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BackgroundSelf-reported residential use of pesticides has consistently been associated with increased risk of childhood leukemia. However, these studies were limited in their ability to identify specific insecticide active ingredients that were associated with risk.ObjectiveWe used household carpet dust measurements of 20 insecticides (two carbamate, 10 organophosphate, two organochlorine, and six pyrethroid) as indicators of exposure and evaluated associations with the risk of childhood acute lymphoblastic leukemia (ALL).MethodsWe conducted a population-based case-control study of 252 ALL cases diagnosed from 1999 to 2007 and 306 birth certificate controls from 35 counties in Central and Northern California. Carpet dust was collected at a second interview (2001-2007) for cases who had not moved since diagnosis (comparable reference date for controls) using a specialized vacuum cleaner in the room where the child spent most of their time or from the household vacuum. Insecticides were categorized as detected (yes/no), or as tertiles or quartiles of their distributions among controls. We calculated odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression adjusting for demographic characteristics, interview year, and season of dust collection.ResultsPermethrin, chlorpyrifos, diazinon, and carbaryl were the most frequently detected insecticide active ingredients. When we compared the highest quartile to the lowest or to non-detections, there was no association with ALL for permethrin (OR Q4 vs. Q1 = 0.81; 95% CI 0.50-1.31), carbaryl (OR Q4 vs. non-detects = 0.61, 95% CI 0.34-1.08) or chlorpyrifos (OR Q4 vs. Q1 = 0.60; 95% CI 0.36-1.00). The highest quartile of diazinon concentration was inversely associated with risk in the single pesticide model but without a monotonic exposure-response (p-trend = 0.14). After adjusting for other common insecticides, the OR was not significant (OR Q4 vs. Q1 = 0.58; 95% CI 0.33-1.05). None of the other insecticides were associated with risk.ConclusionOur results should be interpreted within the limitations of the case-control study design including the use of a single post-diagnosis dust sample and restriction to residentially stable participants, which may have resulted in selection bias. Although difficult to implement, additional studies with assessment of exposure to insecticide active and non-active ingredients are necessary to elucidate the role of these common exposures in childhood leukemia risk.

BackgroundParental smoking is implicated in the etiology of acute lymphoblastic leukemia (ALL), the most common childhood cancer. We recently reported an association between an epigenetic biomarker of early-life tobacco smoke exposure at the AHRR gene and increased frequency of somatic gene deletions among ALL cases.MethodsHere, we further assess this association using two epigenetic biomarkers for maternal smoking during pregnancy-DNA methylation at AHRR CpG cg05575921 and a recently established polyepigenetic smoking score-in an expanded set of 482 B-cell ALL (B-ALL) cases in the California Childhood Leukemia Study with available Illumina 450K or MethylationEPIC array data. Multivariable Poisson regression models were used to test the associations between the epigenetic biomarkers and gene deletion numbers.ResultsWe found an association between DNA methylation at AHRR CpG cg05575921 and deletion number among 284 childhood B-ALL cases with MethylationEPIC array data, with a ratio of means (RM) of 1.31 [95% confidence interval (CI), 1.02-1.69] for each 0.1 β value reduction in DNA methylation, an effect size similar to our previous report in an independent set of 198 B-ALL cases with 450K array data [meta-analysis summary RM (sRM) = 1.32; 95% CI, 1.10-1.57]. The polyepigenetic smoking score was positively associated with gene deletion frequency among all 482 B-ALL cases (sRM = 1.31 for each 4-unit increase in score; 95% CI, 1.09-1.57).ConclusionsWe provide further evidence that prenatal tobacco-smoke exposure may influence the generation of somatic copy-number deletions in childhood B-ALL.ImpactAnalyses of deletion breakpoint sequences are required to further understand the mutagenic effects of tobacco smoke in childhood ALL.

BackgroundPrenatal immune development may play an important role in the etiology of childhood acute lymphoblastic leukemia (ALL).MethodsSeven cytokines, IL1β, IL4, IL6, IL8, GM-CSF, TNFα, and VEGF, were analyzed in blood spots collected at birth from 1,020 ALL cases and 1,003 controls participating in the California Childhood Leukemia Study. ORs and 95% confidence intervals (95% CI) associated with an interquartile range increment in cytokine levels were calculated using logistic regression, adjusting for sociodemographic and birth characteristics.ResultsWe found that patients with ALL were born with higher levels of a group of correlated cytokines than controls [IL1β: OR of 1.18 (95% confidence interval [CI], 1.03-1.35); IL8: 1.19 (1.03-1.38); TNFα: 1.15 (1.01-1.30); VEGF: 1.16 (1.01-1.33)], especially among children of Latina mothers (ORs from 1.31 to 1.40) and for ALL with high hyperdiploidy (ORs as high as 1.27). We found that neonatal cytokine levels were correlated with neonatal levels of endogenous metabolites which had been previously associated with ALL risk; however, there was no evidence that the cytokines were mediating the relationship between these metabolites and ALL risk.ConclusionsWe posit that children born with altered cytokine levels are set on a trajectory towards an increased risk for subsequent aberrant immune reactions that can initiate ALL.ImpactThis is the first study to evaluate the interplay between levels of immunomodulatory cytokines at birth, prenatal exposures, and the risk of childhood ALL.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Thirdhand smoke (THS) is the residual tobacco contamination that remains after the smoke clears. We investigated the effects of THS exposure in utero and during early life in a transgenic Cdkn2a knockout mouse model that is vulnerable to the development of leukemia/lymphoma. Female mice, and their offspring, were exposed from the first day of pregnancy to weaning. Plasma cytokines, body weight and hematologic parameters were measured in the offspring. To investigate THS exposure effects on the development of leukemia/lymphoma, bone marrow (BM) was collected from control and THS-exposed mice and transplanted into BM-ablated recipient mice, which were followed for tumor development for 1 year. We found that in utero and early-life THS exposure caused significant changes in plasma cytokine concentrations and in immune cell populations; changes appeared more pronounced in male mice. Spleen (SP) and BM B-cell populations were significantly lower in THS-exposed mice. We furthermore observed that THS exposure increased the leukemia/lymphoma-free survival in BM transplantation recipient mice, potentially caused by THS-induced B-cell toxicity. A trend towards increased solid tumors in irradiated mice reconstituted with THS-exposed BM stimulates the hypothesis that the immunosuppressive effects of in utero and early-life THS exposure might contribute to carcinogenesis by lowering the host defense to other toxic exposures. Our study adds to expanding evidence that THS exposure alters the immune system and that in utero and early-life developmental periods represent vulnerable windows of susceptibility for these effects.

There has been a growing interest in the literature on multiple environmental risk factors for diseases and an increasing emphasis on assessing multiple environmental exposures simultaneously in epidemiologic studies of cancer. One method used to analyze exposure to multiple chemical exposures is weighted quantile sum (WQS) regression. While WQS regression has been demonstrated to have good sensitivity and specificity when identifying important exposures, it has limitations including a two-step model fitting process that decreases power and model stability and a requirement that all exposures in the weighted index have associations in the same direction with the outcome, which is not realistic when chemicals in different classes have different directions and magnitude of association with a health outcome. Grouped WQS (GWQS) was proposed to allow for multiple groups of chemicals in the model where different magnitude and direction of associations are possible for each group. However, GWQS shares the limitation of WQS of a two-step estimation process and splitting of data into training and validation sets. In this paper, we propose a Bayesian group index model to avoid the estimation limitation of GWQS while having multiple exposure indices in the model. To evaluate the performance of the Bayesian group index model, we conducted a simulation study with several different exposure scenarios. We also applied the Bayesian group index method to analyze childhood leukemia risk in the California Childhood Leukemia Study (CCLS). The results showed that the Bayesian group index model had slightly better power for exposure effects and specificity and sensitivity in identifying important chemical exposure components compared with the existing frequentist method, particularly for small sample sizes. In the application to the CCLS, we found a significant negative association for insecticides, with the most important chemical being carbaryl. In addition, for children who were born and raised in the home where dust samples were taken, there was a significant positive association for herbicides with dacthal being the most important exposure. In conclusion, our approach of the Bayesian group index model appears able to make a substantial contribution to the field of environmental epidemiology.

Individuals are exposed to a large number of diverse environmental chemicals simultaneously and the evaluation of multiple chemical exposures is important for identifying cancer risk factors. The measurement of a large number of chemicals (the exposome) in epidemiologic studies is allowing for a more comprehensive assessment of cancer risk factors than was done in earlier studies that focused on only a few chemicals. Empirical evidence from epidemiologic studies shows that chemicals from different chemical classes have different magnitudes and directions of association with cancers. Given increasing data availability, there is a need for the development and assessment of statistical methods to model environmental cancer risk that considers a large number of diverse chemicals with different effects for different chemical classes. The method of grouped weighted quantile sum (GWQS) regression allows for multiple groups of chemicals to be considered in the model such that different magnitudes and directions of associations are possible for each group of chemicals. In this paper, we assessed the ability of GWQS regression to estimate exposure effects for multiple chemical groups and correctly identify important chemicals in each group using a simulation study. We compared the performance of GWQS regression with WQS regression, the least absolute shrinkage and selection operator (lasso), and the group lasso in estimating exposure effects and identifying important chemicals. The simulation study results demonstrate that GWQS is an effective method for modeling exposure to multiple groups of chemicals and compares favorably with other methods used in mixture analysis. As an application, we used GWQS regression in the California Childhood Leukemia Study (CCLS), a population-based case-control study of childhood leukemia in California to estimate exposure effects for many chemical classes while also adjusting for demographic factors. The CCLS analysis found evidence of a positive association between exposure to the herbicide dacthal and an increased risk of childhood leukemia.

The developing fetus is exposed to chemicals, which are metabolized to electrophiles that form adducts with nucleophilic Cys34 of human serum albumin (HSA). By measuring these adducts in neonatal blood spots (NBS), we obtain information regarding fetal exposures during the last month of gestation. To discover potential risk factors for childhood leukemia resulting from in utero exposures, we used untargeted adductomics to measure HSA-Cys34 adducts in 782 archived NBS, collected from incident cases of childhood acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) and matched population-based controls. Among a total of 28 Cys34 modifications that were measured, we found no differences in adduct abundances between childhood leukemia cases and controls overall. However, cases of T-cell ALL had higher abundances of adducts of reactive carbonyl species and a Cys34 disulfide of homocysteine was present at lower levels in AML cases. These results suggest that oxidative stress and lipid peroxidation may be etiologic factors of T-cell ALL, and alterations in one-carbon metabolism and epigenetic changes may be predictors of AML. Future replication of the results with larger sample sizes is necessary.

E-cigarette use is increasing dramatically among adolescents as social media marketing portrays "vaping" products as healthier alternatives to conventional cigarettes. In September 2018, the Food and Drug Administration (FDA) launched an anti-vaping campaign, in U.S. high schools, on social media and other platforms, emphasizing "The Real Cost" of e-cigarettes. Using a novel deep learning approach, we assessed changes in vaping-related content on Instagram from 2017 to 2019 and drew an inference about the initial impact of the FDA's Real Cost campaign on Instagram. We collected 245,894 Instagram posts that used vaping-related hashtags (e.g., #vape, #ejuice) in four samples from 2017 to 2019. We compared the "like" count from these posts before and after the FDA campaign. We used deep learning image classification to analyze 49,655 Instagram image posts, separating images of men, women, and vaping devices. We also conducted text analysis and topic modeling to detect the common words and themes in the posted captions. Since September 2018, the FDA-sponsored hashtag #TheRealCost has been used about 50 times per month on Instagram, whereas vaping-related hashtags we tracked were used up to 10,000 times more often. Comparing the pre-intervention (2017, 2018) and post-intervention (2019) samples of vaping-related Instagram posts, we found a three-fold increase in the median "like" count (10 vs. 28) and a 6-fold increase in the proportion of posts with more than 100 likes (2 vs. 15%). Over 70% of Instagram vaping images featured e-juices and devices, with a growing number of images depicting a "pod," the type of discrete vaping device that delivers high concentration of nicotine and is favored by novice e-cigarette users. In addition, the Instagram analytics data shared by the vaping influencers we interviewed showed underage Instagram users among their followers.

BackgroundUntargeted metabolomics datasets contain large proportions of uninformative features that can impede subsequent statistical analysis such as biomarker discovery and metabolic pathway analysis. Thus, there is a need for versatile and data-adaptive methods for filtering data prior to investigating the underlying biological phenomena. Here, we propose a data-adaptive pipeline for filtering metabolomics data that are generated by liquid chromatography-mass spectrometry (LC-MS) platforms. Our data-adaptive pipeline includes novel methods for filtering features based on blank samples, proportions of missing values, and estimated intra-class correlation coefficients.ResultsUsing metabolomics datasets that were generated in our laboratory from samples of human blood, as well as two public LC-MS datasets, we compared our data-adaptive filtering method with traditional methods that rely on non-method specific thresholds. The data-adaptive approach outperformed traditional approaches in terms of removing noisy features and retaining high quality, biologically informative ones. The R code for running the data-adaptive filtering method is provided at https://github.com/courtneyschiffman/Metabolomics-Filtering .ConclusionsOur proposed data-adaptive filtering pipeline is intuitive and effectively removes uninformative features from untargeted metabolomics datasets. It is particularly relevant for interrogation of biological phenomena in data derived from complex matrices associated with biospecimens.

Early-life exposures are believed to influence the incidence of pediatric acute lymphoblastic leukemia (ALL). Archived neonatal blood spots (NBS), collected within the first days of life, offer a means to investigate small molecules that reflect early-life exposures. Using untargeted metabolomics, we compared abundances of small-molecule features in extracts of NBS punches from 332 children that later developed ALL and 324 healthy controls. Subjects were stratified by early (1-5 y) and late (6-14 y) diagnosis. Mutually-exclusive sets of metabolic features - representing putative lipids and fatty acids - were associated with ALL, including 9 and 19 metabolites in the early- and late-diagnosis groups, respectively. In the late-diagnosis group, a prominent cluster of features with apparent 18:2 fatty-acid chains suggested that newborn exposure to the essential nutrient, linoleic acid, increased ALL risk. Interestingly, abundances of these putative 18:2 lipids were greater in infants who were fed formula rather than breast milk (colostrum) and increased with the mother's pre-pregnancy body mass index. These results suggest possible etiologic roles of newborn nutrition in late-diagnosis ALL.

Metabolism of chemicals from the diet, exposures to xenobiotics, the microbiome, and lifestyle factors (e.g., smoking, alcohol intake) produce electrophiles that react with nucleophilic sites in circulating proteins, notably Cys34 of human serum albumin (HSA). To discover potential risk factors resulting from in utero exposures, we are investigating HSA-Cys34 adducts in archived newborn dried blood spots (DBS) that reflect systemic exposures during the last month of gestation. The workflow includes extraction of proteins from DBS, measurement of hemoglobin (Hb) to normalize for blood volume, addition of methanol to enrich HSA by precipitation of Hb and other interfering proteins, digestion with trypsin, and detection of HSA-Cys34 adducts via nanoflow liquid chromatography-high-resolution mass spectrometry. As proof-of-principle, we applied the method to 49 archived DBS collected from newborns whose mothers either actively smoked during pregnancy or were nonsmokers. Twenty-six HSA-Cys34 adducts were detected, including Cys34 oxidation products, mixed disulfides with low molecular weight thiols (e.g., cysteine, homocysteine, glutathione, cysteinylglycine), and other modifications. Data were normalized with a novel method ("scone") to remove unwanted technical variation arising from HSA digestion, blood volume, DBS age, mass spectrometry analysis, and batch effects. Using an ensemble of linear and nonlinear models, the Cys34 adduct of cyanide was found to consistently discriminate between newborns of smoking and nonsmoking mothers with a mean fold change (smoking/nonsmoking) of 1.31. These results indicate that DBS adductomics is suitable for investigating in utero exposures to reactive chemicals and metabolites that may influence disease risks later in life.

Genome-wide association studies of childhood acute lymphoblastic leukemia (ALL) have identified regions of association at PIP4K2A and upstream of BMI1 at chromosome 10p12.31-12.2. The contribution of both loci to ALL risk and underlying functional variants remain to be elucidated. We carried out single nucleotide polymorphism (SNP) imputation across chromosome 10p12.31-12.2 in Latino and non-Latino white ALL cases and controls from two independent California childhood leukemia studies, and additional Genetic Epidemiology Research on Aging study controls. Ethnicity-stratified association analyses were performed using logistic regression, with meta-analysis including 3,133 cases (1,949 Latino, 1,184 non-Latino white) and 12,135 controls (8,584 Latino, 3,551 non-Latino white). SNP associations were identified at both BMI1 and PIP4K2A. After adjusting for the lead PIP4K2A SNP, genome-wide significant associations remained at BMI1, and vice-versa (pmeta < 10-10 ), supporting independent effects. Lead SNPs differed by ethnicity at both peaks. We sought functional variants in tight linkage disequilibrium with both the lead Latino SNP among Admixed Americans and lead non-Latino white SNP among Europeans. This pinpointed rs11591377 (pmeta = 2.1 x 10-10 ) upstream of BMI1, residing within a hematopoietic stem cell enhancer of BMI1, and which showed significant preferential binding of the risk allele to MYBL2 (p = 1.73 x 10-5 ) and p300 (p = 1.55 x 10-3 ) transcription factors using binomial tests on ChIP-Seq data from a SNP heterozygote. At PIP4K2A, we identified rs4748812 (pmeta = 1.3 x 10-15 ), which alters a RUNX1 binding motif and demonstrated chromosomal looping to the PIP4K2A promoter. Fine-mapping chromosome 10p12 in a multi-ethnic ALL GWAS confirmed independent associations and identified putative functional variants upstream of BMI1 and at PIP4K2A.

Background: Allergic disease is suspected to play a role in the development of childhood acute lymphoblastic leukemia (ALL). Studies conducted over the last several decades have yielded mixed results.Methods: We examined the association between allergy, a common immune-mediated disorder, and ALL in the California Childhood Leukemia Study (CCLS), a case-control study of 977 children diagnosed with ALL and 1,037 matched controls (1995-2015). History of allergies in the first year of life was obtained from interviews, mainly reported by mothers. Logistic regression analyses were conducted to estimate ORs and 95% confidence intervals (CIs), controlling for birth order, daycare attendance, and mode of delivery. In addition, we conducted meta-analyses with data from the CCLS and 12 published studies and employed a new method to estimate between-study heterogeneity (R_b).Results: Overall, no associations were observed between childhood ALL risk and specific allergy phenotypes or any allergy, as a group. However, having any allergy was associated with an increased risk of ALL among the youngest study participants. In the meta-analysis random-effects models, reduced odds of ALL were associated with hay fever (metaOR = 0.65; 95% CI, 0.47-0.90); however, restricting the analysis to studies that used medical records for assessment of allergy or recently published studies led to null or attenuated results.Conclusions: Overall, our findings do not support a clear association between allergy and childhood ALL.Impact: The degree to which epidemiologic studies can inform the relationship between allergies and risk of childhood ALL is limited by R_b. Cancer Epidemiol Biomarkers Prev; 27(10); 1142-50. ©2018 AACR.

IntroductionFor pediatric diseases like childhood leukemia, a short latency period points to in-utero exposures as potentially important risk factors. Untargeted metabolomics of small molecules in archived newborn dried blood spots (DBS) offers an avenue for discovering early-life exposures that contribute to disease risks.ObjectivesThe purpose of this study was to develop a quantitative method for untargeted analysis of archived newborn DBS for use in an epidemiological study (California Childhood Leukemia Study, CCLS).MethodsUsing experimental DBS from the blood of an adult volunteer, we optimized extraction of small molecules and integrated measurement of potassium as a proxy for blood hematocrit. We then applied this extraction method to 4.7-mm punches from 106 control DBS samples from the CCLS. Sample extracts were analyzed with liquid chromatography high resolution mass spectrometry (LC-HRMS) and an untargeted workflow was used to screen for metabolites that discriminate population characteristics such as sex, ethnicity, and birth weight.ResultsThousands of small molecules were measured in extracts of archived DBS. Normalizing for potassium levels removed variability related to varying hematocrit across DBS punches. Of the roughly 1,000 prevalent small molecules that were tested, multivariate linear regression detected significant associations with ethnicity (3 metabolites) and birth weight (15 metabolites) after adjusting for multiple testing.ConclusionsThis untargeted workflow can be used for analysis of small molecules in archived DBS to discover novel biomarkers, to provide insights into the initiation and progression of diseases, and to provide guidance for disease prevention.

PurposeWe investigated the relationship between the risk of childhood leukemia and home remodeling, a surrogate for indoor chemical exposures.MethodsWe collected information on remodeling activities carried out between birth and diagnosis in homes of 609 acute lymphoblastic leukemia (ALL) cases, 89 acute myeloid leukemia (AML) cases, and 893 matched controls participating in the California Childhood Leukemia Study (1995-2008). We used multivariable logistic regression to estimate the risk of ALL and AML associated with six remodeling activities: construction, painting, recarpeting, reflooring, roofing, and weatherproofing. Models were adjusted for age, sex, Hispanic ethnicity, race, household annual income, and residential mobility.ResultsConstruction in the home between birth and diagnosis was associated with a significant increase in ALL risk (odds ratio [OR]: 1.52, 95% confidence interval [CI]: 1.14-2.02) and a nonsignificant increase in AML risk (OR: 1.75, 95% CI: 0.98-3.15). No other remodeling activities were associated with ALL or AML risk in the main analysis. When stratifying by Hispanic ethnicity, a positive relationship between ALL risk and painting was evident in Hispanic children (OR: 1.47, 95% CI: 1.04-2.07).ConclusionsSpecific home remodeling activities appeared to be associated with increased risk of childhood ALL.

Thirdhand smoke (THS) is the contamination that persists after secondhand tobacco smoke has been emitted into air. It refers to the tobacco-related gases and particles that become embedded in materials, such as the carpet, walls, furniture, blankets, and toys. THS is not strictly smoke, but chemicals that adhere to surfaces from which they can be released back into the air, undergo chemical transformations and/or accumulate. Currently, the hazards of THS are not as well documented as the hazards of secondhand smoke (SHS). In this Perspective, we describe the distribution and chemical changes that occur as SHS is transformed into THS, studies of environmental contamination by THS, human exposure studies, toxicology studies using animal models and in vitro systems, possible approaches for avoiding exposure, remediation of THS contamination, and priorities for further research.

Leukemia is the most common pediatric cancer, affecting 3800 children per year in the United States. Its annual incidence has increased over the last decades, especially among Latinos. Although most children diagnosed with leukemia are now cured, many suffer long-term complications, and primary prevention efforts are urgently needed. The early onset of leukemia-usually before 5 years of age-and the presence at birth of "pre-leukemic" genetic signatures indicate that pre- and postnatal events are critical to the development of the disease. In contrast to most pediatric cancers, there is a growing body of literature-in the United States and internationally-that has implicated several environmental, infectious, and dietary risk factors in the etiology of childhood leukemia, mainly for acute lymphoblastic leukemia, the most common subtype. For example, exposures to pesticides, tobacco smoke, solvents, and traffic emissions have consistently demonstrated positive associations with the risk of developing childhood leukemia. In contrast, intake of vitamins and folate supplementation during the preconception period or pregnancy, breastfeeding, and exposure to routine childhood infections have been shown to reduce the risk of childhood leukemia. Some children may be especially vulnerable to these risk factors, as demonstrated by a disproportionate burden of childhood leukemia in the Latino population of California. The evidence supporting the associations between childhood leukemia and its risk factors-including pooled analyses from around the world and systematic reviews-is strong; however, the dissemination of this knowledge to clinicians has been limited. To protect children's health, it is prudent to initiate programs designed to alter exposure to well-established leukemia risk factors rather than to suspend judgment until no uncertainty remains. Primary prevention programs for childhood leukemia would also result in the significant co-benefits of reductions in other adverse health outcomes that are common in children, such as detriments to neurocognitive development.

Active ingredients in residential and agricultural insecticides have changed over time, due in part to regulatory restrictions. Few studies have evaluated how changes in active ingredients have impacted insecticide levels measured in homes. We measured concentrations of insecticides in one carpet-dust sample from each of 434 homes in California from 2001 to 2006. Analytes included four insecticides sold for indoor home use during our study period (carbaryl, cypermethrin, permethrin, and propoxur) and four that are no longer sold for indoor use including dichlorodiphenyltrichloroethylene (DDT, removed from the market in 1972), chlordane (1988), chlorpyrifos (2001), and diazinon (2004). We considered other potential determinants of concentrations of insecticides in carpet dust, such as home and garden use, occupational exposure, and nearby agricultural applications. We calculated the percentage change in the concentration of each insecticide per year, adjusting for significant determinants. In adjusted models, concentrations of insecticides in carpet dust decreased for three of four insecticides no longer sold for residential use: chlordane (-15% per year), chlorpyrifos (-31%), diazinon (-48%), and propoxur (-34%), which is currently sold for residential use but with increased restrictions since 1997. Concentrations of other insecticides sold for indoor use (carbaryl, cypermethrin, and permethrin) and DDT did not change over time in our study population.

Aberrant telomere lengthening is an important feature of cancer cells in adults and children. In addition to somatic mutations, germline polymorphisms in telomere maintenance genes impact telomere length. Whether these telomere-associated polymorphisms affect risk of childhood malignancies remains largely unexplored. We collected genome-wide data from three groups with pediatric malignancies [neuroblastoma (N = 1516), acute lymphoblastic leukemia (ALL) (N = 958) and osteosarcoma (N = 660)] and three control populations (N = 6892). Using case-control comparisons, we analyzed eight single nucleotide polymorphisms (SNPs) in genes definitively associated with interindividual variation in leukocyte telomere length (LTL) in prior genome-wide association studies: ACYP2, TERC, NAF1, TERT, OBFC1, CTC1, ZNF208 and RTEL1 Six of these SNPs were associated (P < 0.05) with neuroblastoma risk, one with leukemia risk and one with osteosarcoma risk. The allele associated with longer LTL increased cancer risk for all these significantly associated SNPs. Using a weighted linear combination of the eight LTL-associated SNPs, we observed that neuroblastoma patients were predisposed to longer LTL than controls, with each standard deviation increase in genotypically estimated LTL associated with a 1.15-fold increased odds of neuroblastoma (95%CI = 1.09-1.22; P = 7.9×10(-7)). This effect was more pronounced in adolescent-onset neuroblastoma patients (OR = 1.46; 95%CI = 1.03-2.08). A one standard deviation increase in genotypically estimated LTL was more weakly associated with osteosarcoma risk (OR = 1.10; 95%CI = 1.01-1.19; P = 0.017) and leukemia risk (OR = 1.07; 95%CI = 1.00-1.14; P = 0.044), specifically for leukemia patients who relapsed (OR = 1.19; 95%CI = 1.01-1.40; P = 0.043). These results indicate that genetic predisposition to longer LTL is a newly identified risk factor for neuroblastoma and potentially for other cancers of childhood.

We evaluated the relationship between the risk of childhood acute lymphoblastic leukemia (ALL) and the levels of metals in carpet dust. A dust sample was collected from the homes of 142 ALL cases and 187 controls participating in the California Childhood Leukemia Study using a high volume small surface sampler (2001-2006). Samples were analyzed using microwave-assisted acid digestion in combination with inductively coupled plasma mass spectrometry for arsenic, cadmium, chromium, copper, lead, nickel, tin, tungsten, and zinc. Eight metals were detected in at least 85% of the case and control homes; tungsten was detected in

Smokeless tobacco products, such as moist snuff or chewing tobacco, contain many of the same carcinogens as tobacco smoke; however, the impact on children of indirect exposure to tobacco constituents via parental smokeless tobacco use is unknown. As part of the California Childhood Leukemia Study, dust samples were collected from 6 homes occupied by smokeless tobacco users, 6 homes occupied by active smokers, and 20 tobacco-free homes. To assess children's potential for exposure to tobacco constituents, vacuum-dust concentrations of five tobacco-specific nitrosamines, including N'-nitrosonornicotine [NNN] and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone [NNK], as well as six tobacco alkaloids, including nicotine and myosmine, were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We used generalized estimating equations derived from a multivariable marginal model to compare levels of tobacco constituents between groups, after adjusting for a history of parental smoking, income, home construction date, and mother's age and race/ethnicity. The ratio of myosmine/nicotine was used as a novel indicator of the source of tobacco contamination, distinguishing between smokeless tobacco products and tobacco smoke. Median dust concentrations of NNN and NNK were significantly greater in homes with smokeless tobacco users compared to tobacco-free homes. In multivariable models, concentrations of NNN and NNK were 4.8- and 6.9-fold higher, respectively, in homes with smokeless tobacco users compared to tobacco-free homes. Median myosmine/nicotine ratios were lower in homes with smokeless tobacco users (1.8%) compared to homes of active smokers (7.7%), confirming that cigarette smoke was not the predominant source of tobacco constituents in homes with smokeless tobacco users. Children living with smokeless tobacco users may be exposed to carcinogenic tobacco-specific nitrosamines via contact with contaminated dust and household surfaces.

BackgroundHumans are exposed to persistent organic pollutants (POPs) through various routes, including consumption of contaminated food and accidental ingestion of settled dust.ObjectivesWe aimed to identify key routes of exposure to organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) in California women of reproductive age.MethodsBlood was collected from 48 mothers participating in the California Childhood Leukemia Study from 2006 to 2007 and analyzed for POPs using gas chromatography-mass spectrometry. Multivariable linear regression models of natural-log transformed serum concentrations were used to identify determinants of exposure from available questionnaire information on dietary habits, reproductive history, and demographic characteristics, as well as vacuum cleaner dust-POP levels.ResultsAfter adjusting for blood lipid levels, age, body mass index, cumulative lactation, and sampling date, serum concentrations of multiple major PCBs were positively associated with fish consumption, but not dust-PCB levels. After adjusting for blood lipid levels, Hispanic ethnicity, country of origin, and household annual income, serum concentrations of multiple major PBDEs were positively associated with dust-PBDE levels.ConclusionsOur findings suggest that the relative contribution of specific exposure routes to total POP intake varies by chemical class, with dust being a relatively important source of PBDEs and diet being a relatively important source of PCBs.

Eleven novel brominated flame retardants (NBFRs) were analyzed in dust samples from California homes as a part of the Northern California Childhood Leukemia Study (NCCLS) and from the living quarters of California fire stations as a part of the Firefighter Occupational Exposure (FOX) study using high resolution gas chromatography/mass spectrometry. The eleven NBFRs were α- and β-1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (α- and β-DBE-DBCH), 2-bromoallyl 2,3,6-tribromophenylether (BATE), pentabromotoluene (PBT), pentabromoethylbenzene (PBEB), 2,3-dibromopropyl 2,4,6-tribromophenyl ether (TBP-DBPE), hexabromobenzene (HBB), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP), and decabromodiphenylethane (DBDPE). Six of the seven NBFRs that are produced in relatively small quantities (i.e., α-, β-DBE-DBCH, BATE, PBEB, PBT, TBP-DBPE) were measured close to or below the limit of quantitation (0.64 ng/g) in both the NCCLS and FOX samples, and the seventh, HBB, was measured at median concentrations of 1.85 ng/g and 9.40 ng/g in the NCCLS and FOX samples, respectively. The remaining four NBFRs, EH-TBB, BEH-TEBP, BTBPE, and DBDPE, are produced in higher quantities, and were detected at median concentrations of 337 ng/g, 186 ng/g, 22.3 ng/g, and 82.8 ng/g, respectively in the NCCLS samples, and at median concentrations of 2687 ng/g, 2076 ng/g, 28.4 ng/g, and 161 ng/g, respectively, in the FOX samples. Concentrations of NBFRs in the NCCLS and FOX dust samples were several times lower than concentrations of PBDEs previously measured in the same samples. Concentrations of NBFRs in the NCCLS and FOX dust samples were generally comparable to concentrations of NBFRs in other studies of house dust from the US and Canada.

BackgroundHouse dust is a major source of exposure to polybrominated diphenyl ethers (PBDEs), which are found at high levels in U.S. homes.MethodsWe studied 167 acute lymphoblastic leukemia (ALL) cases 0-7 years of age and 214 birth certificate controls matched on date of birth, sex, and race/ethnicity from the Northern California Childhood Leukemia Study. In 2001-2007, we sampled carpets in the room where the child spent the most time while awake; we used a high-volume small-surface sampler or we took dust from the home vacuum. We measured concentrations of 14 PBDE congeners including penta (28, 47, 99, 100, 153, 154), octa (183, 196, 197, 203), and decaBDEs (206-209). Odds ratios (ORs) were calculated using logistic regression, adjusting for demographics, income, year of dust collection, and sampling method.ResultsBDE-47, BDE-99, and BDE-209 were found at the highest concentrations (medians, 1,173, 1,579, and 938 ng/g, respectively). Comparing the highest to lowest quartile, we found no association with ALL for summed pentaBDEs (OR = 0.7; 95% CI: 0.4, 1.3), octaBDEs (OR = 1.3; 95% CI: 0.7, 2.3), or decaBDEs (OR = 1.0; 95% CI: 0.6, 1.8). Comparing homes in the highest concentration (nanograms per gram) tertile to those with no detections, we observed significantly increased ALL risk for BDE-196 (OR = 2.1; 95% CI: 1.1, 3.8), BDE-203 (OR = 2.0; 95% CI: 1.1, 3.6), BDE-206 (OR = 2.1; 95% CI: 1.1, 3.9), and BDE-207 (OR = 2.0; 95% CI: 1.03, 3.8).ConclusionWe found no association with ALL for common PBDEs, but we observed positive associations for specific octa and nonaBDEs. Additional studies with repeated sampling and biological measures would be informative.

We characterized the variability in concentrations of polychlorinated biphenyls (PCBs) measured in residential dust. Vacuum cleaner samples were collected from 289 homes in the California Childhood Leukemia Study during two sampling rounds from 2001 to 2010 and 15 PCBs were measured by high resolution gas chromatography-mass spectrometry. Median concentrations of the most abundant PCBs (i.e., PCBs 28, 52, 101, 105, 118, 138, 153, and 180) ranged from 1.0-5.8 ng per g of dust in the first sampling round and from 0.8-3.4 ng/g in the second sampling round. For each of these eight PCBs, we used a random-effects model to apportion total variation into regional variability (6-11%), intraregional between-home variability (27-56%), within-home variability over time (18-52%), and within-sample variability (9-16%). In mixed-effects models, differences in PCB concentrations between homes were explained by home age, with older homes having higher PCB levels. Differences in PCB concentrations within homes were explained by decreasing time trends. Estimated half-lives ranged from 5-18 years, indicating that PCBs are removed very slowly from the indoor environment. Our findings suggest that it may be feasible to use residential dust for retrospective assessment of PCB exposures in studies of children's health.

BackgroundSmokeless tobacco products, such as chewing tobacco or moist snuff, contain many of the same constituents as tobacco smoke and are also known to cause cancer; however, little attention has been paid to indirect exposure of children to tobacco constituents via parental smokeless tobacco use.MethodsAs part of the California Childhood Leukemia Study, we collected dust samples from 6 residences occupied by smokeless tobacco users, 6 residences occupied by active smokers, and 20 tobacco-free residences. Children's potential for exposure to tobacco constituents was assessed using nicotine concentrations in vacuum dust measured by gas chromatography-mass spectrometry.ResultsMedian nicotine concentrations for residences with smokeless tobacco users were significantly greater than median nicotine concentrations for tobacco-free homes and similar to median nicotine concentrations in homes of active smokers. Using generalized estimating equations derived from a multivariable marginal model to adjust for a history of parental smoking, income, residence construction date, and mother's age and race/ethnicity, we found nicotine levels from homes of smokeless tobacco users to be 21-fold higher than nicotine levels from tobacco-free homes. Based on mass balance equations, we hypothesize that nicotine is transferred to floors in homes of smokeless tobacco users primarily as a constituent of tobacco that is spilled or expectorated.ConclusionsBased on our findings, we conclude that children living with smokeless tobacco users may be exposed to nicotine and other constituents of tobacco via contact with contaminated dust and household surfaces.

BackgroundThere is interest in using residential dust to estimate human exposure to environmental contaminants.ObjectivesWe aimed to characterize the sources of variability for polycyclic aromatic hydrocarbons (PAHs) in residential dust and provide guidance for investigators who plan to use residential dust to assess exposure to PAHs.MethodsWe collected repeat dust samples from 293 households in the Northern California Childhood Leukemia Study during two sampling rounds (from 2001 through 2007 and during 2010) using household vacuum cleaners, and measured 12 PAHs using gas chromatography-mass spectrometry. We used a random- and a mixed-effects model for each PAH to apportion observed variance into four components and to identify sources of variability.ResultsMedian concentrations for individual PAHs ranged from 10 to 190 ng/g of dust. For each PAH, total variance was apportioned into regional variability (1-9%), intraregional between-household variability (24-48%), within-household variability over time (41-57%), and within-sample analytical variability (2-33%). Regional differences in PAH dust levels were associated with estimated ambient air concentrations of PAH. Intraregional differences between households were associated with the residential construction date and the smoking habits of residents. For some PAHs, a decreasing time trend explained a modest fraction of the within-household variability; however, most of the within-household variability was unaccounted for by our mixed-effects models. Within-household differences between sampling rounds were largest when the interval between dust sample collections was at least 6 years in duration.ConclusionsOur findings indicate that it may be feasible to use residential dust for retrospective assessment of PAH exposures in studies of health effects.

Abstract Background There is increasing interest in using chemicals measured in carpet dust as indicators of chemical exposures. However, investigators have rarely sampled dust repeatedly from the same households and therefore little is known about the variability of chemical levels that exist within and between households in dust samples. Results We analyzed 9 polycyclic aromatic hydrocarbons, 6 polychlorinated biphenyls, and nicotine in 68 carpet-dust samples from 21 households in agricultural communities of Fresno County, California collected from 2003-2005. Chemical concentrations (ng per g dust) ranged from < 2-3,609 for 9 polycyclic aromatic hydrocarbons, from < 1-150 for 6 polychlorinated biphenyls, and from < 20-7,776 for nicotine. We used random-effects models to estimate variance components for concentrations of each of these carpet-dust chemicals and calculated the variance ratio, λ, defined as the ratio of the within-household variance component to the between-household variance component. Subsequently, we used the variance ratios calculated from our data, to illustrate the potential effect of measurement error on the attenuation of odds ratios in hypothetical case-control studies. We found that the median value of the estimated variance ratios was 0.33 (range: 0.13-0.72). Correspondingly, in case-control studies of associations between these carpet-dust chemicals and disease, given the collection of only one measurement per household and a hypothetical odds ratio of 1.5, we expect that the observed odds ratios would range from 1.27 to 1.43. Moreover, for each of the chemicals analyzed, the collection of three repeated dust samples would limit the expected magnitude of odds ratio attenuation to less than 20%. Conclusions Our findings suggest that attenuation bias should be relatively modest when using these semi-volatile carpet-dust chemicals as exposure surrogates in epidemiologic studies.

Residential exposure to pesticides has been linked to several adverse health outcomes, including adult cancers, such as non-Hodgkin lymphoma (Colt et al. 2006; Ward et al. 2009) and prostate cancer [...]

Background: Parental smoking is implicated in the etiology of acute lymphoblastic leukemia (ALL), the most common childhood cancer. We recently reported an association between an epigenetic biomarker of early-life tobacco smoke exposure at the AHRR gene and increased frequency of somatic gene deletions among ALL cases. Methods: Here, we further assess this association using two epigenetic biomarkers for maternal smoking during pregnancy--DNA methylation at AHRR CpG cg05575921 and a recently established polyepigenetic smoking score--in an expanded set of 482 B-cell ALL (B-ALL) cases in the California Childhood Leukemia Study with available Illumina 450K or MethylationEPIC array data. Multivariable Poisson regression models were used to test the associations between the epigenetic biomarkers and gene deletion numbers. Results: We found an association between DNA methylation at AHRR CpG cg05575921 and deletion number among 284 childhood B-ALL cases with MethylationEPIC array data, with a ratio of means (RM) of 1.31 [95% confidence interval (CI), 1.02-1.69] for each 0.1 ß value reduction in DNA methylation, an effect size similar to our previous report in an independent set of 198 B-ALL cases with 450K array data [meta-analysis summary RM (sRM) = 1.32; 95% CI, 1.10-1.57]. The polyepigenetic smoking score was positively associated with gene deletion frequency among all 482 B-ALL cases (sRM = 1.31 for each 4-unit increase in score; 95% CI, 1.09-1.57). Conclusions: We provide further evidence that prenatal tobacco-smoke exposure may influence the generation of somatic copy-number deletions in childhood B-ALL. [ABSTRACT FROM AUTHOR]

Firefighters are exposed to chemicals during fire events and we previously demonstrated that fire station dust has high levels of polybrominated diphenyl ethers (PBDEs). In conducting the Fire Station Dust Study, we sought to further characterize the chemicals to which firefighters could be exposed – measuring the emerging class of phosphorous-containing flame retardants (PFRs) in fire stations, for the first time, as well as PBDEs. Dust samples from 26 fire stations in five states were collected from vacuum-cleaner bags and analyzed for PFRs and PBDEs. PFR concentrations were found to be on the same order of magnitude as PBDE concentrations (maximum PFR: 218,000 ng/g; maximum PBDE: 351,000 ng/g). Median concentrations of tri-n-butyl phosphate (TNBP), tris (2-chloroisopropyl) phosphate (TCIPP), and tris(1,3-dichloroisopropyl)phosphate (TDCIPP) in dust from fire stations were higher than those previously reported in homes and other occupational settings around the world. Total PFR levels did not vary significantly among states. Levels of TDCIPP were higher in stations where vacuum cleaners were used to clean surfaces other than the floor. PBDE levels were comparable to those found in our previous study of 20 California fire stations and much higher than levels in California residences. PFR and PBDE levels in fire station dust are higher than in other occupational and residential settings, underscoring the need to identify and control sources of this contamination. [ABSTRACT FROM AUTHOR]

Background: High rates of childhood leukemia incidence have been reported in Latin America and among Hispanic children in the United States. California's large Hispanic population affords an important opportunity to perform a detailed analysis of the leukemia burden among Hispanic children.Methods: Leukemias diagnosed among non-Hispanic white (NHW), Hispanic, African American (AA), and Asian/Pacific Islander (API) children aged birth to 19 years between January 1, 1990 and December 31, 2012 were obtained from the California Cancer Registry (11,084 cases). Age-adjusted incidence rates, standardized rate ratios (SRRs), and secular trends in incidence (annual percent change [APC]) were analyzed by subtype, race/ethnicity, sex, and age.Results: Compared with NHW children, the incidence of acute lymphoblastic leukemia (ALL) was higher among Hispanic (SRR, 1.32) and lower among AA (SRR, 0.55) and API (SRR, 0.91) children. From 1990 to 2012, the incidence of ALL increased overall (APC, 1.1%) and among males (APC, 1.0%), females (APC, 1.3%), Hispanics (APC, 1.1%), AAs (APC, 1.9%), AA males (APC, 2.8%), API males (APC, 1.9%), and Hispanic females (APC, 1.5%). The incidence of ALL increased among Hispanic males aged 15 to 19 years (APC, 2.5%) and Hispanic females aged birth to 4 years and 15 to 19 years (APCs of 2.2% and 1.9%, respectively). The incidence of acute myeloid leukemia did not appear to differ among racial/ethnic groups. From 1990 to 2012, the overall incidence of acute myeloid leukemia remained stable but increased among Hispanics (APC, 1.2%), females (APC, 1.0%), Hispanic females (APC, 2.3%), and Hispanic females aged 15 to 19 years (APC, 3.4%).Conclusions: Notable differences in the incidence of childhood leukemia were observed among 4 racial/ethnic groups in California. Factors that may contribute to these differences include differential exposure to carcinogens and/or genetic susceptibility. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2867-2875. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Firefighters are exposed to chemicals during lire events and may also experience chemical exposure in their fire stations. Dust samples from used vacuum cleaner bags were collected from 20 fire stations in California and analyzed for polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) using gas chromatography--mass spectrometry. Median dust concentrations were higher for PBDEs (e.g., 47 000 ng/g for BDE-209) than for PAHs (e.g., 220 ng/g for benzo[a]pyrene) or PCBs (e.g., 9.3 ng/g for PCB-180). BDE-209 concentrations in dust from California fire stations were among the highest of any previously documented homes or occupational settings in the world. We examined factors such as the frequency of emergency responses, the number of fire vehicles on site, and building age, but we could not account for the high levels of BDE-209 observed in fire station dust. Based on the findings of our pilot study, we hypothesize that possible sources of BDE-209 in fire stations include contaminated ash tracked back from fire events via boots, clothing, and other equipment as well as specialized equipment treated with BDE-209, including turnout gear and fire vehicles. We suggest possible followup studies to confirm these hypotheses. [ABSTRACT FROM AUTHOR]

Abstract: We characterized the sources of variability for polybrominated diphenyl ethers (PBDEs) in residential dust and provided guidance for investigators who plan to use residential dust to assess exposure to PBDEs. We collected repeat dust samples from 292 households in the Northern California Childhood Leukemia Study during two sampling rounds (from 2001 to 2007 and during 2010) using household vacuum cleaners and measured 22 PBDEs using high resolution gas chromatography–high resolution mass spectrometry. Median concentrations for individual PBDEs ranged from <0.1–2500ng per g of dust. For each of eight representative PBDEs, we used a random-effects model to apportion total variance into regional variability (0–11%), intra-regional between-household variability (17–50%), within-household variability over time (38–74%), and within-sample variability (0–23%) and we used a mixed-effects model to identify determinants of PBDE levels. Regional differences in PBDE dust levels were associated with residential characteristics that differed by region, including the presence of furniture with exposed or crumbling foam and the recent installation of carpets in the residence. Intra-regional differences between households were associated with neighborhood urban density, racial and ethnic characteristics, and to a lesser extent, income. For some PBDEs, a decreasing time trend explained a modest fraction of the within-household variability; however, most of the within-household variability was unaccounted for by our mixed-effects models. Our findings indicate that it may be feasible to use residential dust for retrospective assessment of PBDE exposures in studies of children's health (e.g., the Northern California Childhood Leukemia Study). [Copyright &y& Elsevier]

Background: The incidence of testicular germ cell tumors (TGCT) is increasing steadily in the United States, particularly among Latinos. TGCT is thought to be initiated in utero and exposure to endocrine-disrupting chemicals, suspected contributors to TGCT pathogenesis, during this critical developmental period may contribute to the rise.Objectives: To assess the relationship between fetal exposure to agricultural endocrine-disrupting pesticides (EDPs) and TGCT risk among adolescents in a diverse population in California.Methods: We conducted a registry-based case-control study of TGCT. Cases, diagnosed between 1997 and 2011, were 15-19 years of age (n = 381). Controls were matched on birth year and race/ethnicity (n = 762). Quantities (kilograms) of 33 pesticides applied within 3 km and 1 km radii of each individual's address before birth were estimated using the Pesticide Use Reporting database. Odds ratios (OR), 95% confidence intervals (CI), and population attributable risk (PAR) were calculated for each EDP (using log-2 transformed values). Risk models considered race/ethnicity, birth year, and neighborhood socioeconomic status.Results: A doubling of nearby acephate applications (3 km and 1 km radii) and malathion applications (1 km radius) was associated with increased risks of TGCT among Latinos only (OR = 1.09; 95% CI:1.01-1.17; 1.30; 95% CI:1.08-1.57, and 1.19; 95% CI:1.01-1.39, respectively), whereas application of carbaryl within a 3 km radius increased TGCT risk in non-Latinos only (OR = 1.14, 95% CI:1.01-1.28). We estimate that acephate was associated with approximately 10% of the TGCT PAR, malathion with 3% and carbaryl with 1%.Conclusions: TGCT among adolescents in California was associated with prenatal residential proximity to acephate and malathion among Latinos, and with carbaryl among non-Latinos. These results suggest that the rise in TGCT risk among Latinos may be associated with exposure to these pesticides. [ABSTRACT FROM AUTHOR]

Early-life exposures are believed to influence the incidence of pediatric acute lymphoblastic leukemia (ALL). Archived neonatal blood spots (NBS), collected within the first days of life, offer a means to investigate small molecules that reflect early-life exposures. Using untargeted metabolomics, we compared abundances of small-molecule features in extracts of NBS punches from 332 children that later developed ALL and 324 healthy controls. Subjects were stratified by early (1-5 y) and late (6-14 y) diagnosis. Mutually-exclusive sets of metabolic features - representing putative lipids and fatty acids - were associated with ALL, including 9 and 19 metabolites in the early- and late-diagnosis groups, respectively. In the late-diagnosis group, a prominent cluster of features with apparent 18:2 fatty-acid chains suggested that newborn exposure to the essential nutrient, linoleic acid, increased ALL risk. Interestingly, abundances of these putative 18:2 lipids were greater in infants who were fed formula rather than breast milk (colostrum) and increased with the mother's pre-pregnancy body mass index. These results suggest possible etiologic roles of newborn nutrition in late-diagnosis ALL. [ABSTRACT FROM AUTHOR]

Self-reported residential use of pesticides has consistently been associated with increased risk of childhood leukemia. However, these studies were limited in their ability to identify specific insecticide active ingredients that were associated with risk. We used household carpet dust measurements of 20 insecticides (two carbamate, 10 organophosphate, two organochlorine, and six pyrethroid) as indicators of exposure and evaluated associations with the risk of childhood acute lymphoblastic leukemia (ALL). We conducted a population-based case-control study of 252 ALL cases diagnosed from 1999 to 2007 and 306 birth certificate controls from 35 counties in Central and Northern California. Carpet dust was collected at a second interview (2001–2007) for cases who had not moved since diagnosis (comparable reference date for controls) using a specialized vacuum cleaner in the room where the child spent most of their time or from the household vacuum. Insecticides were categorized as detected (yes/no), or as tertiles or quartiles of their distributions among controls. We calculated odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression adjusting for demographic characteristics, interview year, and season of dust collection. Permethrin, chlorpyrifos, diazinon, and carbaryl were the most frequently detected insecticide active ingredients. When we compared the highest quartile to the lowest or to non-detections, there was no association with ALL for permethrin (OR Q4 vs. Q1 = 0.81; 95% CI 0.50–1.31), carbaryl (OR Q4 vs. non-detects = 0.61, 95% CI 0.34–1.08) or chlorpyrifos (OR Q4 vs. Q1 = 0.60; 95% CI 0.36–1.00). The highest quartile of diazinon concentration was inversely associated with risk in the single pesticide model but without a monotonic exposure-response (p-trend = 0.14). After adjusting for other common insecticides, the OR was not significant (OR Q4 vs. Q1 = 0.58; 95% CI 0.33–1.05). None of the other insecticides were associated with risk. Our results should be interpreted within the limitations of the case-control study design including the use of a single post-diagnosis dust sample and restriction to residentially stable participants, which may have resulted in selection bias. Although difficult to implement, additional studies with assessment of exposure to insecticide active and non-active ingredients are necessary to elucidate the role of these common exposures in childhood leukemia risk. • Few studies of pesticides and childhood leukemia use objective exposure measures. • We measured carbamate, organophosphate, and pyrethroid insecticides in house dust. • Detection rates for specific active ingredients in homes ranged from 0.4% to 99.6%. • Dust concentrations were not associated with risk of childhood leukemia. • Evaluation of pre-diagnostic exposure levels during critical periods is warranted. [ABSTRACT FROM AUTHOR]