Parental occupational pesticide exposure and the risk of childhood leukemia in the offspring: findings from the childhood leukemia international consortium.

It has been suggested that parental occupational paint exposure around the time of conception or pregnancy increases the risk of childhood leukemia in the offspring. We obtained individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium. Occupational data were harmonized to a compatible format. Meta-analyses of study-specific odds ratios (ORs) were undertaken, as well as pooled analyses of individual data using unconditional logistic regression. Using individual data from fathers of 8,185 cases and 14,210 controls, the pooled OR for paternal exposure around conception and risk of acute lymphoblastic leukemia (ALL) was 0.93 [95% confidence interval (CI) 0.76, 1.14]. Analysis of data from 8,156 ALL case mothers and 14,568 control mothers produced a pooled OR of 0.81 (95% CI 0.39, 1.68) for exposure during pregnancy. For acute myeloid leukemia (AML), the pooled ORs for paternal and maternal exposure were 0.96 (95% CI 0.65, 1.41) and 1.31 (95% CI 0.38, 4.47), respectively, based on data from 1,231 case and 11,392 control fathers and 1,329 case and 12,141 control mothers. Heterogeneity among the individual studies ranged from low to modest. Null findings for paternal exposure for both ALL and AML are consistent with previous reports. Despite the large sample size, results for maternal exposure to paints in pregnancy were based on small numbers of exposed. Overall, we found no evidence that parental occupational exposure to paints increases the risk of leukemia in the offspring, but further data on home exposure are needed.

Parental Occupational Pesticide Exposure and Childhood Acute Lymphoblastic LeukemiaAbstract Number:2286 Robert Gunier*, Alice Kang, Katharine Hammond, Suzanne Lea, Patricia Quinlan, Kyndaron Reinier, Monique Does, and Catherine Metayer Robert Gunier* University of California, Berkeley, United States, E-mail Address: [email protected] , Alice Kang University of California, Berkeley, United States, E-mail Address: [email protected] , Katharine Hammond University of California, Berkeley, United States, E-mail Address: [email protected] , Suzanne Lea East Carolina University, United States, E-mail Address: [email protected] , Patricia Quinlan University of California, San Francisco , Kyndaron Reinier Cedars-Sinai, United States , Monique Does University of California, Berkeley, United States , and Catherine Metayer University of California, Berkeley, United States AbstractBackground: Most studies investigating the association between parental occupational pesticide exposure and childhood acute lymphoblastic leukemia (ALL) have relied on job titles.Methods: Children diagnosed with ALL (n=669) and age-, sex, race-matched controls (n=1,021) were enrolled in the California Childhood Leukemia Study (2000-2008). We assessed parental pre- and postnatal occupational pesticide exposure using job-title (JT) and corresponding occupational codes from the United States Bureau of Labor Statistics, as well as detailed task-based job modules (JM) and corresponding expert rating. We used unconditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for parental occupational pesticide exposure adjusting for child's sex, age, ethnicity, and household income.Results: The overall specificity of occupational pesticide exposure using JT compared to JM was 94-95% and the sensitivity was 70-77% in both cases and controls. The use of JT to assess paternal postnatal occupational pesticide exposure and risk of ALL resulted in an OR=0.9 (95% CI: 0.6, 1.2); in contrast, the use of JM resulted in ORs equal to 1.5 (95% CI = 1.0, 2.2) and 1.7 (95% CI: 1.1, 2.5) for pre- and postnatal exposure, respectively. Risk of ALL was only elevated in children diagnosed at four years of age or younger, with an OR=2.2 (95% CI: 1.3, 3.9) for postnatal paternal exposure. Maternal occupational pesticide exposure was not associated with ALL during the prenatal or postnatal period. Risk estimates were nearly identical among Hispanic and non-Hispanic children, and were very similar using conditional logistic regression.Conclusions: We observed an increased risk of childhood ALL with paternal occupational pesticide exposure assessed using task-based JM, but not JT. In this study, the use of JT instead of JM resulted in exposure misclassification and underscores the importance of improved exposure assessment.

Introduction: Recent meta-analyses have reported modest but significant associations between birth by cesarean delivery (CD) and subsequent risk of immune-related disorders. An association of CD with childhood leukemia has not been established, although two recent case-control studies showed an increased risk of acute lymphoblastic leukemia (ALL) among young children born by CD, and elective CD (E-CD) in particular. Methods: We pooled data from 12 case-control studies in the Childhood Leukemia International Consortium. We analyzed CD overall and according to indications that likely resulted in E-CD (multiple birth and previous CD). Odds ratios (OR) and 95% confidence intervals (CIs) for risk of ALL and acute myeloid leukemia (AML) were estimated using multivariable logistic regression, adjusting for child's birth weight, sex, age, ethnicity, parental education, maternal age, and study center. Results: Delivery method was known for 8017 ALL cases, 659 AML cases, and 21273 controls. Among three studies with information on indication for CD, data were available for 3677 ALL cases, 114 AML cases, and 3929 controls. The association between CD and ALL (pooled OR: 1.06 [95% CI: 0.99, 1.14]) was not statistically significant, whereas birth by E-CD was associated with an increased risk of ALL (pooled OR: 1.27 [95% CI: 1.06, 1.52]). Subgroup analysis by immunophenotype revealed an association between E-CD and B-ALL (pooled OR: 1.28 [95% CI: 1.04, 1.57]), but not T-ALL. Pooled ORs for AML were 1.02 (95% CI: 0.82, 1.27) for overall CD and 1.39 (95% CI: 0.76, 2.53) for E-CD. Conclusions: Findings derived from a pooled analysis of data from several countries suggest a higher risk of childhood ALL following E-CD. More comprehensive assessment of the indications for E-CD in consortia studies will allow investigators to further explore the potential for confounding by indication. If this association is causal, maladaptive immune activation due to lack of stress response before birth and differential colonization of the microbiome in children born by E-CD should be considered as potential mechanisms. Risk of childhood leukemia associated with cesarean delivery overall and elective cesarean deliveryCesarean delivery (all indications)Pre-labor elective cesarean deliveryNumber of studiesExposed controlsExposed casesOR (95% CI)Number of studiesExposed controlsExposed casesOR (95% CI)Overall12340419241.06 (0.99, 1.14)32513081.27 (1.06, 1.52)ALL12340417491.06 (0.99, 1.14)32512901.27 (1.06, 1.52)AML824781221.02 (0.82, 1.27)1126161.39 (0.76, 2.53)ImmunophenotypeB-cell9313212201.07 (0.99, 1.16)22241961.28 (1.04, 1.57)T-cell931321300.95 (0.77, 1.18)2224241.18 (0.75, 1.88)Age012251561.08 (0.73, 1.60)36102.89 (0.93, 8.89)1-512221212261.05 (0.96, 1.15)31711921.22 (0.98, 1.53)6-10126693481.09 (0.93, 1.28)350591.34 (0.90, 2.01)11-14112721190.97 (0.74, 1.26)324291.25 (0.70, 2.24)Year of birth1970-1979464551.06 (0.70, 1.60)29111.13 (0.46, 2.80)1980-198997235351.01 (0.88, 1.15)31021221.30 (0.99, 1.72)1990-19991215296671.06 (0.95, 1.19)362741.32 (0.92, 1.90)2000-2009810524741.14 (0.98, 1.33)173781.14 (0.78, 1.65)2010-2013336181.93 (0.57, 6.51)1551.81 (0.16, 20.4)Gestational ageEarly preterm11126451.19 (0.67, 2.11)3650.58 (0.10, 3.24)Late preterm112581281.13 (0.84, 1.52)313151.56 (0.61, 3.98)Early term116943481.11 (0.93, 1.32)364851.27 (0.87, 1.86)Full term1113196331.01 (0.90, 1.14)31001311.31 (0.99, 1.72)Late term105482571.02 (0.86, 1.22)3760.95 (0.31, 2.90) Citation Format: Erin Marcotte, Thomas Thomopoulos, Jacqueline Clavel, John Dockerty, Sameera Ezzat, Stephen S. Francis, Claire Infante-Rivard, Corrado Magnani, Catherine Metayer, Ana Maria Mora, Beth A. Mueller, Wafaa M. Rashed, Michael E. Scheurer, Joachim Schuz, Catharina Wesseling, Alkistis Skalkidou, Eleni Petridou, Logan Spector. Cesarean delivery and risk of childhood leukemia: findings from the Childhood Leukemia International Consortium (CLIC). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-194. doi:10.1158/1538-7445.AM2015-LB-194

Nonsyndromic orofacial clefts are common birth defects. Reported risks for orofacial clefts associated with parental occupational pesticide exposure are mixed. To examine the role of parental pesticide exposure in orofacial cleft development in offspring, this study compared population-based case-control data for parental occupational exposures to insecticides, herbicides, and fungicides, alone or in combinations, during maternal (1 month before through 3 months after conception) and paternal (3 months before through 3 months after conception) critical exposure periods between orofacial cleft cases and unaffected controls. Multivariable logistic regression was used to estimate odds ratios, adjusted for relevant covariables, and 95% confidence intervals for any (yes, no) and cumulative (none, low [<median exposure level in controls], high [≥median exposure level in controls]) occupational pesticide exposures and cleft lip ± cleft palate and cleft palate. Associations for cleft lip ± cleft palate tended to be near unity for maternal or paternal occupational pesticide exposures, except for low paternal exposure to any pesticide, which produced a statistically significant inverse association with this subtype. Associations for cleft palate tended to be near unity for maternal exposures and mostly positive, but non-significant, for paternal exposures; a significant positive association was observed between paternal low exposure to insecticide + herbicide + fungicide and cleft palate. Combined parental exposure produced non-significant associations near or below unity for all orofacial cleft cases combined and cleft lip ± cleft palate and positive, but non-significant, associations for cleft palate. This study observed associations mostly near unity between maternal occupational pesticide exposure and orofacial clefts. Associations for paternal occupational pesticide exposures were mostly near or below unity for cleft lip ± cleft palate, and mostly positive for cleft palate. However, due to the limitations of this study, these subtype-specific results should be interpreted cautiously. Future research examining parental occupational pesticide exposure and orofacial clefts should attempt to improve exposure assessment and increase sample size to better facilitate risk estimation.

A task-based assessment of parental occupational exposure to pesticides and childhood acute lymphoblastic leukemia

Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC)

ObjectivesWe conducted a systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure.Data sourcesSearches of MEDLINE (1950–2009) and other electronic databases yielded 31 included studies.Data extractionTwo authors independently abstracted data and assessed the quality of each study.Data synthesisRandom effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs). There was no overall association between childhood leukemia and any paternal occupational pesticide exposure (OR = 1.09; 95% CI, 0.88–1.34); there were slightly elevated risks in subgroups of studies with low total-quality scores (OR = 1.39; 95% CI, 0.99–1.95), ill-defined exposure time windows (OR = 1.36; 95% CI, 1.00–1.85), and exposure information collected after offspring leukemia diagnosis (OR = 1.34; 95% CI, 1.05–1.70). Childhood leukemia was associated with prenatal maternal occupational pesticide exposure (OR = 2.09; 95% CI, 1.51–2.88); this association was slightly stronger for studies with high exposure-measurement-quality scores (OR = 2.45; 95% CI, 1.68–3.58), higher confounder control scores (OR = 2.38; 95% CI, 1.56–3.62), and farm-related exposures (OR = 2.44; 95% CI, 1.53–3.89). Childhood leukemia risk was also elevated for prenatal maternal occupational exposure to insecticides (OR = 2.72; 95% CI, 1.47–5.04) and herbicides (OR = 3.62; 95% CI, 1.28–10.3).ConclusionsChildhood leukemia was associated with prenatal maternal occupational pesticide exposure in analyses of all studies combined and in several subgroups. Associations with paternal occupational pesticide exposure were weaker and less consistent. Research needs include improved pesticide exposure indices, continued follow-up of existing cohorts, genetic susceptibility assessment, and basic research on childhood leukemia initiation and progression.

Maternal prenatal supplementation with folic acid and other vitamins has been inconsistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Little is known regarding the association with acute myeloid leukemia (AML), a rarer subtype. We obtained original data on prenatal use of folic acid and vitamins from 12 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2012), including 6,963 cases of ALL, 585 cases of AML, and 11,635 controls. Logistic regression was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for child's age, sex, ethnicity, parental education, and study center. Maternal supplements taken any time before conception or during pregnancy were associated with a reduced risk of childhood ALL; odds ratios were 0.85 (95% CI = 0.78-0.92) for vitamin use and 0.80 (0.71-0.89) for folic acid use. The reduced risk was more pronounced in children whose parents' education was below the highest category. The analyses for AML led to somewhat unstable estimates; ORs were 0.92 (0.75-1.14) and 0.68 (0.48-0.96) for prenatal vitamins and folic acid, respectively. There was no strong evidence that risks of either types of leukemia varied by period of supplementation (preconception, pregnancy, or trimester). Our results, based on the largest number of childhood leukemia cases to date, suggest that maternal prenatal use of vitamins and folic acid reduces the risk of both ALL and AML and that the observed association with ALL varied by parental education, a surrogate for lifestyle and sociodemographic characteristics.

Hypospadias is a common congenital malformation among men in which the urethral opening is ventrally displaced. Pesticide exposure has been suggested as a possible etiologic factor, but previous epidemiologic studies have produced inconsistent results. We used data from the National Birth Defects Prevention Study (NBDPS), a population-based case-control study, to examine maternal occupational exposure to fungicides, insecticides, and herbicides among 647 hypospadias case infants and 1496 unaffected male control infants with estimated delivery dates from October 1997 to December 2002. Periconceptional (1 month before conception through the first trimester of pregnancy) pesticide exposures were assigned by an expert rater, assisted by a job-exposure matrix (JEM), from a job history completed by mothers during a telephone interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with multivariable logistic regression, and adjusted for relevant covariates. Maternal periconceptional occupational exposure to any pesticides (yes/no) was not associated with an increased risk of hypospadias (OR = 0.78; 95% CI = 0.61-1.01). Maternal occupational periconceptional pesticide exposure type (insecticides, fungicides, and herbicides) and estimated quantity also showed no significantly increased risk of hypospadias and no evidence of a dose-response relationship; however, the estimated pesticide exposure levels in this population were low. Using broad classes of insecticides, herbicides, and fungicides, we found no evidence that low intensity maternal periconceptional occupational pesticide exposure was a risk factor for hypospadias.

It has been suggested that home paint exposure increases the risk of childhood acute lymphoblastic leukemia (ALL). We obtained individual level data from eight case-control studies participating in the Childhood Leukemia International Consortium. All studies had home paint exposure data (sometimes including lacquers and varnishes) for the pregnancy period with additional data for the 1-3-month period before conception in five, the year before conception in two, and the period after birth in four studies, respectively. Cytogenetic subtype data were available for some studies. Data were harmonized to a compatible format. Pooled analyses of individual data were undertaken using unconditional logistic regression. Based on 3,002 cases and 3,836 controls, the pooled odds ratio (OR) for home paint exposure in the 1-3 months before conception and risk of ALL was 1.54 [95% confidence interval (CI) 1.28, 1.85], while based on 1,160 cases and 1,641 controls for exposure in the year before conception, it was 1.00 (95% CI 0.86, 1.17). For exposure during pregnancy, using 4,382 cases and 5,747 controls, the pooled OR was 1.14 (95% CI 1.04, 1.25), and for exposure after birth, the OR was 1.22 (95% CI 1.07, 1.39), based on data from 1,962 cases and 2,973 controls. The risk was greater for certain cytogenetic subtypes and if someone other than the parents did the painting. Home paint exposure shortly before conception, during pregnancy, and/or after birth appeared to increase the risk of childhood ALL. It may be prudent to limit exposure during these periods.

BackgroundLeukaemia is the most common cancer diagnosed in children worldwide, accounting for about one third of all paediatric malignancies in economically developed countries. Despite extensive research, the aetiology of this...

Background: Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemias (ALL) and 17% acute myeloid leukemias (AML). The early onset of the disease is suggestive of genetic predisposition and critical exposures occurring before birth. Maternal prenatal supplementation with folic acid and other vitamins, known to maintain DNA integrity and limit oxidative stress, could play a role in the prevention of childhood leukemia. However, reduced risks of childhood ALL following prenatal supplementation have been reported inconsistently. As for childhood AML, a rarer subtype, little is known regarding the effect of prenatal vitamins. Methods: We pooled original data on socio-demographic characteristics and maternal intake of folic acid, vitamins, and alcohol from 12 case-control studies (1980-2012) participating in CLIC (clic.berkeley.edu). The standardized data included the use of any vitamins, and use of folic acid, given anytime (before and/or during pregnancy) or during a specific period. The pooled analyses included 6,970 cases of ALL, 585 cases of AML, and 19,617 controls. Subgroup analyses were undertaken for vitamin type, period of use, and leukemia subtype. Logistic regression was used to estimate the odds ratios (OR) and 95 % confidence interval (CI), adjusted for age, sex, ethnicity, and other confounders including parental education, and study center. Results: Maternal intake of vitamins and folic acid anytime prenatally was associated with reduced risks of childhood ALL and AML. For ALL, the ORs for vitamin and folic acid intake during pregnancy specifically were 0.78 (95% CI: 0.71-0.85) and 0.82 (95% CI: 0.72-0.94), respectively, and 0.85 (95% CI: 0.64-1.13) and 0.52 (95% CI: 0.31-0.88), respectively, for AML. The observed reduction in ALL risk associated with prenatal vitamin intake was stronger in households where parents had no formal education or a primary education (OR=0.68, 95% CI: 0.56-0.83) and a secondary education (OR=0.75, 95% CI: 0.66-0.85), compared to those with a tertiary education (OR=0.96, 95% CI: 0.86-1.09). A similar trend across education levels was reported for maternal folic acid intake. The association between childhood ALL and maternal vitamin and folic acid intake also appeared stronger among women who did not consume alcohol. Conclusions: Our analyses based on the largest number of childhood ALL and AML cases to date suggest that maternal vitamin and folic acid intake reduces the risk of acute childhood leukemias. The risk seems modified by surrogate markers of nutritional status such as socio-economic status and alcohol consumption. Alternatively, participant selection, recall, access to prenatal care, or genetic susceptibility may vary in low vs. high income populations, therefore possibly contributing to this observation. Citation Format: Catherine Metayer, Elizabeth Milne, John D. Dockerty, Jacqueline Clavel, Maria S. Pombo-de-Oliveira, Catharina Wesseling, Logan G. Spector, Joachim Schüz, Eleni Petridou, Sameera Ezzat, Bruce K. Armstrong, Jérémie Rudant, Sergio Koifman, Peter Kaatsch, Maria Moschovi, Wafaa Rashed, Steve Selvin, Kathryn McCauley, Alice Y. Kang, Rayjean J. Hung, Patricia A. Buffler, Claire Infante-Rivard. Maternal supplementation with folic acid and other vitamins before and during pregnancy and risk of leukemia in the offspring: A childhood leukemia international consortium (CLIC) study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-31. doi:10.1158/1538-7445.AM2013-LB-31 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.

Objective:Tobacco smoke contains carcinogens known to damage somatic and germ cells. In this study, we investigated the effect of tobacco smoking on the risk of childhood acute lymphoblastic leukemia (ALL) and myeloid leukemia (AML).Methods:Information about tobacco smoking exposures of the mother before, during, and after pregnancy was collected via PubMed, Embase, and Web of Science databases through November 5, 2018. We performed to evaluate the association between smoking exposure and the risk of childhood ALL and AML. Study selection, data abstraction, and quality assessment were performed by 2 independent reviewers. Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs).Results:Nineteen case–control studies of childhood leukemia (age < 15 years) conducted in 9 countries from 1974 to 2018. Maternal smoking exposures did not a significant association with childhood ALL (OR = 1.004, 95% CI 0.953–1.058, P = .881) and AML (OR = 0.92, 95% CI 0.815–1.038, P = .177) during exposure time windows. However, there was an association with paternal smoking and ALL (OR = 1.15, 95% CI 1.038–1.275, P = .007). Paternal smoking in AML showed there was no association with smoking exposures and childhood AML (OR = 1.133, 95% CI 0.943–1.362, P = .181). Next, maternal daily cigarettes consumption showed no associations with ALL (OR = 1.08, 95% CI 1.000–1.168, P = .051) during pregnancy. No association with maternal daily smoking and AML (OR = 0.909, 95% CI 0.682–1.211, P = .514). Paternal daily cigarettes consumption was associated with increased risks of childhood ALL (OR = 1.200, 95% CI 1.112–1.302, P = .000). The higher consumption of paternal smoking (more than 10 per day) was significantly related to childhood ALL. Paternal daily smoking consumption also was related to AML (OR = 1.242, 95% CI 1.031–1.496, P = .022).Conclusion:Maternal smoking before, during, or after pregnancy was not associated with childhood ALL or AML. However, paternal smoking was related to a significantly elevated risk of childhood ALL during pregnancy, but not for AML. Maternal daily smoking consumption was not associated with ALL or AML during pregnancy. The higher consumption of paternal smoking were, the higher the risk of childhood ALL or AML.

Some previous studies have suggested that home pesticide exposure before birth and during a child's early years may increase the risk of childhood leukemia. To further investigate this, we pooled individual level data from 12 case-control studies in the Childhood Leukemia International Consortium. Exposure data were harmonized into compatible formats. Pooled analyses were undertaken using multivariable unconditional logistic regression. The odds ratio (ORs) for acute lymphoblastic leukemia (ALL) associated with any pesticide exposure shortly before conception, during pregnancy and after birth were 1.39 (95% confidence interval [CI]: 1.25, 1.55) (using 2,785 cases and 3,635 controls), 1.43 (95% CI: 1.32, 1.54) (5,055 cases and 7,370 controls) and 1.36 (95% CI: 1.23, 1.51) (4,162 cases and 5,179 controls), respectively. Corresponding ORs for risk of acute myeloid leukemia (AML) were 1.49 (95% CI: 1.02, 2.16) (173 cases and 1,789 controls), 1.55 (95% CI: 1.21, 1.99) (344 cases and 4,666 controls) and 1.08 (95% CI: 0.76, 1.53) (198 cases and 2,655 controls), respectively. There was little difference by type of pesticide used. The relative similarity in ORs between leukemia types, time periods and pesticide types may be explained by similar exposure patterns and effects across the time periods in ALL and AML, participants' exposure to multiple pesticides, or recall bias. Although some recall bias is likely, until a better study design can be found to investigate the associations between home pesticide use and childhood leukemia in an equally large sample, it would appear prudent to limit the use of home pesticides before and during pregnancy, and during childhood.

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.