak.
Methods: A cross-sectional study design was used to estimate the point seroprevalence of SARS-CoV-2 antibodies using a rapid IgM-IgG combined point-of-care lateral flow immunoassay among frontline firefighters/paramedics collected over a two-day period, April 16-17, 2020. Fire department personnel were emailed a survey link assessing COVID-19 symptoms and work exposures the day prior to the scheduled drive through antibody testing at a designated fire station. Off- and on-duty firefighter/paramedic personnel drove through the fire station/training facility in their personal vehicles or on-duty engine/rescue trucks for SARS-CoV-2 antibody testing. Three firefighters/paramedics did not participate because of scheduled vacation or religious reasons.
Results: Among the 203 firefighters/paramedics that make up the fire department workforce, 18 firefighters/paramedics (8.9%) tested positive for SARS-CoV-2 antibodies of which 8 firefighters/paramedics (3.9%) were IgG positive only, 8 (3.9%) were IgM positive only, and 2 (0.1%) were IgG/IgM positive. The proportion of firefighters/paramedics who reported symptoms in the 2 weeks prior to antibody testing was greater among those who were positive compared to firefighters/paramedics who were antibody negative (22.2% vs. 7.7%;p=0.041). None of the antibody positive firefighters/paramedics reported receipt of the annual flu vaccine compared to firefighters/paramedics who tested negative for SARS-CoV-2 antibodies (0.0% vs. 21.0%; p=.031).
Conclusions: Rapid SARS-CoV-2 IgM-IgG antibody testing documented early- and late-stage infection in a firefighter workforce providing insight to a broader medical surveillance project on return to work for firefighters/paramedics.
Methods: A cross-sectional study design was used to estimate the point seroprevalence of SARS-CoV-2 antibodies using a rapid IgM-IgG combined point-of-care lateral flow immunoassay among frontline firefighters/paramedics collected over a two-day period, April 16-17, 2020. Fire department personnel were emailed a survey link assessing COVID-19 symptoms and work exposures the day prior to the scheduled drive through antibody testing at a designated fire station. Off- and on-duty firefighter/paramedic personnel drove through the fire station/training facility in their personal vehicles or on-duty engine/rescue trucks for SARS-CoV-2 antibody testing. Three firefighters/paramedics did not participate because of scheduled vacation or religious reasons.
Results: Among the 203 firefighters/paramedics that make up the fire department workforce, 18 firefighters/paramedics (8.9%) tested positive for SARS-CoV-2 antibodies of which 8 firefighters/paramedics (3.9%) were IgG positive only, 8 (3.9%) were IgM positive only, and 2 (0.1%) were IgG/IgM positive. The proportion of firefighters/paramedics who reported symptoms in the 2 weeks prior to antibody testing was greater among those who were positive compared to firefighters/paramedics who were antibody negative (22.2% vs. 7.7%;p=0.041). None of the antibody positive firefighters/paramedics reported receipt of the annual flu vaccine compared to firefighters/paramedics who tested negative for SARS-CoV-2 antibodies (0.0% vs. 21.0%; p=.031).
Conclusions: Rapid SARS-CoV-2 IgM-IgG antibody testing documented early- and late-stage infection in a firefighter workforce providing insight to a broader medical surveillance project on return to work for firefighters/paramedics.
P-0707 - We need to know if the health effects of PM are driven by NLRP3
Abstract Control Number
2934
Abstract Body
Inflammasomes drive maturation of IL-1 family cytokines in reaction to Pathogen Associated Molecular Patterns (PAMPs). The NLRP3 inflammasome, uniquely, responds to Danger Associated Molecular Patterns (DAMPs) including particles of both endogenous (fatty acids, oxLDL, MSU, amyloid) and exogenous (silica, alum, fabricated NPs, ambient ultrafines) origin. Advancement of many chronic diseases - cardiovascular, neurological, metabolic and genetic - is driven by NLRP3. After Charles Dinarello illuminated the role of IL-1 cytokines, a team led by Hal Hoffman (UCSD) discovered the links between NLRP3 and genetic familial diseases (2000). Another team led by Jurg Tschopp and Fabio Martinon (Lausanne) coined the term “inflammasome” to describe molecular platforms that activate inflammatory caspases and drive maturation of IL1 cytokines (2002). Brooke Mossman et al (UVM) tied occupational particle and fiber exposures to NLRP3 (2008+). Paul Ridker’s CANTOS team has linked heart disease, lung cancer and CKD to NLRP3. AHA journals have 150+ papers. Teams at U Mass Worcester (Latz, Fitzgerald, Golenbock et al) and U Michigan (Nunez, Franchi et al) have discovered many of the mechanics of IL-1 sterile inflammation. Research is advancing in Brisbane AUS (Schroeder et al), Bonn GER (Latz et al) and Belfast IRE (Coll et al). Sharif, Wu et al (Harvard 2019) have a 3.8 A NLRP3 model. Inhibitors are a top pharma target. NLRP3 drives diseases of lifestyle and aging. And may underly estimated 2015 global PM2.5 mortalities of 9 million (Burnett 2018). There are a few studies on PM and NLRP3 (e.g., Villarreal Calderon 2012 and Cevallos 2017). And many on PM2.5, UFP and molecules tied to NLRP3 (IL-1b, IL-6, TNF, NFκB, etc.). Franklin Mangan and Latz (2016) have a solid review on crystals and NLRP3. We need to prioritize cohort, animal and cell studies of the relationship of NLRP3, PM and UFP.
P-0812 - Factors influencing household organophosphate pesticide levels in agricultural communities
Abstract Control Number
2823
Abstract Body
Background Organophosphate (OP) pesticide exposure is associated with various cancers, neurodegenerative diseases, and respiratory health outcomes. Proximity to agricultural operations and direct occupational contact are hypothesized to be important routes of exposure. Understanding these routes and exploring methods to estimate exposure will improve epidemiological studies, especially among agricultural communities where pesticide exposure due to drift and indirect contact is disproportionally high. To understand factors that influence household environmental exposures to OPs, we collected dust samples from homes in the Central Valley of California. We hypothesized that OP levels would be higher among samples collected during the agricultural spraying season and from homes in which a household member worked in agriculture. Methods Household dust samples were collected using a high-volume small surface sampler during the agricultural spraying (June) and non-spraying (January) seasons from 28 households located within 200 feet of agricultural fields. T-tests and paired t-tests were conducted to assess differences in total OP levels by occupational status and spraying season. Results A total of 50 samples were analyzed for the presence of OPs. Homes in which a household member worked in agriculture had significantly higher OP levels (130.0 parts per billion (ppb), SD 168.5), compared to homes without anyone working in agriculture (28.7 ppb, SD 24.2; p-value=0.001). No statistically significant differences were detected by spraying season (t=0.41, p-value = 0.69). Conclusions Our results demonstrate that detectable levels of OPs are prevalent in households within 200 feet of agricultural fields. Additionally, OPs may persist indoors for extended periods of time. Although the California Pesticide Use Registry indicates that OP application in our study area is seasonal, dust samples had similar levels across seasons. Our work will inform future research by revealing important factors related to routes of exposure to harmful pesticides experienced by agricultural workers and their families.
P-0536 - Placental cadmium, genetic variations, and birth size
Abstract Control Number
2291
Abstract Body
Background: While maternal cadmium (Cd) burden has been associated with fetal growth markers (including birth weight and head circumference), associations of placental Cd with birth size is less clear. Further, the role of genetics in these associations has not been examined. We investigated associations of placental Cd with birth size and the role of placental genotypes in this relationship. Methods: Participants were 527 mother-child pairs from the OMEGA and Placental Microarray studies. Placental Cd was measured using Agilent 7500 ICP-MS. Placental single nucleotide polymorphisms (13 SNPs) related to metal transport, growth regulation, endocrine response, and cell signaling were genotyped. Multivariable linear regression models were used to examine associations of placental Cd (quartiles) with birth weight, ponderal index and head circumference, adjusted for maternal covariates. Potential effect modification by infant sex or placental SNPs were examined using interaction terms and stratified analyses. Results: The mean maternal age and pre-pregnancy BMI were 33.7 years (SD=4.4) and 23.9 (SD=0.04) respectively. The mean Cd level in placenta was 0.0039 ng/mg tissue (SD=0.0027 ng/mg tissue). Placental Cd was not associated with birth weight (ß=7.579, 95%CI: -38.597, 53.755), ponderal index (ß=-0.015, 95%CI: -2.385, 2.355) or head circumference (ß=-0.095, 95%CI: -0.503, 0.313). SNPs were also not associated with placental Cd and interaction terms with infant sex or SNPs were not significant.Conclusions: In the current study, placental Cd was not associated with birth size or placental genotypes.
P-0998 - Effects of Fine Particulate Matter on Childhood Asthma Exacerbation in the Philadelphia Metropolitan Region
Abstract Control Number
2192
Abstract Body
Background: Fine particulate matter air pollution (PM2.5) is a known risk factor for asthma exacerbation. We aimed to describe the local association between PM2.5 and asthma exacerbation in the Philadelphia region, and to evaluate whether the effect is modified by children’s characteristics or other environmental exposures.
Methods: We conducted a time-stratified case-crossover study of pediatric asthma exacerbation (age ≤18 years) occurring from 2011-2014, identified through electronic health records (EHR) of the Children’s Hospital of Philadelphia (CHOP) Care Network. Modeled, census-tract level estimates of daily PM2.5 concentrations were acquired from the EPA’s Downscaler model. We applied conditional logistic regression to estimate the association within warm (Apr-Sep) and cold (Oct-Mar) months, with PM2.5 level modeled as a natural cubic spline (3 degrees of freedom), and adjusting for temperature, relative humidity, and holidays. We evaluated unlagged effects (i.e., PM2.5 levels on the same day as the exacerbation) and effects lagged up to 5 days.
Results: There were 54,632 asthma exacerbation events during the study period, with the majority occurring among male (60.75%) and black, non-Hispanic (58.99%) children. We found a positive association between PM2.5 and asthma exacerbation in both warm months (odds ratio [OR] comparing 90th to 25th percentile = 1.09, 95% confidence interval [CI]: 1.01-1.18, lag05) and cold months (OR, 90th vs. 25th percentile = 1.08, 95% CI: 1.04-1.12, lag0). During cold months, risk increases started from the lowest pollutant concentrations. Results were robust to multi-pollutant modeling and adjustment for additional covariates, and we found no effect modification by children’s characteristics (e.g., age, race/ethnicity, allergic rhinitis, eczema). During warm months, the PM2.5 effect was higher on days with detected tree pollen.
Conclusion: We found a positive association between PM2.5 and asthma exacerbation. Our results suggest that even small reductions in fine particulate matter air pollution may reduce clinical visits for asthma exacerbation.
Methods: We conducted a time-stratified case-crossover study of pediatric asthma exacerbation (age ≤18 years) occurring from 2011-2014, identified through electronic health records (EHR) of the Children’s Hospital of Philadelphia (CHOP) Care Network. Modeled, census-tract level estimates of daily PM2.5 concentrations were acquired from the EPA’s Downscaler model. We applied conditional logistic regression to estimate the association within warm (Apr-Sep) and cold (Oct-Mar) months, with PM2.5 level modeled as a natural cubic spline (3 degrees of freedom), and adjusting for temperature, relative humidity, and holidays. We evaluated unlagged effects (i.e., PM2.5 levels on the same day as the exacerbation) and effects lagged up to 5 days.
Results: There were 54,632 asthma exacerbation events during the study period, with the majority occurring among male (60.75%) and black, non-Hispanic (58.99%) children. We found a positive association between PM2.5 and asthma exacerbation in both warm months (odds ratio [OR] comparing 90th to 25th percentile = 1.09, 95% confidence interval [CI]: 1.01-1.18, lag05) and cold months (OR, 90th vs. 25th percentile = 1.08, 95% CI: 1.04-1.12, lag0). During cold months, risk increases started from the lowest pollutant concentrations. Results were robust to multi-pollutant modeling and adjustment for additional covariates, and we found no effect modification by children’s characteristics (e.g., age, race/ethnicity, allergic rhinitis, eczema). During warm months, the PM2.5 effect was higher on days with detected tree pollen.
Conclusion: We found a positive association between PM2.5 and asthma exacerbation. Our results suggest that even small reductions in fine particulate matter air pollution may reduce clinical visits for asthma exacerbation.
P-0965 - Short-term effects of ambient particles on mortality in Italy - a national approach
Abstract Control Number
2063
Abstract Body
Background. Short-term exposure to particulate matter (PM) has been related to mortality worldwide. Most evidence comes from studies conducted in major cities, while little is known on the effects of low concentrations of PM and in less urbanized areas. We aim to investigate the relationship between PM and all-cause mortality at national level in Italy.Methods. Daily numbers of all-cause mortality were collected for all 8,092 municipalities of Italy, from 2006 to 2015. A satellite-based spatiotemporal model was developed to estimate daily PM10 (inhalable particles) and PM2.5 (fine particles) concentrations at 1-km resolution. Multivariate Poisson regression models were fit to estimate the association between daily PM and mortality at province level, then results were pooled with a random-effects meta-analysis. Associations were estimated by age, sex and degree of urbanization of the municipalities. Flexible functions were estimated to explore the shape of the associations at low PM concentrations.Results. We analyzed 6,552,257 deaths (40% among subjects older than 85 years, 55% occurring outside the main urban areas). National daily mean (interquartile range) PM10 and PM2.5 concentrations were 23 (12) μg/m3 and 17 (9) μg/m3, respectively. Relative increases of mortality, per 10 μg/m3 variation in lag 0-5 (average of last six days since death) PM10 and PM2.5, were 0.80% (95% Confidence Intervals [CI]: 0.58%, 1.01%) and 0.72% (0.34%, 1.09%) respectively. Associations were highest among elderly and women, similar between rural and urbanized areas, and were present even at low concentrations, e.g. below WHO guidelines. Conclusions. Air pollution was robustly associated with peaks in daily all-cause mortality in Italy, both in large cities and in less urbanized areas of Italy. Current WHO Air Quality Guidelines for PM10 and PM2.5 are not sufficient to protect public health.
P-0858 - PFAS Research, Education, and Action for Community Health
Abstract Control Number
1957
Abstract Body
Communities across the U.S are discovering drinking water contaminated by per- and polyfluoroalkyl substances (PFAS), a group of man-made chemicals widely used in industrial processes and consumer goods. There are currently no federal PFAS drinking water standards in the U.S. despite growing evidence from epidemiological and toxicological studies showing associations between PFAS exposure and a wide range of harmful health effects, including on children’s immune systems. This project will characterize early-life PFAS exposure from firefighting foam-contaminated drinking water among U.S. children using serum biomarkers and will evaluate associations with antibody levels in response to routine vaccinations and metabolomic markers of inflammation. The project will address other important gaps, such as the difficulty for residents of affected communities to interpret blood and water testing results, the absence of a centralized way to connect affected communities, and a lack of understanding of potential health effects from unregulated contaminant exposures by medical professionals. PFAS-REACH (Research, Education, and Action for Community Health) is helping address these gaps by: 1. Evaluating potential effects of PFAS exposure on immune systems of young children at Pease Tradeport in Portsmouth, New Hampshire, and Hyannis, Massachusetts, communities with previous PFAS water contamination; 2. Developing an innovative online resource center, called the PFAS Exchange, with data interpretation tools and educational materials for affected community members, including guidance for medical professionals on how to best respond to patient contamination concerns; and 3. Conducting a social science analysis to assess individual, family, and community-level experiences in areas impacted by PFAS-contaminated drinking water. PFAS-REACH is using a community-based participatory research approach. Project partners include environmental health researchers, social scientists, and community activists. This project will provide both actionable results to protect children’s health and support to help impacted communities reduce their exposures and health risk.
P-0244 - Early-life air pollution exposure and biomarkers of systemic inflammation in young children
Abstract Control Number
1857
Abstract Body
Background/Aims. Air pollution exposure has been associated with adverse health effects in children. Although the exact underlying mechanisms are not clarified, systemic inflammation may play a role in pollution-induced health effects. This study aimed to investigate inflammatory markers in children in relation to early-life air pollution exposure. Methods. We measured 92 inflammatory markers in plasma samples collected at ages 6 months, 1 and 2 years from healthy children residing in Stockholm, Sweden (n=108), using Olink Proteomics (Uppsala, Sweden). Residential time-weighted average (TWA) outdoor exposure to particulate matter with an aerodynamic diameter of <10 μm (PM10) and <2.5 μm (PM2.5), black carbon (BC), nitrogen oxides (NOx) and nitrogen dioxide (NO2) from birth up to age 6 months was estimated by dispersion modeling. Age-specific associations between TWA air pollution exposures and inflammatory markers were investigated using linear regression with inclusion of potential confounding variables. Further, we applied linear mixed-effect models to analyze the temporal patterns of biomarkers during the first 2 years of life in relation to early-life air pollution exposure. Multiple comparisons were accounted for using False Discovery Rate (FDR 5%) adjustment. Results. At age 1 year, tumor necrosis factor (TNF) and chemokine ligand 9 (CXCL9) were inversely associated with TWA exposure to NO2, NOx, and BC (FDR p-value<0.05). However, no clear association was found at ages 6 months or 2 years. In the mixed models, only TNF was associated with NO2, NOx, and BC, but the associations were not significant after adjustment for multiple testing. Conclusions: Our findings suggest that air pollution exposure during the first 6 months of life is related to certain markers of systemic inflammation in children at age 1 year. These markers may be involved in biological processes through which air pollution exposure may modulate systemic inflammation in infants.
P-1144 - GEOHealth Hub Colombia: achievements and challenges of an environmental and occupational health collaboration initiative
Abstract Control Number
1728
Abstract Body
The Global Environmental and Occupational (GEO) Health Hub Colombia is a collaboration initiative between academics and professionals from public and private institutions. The objective of this initiative is to promote high quality research, training, and discussion around fundamental topics of environmental and occupational health in the country, and to provide advice for the formulation of sound policies regarding high-priority environmental and occupational health threats.
The GEOHealth Hub Colombia began in 2012 as a bi-national project between Colombia and the United States, funded under the GEOHealth program of the National Health Institute / Fogarty International Center. The project identified environmental and occupational health experts in the country, who contributed to identify research and training needs in this area. Since 2015 the GEOHealth Hub Colombia has been working to promote collaborative research between different regions of the country and internationally. One of the main achievements has been to scale up local problemas to the national level and develop multicity research projects, including activities of Colombian peace process related with socioenvironmental topics. Recently, the GEO Health Hub Colombia was awarded the first and only environmental health research program funded by the Colombian Government. The program will be conducted with the collaboration of 10 local universities, regional and national health and environmental authorities, and academic institutions from Brazil, Canada, and Mexico. The main challenge of the research collaboration is the lack of a common platform for exchanging data, ideas, discussions, and to provide information to the different audiences: academics, policy makers, and community.
The GEOHealth Hub Colombia also has generated discussion spaces and position public documents related to environmental threats, such us the use of aerial spray of glyphosate to eliminate illicit crops in rural areas. In this regard, support of international societies is needed to face GEO threats in developing countries.
The GEOHealth Hub Colombia began in 2012 as a bi-national project between Colombia and the United States, funded under the GEOHealth program of the National Health Institute / Fogarty International Center. The project identified environmental and occupational health experts in the country, who contributed to identify research and training needs in this area. Since 2015 the GEOHealth Hub Colombia has been working to promote collaborative research between different regions of the country and internationally. One of the main achievements has been to scale up local problemas to the national level and develop multicity research projects, including activities of Colombian peace process related with socioenvironmental topics. Recently, the GEO Health Hub Colombia was awarded the first and only environmental health research program funded by the Colombian Government. The program will be conducted with the collaboration of 10 local universities, regional and national health and environmental authorities, and academic institutions from Brazil, Canada, and Mexico. The main challenge of the research collaboration is the lack of a common platform for exchanging data, ideas, discussions, and to provide information to the different audiences: academics, policy makers, and community.
The GEOHealth Hub Colombia also has generated discussion spaces and position public documents related to environmental threats, such us the use of aerial spray of glyphosate to eliminate illicit crops in rural areas. In this regard, support of international societies is needed to face GEO threats in developing countries.
P-0528 - Effects of prenatal lead exposure on child’s DNA methylation: methylation distribution-specific epigenome-wide association study (MDS-EWAS)
Abstract Control Number
2035
Abstract Body
BACKGROUND: Epigenome-wide association studies (EWAS) frequently use linear regression analysis assuming that methylation levels are continuous variables between 0 and 1 with a unimodal distribution. While 2~5% of CpG sites are known to have bimodal or trimodal (multimodal) distributions, such modality differences are seldom considered in previous EWAS. OBJECTIVES: We have developed a novel EWAS model which takes the distribution of methylation levels into account, namely “methylation distribution-specific (MDS)-EWAS”. METHODS: Blood lead levels were measured from pregnant women at 2nd trimester in the Environment and Development in Children cohort. Methylation profiles were analyzed from sixty 2-year-old children’s blood samples, using the Illumina Infinium HumanMethylation EPIC BeadChip providing 865,688 CpG probes. For conventional EWAS, linear regression was applied to investigate the association between prenatal lead exposure and DNA methylation status at age 2 with covariates adjusted. For MDS-EWAS, unimodal and multimodal CpG sites were classified by dip test. Then, linear regression was applied for unimodal CpG sites. Among multimodal CpG sites, methylation levels at bimodal and trimodal CpG sites were transformed into binary (0 or 1) and categorical (0, 1, or 2) variables, respectively, followed by logistic regression. RESULTS: Out of 865,688 CpG sites, 17,852 CpG sites (2.06%) showed multimodal distribution. After excluding single nucleotide polymorphism-associated CpG sites, conventional EWAS showed no significant results. MDS-EWAS, however, showed two multimodal CpG sites positively associated with prenatal lead level: cg08989084 (P2RX2 coding for ion channels in neuronal signaling)(estimate: 0.00101, p-value: 3.52x10-5) and cg23620282 (IRX4 reported to interact with vitamin D receptor in suppression of
cancer)(estimate: 0.000133, p-value:4.17x10-5)(both FDR corrected p-value <0.05). CONCLUSION: MDS-EWAS may provide a more appropriate statistical model based on actual distributions of methylation status, and may be more sensitive in detecting CpG sites associated with environmental exposures.
cancer)(estimate: 0.000133, p-value:4.17x10-5)(both FDR corrected p-value <0.05). CONCLUSION: MDS-EWAS may provide a more appropriate statistical model based on actual distributions of methylation status, and may be more sensitive in detecting CpG sites associated with environmental exposures.
P-0111 - Metals and breast cancer risk: a prospective study using toenail metal biomarkers
Abstract Control Number
1510
Abstract Body
Background: Certain metals are known or suspected carcinogens and have been found in breast tissue samples. Toenails are a stable matrix that reflect exposure 6-12 months before collection and measurements correlate well over time. We prospectively examined a large panel of toenail metals in relation to breast cancer risk and were the first to consider whether multiple metal biomarkers jointly influence risk. Methods: The Sister Study is prospective cohort of 50,884 women who enrolled between 2003-2009 with follow-up for breast cancer through September 2016. We measured 15 metals in toenails collected at enrollment using a case-cohort design of 1,495 cases and a randomly-selected sub-cohort of 1,605 women. For individual metals, multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression with robust variance. We examined associations overall and stratified by race, estrogen receptor (ER), and menopausal status. Quantile g-computation was used to examine joint associations between multiple metals and breast cancer risk. Results: In individual metal models, arsenic was associated with a non-linear increase in breast cancer risk (2nd vs. 1st tertile, HR=1.22; 95% CI: 1.01-1.49). This association was stronger for ER+ breast cancer (HR=1.31; 95% CI: 1.06-1.62). In non-Hispanic Blacks, zinc was associated with an elevated risk (3rd vs. 1st tertile, HR=1.40; 95% CI: 0.97-2.02). Molybdenum was inversely associated with breast cancer overall (3rd vs. 1st tertile, HR=0.83; 95% CI: 0.68-1.00) and particularly for ER- breast cancer (3rd vs. 1st tertile, HR=0.57; 95% CI: 0.37-0.87). A simultaneous increase in multiple metals was not associated with breast cancer risk. Conclusions: In this prospective study considering multiple toenail metals in relation to breast cancer, we found that individual metals and metal mixtures were not consistently associated with a higher risk. However, a few metals appeared to be related to breast cancer risk in certain subgroups.