Risk Factors For Childhood Leukemia Research Articles

Imputation of Below Detection Limit Missing Data in Chemical Mixture Analysis with Bayesian Group Index Regression.

There is growing scientific interest in identifying the multitude of chemical exposures related to human diseases through mixture analysis. In this paper, we address the issue of below detection limit (BDL) missing data in mixture analysis using Bayesian group index regression by treating both regression effects and missing BDL observations as parameters in a model estimated through a Markov chain Monte Carlo algorithm that we refer to as pseudo-Gibbs imputation. We compare this with other Bayesian imputation methods found in the literature (Multiple Imputation by Chained Equations and Sequential Full Bayes imputation) as well as with a non-Bayesian single-imputation method. To evaluate our proposed method, we conduct simulation studies with varying percentages of BDL missingness and strengths of association. We apply our method to the California Childhood Leukemia Study (CCLS) to estimate concentrations of chemicals in house dust in a mixture analysis of potential environmental risk factors for childhood leukemia. Our results indicate that pseudo-Gibbs imputation has superior power for exposure effects and sensitivity for identifying individual chemicals at high percentages of BDL missing data. In the CCLS, we found a significant positive association between concentrations of polycyclic aromatic hydrocarbons (PAHs) in homes and childhood leukemia as well as significant positive associations for polychlorinated biphenyls (PCBs) and herbicides among children from the highest quartile of household income. In conclusion, pseudo-Gibbs imputation addresses a commonly encountered problem in environmental epidemiology, providing practitioners the ability to jointly estimate the effects of multiple chemical exposures with high levels of BDL missingness.

Risk Factors for Childhood Leukemia: Radiation and Beyond.

Childhood leukemia (CL) is undoubtedly caused by a multifactorial process with genetic as well as environmental factors playing a role. But in spite of several efforts in a variety of scientific fields, the causes of the disease and the interplay of possible risk factors are still poorly understood. To push forward the research on the causes of CL, the German Federal Office for Radiation Protection has been organizing recurring international workshops since 2008 every two to three years. In November 2019 the 6th International Workshop on the Causes of CL was held in Freising and brought together experts from diverse disciplines. The workshop was divided into two main parts focusing on genetic and environmental risk factors, respectively. Two additional special sessions addressed the influence of natural background radiation on the risk of CL and the progress in the development of mouse models used for experimental studies on acute lymphoblastic leukemia, the most common form of leukemia worldwide. The workshop presentations highlighted the role of infections as environmental risk factor for CL, specifically for acute lymphoblastic leukemia. Major support comes from two mouse models, the Pax5+/− and Sca1-ETV6-RUNX1 mouse model, one of the major achievements made in the last years. Mice of both predisposed models only develop leukemia when exposed to common infections. These results emphasize the impact of gene-environment-interactions on the development of CL and warrant further investigation of such interactions — especially because genetic predisposition is detected with increasing frequency in CL. This article summarizes the workshop presentations and discusses the results in the context of the international literature.

Increased Leukemia Risk in Children With Down Syndrome

Research Article| October 01 2021 Increased Leukemia Risk in Children With Down Syndrome AAP Grand Rounds (2021) 46 (4): 45. https://doi.org/10.1542/gr.46-4-45 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Increased Leukemia Risk in Children With Down Syndrome. AAP Grand Rounds October 2021; 46 (4): 45. https://doi.org/10.1542/gr.46-4-45 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: down syndrome, leukemia Source: Marlow EC, Ducore J, Kwan ML, et al Leukemia risk in a cohort of 3.9 million children with and without Down syndrome. J Pediatr. 2021;234:172-180.e3; doi:10.1016/j.jpeds.2021.03.001Google Scholar Investigators from multiple institutions conducted a retrospective cohort study to assess leukemia risks in children with Down syndrome. For the study, they included data on all live births at 7 US healthcare systems and in Ontario, Canada, between 1996 and 2016. Children with Down syndrome were identified by ICD-9 and ICD-10 codes. Cancer diagnoses were obtained from tumor registries in the US and the Pediatric Oncology Group of Ontario Networked Information System. Additional information collected included sex, age, and maternal age at birth; race and ethnicity data were available on US children. Study participants were followed until age 15, any cancer diagnosis, death, or disenrollment from the healthcare system. The primary study outcome was incident diagnosis of primary leukemia and incident diagnosis of specific leukemias including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and megakaryoblastic leukemia (AML-M7) based on the 2008 WHO classification. The incidence of leukemia (overall and by subtype) in children with Down syndrome and those without was compared using Cox proportional hazard models, with analyses stratified by age (<5 and ≥5 years old). Data were analyzed on 3,905,399 children, including 4,401 with Down syndrome (incidence 1.12/1,000 children). Study participants with Down syndrome were more likely to be male (54.7% vs 51.3% in those without Down syndrome), born to mothers ≥40 years old (18.6% vs 3.7%), and in the US cohort more likely to be white (73.1% vs 65.0%) and of Hispanic ethnicity (24.8% vs 19.3%). Among children with Down syndrome, the incidence of AML peaked in the first year of life (incidence 619.4 per 100,000), with ALL becoming more common in those 2 to 4 years old (incidence ranging from 333.3 to 326.8/100,000). For other children, the incidence of AML was low at all ages (≤1.1/100,000); the incidence of ALL peaked at age 3 years (11.2/100,000). Down syndrome was associated with an increased risk for any leukemia (hazard ratio [HR], 75.6; 95% CI, 62.3, 91.6 for those <5 years old; HR, 18.3; 95% CI, 7.8, 43.1 for those ≥5 years old). Among those <5 years old, Down syndrome was associated with an increased risk of AML-M7 (HR, 1,500; 95% CI, 555, 4,070) and other AML (HR, 197; 95% CI, 70, 553). Children with Down syndrome also were at increased risk for ALL (HR, 28.4; 95% CI, 20.4, 39.6 for those <5 years old; HR, 21.4; 95% CI, 12.1, 37.9 for those ≥5 years old). The authors conclude that Down syndrome is a strong risk factor for childhood leukemia. Dr Hogan has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. Down syndrome (DS), arising in an estimated 1 in 800 to 1,000 live births in the US annually,1 is... You do not currently have access to this content.

Residential proximity to plant nurseries and risk of childhood leukemia

BackgroundPesticides are a potential risk factor for childhood leukemia. Studies evaluating the role of prenatal and/or early life exposure to pesticides in the development of childhood leukemia have produced a range of results. In addition to indoor use of pesticides, higher risks have been reported for children born near agricultural crops. No studies have looked at pesticide exposure based on proximity of birth residence to commercial plant nurseries, even though nurseries are located much closer to residences than agricultural crops and can potentially result in chronic year-round pesticide exposure. ObjectivesTo evaluate whether risk of childhood leukemia is associated with pesticide use as determined by distance of residence at birth to commercial, outdoor plant nurseries. MethodsWe conducted a large statewide, record-based case-control study of childhood leukemia in California, which included 5788 childhood leukemia cases and an equal number of controls. Pesticide exposure was based on a spatial proximity model, which combined geographic information system data with aerial satellite imagery. ResultsOverall, the results supported an increased childhood leukemia risk only for birth residences very close to nurseries. For birth residences less than 75 m from plant nurseries, we found an increased risk of childhood leukemia (odds ratio (OR) 2.40, 95% confidence interval (CI) 0.99-5.82) that was stronger for acute lymphocytic leukemia (OR 3.09, 95% CI 1.14-8.34). DiscussionThe association was robust to choices of reference group, cut points and data quality. Our findings suggest that close proximity to plant nurseries may be a risk factor for childhood leukemia and that this relationship should be further evaluated.

Leukemia Risk in a Cohort of 3.9 Million Children with and without Down Syndrome

To assess leukemia risks among children with Down syndrome in a large, contemporary cohort. Retrospective cohort study including 3 905 399 children born 1996-2016 in 7 US healthcare systems or Ontario, Canada, and followed from birth to cancer diagnosis, death, age 15years, disenrollment, or December 30, 2016. Down syndrome was identified using International Classification of Diseases, Ninth and Tenth Revisions, diagnosis codes. Cancer diagnoses were identified through linkages to tumor registries. Incidence and hazard ratios (HRs) of leukemia were estimated for children with Down syndrome and other children adjusting for health system, child's age at diagnosis, birth year, and sex. Leukemia was diagnosed in 124 of 4401 children with Down syndrome and 1941 of 3 900 998 other children. In children with Down syndrome, the cumulative incidence of acute myeloid leukemia (AML) was 1405/100 000 (95% CI 1076-1806) at age 4years and unchanged at age 14years. The cumulative incidence of acute lymphoid leukemia in children with Down syndrome was 1059/100 000 (95% CI 755-1451) at age 4 and 1714/100 000 (95% CI 1264-2276) at age 14years. Children with Down syndrome had a greater risk of AML before age 5years than other children (HR 399, 95% CI 281-566). Largest HRs were for megakaryoblastic leukemia before age 5 years (HR 1500, 95% CI 555-4070). Children with Down syndrome had a greater risk of acute lymphoid leukemia than other children regardless of age (<5years: HR 28, 95% CI 20-40, ≥5years HR 21, 95% CI 12-38). Down syndrome remains a strong risk factor for childhood leukemia, and associations with AML are stronger than previously reported.

Modifiable and Non-Modifiable Factors Affecting the Risk of Childhood Leukemia: An Overview of Meta-Analysis

Background: Numerous meta-analyses of childhood leukemia have been published, but no comprehensive study has examined the factors influencing childhood leukemia. We aimed to scrutinize the modifiable and non-modifiable factors affecting the risk of childhood leukemia. Materials and Methods: In this overview, two independent researchers screened the articles studying the effect of modifiable and non-modifiable factors on the childhood leukemia from the related databases, including Scopus, EMBASE, Cochrane, Web of Science, and Medline, without time and language restrictions from inception up to March 10, 2020. Results: Eight meta-analyses were included in this overview. Breastfeeding compared with non-breastfeeding was associated with 9% reduction in the risk of childhood leukemia (OR = 0.91). The children with the birth weight of ≥4,000 g were at a higher risk of acute lymphoblastic leukemia compared with those with low birth weight (OR = 1.26, 95% CI = 1.17, 1.37). There was a significant relationship between childhood leukemia and residential pesticide exposure (SOR=1.57). There was a relationship between influenza during pregnancy and higher risk of ALL (POR=3.64; 95% CI = 1.34-9.90), and childhood leukemia (POR=1.77). The childhood AML had a statistically significant relationship with no alcohol consumption during pregnancy. The SOR of childhood ALL had an association with paternal smoking. A statistical relationship exists between magnetic field intensity of ≥0.4 μT and childhood leukemia. The exposure to NO2 and benzene exhibited the OR of 1.64 (95% CI = 0.91-2.95) and 1.21 (95% CI = 0.97-1.52), respectively. Conclusion: Decreased breastfeeding, high birth weight, viral infections during pregnancy, alcohol consumption, maternal exposure to direct and indirect smoking, and exposure to electromagnetic fields and airborne pollutants are found to be significant risk factors for childhood leukemia.

Abstract IA09: Environmental contributors to childhood cancers

Abstract Leukemia is the most common cancer in children living in industrialized countries. Its incidence has dramatically increased in the last decades in certain populations, such as Latino children in the United States, who have experienced a 35% increase in incidence rate in the past 40 years. Upward trends have also been observed for other cancers in children and adolescents with some variation by tumor site and geographic region. These observations overall point to the important role of the “environment” in a broad sense, whether acting alone or in concert with genetic factors, but can we say more? Despite decades of epidemiologic research on childhood leukemia, recent reports and publications often start with a general statement like “…we do not know what causes childhood leukemia…” or “…only 10% of childhood leukemia can be explained….” This session will challenge this perception by presenting the most salient results on children’s and parents’ exposures to carcinogens such as those contained in paints, solvents, pesticides, air pollution, and tobacco smoke and the risk of childhood leukemia. Since in utero nutrition is recognized as contributing to the alteration of gene expression and physical development in the fetus, we will also assess whether a healthy maternal diet during pregnancy and prenatal folate/vitamin supplementation reduce the risk of childhood leukemia. Advances in our understanding of actionable risk factors that increase or decrease the risk of childhood leukemia have been made at a faster pace than for most other childhood cancers, yet similar associations with chemical and nutritional factors have also been reported for certain solid tumors, suggesting a cumulative impact of these factors. A critical review of complementary study designs of childhood leukemia studies using various populations and sources of data, biomarkers of exposures, and molecular characterization of childhood leukemia subtypes will be presented to evaluate association vs. causation. Future research directions will be discussed on how to characterize cumulative exposures and how to further integrate genetic and mechanic studies to strengthen the evidence. This presentation will mainly draw from the work conducted in the past decades at the California-based Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE) and the Childhood Leukemia International Consortium (CLIC). CLIC assembled data for up to 40,000 leukemia cases and 350,000 controls from 38 case-control studies worldwide. This unprecedentedly large sample size has allowed to conduct pooled and meta-analyses for major leukemia subtypes and sociodemographic subgroups, providing the most robust findings to date. While the strength of international consortia resides in numbers and geographic variation that enable to examine the disease and exposure heterogeneity, other approaches are needed to provide mechanistic understanding of the observed associations, and to uncover factors that cannot be identified from “traditional” epidemiologic studies that use primarily self-reports or registry-based data. To that effect, the Children’s Center CIRCLE has developed innovative targeted and untargeted environmental and biomarker studies to characterize chemical exposures before and after birth. As evidence on the environmental risk factors for childhood leukemia and other cancer is accumulating, it is prudent to start prevention programs to reduce exposure to harmful environmental exposures and promote a healthy lifestyle, especially targeting vulnerable populations such as Latino families. Despite alarming statistics, federal funding for research that aims to identify causes of childhood cancers and promote prevention has been consistently dismal, putting more children at risk to be diagnosed with cancer and to suffer short- and long-term complications throughout their lives. It is therefore critical to invest in childhood cancer etiologic research and research translation that requires international and multidisciplinary collaborations. References, resources, and funding: (1) Giddings BM, Whitehead TP, Metayer C, Miller MD. Childhood leukemia incidence in California: High and rising in the Hispanic population. Cancer 2016 Sep 15;122(18):2867-75; (2) Whitehead TP, Metayer C, Wiemels JL, Singer AW, Miller MD. Childhood leukemia and primary prevention. Curr Probl Pediatr Adolesc Health Care 2016 Oct;46(10):317-352; (3) CIRCLE website is available at www.circle.berkeley.edu; (4) CIRCLE is supported by grants from the NIEHS (#P50ES018172) and USEPA (#RD83615901) Citation Format: Catherine Metayer. Environmental contributors to childhood cancers [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr IA09.

The role of dwelling type when estimating the effect of magnetic fields on childhood leukemia in the California Power Line Study (CAPS)

The type of dwelling where a child lives is an important factor when considering residential exposure to environmental agents. In this paper, we explore its role when estimating the potential effects of magnetic fields (MF) on leukemia using data from the California Power Line Study (CAPS). In this context, dwelling type could be a risk factor, a proxy for other risk factors, a cause of MF exposure, a confounder, an effect-measure modifier, or some combination. We obtained information on type of dwelling at birth on over 2,000 subjects. Using multivariable-adjusted logistic regression, we assessed whether dwelling type was a risk factor for childhood leukemia, which covariates and MF exposures were associated with dwelling type, and whether dwelling type was a potential confounder or an effect-measure modifier in the MF-leukemia relationship under the assumption of no-uncontrolled confounding. A majority of children lived in single-family homes or duplexes (70%). Dwelling type was associated with race/ethnicity and socioeconomic status but not with childhood leukemia risk, after other adjustments, and did not alter the MF-leukemia relationship upon adjustment as a potential confounder. Stratification revealed potential effect-measure modification by dwelling type on the multiplicative scale. Dwelling type does not appear to play a significant role in the MF-leukemia relationship in the CAPS dataset as a leukemia risk factor or confounder. Future research should explore the role of dwelling as an effect-measure modifier of the MF-leukemia association.

Radiation exposure from computerized tomography and risk of childhood leukemia: Finnish register-based case-control study of childhood leukemia (FRECCLE).

The only well-established risk factors for childhood leukemia are high-dose ionizing radiation and Down syndrome. Computerized tomography is a common source of low-dose radiation. In this study, we examined the magnitude of the risk of childhood leukemia after pediatric computed tomography examinations. We evaluated the association of computed tomography scans with risk of childhood leukemia in a nationwide register-based case-control study. Cases (n=1,093) were identified from the population-based Finnish Cancer Registry and three controls, matched by gender and age, were randomly selected for each case from the Population Registry. Information was also obtained on birth weight, maternal smoking, parental socioeconomic status and background gamma radiation. Data on computed tomography scans were collected from the ten largest hospitals in Finland, covering approximately 87% of all pediatric computed tomography scans. Red bone marrow doses were estimated with NCICT dose calculation software. The data were analyzed using exact conditional logistic regression analysis. A total of 15 cases (1.4%) and ten controls (0.3%) had undergone one or more computed tomography scans, excluding a 2-year latency period. For one or more computed tomography scans, we observed an odds ratio of 2.82 (95% confidence interval: 1.05 – 7.56). Cumulative red bone marrow dose from computed tomography scans showed an excess odds ratio of 0.13 (95% confidence interval: 0.02 – 0.26) per mGy. Our results are consistent with the notion that even low doses of ionizing radiation observably increase the risk of childhood leukemia. However, the observed risk estimates are somewhat higher than those in earlier studies, probably due to random error, although unknown predisposing factors cannot be ruled out.

Untargeted adductomics of newborn dried blood spots identifies modifications to human serum albumin associated with childhood leukemia

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

Childhood leukaemia risk and residential proximity to busy roads

BackgroundCurrent evidence suggests that childhood leukaemia can be associated with residential traffic exposure; nevertheless, more results are needed to support this conclusion. ObjectivesTo ascertain the possible effects of residential proximity to road traffic on childhood leukaemia, taking into account traffic density, road proximity and the type of leukaemia (acute lymphoid leukaemia or acute myeloid leukaemia). MethodsWe conducted a population-based case-control study of childhood leukaemia in Spain, covering the period 1990–2011. It included 1061 incidence cases gathered from the Spanish National Childhood Cancer Registry and those Autonomous Regions with 100% coverage, and 6447 controls, individually matched by year of birth, sex and autonomous region of residence. Distances were computed from the respective participant's residential locations to the different types of roads and four different buffers. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs), were calculated for four different categories of distance to roads. ResultsCases of childhood leukaemia had more than three-fold increased odds of living at <50 m of the busiest motorways compared to controls (OR = 2.90; 95%CI = 1.30–6.49). The estimates for acute lymphoid leukaemia (ALL) were slightly higher (OR = 2.95; 95%CI = 1.22–7.14), while estimates for cases with the same address at birth and at diagnosis were lower (OR = 2.40; 95%CI = 0.70–8.30). ConclusionsOur study agrees with the literature and furnishes some evidence that living near a busy motorway could be a risk factor for childhood leukaemia.

Radiation exposure from computerized tomography and risk of childhood leukemia: Finnish register-based case-control study of childhood leukemia (FRECCLE).

The only well-established risk factors for childhood leukemia are high-dose ionizing radiation and Down syndrome. Computerized tomography is a common source of low-dose radiation. In this study, we examined the magnitude of the risk of childhood leukemia after pediatric computed tomography examinations. We evaluated the association of computed tomography scans with risk of childhood leukemia in a nationwide register-based case-control study. Cases (n=1,093) were identified from the population-based Finnish Cancer Registry and three controls, matched by gender and age, were randomly selected for each case from the Population Registry. Information was also obtained on birth weight, maternal smoking, parental socioeconomic status and background gamma radiation. Data on computed tomography scans were collected from the ten largest hospitals in Finland, covering approximately 87% of all pediatric computed tomography scans. Red bone marrow doses were estimated with NCICT dose calculation software. The data were analyzed using exact conditional logistic regression analysis. A total of 15 cases (1.4%) and ten controls (0.3%) had undergone one or more computed tomography scans, excluding a 2-year latency period. For one or more computed tomography scans, we observed an odds ratio of 2.82 (95% confidence interval: 1.05 – 7.56). Cumulative red bone marrow dose from computed tomography scans showed an excess odds ratio of 0.13 (95% confidence interval: 0.02 – 0.26) per mGy. Our results are consistent with the notion that even low doses of ionizing radiation observably increase the risk of childhood leukemia. However, the observed risk estimates are somewhat higher than those in earlier studies, probably due to random error, although unknown predisposing factors cannot be ruled out.

A Meta-Analysis of Prenatal and Maternal Risk Factors for Childhood Leukemia in Iran, Case-Control Studies Approach

Context: Few possible risk factors for childhood leukemia including environmental, genetic, and infectious causes can be explained by epidemiologic studies but the etiology of most childhood leukemia is unknown. Objectives: In this systematic review and meta-analysis, we aimed to find the relationship between prenatal and maternal risk factors with leukemia children in Iran. Data Sources: Relevant studies published in English databases (PubMed, Scopus, and ISI) and Persian databases (Magiran, Medlib, SID, and Iran Medex)) were systematically searched. Study Selection: The study included all case-control studies that estimated the effects of prenatal and maternal risk factors on leukemia children in Iran during years 2004 to 2016, and a standardized manner was used for the extraction of information. Data Extraction: After reviewing all searched articles (title, abstract, and entire text), irrelevant studies were excluded and related ones were selected. Results: We identified 10 case-control studies. The first relative history of leukemia was associated with four times raises of leukemia in children aged 15 > years (OR = 4.58, 95 CI = 1.16 - 7.99). Other significant risk factors were mothers with birth order 3 35, ORs for these factors were respectively (OR = 2.39, 95 CI = 0.79 - 3.99) and OR = 2.25, 95 CI = 1.09 - 3.41). Conclusions: Our results indicate that among maternal and prenatal risk factors, birth order >= 3, birth weight < 2,500 g, and first relative history of leukemia increased the risk of childhood leukemia; in contrast, breastfeeding was a protective factor.

The association between high birth weight and the risks of childhood CNS tumors and leukemia: an analysis of a US case-control study in an epidemiological database

BackgroundHigh birth weight (BW), 4000 g or larger, is an established risk factor for childhood leukemia. However, its association with central nervous system (CNS) tumor risk is yet unclear. The present study examined it, analyzing data obtained from a case-control study conducted among three states from the US. The association with childhood leukemia risk was also further examined.MethodsIn this study, a data set provided by the Comprehensive Epidemiologic Data Resource was analyzed with an official permission. The original case-control study was conducted to examine the association between paternal preconception exposure to ionizing radiation and childhood cancer risk. Cases with childhood cancer were mainly ascertained from local hospitals, and controls were selected, matched with birth year (1-year category), county of residence, sex, ethnicity and maternal age (+/−2 years). Since the ID numbers were unavailable, conventional logistic analyses were conducted adjusting for those matching variables except for the county of residence. In addition to those variables, gestational age, age at diagnosis and study sites as covariables were included in the logistic models.ResultsAnalyzed subjects were 72 CNS tumor cases, 124 leukemia cases and 822 controls born from 1945 to 1989. The odds ratios (ORs) of CNS tumor risk for children with low BWs (<2500 g) and high BWs (>4000 g) were 2.0 (95% confidence interval [CI]) = 0.7, 5.9) and 2.5 (95%CI = 1.2, 5.2)], respectively. When high-BW children were restricted to those who were large for gestational age (LGA), the OR for high-BW children remained similar (OR = 2.7; 95%CI = 1.1, 6.2). On the other hand, the ORs of leukemia risk for children with low and high BWs were 0.8 (95%CI = 0.2, 3.0) and 1.4 (95%CI = 0.7, 2.6), respectively. In the normal range of BW (2500–4000 g), higher BW was positively associated with CNS tumor risk (beta = 0.0011, p for trend = 0.012). However, the association with leukemia risk was not significant (beta = −0.0002, p for trend = 0.475).ConclusionHigh-BW and LGA children had an elevated childhood CNS tumor risk. In the normal BW range, the BW itself was positively related to CNS tumor risk. No significant association between BW and childhood leukemia risk was observed in this study.

Passive exposure to agricultural pesticides and risk of childhood leukemia in an Italian community

Exposure to pesticides has been suggested as a risk factor for childhood leukemia, but definitive evidence on this relation and the specific pesticides involved is still not clear. We carried out a population-based case-control study in a Northern Italy community to assess the possible relation between passive exposure to agricultural pesticides and risk of acute childhood leukemia. We assessed passive pesticide exposure of 111 childhood leukemia cases and 444 matched controls by determining density and type of agricultural land use within a 100-m radius buffer around children's homes. We focused on four common crop types, arable, orchard, vineyard and vegetable, characterized by the use of specific pesticides that are potentially involved in childhood induced leukemia. The use of these pesticides was validated within the present study. We computed the odds ratios (OR) of the disease and their 95% confidence intervals (CI) according to type and density of crops around the children's homes, also taking into account traffic pollution and high-voltage power line magnetic field exposure. Childhood leukemia risk did not increase in relation with any of the crop types with the exception of arable crops, characterized by the use of 2.4-D, MCPA, glyphosate, dicamba, triazine and cypermethrin. The very few children (n=11) residing close to arable crops had an OR for childhood leukemia of 2.04 (95% CI 0.50-8.35), and such excess risk was further enhanced among children aged <5 years. Despite the null association with most crop types and the statistical imprecision of the estimates, the increased leukemia risk among children residing close to arable crops indicates the need to further investigate the involvement in disease etiology of passive exposure to herbicides and pyrethroids, though such exposure is unlikely to play a role in the vast majority of cases.

Risk for childhood leukemia associated with maternal and paternal age.

The role of reproductive factors, such as parental age, in the pathogenesis of childhood leukemias is being intensively examined; the results of individual studies are controversial. This meta-analysis aims to quantitatively synthesize the published data on the association between parental age and risk of two major distinct childhood leukemia types in the offspring. Eligible studies were identified and pooled relative risk (RR) estimates were calculated using random-effects models, separately for childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Subgroup analyses were performed by study design, geographical region, adjustment factors; sensitivity analyses and meta-regression analyses were also undertaken. 77 studies (69 case-control and eight cohort) were deemed eligible. Older maternal and paternal age were associated with increased risk for childhood ALL (pooled RR = 1.05, 95 % CI 1.01-1.10; pooled RR = 1.04, 95 % CI 1.00-1.08, per 5 year increments, respectively). The association between maternal age and risk of childhood AML showed a U-shaped pattern, with symmetrically associated increased risk in the oldest (pooled RR = 1.23, 95 % CI 1.06-1.43) and the youngest (pooled RR = 1.23, 95 % CI 1.07-1.40) extremes. Lastly, only younger fathers were at increased risk of having a child with AML (pooled RR = 1.28, 95 % CI 1.04-1.59). In conclusion, maternal and paternal age represents a meaningful risk factor for childhood leukemia, albeit of different effect size by leukemia subtype. Genetic and socio-economic factors may underlie the observed associations. Well-adjusted studies, scheduled by large consortia, are anticipated to satisfactorily address methodological issues, whereas the potential underlying genetic mechanisms should be elucidated by basic research studies.

Childhood leukemia and residential proximity to industrial and urban sites

BackgroundFew risk factors for the childhood leukemia are well established. While a small fraction of cases of childhood leukemia might be partially attributable to some diseases or ionizing radiation exposure, the role of industrial and urban pollution also needs to be assessed. ObjectivesTo ascertain the possible effect of residential proximity to both industrial and urban areas on childhood leukemia, taking into account industrial groups and toxic substances released. MethodsWe conducted a population-based case–control study of childhood leukemia in Spain, covering 638 incident cases gathered from the Spanish Registry of Childhood Tumors and for those Autonomous Regions with 100% coverage (period 1990-2011), and 13,188 controls, individually matched by year of birth, sex, and autonomous region of residence. Distances were computed from the respective subject’s residences to the 1068 industries and the 157 urban areas with ≥10,000 inhabitants, located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to industrial and urban pollution sources were calculated, with adjustment for matching variables. ResultsExcess risk of childhood leukemia was observed for children living near (≤2.5km) industries (OR=1.31; 95%CI=1.03–1.67) – particularly glass and mineral fibers (OR=2.42; 95%CI=1.49–3.92), surface treatment using organic solvents (OR=1.87; 95%CI=1.24–2.83), galvanization (OR=1.86; 95%CI=1.07–3.21), production and processing of metals (OR=1.69; 95%CI=1.22–2.34), and surface treatment of metals (OR=1.62; 95%CI=1.22–2.15) – , and urban areas (OR=1.36; 95%CI=1.02–1.80). ConclusionsOur study furnishes some evidence that living in the proximity of industrial and urban sites may be a risk factor for childhood leukemia.

Infant birthweight and risk of childhood cancer: international population-based case control studies of 40 000 cases.

High birthweight is an established risk factor for childhood leukaemia. Its association with other childhood cancers is less clear, with studies hampered by low case numbers. We used two large independent datasets to explore risk associations between birthweight and all subtypes of childhood cancer. Data for 16 554 cases and 53 716 controls were obtained by linkage of birth to cancer registration records across five US states, and 23 772 cases and 33 206 controls were obtained from the UK National Registry of Childhood Tumours. US, but not UK, data were adjusted for gestational age, birth order, plurality, and maternal age and race/ethnicity. Risk associations were found between birthweight and several childhood cancers, with strikingly similar results between datasets. Total cancer risk increased linearly with each 0.5 kg increase in birthweight in both the US [odds ratio 1.06 (95% confidence interval 1.04, 1.08)] and UK [1.06 (1.05, 1.08)] datasets. Risk was strongest for leukaemia [USA: 1.10 (1.06, 1.13), UK: 1.07 (1.04, 1.10)], tumours of the central nervous system [USA: 1.05 (1.01, 1.08), UK: 1.07 (1.04, 1.10)], renal tumours [USA: 1.17 (1.10, 1.24), UK: 1.12 (1.06, 1.19)] and soft tissue sarcomas [USA: 1.12 (1.05, 1.20), UK: 1.07 (1.00, 1.13)]. In contrast, increasing birthweight decreased the risk of hepatic tumours [USA: 0.77 (0.69, 0.85), UK: 0.79 (0.71, 0.89) per 0.5 kg increase]. Associations were also observed between high birthweight and risk of neuroblastoma, lymphomas, germ cell tumours and malignant melanomas. For some cancer subtypes, risk associations with birthweight were non-linear. We observed no association between birthweight and risk of retinoblastoma or bone tumours. Approximately half of all childhood cancers exhibit associations with birthweight. The apparent independence from other factors indicates the importance of intrauterine growth regulation in the aetiology of these diseases.

Risk factors of childhood leukemia

Background The incidence of childhood leukemia has increasedannually. Recent studies have shown that childhood leukemia isinitiated in utero, and have focused on prenatal risk factors suchas birth weight and parental age. Exposure to pesticides andradiation, as well as parental smoking, breastfeeding, and thenumber of older siblings have also been sugges ted as risk factorsfor childhood leukemia.Objective To evaluate possible risk factors for childhood leukemia,including birth weight, parental age, and other risk factors.Methods This case-con trol study was conducted from October2011 to February 2012 in Haji Adam Malik Hospital, Medan .Case subjects were children aged below 18 years and diagnosedwith leukemia. Control subjects were children aged below 18years who were diagnosed with any non-cancerous acute illnessesin this hospital, and individually matched for age and gen der tothe case subject group. Patients and parents were asked to fill astructured questionnaire. Data was analyzed using conditionallogistic regression .Results A total of 140 subjects were eligible, with 70 subjects ineach group. Birth weight 2: 4000 g and maternal age 2:35 yearswere significant risk factors with OR 10.13 (95%CI 1.124 to 91.2 7)and OR 4.98 (95%CI 1.276 to 19.445), respectively. Paternal ageof 2:35 years was not a significant risk factor. Exposure to pesticideswas also noted as another significant risk factor (OR= 6.66; 95%CI2.021 to 21.966) .Conclusion High birth weight, advan ced maternal age, andexposure to pesticides are risk factors of childhood leukemia.

Maternal reproductive history, fertility treatments and folic acid supplementation in the risk of childhood acute leukemia: the ESTELLE study.

To investigate the potential involvement of fertility treatments and other conditions of becoming pregnant (infertility, getting pregnant on birth control, maternal history of fetal loss) and folic acid supplements in the etiology of childhood leukemia (CL). The ESTELLE study included 747 cases of CL [636 cases of acute lymphoblastic leukemia (ALL) and 100 of acute myeloblastic leukemia (AML)] diagnosed in France in 2010-2011 and 1,421 population controls frequency-matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to mothers. The odds ratios (OR) and their 95% confidence intervals were estimated using unconditional regression models adjusted for potential confounders. CL was not associated with difficulty in becoming pregnant [OR 0.9 (0.7-1.2)], in vitro fertilisation [OR 0.6 (0.3-1.5)] or the use of any fertility treatment [OR 0.8 (0.5-1.1)] for the index pregnancy. CL was not significantly associated with becoming pregnant on contraception [OR 1.2 (0.8-1.8)], but a positive association was observed for third generation oral contraception [OR 4.3 (1.2-16.2)]; however, the result is based on small numbers. Folic acid supplementation during pregnancy was not associated with CL, but an inverse borderline association was observed for supplementation initiated in the 3 months preceding pregnancy [OR 0.7 (0.5-1.0)]. In addition, maternal histories of stillbirth and miscarriage were associated with ALL [OR 2.6 (1.1-5.9)] and AML [OR 1.8 (1.1-2.8)], respectively. The findings do not suggest that infertility and fertility treatments are risk factors for CL. They suggest that maternal histories of stillbirth and miscarriage may be more frequent among mothers of CL cases and that folic acid supplementation during preconception may reduce the risk of CL.