Role Of Environmental Exposures Research Articles

The Role of Environmental Exposures on Survival After Non-Small Cell Lung Cancer Resection

BackgroundSocioeconomic status and pollution exposure have been described as risk factors for poor survival in patients with non-small cell lung cancer (NSCLC). However, the relationship between these factors is complex and inadequately studied. This study aimed to evaluate the relationship between environmental and social factors and their impact on survival after NSCLC resection. MethodsA prospective database for all patients with NSCLC who underwent primary resection from 2006 to 2021 was analyzed. Ambient fine particulate matter (air pollution smaller than 2.5 μm [PM2.5]), greenness, and deprivation index (a measure of neighborhood-level material deprivation composed of 6 factors) were linked to individual patients by geocoding their residential address. ResultsA total of 661 patients who underwent pulmonary resection for NSCLC were evaluated. Black patients had increased levels of community deprivation compared with White patients; however, there was no difference in PM2.5 exposure or overall survival between races. Increased PM2.5 exposure was an independent predictor of worse survival on univariable and multivariable analysis (hazard ratio, 1.06; P = .003). ConclusionsIncreased PM2.5 exposure is associated with worse overall survival in resected NSCLC and was a more significant factor than race and material deprivation in this population. Interventions to reduce environmental air pollution could improve lung cancer survival.

Association between early life exposure to agriculture, biodiversity, and green space and risk of inflammatory bowel disease: a population-based cohort study

Specific pollutants and environmental exposures are implicated in modulating inflammatory bowel disease (IBD) risk. However, the role of environmental exposures, particularly during the early life period, towards IBD risk, has not been systematically evaluated. We conducted a nationwide population-based cohort study during the study period extending from January 1, 1995, to September 1, 2020, using cross-linked Danish registers, maps, and inventories to ascertain the impact of agricultural land use, biodiversity, green space, urban space, blue space, and normalized difference vegetation index during pregnancy and the first two years of life on IBD, Crohn's disease (CD), and ulcerative colitis (UC) risk, using adjusted Cox proportional hazards regression analyses. We adjusted for covariates sex, maternal age at delivery, calendar year of birth, municipal-level socioeconomic status, and first-degree relative with IBD. Of 1,438,487 individuals included in the study who were followed from age 2 years until a median (IQR) age of 14 (8-20) years, 3768 individuals were diagnosed with IBD. Exposure to the second, third and highest quartiles of agriculture land use during early life, relative to the lowest quartile, were associated with increased CD risk (aHR 1.12, 95% CI 1.01, 1.26, 1.19, 95% CI 1.05, 1.34 and, 1.24 95% CI 1.06, 1.46, respectively). There was no association of agriculture land use with UC risk. Conversely, exposure to the third quartile of biodiversity in early life, compared to the lowest quartile, were associated with a lower CD risk (aHR 0.86, 95% CI 0.75, 0.98). A protective effect of greenspace was noted in the highest quartile for CD (aHR 0.87, 95% CI 0.78, 0.98). In a nationwide cohort with long-term follow up data, early life environmental exposures were associated with modulation of CD risk, with a harmful effect of agriculture land use and protective effect of biodiversity and green space. Danish National Research Foundation, the International Organization for the Study of Inflammatory Bowel Disease, the National Institute of Diabetes and Digestive and Kidney Diseases.

P1093 Early life exposure to agriculture and biodiversity influences Crohn’s disease risk in a population-based cohort study

Abstract Background Specific pollutants and environmental exposures are implicated in modulating inflammatory bowel disease (IBD) risk. Crohn’s disease (CD) clustering has been reported in agricultural areas. However, the role of environmental exposures, particularly in early life, towards IBD risk, has not been systematically evaluated. Methods We conducted a nationwide population-based cohort study during the study period extending from January 1, 1995, to September 1, 2020, using cross-linked Danish registers, maps, and inventories to ascertain the impact of agricultural land use, biodiversity, green space, urban space, blue space, and natural vegetation density index during pregnancy and the first two years of life on IBD, CD, and ulcerative colitis (UC) risk, using adjusted Cox proportional hazards regression analyses. We adjusted for the following covariates: sex, maternal age at delivery, calendar year of birth, municipal-level socioeconomic status, and first-degree relative with IBD. Results Of 1,438,487 individuals included in the study who were followed from age 2 years until a median (IQR) age of 14 (8-20) years, 3,768 individuals were diagnosed with IBD. Exposure to the highest and third quartiles of agriculture land use during early life, relative to the lowest quartile, were associated with increased IBD risk (aHR 1.16, 95% CI 1.02, 1.31 and 1.19, 95% CI 1.07, 1.32, respectively). Conversely, exposure to the highest and third quartiles of biodiversity in early life, compared to the lowest quartile, were associated with a lower IBD risk (aHR 0.90, 95% CI 0.82, 1.00 and 0.90, 95% CI 0.82, 0.99, respectively). These associations were driven by differences in CD risk (Figure), but there was no association with UC risk. Other environmental exposures were not associated with IBD risk. Conclusion In a nationwide cohort with long-term follow up data, early life exposure to agriculture land use was associated with an increase in CD risk, while higher biodiversity was protective.

Exposure to per- and polyfluoroalkyl substances in early pregnancy and risk of cerebral palsy in children

BackgroundMost cerebral palsy (CP) cases have an unexplained etiology, but a role for environmental exposures has been suggested. One purported environmental risk factor is exposure to endocrine-disrupting pollutants specifically per- and polyfluoroalkyl substances (PFAS). ObjectivesWe investigated the association between prenatal PFAS exposures and CP in Swedish children. MethodsIn this case-control study, 322 CP cases, 343 population controls, and 258 preterm controls were identified from a birth registry in combination with a CP follow-up program from 1995 to 2014 and linked to a biobank which contains serum samples from week 10–14 of pregnancy. Maternal serum concentrations of four PFAS compounds: perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctane sulfonate (PFOS) were analyzed using liquid chromatography-tandem-mass-spectrometry. We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for CP and each PFAS in quartiles and as continuous variables controlling for various sociodemographic and lifestyle factors. ResultsIn crude and adjusted analyses, we did not find consistent evidence of associations between serum PFHxS, PFOA, PFNA, PFOS and concentrations in early pregnancy and CP, except in preterm infants. The ORs comparing the highest PFAS quartiles to the lowest were 1.05 (95 % CI: 0.63–1.76), 0.96 (95 % CI: 0.55–1.68), 0.71 (95 % CI: 0.41–1.25), and 1.17 (95 % CI: 0.61–2.26), for PFHxS, PFOA, PFNA, and PFOS, respectively. Some positive associations were observed for preterm infants, but the results were imprecise. Similar patterns were observed in analyses treating PFAS as continuous variables. ConclusionsIn this study, we found little evidence that early pregnancy prenatal exposure to PFHxS, PFOA, PFNA, or PFOS increases the risk of CP. However, some positive associations were observed for preterm cases and warrant further investigation.

A Review on The Role of Environmental Exposures in IgG4-Related Diseases.

Immunoglobulin G4-related diseases (IgG4-RDs) are immune-mediated fibroinflammatory multisystemic conditions identified by the presence of tumefactive lesions with a rich infiltrate of IgG4-positive plasma cells, and often by a high IgG4 serum concentration. IgG-RDs have a prevalence of at least 1 case every 100,000 persons, and they are mostly diagnosed after age 50, with a male to female ratio of about 3:1. IgG4-RD pathophysiology is still uncertain: it has been proposed that both genetic predisposition and chronic environmental exposures may play a role by triggering abnormal immune activation that perpetuates the disease. The purpose of this review is to summarize the evidences supporting the hypothesis that certain environmental/occupational exposures can trigger IgG4-RDs, focusing on the possible role of asbestos in an emerging IgG4-RD called idiopathic retroperitoneal fibrosis (IRF). Although some studies suggested a relationship between tobacco smoking and IgG4-RD risk, occupational exposures seem to have the most interesting effects. Positive history of blue-collar work increases the risk of developing an IgG4-RD, and mineral dusts and asbestos were the most strongly associated industrial compounds. Asbestos has been found to be a risk factor for IRF years before its classification as IgG4-RD, and later in two large case-control studies. In the most recent one, conducted on 90 patients and 270 controls, asbestos exposure conferred an increased IRF risk, quantified by odds ratios from 2.46 to 7.07. Further structured studies including serum IgG4 evaluation should be conducted to clarify the effect of asbestos on patients with confirmed diagnosis of IgG4-related IRF. Environmental exposures, especially of occupational origin, appear to play a role in the development of different types of IgG-RDs. In particular, although first suggested very recently, the relationship between asbestos and IRF deserves to be explored in more structured studies, especially because of the biological plausibility of the role of asbestos in IRF pathogenesis.

Precision and personalized medicine: What their current definition says and silences about the model of health they promote. Implication for the development of personalized health.

The US National Human Genome Research Institute defines precision medicine as follows: "Precision medicine (generally considered analogous to personalized medicine or individualized medicine) is an innovative approach that uses information about an individual's genomic, environmental, and lifestyle information to guide decisions related to their medical management. The goal of precision medicine is to provide a more precise approach for the prevention, diagnosis, and treatment of disease." In this perspective article, we question this definition of precision medicine and the risks linked to its current practice and development. We highlight that in practice, precision medicine is based on the use of large volumes of biological data for individual purposes mostly in line with the biomedical model of health, which carries the risk of the biological reductionism of the person. A more comprehensive, precise, and even "personal" approach to health would require taking into account environmental, socio-economic, psychological, and biological determinants, an approach more in line with the biopsychosocial model of health. The role of environmental exposures, in a broad sense, is highlighted more and more, notably in the field of exposome research. Not considering the conceptual framework in which precision medicine is deployed leads to the concealment of the different responsibilities that can be mobilized within the health system. Anchoring precision medicine in a model that does not limit its definition to its biological and technical components makes it possible to envisage a personalized and more precise medicine, integrating a greater share of interventions centered on the skills and life contexts of individuals.

Toxicoproteomics of Mono(2-ethylhexyl) phthalate and Perfluorooctanesulfonic Acid in Models of Prostatic Diseases.

Benign and malignant prostatic diseases are common, costly, and burdensome; moreover, they share fundamental underlying molecular processes. Several ubiquitous contaminants may perturb these processes, possibly via peroxisome proliferator-activated receptor (PPAR) signaling, but the role of environmental exposures─particularly mixtures─in prostatic diseases is undefined. In the present study, nontumorigenic prostate stromal cells and metastatic prostate epithelial cells were exposed to ubiquitous exogenous PPAR ligands under different dosing paradigms, including a mixture, and effects were assessed via mass spectrometry-based global proteomics. In prostate stromal cells, environmentally relevant levels of mono(2-ethylhexyl) phthalate (MEHP), alone and in combination with perfluorooctanesulfonic acid, led to significant changes in proteins involved in key processes underlying prostatic diseases: oxidative stress defense, proteostasis, damage-associated molecular pattern signaling, and innate immune response signaling. A follow-up experiment in metastatic prostate epithelial cells showed that the occupationally relevant levels of MEHP perturbed similar processes, including lipid, cholesterol, steroid, and alcohol metabolism; apoptosis and coagulation regulation; wound response; and aging. This work shows that environmental exposures may contribute to prostatic diseases by perturbing key processes of a proposed adverse outcome pathway, including lipid metabolism, oxidative stress, and inflammation. Future in vivo research will investigate the role of contaminants in prostatic diseases and in preventative agents.

Epigenetics Beyond Fetal Growth Restriction: A Comprehensive Overview.

Fetal growth restriction is a pathological condition occurring when the fetus does not reach the genetically determined growth potential. The etiology of fetal growth restriction is expected to be multifactorial and include fetal, maternal, and placental factors, the latter being the most frequent cause of isolated fetal growth restriction. Severe fetal growth restriction has been related to both an increased risk of perinatal morbidity and mortality, and also a greater susceptibility to developing diseases (especially cardio-metabolic and neurologicaldisorders) later in life. In the last decade, emerging evidence has supported the hypothesis of the Developmental Origin of Health and Disease, which states that individual developmental 'programming' takes place via a delicate fine tuning of fetal genetic and epigenetic marks in response to a large variety of 'stressor' exposures during pregnancy. As the placenta is the maternal-fetal interface, it has a crucial role in fetal programming, such that any perturbation altering placental function interferes with both in-utero fetal growth and also with the adult life phenotype. Several epigenetic mechanisms have been highlighted in modulating the dynamic placental epigenome, including alterations in DNA methylation status, post-translational modification of histones, and non-coding RNAs. This review aims to provide a comprehensive and critical overview of the available literature on the epigenetic background of fetal growth restriction. A targeted research strategy was performed using PubMed, MEDLINE, Embase, and The Cochrane Library up to January 2022. A detailed and fully referenced synthesis of available literature following the Scale for the Assessment of Narrative Review Articles guidelines is provided. A variety of epigenetic marks predominantly interfering with placental development, function, and metabolism were found to be potentially associated with fetal growth restriction. Available evidence on the role of environmental exposures in shaping the placental epigenome and the fetal phenotype were also critically discussed. Because of the highly dynamic crosstalk between epigenetic mechanisms and the extra level of complexity in interpreting the final placental transcriptome, a full comprehension of these phenomenon is still lacking and advances in multi-omics approaches are urgently needed. Elucidating the role of epigenetics in the developmental origins of health and disease represents a new challenge for the coming years, with the goal of providing early interventions and prevention strategies and, hopefully, new treatment opportunities.

The role of environmental exposures and gene-environment interactions in the etiology of systemic lupus erythematous.

Systemic lupus erythematosus (SLE) is a complex, chronic autoimmune disease, whose etiology includes both genetic and environmental factors. Individual genetic risk factors likely only account for about one-third of observed heritability among individuals with a family history of SLE. A large portion of the remaining risk may be attributable to environmental exposures and gene-environment interactions. This review focuses on SLE risk associated with environmental factors, ranging from chemical and physical environmental exposures to lifestyle behaviors, with the weight of evidence supporting positive associations between SLE and occupational exposure to crystalline silica, current smoking, and exogenous estrogens (e.g., oral contraceptives and postmenopausal hormones). Other risk factors may include lifestyle behaviors (e.g., dietary intake and sleep) and other exposures (e.g., ultraviolet [UV] radiation, air pollution, solvents, pesticides, vaccines and medications, and infections). Alcohol use may be associated with decreased SLE risk. We also describe the more limited body of knowledge on gene-environment interactions and SLE risk, including IL-10, ESR1, IL-33, ITGAM, and NAT2 and observed interactions with smoking, UV exposure, and alcohol. Understanding genetic and environmental risk factors for SLE, and how they may interact, can help to elucidate SLE pathogenesis and its clinical heterogeneity. Ultimately, this knowledge may facilitate the development of preventive interventions that address modifiable risk factors in susceptible individuals and vulnerable populations.

Prevalence of ANCA-associated vasculitis amid natural gas drilling sites in West Virginia

The epidemiology of ANCA-associated vasculitis (AAV) varies by ethnicity and region. Environmental exposure has been implicated in the pathophysiology of MPO-AAV. The aim of this study was to evaluate the epidemiology of AAV and explore a potential relationship with environmental factors in north central West Virginia. This is a retrospective cohort study of 212 patients diagnosed with AAV at West Virginia University and its affiliated hospitals from January 1, 1990 to December 31, 2019. We assessed prevalence of AAV over time according to patient's zip codes and counties. Silica exposure through natural gas extraction was considered as a possible environmental factor. The proportion of patients with MPO-ANCA increased after 2010 (37.5% before 2010 vs 61% after 2010, p = 0.008). At the same time, the prevalence of AAV in Monongalia and surrounding counties has increased significantly after 2010 from 64.8 to 141.9 cases per million (p = 0.001). The increase in prevalence of AAV was primarily due to an increase in MPO-AAV (43 vs 101.7 cases per million before and after 2010, respectively, p = 0.028). During this time, the production of natural gas through fracking increased, rising more than tenfold after 2010 (p-value < 0.001). Heat mapping reveals that the increase in cases of AAV occurred in areas of increased fracking activity. There was an increase in the prevalence of patients who were newly diagnosed with AAV over time in north central West Virginia. Further studies are required to ascertain the potential role of environmental exposure in the pathophysiology of AAV.

ЛЕГЕНЕВИЙ СИНДРОМ «ГАРЯЧОЇ ВАННИ»

HOT TUB LUNG Y. O. Dziublyk Abstract This review deals with current approaches to etiology, pathogenesis, clinical features and diagnostics of hot tub lung. The aim of the report is to extend the knowledge of practicing physicians in the area of interstitial lung diseases considering possible role of environmental exposures. Hot tub lung is a granulomatous lung disease, resulted in hyperreactive response of immune system to airborne exposure with nontuberculous mycobacteria (NTM). ATS diagnostic criteria for hot tub lung include the sub-acute onset of respiratory symptoms associated with hot tub exposure, positive mycobacterial cultures from respiratory and water samples, and characteristic radiographic findings. Treatment of this condition rests on avoidance of exposure with bacterial antigens and a trial of corticosteroid therapy. Better understanding of this pathology would help physician with sometimes difficult differential diagnosis of interstitial lung diseases. Key words: hot tub lung, nontuberculous mycobacteria, hypersensitivity pneumonitis. Ukr. Pulmonol. J. 2022;30(1):25–29.

Coronavirus Disease 2019–Associated Mucormycosis: Risk Factors and Mechanisms of Disease

The severe surge of COVID-19 cases in the Indian subcontinent in early 2021 was marked by an unusually high number of cases of COVID-19 associated mucormycosis (CAM) reported during this period. This is significantly higher than predicted based on available data about prevalence or risk factors for this condition. This may be from an unusual alignment of multiple risk factors for this condition. There is high background prevalence of mucormycosis in India probably from high prevalence of risk factors, including undiagnosed or poorly controlled diabetes. COVID-19 induced immune dysregulation, and immune suppression from steroid therapy increase the risk. The role of environmental exposure is unclear. System factors like lack of access to healthcare during a pandemic may result in delayed diagnosis or suboptimal management with potentially poor outcomes. This is a review of currently identified risk factors and pathogenesis of CAM in a pandemic surge.

Exposure to perfluoroalkyl substances in early pregnancy and risk of sporadic first trimester miscarriage

Many first trimester sporadic miscarriages are unexplained and the role of environmental exposures is unknown. The present aim was to study if levels of Perfluoroalkyl substances (PFASs) in early pregnancy are associated with unexplained, sporadic first trimester miscarriage. The study was performed within the Swedish SELMA pregnancy cohort. Seventy-eight women with non-recurrent first trimester miscarriage were included and 1449 women were available as live birth controls. Eight PFASs were measured in first trimester serum. A doubling of perfluorooctanoic acid (PFOA) exposure, corresponding to an inter-quartile increase, was associated with an odds ratio (95%CI) for miscarriage of 1.48 (1.09–2.01) when adjusting for parity, age and smoking. Analyses per quartiles of PFOA exposure indicated a monotonic dose response association with miscarriage. A similar, but not significant, pattern was observed for perfluorononanoic acid (PFNA). For other PFAS, there were no associations with miscarriage. We have previously shown associations between early pregnancy PFAS exposures and preeclampsia, as well as lower birth weight. Now we report an association between PFOA and miscarriage within the same cohort, which may suggest shared but unknown mechanisms. The study can only represent a period of early placentation and clinical pregnancy loss during the second half of the first trimester.

A time series analysis of the ecologic relationship between acute and intermediate PM2.5 exposure duration on neonatal intensive care unit admissions in Florida

Admissions of newborn infants into Neonatal Intensive Care Units (NICU) has increased in the US over the last decade yet the role of environmental exposures as a risk factor for NICU admissions is under studied. Our study aims to determine the ecologic association between acute and intermediate ambient PM2.5 exposure durations and rates of NICU admissions, and to explore whether this association differs by area-level social stressors and meteorological factors. We conducted an ecologic time-series analysis of singleton neonates (N = 1,027,797) born in Florida hospitals between December 26, 2011 to April 30, 2019. We used electronic medical records (EMRs) in the OneFlorida Data Trust and included infants with a ZIP code in a Metropolitan Statistical Areas (MSA) and excluded extreme preterm births (<24wks gestation). The study outcome is the number of daily NICU admission at 28 days old or younger for each ZIP code in the study area. The exposures of interest are average same day, 1- and 2-day lags, and 1–3 weeks ambient PM2.5 concentration at the ZIP code-level estimated using inverse distance weighting (IDW) for each day of the study period. We used a zero-inflated Poisson regression mixed effects models to estimate adjusted associations between acute and intermediate PM2.5 exposure durations and NICU admissions rates. NICU admissions rates increased over time during the study period. Ambient 7-day average PM2.5 concentrations was significantly associated with incidence of NICU admissions, with an interquartile range (IQR = 2.37 μg/m3) increase associated with a 1.4% (95% CI: 0.4%, 2.4%) higher adjusted incidence of daily NICU admissions. No other exposure duration metrics showed a significant association with daily NICU admission rates. The magnitude of the association between PM2.5 7-day average concentrations with NICU admissions was significantly (p < 0.05) higher among ZIP codes with higher proportions of non-Hispanic Blacks, ZIP codes with household incomes in the lowest quartile, and on days with higher relative humidity. Our data shows a positive relationship between acute (7-day average) PM2.5 concentrations and daily NICU admissions in Metropolitan Statistical Areas of Florida. The observed associations were stronger in socioeconomically disadvantaged areas, areas with higher proportions with non-Hispanic Blacks, and on days with higher relative humidity. Further research is warranted to study other air pollutants and multipollutant effects and identify health conditions that are driving these associations with NICU admissions.

Inflammatory Bowel Disease Environmental Risk Factors: Diet and Gut Microbiota.

This review specifically explores the affect that diet has on the gut microbiota and its role on the increasing incidence of IBD around the world in developing countries. This is a The emergence of IBD is consistently observed as a society becomes developed and westernized implicating the critical role that environmental factors play. Environmental factors that could play a significant role in the pathogenesis of IBD include westernization of diet and improved hygiene statust. Westernization of diet is associated with changes in the gastrointestinal microbiota, which could affect the development of the immune system and thus influence the risk of disease occurrence. There remains an important need for extensive and rigorous studies focused on the role of environmental exposures on IBD management. Specifically, if environmental factors can be modified to decrease the possibility of relapse or improve patient quality of life.

The Role of Environmental Exposures in Atopic Dermatitis.

Although genetic factors clearly play a role in the development of atopic dermatitis (AD), the recent dramatic increase in the prevalence of AD in low- and middle-income countries is not consistent with only a role of genetic factors. These findings strongly suggest that environmental factors may play an important role in the pathogenesis of AD. We reviewed the role of gene-environment studies; in utero exposures including tobacco smoke, alcohol, maternal stress, various digestive supplements, and gestational diabetes; early-life exposures including diet, gut microbiota, antibiotics, and breastfeeding; climate including temperature, ultraviolet radiation exposure, and air pollution; and household products, indoor allergens, water hardness, pH, and skin microbiota and their effects on AD. Environmental factors definitely play a role in the pathogenesis of AD. However, identifying definitive factors continues to be difficult in the setting of conflicting evidence and the complex interactions between genotypes and the environment resulting in a multitude of AD phenotypes. All of the different environmental interactions discussed highlight the importance of intervening on multiple levels in a patient's environment to improve or even prevent AD symptoms. Further, the importance of modifying environmental factors early on in a person's life is demonstrated. When possible, all of these environmental factors should be considered in treating a patient with AD and the appropriate modifications should be made at population and individual levels.

Early life antibiotic exposure and host health: Role of the microbiota–immune interaction

The neonatal population is at high risk for infections secondary to a unique, developing immune system. While a multitude of factors direct the development of the immune system, the role of environmental exposures on the microbiota may play a critical and potentially modifiable role. Recent evidence suggests that the disruption of the microbiota through the use of antibiotics not only leads to an immediately increased risk for neonatal complications but also long-term health issues related to autoimmune and inflammatory diseases. The exact cellular and molecular mechanisms behind these associations between the microbiota and neonatal outcomes are still under investigation. This review will examine the mechanistic interactions between the microbiota and the immune system, particularly in early life, along with how antibiotic mediated aberrations of the microbiome potentially lead to disease.

Abstract A11: Neighborhood clustering of bladder cancer incidence in Utah: Analyzing census data linked to cancer records

Abstract Evaluating risk factors across the lifespan (using the life course perspective) is important when considering the role of environment on BCa risk. Spatial cluster detection methods offer unique opportunities to identify shared exposures of individuals with BCa on the local level and formulate hypotheses about the potential role of environmental exposures. This study tests for evidence of spatial clustering of BCa incidence based on neighborhoods defined as 1940 US Census enumeration districts (ED). Data were extracted from the Utah Population Database (UPDB). UPDB holds birth, death, historic US Census, and driver license records that allow tracking of an individual’s location across the lifespan. UPDB is linked to the Utah Cancer Registry, an original member of the Surveillance, Epidemiology, and End Results program. Incident BCa cases from 1966 to 2017 were identified in the UCR or by death records and linked to UPDB. We geocoded all 1940 US Census ED centroids in Utah using US Census maps and ArcGIS software. The cohort comprises all individuals age 0–40 years at the time of the 1940 Census (Ncohort=343,521). We excluded individuals with an absence of follow-up information (Nexcluded=82,726). Our final cohort size was 260,795 individuals who contributed 13,816,670 person-years. SatScan software was used to identify spatial clustering of EDs with high rates of BCa. BCa was diagnosed in 2,654 individuals during follow-up (rate=19.2 cases per 100,000 person-years). Approximately 78.4% of cases were male. Average follow-up time was 53 years (range 1-78 years). We identified a circular cluster of 1.54 kilometers in diameter containing 23 ED centroids in an urban area, with a rate of 32.7 cases per 100,000 person-years (relative risk = 1.73, p=0.0023). We found evidence of spatial clustering of BCa incidence in an urban area of Salt Lake City, Utah for individuals in early life (0-40 years) at the time of the 1940 US Census. Individuals residing in this shared space were significantly more likely to develop BCa later in life, with a 73% increase in the incidence rate. Shared space in this context is presumed to be a proxy for environmental exposures. Environmental exposures including arsenic in drinking water and exposure to carcinogenic chemicals are associated with bladder cancer incidence. While this study was hypothesis generating and did not test for contaminants directly, future studies would benefit from the inclusion of contamination data. Additionally, we were limited by the use of residential history at a single time point and lack of data on personal behaviors (e.g., smoking). Strengths of this study include large cohort size, long follow-up time, and ability to expand to an early census. A life course perspective on cancer incidence provides for innovative methods to explore the environmental contexts of disease. Citation Format: Claire L. Leiser, Marissa Taddie, Rebecca Richards-Steed, James A. VanDerslice, Brock O’Neil, Heidi A. Hanson. Neighborhood clustering of bladder cancer incidence in Utah: Analyzing census data linked to cancer records [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A11.

Abstract IA38: What causes the increased risk of acute lymphoblastic leukemia in Latinos?

Abstract Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and, despite high cure rates, remains one of the leading causes of cancer-related mortality in children. Moreover, childhood ALL survivors are faced with severe long-term treatment-related morbidities, including increased risk of cardiovascular disease, secondary cancers, and pulmonary disease. Children of Latino ethnicity have the highest incidence of ALL in the United States. This increased risk likely has a genetic component, although the rising incidence of ALL in recent decades, which is increasing fastest in Latinos, points towards a role for environmental exposures. In this talk, I will discuss recent research from our group and others that has shed light on the potential etiologies of the increased ALL risk in Latinos. Genome-wide association studies (GWAS) of childhood ALL have pinpointed several risk loci at genes involved in B-cell development and hematopoiesis. In our earlier studies of ALL in the genetically admixed Latino population of California, we capitalized on their altered linkage disequilibrium patterns (compared to non-Latino whites) to identify putative causal variants, including a missense SNP in CDKN2A. More recently, we performed a large multiethnic GWAS of ALL including Latinos, non-Latino whites, and African-Americans, and identified new ALL risk loci at 8q24 and IKZF3. Fine-mapping at known loci also helped to confirm an independent risk locus at chromosome 10p12.31 and pinpointed a likely causal variant in an enhancer region for BMI1. Our group and others previously showed that the risk allele frequencies of several loci, including ARID5B, PIP4K2A, and GATA3, are higher in Latino populations and are associated with Native American ancestry. In two recent, independent GWAS of ALL in Latinos, a novel risk locus was identified at the erythroblast transformation-specific (ETS)-related gene (ERG) on chromosome 21, which was found to confer stronger leukemia risk in Latinos than in non-Latino whites. Moreover, within Latinos the effect of this risk locus increased with increasing Native American ancestry. We subsequently confirmed ERG as the first identified genetic risk locus for ALL in children with Down syndrome (DS-ALL), in which the effect size was again stronger in Latino than in non-Latino white children with DS. Our research group has also identified varied associations between Latinos and non-Latino whites for risk factors pertaining to immune stimulation (childhood contacts) and infection (cytomegalovirus). Future studies of ALL risk factors in Latinos, including even larger GWAS, polygenic risk score analysis, admixture mapping, as well as continued investigation of environmental risk factors, will be critical for our understanding the etiology of this disease and for identifying possible avenues to reduce the ethnic disparity in ALL incidence. Citation Format: Adam J. de Smith, Qianxi Feng, Kyle M. Walsh, Soyoung Jeon, Libby M. Morimoto, Andrew T. DeWan, Charleston Chiang, Catherine Metayer, Xiaomei Ma, Joseph L. Wiemels. What causes the increased risk of acute lymphoblastic leukemia in Latinos? [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr IA38.

Occupational Exposures to Organic Dust in Irish Bakeries and a Pizzeria Restaurant.

For decades, occupational exposure to flour dust has been linked to a range of respiratory diseases, including occupational asthma, thought to result from exposure to fungi present in the flour. Antifungal resistance is of increasing prevalence in clinical settings, and the role of occupational and environmental exposures, particularly for specific fungal species, is of concern. Occupational exposure to flour dust can occur in a range of occupational settings, however, few studies have focused on restaurant workers. The objective of this study was to measure occupational exposure to flour and microbial contamination, including azole resistance screening, in two small commercial bakeries and in a pizzeria. Personal full shift inhalable dust measurements were collected from workers, and were analyzed for inhalable dust and fungi, bacteria, azole resistance, and mycotoxins. Samples of settled dust were collected, and electrostatic dust cloths (EDC) were deployed and analyzed for microbial contamination, including azole resistance screening, and mycotoxins. Geometric mean exposures of 6.5 mg m−3 were calculated for inhalable dust, however, exposures of up to 18.30 mg m−3 were measured—70% of personal exposure measurements exceeded the occupational exposure limit for flour dust of 1.0 mg m−3. The air and EDC fungal counts were similar to those reported in previous studies for similar occupational environments. The fungi were dominated by Penicillium genera, however Aspergillus genera, including Fumigati and Flavi sections, were observed using culture-based methods, and the Fumigati section was also observed by molecular tools. Both Aspergillus sections were identified on the azole resistance screening. Mycotoxins were also detected in the settled dust samples, dominated by deoxynivalenol (DON). The role of environmental exposure in both the development of antimicrobial resistance and the total mycotoxin body burden is a growing concern; therefore, the presence of azole-resistant fungi and mycotoxin contamination, although low in magnitude, is of concern and warrants further investigation.