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BackgroundMaternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer.MethodsThe present study included 15,744 cancer cases (aged 0-19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998-2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned "ever/never" and "high/low exposed/unexposed" exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy.Results1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the "ever exposed" group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74).ConclusionsOverall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.

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.To examine the relationship between childhood retinoblastoma and prenatal exposure to pesticides through residential proximity to agricultural pesticide applications.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.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).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.

Pesticides are widely used in the agricultural Central Valley region of California. Historically, this has included organophosphates (OPs), organochlorines (OCs), and pyrethroids (PYRs). This study aimed to identify perturbations of the serum metabolome in response to each class of pesticide and mutual associations between groups of metabolites and multiple pesticides. We conducted high-resolution metabolomic profiling of serum samples from 176 older adults living in the California Central Valley using liquid chromatography with high-resolution mass spectrometry. We estimated chronic pesticide exposure (from 1974 to year of blood draw) to OPs, OCs, and PYRs from ambient sources at homes and workplaces with a geographic information system (GIS)-based model. Based on partial least-squares regression and pathway enrichment analysis, we identified metabolites and metabolic pathways associated with one or multiple pesticide classes, including mitochondrial energy metabolism, fatty acid and lipid metabolism, and amino acid metabolism. Utilizing an integrative network approach, we found that the fatty acid β-oxidation pathway is a common pathway shared across all three pesticide classes. The disruptions of the serum metabolome suggested that chronic pesticide exposure might result in oxidative stress, inflammatory reactions, and mitochondrial dysfunction, all of which have been previously implicated in a wide variety of diseases. Overall, our findings provided a comprehensive view of the molecular mechanisms of chronic pesticide toxicity, and, for the first time, our approach informs exposome research by moving from macrolevel population exposures to microlevel biologic responses.

BackgroundPyrethroid pesticide use is increasing worldwide, although the full extent of associated health effects is unknown. An epigenome-wide association study (EWAS) with exploratory pathway analysis may help identify potential pyrethroid-related health effects.MethodsWe performed an exploratory EWAS of chronic ambient pyrethroid exposure using control participants' blood in the Parkinson's Environment and Genes Study in the Central Valley of California (N = 237). We estimated associations of living and working near agricultural pyrethroid pesticide applications in the past 5 years (binary) with site-specific differential methylation, and used a false discovery rate (FDR) cut off of 0.05 for significance. We controlled for age, sex, education, cell count, and an ancestral marker for Hispanic ethnicity. We normalized methylation values for Type I/II probe bias using Beta-Mixture Quantile (BMIQ) normalization, filtered out cross-reactive probes, and evaluated for remaining bias with Surrogate Variable Analysis (SVA). We also evaluated the effects of controlling for cell count and normalizing for Type I/II probe bias by comparing changes in effect estimates and p-values for the top hits across BMIQ and GenomeStudio normalization methods, and controlling for cell count. To facilitate broader interpretation, we annotated genes to the CpG sites and performed gene set overrepresentation analysis, using genes annotated to CpG sites that were associated with pyrethroids at a raw p

BackgroundA number of epidemiologic studies with a variety of exposure assessment approaches have implicated pesticides as risk factors for childhood cancers. Here we explore the association of pesticide exposure in pregnancy and early childhood with childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) utilizing land use and pesticide use data in a sophisticated GIS tool.MethodsWe identified cancer cases less than 6 years of age from the California Cancer Registry and cancer-free controls from birth certificates. Analyses were restricted to those living in rural areas and born 1998-2011, resulting in 162 cases of childhood leukemia and 9,805 controls. Possible carcinogens were selected from the Environmental Protection Agency's classifications and pesticide use was collected from the California Department of Pesticide Regulation's (CDPR) Pesticide Use Reporting (PUR) system and linked to land-use surveys. Exposures for subjects were assessed using a 4000m buffer around the geocoded residential addresses at birth. Unconditional logistic and hierarchical regression models were used to assess individual pesticide and pesticide class associations.ResultsWe observed elevated risks for ALL with exposure to any carcinogenic pesticide (adjusted Odds Ratio (aOR): 2.83, 95% CI: 1.67-4.82), diuron (Single-pesticide model, adjusted (OR): 2.38, 95% CI: 1.57-3.60), phosmet (OR: 2.10, 95% CI: 1.46-3.02), kresoxim-methyl (OR: 1.77, 95% CI: 1.14-2.75), and propanil (OR: 2.58, 95% CI: 1.44-4.63). Analyses based on chemical classes showed elevated risks for the group of 2,6-dinitroanilines (OR: 2.50, 95% CI: 1.56-3.99), anilides (OR: 2.16, 95% CI: 1.38-3.36), and ureas (OR: 2.18, 95% CI: 1.42-3.34).ConclusionOur findings suggest that in rural areas of California exposure to certain pesticides or pesticide classes during pregnancy due to residential proximity to agricultural applications may increase the risk of childhood ALL and AML. Future studies into the mechanisms of carcinogenicity of these pesticides may be beneficial.

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.

Studies of environmental exposures and childhood cancers that rely on records often only use maternal address at birth or address at cancer diagnosis to assess exposures in early childhood, possibly leading to exposure misclassification and questionable validity due to residential mobility during early childhood. Our objective was to assess patterns and identify factors that may predict residential mobility in early childhood, and examine the impact of mobility on early childhood exposure assessment for agriculturally applied pesticides and childhood cancers in California. We obtained the addresses at diagnosis of all childhood cancer cases born in 1998-2011 and diagnosed at 0-5 years of age (n = 6478) from the California Cancer Registry (CCR), and their birth addresses from linked birth certificates. Controls were randomly selected from California birth records and frequency matched (20:1) to all cases by year of birth. We obtained residential histories from a public-record database LexisNexis for both case (n = 3877 with age at diagnosis 1-5 years) and control (n = 99,262) families. Logistic regression analyses were conducted to assess the socio-demographic factors in relation to residential mobility in early childhood. We employed a Geographic Information System (GIS)-based system to estimate children's first year of life exposures to agriculturally applied pesticides based on birth vs diagnosis address or residential histories based upon Lexis-Nexis Public Records and assessed agreement between exposure measures using Spearman correlations and kappa statistics. Over 20% of case and control children moved in their first year of life, and 55% of children with cancer moved between birth and diagnosis. Older age at diagnosis, younger maternal age, lower maternal education, not having a Hispanic ethnic background, use of public health insurance, and non-metropolitan residence at birth were predictors of higher residential mobility. There was moderate to strong correlation (Spearman correlation = 0.76-0.83) and good agreement (kappa = 0.75-0.81) between the first year of life exposure estimates for agricultural pesticides applied within 2 km of a residence relying on an address at birth or at diagnosis or LexisNexis addresses; this did not differ by outcome status, but agreement decreased with decreasing buffer size, and increasing distance moved or age at diagnosis. These findings suggest that residential addresses collected at one point in time may represent residential history in early childhood to a reasonable extent; nevertheless, they exposure misclassification in the first year of life remains an issue. Also, the highest proportion of women not captured by LexisNexis were Hispanic women born in Mexico and those living in the lowest SES neighborhoods, i.e. possibly those with the higher environmental exposures, as well as younger women and those with less than high school education. Though LexisNexis only captures a sub-population, its data may be useful for augmenting address information and assessing the extent of exposure misclassification when estimating environmental exposures in large record linkage studies. Future research should investigate how to correct for exposure misclassification introduced by residential mobility that is not being captured by records.

BackgroundMelanoma, the deadliest form of skin cancer, is the second most common cancer diagnosed before age 30. Little is known about potentially modifiable or intervenable risk factors specific to developing melanoma at a young age. The objective was to determine if high birth weight or higher early-life ultraviolet (UV) radiation exposure would be associated with increased risk of melanoma in young patients.MethodsPopulation-based, case-control study of 1,396 cases of melanoma diagnosed before age 30 in 1988-2013 and 27,920 controls, obtained by linking cancer registry data to birth records in California.ResultsHigh birth weight (>4,000 g) was associated with 19% higher risk of melanoma (OR = 1.19; 95% CI = 1.02, 1.39), while low birth weight (

AimsStudies of environmental exposures and childhood leukemia studies do not usually account for residential mobility. Yet, in addition to being a potential risk factor, mobility can induce selection bias, confounding, or measurement error in such studies. Using data collected for California Powerline Study (CAPS), we attempt to disentangle the effect of mobility.MethodsWe analyzed data from a population-based case-control study of childhood leukemia using cases who were born in California and diagnosed between 1988 and 2008 and birth certificate controls. We used stratified logistic regression, case-only analysis, and propensity-score adjustments to assess predictors of residential mobility between birth and diagnosis, and account for potential confounding due to residential mobility.ResultsChildren who moved tended to be older, lived in housing other than single-family homes, had younger mothers and fewer siblings, and were of lower socioeconomic status. Odds ratios for leukemia among non-movers living

ObjectiveTo investigate three expression-altering NFE2L2 SNPs and four PPARGC1α previously implicated SNPs and pesticides on Parkinson's disease (PD) risk and symptom progression.MethodsIn 472 PD patients and 532 population-based controls, we examined variants and their interactions with maneb and paraquat (MB/PQ) pesticide exposure on PD onset (logistic regression) and progression of motor symptoms and cognitive decline (n = 192; linear repeated measures).ResultsNFE2L2 rs6721961 T allele was associated with a reduced risk of PD (OR = 0.70, 95% CI = 0.53, 0.94) and slower cognitive decline (β = 0.095; p = 0.0004). None of the PPARGC1α SNPs were marginally associated with PD risk. We estimate statistical interactions between MB/PQ and PPARGC1α rs6821591 (interaction p = 0.009) and rs8192678 (interaction p = 0.05), such that those with high exposure and the variant allele were at an increased risk of PD (OR ≥ 1.30, p ≤ 0.05). PPARGC1α rs6821591 was also associated with faster motor symptom progression as measured with the UPDRS-III (β = 0.234; p = 0.001).ConclusionOur study provides support for the involvement of both NFE2L2 and PPARGC1α in PD susceptibility and progression, marginally and through pathways involving MB/PQ exposure.

BackgroundCognitive impairment is a major health concern among older Mexican Americans, associated with significant morbidity and mortality, and may be influenced by environmental exposures.ObjectivesTo investigate whether agricultural based ambient organophosphorus (OP) exposure influences 1) the rate of cognitive decline and mortality and 2) whether these associations are mediated through metabolic or inflammatory biomarkers.MethodsIn a subset of older Mexican Americans from the Sacramento Area Latino Study on Aging (n = 430), who completed modified mini-mental state exams (3MSE) up to 7 times (1998-2007), we examined the relationship between estimated ambient OP exposures and cognitive decline (linear repeated measures model) and time to dementia or being cognitively impaired but not demented (CIND) and time to mortality (cox proportional hazards model). We then explored metabolic and inflammatory biomarkers as potential mediators of these relationships (additive hazards mediation). OP exposures at residential addresses were estimated with a geographic information system (GIS) based exposure assessment tool.ResultsParticipants with high OP exposure in the five years prior to baseline experienced faster cognitive decline (β = 0.038, p = 0.02) and higher mortality over follow-up (HR = 1.91, 95% CI = 1.12, 3.26). The direct effect of OP exposure was estimated at 241 (95% CI = 27-455) additional deaths per 100,000 person-years, and the proportion mediated through the metabolic hormone adiponectin was estimated to be 4% 1.5-19.2). No other biomarkers were associated with OP exposure.ConclusionsOur study provides support for the involvement of OP pesticides in cognitive decline and mortality among older Mexican Americans, possibly through biologic pathways involving adiponectin.

BackgroundThe incidence of childhood cancers has been increasing and environmental exposure to air toxics has been suggested as a possible risk factor. This study aims to explore ambient exposure to dichloromethane (methylene chloride).MethodsWe frequency matched by birth year approximately 20 cancer-free controls identified from birth records to all childhood cancers ages 0-5 in the California Cancer Registry diagnosed from 1988 to 2012; i.e. 13,636 cases and a total of 270,673 controls. Information on industrial releases of dichloromethane within 3km of birth addresses was retrieved from mandatory industry reports to the EPA's Toxics Release Inventory (TRI). We derived exposure to dichloromethane within close vicinity of birth residences using several modeling techniques including unconditional logistic regression models with multiple buffer distances, inverse distance weighting, and quadratic decay models.ResultsWe observed elevated risks for germ cell tumors [Odds Ratio (OR): 1.52, 95% Confidence Interval (CI) 1.11, 2.08], particularly teratomas (OR: 2.08, 95% CI 1.38-3.13), and possible increased risk for acute myeloid leukemias (AML) (OR: 1.64, 95% CI 1.15-2.32 in the quadratic decay model). Risk estimates were similar in magnitude whether releases occurred in pregnancy or the child's first year of life.ConclusionOur findings suggest that exposure to industrial dichloromethane releases may be a risk factor for childhood germ cell tumors, teratomas, and possibly AML.

PurposeStudies have reported an increased risk of childhood leukemia associated with exposure to magnetic fields. We conducted a large records-based case-control study of childhood leukemia risk and exposure to magnetic fields from power lines in California.MethodsThe study included 5,788 childhood leukemia cases (born in and diagnosed in California 1986-2008) matched to population-based controls on age and sex. We calculated magnetic fields at birth addresses using geographic information systems, aerial imagery, historical information on load and phasing, and site visits.ResultsBased on unconditional logistic regression controlling for age, sex, race/ethnicity, and socioeconomic status using subjects geocoded to a basic standard of accuracy, we report a slight risk deficit in two intermediate exposure groups and a small excess risk in the highest exposure group (odds ratio of 1.50 (95% confidence interval [0.70, 3.23])). Subgroup and sensitivity analyses as well as matched analyses gave similar results. All estimates had wide confidence intervals.ConclusionOur large, statewide, record-based case-control study of childhood leukemia in California does not in itself provide clear evidence of risk associated with greater exposure to magnetic fields from power lines, but could be viewed as consistent with previous findings of increased risk.

BackgroundParkinson's disease (PD) has motor and non-motor features that contribute to its phenotype and functional decline. Organophosphate (OP) pesticides and PON1 L55M, which influences OP metabolism, have been implicated in multiple mechanisms related to neuronal cell death and may influence PD symptom progression.ObjectiveTo investigate whether ambient agricultural OP exposure and PON1 L55M influence the rate of motor, cognitive, and mood-related symptom progression in PD.MethodsWe followed a longitudinal cohort of 246 incident PD patients on average over 5years (7.5years after diagnosis), repeatedly measuring symptom progression with the Mini-Mental State Exam (MMSE), Unified Parkinson's Disease Rating Scale (UPDRS), and Geriatric Depressive Scale (GDS). OP exposures were generated with a geographic information system (GIS) based exposure assessment tool. We employed repeated-measures regression to assess associations between OP exposure and/or PON1 L55M genotype and progression.ResultsHigh OP exposures were associated with faster progression of motor (UPDRS β=0.24, 95% CI=-0.01, 0.49) and cognitive scores (MMSE β=-0.06, 95% CI=-0.11, -0.01). PON1 55MM was associated with faster progression of motor (UPDRS β=0.28, 95% CI=0.08, 0.48) and depressive symptoms (GDS β=0.07; 95% CI=0.01, 0.13). We also found the PON1 L55M variant to interact with OP exposures in influencing MMSE cognitive scores (β=-1.26, 95% CI=-2.43, -0.09).ConclusionOur study provides preliminary support for the involvement of OP pesticides and PON1 in PD-related motor, cognitive, or depressive symptom progression. Future studies are needed to replicate findings and examine whether elderly populations generally are similarly impacted by pesticides or PON1 55M genotypes.

Background: Neighborhood socioeconomic status (nSES) has been found to be associated with breast cancer risk. It remains unclear whether this association applies across racial/ethnic groups independent of individual-level factors and is attributable to other neighborhood characteristics.Methods: We examined the independent and joint associations of education and nSES with odds of breast cancer. Residential addresses were geocoded for 2,838 cases and 3,117 controls and linked to nSES and social and built environment characteristics. We estimated ORs and 95% confidence intervals (CI) using multilevel logistic regression controlling for individual-level breast cancer risk factors and assessed the extent to which nSES associations were due to neighborhood characteristics.Results: Women living in the highest versus lowest nSES quintile had a nearly 2-fold greater odds of breast cancer, with elevated odds (adjusted ORs, 95% CI) for non-Hispanic whites (NHWs; 2.27; 1.45-3.56), African Americans (1.74; 1.07-2.83), U.S.-born Hispanics (1.82; 1.19-2.79), and foreign-born Hispanics (1.83; 1.06-3.17). Considering education and nSES jointly, ORs were increased for low education/high nSES NHWs (1.83; 1.14-2.95), high education/high nSES NHWs (1.64; 1.06-2.54), and high education/high nSES foreign-born Hispanics (2.17; 1.52-3.09) relative to their race/ethnicity/nativity-specific low education/low nSES counterparts. Adjustment for urban and mixed-land use characteristics attenuated the nSES associations for most racial/ethnic/nativity groups except NHWs.Conclusions: Our study provides empirical evidence for a role of neighborhood environments in breast cancer risk, specifically social and built environment attributes.Impact: Considering the role of neighborhood characteristics among diverse populations may offer insights to understand racial/ethnic disparities in breast cancer risk. Cancer Epidemiol Biomarkers Prev; 26(4); 541-52. ©2017 AACR.

Incidence rates of childhood leukemia in the United States have steadily increased over the last several decades, but only recently have disparities in the increase in incidence been recognized. In the current analysis, Surveillance, Epidemiology and End Results (SEER) data were used to evaluate recent trends in the incidence of childhood leukemia diagnosed at age 0-19 years from 1992 to 2013, overall and by age, race/ethnicity, gender and histologic subtype. Hispanic White children were more likely than non-Hispanic White, non-Hispanic Black or non-Hispanic Asian children to be diagnosed with acute lymphocytic leukemia (ALL) from 2009 to 2013. From 1992 to 2013, a significant increase in ALL incidence was observed for Hispanic White children [annual percent change (APC)Hispanic  = 1.08, 95% CI: 0.59, 1.58]; no significant increase was observed for non-Hispanic White, Black or Asian children. ALL incidence increased by about 3% per year from 1992 to 2013 for Hispanic White children diagnosed from 15 to 19 years (APC = 2.67; 95% CI: 0.88, 4.49) and by 2% for those 10-14 years (APC = 2.09; 95% CI: 0.57, 3.63), while no significant increases in incidence were observed in non-Hispanic White, Black, or Asian children of the same age. Acute myeloid leukemia (AML) incidence increased among non-Hispanic White children under 1 year at diagnosis, and among Hispanic White children diagnosed at age 1-4. The increase in incidence rates of childhood ALL appears to be driven by rising rates in older Hispanic children (10-14, and 15-19 years). Future studies are needed to evaluate reasons for the increase in ALL among older Hispanic children.

Introduction Demand for dermatologic services in safety net hospitals, which disproportionately serve patients with darker coloured skin, is growing. Teledermatology has the potential to increase access and improve outcomes, but studies have yet to demonstrate the reliability of teledermatology for all Fitzpatrick skin types. Methods We assessed the reliability of teledermatologists' diagnoses and management recommendations for store-and-forward teledermatology in patients with lightly pigmented (Fitzpatrick skin types I-III) versus darkly pigmented (Fitzpatrick skin types IV-VI) skin, when compared to in-person diagnosis and management decisions. This prospective study enrolled 232 adult patients, presenting with new, visible skin complaints in a Los Angeles county dermatology clinic. Forty-seven percent of patients were Fitzpatrick skin types I-III, and 53% were Fitzpatrick skin types IV-VI. Results Percent concordance for the identical primary diagnosis was 53.2% in lighter (Fitzpatrick I-III) skin types and 56.0% in darker (Fitzpatrick IV-VI) skin types. There was no statistically significant difference in concordance rates between lighter and darker skin types for primary diagnosis. Concordance rates for diagnostic testing, clinic-based therapy, and treatments were similar in both groups of Fitzpatrick skin types. Discussion These results suggest that teledermatology is reliable for the diagnosis and management of patients with all Fitzpatrick skin types.

BackgroundPreterm birth (PTB) has been associated with exposure to air pollution, but it is unclear whether effects might vary among air pollution sources and components.ObjectivesWe studied the relationships between PTB and exposure to different components of air pollution, including gases and particulate matter (PM) by size fraction, chemical composition, and sources.MethodsFine and ultrafine PM (respectively, PM2.5 and PM0.1) by source and composition were modeled across California over 2000-2008. Measured PM2.5, nitrogen dioxide, and ozone concentrations were spatially interpolated using empirical Bayesian kriging. Primary traffic emissions at fine scale were modeled using CALINE4 and traffic indices. Data on maternal characteristics, pregnancies, and birth outcomes were obtained from birth certificates. Associations between PTB (n = 442,314) and air pollution exposures defined according to the maternal residence at birth were examined using a nested matched case-control approach. Analyses were adjusted for maternal age, race/ethnicity, education and neighborhood income.ResultsAdjusted odds ratios for PTB in association with interquartile range (IQR) increases in average exposure during pregnancy were 1.133 (95% CI: 1.118, 1.148) for total PM2.5, 1.096 (95% CI: 1.085, 1.108) for ozone, and 1.079 (95% CI: 1.065, 1.093) for nitrogen dioxide. For primary PM, the strongest associations per IQR by source were estimated for onroad gasoline (9-11% increase), followed by onroad diesel (6-8%) and commercial meat cooking (4-7%). For PM2.5 composition, the strongest positive associations per IQR were estimated for nitrate, ammonium, and secondary organic aerosols (11-14%), followed by elemental and organic carbon (2-4%). Associations with local traffic emissions were positive only when analyses were restricted to births with residences geocoded at the tax parcel level.ConclusionsIn our statewide nested case-control study population, exposures to both primary and secondary pollutants were associated with an increase in PTB.CitationLaurent O, Hu J, Li L, Kleeman MJ, Bartell SM, Cockburn M, Escobedo L, Wu J. 2016. A statewide nested case-control study of preterm birth and air pollution by source and composition: California, 2001-2008. Environ Health Perspect 124:1479-1486; http://dx.doi.org/10.1289/ehp.1510133.

Smoking during pregnancy is a plausible risk factor for childhood cancer, yet previous studies have yielded conflicting results, and few prospective studies have been published. Data on maternal smoking were obtained from California birth certificates. We linked California birth certificates (births 2007-2011) with California Cancer Registry records for childhood cancer cases (diagnosed January 2007-September 2013) that were ages 5 or younger at diagnosis (N cases = 2,021). Controls (N = 40,356) were frequency-matched by birth year and randomly selected from birth certificate records. We used unconditional logistic regression to obtain odds ratios (OR) and 95% confidence intervals (CI) to assess the association between smoking during pregnancy and childhood cancer. We observed positive associations for gliomas (OR = 1.8, 95% CI: 1.0-3.4) and retinoblastoma (OR = 3.0, 95% CI: 1.4-6.6), particularly bilateral retinoblastoma (OR = 9.4, 95% CI 3.6-24.7) with maternal smoking in pregnancy. Maternal smoking during pregnancy may be a risk factor for retinoblastoma and certain types of childhood brain tumors.

IntroductionIntrauterine growth restriction has been associated with exposure to air pollution, but there is a need to clarify which sources and components are most likely responsible. This study investigated the associations between low birth weight (LBW,

BackgroundStudies have reported an increased risk of childhood leukaemia associated with living near high-voltage electric power transmission lines that extend to distances at which magnetic fields from lines are negligible. We conducted a large records-based case-control study of childhood leukaemia risk in the population living near power lines in California.MethodsThe study included 5788 childhood leukaemia and 3308 central nervous system (CNS) cancer cases (for comparison) born in and diagnosed in California (1986-2008), and matched to population-based controls by age and sex. We geocoded birth address and estimated the distance from residence to transmission lines using geographic information systems, aerial imagery, and, for some residences, site visits.ResultsFor leukaemia, there was a slight excess of cases within 50 m of a transmission line over 200 kV (odds ratio 1.4, 95% confidence interval 0.7-2.7). There was no evidence of increased risk for distances beyond 50 m, for lower-voltage lines, or for CNS cancers.ConclusionsOur findings did not clearly support an increased childhood leukaemia risk associated with close proximity (

ImportanceThe Hispanic epidemiologic paradox is the phenomenon that non-US-born Hispanic mothers who immigrate to the United States have better pregnancy outcomes than their US-born counterparts. It is unknown whether this advantage extends to childhood cancer risk.ObjectiveTo determine whether the risk for childhood cancers among Hispanic children varies by maternal birthplace.Design, setting, and participantsIn this population-based case-control study conducted in June 2015, cohort members were identified through California birth records of children born in California from January 1, 1983, to December 31, 2011. Information on cancer diagnoses was obtained from California Cancer Registry records from 1988 to 2012. Cases (n = 13 666) were identified from among children younger than 6 years in the California Cancer Registry and matched to California birth certificates. Control children (n = 15 513 718) included all other children born in California during the same period. Maternal birthplace and ethnic ancestry were identified from the birth certificate.Main exposuresMaternal race/ethnicity and birthplace.Main outcomes and measuresWe used Cox proportional hazards modeling to estimate hazard ratios (HRs) of childhood cancer.ResultsIncluded in the study were 4 246 295 children of non-Hispanic white mothers (51.3% male), 2 548 822 children of US-born Hispanic mothers (51.0% male), and 4 397 703 children of non-US-born Hispanic mothers (51.0% male). Compared with children of non-Hispanic white mothers, the children of non-US-born Hispanic mothers had a reduced risk for glioma (HR, 0.50; 95% CI, 0.44-0.58), astrocytoma (HR, 0.43; 95% CI, 0.36-0.51), neuroblastoma (HR, 0.47; 95% CI, 0.40-0.54), and Wilms tumor (HR, 0.70; 95% CI, 0.59-0.82). For these cancer types, the risk estimates for children of US-born Hispanic mothers fell between those of the children of US-born white and non-US-born Hispanic mothers. Children of Mexican-born mothers had a higher risk of yolk sac tumors (HR, 1.46; 95% CI, 0.99-2.17), while children of US-born Hispanic mothers with ancestry from countries other than Mexico had a higher risk for unilateral retinoblastoma (HR, 2.03; 95% CI, 1.33-3.11).Conclusions and relevanceFor several cancers, we observed differential risk by maternal place of birth. Examining the differences in health behaviors and environment between Hispanic groups may shed light on childhood cancer etiology.

BackgroundStudies suggested that variants in the ABCB1 gene encoding P-glycoprotein, a xenobiotic transporter, may increase susceptibility to pesticide exposures linked to Parkinson's Disease (PD) risk.ObjectivesTo investigate the joint impact of two ABCB1 polymorphisms and pesticide exposures on PD risk.MethodsIn a population-based case control study, we genotyped ABCB1 gene variants at rs1045642 (c.3435C/T) and rs2032582 (c.2677G/T/A) and assessed occupational exposures to organochlorine (OC) and organophosphorus (OP) pesticides based on self-reported occupational use and record-based ambient workplace exposures for 282 PD cases and 514 controls of European ancestry. We identified active ingredients in self-reported occupational use pesticides from a California database and estimated ambient workplace exposures between 1974 and 1999 employing a geographic information system together with records for state pesticide and land use. With unconditional logistic regression, we estimated marginal and joint contributions for occupational pesticide exposures and ABCB1 variants in PD.ResultsFor occupationally exposed carriers of homozygous ABCB1 variant genotypes, we estimated odds ratios of 1.89 [95% confidence interval (CI): (0.87, 4.07)] to 3.71 [95% CI: (1.96, 7.02)], with the highest odds ratios estimated for occupationally exposed carriers of homozygous ABCB1 variant genotypes at both SNPs; but we found no multiplicative scale interactions.ConclusionsThis study lends support to a previous report that commonly used pesticides, specifically OCs and OPs, and variant ABCB1 genotypes at two polymorphic sites jointly increase risk of PD.

BackgroundWe conducted a large registry-based study in California to investigate the association between race/ethnicity and childhood leukaemia focusing on two subtypes: acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML).MethodsWe obtained information on 5788 cases and 5788 controls by linking California cancer and birth registries. We evaluated relative risk of childhood leukaemia by race and ethnicity of the child and their parents using conditional logistic regression, with adjustment for potential confounders.ResultsCompared with Whites, Black children had lower risk of ALL (OR=0.54, 95% CI 0.45 to 0.66) as well as children of Black/Asian parents (OR=0.31, 95% CI 0.10 to 0.94). Asian race was associated with increased risk of AML with OR=1.643, 95% CI 1.10 to 2.46 for Asian vs Whites; and OR=1.67, 95% CI 1.04 to 2.70 for Asian/Asian vs White/White. Hispanic ethnicity was associated with increased risk of ALL (OR=1.37, 95% CI 1.22 to 1.52). A gradient in risk of ALL was observed while comparing Hispanic children with both parents Hispanic, one parent Hispanic and non-Hispanic children (p Value for trend

IntroductionA high prevalence of vitamin D deficiency has been reported in Parkinson's disease (PD). Epidemiologic studies examining variability in genes involved in vitamin D metabolism have not taken into account level of exposure to ultraviolet radiation (UVR). We examined whether exposure to UVR (as a surrogate for vitamin D levels) and variations in the vitamin D receptor gene (VDR) are associated with PD.MethodsWithin a geographical information system (GIS) we linked participants' geocoded residential address data to ground level UV data to estimate historical exposure to UVR. Six SNPs in VDR were genotyped in non-Hispanic Caucasian subjects.ResultsAverage lifetime UVR exposure levels were >5000 Wh/m(2), which was higher than levels for populations in previous studies, and UVR exposure did not differ between cases and controls. Homozygotes for the rs731236 TT (major allele) genotype had a 31% lower risk of PD risk (OR=0.69; 95% CI=0.49, 0.98; p=0.04 for TT vs. TC+CC). The rs7975232 GG (minor allele) genotype was also associated with decreased risk of PD (OR=0.63; 95% CI=0.42, 0.93; p=0.02 for GG vs. TG+TT). The association between PD risk and a third locus, rs1544410 (BsmI), was not statistically significant after adjustment for covariates, although there was a trend for lower risk with the GG genotype.ConclusionsThis study provides initial evidence that VDR polymorphisms may modulate risk of PD in a population highly exposed to UVR throughout lifetime.

We examined ambient exposure to specific air toxics in the perinatal period in relation to retinoblastoma development. Cases were ascertained from California Cancer Registry records of children diagnosed between 1990 and 2007 and matched to California birth certificates. Controls were randomly selected from state birth records for the same time period. We chose 27 air toxics for the present study that had been listed as possible, probable, or established human carcinogens by the International Agency for Research on Cancer. Children (103 cases and 30,601 controls) included in the study lived within 5 miles of an air pollution monitor. Using logistic regression analyses, we modeled the risk of retinoblastoma due to air toxic exposure, separately for exposures in pregnancy and the first year of life. With a per interquartile range increase in air toxic exposure, retinoblastoma risk was found to be increased with pregnancy exposure to benzene (OR=1.67, 95% CI: 1.06, 2.64) and other toxics which primarily arise from gasoline and diesel combustion: toluene, 1,3-butadiene, ethyl benzene, ortho-xylene, and meta/para-xylene; these six toxics were highly correlated. Retinoblastoma risk was also increased with pregnancy exposure to chloroform (OR=1.35, 95% CI: 1.07, 1.70), chromium (OR=1.29, 95% CI: 1.04, 1.60), para-dichlorobenzene (OR=1.24, 95% CI: 1.04, 1.49), nickel (OR=1.48, 95% CI: 1.08, 2.01), and in the first year of life, acetaldehyde (OR=1.62, 95% CI: 1.06, 2.48). Sources of these agents are discussed.

We conducted a large epidemiologic case-control study in California to examine the association between childhood cancer risk and distance from the home address at birth to the nearest high-voltage overhead transmission line as a replication of the study of Draper et al. in the United Kingdom. We present a detailed description of the study design, methods of case ascertainment, control selection, exposure assessment and data analysis plan. A total of 5788 childhood leukemia cases and 3308 childhood central nervous system cancer cases (included for comparison) and matched controls were available for analysis. Birth and diagnosis addresses of cases and birth addresses of controls were geocoded. Distance from the home to nearby overhead transmission lines was ascertained on the basis of the electric power companies' geographic information system (GIS) databases, additional Google Earth aerial evaluation and site visits to selected residences. We evaluated distances to power lines up to 2000 m and included consideration of lower voltages (60-69 kV). Distance measures based on GIS and Google Earth evaluation showed close agreement (Pearson correlation >0.99). Our three-tiered approach to exposure assessment allowed us to achieve high specificity, which is crucial for studies of rare diseases with low exposure prevalence.

BackgroundGenetic and environmental factors are believed to contribute to the development of autism, but relatively few studies have considered potential environmental risks. Here, we examine risks for autism in children related to in utero exposure to monitored ambient air toxics from urban emissions.MethodsAmong the cohort of children born in Los Angeles County, California, 1995-2006, those whose mothers resided during pregnancy in a 5-km buffer around air toxics monitoring stations were included (n = 148,722). To identify autism cases in this cohort, birth records were linked to records of children diagnosed with primary autistic disorder at the California Department of Developmental Services between 1998 and 2009 (n = 768). We calculated monthly average exposures during pregnancy for 24 air toxics selected based on suspected or known neurotoxicity or neurodevelopmental toxicity. Factor analysis helped us identify the correlational structure among air toxics, and we estimated odds ratios (ORs) for autism from logistic regression analyses.ResultsAutism risks were increased per interquartile range increase in average concentrations during pregnancy of several correlated toxics mostly loading on 1 factor, including 1,3-butadiene (OR = 1.59 [95% confidence interval = 1.18-2.15]), meta/para-xylene (1.51 [1.26-1.82]), other aromatic solvents, lead (1.49 [1.23-1.81]), perchloroethylene (1.40 [1.09-1.80]), and formaldehyde (1.34 [1.17-1.52]), adjusting for maternal age, race/ethnicity, nativity, education, insurance type, parity, child sex, and birth year.ConclusionsRisks for autism in children may increase following in utero exposure to ambient air toxics from urban traffic and industry emissions, as measured by community-based air-monitoring stations.

BackgroundLow birth weight (LBW,

There are few established causes of leukemia, the most common type of cancer in children. Studies in adults suggest a role for specific environmental agents, but little is known about any effect from exposures in pregnancy to toxics in ambient air. In our case-control study, we ascertained 69 cases of acute lymphoblastic leukemia (ALL) and 46 cases of acute myeloid leukemia (AML) from California Cancer Registry records of children

BackgroundEpidemiologic studies indicate that infections in early childhood may protect against pediatric acute lymphoblastic leukemia (ALL).MethodsWe 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.ResultsWe 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).ConclusionOur results support the hypothesis that infections in early childhood decrease risk of ALL.ImpactOur findings implicate early life exposure to infections as protective factors for ALL in young children.

ObjectiveTo study prenatal air toxic exposure and Wilms' tumor in children.MethodsWe identified 337 Wilms' tumor cases among children younger than 6 years (1988 to 2008) from the California Cancer Registry, randomly selected 96,514 controls from California birth rolls in 20:1 ratio matched to all cancer cases, then linked birth addresses to air monitors within 15 miles to assess exposures. Multiple logistic regressions were applied to estimate effects.ResultsChildren prenatally exposed to formaldehyde, polycyclic aromatic hydrocarbons, perchloroethylene, or acetaldehyde in the third trimester had an increased odds of Wilms' tumor per interquartile increase in concentration (odds ratio [95% confidence interval]: 1.28 [1.12 to 1.45], 1.10 [0.99 to 1.22], 1.09 [1.00 to 1.18], 1.25 [1.07 to 1.45], respectively).ConclusionsWe found positive associations for four air toxics. This is the first study of this kind. Future studies are needed to confirm our findings.

BackgroundResearch is limited on the independent and joint effects of individual- and neighborhood-level socioeconomic status (SES) on breast cancer survival across different racial/ethnic groups.MethodsWe studied individual-level SES, measured by self-reported education, and a composite neighborhood SES (nSES) measure in females (1,068 non-Hispanic whites, 1,670 Hispanics, 993 African-Americans, and 674 Asian-Americans), ages 18 to 79 years and diagnosed 1995 to 2008, in the San Francisco Bay Area. We evaluated all-cause and breast cancer-specific survival using stage-stratified Cox proportional hazards models with cluster adjustment for census block groups.ResultsIn models adjusting for education and nSES, lower nSES was associated with worse all-cause survival among African-Americans (P trend = 0.03), Hispanics (P trend = 0.01), and Asian-Americans (P trend = 0.01). Education was not associated with all-cause survival. For breast cancer-specific survival, lower nSES was associated with poorer survival only among Asian-Americans (P trend = 0.01). When nSES and education were jointly considered, women with low education and low nSES had 1.4 to 2.7 times worse all-cause survival than women with high education and high nSES across all races/ethnicities. Among African-Americans and Asian-Americans, women with high education and low nSES had 1.6 to 1.9 times worse survival, respectively. For breast cancer-specific survival, joint associations were found only among Asian-Americans with worse survival for those with low nSES regardless of education.ConclusionsBoth neighborhood and individual SES are associated with survival after breast cancer diagnosis, but these relationships vary by race/ethnicity.ImpactA better understanding of the relative contributions and interactions of SES with other factors will inform targeted interventions toward reducing long-standing disparities in breast cancer survival.

ObjectivesThere is a general consensus that pesticides are involved in the aetiology of Parkinson's disease (PD), although associations between specific pesticides and the risk of developing PD have not been well studied. This study examines the risk of developing PD associated with specific organophosphate (OP) pesticides and their mechanisms of toxicity.MethodsThis case-control study uses a geographic information system-based exposure assessment tool to estimate ambient exposure to 36 commonly used OPs from 1974 to 1999. All selected OPs were analysed individually and also in groups formed according to their presumed mechanisms of toxicity.ResultsThe study included 357 incident PD cases and 752 population controls living in the Central Valley of California. Ambient exposure to each OP evaluated separately increased the risk of developing PD. However, most participants were exposed to combinations of OPs rather than a single pesticide. Risk estimates for OPs grouped according to different presumed functionalities and toxicities were similar and did not allow us to distinguish between them. However, we observed exposure-response patterns with exposure to an increasing number of OPs.ConclusionsThis study adds strong evidence that OPs are implicated in the aetiology of idiopathic PD. However, studies of OPs at low doses reflective of real-world ambient exposure are needed to determine the mechanisms of neurotoxicity.

BackgroundLymphoma is the third most common childhood malignancy and comprises two types, Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). The etiology of pediatric lymphomas is largely unknown, but has been suggested to have prenatal origins.MethodsIn this population-based study, California birth certificates were identified for 478 lymphoma cases diagnosed in children 0-5 years of age between 1988 and 2007; 208,015 controls frequency-matched by birth year were randomly selected from California birth records.ResultsCompared to non-Hispanic whites, Hispanic children had an increased risk of HL (odds ratio (OR) and 95% confidence interval (CI) 2.43 [1.14, 5.17]), and in particular, were diagnosed more often with the mixed cellularity subtype. For all types of lymphoma, we observed an about twofold risk increase with indicators for high risk pregnancies including tocolysis, fetopelvic disproportion and previous preterm birth. NHL risk doubled with the complication premature rupture of membranes (OR and 95% CI 2.18 [1.12, 4.25]) and HL with meconium staining of amniotic fluids (OR and 95% CI 2.55 [1.01, 6.43]).ConclusionThese data support previously reported associations between Hispanic ethnicity and HL and suggest that pregnancy related factors, such as intra-uterine infections and factors associated with preterm labor, may be involved in lymphoma pathogenesis.

BackgroundThe literature on traffic-related air pollution and childhood cancers is inconclusive, and little is known on rarer cancer types.ObjectivesWe sought to examine associations between childhood cancers and traffic-related pollution exposure.MethodsThe present study included children < 6 years of age identified in the California Cancer Registry (born 1998-2007) who could be linked to a California birth certificate (n = 3,590). Controls were selected at random from California birthrolls (n = 80,224). CAlifornia LINE Source Dispersion Modeling, version 4 (CALINE4) was used to generate estimates of local traffic exposures for each trimester of pregnancy and in the first year of life at the address indicated on the birth certificate. We checked our findings by additionally examining associations with particulate matter (≤ 2.5 μm in aerodynamic diameter; PM2.5) pollution measured by community-based air pollution monitors, and with a simple measure of traffic density.ResultsWith unconditional logistic regression, a per interquartile range increase in exposure to traffic-related pollution during the first trimester (0.0538 ppm carbon monoxide, estimated using CALINE4) was associated with acute lymphoblastic leukemia [ALL; first trimester odds ratio (OR) = 1.05; 95% CI: 1.01, 1.10]; germ cell tumors (OR = 1.16; 95% CI: 1.04, 1.29), particularly teratomas (OR = 1.26; 95% CI: 1.12, 1.41); and retinoblastoma (OR = 1.11; 95% CI: 1.01, 1.21), particularly bilateral retinoblastoma (OR = 1.16; 95% CI: 1.02, 1.33). Retinoblastoma was also associated with average PM2.5 concentrations during pregnancy, and ALL and teratomas were associated with traffic density near the child's residence at birth.ConclusionsWe estimated weak associations between early exposure to traffic pollution and several childhood cancers. Because this is the first study to report on traffic pollution in relation to retinoblastoma or germ cell tumors, and both cancers are rare, these findings require replication in other studies.

In the mid-1980s, there was a rise in incidence rates of childhood brain tumors (CBT) in the United States that appeared to stabilize at a higher rate in the early 1990 s. An updated analysis of the pattern of CBT over the past 2 decades, with commentary on whether the elevated incidence rate has continued, is past due. We used Surveillance, Epidemiology and End Results (SEER) data to examine trends in incidence of CBT from 1973 through 2009. We examined age-adjusted incidence rates (AAIRs) and secular trends for all malignant brain tumors combined (SEER classification) by histologic tumor type and anatomic site. The incidence of CBT remained stable from 1987 to 2009 [annual percent change (APC) = 0.10; 95 % confidence intervals (CI) -0.39 to 0.61] with an AAIR for all CBT of 3.32 (95 % CI 3.22-3.42). The stability of rates in these two decades contrast the change that occurred in the mid-1980s (1983-1986), when the incidence of CBT increased by 53 % (APC = 14.06; 95 % CI 4.05-25.0). From 1983 to 1986, statistically significant rate increases were observed for pilocytic astrocytoma, PNET/medulloblastoma, and mixed glioma. Further, the rate of increase in pilocytic astrocytoma was similar to the rate of decrease for astrocytomas NOS from 1981 to 2009, suggesting a change from a more general to more specific classification. After the increase in rates in the mid-1980s, rates of CBT over the past two decades have stabilized. Changes in incidence rates of subtypes of tumors over this time period reflect changes both in classification of CBT and in diagnostic techniques.

Little is known about the etiology of neuroblastoma, the most common cancer in infancy. In this study, we examined maternal exposure to ambient air toxics in pregnancy in relation to neuroblastoma in the child. We ascertained all cases of neuroblastoma listed in the California Cancer Registry 1990-2007 that could be linked to a California birth certificate, and controls were selected at random from California birth records. Average air toxics exposures during pregnancy were determined based upon measures from community-based air pollution monitors. The study included 75 cases and 14,602 controls who lived with 5 km of an air pollution monitor, and we additionally examined results for those living within a smaller radius around the monitor (2.5 km). Logistic regression was used to determine the risk of neuroblastoma with one interquartile range increase in air toxic exposure. Neuroblastoma risk was increased with higher maternal exposure to carbon tetrachloride (OR=2.65, 95%CI 1.07, 6.53) and polycyclic aromatic hydrocarbons (OR=1.39, 95%CI 1.05, 1.84), particularly indeno(1,2,3-cd)pyrene and dibenz(a,h)anthracene. Hexavalent chromium was associated with neuroblastoma at the 5 km distance (OR=1.32, 95%CI 1.00, 1.74) but not at the 2.5 km distance. This is one of the first studies to report associations between neuroblastoma and these air toxics.

Exposure to air pollution during pregnancy has been linked to the risk of childhood cancer, but the evidence remains inconclusive. In the present study, we used land use regression modeling to estimate prenatal exposures to traffic exhaust and evaluate the associations with cancer risk in very young children. Participants in the Air Pollution and Childhood Cancers Study who were 5 years of age or younger and diagnosed with cancer between 1988 and 2008 were had their records linked to California birth certificates, and controls were selected from birth certificates. Land use regression-based estimates of exposures to nitric oxide, nitrogen dioxide, and nitrogen oxides were assigned based on birthplace residence and temporally adjusted using routine monitoring station data to evaluate air pollution exposures during specific pregnancy periods. Logistic regression models were adjusted for maternal age, race/ethnicity, educational level, parity, insurance type, and Census-based socioeconomic status, as well as child's sex and birth year. The odds of acute lymphoblastic leukemia increased by 9%, 23%, and 8% for each 25-ppb increase in average nitric oxide, nitrogen dioxide, and nitrogen oxide levels, respectively, over the entire pregnancy. Second- and third-trimester exposures increased the odds of bilateral retinoblastoma. No associations were found for annual average exposures without temporal components or for any other cancer type. These results lend support to a link between prenatal exposure to traffic exhaust and the risk of acute lymphoblastic leukemia and bilateral retinoblastoma.

Cytoplasmic inclusions known as Lewy bodies, a hallmark of Parkinson's disease (PD) pathology, may protect against cytotoxic proteins. Since the ubiquitin-proteasome system (UPS) degrades cytotoxic proteins, dysfunction in the UPS may contribute to PD etiology. Our goal in this study was to screen pesticides for proteasome inhibition and investigate (i) whether ambient exposures to pesticides that inhibit the UPS increase PD risk and (ii) whether genetic variation in candidate genes of the UPS pathway modify those increased risks. We assessed 26S UPS activity in SK-N-MC(u) cells by fluorescence. We recruited idiopathic PD cases (n=360) and population-based controls (n=816) from three counties in California with considerable commercial agriculture. We determined ambient pesticide exposure by our validated GIS-based model utilizing residential and workplace address histories. We limited effect measure modification assessment to Caucasians (287 cases, 453 controls). Eleven of 28 pesticides we screened inhibited 26S UPS activity at 10 µM. Benomyl, cyanazine, dieldrin, endosulfan, metam, propargite, triflumizole, and ziram were associated with increased PD risk. We estimated an odds ratio of 2.14 (95% CI: 1.42, 3.22) for subjects with ambient exposure to any UPS-inhibiting pesticide at both residential and workplace addresses; this association was modified by genetic variation in the s-phase kinase-associated protein 1 gene (SKP1; interaction p-value=0.005). Our results provide evidence that UPS-inhibiting pesticides play a role in the etiology of PD and suggest that genetic variation in candidate genes involved in the UPS pathway might exacerbate the toxic effects of pesticide exposures.

BackgroundHepatoblastoma is a malignant embryonal tumor typically diagnosed in children younger than five years of age. Little is known on hepatoblastoma etiology.MethodsWe matched California Cancer Registry records of hepatoblastomas diagnosed in children younger than age 6 from 1988 to 2007 to birth records using a probabilistic record linkage program, yielding 261 cases. Controls (n=218,277), frequency matched by birth year to all cancer cases in California for the same time period, were randomly selected from California birth records. We examined demographic and socioeconomic information, birth characteristics, pregnancy history, complications in pregnancy, labor and delivery, and abnormal conditions and clinical procedures relating to the newborn, with study data taken from birth certificates.ResultsWe observed increased risks for hepatoblastoma among children with low [1500-2499 g, Odds Ratio (OR)=2.02, 95% confidence interval (CI) 1.29-3.15] and very low birthweight (

BackgroundStudies have shown that higher solar UV radiation exposure (UVR) may be related to lower risk of some cancers in adults. Recently, an ecologic study reported lower risks of some cancers among children living in higher UVR cities and countries. In a large population-based case-control study in California, we tested the hypothesis that childhood cancers may be influenced by UVR.MethodsCancers in children ages 0 to 5 years were identified from California Cancer Registry records for 1988 to 2007 and linked to birth certificate data. Controls were sampled from the birth certificates at a ratio of 20:1. Based on birth address, we assigned UVR exposure in units of Watt-hours/m(2) using a geostatistical exposure model developed with data from the National Solar Radiation Database.ResultsFor cases with UVR exposure of 5,111 Watt-hours/m(2) or above, we estimated a reduction in odds of developing acute lymphoblastic leukemia (OR: 0.89, 95% CI: 0.81-0.99), hepatoblastoma (OR: 0.69, 95% CI: 0.48-1.00), and non-Hodgkin's lymphoma (OR: 0.71, 95% CI: 0.50-1.02) adjusting for mother's age, mother's race, and child's year of birth. We also observed a small increase in odds for intracranial/intraspinal embryonal tumors (OR: 1.29, 95% CI: 1.01-1.65).ConclusionsOur findings suggest that UVR during pregnancy may decrease the odds of some childhood cancers. Future studies should explore additional factors that may be correlated with UVR exposure and possibly include biomarkers of immune function and vitamin D.ImpactThis study shows protective associations of UVR with some childhood cancers.

BackgroundRhabdoid tumors are a rare and aggressive cancer subtype which is usually diagnosed in early childhood. Little is known about their etiology. The purpose of this study was to describe the epidemiology of rhabdoid tumors and examine their relation to perinatal characteristics.MethodsWe identified 44 atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system (CNS) and 61 rhabdoid sarcomas (renal and extra-renal non-CNS tumors) from California Cancer Registry records of diagnoses 1988-2007 among children 42 weeks, OR = 3.66, 95% CI 1.54, 8.71) also increased risk of rhabdoid sarcomas. Rhabdoid sarcoma cases (OR = 3.08, 95% CI 1.11, 8.55) and AT/RT cases (OR = 3.16, 95% CI 1.23, 8.13) also were more likely to be multiple births.ConclusionThe excess of twin pregnancies may suggest an association with infertility treatments. This is the first population-based epidemiologic study to examine these rare tumors.

PurposeThe etiology of retinoblastoma remains poorly understood. In the present study, we examined associations between perinatal factors and retinoblastoma risk in California children.MethodsWe identified 609 retinoblastoma cases (420 unilateral, 187 bilateral, and 2 with laterality unknown) from California Cancer Registry records of diagnoses 1988-2007 among children

BackgroundNumerous studies have linked criteria air pollutants with adverse birth outcomes, but there is less information on the importance of specific emission sources, such as traffic, and air toxics.ObjectivesWe used three exposure data sources to examine odds of term low birth weight (LBW) in Los Angeles, California, women when exposed to high levels of traffic-related air pollutants during pregnancy.MethodsWe identified term births during 1 June 2004 to 30 March 2006 to women residing within 5 miles of a South Coast Air Quality Management District (SCAQMD) Multiple Air Toxics Exposure Study (MATES III) monitoring station. Pregnancy period average exposures were estimated for air toxics, including polycyclic aromatic hydrocarbons (PAHs), source-specific particulate matter < 2.5 μm in aerodynamic diameter (PM2.5) based on a chemical mass balance model, criteria air pollutants from government monitoring data, and land use regression (LUR) model estimates of nitric oxide (NO), nitrogen dioxide (NO2) and nitrogen oxides (NOx). Associations between these metrics and odds of term LBW (< 2,500 g) were examined using logistic regression.ResultsOdds of term LBW increased approximately 5% per interquartile range increase in entire pregnancy exposures to several correlated traffic pollutants: LUR measures of NO, NO2, and NOx, elemental carbon, and PM2.5 from diesel and gasoline combustion and paved road dust (geological PM2.5).ConclusionsThese analyses provide additional evidence of the potential impact of traffic-related air pollution on fetal growth. Particles from traffic sources should be a focus of future studies.

Lack of disaggregated data for Native Hawaiians and Pacific Islanders (NHPIs) in the U.S. has resulted in severe gaps in understanding health disparities and unique health needs of NHPIs. Telephone interviews were conducted with 272 cancer patients identified by a population-based cancer registry. The self-reported NHPIs status was compared with that identified by the registry. Sensitivity, Specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) were calculated. Alternative NHPIs identification methods were explored. The registry had acceptable sensitivity (89%), specificity (96%) and NPV (99%), but low PPV (62%) in identifying NHPIs. Using additional information on surname and birthplace from the registry improved the identification of NHPIs, but either increased the false positive or decreased the counts of true NHPIs cases. Improved data collection methods and practices in identifying NHPIs in population-based cancer registries are needed and caution in interpreting cancer data for NHPIs is warranted.

IntroductionInvestigators have hypothesized that consuming pesticide-contaminated well water plays a role in Parkinson's disease (PD), and several previous epidemiologic studies support this hypothesis.ObjectivesWe investigated whether consuming water from private wells located in areas with documented historical pesticide use was associated with an increased risk of PD.MethodsWe employed a geographic information system (GIS)-based model to estimate potential well-water contamination from agricultural pesticides among 368 cases and 341 population controls enrolled in the Parkinson's Environment and Genes Study (PEG). We separately examined 6 pesticides (diazinon, chlorpyrifos, propargite, paraquat, dimethoate, and methomyl) from among 26 chemicals selected for their potential to pollute groundwater or for their interest in PD, and because at least 10% of our population was exposed to them.ResultsCases were more likely to have consumed private well water and to have consumed it on average 4.3 years longer than controls (p = 0.02). High levels of possible well-water contamination with methomyl [odds ratio (OR) = 1.67; 95% confidence interval (CI), 1.00-2.78]), chlorpyrifos (OR = 1.87; 95% CI, 1.05-3.31), and propargite (OR = 1.92; 95% CI, 1.15-3.20) resulted in approximately 70-90% increases in relative risk of PD. Adjusting for ambient pesticide exposures only slightly attenuated these increases. Exposure to a higher number of water-soluble pesticides and organophosphate pesticides also increased the relative risk of PD.ConclusionOur study, the first to use agricultural pesticide application records, adds evidence that consuming well water presumably contaminated with pesticides may play a role in the etiology of PD.

BackgroundResearch suggests that independent and joint effects of genetic variability in the dopamine transporter (DAT) locus and pesticides may influence Parkinson's disease (PD) risk.MaterialsMethodsIn 324 incident PD patients and 334 population controls from our rural California case-control study, we genotyped rs2652510, rs2550956 (for the DAT 5' clades), and the 3' variable number of tandem repeats (VNTR). Using geographic information system methods, we determined residential exposure to agricultural maneb and paraquat applications. We also collected occupational pesticide use data. Employing logistic regression, we calculated odds ratios (ORs) for clade diplotypes, VNTR genotype, and number of susceptibility (A clade and 9-repeat) alleles and assessed susceptibility allele-pesticide interactions.ResultsPD risk was increased separately in DAT A clade diplotype carriers [AA vs. BB: OR = 1.66; 95% confidence interval (CI), 1.08-2.57] and 3' VNTR 9/9 carriers (9/9 vs. 10/10: OR = 1.8; 95% CI, 0.96-3.57), and our data suggest a gene dosing effect. Importantly, high exposure to paraquat and maneb in carriers of one susceptibility allele increased PD risk 3-fold (OR = 2.99; 95% CI, 0.88-10.2), and in carriers of two or more alleles more than 4-fold (OR = 4.53; 95% CI, 1.70-12.1). We obtained similar results for occupational pesticide measures.DiscussionUsing two independent pesticide measures, we a) replicated previously reported gene-environment interactions between DAT genetic variants and occupational pesticide exposure in men and b) overcame previous limitations of nonspecific pesticide measures and potential recall bias by employing state records and computer models to estimate residential pesticide exposure.ConclusionOur results suggest that DAT genetic variability and pesticide exposure interact to increase PD risk.