Northern California Childhood Leukemia Study Research Articles

P.3.d.046 - Two years of maintenance therapy with paliperidone long-acting in schizophrenia and schizoaffective disorder: a study with plasma levels

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.

Comparison of Self-Reported Pest Treatments and Insecticide Concentrations in Carpet Dust in the Northern California Childhood Leukemia Study

Background: Parental self-reported pesticide use has been the usual exposure assessment method in studies of pesticide exposures and childhood leukemia. This approach does not identify active ingredients and may suffer from recall bias. Measuring pesticides in carpet dust is an objective method for determining chemical concentrations in homes and may be a useful exposure indicator for children. Methods: In the Northern California Childhood Leukemia Study, parents of 277 cases and 306 controls were interviewed about household treatment (yes/no) in the prior 12 months for flying insects, fleas/ticks, termites/carpenter ants, lawn/garden insects, and professional indoor and outdoor insect treatments. Carpet dust samples were collected in 2001-2007 and analyzed for nine insecticides using gas chromatography/mass spectrometry. Using multivariable linear regression, we modeled the relationship between log-transformed concentrations of the insecticides and pest treatments, adjusting for home characteristics and other factors. Results: Among both cases and controls, reported flea/tick treatment was associated with 2 to 3- fold higher concentrations of cypermethrin, permethrin and piperonyl butoxide compared to households not treating fleas/ticks (p<0.05). In both groups, lawn/garden insect treatment increased chlorpyrifos concentrations by 1.6 times (p<0.05), and professional outdoor applications increased cyfluthrin 4-fold in cases and 10-fold in controls (p<0.05). For the most part, associations between reported treatments and insecticide measurements were consistent between cases and controls, suggesting minimal effect of recall bias. Conclusions: The statistically significant associations between self-reported pest treatments and insecticide concentrations in carpet dust, which were generally consistent between cases and controls, lend credibility to the use of both methods for characterizing residential exposure to pesticides.

Levels of non-polybrominated diphenyl ether brominated flame retardants in residential house dust samples and fire station dust samples in California

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 (0.64ng/g) in both the NCCLS and FOX samples, and the seventh, HBB, was measured at median concentrations of 1.85ng/g and 9.40ng/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 337ng/g, 186ng/g, 22.3ng/g, and 82.8ng/g, respectively in the NCCLS samples, and at median concentrations of 2687ng/g, 2076ng/g, 28.4ng/g, and 161ng/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.

Residential levels of polybrominated diphenyl ethers and risk of childhood acute lymphoblastic leukemia in California.

Background: House dust is a major source of exposure to polybrominated diphenyl ethers (PBDEs), which are found at high levels in U.S. homes.Methods: We 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.Results: BDE-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).Conclusion: We 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.Citation: Ward MH, Colt JS, Deziel NC, Whitehead TP, Reynolds P, Gunier RB, Nishioka M, Dahl GV, Rappaport SM, Buffler PA, Metayer C. 2014. Residential levels of polybrominated diphenyl ethers and risk of childhood acute lymphoblastic leukemia in California. Environ Health Perspect 122:1110–1116; http://dx.doi.org/10.1289/ehp.1307602

Potential role of selection bias in the association between childhood leukemia and residential magnetic fields exposure: A population-based assessment

PurposeData from the Northern California Childhood Leukemia Study (NCCLS) were used to assess whether selection bias may explain the association between residential magnetic fields (assessed by wire codes) and childhood leukemia as previously observed in case–control studies. MethodsWiring codes were calculated for participating cases, n=310; and non-participating cases, n=66; as well as for three control groups: first-choice participating, n=174; first-choice non-participating, n=252; and replacement (non-first choice participating controls), n=220. ResultsParticipating controls tended to be of higher socioeconomic status than non-participating controls, and lower socioeconomic status was related to higher wire-codes. The odds ratio (OR) for developing childhood leukemia associated with high wire-codes was 1.18 (95% CI: 0.85, 1.64) when all cases were compared to all first-choice controls (participating and non-participating). The OR for developing childhood leukemia in the high current category was 1.43 (95% CI: 0.91, 2.26) when participating cases were compared to first-choice participating controls, but no associations were observed when participating cases were compared to non-participating controls (OR=1.06, 95% CI: 0.71, 1.57) or to replacement controls (OR=1.06, 95% CI: 0.71, 1.60). ConclusionsThe observed risk estimates vary by type of control group, and no statistically significant association between wire codes and childhood leukemia is observed in the California population participating in the NCCLS.

SNP Association Mapping across the Extended Major Histocompatibility Complex and Risk of B-Cell Precursor Acute Lymphoblastic Leukemia in Children

The extended major histocompatibility complex (xMHC) is the most gene-dense region of the genome and harbors a disproportionately large number of genes involved in immune function. The postulated role of infection in the causation of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) suggests that the xMHC may make an important contribution to the risk of this disease. We conducted association mapping across an approximately 4 megabase region of the xMHC using a validated panel of single nucleotide polymorphisms (SNPs) in childhood BCP-ALL cases (n=567) enrolled in the Northern California Childhood Leukemia Study (NCCLS) compared with population controls (n=892). Logistic regression analyses of 1,145 SNPs, adjusted for age, sex, and Hispanic ethnicity indicated potential associations between several SNPs and childhood BCP-ALL. After accounting for multiple comparisons, one of these included a statistically significant increased risk associated with rs9296068 (OR=1.40, 95% CI=1.19-1.66, corrected p=0.036), located in proximity to HLA-DOA. Sliding window haplotype analysis identified an additional locus located in the extended class I region in proximity to TRIM27 tagged by a haplotype comprising rs1237485, rs3118361, and rs2032502 (corrected global p=0.046). Our findings suggest that susceptibility to childhood BCP-ALL is influenced by genetic variation within the xMHC and indicate at least two important regions for future evaluation.

Polybrominated diphenyl ethers in residential dust: Sources of variability

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).

Polycyclic Aromatic Hydrocarbons in Residential Dust: Sources of Variability

Background: There is interest in using residential dust to estimate human exposure to environmental contaminants.Objectives: We 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.Methods: We 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.Results: Median 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.Conclusions: Our findings indicate that it may be feasible to use residential dust for retrospective assessment of PAH exposures in studies of health effects.

Determinants of polychlorinated biphenyls in dust from homes in California, USA.

Polychlorinated biphenyl (PCB) production ceased in the U.S. over 30 years ago, but these persistent chemicals remain ubiquitous contaminants. Here, we evaluate potential determinants of PCB levels in dust from California homes including characteristics of the residence as well as the residents' habits and occupations. Dust was collected from 415 households as part of a large case-control study (the Northern California Childhood Leukaemia Study), using a high-volume small surface sampler. Dust concentrations of 6 PCBs (PCB-105, PCB-118, PCB-138, PCB-153, PCB-170, and PCB-180) were measured using gas chromatography-mass spectrometry. Individual PCB detection rates ranged from 9% to 54% with PCB concentrations ranging from below detection (1 or 2 ng g (-1)) to 270 ng g(-1) and PCB loadings ranging from below detection to 960 ng m (-2). Multivariable linear and logistic regression models were used to identify potential determinants of residential PCB contamination based on in-home interviews and residential geographic locations. We observed that residences built prior to 1980 had higher odds of PCB detection and higher PCB loadings than more recently constructed homes. Households where residents typically did not remove their shoes had higher PCB dust loadings than households where residents did. PCBs were less likely to be detected in carpet dust from households that had frequently vacuumed or replaced carpets compared to other households. Since we used a cross-sectional dust sampling protocol and report significant, but modest, effects of these determinants on levels of PCBs in residential dust, our results should be interpreted with caution. Longitudinal studies to determine optimal strategies for reducing PCBs in homes are warranted.

Characterization of Residential Pesticide Use and Chemical Formulations through Self-Report and Household Inventory: The Northern California Childhood Leukemia Study

Background: Home and garden pesticide use has been linked to cancer and other health outcomes in numerous epidemiological studies. Exposure has generally been self-reported, so the assessment is potentially limited by recall bias and lack of information on specific chemicals.Objectives: As part of an integrated assessment of residential pesticide exposure, we identified active ingredients and described patterns of storage and use.Methods: During a home interview of 500 residentially stable households enrolled in the Northern California Childhood Leukemia Study during 2001–2006, trained interviewers inventoried residential pesticide products and queried participants about their storage and use. U.S. Environmental Protection Agency registration numbers, recorded from pesticide product labels, and pesticide chemical codes were matched to public databases to obtain information on active ingredients and chemical class. Poisson regression was used to identify independent predictors of pesticide storage. Analyses were restricted to 259 participating control households.Results: Ninety-five percent (246 of 259) of the control households stored at least one pesticide product (median, 4). Indicators of higher sociodemographic status predicted more products in storage. We identified the most common characteristics: storage areas (garage, 40%; kitchen, 20%), pests treated (ants, 33%; weeds, 20%), pesticide types (insecticides, 46%; herbicides, 24%), chemical classes (pyrethroids, 77%; botanicals, 50%), active ingredients (pyrethrins, 43%) and synergists (piperonyl butoxide, 42%). Products could contain multiple active ingredients.Conclusions: Our data on specific active ingredients and patterns of storage and use will inform future etiologic analyses of residential pesticide exposures from self-reported data, particularly among households with young children.

Abstract 676: Serological levels of folate at birth and risk of childhood acute lymphoblastic leukemia

Abstract A role for folate in the etiology of childhood acute lymphoblastic leukemia (ALL) has long been suspected due to folate's dual role in control of DNA methylation as well as maintenance of DNA synthesis. Case-control studies examining self-reported maternal folate intake and supplementation during pregnancy have been inconclusive. Furthermore, while studies of children's own folate metabolism and transport genes have identified potential disease loci, the results have been mixed on the whole. A child's exposure to folate in utero is modulated by a number of factors, including maternal intake/supplementation, maternal genes, and child's genes. Therefore, we examined the role of folate in childhood ALL risk more directly by utilizing a quantitative microbiologic assay to measure newborn red blood cell folate levels in archived dried bloodspots collected at birth from 319 incident cases and 413 matched population-based controls who enrolled in the Northern California Childhood Leukemia Study between 1995 and 2002. After adjustment for income, race/ethnicity, gender, and age, we found no difference in newborn folate levels between cases and controls overall (971 vs. 968 nmol/L, p=0.94). In addition, no differences between cases and controls were observed after stratification by birth year to account for the start of folate fortification of grain products in the US (1982-1994: 953 vs. 952 nmol/L, p=0.98; 1995-1998: 1018 vs. 975 nmol/L, p=0.34; and 1999-2002: 878 vs. 990 nmol/L, p=0.23). Children whose mothers reported pre-pregnancy supplement use had somewhat higher newborn folate levels overall, but we observed no case-control differences in folate levels after stratification by supplement use. Our results do not support an association between folate levels at birth and risk of childhood ALL. However, our results do not rule out a role for folate exposures after birth. Future epidemiologic studies of childhood ALL should pay particular attention to post-natal folate exposures. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 676. doi:1538-7445.AM2012-676

Reliability of maternal-reports regarding the use of household pesticides: Experience from a case–control study of childhood leukemia

Introduction: Self-reported household pesticide use has been associated with higher risk of childhood leukemia in a number of case–control studies. The aim of this study is to assess the reliability of self-reported household use of pesticides and potential differences in reliability by case–control status, and by socio-demographic characteristics. Methods: Analyses are based on a subset of the Northern California Childhood Leukemia Study population. Eligible households included those with children less than 8 years old who lived in the same residence since diagnosis (reference date for controls). The reliability was based on two repeated in-person interviews. Kappa, percent positive and negative agreements were used to assess reliability of responses to ever/never use of six pesticides categories. Results: Kappa statistics ranged from 0.31 to 0.61 (fair to substantial agreement), with 9 out of the 12 tests indicating moderate agreement. The percent positive agreement ranged from 46 to 80% and the percent negative agreement from 54 to 95%. Reliability for all pesticide types as assessed by the three reliability measures did not differ significantly for cases and controls as confirmed by bootstrap analysis. For most pesticide types, Kappa and percent positive agreement were higher for non-Hispanics than Hispanics and for households with higher income vs. lower income. Conclusions: Reproducibility of maternal-reported pesticide use was moderate to high and was similar among cases and controls suggesting that differential recall is not likely to be a major source of bias.

The Relationship between Residential Magnetic Fields and Contact Voltage: A Pooled Analysis

It has been suggested that residential exposure to contact currents may be more directly associated with the potential for an increased risk of leukemia in childhood than magnetic fields. Contact current exposure occurs when a child contacts a bathtub's water fixtures, which are usually contiguous with a residence's electrical ground, and when the drainpipe is conductive. The Northern California Childhood Leukemia Study (NCCLS) is the only epidemiological study known to address whether contact current may confound the reported association between residential magnetic fields and childhood leukemia. The study contributed contact voltage and magnetic-field data for over 500 residences of leukemia cases and control children. We combined these data with the results of previous measurement studies of contact voltage in other communities to conduct an analysis of the relationship of magnetic fields with contact voltage for a total sample of 702 residences. The Spearman correlation of magnetic field with contact voltage was 0.29 (Spearman, P < 0.0001). Magnetic-field and contact voltage data were both divided into tertiles, with an upper magnetic-field cutpoint of 0.3 μT suggested by values used in epidemiological results and an upper contact voltage cutpoint of 60 mV based on dosimetric considerations. Expressed as an exposure odds ratios (EOR), we report an association of contact voltage with magnetic fields of 15.1 (95% CI 3.6-61) as well as a statistically significant positive trend across magnetic-field strata (EOR of 4.2 per stratum with 95% CI 2.4-7.4). The associations appear to be large enough to support the possibility that contact current could be responsible for the association of childhood leukemia with magnetic fields.

Early life exposure to infections and risk of childhood acute lymphoblastic leukemia

Evidence from a growing number of studies indicates that exposure to common infections early in life may be protective against childhood acute lymphoblastic leukemia (ALL). We examined the relationship between three measures of early life exposure to infections-daycare attendance, birth order and common childhood infections in infancy-with the risk of ALL in non-Hispanic white and Hispanic children, two ethnicities that show sociodemographic differences. The analysis included 669 ALL cases (284 non-Hispanic whites and 385 Hispanics) and 977 controls (458 non-Hispanic whites and 519 Hispanics) ages 1-14 years enrolled in the Northern California Childhood Leukemia Study (NCCLS). When the three measures were evaluated separately, daycare attendance by the age of 6 months (odds ratio [OR] for each thousand child-hours of exposure = 0.90, 95% confidence interval [CI]: 0.82-1.00) and birth order (OR for having an older sibling = 0.68, 95% CI: 0.50-0.92) were associated with a reduced risk of ALL among non-Hispanic white children but not Hispanic children, whereas ear infection before age 6 months was protective in both ethnic groups. When the three measures were assessed simultaneously, the influence of daycare attendance (OR = 0.83, 95% CI: 0.73-0.94) and having an older sibling (OR = 0.59, 95% CI: 0.43-0.83) became stronger for non-Hispanic white children. In Hispanic children, a strong reduction in risk associated with ear infections persisted (OR = 0.45, 95% CI: 0.25-0.79). Evidence of a protective role for infection-related exposures early in life is supported by findings in both the non-Hispanic white and Hispanic populations within the NCCLS.

Exposure to Electrical Contact Currents and the Risk of Childhood Leukemia

The objectives of this study were to examine the association between contact current exposure and the risk of childhood leukemia and to investigate the relationship between residential contact currents and magnetic fields. Indoor and outdoor contact voltage and magnetic-field measurements were collected for the diagnosis residence of 245 cases and 269 controls recruited in the Northern California Childhood Leukemia Study (2000-2007). Logistic regression techniques produced odds ratios (OR) adjusted for age, sex, Hispanic ethnicity, mother's race and household income. No statistically significant associations were seen between childhood leukemia and indoor contact voltage level [exposure ≥90th percentile (10.5 mV): OR = 0.83, 95% confidence interval (CI): 0.45, 1.54], outdoor contact voltage level [exposure ≥90th percentile (291.2 mV): OR = 0.89, 95% CI: 0.48, 1.63], or indoor magnetic-field levels (>0.20 µT: OR = 0.76, 95% CI: 0.30, 1.93). Contact voltage was weakly correlated with magnetic field; correlation coefficients were r = 0.10 (P = 0.02) for indoor contact voltage and r = 0.15 (P = 0.001) for outdoor contact voltage. In conclusion, in this California population, there was no evidence of an association between childhood leukemia and exposure to contact currents or magnetic fields and a weak correlation between measures of contact current and magnetic fields.

Determinants of polycyclic aromatic hydrocarbon levels in house dust

Estimation of human exposures to polycyclic aromatic hydrocarbons (PAHs) is often desired for the epidemiological studies of cancer. One way to obtain information about indoor levels of PAHs is to measure these chemicals in house dust. In this study, we evaluated the predictive value of self-reported and geographic data for estimating measured levels of nine PAHs in house dust from 583 households in the Northern California Childhood Leukemia Study (NCCLS). Using multivariable linear regression models, we evaluated the effects on house-dust PAH concentrations from the following covariates: residential heating sources, smoking habits, house characteristics, and outdoor emission sources. House dust was collected from 2001 to 2007, using both high-volume surface samplers and household vacuum cleaners, and was analyzed for nine PAHs using gas chromatography-mass spectrometry. All nine PAHs were detected in more than 93% of dust samples, with median concentrations ranging from 14 to 94 ng/g dust. Statistically significant effects on PAH concentrations in house dust were found for gas heating, outdoor PAH concentrations, and residence age. Yet, the optimal regression model only explained 15% of the variation in PAH levels in house dust. As self-reported data and outdoor PAH sources were only marginally predictive of observed PAH levels, we recommend that PAH concentrations be measured directly in dust samples for use in epidemiological studies.

Residential Exposure to Polychlorinated Biphenyls and Organochlorine Pesticides and Risk of Childhood Leukemia

ISEE-0490 Background: The etiologic role of persistent organochlorine chemicals in childhood cancer risk has not been evaluated in population-based studies. House dust is a reservoir for chemicals used in the home and nearby environment. Ingestion of house dust is an important route of chemical exposure for young children. We estimated the risk of childhood leukemia associated with persistent organochlorine chemicals using carpet dust as an exposure indicator. Methods: We studied 184 acute lymphocytic leukemia (ALL) cases 0–7 years of age and 212 birth certificate controls from the Northern California Childhood Leukemia Study (2000–2006). Using a high volume surface sampler (HVS3) vacuum, we sampled carpets that were present in the home before the diagnosis/reference date. We measured concentrations (ng/g) of six polychlorinated biphenyl (PCB) congeners (105, 118, 138, 153, 170, 180) and the organochlorine pesticides chlordane, p,p'-DDT and its metabolite p,p'-DDE, methoxychlor, and pentachlorophenol. Odds ratios were calculated using unconditional logistic regression analysis adjusting for demographics, age of the home, sampling season (for organochlorine pesticides), and breastfeeding (PCBs). Results: Detection of any PCB congener in the dust conferred a two-fold increased risk of ALL (OR = 1.97, 95% Confidence Interval [CI] 1.22–3.17). Compared to those in the lowest quartile of total PCBs, the highest quartile was associated with about a three-fold risk (OR = 2.78, 95% CI 1.41–5.48; p trend = 0.02). We observed significant positive trends in risk associated with concentrations of the PCB congeners 118, 138, and 153 (P for trend = 0.02, 0.03, 0.02, respectively). The associations with PCBs were stronger among non-Hispanic Whites, despite a similar distribution of exposure among all ethnic/racial groups. We observed no significant association with concentrations of chlordane, p,p'-DDT, p,p'-DDE, methoxychlor, or pentachlorphenol. Conclusion: Our findings suggest that PCBs, which are considered probable human carcinogens and cause perturbations of the immune system, may be a risk factor for childhood leukemia.

Residential proximity to agricultural pesticide applications and childhood acute lymphoblastic leukemia

Ambient exposure from residential proximity to applications of agricultural pesticides may contribute to the risk of childhood acute lymphoblastic leukemia (ALL). Using residential histories collected from the families of 213 ALL cases and 268 matched controls enrolled in the Northern California Childhood Leukemia Study, the authors assessed residential proximity within a half-mile (804.5m) of pesticide applications by linking address histories with reports of agricultural pesticide use. Proximity was ascertained during different time windows of exposure, including the first year of life and the child's lifetime through the date of diagnosis for cases or reference for controls. Agricultural pesticides were categorized a priori into groups based on similarities in toxicological effects, physicochemical properties, and target pests or uses. The effects of moderate and high exposure for each group of pesticides were estimated using conditional logistic regression. Elevated ALL risk was associated with lifetime moderate exposure, but not high exposure, to certain physicochemical categories of pesticides, including organophosphates, chlorinated phenols, and triazines, and with pesticides classified as insecticides or fumigants. A similar pattern was also observed for several toxicological groups of pesticides. These findings suggest future directions for the identification of specific pesticides that may play a role in the etiology of childhood leukemia.

Maternal Immunoglobulin E and Childhood Leukemia

Childhood leukemia, particularly acute lymphoblastic leukemia (ALL), has long been hypothesized to be affected by abnormal immune responses to microbial challenges stemming from a lack of immune modulation in early childhood. Studies of allergies suggest that a child's immune development may be modulated by maternal immune status. We conducted a study to explore the relationship between maternal immunoglobulin E (IgE) and childhood leukemia and to investigate whether maternal immune status can influence childhood leukemia risk. Serum total and specific IgE (respiratory and food) were measured in biological mothers of 352 children (193 healthy controls and 159 leukemia cases, including 139 ALL cases) ages <8 years who were enrolled in the Northern California Childhood Leukemia Study. Odds ratios associated with maternal IgE were calculated using unconditional logistic regression adjusted for child's age, sex, race/ethnicity, and annual household income. A positive association between childhood leukemia or ALL and elevated levels of maternal serum total IgE was observed, especially among Hispanics. In addition, a positive association was observed between childhood leukemia or ALL and maternal respiratory or food IgE status. These results suggest that maternal immune function may play a crucial role in the etiology of childhood leukemia, although additional studies need to be conducted to confirm the results of this study and provide a perspective on mechanisms.

Maternal Diet and Risk of Childhood Acute Lymphoblastic Leukemia

Intrauterine environmental factors, including maternal diet, may play an etiologic role in acute lymphoblastic leukemia (ALL), a common childhood cancer. Expanding on previous findings from phase 1 of the Northern California Childhood Leukemia Study (NCCLS), a population-based case-control study, we sought to further elucidate and replicate the relationships between maternal diet and ALL risk. We matched 282 case-control sets of children (205 pairs and 77 triplets) from phases 1 and 2 of the NCCLS on sex, date of birth, mother's race, Hispanic racial/ethnic status, and county of residence at birth. We used an interviewer-administered food frequency questionnaire to obtain information on maternal dietary intake in the 12 months prior to pregnancy. Risk of ALL was inversely associated with maternal consumption of vegetable (adjusted odds ratio [AOR] = 0.65, 95% confidence interval [CI] 0.50, 0.84); protein sources (AOR = 0.55, 95% CI 0.32, 0.96); fruit (AOR = 0.81, 95% CI 0.65, 1.00); and legume food groups (AOR = 0.75, 95% CI 0.59, 0.95). The risk reduction was strongest for consumption of the protein sources and vegetable food groups, independent of the child's diet up to age 2 years, and consistent across phases 1 and 2 of data collection for vegetable consumption. These data suggest that it may be prudent for women to consume a diet rich in vegetables and adequate in protein prior to and during pregnancy as a possible means of reducing childhood ALL risk in their offspring.