Childhood leukemia and 50 Hz magnetic fields: findings from the Italian SETIL case-control study.

We report on an Italian case-control study on childhood leukemia and exposure to extremely low frequency magnetic fields (ELF-MF). Eligible for inclusion were 745 leukemia cases, aged 0-10 years at diagnosis in 1998-2001, and 1475 sex- and age-matched population controls. Parents of 683 cases and 1044 controls (92% vs. 71%) were interviewed. ELF-MF measurements (24-48 h), in the child's bedroom of the dwelling inhabited one year before diagnosis, were available for 412 cases and 587 controls included in the main conditional regression analyses. The magnetic field induction was 0.04 µT on average (geometric mean), with 0.6% of cases and 1.6% of controls exposed to >0.3 µT. The impact of changes in the statistical model, exposure metric, and data-set restriction criteria was explored via sensitivity analyses. No exposure-disease association was observed in analyses based on continuous exposure, while analyses based on categorical variables were characterized by incoherent exposure-outcome relationships. In conclusion, our results may be affected by several sources of bias and they are noninformative at exposure levels >0.3 µT. Nonetheless, the study may contribute to future meta- or pooled analyses. Furthermore, exposure levels among population controls are useful to estimate attributable risk.

SETIL: Italian multicentric epidemiological case-control study on risk factors for childhood leukaemia, non hodgkin lymphoma and neuroblastoma: study population and prevalence of risk factors in Italy.

BACKGROUND: Aetiology of childhood leukaemia and childhood neoplasm is poorly understood. Information on the prevalence of risk factors in the childhood population is limited. SETIL is a population based case-control study on childhood leukaemia, conducted with two companion studies on non-Hodgkin Lymphoma (NHL) and neuroblastoma. The study relies on questionnaire interviews and 50 Hz magnetic field (ELF-MF) indoor measurements. This paper discusses the SETIL study design and includes descriptive information. METHODS: The study was carried out in 14 Italian regions (78.3% of Italian population aged 0-10). It included leukaemia, NHL and neuroblastoma cases incident in 0-10 year olds in 1998-2001, registered by the Italian Association of Paediatric Haematology and Oncology (AIEOP) (accrual over 95% of estimated incidence). Two controls for each leukaemia case were randomly sampled from the Local Health Authorities rolls, matched by gender, birthdate and residence. The same controls were used in NHL and neuroblastoma studies. Parents were interviewed at home on: physical agents (ELF-MF and ionizing radiation), chemicals (smoking, solvents, traffic, insecticides), occupation, medical and personal history of children and parents, infectious diseases, immunizations and associated factors. Occupational exposure was collected using job specific modules. ELF-MF was measured in the main rooms (spot measurement) and close to child's bed (48 hours measurement). RESULTS: The study included: 683 leukaemia cases (87% ALL, 13% AnLL), 97 NHL, 155 neuroblastomas, and 1044 controls. CONCLUSIONS: SETIL represents a data source on exposure of Italian children to a broad array of potential carcinogenic factors.

Tobacco smoke and risk of childhood acute non-lymphocytic leukemia: findings from the SETIL study.

BACKGROUND: Parental smoking and exposure of the mother or the child to environmental tobacco smoke (ETS) as risk factors for Acute non-Lymphocytic Leukemia (AnLL) were investigated. METHODS: Incident cases of childhood AnLL were enrolled in 14 Italian Regions during 1998-2001. We estimated odds ratios (OR) and 95% confidence intervals (95%CI) conducting logistic regression models including 82 cases of AnLL and 1,044 controls. Inverse probability weighting was applied adjusting for: age; sex; provenience; birth order; birth weight; breastfeeding; parental educational level age, birth year, and occupational exposure to benzene. RESULTS: Paternal smoke in the conception period was associated with AnLL (OR for ≥ 11 cigarettes/day  = 1.79, 95% CI 1.01-3.15; P trend 0.05). An apparent effect modification by maternal age was identified: only children of mothers aged below 30 presented increased risks. We found weak statistical evidence of an association of AnLL with maternal exposure to ETS (OR for exposure>3 hours/day  = 1.85, 95%CI 0.97-3.52; P trend 0.07). No association was observed between AnLL and either maternal smoking during pregnancy or child exposure to ETS. CONCLUSIONS: This study is consistent with the hypothesis that paternal smoke is associated with AnLL. We observed statistical evidence of an association between maternal exposure to ETS and AnLL, but believe bias might have inflated our estimates.

Tobacco smoke and risk of childhood acute lymphoblastic leukemia: findings from the SETIL case-control study.

PURPOSE: Tobacco smoke could cause childhood acute lymphoblastic leukemia (ALL) through at least three pathways: (1) prenatal parental smoking; (2) fetal exposure through maternal smoking during pregnancy; and (3) childhood exposure to secondhand smoke (SHS). We tested these hypotheses in a large population-based case-control study (SETIL) primarily designed to evaluate the role of electromagnetic fields in childhood hematopoietic malignancies. METHODS: From 1998 to 2003, we enrolled 602 incident cases of ALL from 14 Italian Regions, and 918 controls were individually matched by birthdate, sex, and area of residence. Cases (n = 557) and controls (n = 855) with complete information were analyzed; odds ratios (OR) and 95 % confidence intervals (95 % CI) were estimated with logistic regression models conditioned on matching variables and adjusted by birth order, birthweight, duration of breastfeeding, parental age at delivery, education, and occupational exposure to benzene. RESULTS: No evidence associating paternal smoking in the conception period or maternal smoking during the pregnancy with ALL was found. An association of ALL with maternal exposure to SHS during pregnancy (adjusted OR for mothers exposed more than 4 h/day = 2.18, 95 % CI 1.39-3.42) was observed, but recall bias cannot be excluded. Exposure of the children to SHS was associated with ALL only in unadjusted analysis (unadjusted OR for highly exposed children = 1.64; 95 % CI 1.10-2.45). CONCLUSIONS: This study does not support the hypothesis that parental active smoking is associated with ALL. We found very weak evidence of increased risk of ALL for children exposed to SHS. Maternal exposure to SHS was associated with ALL, but recall bias is likely to inflate our estimates.

Risk of childhood leukaemia and non-Hodgkin's lymphoma after parental occupational exposure to solvents and other agents: the SETIL Study.

AIM: In the context of the Italian Multicentric Epidemiological Study on Risk Factors for Childhood Leukaemia and Non-Hodgkin's Lymphoma (SETIL), the risk of childhood cancer was investigated in relation to parental occupational exposures. METHODS: All cases of childhood leukaemia and non-Hodgkin's lymphoma (NHL) in children aged 0-10 years were identified. Controls were chosen at random from the local population in each region. Parents were interviewed using a structured questionnaire. The collected data were blindly reviewed by expert industrial hygienists in order to estimate exposure to a list of agents. Statistical analyses were performed for each agent using unconditional multivariable logistic regression models, taking into account timing of exposure. RESULTS: 683 cases of acute childhood leukaemia, 97 cases of NHL and 1044 controls were identified. Increased risk of childhood leukaemia was found for maternal exposure to aliphatic (OR 4.3) or aromatic hydrocarbons (OR 3.8) in the preconception period, and for paternal exposure to diesel exhaust (OR 1.4), lead exposure (OR 1.7) and mineral oils (OR 1.4)[corrected]. Risk of NHL appeared to be related to paternal exposure to oxygenated solvents (OR 2.5) and petrol exhaust (OR 2.2). CONCLUSIONS: We found increased risk for childhood leukaemia associated with maternal occupational exposure to aromatic and aliphatic hydrocarbons, particularly in the preconception period; increased risks were also observed for paternal exposure to diesel exhaust fumes, mineral oils and lead. The risk of NHL appeared to be related to paternal exposure to oxygenated solvent and petrol exhausts.

Local influence analysis when interfacing toxicokinetic and proportional hazard models.

We present a local influence analysis to assigned model quantities in the context of a dose-response analysis of cancer mortality in relation to estimated absorbed dose of dioxin. The risk estimation is performed using dioxin dose as a time-dependent explanatory variable in a proportional hazard model. The dioxin dose is computed using a toxicokinetic model, which depends on some factors, such as assigned constants and estimated parameters. We present a local influence analysis to assess the effects on final results of minor perturbations of toxicokinetic model factors. In the present context, there is no evidence of local influence in risk estimates. It is however possible to identify which factors are more influential.

Population toxicokinetic analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin using Bayesian techniques.

Understanding the kinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations in humans is an important step for TCDD cancer risk assessment. In this paper longitudinal series of serum TCDD concentration measurements on U.S. veterans of the Vietnam war, who were exposed to dioxin during herbicide-spraying operations, are studied. The overall aim is to use these data to infer the dynamics of TCDD concentrations in humans. This is done by identifying a kinetic model describing the dioxin time course at the individual level. The individual toxicokinetic model is then expanded into a population model within a Bayesian hierarchical framework which allows residual variations across subjects that cannot be explained by observed covariates. Other complications in the data, such as unknown exposure histories, are also resolved implicitly through the hierarchical model. Moreover, the choice of a Bayesian approach enables the accumulation of external source of information in the form of prior distributions. The model is subjected to various diagnostic checks and analyses of sensitivity to distributional assumptions showing a good fit in terms of both the population and the kinetic features.