Ghislaine Bouvier

Mobile phone use and brain tumours in the CERENAT case-control study

The carcinogenic effect of radiofrequency electromagnetic fields in humans remains controversial. However, it has been suggested that they could be involved in the aetiology of some types of brain tumours. Objectives The objective was to analyse the association between mobile phone exposure and primary central nervous system tumours (gliomas and meningiomas) in adults. Methods CERENAT is a multicenter case-control study carried out in four areas in France in 2004–2006. Data about mobile phone use were collected through a detailed questionnaire delivered in a face-to-face manner. Conditional logistic regression for matched sets was used to estimate adjusted ORs and 95% CIs. Results A total of 253 gliomas, 194 meningiomas and 892 matched controls selected from the local electoral rolls were analysed. No association with brain tumours was observed when comparing regular mobile phone users with non-users (OR=1.24; 95% CI 0.86 to 1.77 for gliomas, OR=0.90; 95% CI 0.61 to 1.34 for meningiomas). However, the positive association was statistically significant in the heaviest users when considering life-long cumulative duration (≥896 h, OR=2.89; 95% CI 1.41 to 5.93 for gliomas; OR=2.57; 95% CI 1.02 to 6.44 for meningiomas) and number of calls for gliomas (≥18 360 calls, OR=2.10, 95% CI 1.03 to 4.31). Risks were higher for gliomas, temporal tumours, occupational and urban mobile phone use. Conclusions These additional data support previous findings concerning a possible association between heavy mobile phone use and brain tumours.

Brain tumors and hormonal factors: review of the epidemiological literature

BackgroundTo date, the etiology of primary tumors of the central nervous system (mainly gliomas and meningiomas) is poorly understood. The role of sex hormones has been suggested, based on clinical, experimental, biological, and epidemiological data.ObjectiveTo review the epidemiological studies on the relation between hormonal factors and the occurrence of glioma and meningioma, in order to identify new research developments.MethodsArticles published until September 2010 were selected by considering exogenous and endogenous exposures and specific brain tumors. Standardized information was collected from 20 articles: 15 concerning gliomas and 13 meningiomas.ResultsAn increased glioma risk was observed with later menarche and menopause, while a reduced glioma risk was observed with hormone replacement therapy (HRT) and oral contraceptive use, despite duration of use had no effect on risk. Meningioma risk increased after menopause and with HRT use. No clear association was found with pregnancy and breastfeeding.ConclusionResults are globally concordant with the biologic hypothesis assuming that female sex hormones are protective against glioma and may increase the risk of meningioma. However, new epidemiological studies should be conducted in order to confirm these associations and to refine the role of hormonal factors in brain etiology.

Association of STAT1, STAT3 and STAT5 proteins with the IL‐2 receptor involves different subdomains of the IL‐2 receptor β chain

Upon IL‐2 stimulation of T lymphocytes, the IL‐2 receptor (IL‐2R) becomes phosphorylated on specific tyrosine residues which serve as docking sites for proteins containing SH2 or phosphotyrosine binding domains. To study the interaction of the IL‐2Rβ chain with Shc and STAT proteins, subdomains of the IL‐2Rβ chain were expressed as tyrosine‐phosphorylated glutathione S‐transferase fusion proteins and used to pull‐down interacting proteins from Kit 225 cell lysates. These experiments provide direct biochemical evidence that binding to the IL‐2R of the adaptor protein Shc requires phosphorylation of Tyr‐338 in the IL‐2Rβ acidic subdomain. In addition, we report that STAT proteins that are activated by IL‐2, i.  e. STAT1, STAT3 and STAT5, indeed associate with the IL‐2Rβ chain. Both the A and B isoforms of STAT5 were found to associate with Tyr‐510 of the IL‐2Rβ C‐terminal region, depending on its phosphorylation. In contrast, STAT1 and STAT3 associated with the IL‐2Rβ chain through its acidic subdomain. These results indicate that the interaction between IL‐2Rβ and STAT1 or 3 does not require either phosphorylation of the receptor or even the presence of tyrosine residues of IL‐2Rβ. Thus, the IL‐2R recruits STAT proteins through different modes of interaction.

Cognitive Disorders and Occupational Exposure to Organophosphates: Results From the PHYTONER Study

The involvement of organophosphate insecticides in cognitive disorders is supported by epidemiologic and biological evidence, but the effects of long-term exposure remain debated. We studied the association between organophosphate exposure and cognitive performance in vine workers from the PHYTONER study cohort in the Bordeaux area of France. Results from interviews of 614 subjects conducted at the 4-year follow-up between 2001 and 2003 were analyzed. Exposure to pesticides since 1950 was assessed with cumulative exposure scores for 34 organophosphates combining an historical crop-exposure pesticide matrix and field exposure studies, taking into account the characteristics of treatment (mixing, spraying, equipment cleaning) and reentry tasks. For the 11 organophosphates retained in the analysis, exposure (ever vs. never) was associated with low cognitive performance. No dose-effect relationship was found, but an increased risk was observed with a 50-mg increase in the cumulative score, which was greater with mevinphos (Benton Visual Retention Test: odds ratio = 3.26, 95% confidence interval: 1.54, 6.88; Trail Making Test, part A: odds ratio = 3.03, 95% confidence interval: 1.39, 6.62). Our results support the hypothesis that cognitive disorders observed in vine workers may be associated with exposure to specific organophosphates.

Levels and determinants of pesticide exposure in operators involved in treatment of vineyards: results of the PESTEXPO Study

Exposure assessment is a critical point for epidemiological studies on pesticide health effects. PESTEXPO study provides data on levels of exposure and their determinants in real conditions of pesticide use. We described levels of exposure in vineyards during treatment tasks (mixing, spraying and cleaning) and we analysed their determinants. Sixty-seven operators using dithiocarbamates or folpet were observed. Detailed information on the tasks (general conditions, operator, farm and equipment characteristics) were collected and dermal contamination was measured, using patches placed onto the skin on eleven body parts, and washing the hands at the end of each phase. The spraying phase represented roughly half of the contamination, whereas mixing and equipment cleaning accounted for 30% and 20% of the contamination, respectively. The main determinants of exposure were the number of phases, the characteristics of the equipment, the educational level of the operator and his status (farm -worker or -owner) and the general characteristics of the vines. Algorithms were built to estimate daily external contamination, according to these characteristics during mixing, spraying or equipment cleaning. With additional information of frequency and duration of use, they will enable to develop exposure indices usable in epidemiological studies on farmers’ health.

A French crop-exposure matrix for use in epidemiological studies on pesticides: PESTIMAT

Pesticide exposure assessment is a key methodological issue for epidemiological studies. The history of pesticide has proven difficult to obtain from individuals’ report because of the wide range of active ingredients (AIs). We developed a crop-exposure matrix, which intends to reconstitute parameters of pesticide exposure in France since 1950. PESTIMAT is composed of tables crossing crops and AIs by year and providing the following metrics: (1) probability (proportion of farmers having used the AIs); (2) frequency (number of treatment days); and (3) intensity (application rate of the AIs in kg/ha). Metrics were obtained by the combination of six sources: (i) registration information from the Agriculture Ministry; (ii) information from agricultural bodies on products marketed; (iii) agricultural recommendations by the Plant Health Protection body; (iv) treatment calendars provided by farmers; (v) data from associations of farmers; and (vi) data from the industry. To date, 529 AIs usable between 1950 and 2010 are included in PESTIMAT: 160 fungicides; 160 herbicides; and 209 insecticides. When combined with duration and determinants of intensity, the metrics in PESTIMAT will make it possible to calculate exposure scores and to search for dose–effect relationships, an important criterion for causality judgment in epidemiology.

Biochemical analysis of interleukin-2 receptor β chain phosphorylation by p56lck

Tyrosine phosphorylation of multiple proteins, including the receptor itself, is an initial event in IL‐2 signaling and leads to recruitment of SH2 or PTB domain‐containing proteins to the receptor. In this study, we have used subdomains of the IL‐2 receptor β chain (IL‐2Rβ) expressed in Escherichia coli as GST fusion proteins to identify the tyrosine residues that could be phosphorylated by p56lck, one of the critical tyrosine kinases activated by IL‐2. We report that recombinant p56lck phosphorylates in vitro tyrosine residues within the IL‐2Rβ chain but not those within the IL‐2Rγ chain. p56lck phosphorylates tyrosine residues 355, 358 and 361 but not 338 of the IL‐2Rβ chain acidic subdomain. Interestingly, phosphorylation of Tyr‐358 appears to require the presence of either Tyr‐355 or Tyr‐361. p56lck also phosphorylates very efficiently the two tyrosines present in the IL‐2Rβ chain C‐terminal region, Tyr‐392 and Tyr‐510. We also investigated the association of p56lck with the IL‐2Rβ chain which was found to depend on a short stretch of the IL‐2Rβ chain acidic subdomain, and to be independent of the presence of its tyrosine residues.

Use of job-exposure matrices to estimate occupational exposure to pesticides: A review.

The health effects of pesticides have been extensively studied in epidemiology, mainly in agricultural populations. However, pesticide exposure assessment remains a key methodological issue for epidemiological studies. Besides self-reported information, expert assessment or metrology, job-exposure matrices still appear to be an interesting tool. We reviewed all existing matrices assessing occupational exposure to pesticides in epidemiological studies and described the exposure parameters they included. We identified two types of matrices, (i) generic ones that are generally used in case–control studies and document broad categories of pesticides in a large range of jobs, and (ii) specific matrices, developed for use in agricultural cohorts, that generally provide exposure metrics at the active ingredient level. The various applications of these matrices in epidemiological studies have proven that they are valuable tools to assess pesticide exposure. Specific matrices are particularly promising for use in agricultural cohorts. However, results obtained with matrices have rarely been compared with those obtained with other tools. In addition, the external validity of the given estimates has not been adequately discussed. Yet, matrices would help in reducing misclassification and in quantifying cumulated exposures, to improve knowledge about the chronic health effects of pesticides.

Increase in the Risk of Respiratory Disorders in Adults and Children Related to Crop-Growing in Niger

Background and Objective. Environmental factors are an increasing concern for respiratory health in developing countries. The objective of this study was to investigate whether Nigerien people living in cultivated areas have more respiratory symptoms than those living in pastoral areas. Method. A cross-sectional study was conducted in 2013 in two populations during the rainy season when land is cultivated. Environmental factors including pesticide use and respiratory symptoms were collected in adults and children during face-to-face interviews. Multivariate analysis between exposures and symptoms was performed in children and in adults separately. Results. The study included 471 adults and 229 children. Overall, none of the households reported the use of pesticides for agricultural purposes. However, 87.2% reported the use of insecticides at home. Multivariate analysis showed that people living in agricultural areas compared to those in pastoral areas had an increased risk of respiratory symptoms in adults (wheezing, dyspnea, sudden shortness of breath, and cough without fever) and in children (cough without fever). The use of insecticides showed no effect on respiratory symptoms after adjustment. Conclusion. This first epidemiological study on the environment and respiratory health conducted in Niger demonstrates a significant relationship between respiratory manifestations and the agricultural characteristics of the living area. However only the effect of insecticides in the home on respiratory health was observed.

Author’s response: Re ‘Mobile phone use and brain tumours in the CERENAT case–control study’

We thank Dr Hardell for his comment1 on our article concerning analyses regarding head position of mobile phone use.2 In our analysis on ipsilateral use, we included cases who used their mobile phone on the same side as the tumour or on both sides of the head, cases who were not regular users (the reference category) and all their matched controls. In our analysis on contralateral use, we used cases who used their mobile phone on the opposite side as the tumour, cases who were not …