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Objective To examine environmental factors that influence risk of thyroid cancer. Methods We performed a case-control study utilizing thyroid cancer cases from the California Cancer Registry (1999-2012) and controls sampled in a population-based manner. Study participants were included if they were diagnosed with thyroid cancer, lived in the study area at their time of diagnosis, and were ≥35 years of age. Controls were recruited from the same area and eligible to participate if they were ≥35 years of age and had been living in California for at least 5 years prior to the interview. We examined residential exposure to 29 agricultural use pesticides, known to cause DNA damage in vitro or are known endocrine disruptors. We employed a validated geographic information system–based system to generate exposure estimates for each participant. Results Our sample included 2067 cases and 1003 controls. In single pollutant models and within a 20-year exposure period, 10 out of 29 selected pesticides were associated with thyroid cancer, including several of the most applied pesticides in the United States such as paraquat dichloride [odds ratio (OR): 1.46 (95% CI: 1.23, 1.73)], glyphosate [OR: 1.33 (95% CI: 1.12, 1.58)], and oxyfluorfen [OR: 1.21 (95% CI: 1.02, 1.43)]. Risk of thyroid cancer increased proportionately to the total number of pesticides subjects were exposed to 20 years before diagnosis or interview. In all models, paraquat dichloride was associated with thyroid cancer. Conclusions Our study provides first evidence in support of the hypothesis that residential pesticide exposure from agricultural applications is associated with an increased risk of thyroid cancer.

Epidemiologic studies of low-frequency exposures or outcomes using metabolomics analyses of neonatal dried blood spots (DBS) often require assembly of samples with substantial differences in duration of storage. Independent assessment of stability of metabolites in archived DBS will enable improved design and interpretation of epidemiologic research utilizing DBS. Neonatal DBS routinely collected and stored as part of the California Genetic Disease Screening Program between 1983 and 2011 were used. The study population included 899 children without cancer before age 6 born in California. High-resolution metabolomics with liquid chromatography mass spectrometry (LC-MS) was performed and the relative ion intensities of common metabolites and selected xenobiotic metabolites of nicotine (cotinine and hydroxycotinine) were evaluated. In total, we detected 26,235 mass spectral features across two separate chromatography methods (C18 and HILIC). For most of the 39 metabolites related to nutrition and health status, we found no statistically significant annual trends across the years of storage. Nicotine metabolites were captured in the DBS with relatively stable intensities. This study supports the usefulness of DBS stored long-term for epidemiological studies of the metabolome. Omics-based information gained from DBS may also provide a valuable tool for assessing prenatal environmental exposures in child health research.

BackgroundMaternal migraine has been linked to adverse birth outcomes including low birth weight and preterm birth, as well as congenital anomalies in offspring. It has been speculated that this may be due to the use of medications in pregnancy, but lifestyle, genetic, hormonal, and neurochemical factors could also play a role. There is evidence for varying cancer incidences among adults with migraine. Here, we utilized data from national registries in Denmark to examine associations between maternal diagnoses of migraine and risk for cancer in offspring.MethodsWe linked several national registries in Denmark to identify cases from the Cancer Registry among children less than 20years (diagnoses 1996–2016) and controls from the Central Population Register, matched to cases by birth year and sex (25:1 matching rate). Migraine diagnoses were identified from the National Patient Register using International Classification of Diseases, versions 8 and 10 codes and migraine-specific acute or prophylactic treatment recorded in the National Pharmaceutical Register. We used logistic regression to estimate the risk of childhood cancers associated with maternal migraine.ResultsMaternal migraine was positively associated with risk for non-Hodgkin lymphoma (odds ratio [OR]=1.70, 95% confidence interval [CI]: 1.01–2.86), central nervous system tumors ([OR=1.31, 95% CI: 1.02–1.68], particularly glioma [OR=1.64, 95% CI: 1.12–2.40]), neuroblastoma (OR=1.75, 95% CI: 1.00–3.08), and osteosarcoma (OR=2.60, 95% CI: 1.18–5.76).ConclusionsAssociations with maternal migraine were observed for several childhood cancers, including neuronal tumors. Our findings raise questions about the role of lifestyle factors, sex hormones, genetic, and neurochemical factors in the relationship between migraine and childhood cancers.

Objective: Results from studies investigating the association between maternal or child epilepsy, use of anticonvulsants in pregnancy, and childhood cancer are inconsistent and at times contradictory. Methods: Linking Danish national databases, we obtained epilepsy and childhood cancer diagnoses, and anticonvulsant use data. We estimated adjusted odds ratios of all or specific childhood cancers in relation to maternal or child epilepsy and anticonvulsant therapies using conditional logistic regression. Results: Maternal epilepsy was positively associated with all childhood cancers in offspring, specifically, with acute lymphoblastic leukemia (Odds Ratio (OR) = 1.68, 95% Confidence Interval (CI) = 1.16, 2.43) and Wilms tumor (OR = 2.13, 95%CI = 0.97, 4.68). When considering maternal ever (lifetime) ingestion of anticonvulsants, a positive association was found with all cancers (OR = 1.15, 95%CI = 1.01, 1.31), and central nervous system tumors (OR = 1.32, 95%CI = 1.03, 1.69) as well as neuroblastoma (OR = 2.05, 95%CI = 1.29, 3.28) among offspring. Maternal anticonvulsant use before or during the index pregnancy was related to CNS tumors in offspring (OR = 1.78, 95%CI = 0.99, 3.21), however the confidence interval included the null. Significance: Maternal use of certain anticonvulsant medications may be a risk factor for cancer in offspring. Medical providers may need to consider what type of treatments to prescribe to pregnant mothers with epilepsy.

PDF file - 43K, Analysis of Birth Month in a Study of Leukemia Risk Among California Children Diagnosed Between 1988 and 2007.

PDF file - 222K, Analysis of age at First Exposure to an RSV Season in a Study of Leukemia Risk Among California Children Diagnosed Between 1999 and 2007.

Background: Epidemiologic studies indicate that infections in early childhood may protect against pediatric acute lymphoblastic leukemia (ALL).Methods: We identified 3,402 ALL cases among children 0 to 5 years of age using the California Cancer Registry. From California birth records we randomly selected controls in a 20:1 ratio and frequency matched them to cases by birth year. We investigated markers of exposure to infections, including month of birth, timing of birth in relation to influenza and respiratory syncytial virus (RSV) seasons, and birth order based on data from California birth certificates and national infection surveillance systems.Results: We observed an increased risk of ALL for spring and summer births, and for those first exposed to an influenza or RSV season at nine to twelve months of age compared with those exposed during the first three months of life, and this association was stronger among first born children [odds ratios (OR), 1.44 and 95% confidence intervals (CI), 1.13–1.82, for influenza exposure at nine to twelve months of age]. Decreased risk was observed with increasing birth order among non-Hispanic whites but not Hispanics (OR, 0.76 and 95% CI, 0.59–096, for fourth or higher birth order among whites).Conclusion: Our results support the hypothesis that infections in early childhood decrease risk of ALL.Impact: Our findings implicate early life exposure to infections as protective factors for ALL in young children. Cancer Epidemiol Biomarkers Prev; 23(7); 1195–203. ©2014 AACR.

Childhood cancer may be related to maternal health in pregnancy. Maternal anemia is a common condition in pregnancy, especially in low-income countries, but the association between maternal anemia and childhood cancer has not been widely studied.To examine the potential relation between maternal anemia during pregnancy and childhood cancers in a population-based cohort study in Taiwan.We examined the relationship between maternal anemia and childhood cancer in Taiwan (N = 2160 cancer cases, 2,076,877 noncases). Cases were taken from the National Cancer Registry, and noncases were selected from birth records. Using national health registries, we obtained maternal anemia diagnoses. We estimated the risks for childhood cancers using Cox proportional hazard analysis.There was an increased risk of cancers in children born to mothers with nutritional anemia (hazard ratio (HR): 1.32, 95% CI 0.99, 1.76). Iron deficiency anemia (HR: 1.30, 95% CI 0.97-1.75) carried an increased risk, while non-nutritional anemias were not associated with childhood cancer risk.Our results provide additional support for screening for anemia during pregnancy. Adequate nutrition and vitamin supplementation may help to prevent some childhood cancer.

Purpose The aim of this study was to examine whether use of regular aspirin and/or other non-steroidal anti-inflammatory drugs (NSAIDs) is associated with the development of age-related macular degeneration (AMD). Methods In the California Teachers Study cohort (N = 88,481) we identified diagnoses of AMD up to December 31, 2012 by linkage to statewide hospital discharge records. Aspirin, ibuprofen, other NSAIDs, and acetaminophen use and comprehensive risk factor information were collected via self-administered questionnaires at baseline in 1995–1996 and a follow-up questionnaire in 2005–2006. We employed Cox proportional hazard regression to model AMD risk. Results We did not find any associations between AMD and frequency and duration of aspirin or ibuprofen use reported at baseline. In the subsample with more specific information on medication use, we observed a 20% decrease in risk of AMD among low-dose aspirin users (HR 0.81, 95% CI 0.70–0.95) and a 55% decrease among cyclooxygenase-2 (COX-2) inhibitor users (HR 0.45, 95% CI 0.26–0.78) during 6.3 years of average follow-up. Conclusion The decrease in risk of intermediate- or late-stage AMD among women who reported regular use of low-dose aspirin or specific COX-2 inhibitors suggests a possible protective role for medications with COX-2 inhibitory properties or aspirin at doses used for cardiovascular disease prevention.

Childhood cancer risk is associated with maternal health during pregnancy. Anemia in pregnancy is a common condition, especially in low-income countries, but a possible association between maternal anemia and childhood cancer has not been widely studied.We examined the relation in a population-based study in Denmark (N=6420 cancer cases, 160,485 controls). Cases were taken from the Danish Cancer Registry, and controls were selected from national records. We obtained maternal anemia diagnoses from the National Patient and Medical Births registries. In a separate analysis within the years available (births 1995-2014), we examined cancer risks among mothers taking prescribed vitamin supplements, using data from the National Prescription Register. We estimated the risks of childhood cancer using conditional logistic regression.The risks of neuroblastoma [odds ratio (OR= 1.83, 95% confidence interval (CI): 1.04, 3.22] and acute lymphoblastic leukemia (OR= 1.46, 95% CI 1.09, 1.97) were increased in children born to mothers with anemia in pregnancy. There was a two-fold increased risk for bone tumors (OR= 2.59, 95% CI: 1.42, 4.72), particularly osteosarcoma (OR= 3.54, 95% CI 1.60, 7.82). With regards to prescribed supplement use, mothers prescribed supplements for B12 and folate deficiency anemia (OR= 4.03, 95% CI 1.91, 8.50) had an increased risk for cancer in offspring.Our results suggest that screening for anemia in pregnancy and vitamin supplementation may be an actionable strategy to prevent some cases of childhood cancer.

BACKGROUND: Retinoblastoma is a rare tumor of the retina, most commonly found in young children. Due to the rarity of this childhood cancer, few studies have been able to examine prenatal pesticide exposure as a risk factor. OBJECTIVE: To examine the relationship between childhood retinoblastoma and prenatal exposure to pesticides through residential proximity to agricultural pesticide applications. METHODS: We conducted a population-based case-control study using cases aged 5 and younger identified from the California Cancer Registry, and controls randomly selected from California birth certificates. Frequency matching cases to controls by age resulted in 221 cases of unilateral retinoblastoma and 114 cases of bilateral retinoblastoma, totaling 335 cases and 123,166 controls. Based on addresses from birth certificates we employed Pesticide Use Reports and land use information within a geographic information system approach to individually assess exposures to specific pesticides within 4000 m of the residence reported on birth certificates. The associations between retinoblastoma (all types combined and stratified by laterality) and individual pesticides were expressed as odds ratios estimates obtained from unconditional logistic regression models including a single pesticide, and from a hierarchical logistic regression model including all pesticides. RESULTS: We found that exposures to acephate (OR: 1.70, 95% CI: 1.20, 2.41) and bromacil (OR: 1.87, 95% CI: 1.07, 3.26) were associated with increased risk for unilateral retinoblastoma. In addition to acephate, we found that pymetrozine (OR: 1.45, 95% CI: 1.00, 2.08) and kresoxim-methyl (OR: 1.60, 95% CI: 1.00, 2.56) were associated with retinoblastoma (all types combined). CONCLUSION: Our findings suggest that certain types of prenatal ambient pesticide exposure from residing near agricultural fields may play a role in the development of childhood retinoblastoma.

Psoriasis is associated with metabolic syndrome; however, the relationship of psoriasis severity with individual cardiometabolic risk factors is not clear. There is a reporting gap between the cardiometabolic risks among patients with psoriasis and what has been reported in the literature using US samples. The objective of this study was to examine the disease burden of psoriasis and assess the associations of psoriasis severity and cardiometabolic risk factors in a nationally representative sample. We conducted a cross-sectional study using the weighted pooled data from the National Ambulatory Medical Care Survey (NAMCS) 2007 through 2016. The NAMCS data were collected from US office-based physicians. Each physician was randomly assigned a specific week to report a sample of their cases. Patients were categorized as severe psoriasis if they were prescribed at least one systemic therapy. We used logistic regression models adjusting for potential confounders to estimate the associations of psoriasis severity with individual cardiometabolic factors. There were about 3.3 million office-based psoriasis visits per year with a mean age of 50 years, a female-to-male ratio of 1:1, and severe disease in 23%. We observed greater values of blood pressure, lipid profiles, and higher body mass index among patients with psoriasis, compared with patients without psoriasis. A higher proportion of the psoriasis patient group were overweight and obese (73.6% vs 62.9% in the non-psoriasis patient group). Compared to mild case groups, severe case groups tended to have a higher proportion of overweight/obese with a body mass index ≥ 25 kg/m2 (77% vs 73%). Obesity was weakly associated with psoriasis severity (adjusted odds ratio = 1.37, 95% confidence interval 0.98–1.91 for mild disease and adjusted odds ratio = 1.42, 95% confidence interval 0.80–2.52 for severe cases). Cardiometabolic factors are related health issues in psoriasis, and obesity is associated with greater psoriasis severity.

Purpose To examine associations between parental occupation and childhood germ cell tumors (GCTs) in offspring while distinguishing by common histologic subtype (i.e., yolk sac tumor and teratoma). Methods This population-based case–control study included childhood GCT cases in Denmark diagnosed 1968–2015 ( Results Overall, 178 childhood GCT cases (50 yolk sac tumors; 65 teratomas) and 4,355 controls were included for analysis. Maternal employment in education during pregnancy was associated with offspring GCTs (OR 2.45, 95% CI 1.23–4.90), especially yolk sac tumors (OR 5.27, 95% CI 1.94–14.28). High levels of both maternal and paternal occupational social contact were also associated with offspring yolk sac tumors across all exposure periods (ORs 2.30–4.63). No signals were observed for paternal occupational solvent exposure, while imprecise associations were estimated for maternal exposure (e.g., dichloromethane exposure during pregnancy, OR 1.51, 95% CI 0.77–2.95). Conclusion Our findings suggest that parental occupation is associated with offspring GCTs, with most consistent evidence supporting an association between maternal employment in education or other high social contact jobs and offspring yolk sac tumors.

OBJECTIVE: Retinoblastoma is the most common primary intraocular tumor affecting children. We examine the role of parental occupational exposures and risk of retinoblastoma among offspring. METHODS: Our population-based case-control study linked data from four nationwide Danish registries and included all cases of retinoblastoma diagnosed in Danish children (

BackgroundHead trauma has been associated with increased brain tumor risk in adults. Instrument assisted delivery can be a cause of head trauma in newborns. The goal of this study was to determine if instrument-assisted deliveries influenced the odds of childhood brain tumors in Denmark.MethodsWe conducted a matched case-control study of childhood (

Background Maternal exposure to traffic-related air pollution during pregnancy has been shown to increase the risk of adverse birth outcomes and childhood disorders. High-resolution metabolomics (HRM) has previously been employed to identify metabolic responses to traffic-related air pollution in adults, including pregnant women. Thus far, no studies have examined metabolic effects of air pollution exposure in utero on neonates. Methods We retrieved stored neonatal blood spots for 241 children born in California between 1998 and 2007. These children were randomly selected from all California birth rolls to serve as birth-year matched controls for children with retinoblastoma identified from the California cancer registry for a case control study of childhood cancer. We estimated prenatal traffic-related air pollution exposure (particulate matter less than 2.5 μm (PM2.5)) during the third-trimester using the California Line Source Dispersion Model, version 4 (CALINE4) based on residential addresses recorded at birth. We employed untargeted HRM to obtain metabolic profiles, and metabolites associated with air pollution exposure were identified using partial least squares (PLS) regression and linear regressions. Biological effects were characterized using pathway enrichment analyses adjusting for potential confounders including maternal age, race/ethnicity, and education. Results In total we extracted 4038 and 4957 metabolite features from neonatal blood spots in hydrophilic interaction (HILIC) chromatography (positive ion mode) and C18 reverse phase columns (negative ion mode), respectively. After controlling for confounding factors, partial least square regression (Variable Importance in Projection (VIP) ≥ 2) selected 402 HILIC positive and 182 C18 negative features as statistically significantly associated with increasing third trimester PM2.5 exposure. Using pathway enrichment analysis, we identified metabolites in oxidative stress and inflammation pathways as being altered, primarily involving lipid metabolism. Conclusion The metabolite features and pathways associated with air pollution exposure in neonates suggest that maternal exposure during late pregnancy contributes to oxidative stress and inflammation in newborn children.

BackgroundAlthough viral hepatitis causes paediatric hepatocellular carcinoma and hepatic and extrahepatic cancers in adults, there are few epidemiologic studies on paediatric-cancer risks from parental viral hepatitis. In a nationwide study in a viral hepatitis endemic region and with confirmation in another population-based sample, we examined associations between parental hepatitis B (HBV) and C (HCV) infections and risks of cancers in offspring.MethodsWe included all children born in Taiwan in 2004–2014 (N = 2 079 037) with 2160 cancer cases ascertained from the Cancer Registry. We estimated risks for paediatric cancers using Cox proportional-hazard regressions. We checked these associations in a nationwide case–control study in Denmark (6422 cases, 160 522 controls).ResultsIn Taiwan, paternal HBV was related to child’s hepatoblastoma [hazard ratio (HR) = 1.77, 95% confidence interval (CI) = 1.05, 2.97] when identified at any time in the medical record, and when analyses were limited to hepatitis diagnoses occurring before the child’s birth, risks increased (HR = 2.08, 95% CI = 1.13–3.80). Paternal HCV was related to child’s non-Hodgkin lymphoma (HR = 2.06, 95% CI = 1.13–3.74). Maternal HCV was weakly related to increased risks of all childhood cancers [all types combined; HR = 1.45, 95% CI = 0.95–2.22]. The population-attributable fraction of hepatoblastoma for maternal, paternal and child HBV was 2.6%, 6.8% and 2.8%, respectively.ConclusionsParental HBV and HCV may be risk factors for hepatic and non-hepatic cancers in children. If associations are causal, then parental screening and treatment with antivirals may prevent some paediatric cancers.

Background The effect of maternal diabetes on childhood cancer has not been widely studied. Methods We examined this in two population-based studies in Denmark (N = 6420 cancer cases, 160,484 controls) and Taiwan (N = 2160 cancer cases, 2,076,877 non-cases) using logistic regression and Cox proportional hazard regression adjusted for birth year, child’s sex, maternal age and birth order. Results Gestational diabetes in Denmark [odds ratio (OR) = 0.98, 95% confidence interval (CI): 0.71–1.35] or type II and gestational diabetes in Taiwan (type II: hazard ratio (HR) = 0.81, 95% CI: 0.63–1.05; gestational diabetes: HR = 1.06, 95% CI: 0.92–1.22) were not associated with cancer (all types combined). In Denmark, maternal type I diabetes was associated with the risk of glioma (OR = 2.33, 95% CI: 1.04–5.22), while in Taiwan, the risks of glioma (HR = 1.59, 95% CI: 1.01–2.50) were elevated among children whose mothers had gestational diabetes. There was a twofold increased risk for hepatoblastoma with maternal type II diabetes (HR = 2.02, 95% CI: 1.02–4.00). Conclusions Our results suggest that maternal diabetes is an important risk factor for certain types of childhood cancers, emphasising the need for effective interventions targeting maternal diabetes to prevent serious health effects in offspring.

Statistically significantly increased cancer incidence has been reported from 3 cohorts of World Trade Center (WTC) disaster rescue and recovery workers. We pooled data across these cohorts to address ongoing public concerns regarding cancer risk 14 years after WTC exposure.From a combined deduplicated cohort of 69 102 WTC rescue and recovery workers, a sample of 57 402 workers enrolled before 2009 and followed through 2015 was studied. Invasive cancers diagnosed in 2002-2015 were identified from 13 state cancer registries. Standardized incidence ratios (SIRs) were used to assess cancer incidence. Adjusted hazard ratios (aHRs) were estimated from Cox regression to examine associations between WTC exposures and cancer risk.Of the 3611 incident cancers identified, 3236 were reported as first-time primary (FP) cancers, with an accumulated 649 724 and 624 620 person-years of follow-up, respectively. Incidence for combined FP cancers was below expectation (SIR = 0.96, 95% confidence interval [CI] = 0.93 to 0.99). Statistically significantly elevated SIRs were observed for melanoma-skin (SIR = 1.43, 95% CI = 1.24 to 1.64), prostate (SIR = 1.19, 95% CI = 1.11 to 1.26), thyroid (SIR = 1.81, 95% CI = 1.57 to 2.09), and tonsil (SIR = 1.40, 95% CI = 1.00 to 1.91) cancer. Those arriving on September 11 had statistically significantly higher aHRs than those arriving after September 17, 2001, for prostate (aHR = 1.61, 95% CI = 1.33 to 1.95) and thyroid (aHR = 1.77, 95% CI = 1.11 to 2.81) cancers, with a statistically significant exposure-response trend for both.In the largest cohort of 9/11 rescue and recovery workers ever studied, overall cancer incidence was lower than expected, and intensity of WTC exposure was associated with increased risk for specific cancer sites, demonstrating the value of long-term follow-up studies after environmental disasters.

Author(s): Hall, Clinton; Heck, Julia E; Ritz, Beate; Cockburn, Myles; Escobedo, Loraine A; von Ehrenstein, Ondine S | Abstract: ObjectiveTo assess prenatal air toxics exposure and risk for childhood germ cell tumors (GCTs) by histological subtype (yolk sac tumor and teratoma).MethodsIn this case-control study, GCT cases less than 6 years (n = 243) identified from California Cancer Registry records were matched by birth year to cancer-free population controls (n = 147,100), 1984 to 2013. Routinely monitored air toxic exposures were linked to subjects' birth address. Logistic regression estimated GCT risks per interquartile range increase in exposure.ResultsPrenatal exposure to various highly-correlated, traffic-related air toxics during the second trimester increased GCT risk, particularly 1,3-butadiene (odds ratio [OR] = 1.51; 95% confidence interval [CI] = 1.01, 2.26) and meta/para-xylene (OR = 1.56; 95% CI = 1.10, 2.21). Analyses by subtype indicated elevated ORs for yolk sac tumors but not teratomas.ConclusionOur estimated ORs are consistent with positive associations between some prenatal traffic-related air toxics and GCT risk, notably yolk sac tumors.

Psoriasis is associated with metabolic syndrome; however, the relationship of psoriasis severity with individual cardiometabolic risk factors is not clear. There is a reporting gap between the cardiometabolic risks among patients with psoriasis and what has been reported in the literature using US samples.The objective of this study was to examine the disease burden of psoriasis and assess the associations of psoriasis severity and cardiometabolic risk factors in a nationally representative sample.We conducted a cross-sectional study using the weighted pooled data from the National Ambulatory Medical Care Survey (NAMCS) 2007 through 2016. The NAMCS data were collected from US office-based physicians. Each physician was randomly assigned a specific week to report a sample of their cases. Patients were categorized as severe psoriasis if they were prescribed at least one systemic therapy. We used logistic regression models adjusting for potential confounders to estimate the associations of psoriasis severity with individual cardiometabolic factors.There were about 3.3 million office-based psoriasis visits per year with a mean age of 50 years, a female-to-male ratio of 1:1, and severe disease in 23%. We observed greater values of blood pressure, lipid profiles, and higher body mass index among patients with psoriasis, compared with patients without psoriasis. A higher proportion of the psoriasis patient group were overweight and obese (73.6% vs 62.9% in the non-psoriasis patient group). Compared to mild case groups, severe case groups tended to have a higher proportion of overweight/obese with a body mass index ≥ 25 kg/mCardiometabolic factors are related health issues in psoriasis, and obesity is associated with greater psoriasis severity.

Background Pesticide exposures have been examined previously as risk factors for childhood brain cancers, but few studies were able to assess risk from specific agents. Objective To evaluate risks for childhood central nervous system tumors associated with residential proximity to agricultural pesticide applications. Methods Using the California Cancer Registry, we identified cancer cases less than 6 years of age and frequency matched them by year of birth to 20 cancer-free controls identified from birth certificates. We restricted analyses to mothers living in rural areas and births occurring between 1998 and 2011, resulting in 667 cases of childhood central nervous system tumors and 123,158 controls. Possible carcinogens were selected per the Environmental Protection Agency's (US. EPA) classifications, and prenatal exposure was assessed according to pesticides reported by the California Department of Pesticide Regulation's (CDPR) Pesticide Use Reporting (PUR) system as being applied within 4000m of the maternal residence at birth. We computed odds ratios for individual pesticide associations using unconditional logistic and hierarchical regression models. Results We observed elevated risks in the hierarchical models for diffuse astrocytoma with exposure to bromacil (OR: 2.12, 95% CI: 1.13–3.97), thiophanate-methyl (OR: 1.64, 95% CI: 1.02–2.66), triforine (OR: 2.38, 95% CI: 1.44–3.92), and kresoxim methyl (OR: 2.09, 95% CI: 1.03–4.21); elevated risks for medulloblastoma with exposure to chlorothalonil (OR: 1.78, 95% CI: 1.15–2.76), propiconazole (OR: 1.60, 95% CI: 1.02, 2.53), dimethoate (OR: 1.60, 95% CI: 1.06, 2.43), and linuron (OR: 2.52, 95% CI: 1.25, 5.11); and elevated risk for ependymoma with exposure to thiophanate-methyl (OR: 1.72, 95% CI: 1.10–2.68). Conclusion Our study suggests that exposure to certain pesticides through residential proximity to agricultural applications during pregnancy may increase the risk of childhood central nervous system tumors.

BACKGROUND: Previously, numerous epidemiologic studies reported an association between autism spectrum disorder (ASD) and exposure to air pollution during pregnancy. However, there have been no metabolomics studies investigating the impact of pregnancy pollution exposure to ASD risk in offspring. OBJECTIVES: To identify differences in maternal metabolism that may reflect a biological response to exposure to high air pollution in pregnancies of offspring who later did or did not develop ASD. METHODS: We obtained stored mid-pregnancy serum from 214 mothers who lived in California’s Central Valley and experienced the highest levels of air pollution during early pregnancy. We estimated each woman’s average traffic-related air pollution exposure (carbon monoxide, nitric oxides, and particulate matter

Background/Aim: The International Agency for Research on Cancer has classified benzo(a)pyrene (BaP) as carcinogenic to humans, based on sufficient evidence of carcinogenicity in experimental animal...

Sustained and inadequately controlled hypertension can promote the development of age-related macular degeneration (AMD) through multiple biologic pathways. Epidemiologic studies of high blood pressure, antihypertensive therapies, and the risk of AMD thus far have been inconclusive. However, few studies evaluated risks according to the use of different classes of antihypertensive drugs or took combinations of use into account. We performed a prospective cohort study by linking the California Teachers Study (CTS) cohort (N = 88 481) to statewide hospital discharge records up to December 31, 2012. History of high blood pressure, regular use of antihypertensive medications, and comprehensive risk factor information was collected via self-administered questionnaires at baseline in 1995-1996, and information on specific classes of antihypertensive drugs was provided by a subsample of CTS participants who completed a follow-up questionnaire in 2000. We identified 1762 female teachers with AMD during 14.8 years of follow-up on average. Applying Cox proportional hazard regression, we estimated increased risks of AMD among women treated for hypertension at baseline (HR = 1.15, 95% CI: 1.03, 1.30); the magnitude of the association increased with longer duration of antihypertensive treatment. In the subsample with more specific information on type of medication use, we estimated a 45% increased risk of AMD among women receiving diuretics as monotherapy compared to women with medications more potent than diuretics (HR = 1.45, 95% CI 1.10, 1.90). In women treated with a combination of antihypertensive drugs, we observed no increased risk of AMD for any individual class of drugs.

Spina bifida has been reported to co-occur with pediatric cancer, but comprehensive evaluations remained elusive. We investigated this co-occurrence in two large, population-based studies in Taiwan (N = 1900 cancer cases, 2,077,137 controls) and Denmark (N = 5508 cases, 137,700 controls). Analyses in Denmark were restricted to the period before prenatal diagnostics became available (2004) and pregnancy terminations of fetuses with birth defects became more common. Using national patient and cancer registries, we linked spina bifida and cancer diagnoses among cases and non-cases. The risk of spina bifida among all cancer cases was increased and similar in Denmark [odds ratio (OR)=8.4, 95% confidence interval (CI) 5.1-13.8] and Taiwan (OR = 8.5, 95% CI 4.0-17.8), particularly for central nervous system (CNS) tumors (Denmark: OR = 16.3, 95% CI 8.1-33.0; Taiwan: OR = 26.6, 95% CI 8.5, 83.1), including benign CNS tumors (Denmark: OR = 41.5, 95% CI 21.2, 81.4). These findings suggest the need for comprehensive investigation of shared risk factors in the link between spina bifida and pediatric cancer.

Author(s): Heck, Julia E; Huang, Xiwen; Calkins, Kara L; Sun, Yuelian; Olsen, Jorn; Ritz, Beate; Hansen, Johnni

Objectives Recent meta-analyses suggest a physical activity health paradox: high levels of occupational physical activity (OPA) increase cardiovascular disease (CVD) risk, while leisure-time physical activity (LTPA) decreases risk. However, studies of women and cerebrovascular disease are limited. This report examines physical activity effects on stroke and transient ischemic attack (TIA) among working women in the United States. Methods OPA history, health status, and lifestyle were assessed by baseline interviews of 31 270 employed Sister Study participants aged 35-74 years. OPA was assessed at six intensity levels (lowest: "mostly sitting"); the highest three were combined as "high intensity work." Independent OPA and LTPA effects on 6-year cerebrovascular disease incidence were estimated in adjusted Cox proportional hazard models. Results Stroke (N=441) and TIA (N=274) risk increased with more standing and higher intensity work at current and longest held job. Compared with mostly sitting, high intensity work at the current job increased TIA risk by 57%25 [hazard ratio (HR) 1.57, 95%25 confidence interval (CI) 1.04-2.38]. High intensity OPA at the longest held job increased risk for stroke by 44%25 (HR 1.44; 95%25 CI 1.08-1.93). Among women with CVD, sitting and standing equally, especially at the current job, increased risks up to two-fold (TIA HR 1.98, 95%25 CI 1.10-3.55) compared with mostly sitting at work. LTPA showed inverse associations. Conclusions Higher intensity levels of OPA increased stroke and TIA risks, while LTPA decreased risks; results corroborate the physical activity health paradox for women and cerebrovascular disease. More standing at work increased cerebrovascular disease risks, especially for women with CVD.

Advanced parental age has been associated with adverse health effects in the offspring including childhood (0-14years) acute lymphoblastic leukemia (ALL), as reported in our meta-analysis of published studies. We aimed to further explore the association using primary data from 16 studies participating in the Childhood Leukemia International Consortium. Data were contributed by 11 case-control (CC) studies (7919 cases and 12,942 controls recruited via interviews) and five nested case-control (NCC) studies (8801 cases and 29,690 controls identified through record linkage of population-based health registries) with variable enrollment periods (1968-2015). Five-year paternal and maternal age increments were introduced in two meta-analyses by study design using adjusted odds ratios (OR) derived from each study. Increased paternal age was associated with greater ALL risk in the offspring (ORCC 1.05, 95% CI 1.00-1.11; ORNCC 1.04, 95% CI 1.01-1.07). A similar positive association with advanced maternal age was observed only in the NCC results (ORCC 0.99, 95% CI 0.91-1.07, heterogeneity I2 = 58%, p = 0.002; ORNCC 1.05, 95% CI 1.01-1.08). The positive association between parental age and risk of ALL was most marked among children aged 1-5years and remained unchanged following mutual adjustment for the collinear effect of the paternal and maternal age variables; analyses of the relatively small numbers of discordant paternal-maternal age pairs were not fully enlightening. Our results strengthen the evidence that advanced parental age is associated with increased childhood ALL risk; collinearity of maternal with paternal age complicates causal interpretation. Employing datasets with cytogenetic information may further elucidate involvement of each parental component and clarify underlying mechanisms.

The Inaugural Symposium on Childhood Cancer Health Disparities was held in Houston, Texas, on November 2, 2016. The symposium was attended by 109 scientists and clinicians from diverse disciplinary back-grounds with interests in pediatric cancer disparities and focused on reviewing our current knowledge of disparities in cancer risk and out-comes for select childhood cancers. Following a full day of topical sessions, everyone participated in a brainstorming session to develop a working strategy for the continued expansion of research in this area. This meeting was designed to serve as a springboard for examination of childhood cancer disparities from a more unified and systematic approach and to enhance awareness of this area of need.

Geolocation uncertainty is common in epidemiological studies that depend on addresses to determine exposure. We developed a spatial construct and statistical framework by which to characterize geolocation uncertainty, develop analysis methods, and compare those methods. Exposure is represented by a three-dimensional step function over the partitioned spatial surface and a person’s geolocation boundary is defined as the union of partition elements that cover the possible index location. Disease rates are defined by exposures from the partitioned surface. Standard process theory was used for analytic results and an empirical evaluation computer simulation method was used to compare methods. A case-control study of pesticide exposure and childhood cancer was used to illustrate the problem. Pesticide exposure was derived from geolocations determined from birth residences, where about half the reference addresses resolved to ZIP Codes while the rest resolve to smaller areas. We found that the centroid method has much worse power (0.35) to detect pesticide–disease effects than using either whole area proportion exposed (0.52) or when using an induced intensity approach (0.79). The latter approach properly accounted for the geolocation uncertainty even if only ZIP Code address information was used. ZIP Code address data had twice the variance compared to using the actual geolocation boundaries which had twice the variance compared to if there were no geolocation uncertainty. Our area based analytic approach confirms that geolocation ambiguity should be considered in the context of exposure–disease investigations that rely on address data for determining exposure.

ObjectivesUsing nationwide register data, we investigated the association between maternal and paternal perinatal employment in industries with exposure to diesel engine exhaust and risk of leukaemia and central nervous system (CNS) cancers, including certain subtypes.MethodsChildren aged≤19 years and diagnosed with childhood cancer from 1968 to 2016 were identified in the Danish Cancer Registry and 25 randomly selected cancer-free controls per case were matched by age and sex. Parents were identified in the Danish Civil Registration System and employment histories were retrieved from a nationwide mandatory pension fund. The probability of exposure to diesel engine exhaust was assessed using a validated job exposure matrix. Conditional logistic regression was used for estimation of ORs, including their 95% CIs.ResultsMaternal employment in industries with diesel engine exhaust exposure was associated with an increased risk of CNS cancers (OR 1.31, 95% CI 0.99 to 1.74) and of astrocytoma (OR 1.49, 95% CI 1.04 to 2.14) in offspring. The highest OR for these cancers were seen for mothers with highest probability of exposure to diesel engine exhaust. For fathers, ORs for cancers under study were close to one. No increased risks of leukaemias were found for either mothers or fathers employed in diesel industries.ConclusionsRisks were increased for CNS and astrocytoma for maternal employment in industries with diesel engine exhaust.

Background: The etiology of childhood cancer is largely unknown, though some research suggests an infectious origin of hematopoietic, central nervous system (CNS) and bone cancers. Methods: We examined parental occupational social contact as a proxy for exposure to infectious agents and risk of childhood cancer. This population-based case-control study utilized a linkage of four Danish data-registries, and included 3581 cases (

Background: Maternal exposure to traffic-related air pollution during pregnancy has been shown to increase the risk of adverse birth outcomes and neurodevelopmental disorders. By utilizing high-resolution metabolomics (HRM), we investigated perturbations of the maternal serum metabolome in response to traffic-related air pollution to identify biological mechanisms. Methods: We retrieved stored mid-pregnancy serum samples from 160 mothers who lived in the Central Valley of California known for high air particulate levels. We estimated prenatal traffic-related air pollution exposure (carbon monoxide, nitric oxides, and particulate matter

Objectives Parental exposures and offspring's risk of cancer have been studied with inconsistent results. We investigated parental employment in painting and printing industries and risk of childhood leukemia, central nervous system (CNS) cancers, and prenatal cancers (acute lymphoblastic leukemia, Wilms tumor, medulloblastoma, neuroblastoma, retinoblastoma, and hepatoblastoma). Methods Using Danish registries, children aged ≤19 years diagnosed from 1968-2015 with leukemia (N=1999), CNS cancers (N=1111) or prenatal cancers (N=2704) were linked to parents and their employment history one year before birth to birth for fathers, and one year before birth to one year after for mothers. Twenty randomly selected controls per case were matched by age and sex. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression. Results For fathers, we found increased risks for acute myeloid leukemia (AML) consistent in painting (OR 2.26, 95% CI 1.07-4.80) and printing industries (OR 2.43, 95% CI 0.94-6.23) and these industries combined (OR 2.10, 95% CI 1.14-3.87). For mothers, increased risks of CNS cancers were found for painting industries (OR 2.34, 95% CI 1.10-4.95) and painting and printing combined (OR 1.97, 95% CI 1.08-3.64). For fathers working in combined industries, the OR for CNS was increased (OR 1.54, 95% CI 1.02-2.31), most prominently in printing industries (OR 2.09, 95% CI 1.17-3.75). Conclusion We observed increased risks of CNS tumors in offspring after parental employment in painting and printing industries. Children of fathers employed in painting and printing industries had a two-fold increase in AML.

BACKGROUND: Parental occupational exposures are suggested as contributing causes of childhood cancer. METHODS: Children age

ObjectivesOnly a small number of studies have reported on the association of parental occupational exposure to benzene and risk of childhood and adolescent leukaemias. We examined associations with acute lymphoblastic leukaemia (ALL) in this population-based study in Denmark.MethodsBenzene was largely banned from Danish workplaces after 1975, thus this case-control study focused on the immediately prior years. Paediatric cancer cases (ResultsWe identified 217 employed case fathers and 169 employed case mothers, of which 22 (10.1%) and 11 (6.5%), respectively, were exposed to benzene (vs 6.7% and 2.9% of control fathers and mothers). Most exposed parents worked as machine or engine mechanics, or in the shoe industry. Maternal occupational exposure to benzene in pregnancy was related to increased risk of ALL in offspring (adjusted OR=2.28, 95% CI 1.17 to 4.41), while paternal preconceptional benzene exposure was not as strongly associated (adjusted OR=1.40, 95% CI 0.88 to 2.22).ConclusionsOur study supports an increased risk for ALL with parental occupational benzene exposure.

Evidence for an association of foetal growth with acute myeloid leukaemia (AML) is inconclusive. AML is a rare childhood cancer, relatively more frequent in girls, with distinct features in infancy. In the context of the Childhood Leukemia International Consortium (CLIC), we examined the hypothesis that the association may vary by age, sex and disease subtype using data from 22 studies and a total of 3564 AML cases.Pooled estimates by age, sex and overall for harmonised foetal growth markers in association with AML were calculated using the International Fetal and Newborn Growth Consortium for the 21st Century Project for 17 studies contributing individual-level data; meta-analyses were, thereafter, conducted with estimates provided ad hoc by five more studies because of administrative constraints. Subanalyses by AML subtype were also performed.A nearly 50% increased risk was observed among large-for-gestational-age infant boys (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03-2.14), reduced to 34% in boys aged2 years (OR: 1.34, 95% CI: 1.05-1.71) and 25% in boys aged 0-14 years (OR: 1.25, 95% CI: 1.06-1.46). The association of large for gestational age became stronger in boys with M0/M1subtype (OR: 1.80, 95% CI: 1.15-2.83). Large birth length for gestational age was also positively associated with AML (OR: 1.38, 95% CI: 1.00-1.92) in boys. By contrast, there were null associations in girls, as well as with respect to associations of decelerated foetal growth markers.Accelerated foetal growth was associated with AML, especially in infant boys and those with minimally differentiated leukaemia. Further cytogenetic research would shed light into the underlying mechanisms.

Objective: To examine associations with occupational livestock or other animal dust exposure and offspring cancer risk. Methods: In this population-based case–control study of Danish children aged < 17 years old, 5078 childhood cancer cases diagnosed 1968–2016 were matched to cancer-free controls by birth year and sex (n = 123,228). Occupational livestock or animal dust exposure was identified using a job-exposure matrix. We employed multivariable conditional logistic regression models to estimate associations with offspring cancer for births 1968–2016 and 1989–2016, with the latter timeframe reflecting a period of presumed higher exposure due to changes in Danish farming practices. Sensitivity analyses considered place of birth (urban areas vs. rural areas and small towns). Results: For births 1968–2016, paternal exposure from offspring birth to cancer diagnosis was associated with central nervous system tumors (adjusted odds ratio [OR] = 1.30, 95% confidence interval [CI] 1.04–1.63) and germ cell tumors (OR = 1.82, 95% CI 1.05–3.27), while maternal pregnancy exposure was associated with astrocytoma (OR = 1.89, 95% CI 1.00–3.57). For births 1989–2016, paternal exposure from offspring birth to cancer diagnosis was negatively associated with acute lymphoid leukemia (OR = 0.58, 95% CI 0.33–1.00). For births in rural areas only, maternal exposure from offspring birth to cancer diagnosis was positively associated with acute myeloid leukemia (OR = 2.16, 95% CI 1.09–4.29). Conclusions: This study suggests that paternal occupational animal exposure is associated with offspring germ cell tumors, and maternal pregnancy exposure with astrocytomas. Our results are mixed with respect to leukemia subtypes.

Gestational risk factors such as birth weight, gestational age and parity have been repeatedly found to be related to pediatric cancers, but few reports have emerged from Asian countries. Here we report on demographic and gestational factors in a Taiwanese cohort. Our study included all children born in Taiwan 2004–2014 for whom there was a birth record (n = 2,079,037), of which 1900 children had been diagnosed with cancer prior to age 12. We conducted multivariable hazard regression to examine associations between demographic and gestational factors with cancer. Greater parity (family with 2+ older children) was related to acute myeloid leukemia [Hazard ratio (HR) = 2.15, 95% confidence interval (CI): 1.31, 3.55), central nervous system tumors (HR = 1.67, CI: 1.13, 2.48) and neuroblastoma (HR = 1.67, CI: 1.07, 2.63). Hepatoblastoma cases had a higher risk of low birth weight (