Brain tumors in children and adolescents and exposure to animals and farm life: a multicenter case-control study (CEFALO).

OBJECTIVES: The etiology of brain tumors in children and adolescents is largely unknown, and very few environmental risk factors have been identified. The aim of this study was to examine the relationship between pre- or postnatal animal contacts or farm exposures and the risk of childhood brain tumors (CBTs), since infectious agents may pose a risk factor and a proposed mechanism is transferral of infectious agents from animals to humans. METHODS: The case-control study conducted in Denmark, Norway, Sweden, and Switzerland included brain tumor cases diagnosed from 2004 to 2008 aged 7-19 years at diagnosis. Three hundred and fifty-two cases (83 % participation rate) were matched to 646 population-based controls (71 % participation rate). Conditional logistic regression was used to estimate odds ratios. RESULTS: Maternal farm residence during pregnancy was inversely related to all CBTs combined (adjusted odds ratio (aOR) = 0.40, 95 % confidence interval (CI) = 0.19-0.88), as was the child's farm residence but not statistically significantly so (aOR = 0.57, 95 % CI = 0.28-1.17). Exposure to animals was in general not related to CBT risk except postnatal contact with birds showing reduced aORs of all CBTs (0.67, 95 % CI = 0.46-0.97) and primitive neuroectodermal tumor (0.28, 95 % CI = 0.10-0.83). Sensitivity analyses focusing on early exposure of the child did not change the associations observed for the entire exposure period with the exception of exposure to goats and sheep which was associated with reduced risks of both all CBTs (aOR = 0.48, 95 % CI = 0.24-0.97) and astrocytomas (aOR = 0.29, 95 % CI = 0.10-0.87). CONCLUSION: Altogether, our data indicate an inverse association between the mother during pregnancy or the child living on a farm and CBT risk, which contrasts with the existing literature and merits further attention. With respect to exposure to animals, we did not observe any systematic pattern. This suggests that a potential protective effect of farm residence is mediated by some other factor than animal contact.

Childhood brain tumours and use of mobile phones: comparison of a case-control study with incidence data.

The first case-control study on mobile phone use and brain tumour risk among children and adolescents (CEFALO study) has recently been published. In a commentary published in Environmental Health, Söderqvist and colleagues argued that CEFALO suggests an increased brain tumour risk in relation to wireless phone use. In this article, we respond and show why consistency checks of case-control study results with observed time trends of incidence rates are essential, given the well described limitations of case-control studies and the steep increase of mobile phone use among children and adolescents during the last decade. There is no plausible explanation of how a notably increased risk from use of wireless phones would correspond to the relatively stable incidence time trends for brain tumours among children and adolescents observed in the Nordic countries. Nevertheless, an increased risk restricted to heavy mobile phone use, to very early life exposure, or to rare subtypes of brain tumours may be compatible with stable incidence trends at this time and thus further monitoring of childhood brain tumour incidence rate time trends is warranted.

Impact of random and systematic recall errors and selection bias in case--control studies on mobile phone use and brain tumors in adolescents (CEFALO study).

Whether the use of mobile phones is a risk factor for brain tumors in adolescents is currently being studied. Case--control studies investigating this possible relationship are prone to recall error and selection bias. We assessed the potential impact of random and systematic recall error and selection bias on odds ratios (ORs) by performing simulations based on real data from an ongoing case--control study of mobile phones and brain tumor risk in children and adolescents (CEFALO study). Simulations were conducted for two mobile phone exposure categories: regular and heavy use. Our choice of levels of recall error was guided by a validation study that compared objective network operator data with the self-reported amount of mobile phone use in CEFALO. In our validation study, cases overestimated their number of calls by 9% on average and controls by 34%. Cases also overestimated their duration of calls by 52% on average and controls by 163%. The participation rates in CEFALO were 83% for cases and 71% for controls. In a variety of scenarios, the combined impact of recall error and selection bias on the estimated ORs was complex. These simulations are useful for the interpretation of previous case-control studies on brain tumor and mobile phone use in adults as well as for the interpretation of future studies on adolescents.

Predictors and overestimation of recalled mobile phone use among children and adolescents.

A growing body of literature addresses possible health effects of mobile phone use in children and adolescents by relying on the study participants' retrospective reconstruction of mobile phone use. In this study, we used data from the international case-control study CEFALO to compare self-reported with objectively operator-recorded mobile phone use. The aim of the study was to assess predictors of level of mobile phone use as well as factors that are associated with overestimating own mobile phone use. For cumulative number and duration of calls as well as for time since first subscription we calculated the ratio of self-reported to operator-recorded mobile phone use. We used multiple linear regression models to assess possible predictors of the average number and duration of calls per day and logistic regression models to assess possible predictors of overestimation. The cumulative number and duration of calls as well as the time since first subscription of mobile phones were overestimated on average by the study participants. Likelihood to overestimate number and duration of calls was not significantly different for controls compared to cases (OR=1.1, 95%-CI: 0.5 to 2.5 and OR=1.9, 95%-CI: 0.85 to 4.3, respectively). However, likelihood to overestimate was associated with other health related factors such as age and sex. As a consequence, such factors act as confounders in studies relying solely on self-reported mobile phone use and have to be considered in the analysis.

Mobile phone use and brain tumors in children and adolescents: a multicenter case-control study.

BACKGROUND: It has been hypothesized that children and adolescents might be more vulnerable to possible health effects from mobile phone exposure than adults. We investigated whether mobile phone use is associated with brain tumor risk among children and adolescents. METHODS: CEFALO is a multicenter case-control study conducted in Denmark, Sweden, Norway, and Switzerland that includes all children and adolescents aged 7-19 years who were diagnosed with a brain tumor between 2004 and 2008. We conducted interviews, in person, with 352 case patients (participation rate: 83%) and 646 control subjects (participation rate: 71%) and their parents. Control subjects were randomly selected from population registries and matched by age, sex, and geographical region. We asked about mobile phone use and included mobile phone operator records when available. Odds ratios (ORs) for brain tumor risk and 95% confidence intervals (CIs) were calculated using conditional logistic regression models. RESULTS: Regular users of mobile phones were not statistically significantly more likely to have been diagnosed with brain tumors compared with nonusers (OR = 1.36; 95% CI = 0.92 to 2.02). Children who started to use mobile phones at least 5 years ago were not at increased risk compared with those who had never regularly used mobile phones (OR = 1.26, 95% CI = 0.70 to 2.28). In a subset of study participants for whom operator recorded data were available, brain tumor risk was related to the time elapsed since the mobile phone subscription was started but not to amount of use. No increased risk of brain tumors was observed for brain areas receiving the highest amount of exposure. CONCLUSION: The absence of an exposure-response relationship either in terms of the amount of mobile phone use or by localization of the brain tumor argues against a causal association.