Case-control Study In California Research Articles

Mixed methods approach to examining the implementation experience of a phone-based survey for a SARS-CoV-2 test-negative case-control study in California.

To describe the implementation of a test-negative design case-control study in California during the Coronavirus Disease 2019 (COVID-19) pandemic. Test-negative case-control study. Between February 24, 2021 - February 24, 2022, a team of 34 interviewers called 38,470 Californians, enrolling 1,885 that tested positive for SARS-CoV-2 (cases) and 1,871 testing negative for SARS-CoV-2 (controls) for 20-minute telephone survey. We estimated adjusted odds ratios for answering the phone and consenting to participate using mixed effects logistic regression. We used a web-based anonymous survey to compile interviewer experiences. Cases had 1.29-fold (95% CI: 1.24-1.35) higher adjusted odds of answering the phone and 1.69-fold (1.56-1.83) higher adjusted odds of consenting to participate compared to controls. Calls placed from 4pm to 6pm had the highest adjusted odds of being answered. Some interviewers experienced mental wellness challenges interacting with participants with physical (e.g., food, shelter, etc.) and emotional (e.g., grief counseling) needs, and enduring verbal harassment from individuals called. Calls placed during afternoon hours may optimize response rate when enrolling controls to a case-control study during a public health emergency response. Proactive check-ins and continual collection of interviewer experience(s) and may help maintain mental wellbeing of investigation workforce. Remaining adaptive to the dynamic needs of the investigation team is critical to a successful study, especially in emergent public health crises, like that represented by the COVID-19 pandemic.

Pre- and Postnatal Exposures to Tobacco Smoking and Survival of Childhood Acute Lymphoblastic and Myeloid Leukemias in California, United States.

Tobacco smoke adversely affects the prognosis of adult cancers including myeloid leukemia, but less is known in children. We evaluated whether pre- and postnatal exposures to tobacco smoke decrease 5-year survival of 1,235 childhood acute lymphoblastic leukemia (ALL) and 188 childhood acute myeloid leukemia (AML) cases derived from a population-based case-control study in California. Cases were diagnosed between 1995 and 2015 (median follow-up time of 13.2 years overall). We obtained data on tobacco smoking (before conception, during pregnancy, after birth), parental education and income, clinical features, and vital status through 2020. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for mortality associated with smoking, adjusting for sociodemographic characteristics and risk group (ALL only). About 23% of mothers and 39% of fathers reported smoking and 130 children with ALL and 52 with AML died within 5 years. For AML, increased risks of death were observed among children whose fathers smoked before conception compared with nonsmoking fathers [HR = 1.41; 95% confidence interval (CI), 0.95-3.44 and 3.47; 95% CI, 1.37-8.81, respectively for <20 vs. ≥20 cigarettes per day; Ptrend = 0.01]. HR for child's passive smoking was 1.74, 95% CI, 0.81-3.73. Paternal preconception smoking may also reduce 5-year survival among ALL with favorable prognostic molecular subtypes (high hyperdiploidy and absence of IKZF1 gene deletion), although the associations did not reach statistical significance (Pheterogeneity = 0.07). Paternal preconception smoking decreased 5-year survival of childhood AML. Knowledge of exposure to tobacco smoking should be integrated in the treatment plan of childhood leukemias.

BIOMARKERS OF MATERNAL SMOKING AND THE RISK OF RETINOBLASTOMA IN OFFSPRING.

Previous studies examining the risk of retinoblastoma with maternal smoking were inconclusive, likely due in part to the reliance on self-reported maternal smoking. This study uses biomarkers of tobacco smoking in neonatal dried blood spots to investigate associations between maternal smoking and retinoblastoma in offspring. The authors randomly selected 498 retinoblastoma cases and 895 control subjects born between 1983 and 2011 from a population-based case-control study in California. Maternal pregnancy-related smoking was measured using the following three metrics: provider or self-reported smoking during pregnancy, cotinine, and hydroxycotinine in neonatal blood. The authors used multivariable logistic regression to estimate the effects of maternal tobacco smoking on retinoblastoma. Using all metrics (biomarkers or self-report), maternal smoking late in pregnancy or early postpartum was related to retinoblastoma (all types; odds ratio = 1.44, 95% confidence interval: 1.00-2.09). Relying on cotinine or hydroxycotinine to ascertain smoking, maternal smoking was related to unilateral retinoblastoma (odds ratio = 1.66, 95% confidence interval: 1.08-2.57). The results indicate that maternal smoking during pregnancy may be a risk factor for retinoblastoma, particularly among unilateral cases.

Proximity to endocrine-disrupting pesticides and risk of testicular germ cell tumors (TGCT) among adolescents: A population-based case-control study in California.

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. To assess the relationship between fetal exposure to agricultural endocrine-disrupting pesticides (EDPs) and TGCT risk among adolescents in a diverse population in California. 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. A doubling of nearby acephate applications (3km and 1km radii) and malathion applications (1km 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 3km 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%. 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.

Greenspace, Air Pollution, Neighborhood Factors, and Preeclampsia in a Population-Based Case-Control Study in California.

To investigate preeclampsia etiologies, we examined relationships between greenspace, air pollution, and neighborhood factors. Data were from hospital records and geocoded residences of 77,406 women in San Joaquin Valley, California from 2000 to 2006. Preeclampsia was divided into mild, severe, or superimposed onto pre-existing hypertension. Greenspace within 100 and 500 m residential buffers was estimated from satellite data using normalized difference vegetation index (NDVI). Air quality data were averaged over pregnancy from daily 24-h averages of nitrogen dioxide, particulate matter <10 µm (PM10) and <2.5 µm (PM2.5), and carbon monoxide. Neighborhood socioeconomic (SES) factors included living below the federal poverty level and median annual income using 2000 US Census data. Odds of preeclampsia were estimated using logistic regression. Effect modification was assessed using Wald tests. More greenspace (500 m) was inversely associated with superimposed preeclampsia (OR = 0.57). High PM2.5 and low SES were associated with mild and severe preeclampsia. We observed differences in associations between greenspace (500 m) and superimposed preeclampsia by neighborhood income and between greenspace (500 m) and severe preeclampsia by PM10, overall and among those living in higher SES neighborhoods. Less greenspace, high particulate matter, and high-poverty/low-income neighborhoods were associated with preeclampsia, and effect modification was observed between these exposures. Further research into exposure combinations and preeclampsia is warranted.

Association Between Midpregnancy Polyunsaturated Fatty Acid Levels and Offspring Autism Spectrum Disorder in a California Population-Based Case-Control Study.

Polyunsaturated fatty acids (PUFAs) are critical for brain development and have been linked with neurodevelopmental outcomes. We conducted a population-based case-control study in California to examine the association between PUFAs measured in midpregnancy serum samples and autism spectrum disorder (ASD) in offspring. ASD cases (n=499) were identified through the California Department of Developmental Services and matched to live-birth population controls (n=502) on birth month, year (2010 or 2011), and sex. Logistic regression models were used to examine crude and adjusted associations. In secondary analyses, we examined ASD with and without co-occurring intellectual disability (ID; n=67 and n = 432, respectively) and effect modification by sex and ethnicity. No clear patterns emerged, though there was a modest inverse association with the top quartile of linoleic acid level (highest quartile vs. lowest: adjusted odds ratio=0.74, 95% confidence interval: 0.49, 1.11; P for trend=0.10). Lower levels of total and ω-3 PUFAs were associated with ASD with ID (lowest decile of total PUFAs vs. deciles 4-7: adjusted odds ratio=2.78, 95% confidence interval: 1.13, 6.82) but not ASD without ID. We did not observe evidence of effect modification by the factors examined. These findings do not suggest a strong association between midpregnancy PUFA levels and ASD. In further work, researchers should consider associations with ASD with ID and in other time windows.

Seven-Year Case-Control Study in California of Risk Factors for Infant Botulism

To ascertain possible risk factors for infant botulism, the intestinal infectious form of human botulism, in the years immediately following its initial recognition in California in1976. Parents of 159 California laboratory-confirmed cases of infant botulism from 1976 to 1983 and 318 healthy controls were interviewed using a comprehensive (>300 factors) questionnaire. "Neighborhood controls" (n=184) were matched on date of birth, sex, race/ethnicity, and neighborhood of residence. "County controls" (n=134) were matched only on date of birth, sex, and county of residence. Age-stratified bivariate and multivariate conditional logistic regression analyses were performed using SAS. All cases required hospitalization. Bivariate analyses identified several risk factors that in multivariate analyses were not significant. In multivariate analyses, risk factors differed with stratification by age. For the ≤2 month-old neighborhood controls comparison, birth order >1, cesarean delivery, ≤1 bowel movements (BMs) per day, and windy residence area were associated with illness hospitalization, and for the county controls comparison, only pacifier use was associated. For the <2 month-old neighborhood controls comparison, <1 bowel movements (BMs) per day, cesarean delivery, birth order >1, and windy residence area were associated with illness hospitalization, and for the county controls comparison, pets in the home was an additional risk factor. With the exception of the ≤2-month-old county controls group, slower intestinal transit time (≤1 BM/d) was associated with illness. Otherwise, our case-control investigation identified few physiologic, environmental, and maternal factors associated with infant botulism hospitalization in California.

Residential magnetic fields exposure and childhood leukemia: a population-based case-control study in California.

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

Tobacco Smoke and Ras Mutations Among Latino and Non-Latino Children with Acute Lymphoblastic Leukemia

Childhood acute lymphoblastic leukemia (ALL) is a biologically heterogeneous disease, and mutations in the KRAS and NRAS oncogenes are present at diagnosis in about one-fifth of cases. Ras mutations were previously associated with environmental exposures in leukemias as well as in many other cancer types. This study examined whether Ras mutation could define a unique etiologic group of childhood ALL associated with tobacco smoke, a well-established mutagen and carcinogen. We included 670 children with ALL enrolled in a case-control study in California (1995-2013), including 50.6% Latinos. Parental and child exposure to tobacco smoke was obtained from interviews. Sanger sequencing was used to detect the common KRAS and NRAS hotspot mutations in diagnostic bone marrow DNA. ALL cases were also characterized for common chromosome abnormalities. In case-case analyses, logistic regression analyses were used to estimate odds ratios to describe the association between tobacco smoke exposure and childhood ALL with Ras mutations. KRAS or NRAS mutations were detected in ∼18% of children diagnosed with ALL. Ras mutations were more common among Latino cases compared with non-Latino whites and in high-hyperdiploid ALL. No associations were observed between parental smoking or child's passive exposure to smoke and Ras positive ALL. The apparent lack of association between tobacco smoke and Ras mutation in childhood ALL suggests that Ras mutations do not specifically define a tobacco-related etiologic pathway. Reasons for racial and ethnic differences in ALL are not well understood and could reflect differences in etiology that warrant further examination.

Maternal diet quality before pregnancy and risk of childhood leukaemia.

Previous studies on maternal nutrition and childhood leukaemia risk have focused on the role of specific nutrients such as folate and have not considered broader measures of diet quality, which may better capture intake of diverse nutrients known to impact fetal development. We examined the relationship between maternal diet quality before pregnancy, as summarised by a diet quality index, and risk of childhood acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in a case-control study in California. Dietary intake in the year before pregnancy was assessed using FFQ in 681 ALL cases, 103 AML cases and 1076 matched controls. Conditional logistic regression was used to estimate OR and 95 % CI for diet quality continuous score and quartiles (Q1-Q4). Higher maternal diet quality score was associated with reduced risk of ALL (OR 0·66; 95 % CI 0·47, 0·93 for Q4 v. Q1) and possibly AML (OR 0·42; 95 % CI 0·15, 1·15 for Q4 v. Q1). No single index component appeared to account for the association. The association of maternal diet quality with risk of ALL was stronger in children diagnosed under the age of 5 years and in children of women who did not report using vitamin supplements before pregnancy. These findings suggest that the joint effects of many dietary components may be important in influencing childhood leukaemia risk.

Gene variants as risk factors for gastroschisis.

In a population‐based case‐control study in California of 228 infants, we investigated 75 genetic variants in 20 genes and risk of gastroschisis with regard to maternal age, race/ethnicity, vitamin use, and smoking exposure. We hypothesized that genes related to vascular compromise may interact with environmental factors to affect the risk of gastroschisis. Haplotypes were constructed for 75 gene variants using the HaploView program. Risk for gastroschisis associated with each gene variant was calculated for both the homozygotes and the heterozygotes, with the homozygous wildtypes as the referent. Risks were estimated as odds ratios (ORs) with 95% confidence intervals (CIs) by logistic regression. We found 11 gene variants with increased risk and four variants with decreased risk of gastroschisis for heterozygous (ORh) or homozygous variants (ORv) genotypes. These included NOS3 (rs1036145) ORh = 0.4 (95% CI: 0.2–0.7); NOS3 (rs10277237) ORv = 2.7 (95% CI: 1.3–6.0); ADD1 (rs12503220) ORh = 2.9 (95% CI: 1.6–5.4), GNB3 (rs5443) ORh = 0.2 (95% CI: 0.1–0.5), ORv = 0.4 (95% CI: 0.2–0.9); ICAM1 (rs281428) ORv = 6.9 (95% CI: 2.1–22.9), ICAM1 (rs3093030) ORv = 2.6 (95% CI: 1.2–5.6); ICAM4 (rs281438) ORv = 4.9 (95% CI: 1.4–16.6), ICAM5 (rs281417) ORh = 2.1 (95% CI: 1.1–4.1), ORv = 4.8 (95% CI: 1.7–13.6); ICAM5 (rs281440) ORh = 23.7 (95% CI: 5.5–102.5), ORv = 20.6 (95% CI: 3.4–124.3); ICAM5 (rs2075741) ORv = 2.2 (95% CI: 1.1–4.4); NAT1 ORv = 0.3 (95% CI: 0.1–0.9). There were additional associations between several gene variants and gastroschisis among women aged 20–24 and among mothers with and without vitamin use. NOS3, ADD1, ICAM1, ICAM4, and ICAM5 warrant further investigation in additional populations and with the interaction of additional environmental exposures. © 2016 Wiley Periodicals, Inc.

In Utero and Early-Life Exposure to Ambient Air Toxics and Childhood Brain Tumors: A Population-Based Case-Control Study in California, USA.

Background:Little is known about the influence of environmental factors on the etiology of childhood brain tumors.Objectives:We examined risks for brain tumors in children after prenatal and infant exposure to monitored ambient air toxics.Methods:We ascertained all cases of medulloblastoma, central nervous system primitive neuroectodermal tumor (PNET), and astrocytoma before 6 years of age diagnosed in 1990–2007 from the California Cancer Registry and selected controls randomly from birth rolls matched by birth year. Exposures to air toxics during pregnancy/infancy for 43 PNET, 34 medulloblastoma, and 106 astrocytoma cases and 30,569 controls living within 5 mi of a monitor were determined. With factor analysis we assessed the correlational structures of 26 probable carcinogenic toxics, and estimated odds ratios by brain tumor type in logistic regression models.Results:PNETs (≤ 38 cases) were positively associated with interquartile range (IQR) increases in prenatal exposure to acetaldehyde [odds ratio (OR) = 2.30; 95% CI: 1.44, 3.67], 1,3-butadiene (OR = 2.23; 95% CI: 1.28, 3.88), benzene, and toluene; and with IQR increases in exposure during the first year of life to ortho-dichlorobenzene (OR = 3.27; 95% CI: 1.17, 9.14), 1,3-butadiene (OR = 3.15; 95% CI: 1.57, 6.32), and benzene. All exposures except ortho-dichlorobenzene loaded on the same factor. Medulloblastoma (≤ 30 cases) was associated with prenatal exposure to polycyclic aromatic hydrocarbons (PAHs combined: OR = 1.44; 95% CI: 1.15, 1.80). Exposures to lead and some PAHs during the first year of life were positively associated with astrocytoma, but the confidence intervals included the null value (e.g., for lead, OR = 1.40; 95% CI: 0.97, 2.03).Conclusions:Our data suggest that in utero and infancy exposures to air toxics generated by industrial and road traffic sources may increase the risk of PNET and medulloblastoma, with limited support for increased risks for astrocytoma in children up to age 6.Citation:von Ehrenstein OS, Heck JE, Park AS, Cockburn M, Escobedo L, Ritz B. 2016. In Utero and early-life exposure to ambient air toxics and childhood brain tumors: a population-based case–control study in California, USA. Environ Health Perspect 124:1093–1099; http://dx.doi.org/10.1289/ehp.1408582

A Task-Based Assessment of Parental Occupational Exposure to Organic Solvents and Other Compounds and Risk of Acute Lymphoblastic Leukemia in the Offspring

A Task-Based Assessment of Parental Occupational Exposure to Organic Solvents and Other Compounds and Risk of Acute Lymphoblastic Leukemia in the OffspringAbstract Number:2249 Catherine Metayer*, Ghislaine Scélo, Alice Y. Kang, Robert B. Gunier, Kyndaron Reinier, C. Suzanne Lea, Jeffrey S. Chang, Steve Selvin, Janice Kirsch, Monique Does, Patricia Quinlan, and S. Katharine Hammond Catherine Metayer* University of California, Berkeley, United States, E-mail Address: [email protected] Search for more papers by this author , Ghislaine Scélo International Agency for Research on Cancer, France, E-mail Address: [email protected] Search for more papers by this author , Alice Y. Kang University of California, Berkeley, United States, E-mail Address: [email protected] Search for more papers by this author , Robert B. Gunier University of California, Berkeley, United States, E-mail Address: [email protected] Search for more papers by this author , Kyndaron Reinier Cedars-Sinai Medical Center, United States, E-mail Address: [email protected] Search for more papers by this author , C. Suzanne Lea East Carolina University, United States, E-mail Address: [email protected] Search for more papers by this author , Jeffrey S. Chang National Institute of Cancer Research, Taiwan, E-mail Address: [email protected] Search for more papers by this author , Steve Selvin University of California, Berkeley, United States, E-mail Address: [email protected] Search for more papers by this author , Janice Kirsch Medical oncologist and hematologist, United States, E-mail Address: [email protected] Search for more papers by this author , Monique Does University of California, Berkeley, United States, E-mail Address: [email protected] Search for more papers by this author , Patricia Quinlan University of California, San Francisco, United States, E-mail Address: [email protected] Search for more papers by this author , and S. Katharine Hammond University of California, Berkeley, United States, E-mail Address: [email protected] Search for more papers by this author AbstractBackground: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Studies examining paternal occupational exposures and risk of childhood ALL have mainly relied on job titles lacking specificity.Methods: We examined the relationship between the father’s workplace exposures before and after birth and risk of ALL in the offspring. Children with ALL (n=667) and controls (n=1,020) were enrolled in a population-based case-control study in California (2000-2008). We developed 19 task-based job modules (JMs) based on the prevalence of occupations in the study area and the probability of exposures to carcinogens. Expert assessment was then applied to estimate exposure to organic solvents and other compounds. Unconditional logistic regression models adjusted for socio-demographic factors were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).Results: Of 1,634 fathers, 903 were assigned a JM and 643 (71%) completed the interview (55% Hispanic origin). Occupations were stable over time. Among children with non-Hispanic fathers, no associations were observed with any exposures evaluated. In contrast in children with Hispanic fathers, the OR for exposure to organic solvents was 1.48 (95% CI: 1.01-2.16). In multivariable analyses, the OR for chlorinated hydrocarbons was 2.28 (95% CI: 0.97- 5.37; n=31 exposed cases vs. 17 controls) and close to one for aromatic hydrocarbons, glycol ethers, and other hydrocarbon mixtures. Moderate elevated risks were seen with exposure to combustion exhausts, metals, paints, structural pesticides (data on agricultural pesticides are presented separately), and wood dust, although not statistically significant in univariate or multivariable models.Conclusion: Our data support associations between paternal occupational exposures to known carcinogens contained in organic solvents for children of Hispanic origins, specifically chlorinated hydrocarbons. Explanations for ethnic differences are under investigation.

Job Exposure Matrix (JEM) derived estimates of life-time occupational pesticide exposure and the risk of Parkinson’s Disease

Background: Previous studies repeatedly suggested that Parkinson’s disease (PD) is associated with occupational pesticide exposure, but in many studies exposures were self-reported and none adjusted for concomitant ambient pesticide exposures. Objective: To investigate whether occupational exposure to pesticides increases the risk of PD in California’s heavily agricultural region. Methods: We enrolled 357 incident PD cases and 750 population controls in a case-control study in California’s Central Valley between 2001 to 2011. A comprehensive Job Exposure Matrix (JEM) was developed to assess participant’s life-time cumulative occupational pesticide exposure based on work history and detailed job tasks information. Results: PD risk was estimated to be more than 2-fold higher (OR=2.19 95%CI 1.26, 3.82) in men who were classified as highly occupational exposed with our data suggesting an exposure-response (trend p=0.007). Farming tasks with more direct and intense pesticide exposures such as applying, spraying and mixing of pesticides resulted in greater risks than indirect exposures from general tasks such as planting, harvesting, packing, sorting, etc. Results did not change when we adjusted for residential and occupational ambient pesticide exposures estimated based on a Geographic Information System (GIS) model. Conclusion: We provide further evidence that occupational pesticide exposure increases the risk of PD in men and ambient exposures did not confound these associations.

Epidemiologic study of residential proximity to transmission lines and childhood cancer in California: description of design, epidemiologic methods and study population.

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

Genetic variants in ARID5B and CEBPE are childhood ALL susceptibility loci in Hispanics

Recent genome-wide studies conducted in European Whites have identified novel susceptibility genes for childhood acute lymphoblastic leukemia (ALL). We sought to examine whether these loci are susceptibility genes among Hispanics, whose reported incidence of childhood ALL is the highest of all ethnic groups in California, and whether their effects differ between Hispanics and non-Hispanic Whites (NHWs). We genotyped 13 variants in these genes among 706 Hispanic (300 cases, 406 controls) and 594 NHW (225 cases, 369 controls) participants in a matched population-based case–control study in California. We found significant associations for the five studied ARID5B variants in both Hispanics (p values of 1.0 × 10−9 to 0.004) and NHWs (p values of 2.2 × 10−6 to 0.018). Risk estimates were in the same direction in both groups (ORs of 1.53–1.99 and 1.37–1.84, respectively) and strengthened when restricted to B-cell precursor high-hyperdiploid ALL (>50 chromosomes; ORs of 2.21–3.22 and 1.67–2.71, respectively). Similar results were observed for the single CEBPE variant. Hispanics and NHWs exhibited different susceptibility loci at CDKN2A. Although IKZF1 loci showed significant susceptibility effects among NHWs (p < 1 × 10−5), their effects among Hispanics were in the same direction but nonsignificant, despite similar minor allele frequencies. Future studies should examine whether the observed effects vary by environmental, immunological, or lifestyle factors.

Abstract 662: Effect of tobacco smoking on the risks of childhood acute lymphocytic and myeloid leukemias, by phenotypic and cytogenetic subtype

Abstract Background: Tobacco smoke contains several myelotropic carcinogens (i.e., benzene, 1,3 butadiene and formaldehyde) and is strongly suspected of damaging pluripotential hematopoietic stem cells. Objective: To examine the role of tobacco smoking in the etiology of childhood acute lymphocytic leukemia (ALL) and myeloid leukemia (AML), defined by phenotypic feature and type of chromosomal aberrations at diagnosis, such as translocation t(12:21) or high hyperdiploidy (51+ chromosomes). Method: Children (0-14 years old) newly diagnosed with ALL (n=839) and AML (n=145) were enrolled in a case-control study in California (1995-2008). Population-based controls (n=1226) were matched to cases on age, sex, Hispanic status, and maternal race. Parents provided information on exposure to tobacco smoking before and after their child's birth. Conventional karyotype and fluorescence in situ hybridization (FISH) data were abstracted from the medical reports. Additional FISH assays using pre-treatment bone marrow specimens were conducted to complete cytogenetic classification. Unconditional logistic regression analyses were used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for developing leukemia, using binary variable for ever/never smoked (ORbinary) and continuous variable for number of cigarettes smoked per day (ORcig). All models included the matching factors and household income. Results: In univariate analyses, elevated risks of B-cell ALL (n=722) were associated with pre-conception paternal smoking (“PCPS”) (ORcig= 1.02; 95% CI:1.00-1.03; p=0.04) and child's passive smoking (“CPS”) after birth (ORbinary=1.32; 95% CI:1.21-3.50; p=0.02). Analyses using mutually exclusive exposure variables (i.e., only “PCPS,” only “CPS,” and both “PCPS-CPS,” compared to no smoking) showed that the elevated risk of B-cell ALL was limited to children exposed to both “PCPS-CPS” (OR=1.50, 95% CI:1.10-2.04). The magnitude of this association increased for 133 B-cell ALL cases harboring chromosomal translocation t(12;21) (OR=2.37; 95% CI:1.41-4.01). Weaker associations were seen between “PCPS” and “CPS” and B-cell ALL harboring other chromosome translocations (n=82) or deletions (n=63). Tobacco smoking did not appear to be associated with hyperdiploid B-cell ALL (n=228) and T-cell ALL (n=70). Child's passive smoking conferred a 1.5-fold increased risk of AML (95% CI:0.98-2.26; p=0.06), with a higher risk observed for those with chromosome aberrations linked to a “favorable” prognosis (ORbinary=1.94; p=0.07; n=80). No excess risks were seen with maternal smoking during pregnancy, after accounting for other sources of smoking. Conclusions: Exposure to tobacco smoking is an important predictor of childhood ALL, and possibly AML. The observed risks contrast by phenotypic and cytogenetic subtype, providing insights in the etiology of the disease. 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 662. doi:1538-7445.AM2012-662

Abstract 665: Association between early life factors and childhood rhabdomyosarcoma

Abstract Background: Rhabdomyosarcoma (RMS) is the most common type of soft-tissue sarcoma among 0-19 year olds, with the incidence rate highest among children of ages 0-4. Since, childhood cancers tend to have relatively shorter lag time between exposure and disease, early childhood cancer such as RMS could be due to exposures during pregnancy or early infancy. Very little is known about environmental factors that may increase the susceptibility to RMS. Two major subtypes_embryonal and alveolar_have been linked with overexpression of the gene encoding insulin-like growth factor 2 (IFG2), which is also associated with fetal overgrowth syndrome. A couple of studies have suggested accelerated fetal growth as a risk factor, but needs to be confirmed. We examined associations between fetal growth measures and all RMS, and separately for the two major subtypes. We also examined other prenatal/perinatal factors including prenatal care, parental age, and parity. Methods: We conducted a population based case-control study in California by linking California Cancer registry and birth certificate data. Incident cases in children 0-5 ages (overall n=359, embryonal RMS=218, alveolar RMS=81) diagnosed in 1988-2008 and controls, frequency matched on birth year (1986-2007, n=205,230) were included. Logistic regression was applied to examine the associations of interest in crude and adjusted models. Results: The point estimates in adjusted models suggested an increased risk for embryonal RMS for all fetal growth measures employed, i.e., high birthweight (4000-5250 gms) at term births only, for high birth weight (4000-5250 gms) adjusted for gestational age, and large for gestational age births (OR (95%CI): 1.28 (0.85, 1.92); 1.21 (0.81, 1.81); 1.13 (0.73, 1.75) respectively), but not for alveolar RMS or overall RMS cases. We found increased risk for alveolar RMS among those with prenatal care starting after the first trimester or no care at all compared to prenatal care in the first trimester (OR(95%CI): 1.68 (1.01, 2.80)). Findings for other factors including higher risk among male and higher parental age at child birth were consistent with findings from existing studies. Conclusion: We did not find a convincingly positive association between fetal growth and RMS, although our data suggested small risk increases particularly for embryonal RMS. However, our findings on starting time of prenatal care and parental age at childbirth further support the notion that the early fetal/embryonic environment may be important for developing RMS in early childhood. Larger studies examining well-measured early life environment that may cause genetic and epigenetic alteration observed in RMS cases are needed to improve our understanding of the RMS etiology. 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 665. doi:1538-7445.AM2012-665

EXPOSURE TO HERBICIDES IN HOUSE DUST AND RISK OF CHILDHOOD LEUKEMIA

Background and Aims: Previous studies investigating the risk of childhood leukemia in relation to self-reported use of herbicides have produced mixed results. We measured herbicide concentrations in house dust–a reservoir for household chemicals--to estimate the association of childhood acute lymphoblastic leukemia (ALL) with exposure to these compounds. Methods: A total of 269 ALL cases and 333 healthy controls (&lt;8 years of age at diagnosis/reference date and residentially stable) from a case-control study in California (2001-2007) received a second interview with collection of carpet dust samples. Dust samples were obtained using a high-volume surface sampler or from the household vacuum cleaner. Herbicides were selected for analysis based on frequency of use in California and feasibility of laboratory quantification and included agricultural herbicides (alachlor, bromoxynil, simazine, and pendimethalin) and lawn and garden herbicides (trifluralin, MCPA, MCPP, 2,4-D, dacthal, and dicamba). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. Models included log-transformed concentrations for herbicides detected in at least 50% of homes or binary variables (detect/non-detect) for herbicides detected in 5% to &lt;50% of homes. All models included child’s age, sex, race/ethnicity, household income, year and season of dust sampling, residence location (urban, suburban, rural), and residence type. Results: Simazine, 2,4-D, and MCPP were the most prevalent herbicides (84%, 84%, and 73% detections, respectively). Dacthal was detected in 40% of case homes vs. 31% of control homes (OR=1.47, 95% CI 1.01, 2.14). Increasing dacthal concentrations were associated with a positive trend in risk among non-Hispanics but not other racial/ethnic groups. No other herbicides were associated with ALL risk. Conclusions: In non-Hispanics, we observed increased risk of ALL associated with household exposure to dacthal, but no associations for other herbicides. A strength of this study is the use of household dust samples to estimate exposure to specific herbicides rather than self-reports.

Prostate Cancer and Ambient Pesticide Exposure in Agriculturally Intensive Areas in California

In a population-based case-control study in California's intensely agricultural Central Valley (2005-2006), the authors investigated relations between environmental pesticide/fungicide exposure and prostate cancer. Cases (n = 173) were obtained from a population-based cancer registry, and controls (n = 162) were obtained from Medicare listings and tax assessor mailings. Past ambient exposures to pesticides/fungicides were derived from residential history and independently recorded pesticide and land-use data, using a novel geographic information systems approach. In comparison with unexposed persons, increased risks of prostate cancer were observed among persons exposed to compounds which may have prostate-specific biologic effects (methyl bromide (odds ratio = 1.62, 95% confidence interval: 1.02, 2.59) and a group of organochlorines (odds ratio = 1.64, 95% confidence interval: 1.02, 2.63)) but not among those exposed to other compounds that were included as controls (simazine, maneb, and paraquat dichloride). The authors assessed the possibility of selection bias due to less-than-100% enrollment of eligible cases and controls (a critical methodological concern in studies of this kind) and determined that there was little evidence of bias affecting the estimated effect size. This study provides evidence of an association between prostate cancer and ambient pesticide exposures in and around homes in intensely agricultural areas. The associations appear specific to compounds with a plausible biologic role in prostate carcinogenesis.