Search

According to the International Agency for Research on Cancer, leukemia ranks 14th in incidence and 11th in mortality and has a 5-year prevalence of approximately 1300,000 cases. Acute lymphoblastic leukemia is the most common hematopoietic syndrome in children during the first 5 years of life and represents approximately 75 % of all neoplasms among the pediatric population. The development of leukemia is strongly governed by DNA alterations that accelerate the growth of bone marrow cells. Currently, the most examined factor in pediatric leukemia is exposure to multiple compounds, such as hydrocarbons. Benzene, an aromatic hydrocarbon, can cause health challenges and is categorized as a carcinogen. Benzene toxicity has been widely associated with occupational exposure. Importantly, studies are underway to generate evidence that can provide clues regarding the risk of environmental benzene exposure and hematological problems in children. In this review, we summarize the existing evidence regarding the effects of benzene on pediatric leukemia, the associations between the effect of benzene on carcinogenesis, and the presence of certain molecular signatures in benzene-associated pediatric leukemia. Although there is sufficient evidence regarding the effects of benzene on carcinogenesis and leukemia, epidemiological research has primarily focused on occupational risk. Moreover, most benzene-induced molecular and cytogenetic alterations have been widely described in adults but not in the pediatric population. Thus, epidemiological efforts are crucial in the pediatric population in terms of epidemiological, clinical, and biomedical research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The 5-year overall survival (OS) in childhood acute lymphoblastic leukemia (ALL) has reached 90% in high-income countries, levels that can no be longer overcome with strategies based on intensification of treatment. Other approaches in the search for new and modifiable prognostic factors are necessary to continue to improve these rates. The importance of environmental factors in the etiopathogenesis of childhood ALL has been regaining interest but its role in the prognosis and survival of this disease is not well explored. We aim to investigate the association between secondhand smoke (SHS) and survival in children diagnosed with ALL., Methods: We analyzed survival rates in 146 patients under the age of 15 years diagnosed with ALL between January 1998 and May 2016 in the Region of Murcia, Spain. Evaluation of parental SHS and other known prognostic factors (sex, age, white blood cell count at diagnosis, cytogenetics, NCI/Rome Criteria, early response to therapy, and relapse) were assessed for impact on OS, event-free survival (EFS), cumulative incidence of relapse (CIR), and treatment-related mortality (CITRM) using Kaplan-Meier analysis, Cox regression, and Fine-Gray model., Results: The mean follow-up time was 105.3 months (±66.5). Prenatal exposure to SHS due to parental smoking was highly prevalent. Of the mothers, 44.4% and 55.5% of the fathers smoked at some point during pregnancy. After the child's diagnosis of ALL 39.7% of mothers and 45.9% of fathers reported smoking. The Cox proportional hazards model showed that maternal smoking during pregnancy and after diagnosis (HR = 4.396, 95% CI: 1.173-16.474, p = 0.028); and relapse (HR = 7.919; 95% CI: 2.683-21.868; p < 0.001) are independent prognostic factors in determining survival. The Fine-Gray model showed that maternal smoking during pregnancy and after diagnosis (HR = 14.525, 95% CI: 4.228-49.90, p < 0.001) is an independent prognostic factor in CITRM., Conclusions: Persistent SHS worsens OS and TRM in children with ALL. This negative impact contributes to a different prognosis and may possibly provide an exceptional insight into new therapeutic approaches, including environmental aspects such as prevention and smoking cessation to improve survival outcomes., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate an association between maternal prenatal exposure to several environmental factors and risk of childhood acute lymphocytic leukemia (ALL), and the possible interactions in the Chinese population., Methods: 345 cases with ALL and their 1:1 age, gender, residence region matched controls aged 0-15 years were recruited from four hospitals in Henan Province from 2014 to 2016. Information was collected by interviews using a questionnaire. Unconditional logistic regression adjusted for age, gender, residence region and relevant confounders was carried out to generate the odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Our data indicate that maternal prenatal exposure to interior housing renovation (adjusted OR: 2.98, 95% CI: 1.51-5.86) or pesticides (adjusted OR: 1.48, 95% CI: 1.67-2.28) increased the risk of childhood ALL. Various subgroup analyses stratified by child's gender, age at diagnosis and other factors also supported these results. However, no interaction was detected between exposure to internal housing renovation and pesticides using an additive model. No significant links between maternal exposures to, environmental tobacco smoking (ETS), antipyretic analgesia intake, or viral infectious diseases with risk of ALL were detected., Conclusion: Findings in our study are in line with the existing literatures, which support the hypothesis that maternal prenatal exposure to interior housing renovation and pesticides are risk factors for childhood ALL. Notably, we found no interaction between these two risk factors, these findings may inform prevention and early detection strategies., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Determine of the influence of adverse environmental factors, including irradiation, on the survival ofchildren with acute leukemia in the long-term period after the Chornobyl accident (2008-2017)., Materials and Methods: Examined 74 children with acute leukemia (АL): 64 with acute lymphoblastic leukemia(ALL); 10 - acute myeloblastic leukemia (AML). The influence of negative environmental factors was assessed bythe degree of integrated pollution of the atmospheric air, surface waters and soils with pesticides, heavy metals (Pb,Cu, Ni, Cr, Mn, Zn, Fe) and cesium isotope 137Cs. These regions were ranked on a moderately polluted (1), polluted (2),very (3) and extremely (4) polluted territories. Took into account the age of children, blood test, immunophenotyp-ic of variant the acute leukemia, survival of patients and place of residence (city / village), serum ferritin level (SF)., Results: Exposure doses of children were in the range from 0.4 mSv to 35.0 mSv (average values were (4.25 ± 0.63 mSv)and did not affect the prognosis and variants of AL. 52 children lived in moderately and polluted territories (30 wereresidents of cities, 22 - villages). 22 patients were lived in very and extremely polluted territories (4 were residentsof cities, 18 - villages). Of 74 patients with ALL and AML 24 children died (32.4 %). The smallest number ofchildren, who died, were patients with «general type» В-ALL (18.7 %), most of all children with pro-В-ALL (8 out of10) and Т-ALL (3 of 4). Of the 52 patients, the inhabitants of moderately and polluted regions, 13 patients died (25%), while out of 22 patients, who lived in very and extremely polluted areas, 11 children died (50 % share)(rs = 0.39; p < 0.05). Of the 10 patients with AML, 4 children died. Most often, children died, who were residents ofvillages. Moreover, the level of SF was significantly higher in children over 6 years, the inhabitants of villages -(406.8 ± 40.6) ng/ml, compared to younger patients - (211.2 ± 32.1) ng/ml) and residents of of cities: up to 6years - (297.4 ± 52.3) ng/ml; over 6 years - (275.6 ± 29.8) ng/ml., Conclusions: The obtained data testify to the negative influence of environmental factors, including iron, and canbe the basis for understanding the mechanisms of potentiating influence of metals and their compounds on thedevelopment of malignant diseases of the blood system in children., (V. G. Bebeshko, K. M. Bruslova, N. M. Tsvietkova, L. О. Lyashenko, T. I. Pushkareva, L. O. Honchar, A. S. Sergeeva, M. Yatsemyrskii, Y. M. Samson, I. V.Trihlib, O. I. Makovey.)

The associations between childhood acute lymphoblastic leukemia (ALL) and several factors related to early stimulation of the immune system, that is, farm residence and regular contacts with farm animals (livestock, poultry) or pets in early childhood, were investigated using data from 13 case-control studies participating in the Childhood Leukemia International Consortium. The sample included 7847 ALL cases and 11,667 controls aged 1-14 years. In all studies, the data were obtained from case and control parents using standardized questionnaires. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Contact with livestock in the first year of life was inversely associated with ALL (OR = 0.65, 95% CI: 0.50, 0.85). Inverse associations were also observed for contact with dogs (OR = 0.92, 95% CI: 0.86, 0.99) and cats (OR = 0.87, 95% CI: 0.80, 0.94) in the first year of life. There was no evidence of a significant association with farm residence in the first year of life. The findings of these large pooled and meta-analyses add additional evidence to the hypothesis that regular contact with animals in early childhood is inversely associated with childhood ALL occurrence which is consistent with Greaves' delayed infection hypothesis., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Although childhood cancer is a leading cause of childhood mortality in the US, evidence regarding the etiology is lacking. The goal of this study was to evaluate the association between benzene, a known carcinogen, and childhood acute leukemia., Methods: We conducted a case-control study including cases diagnosed with acute leukemia between 1997 and 2012 (n = 307) from the Oklahoma Central Cancer Registry and controls matched on week of birth from birth certificates (n = 1013). We used conditional logistic regression to evaluate the association between benzene, measured with the 2005 National-Scale Air Toxics Assessment (NATA) at census tract of the birth residence, and childhood acute leukemia., Results: We observed no differences in benzene exposure overall between cases and controls. However, when stratified by year of birth, cases born from 2005 to 2010 had a three-fold increased unadjusted odds of elevated exposure compared to controls born in this same time period (4th Quartile OR: 3.53, 95% CI: 1.35, 9.27). Furthermore, the estimates for children with acute myeloid leukemia (AML) were stronger than those with acute lymphoid leukemia, though not statistically significant., Conclusions: While we did not observe an association between benzene and childhood leukemia overall, our results suggest that acute leukemia is associated with increased benzene exposure among more recent births, and children with AML may have increased benzene exposure at birth. Using the NATA estimates allowed us to assess a specific pollutant at the census tract level, providing an advantage over monitor or point source data. Our study, however, cannot rule out the possibility that benzene may be a marker of other traffic-related exposures and temporal misclassification may explain the lack of an association among earlier births., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Oil and gas development emits known hematological carcinogens, such as benzene, and increasingly occurs in residential areas. We explored whether residential proximity to oil and gas development was associated with risk for hematologic cancers using a registry-based case-control study design., Methods: Participants were 0-24 years old, living in rural Colorado, and diagnosed with cancer between 2001-2013. For each child in our study, we calculated inverse distance weighted (IDW) oil and gas well counts within a 16.1-kilometer radius of residence at cancer diagnosis for each year in a 10 year latency period to estimate density of oil and gas development. Logistic regression, adjusted for age, race, gender, income, and elevation was used to estimate associations across IDW well count tertiles for 87 acute lymphocytic leukemia (ALL) cases and 50 non-Hodgkin lymphoma (NHL) cases, compared to 528 controls with non-hematologic cancers., Findings: Overall, ALL cases 0-24 years old were more likely to live in the highest IDW well count tertiles compared to controls, but findings differed substantially by age. For ages 5-24, ALL cases were 4.3 times as likely to live in the highest tertile, compared to controls (95% CI: 1.1 to 16), with a monotonic increase in risk across tertiles (trend p-value = 0.035). Further adjustment for year of diagnosis increased the association. No association was found between ALL for children aged 0-4 years or NHL and IDW well counts. While our study benefited from the ability to select cases and controls from the same population, use of cancer-controls, the limited number of ALL and NHL cases, and aggregation of ages into five year ranges, may have biased our associations toward the null. In addition, absence of information on O&G well activities, meteorology, and topography likely reduced temporal and spatial specificity in IDW well counts., Conclusion: Because oil and gas development has potential to expose a large population to known hematologic carcinogens, further study is clearly needed to substantiate both our positive and negative findings. Future studies should incorporate information on oil and gas development activities and production levels, as well as levels of specific pollutants of interest (e.g. benzene) near homes, schools, and day care centers; provide age-specific residential histories; compare cases to controls without cancer; and address other potential confounders, and environmental stressors.

Childhood leukemia is the most common cancer diagnosed in children worldwide. However, only a few causes have been established so far, mainly some genetic syndromes and high doses of ionizing radiation. Major efforts have been undertaken to study the relationship between environmental factors and the risk of childhood leukemia, inspired by geographical variation in incidence rates. Some evidence has emerged for parental occupational exposures to pesticides, whereas there is less evidence for an association with postnatal pesticide exposure. Diagnostic radiation and radon exposure have been suggested but there remains a lack of convincing studies. Extremely low-frequency magnetic fields consistently showed a small increase in risk in numerous studies, but bias and confounding cannot be ruled out as possible explanations. From among factors other than environmental and radiation-related, the most promising candidate is abnormal patterns to common infections, but which children are most at risk and the pathways are not fully understood. In conclusion, although childhood leukemia shows some distinct incidence patterns by sex, age, and geography suggesting a role of the environment in its etiology, no major environmental risk factors including radiation have been established as major contributors to the global childhood leukemia burden. Due to the young age at diagnosis and evidence of chromosomal damage before birth in many of the affected children, parental exposures remain of high interest. Although cure rates of childhood leukemia are high in economically developed countries, because of the adverse late effects of the disease and its treatment, identification of modifiable risk factors for implementing primary prevention remains the ultimate goal., (Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to investigate the association between exposure to environmental chemicals and the risk of childhood acute lymphocytic leukemia(cALL). Methods: A case-controlled study was conducted in Shenzhen Children's Hospital, China from January 2015 to January 2016. The cases were selected from the section of Hematology and Oncology, and the controls were selected from Orthopedics by 1∶2 matching of cases according to sex and age. A questionnaire including population data and chemical exposure characteristics was conducted on the children's parents, and urine and EDTA-blood were collected from the children. Then, we quantitatively measured the internal dose of formaldehyde(i.e., formaldehyde-human serum albumin)by enzyme-linked immunosorbent assay and the doses of metabolites benzene, toluene, and xylene(i.e., trans-muconic acid, hippuric acid, and methylhippuric acid)by high-performance liquid chromatography. Logistic regression models were used to analyze the relationships between exposure factors measured from children and their parents and cALL. Results: In the study, 71 cases(average age: 6.08±3.61 years), and 142 controls(average age: 5.91±3.57 years)were assessed; there were no differences in general demographics between two groups. The self-reported results showed that living in a home that had been painted in the past 10 years( OR= 4.39, 95% CI : 1.87-10.31), maternal chemical exposure during pregnancy( OR= 11.78, 95% CI : 1.65-83.88), paternal diesel or gasoline exposure( OR= 8.15, 95% CI : 2.68-24.83), paternal dye exposure( OR= 7.77, 95% CI : 1.52-39.67)and trash burning near the child's residence( OR= 6.08, 95% CI : 1.17-31.66)were associated with increased risk of cALL. The positive detection rates of only benzene metabolites were significantly higher in cases(40/44)than controls(81/111)(χ 2 =5.92, P= 0.021). The median formaldehyde and benzene concentrations in cases(32.120 pg/ml, 2.505 μg/gCr)were significantly higher than those in controls(18.705 pg/ml, 0.672 μg/gCr; Z values:-1.98 and-3.95, P values: 0.047 and<0.001, respectively). Multiple logistic regression analysis showed that benzene exposure( OR= 1.09, 95% CI : 1.00-1.19), home painting in the past 10 years( OR= 3.56, 95% CI : 1.20-10.53)and paternal diesel or gasoline exposure( OR= 3.75, 95% CI : 1.06-13.22)were associated with increased risk of cALL. Conclusion: A variety of environmental chemistry factors, such as benzene exposure, increase the risk of cALL, and further studies are warranted to explore their specific roles.

Purpose: It has been suggested that home paint exposure increases the risk of childhood acute lymphoblastic leukemia (ALL)., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: The authors declare that they have no conflict of interest.

Childhood acute lymphoblastic leukemia (ALL) is one of the most common hematologic malignancies, accounting for one fourth of all childhood cancer cases. Exposure to environmental factors around the time of conception or pregnancy can increase the risk of ALL in the offspring.This study aimed to evaluted the role of prenatal and postnatal exposure to high voltage power lines on the incidence of childhood ALL.This cross-sectional case control study was carried out on 22 cases and 100 controls who were born and lived in low socioeconomic families in Isfahan and hospitalized for therapeutic purposes in different hospitals from 2013-2014.With regard to the underlying risk factors, familial history and parental factors were noted but in this age, socioeonomic and zonal matched case control study, prenatal and childhood exposure to high voltage power lines was considered as the most important environmental risk factors of ALL (p=0.006, OR=3.651, CI 95%, 1.692-7.878). As the population was of low socioeconomic background, use of mobiles, computers and microwave was negligible. Moreover prenatal and postnatal exposure to indoor electrically charged objects was not determined to be a significant environmental factor. Thus, pre and post natal exposure to high voltage power lines and living in pollutant regions as well as familial influence could be described as risk factors of ALL for the first time in a low socioeconomic status Iranian population.

Down syndrome (DS) is a common congenital anomaly, and children with DS have a substantially higher risk of leukemia. Although understanding of genetic and epigenetic changes of childhood leukemia has improved, the causes of childhood leukemia and the potential role of environmental exposures in leukemogenesis remain largely unknown. Although many epidemiologic studies have examined a variety of environmental exposures, ionizing radiation remains the only generally accepted environmental risk factor for childhood leukemia. Among suspected risk factors, infections, exposure to pesticides, and extremely low frequency magnetic fields are notable. While there are well-defined differences between leukemia in children with and without DS, studies of risk factors for leukemia among DS children are generally consistent with trends seen among non-DS (NDS) children. We provide background on DS epidemiology and review the similarities and differences in biological and epidemiologic features of leukemia in children with and without DS. We propose that both acute lymphoblastic and acute myeloblastic leukemia among DS children can serve as an informative model for development of childhood leukemia. Further, the high rates of leukemia among DS children make it possible to study this disease using a cohort approach, a powerful method that is unfeasible in the general population due to the rarity of childhood leukemia., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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

Significant amounts of pyrethroid pesticides are used throughout China. Previous studies have suggested that exposure to pesticides may increase the risk of childhood cancer; however, few studies have focused on pyrethroid metabolites. We investigated five nonspecific metabolites of pyrethroid pesticides found in children's urine and examined the correlation with childhood leukemia. We conducted a hospital-based case-control study of childhood acute lymphocytic leukemia (ALL) in Shanghai between 2010 and 2011. The study included 176 children aged 0-14 years and 180 controls matched for age and sex. Compared with those in the lowest quartiles of total and individual metabolites, the highest quartiles were associated with an approximate 2-fold increased risk of ALL [total metabolites: odds ratio (OR) = 2.75, 95% confidence interval (CI), 1.43-5.29; cis-DCCA: OR = 2.21, 95% CI, 1.16-4.19; trans-DCCA: OR = 2.33, 95% CI, 1.23-4.41; and 3-PBA: OR = 1.84, 95% CI, 1.00-3.38], and most of the positive trends were significant (p < 0.05). Our findings suggest that urinary levels of pyrethroid metabolites may be associated with an elevated risk of childhood ALL and represent a previously unreported quantitative exposure assessment for childhood leukemia.

Background: Recent studies suggest that environmental exposures to pesticides, tobacco, and other xenobiotic chemicals may increase risk of childhood acute lymphoblastic leukemia (ALL). We sought to evaluate the role of genes involved in xenobiotic transport and metabolism in childhood ALL risk, both alone and in conjunction with household chemical exposures previously found to be associated with childhood ALL risk., Methods: We conducted a population-based epidemiologic study of 377 cases and 448 controls in California, utilizing a haplotype-based approach to evaluate 42 xenobiotic transport and metabolism genes in conjunction with data on self-reported household chemical exposures., Results: We identified significant associations of childhood ALL risk with haplotypes of ABCB1, ARNT, CYP2C8, CYP1A2, CYP1B1, and IDH1. In addition, certain haplotypes showed significant joint effects with self-reported household chemical exposures on risk of childhood ALL. Specifically, elevated risks associated with use of paints in the home (ever) and indoor insecticides (pre-birth) were limited to subjects carrying specific haplotypes of CYP2C8 and ABCB1, respectively., Conclusions: Our results provide support for a role of xenobiotic transport and metabolism pathways in risk of childhood ALL and indicate that genes in these pathways may modulate the risk of disease associated with use of common household chemicals. Additional studies are needed to confirm these findings and localize specific causal variants.

Environmental links to disease are difficult to uncover because environmental exposures are variable in time and space, contaminants occur in complex mixtures, and many diseases have a long time delay between exposure and onset. Furthermore, individuals in a population have different activity patterns (e.g., hobbies, jobs, and interests), and different genetic susceptibilities to disease. As such, there are many potential confounding factors to obscure the reasons that one individual gets sick and another remains healthy. An important method for deducing environmental associations with disease outbreak is the retrospective case-control study wherein the affected and control subject cohorts are studied to see what is different about their previous exposure history. Despite success with infectious diseases (e.g., food poisoning, and flu), case-control studies of cancer clusters rarely have an unambiguous outcome. This is attributed to the complexity of disease progression and the long-term latency between exposure and disease onset. In this article, we consider strategies for investigating cancer clusters and make some observations for improving statistical power through broader non-parametric approaches wherein sub-populations (i.e., whole towns), rather than individuals, are treated as the cases and controls, and the associated cancer rates are treated as the dependent variable. We subsequently present some ecological data for tungsten and cobalt from studies by University of Arizona researchers who document elevated levels of tungsten and cobalt in Fallon, NV. These results serve as candidates for future hybrid ecologic case-control investigations of childhood leukemia clusters., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Despite the fact that animal and human epidemiological studies confirmed a link between radon exposure in homes and increased risk of lung cancer in general population, other types of cancers induced by radon, such as leukemia, have not been consistently demonstrated. The aim of this review was to summarize data published thus far from ecological and case-control studies in exposed populations, taking into account radon dose estimation and evidence of radon-induced genotoxicity, in an effort to clarify the correlation between home radon exposure and incidence of childhood leukemia. Among 12 ecological studies, 11 reported a positive association between radon levels and elevated frequency of childhood leukemia, with 8 being significant. In conjunction with ecological studies, several case-control studies on indoor radon exposure and childhood leukemia were examined, and most investigations indicated a weak association with only a few showing significance. A major source of uncertainty in radon risk assessment is radon dose estimate. Methods for radon exposure measurement in homes of children are one of the factors that affect the risk estimates in a case-control study. The effects of radon-induced genetic damage were studied both in vitro and in vivo using genetic endpoints including chromosomal aberration (CA), micronuclei (MN) formation, gene mutation, and deletions and insertions. By applying a meta-analysis, an increased risk of childhood leukemia induced by indoor radon exposure was noted for overall leukemia and for acute lymphoblastic leukemia (ALL). Data thus indicated an association between environmental radon exposure and elevated leukemia incidence, but more evidence is required in both human investigations and animal mechanistic research before this assumption may be confirmed with certainty.

It is plausible that exposure of the parents before birth or of the child to sources of benzene increases the risk of childhood acute lymphoblastic leukaemia (ALL). The aim of this analysis was to investigate whether refuelling a vehicle with petrol before birth or burning wood to heat the home before or after the child's birth increased the risk of childhood ALL. Data from 389 cases and 876 frequency-matched controls were analysed using unconditional logistic regression, adjusting for study matching factors and potential confounders. The odds ratio (OR) for the mother ever refuelling a vehicle with petrol for non-occupational purposes before or during the pregnancy was 0.97 [95% confidence interval (CI) 0.69, 1.38]. The OR for the father for this exposure in the year before conception was 0.88 [95% CI 0.52, 1.48]. The OR for use of a closed wood burner to heat the home in the year before or during pregnancy was 1.41 [95% CI 1.02, 1.94] and 1.25 [95% CI 0.92, 1.70] after birth. We found no evidence that non-occupational refuelling a vehicle with petrol in the year before or during pregnancy increased the risk of ALL in the offspring. There was weak evidence that burning wood in a closed burner to heat the home increased the risk, but there was no dose-response relationship and chance could explain the finding., (© 2011 Blackwell Publishing Ltd.)

Previous studies suggest that exposure to pesticides increases the risk of childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to investigate whether professional pest treatments in or around the home before birth or during childhood increased the risk of childhood ALL. Data from 388 cases and 870 frequency-matched controls were analyzed using unconditional logistic regression, adjusting for study matching variables and potential confounders, to calculate odds ratios (ORs). A meta-analysis of our findings with the published findings of previous studies was also conducted. The ORs for any professional pest control treatments were 1.19 (95% CI 0.83, 1.69) in the year before pregnancy, 1.30 (95% CI 0.86, 1.97) during pregnancy and 1.24 (95% CI 0.93, 1.65) for those done after the child's birth. The ORs for exposure after birth were highest when it occurred between the ages of two and three years. ORs were elevated for termite treatments before birth. ORs were higher for pre-B than T cell ALL and for t(12;21) (ETV6-Runx-1) than other cytogenetic sub-types. The pooled OR from a meta-analysis of our study with three previous studies of professional pest control treatments during pregnancy was 1.37 (95% CI 1.00, 1.88). Our results, and those of our meta-analysis, provide some evidence of a modestly increased risk of ALL for professional pest control treatments done during the index pregnancy and possibly in the child's early years. The analysis of pooled data from international collaborations may provide more certainty regarding these potentially important associations., (Copyright © 2011 UICC.)

Introduction: The objective of this study was to determine the risk factors for childhood acute lymphoblastic leukemia (ALL) and, in particular, the role of parental occupational exposure to carcinogenic and probably carcinogenic hydrocarbons before the child's conception., Methods: For this case-control study, cases were children younger than 15 years who were newly diagnosed with ALL between January 2000 and March 2005 at 1 of 6 Colombian hospitals. An interview with both parents of 170 children (85 cases and 85 individually matched neighborhood controls) gathered information about each child's exposures and parental demographic and occupational characteristics, medical history, health risk behaviors, and pregnancy and birth history. A job-exposure matrix was used to classify parental exposure to hydrocarbons on the basis of the main industrial activity of each workplace where parents worked before (both parents) or during the index pregnancy (mother only). Conditional odds ratios and 95% confidence intervals were calculated by period of exposure (preconception, pregnancy, and childhood)., Results: The risk of childhood ALL was linked to 1) parental occupational exposure to hydrocarbons before conception, 2) parental smoking before conception, 3) maternal low socioeconomic status during pregnancy, and 4) higher maternal age (≥35 y) at the child's birth., Conclusion: These findings suggest an association between childhood ALL and parental occupational exposure to carcinogenic and probably carcinogenic hydrocarbons before conception. Outcomes depended on the parent exposed. Future research should investigate the additive or multiplicative role of other environmental sources of hydrocarbons.

At least in economically developed countries, in the last decades, the incidence of childhood cancer has increased and the increase is unlikely to be an artefact. Causes of the increase have not been identified: a role of preventable environmental exposures is possible. Changes have also occurred in the age distribution of acute lymphoblastic leukaemia.Currently, children with cancer can be successfully treated and cured. However, access to the best therapy differs widely among countries because of the unequal distribution of resources for cancer care. Any double standard in the fate of children with cancer is ethically unacceptable., (© 2011 Terracini; licensee BioMed Central Ltd.)

The goal of this study was to investigate the potential for selection bias in published case-control studies on household exposure to pesticides and childhood acute leukemia; most studies have reported positive findings. Items to evaluate the potential for selection bias were first developed. They focused on the source populations that gave rise to cases and controls, the probabilistic selection of subjects from the source, and the losses of the subjects actually selected. A quantitative assessment of bias was also carried out. Potential sources of selection bias were found in all the studies, but none of them were observed across all the studies. Main sources of potential bias were a non-concurrent selection of controls with respect to cases, the use of control diagnoses possibly caused by pesticide exposure in hospital-based studies, and non-participation of selected eligible subjects. A quantitative assessment of bias concluded that non-participation alone could not explain the reported positive associations. We conclude that overall, selection bias, as a likely source of bias in these studies, does not seem to explain their positive findings. Our analysis provides arguments strengthening the conclusions on associations reported in earlier studies.

This study aimed to investigate association of living near high voltage power lines with occurrence of childhood acute lymphoblastic leukemia (ALL). Through a case-control study 300 children aged 1-18 years with confirmed ALL were selected from all referral teaching centers for cancer. They interviewed for history of living near overhead high voltage power lines during at least past two years and compared with 300 controls which were individually matched for sex and approximate age. Logistic regression, chi square and paired t-tests were used for analysis when appropriate. The case group were living significantly closer to power lines (P<0.001). More than half of the cases were exposed to two or three types of power lines (P<0.02). Using logistic regression, odds ratio of 2.61 (95%CI: 1.73 to 3.94) calculated for less than 600 meters far from the nearest lines against more than 600 meters. This ratio estimated as 9.93 (95%CI: 3.47 to 28.5) for 123 KV, 10.78 (95%CI: 3.75 to 31) for 230 KV and 2.98 (95%CI: 0.93 to 9.54) for 400 KV lines. Odds of ALL decreased 0.61 for every 600 meters from the nearest power line. This study emphasizes that living close to high voltage power lines is a risk for ALL.

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

Leukemia incidence in children has increased worldwide in recent decades, particularly due to the rise in acute lymphoblastic leukemia. Studies have associated exposure to non-ionizing radiation generated by low frequency magnetic fields with childhood leukemia. The current article reviews the case-control studies published on this subject. Of 152 articles tracked in different databases, ten studies from North America, Asia, and Europe met the defined selection criteria, with patients diagnosed from 1960 to 2004. Methodological limitations were observed in these articles, including difficulties with the procedures for assessing exposure. An association may exist between exposure to low frequency magnetic fields and acute lymphoblastic leukemia in children, but this association is weak, preventing the observation of consistency in the findings. Future studies from a wider range of geographic regions should focus on the analysis of acute lymphoblastic leukemia, which is the subtype with the greatest impact on the increasing overall incidence of childhood leukemia.

Leukemia and brain cancer patients under age 15 years, along with controls with respiratory illnesses who were matched to cases on age, sex, and year of diagnosis (1993-1999), were selected from 14 South Korean hospitals using the South Korean Medical Insurance Data System. Diagnoses were confirmed through the South Korean National Cancer Registry. Residential addresses were obtained from medical records. A newly developed prediction program incorporating a geographic information system that was modified by the results of actual measurements was used to estimate radio-frequency radiation (RFR) exposure from 31 amplitude modulation (AM) radio transmitters with a power of 20 kW or more. A total of 1,928 leukemia patients, 956 brain cancer patients, and 3,082 controls were analyzed. Cancer risks were estimated using conditional logistic regression adjusted for residential area, socioeconomic status, and community population density. The odds ratio for all types of leukemia was 2.15 (95% confidence interval (CI): 1.00, 4.67) among children who resided within 2 km of the nearest AM radio transmitter as compared with those resided more than 20 km from it. For total RFR exposure from all transmitters, odds ratios for lymphocytic leukemia were 1.39 (95% CI: 1.04, 1.86) and 1.59 (95% CI: 1.19, 2.11) for children in the second and third quartiles, respectively, versus the lowest quartile. Brain cancer and infantile cancer were not associated with AM RFR.

Many investigators have studied the effects of Extremely Low Frequency-Magnetic Fields generated by ordinary and domestic power lines, as a risk factor in acute leukaemias of children, but there are limited information available regarding very high voltage overhead power lines. Children in developing countries sometimes live very close to such structures and we have registered several patients with acute leukaemias appearing in clusters. In the present study we have analyzed 60 consecutively diagnosed patients with acute leukaemias, and 59 matched controls in a provincial capital city in North-Western Iran. After provision of consent, a detailed form was filled in, and a visit to the present (or previous) residential areas of both groups was arranged. The locations of the very high voltage power lines (123, 230, 400 kilo volts), were noted in each area, if present, and their distances from the houses under study were detected. The expected intensities of the Magnetic Fields (B) were calculated having the mean intensity of the electrical current and other line characteristics, by means of relevant equations. Fourteen patients in the case group (23.5%) were living near the high voltage power lines in distances < or = 500 meters. (Mean B = 0.6 microTeslas, microT). In the control group at the same distance, the figure was 2 children (3.3%) (Mean B = 0.35 microT). Statistically, the likelihood of leukaemia was increased considerably in this distance (Odds ratio (OR) = 8.67, 95% Confidence Interval (CI) = 1.74- 58.4, P value= 0.001). On the other hand 15 pts (25 %) in the leukaemia group were experiencing Magnetic fields above 0.45 microT in comparison to 5 in the control group ( 8.5% )(OR = 3.60, 95% CI = 1.11-12.39, P = 0.01). More children in developing countries like Iran live close to very high voltage lines, and they experience relatively more harmful effects from the Magnetic Fields, in comparison with children in developed countries. Residence near very high voltage overhead power lines, in distances < or = 500 meters, and Magnetic Fields >0.45 microT, should be considered a risk factor for the pathogenesis of acute leukaemias in children.

Background: Sixteen children diagnosed with acute leukemia between 1997 and 2002 lived in Churchill County, Nevada, at the time of or before their illness. Considering the county population and statewide cancer rate, fewer than two cases would be expected., Objectives: In March 2001, the Centers for Disease Control and Prevention led federal, state, and local agencies in a cross-sectional, case-comparison study to determine if ongoing environmental exposures posed a health risk to residents and to compare levels of contaminants in environmental and biologic samples collected from participating families., Methods: Surveys with more than 500 variables were administered to 205 people in 69 families. Blood, urine, and cheek cell samples were collected and analyzed for 139 chemicals, eight viral markers, and several genetic polymorphisms. Air, water, soil, and dust samples were collected from almost 80 homes to measure more than 200 chemicals., Results: The scope of this cancer cluster investigation exceeded any previous study of pediatric leukemia. Nonetheless, no exposure consistent with leukemia risk was identified. Overall, tungsten and arsenic levels in urine and water samples were significantly higher than national comparison values; however, levels were similar among case and comparison groups., Conclusions: Although the cases in this cancer cluster may in fact have a common etiology, their small number and the length of time between diagnosis and our exposure assessment lessen the ability to find an association between leukemia and environmental exposures. Given the limitations of individual cancer cluster investigations, it may prove more efficient to pool laboratory and questionnaire data from similar leukemia clusters.

We examined the association between magnetic field (MF) exposure and the presence of prognostic risk factors among 482 children diagnosed with acute lymphoblastic leukemia (ALL) between 1996 and 2001. Personal 24-h MF measurements were obtained for 412 children; 386 children were included in analyses. There were no trends seen between increasing exposure to MF and the presence of adverse clinical and tumor-specific prognostic factors. Our results suggest that exposure to MF is not associated with the presence of unfavorable cytogenetic abnormalities in leukemic blast cells or with clinical factors at the time of diagnosis that predict poor survival.

During the past 25 years concern has been raised about the possible health effects of extremely low frequency (ELF) electric and magnetic fields (EMFs), particularly regarding childhood leukemia. Comparison of changes in electricity consumption (a surrogate for exposure) to changes in childhood-leukemia rates, known as ecologic correlation, have been used to argue both for and against the association between magnetic fields and childhood leukemia. In this paper we explore what can be learned from such an ecologic approach. We first examine separately the evidence on trends in exposure to EMFs and on trends in leukemia rates, and then compare the two. Both incidence rates and exposures have increased, but there are so many approximations and assumptions involved in connecting the two trends that we cannot regard the ecologic evidence as providing any meaningful evidence for or against a causal link.

Objective: To test the hypothesis that reduced exposure to common infections in the first year of life increases the risk of developing acute lymphoblastic leukaemia. Design and setting The United Kingdom childhood cancer study (UKCCS) is a large population based case-control study of childhood cancer across 10 regions of the UK., Participants: 6305 children (aged 2-14 years) without cancer; 3140 children with cancer (diagnosed 1991-6), of whom 1286 had acute lymphoblastic leukaemia (ALL)., Main Outcome Measure: Day care and social activity during the first year of life were used as proxies for potential exposure to infection in infancy., Results: Increasing levels of social activity were associated with consistent reductions in risk of ALL; a dose-response trend was seen. When children whose mothers reported no regular activity outside the family were used as the reference group, odds ratios for increasing levels of activity were 0.73 (95% confidence interval 0.62 to 0.87) for any social activity, 0.62 (0.51 to 0.75) for regular day care outside the home, and 0.48 (0.37 to 0.62) for formal day care (attendance at facility with at least four children at least twice a week) (P value for trend < 0.001). Although not as striking, results for non-ALL malignancies showed a similar pattern (P value for trend < 0.001). When children with non-ALL malignancies were taken as the reference group, a significant protective effect for ALL was seen only for formal day care (odds ratio = 0.69, 0.51 to 0.93; P = 0.02). Similar results were obtained for B cell precursor common ALL and other subgroups, as well as for cases diagnosed above and below age 5 years., Conclusion: These results support the hypothesis that reduced exposure to infection in the first few months of life increases the risk of developing acute lymphoblastic leukaemia.

The objective of this study was to evaluate the ecological association between indoor radon concentration and acute leukaemia incidence among children under 15 years of age in the 348 geographical units (zones d'emploi, ZE) of France between 1990 and 1998. During that period, 4015 cases were registered by the French National Registry of Childhood Leukaemia and Lymphoma. Exposure assessment was based on a campaign of 13 240 measurements covering the whole country. The arithmetic mean radon concentration was 85 Bq/m (range, 15-387 Bq/m) and the geometric mean, 59 Bq/m (range: 13-228 Bq/m). A positive ecological association, on the borderline of statistical significance (P=0.053), was observed between indoor radon concentration and childhood leukaemia incidence. The association was highly significant for acute myeloid leukaemia (AML) (P=0.004) but not for acute lymphocytic leukaemia (ALL) (P=0.49). The standardized incidence ratio (SIR) increased by 7, 3 and 24% for all acute leukaemia, ALL and AML, respectively, when radon concentration increased by 100 Bq/m. In conclusion, the present ecological study supports the hypothesis of a moderate association between indoor radon concentration and childhood acute myeloid leukaemia. It is consistent with most previous ecological studies. Since the association is moderate, this result does not appear inconsistent with the five published case-control studies, most of which found no significant association.

Electric and magnetic fields are ubiquitous in the modern society, and concerns have been expressed regarding possible adverse effects of these exposures. This review covers epidemiologic research on health effects of exposures to static, extremely low-frequency (ELF), and radio frequency (RF) fields. Research on ELF fields has been performed for more than two decades, and the methodology and quality of studies have improved over time. Studies have consistently shown increased risk for childhood leukemia associated with ELF magnetic fields, whereas ELF fields most likely are not a risk factor for breast cancer and cardiovascular disease. There are still inadequate data for other outcomes. More recently, focus has shifted toward RF exposures from mobile telephony. There are no persuasive data suggesting a health risk, but this research field is still immature with regard to the quantity and quality of available data. This technology is constantly changing and there is a need for continued research on this issue. Almost no epidemiologic data are available for static fields.

Aim: To analyse the association between potential environmental exposure to hydrocarbons and the risk of acute childhood leukaemia., Methods: A hospital based multicentre case control study, stratified on centre, age, and sex, with 280 leukaemia cases and 285 controls was carried out. Data were collected by a standardised interview of the mothers., Results: No clear association was seen between maternal occupational exposure to hydrocarbons during pregnancy and leukaemia, or between residential traffic density and leukaemia. There was an association between dwellings neighbouring a petrol station or a repair garage during childhood and the risk of childhood leukaemia (OR 4.0, 95% CI 1.5 to 10.3), with a duration trend. The association, which appeared particularly strong for acute non-lymphocytic leukaemia (OR 7.7, 95% CI 1.7 to 34.3), was not altered by adjustment for potential confounding factors., Conclusions: Results showed an association between acute childhood leukaemia and dwellings neighbouring auto repair garages and petrol stations, which are benzene emitting sources. These findings could be due to chance, although the strength of the association and the duration trend are arguments for a causal association.

Background: The aim of the study was to independently test the hypothesis that leukaemia incidence is higher in proximity to estuaries., Methods: Electoral wards were classified as to whether they included estuarine, coastal or only inland features. Rates of different adult and childhood leukaemias were computed for each ward category; that is, acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML) aged 0-79 and for all childhood leukaemias combined (aged 0-14)., Results: Poisson regression analysis controlling for the effects of sex, age, and socioeconomic and urban-rural status, showed no statistically significant differences in incidence between wards with different levels of estuarine classification., Conclusion: The hypothesis created from an earlier dataset that a link exists between leukaemia and residence near estuaries is not upheld.

In certain special situations, simplification of an exposure measure into a dichotomy results in no bias from nondifferential misclassification when estimating the attributable fraction for "any exposure." This fact has led to recommendations to use a broad definition of exposure when estimating attributable fractions. I here review the assumptions underlying exposure simplification, focusing on the assumptions that the source and target populations have the same exposure distribution and that complete risk removal is possible. I argue that attributable fraction estimates based on dichotomization can be especially sensitive to violations of these assumptions, and hence misleading for projecting the impact of exposure reduction. I conclude that it is important to obtain and use detailed exposure and covariate information for attributable-fraction estimation.

Objectives: This study explored the risk of childhood acute lymphoblastic leukemia (ALL) associated with participation by household members in hobbies or other home projects involving organic solvents., Methods: Participants in this case-control study were 640 subjects with ALL and 640 matched controls., Results: Childhood ALL was associated with frequent (> 4 times/month) exposure to model building (odds ratio [OR] = 1.9; 95% confidence interval [95% CI] = 0.7, 5.8) and artwork using solvents (OR = 4.1; 95% CI = 1.1, 15.1). We also found elevated risk (OR = 1.7; 95% CI = 1.1, 2.7) among children whose mothers lived in homes painted extensively (> 4 rooms) in the year before the children's birth., Conclusions: In this exploratory study, substantial participation by household members in some common household activities that involve organic solvents was associated with elevated risks of childhood ALL.

In the National Cancer Institute/Children's Cancer Group case-control study of childhood acute lymphoblastic leukemia (1989-1993), living in a home with a high-voltage wire code was not associated with disease risk. To further investigate risk near power lines, the authors analyzed distance to transmission and three-phase primary distribution lines within 40 m of homes and created an exposure index of distance and strength of multiple power lines (408 case-control pairs). Neither distance nor exposure index was related to risk of childhood acute lymphoblastic leukemia, although both were associated with in-home magnetic field measurements. Residence near high-voltage lines did not increase risk.

Objectives: To investigate the reproducibility of wire codes to characterise residential power line configurations and to determine the extent to which wire codes provide a proxy measure of residential magnetic field strength in a case-control study of childhood leukaemia conducted in nine states within the United States., Methods: Misclassification of wire codes was assessed with independent measurements by two technicians for 187 residences. The association between categories of wire code and measured level of magnetic field was evaluated in 858 residences with both a wire code measurement and a 24 hour measurement of the magnetic field in the bedroom. The strength of the association between category of wire code and risk of leukaemia was examined in two regions with different average levels of magnetic field in homes with high categories of wire code., Results: The reproducibility of any of three different classifications of wire codes was excellent (kappa > or = 0.89). Mean and median magnetic fields, and the percentage of homes with high magnetic fields increased with increasing category for each of the wire code classification schemes. The size of the odds ratios for risk of leukaemia and high categories of wire code did not reflect the mean levels of the magnetic field in those categories in two study regions., Conclusion: Misclassification of categories of wire code is not a major source of bias in the study. Wire codes provide a proxy measure of exposure to residential magnetic fields. If magnetic fields were a risk factor for leukaemia, however, there would be some attenuation of risk estimates based on wire codes because of misclassification of exposure to magnetic fields at both extremes of the wire code range. The lack of an association between high categories of wire code and risk of leukaemia cannot be explained by a failure of the wire code classification schemes to estimate exposure to magnetic fields in the study area.

Introduction: Recent findings of an apparent association between incidence of childhood leukaemia and radio frequency radiation (RFR) from television transmission antennas in Sydney, NSW, are examined., Methods: Incidence of childhood (0-14 years) acute lymphoblastic leukaemia (ALL) at the local government area (LGA) level is related to estimated exposure levels of RFR from television transmission antennas, using Poisson regression techniques., Results: Most of the association between ALL incidence and television transmission RFR is shown to be the result of an influential observation: one of the highly exposed LGAs contributes all the excess, while in a similarly exposed LGA childhood ALL incidence was found to be no higher than the rate expected for NSW. With the influential observation excluded from the analysis, no positive correlation between exposure to RFR and leukaemia is evident. Conversely, under the assumption of an association with RFR, the low probability of the observed incident cases in LGAs under conditions of relatively high exposure to RFR conflicts with the assumption of an effect., Conclusion: The apparent association between childhood ALL incidence and RFR radiation from television towers is weaker when an LGA-level analysis is conducted.

Epidemiologic evaluation of the relation between magnetic field exposures and cancer depends critically on study design, particularly the methods used for exposure assessment. We incorporated a complex magnetic field exposure assessment protocol into a large incident case-control study of childhood leukemia. We measured residential magnetic fields using a standard protocol in current and former homes of 638 cases and 620 controls and determined wire codes for 414 case-control pairs. We chose a time-weighted average of magnetic field measurements in each eligible home, weighted by the time the subject lived in each home as the main exposure metric for each subject. We found that 24-hour bedroom magnetic field measurements adequately characterize children's residential exposure and that measuring other rooms contributes only slightly to the estimate of average residential exposure to magnetic fields. Front door measured fields provide useful exposure information when interior measurements are missing. If feasible, measuring multiple homes in which the subject has resided is preferable to measuring a single home. A similar distribution of wire codes for controls agreeing or refusing to participate in our study implies that risk estimates derived from wire code data will not be influenced by response bias.

A temporal cluster of cases may result from exposure to a new carcinogen, but it may also occur under stable conditions or as result of another factor, such as changes in medical practice. In this study, we used several complementary methods to detect a cluster and to conduct an initial investigation regarding its cause. The analyses included three stages, and were based on the time interval between consecutive diagnoses. First, we applied the sets monitoring technique to detect clustering. Following the detection (alarm), a confirmatory analysis was conducted in order to confirm or refute it as a true alarm. We applied this analysis to the first five cases diagnosed subsequent to the alarm. With a graphical display of the temporal pattern of the diagnoses, we considered the possible causes leading to the cluster. The data included registered diagnoses of leukaemia cases made from 1960 to 1990 among residents of Ashkelon, Israel. Clustering was detected for acute lymphatic leukaemia and for chronic myeloid leukaemia. We found that the temporal patterns of the diagnoses consistent with the possibility that these two clusters are due to exposure to a common local carcinogen. We cannot however, rule out the possibility that these clusters are due to unknown factors.

Background: Previous studies found associations between childhood leukemia and surrogate indicators of exposure to magnetic fields (the power-line classification since known as "wire coding"), but not between childhood leukemia and measurements of 60-Hz residential magnetic fields., Methods: We enrolled 638 children with acute lymphoblastic leukemia (ALL) who were under 15 years of age and were registered with the Children's Cancer Group and 620 controls in a study of residential exposure to magnetic fields generated by nearby power lines. In the subjects' current and former homes, data collectors measured magnetic fields for 24 hours in the child's bedroom and for 30 seconds in three or four other rooms and outside the front door. A computer algorithm assigned wire-code categories; based on the distance and configuration of nearby power lines, to the subjects' main residences (for 416 case patients and 416 controls) and to those where the family had lived during the mother's pregnancy with the subject (for 230 case patients and 230 controls)., Results: The risk of childhood ALL was not linked to summary time-weighted average residential magnetic-field levels, categorized according to a priori criteria. The odds ratio for ALL was 1.24 (95 percent confidence interval, 0.86 to 1.79) at exposures of 0.200 mu T or greater as compared with less than 0.065 mu T. The risk of ALL was not increased among children whose main residences were in the highest wire-code category (odds ratio as compared with the lowest category, 0.88; 95 percent confidence interval, 0.48 to 1.63). Furthermore, the risk was not significantly associated with either residential magnetic-field levels or the wire codes of the homes mothers resided in when pregnant with the subjects., Conclusions: Our results provide little evidence that living in homes characterized by high measured time-weighted average magnetic-field levels or by the highest wire-code category increases the risk of ALL in children.

A total of 872 children aged up to 14 years, who were diagnosed with leukemia in Greece during the decade 1980-89, were allocated by place of residence to the 601 administrative districts of the country. Evaluation of spatial clustering was done using the Potthoff-Whittinghill method, which validly assesses heterogeneity of leukemia risk among districts with variable expected numbers of cases. There was highly significant evidence for spatial clustering occurring particularly among children living in urban and, to a lesser extent, semi-urban areas. The evidence was stronger for children younger than 10 years old, applied also to children in different five-year age groups, and persisted when cases of acute lymphoblastic leukemia were analyzed separately. These findings provide support to the hypothesis that localized environmental exposures could contribute to the etiology of childhood leukemia, but they cannot distinguish between exposures of physical or chemical nature, nor can they exclude socially conditioned patterns of exposure to infectious agents.