Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
OBJECTIVES: The time from the prenatal period through early childhood is an important window of vulnerability for the developing immune and respiratory systems, both sensitive to environmental chemicals such as solvents. This study sought to examine the effects of solvent exposure during the prenatal and postnatal periods on wheezing, eczema and food allergies in early childhood. METHODS: This study, based on the PELAGIE cohort, included 1505 mother-child pairs with measurements of prenatal and postnatal solvent exposures and data on wheezing, eczema or food allergies. The maternal occupation reported at inclusion, in early pregnancy allowed us to define prenatal occupational solvent exposure (by three specific job-exposure matrices). Data on prenatal and postnatal domestic solvent exposure, that is exposure to products that contain solvents, were obtained from self-administered questionnaires, once at inclusion and again when the child was 2 years old. Outcome data was collected at the 2-year follow-up. Associations between exposures and outcomes were estimated by logistic regression models, after adjustment for potential confounders. RESULTS: No association was observed between prenatal exposure to solvents and the outcomes studied. Postnatal exposure was associated with an increased risk of wheezing (OR=1.80 (95% CI 1.25 to 2.59)) which persisted after adjustment for prenatal exposure. No significant association was observed with eczema or food allergies. CONCLUSIONS: Postnatal exposure to solvent-containing products in the home may increase the risk of wheezing in early childhood. Follow-up studies are needed to determine if the health effects observed at age 2 persist at later ages.
ISSN: 1351-0711

hal-01063913
https://hal.archives-ouvertes.fr/hal-01063913
DOI : 10.1136/oemed-2013-102036
PUBMED : 24996679

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
BACKGROUND: Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson's disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families. METHODS: We performed extensive mutation analyses of all 51 coding exons of the LRRK2 gene in index cases from 226 Parkinson's disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14). RESULTS: We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein. CONCLUSION: This study leads us to conclude that LRRK2 mutations are a common cause of autosomal dominant Parkinson's disease in Europe and North Africa.
ISSN: 0022-2593

inserm-00529272
http://www.hal.inserm.fr/inserm-00529272
DOI : 10.1136/jmg.2008.062612
PUBMED : 19357115

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : For the ICARE Study Group
International audience
Objective Our objective was to investigate the association between head and neck cancer and occupational exposure to chlorinated, oxygenated and petroleum solvents in women.Methods Investigation of occupational and environmental CAuses of REspiratory cancers (ICARE), a French population-based case–control study, included 296 squamous cell carcinomas of the head and neck (HNSCC) in women and 775 female controls. Lifelong occupational history was collected. Job-exposure matrices allowed to assess exposure to 5 chlorinated solvents (carbon tetrachloride; chloroform; methylene chloride; perchloroethylene; trichloroethylene), 5 petroleum solvents (benzene; special petroleum product; gasoline; white spirits and other light aromatic mixtures; diesel, fuels and kerosene) and 5 oxygenated solvents (alcohols; ketones and esters; ethylene glycol; diethyl ether; tetrahydrofuran). OR and 95% CIs, adjusted for smoking, alcohol drinking, age and geographical area, were estimated with logistic models.Results Elevated ORs were observed among women ever exposed to perchloroethylene (OR=2.97, 95% CI 1.05 to 8.45) and trichloroethylene (OR=2.15, 95% CI 1.21 to 3.81). These ORs increased with exposure duration (OR=3.75, 95% CI 0.64 to 21.9 and OR=4.44, 95% CI 1.56 to 12.6 for 10 years or more, respectively). No significantly increased risk of HNSCC was found for occupational exposure to the other chlorinated, petroleum or oxygenated solvents.Conclusions These findings suggest that exposure to perchloroethylene or trichloroethylene may increase the risk of HNSCC in women. In our study, there is no clear evidence that the other studied solvents are risk factors for HNSCC.
ISSN: 2044-6055

Droits : http://creativecommons.org/licenses/by-nc/
hal-01438872
http://hal.upmc.fr/hal-01438872
http://hal.upmc.fr/hal-01438872/document
http://hal.upmc.fr/hal-01438872/file/e012833.full.pdf
DOI : 10.1136/bmjopen-2016-012833

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
Annual European Congress of Rheumatology (EULAR)
ISSN: 0003-4967

hal-01560154
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560154
DOI : 10.1136/annrheumdis-2016-eular.4936

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
We read with interest the report by Desrosiers et al 1 on the association between maternal occupational exposure to organic solvents and some birth defects. Their case-control study examined occupational exposure to three classes of solvents (chlorinated, aromatic and Stoddard) and found one association--between neural tube defects (mainly spinal bifida) and maternal occupational exposure to chlorinated solvents, but no association with the other solvent classes or with oral clefts. In their discussion, the authors noted that previous findings on maternal occupational exposure to solvents and oral clefts were from European, mainly French, populations and they hypothesised that the inconsistency between their results and these previous studies might be due to different exposure profiles (eg, intensity and solvent formulation). Although this explanation is plausible, another explanation must be discussed: differences in the definition of exposure. Our research team conducted four of the five studies with positive results cited by Desrosiers et al.2-5 All four were population based and included, in addition to the solvent classes considered by Desrosiers et al, oxygenated solvents, for example, alcohols or glycol ethers. Exposure limited to only oxygenated solvents appears to be very frequent among working women: more than half of the solvent exposure group in Chevrier et al 4 were exposed only to that solvent class. Because previous studies found an increased risk of oral clefts to be associated principally with that specific exposure, failure to consider this association could explain the negative findings for oral clefts. Moreover, women who were exposed only to oxygenated solvents are included in the reference ('non-exposed') group here, which would result in underestimating associations with chlorinated and petroleum solvents. For both these reasons, we believe that the failure to consider oxygenated solvents led to underestimating the risk estimates for oral clefts.
ISSN: 1351-0711

hal-00875943
https://hal.archives-ouvertes.fr/hal-00875943
DOI : 10.1136/oemed-2012-100999
PUBMED : 22843438

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
BACKGROUND: The association between lung cancer and occupational exposure to organic solvents is discussed. Since different solvents are often used simultaneously, it is difficult to assess the role of individual substances. OBJECTIVES: The present study is focused on an in-depth investigation of the potential association between lung cancer risk and occupational exposure to a large group of organic solvents, taking into account the well-known risk factors for lung cancer, tobacco smoking and occupational exposure to asbestos. METHODS: We analysed data from the Investigation of occupational and environmental causes of respiratory cancers (ICARE) study, a large French population-based case-control study, set up between 2001 and 2007. A total of 2276 male cases and 2780 male controls were interviewed, and long-life occupational history was collected. In order to overcome the analytical difficulties created by multiple correlated exposures, we carried out a novel type of analysis based on Bayesian profile regression. RESULTS: After analysis with conventional logistic regression methods, none of the 11 solvents examined were associated with lung cancer risk. Through a profile regression approach, we did not observe any significant association between solvent exposure and lung cancer. However, we identified clusters at high risk that are related to occupations known to be at risk of developing lung cancer, such as painters. CONCLUSIONS: Organic solvents do not appear to be substantial contributors to the occupational risk of lung cancer for the occupations known to be at risk
ISSN: 1351-0711

hal-01282444
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282444
DOI : 10.1136/oemed-2015-103177
PUBMED : 26911986

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
BACKGROUND: Chronic HCV infection is associated with the development of hepatic fibrosis. The direct role of HCV in the fibrogenic process is unknown. Specifically, whether HCV is able to infect hepatic stellate cells (HSCs) is debated. OBJECTIVE: To assess whether human HSCs are susceptible to HCV infection. DESIGN: We combined a set of original HCV models, including the infectious genotype 2a JFH1 model (HCVcc), retroviral pseudoparticles expressing the folded HCV genotype 1b envelope glycoproteins (HCVpp) and a subgenomic genotype 1b HCV replicon, and two relevant cellular models, primary human HSCs from different patients and the LX-2 cell line, to assess whether HCV can infect/replicate in HSCs. RESULTS: In contrast with the hepatocyte cell line Huh-7, neither infectious HCVcc nor HCVpp infected primary human HSCs or LX-2 cells. The cellular expression of host cellular factors required for HCV entry was high in Huh-7 cells but low in HSCs and LX-2 cells, with the exception of CD81. Finally, replication of a genotype 2a full-length RNA genome and a genotype 1b subgenomic replicon was impaired in primary human HSCs and LX-2 cells, which expressed low levels of cellular factors known to play a key role in the HCV life-cycle, suggesting that human HSCs are not permissive for HCV replication. CONCLUSIONS: Human HSCs are refractory to HCV infection. Both HCV entry and replication are deficient in these cells, regardless of the HCV genotype and origin of the cells. Thus, HCV infection of HSCs does not play a role in liver fibrosis. These results do not rule out a direct role of HCV infection of hepatocytes in the fibrogenic process.
ISSN: 0017-5749

hal-01063909
https://hal.archives-ouvertes.fr/hal-01063909
DOI : 10.1136/gutjnl-2013-305634
PUBMED : 25063678

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
OBJECTIVES: To compare the quality of life (QoL) in three groups of workers suffering or not from shoulder pain (SP) lasting more than one month during the preceding 12 months. METHOD: Between 2002-2005, 3710 workers were randomly included in a French surveillance system of work-related musculoskeletal disorders. In 2007, 2332 responded to a follow-up questionnaire, 2049 were still active. Workers completed the Nordic Questionnaire to assess SP and the SF-36 for QoL. Three groups were defined according to health status at follow-up: Group 1: workers without SP (men: 87.9%; women: 79.2%) Group 2: workers with SP without neck, elbow and hand/wrist pain lasting more than one month during the preceding 12 months (men: 4.2%; women: 6.0%) Group 3: workers with SP and neck, elbow or hand/wrist pain lasting more than one month during the preceding 12 months (men 7.9%; women 14.8%) The mean scores of SF-36 were compared with Kruskall-Wallis test and post-hoc comparisons were performed. Analyses were stratified by gender. RESULTS: Workers in group 2 had lower scores of physical health compared to workers in group 1, whatever the gender. Workers in group 3 had lower scores of physical and mental health compared to workers in group 1. Two dimensions of mental health in men and the four dimensions of physical health and one dimension of mental health in women had lower scores in group 3 compared to group 2. CONCLUSIONS: Workers with SP and upper-limb pain have poorer QoL compared to workers without SP and workers with SP without upper-limb pain.
ISSN: 1351-0711

hal-01063898
https://hal.archives-ouvertes.fr/hal-01063898
DOI : 10.1136/oemed-2014-102362.258

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
OBJECTIVES: Many women who work during pregnancy are occupationally exposed to toxicants. The developing central nervous system is highly vulnerable to neurotoxicants such as solvents. Although the neurotoxicity of solvents to adults is well established, very few studies have examined their effects on children's behaviour following prenatal exposure. METHODS: Women from the Perturbateurs endocriniens: Étude Longitudinale sur les Anomalies de la Grossesse, l'Infertilité et l'Enfance (PELAGIE) mother-child cohort (including 3005 working women) were recruited in Brittany (France) between 2002 and 2006, at the beginning of pregnancy, to assess occupational exposure to solvents at that time. Child behaviour was documented at age 2 by mothers (n=1278) assessing components of attention deficit/hyperactivity, aggression, opposition and emotionality. We used a multiple linear regression analysis to evaluate the association between occupational solvent exposure and children's behaviour. Complementary sensitivity analyses allowed us to handle missing data, due mostly to attrition. RESULTS: 20% of women reported occasional exposure and 31% regular exposure to solvents. Children prenatally exposed were more likely to have higher scores of attention deficit/hyperactivity and aggression, and dose-response relations were observed. CONCLUSIONS: The dose-response effect and the high prevalence of children potentially exposed to solvents from their mother's workplace exposure underline the public health relevance of this result. Our results should be replicated in further studies designed to identify which solvents are most deleterious and to assess child behaviour at school age.
ISSN: 1351-0711

inserm-00795043
http://www.hal.inserm.fr/inserm-00795043
http://www.hal.inserm.fr/inserm-00795043/document
http://www.hal.inserm.fr/inserm-00795043/file/Occupationnal_solvent_exposure_child_behavior_HAL.pdf
DOI : 10.1136/oemed-2012-100892

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
ISSN: 0959-8138

hal-01483389
http://hal.univ-reunion.fr/hal-01483389
DOI : 10.1136/bmj.i4850

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
OBJECTIVE:To identify local meteorological drivers of dengue fever in French Guiana, we applied an original data mining method to the available epidemiological and climatic data. Through this work, we also assessed the contribution of the data mining method to the understanding of factors associated with the dissemination of infectious diseases and their spatiotemporal spread.METHODS:We applied contextual sequential pattern extraction techniques to epidemiological and meteorological data to identify the most significant climatic factors for dengue fever, and we investigated the relevance of the extracted patterns for the early warning of dengue outbreaks in French Guiana.RESULTS:The maximum temperature, minimum relative humidity, global brilliance, and cumulative rainfall were identified as determinants of dengue outbreaks, and the precise intervals of their values and variations were quantified according to the epidemiologic context. The strongest significant correlations were observed between dengue incidence and meteorological drivers after a 4-6-week lag.DISCUSSION:We demonstrated the use of contextual sequential patterns to better understand the determinants of the spatiotemporal spread of dengue fever in French Guiana. Future work should integrate additional variables and explore the notion of neighborhood for extracting sequential patterns.CONCLUSIONS:Dengue fever remains a major public health issue in French Guiana. The development of new methods to identify such specific characteristics becomes crucial in order to better understand and control spatiotemporal transmission.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
ISSN: 1067-5027

lirmm-01379072
https://hal-lirmm.ccsd.cnrs.fr/lirmm-01379072
DOI : 10.1136/amiajnl-2013-002348
PUBMED : 24549761

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
OBJECTIVES: Social position and social mobility are associated with cancer incidence and mortality, yet little is known about their association with mediating factors such as occupational exposures to carcinogens. Our aim was to assess the association between the type of professional trajectory and multiple occupational exposure profiles. METHOD: Data were extracted from the Giscop93 study (n = 1 009), which is a cohort of cancer patients with (mainly) respiratory tumours. Job histories were reconstructed through interview, then a multi-disciplinary expert group examined the probability of occupational exposure to a list of 54 potentially carcinogenic agents. The typology of professional trajectories was built based on employment stability, employment continuity, job qualification trend, and multiple skills through Multiple Correspondence Analysis followed by Ascending Hierarchical Classification. Association with multiple-exposure profiles was then assessed through multiple logistic regression. RESULTS: Men and women differed in terms of predominant job category over the lifecourse (68,2% of blue-collar-workers among men, 57,3% of employees among women, p extless 0.0001). Professional trajectories were grouped in four classes as "stable qualified, employee" (21,3%), "stable manual, independent blue-collar-worker" (24,4%), "stable tiring, no gain in qualification" (30,5%), and "very unstable, precarious" (23,8%). Among men, the last two categories were associated with exposure to at least five different occupational carcinogens (ORstable_tiring/stable_qualified=2,0 [1,3;3,1], ORvery_unstable/stable_qualified=2,6 [1,6;4,2]). No such association was found among women. CONCLUSIONS: The association found between the type of professional trajectory and multiple occupational exposures among men should be replicated among people not suffering cancer. Forthcoming analysis will investigate the gendered differences observed.
ISSN: 1351-0711

hal-01063899
https://hal.archives-ouvertes.fr/hal-01063899
DOI : 10.1136/oemed-2014-102362.266

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
OBJECTIVE: To investigate the role of occupational exposure to chlorinated solvents in lung cancer aetiology. METHODS: ICARE (Investigation of occupational and environmental CAuses of REspiratory cancers) is a French, multicentre, population-based, case-control study. Information on the lifelong work history of 2926 cases and 3555 controls was collected using standardised questionnaires. Occupational exposures were assessed using job-exposure matrices for five chlorinated solvents. Solvents were studied separately and in combinations. ORs were computed using unconditional logistic regression models adjusted for classic risk factors, including a history of cigarette smoking and exposure to asbestos. Adjustment for socioeconomic status (SES) was also made. RESULTS: After adjustment for exposure to asbestos, we observed a positive, statistically significant association with lung cancer for men and women exposed to a combination of perchloroethylene (PCE), trichloroethylene and dichloromethane (DCM). Further adjustment for SES slightly decreased this association. In contrast, no statistically significant associations were found for other solvent combinations. CONCLUSIONS: These results suggest that exposure to PCE may constitute a risk factor for lung cancer, especially among women, who seem to have a higher prevalence of exposure than men.
ISSN: 1351-0711

hal-01063908
https://hal.archives-ouvertes.fr/hal-01063908
DOI : 10.1136/oemed-2014-102182
PUBMED : 25015929

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
ISSN: 1351-0711

hal-00875885
https://hal.archives-ouvertes.fr/hal-00875885
DOI : 10.1136/oemed-2013-101631
PUBMED : 24143016

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
Annual European Congress of Rheumatology (EULAR)
ISSN: 0003-4967

hal-01560153
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560153
DOI : 10.1136/annrheumdis-2016-eular.4920

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
Objective The potential impact of environmental exposure to pyrethroid insecticides on child neurodevelopment has only just started to receive attention despite their widespread use. We investigated the associations between prenatal and childhood exposure to pyrethroid insecticides and behavioural skills in 6-year-olds. Methods The PELAGIE cohort enrolled 3421 pregnant women from Brittany, France between 2002 and 2006. 428 mothers were randomly selected for the study when their children turned 6, and 287 (67%) agreed to participate. Children's behaviour was assessed using the Strengths and Difficulties Questionnaire (SDQ). Three subscales (prosocial behaviour, internalising disorders and externalising disorders) were considered. Five pyrethroid metabolites were measured in maternal and child urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Logistic regression and reverse-scale Cox regression models were used to estimate the associations between SDQ scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Results Increased prenatal cis-3-(2,2-dichlorovinyl)-2,2dimethylcyclopropane carboxylic acid (DCCA) concentrations were associated with internalising difficulties (Cox p value=0.05). For childhood 3phenoxybenzoic acid (PBA) concentrations, a positive association was observed with externalising difficulties (Cox p value=0.04) and high ORs were found for abnormal or borderline social behaviour (OR 2.93, 95% CI 1.27 to 6.78, and OR 1.91, 95% CI 0.80 to 4.57, for the intermediate and highest metabolite categories, respectively). High childhood trans-DCCA concentrations were associated with reduced externalising disorders (Cox p value=0.03). Conclusions The present study suggests that exposure to certain pyrethroids, at environmental levels, may negatively affect neurobehavioral development by 6 years of age.
ISSN: 1351-0711

hal-01519255
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519255
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519255/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519255/file/Behavioural%20disorders%20in%206-year-old%20children_JFViel_HAL.pdf
DOI : 10.1136/oemed-2016-104035

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
Annual European Congress of Rheumatology (EULAR)
ISSN: 0003-4967

hal-01560156
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560156
DOI : 10.1136/annrheumdis-2016-eular.4902