Occupational exposure to pesticides and central nervous system tumors: results from the CERENAT case-control study.

BACKGROUND: The etiology of the central nervous system (CNS) tumors remains largely unknown. The role of pesticide exposure has been suggested by several epidemiological studies, but with no definitive conclusion. OBJECTIVE: To analyze associations between occupational pesticide exposure and primary CNS tumors in adults in the CERENAT study. METHODS: CERENAT is a multicenter case-control study conducted in France in 2004-2006. Data about occupational pesticide uses-in and outside agriculture-were collected during detailed face-to-face interviews and reviewed by experts for consistency and exposure assignment. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated with conditional logistic regression. RESULTS: A total of 596 cases (273 gliomas, 218 meningiomas, 105 others) and 1 192 age- and sex-matched controls selected in the general population were analyzed. Direct and indirect exposures to pesticides in agriculture were respectively assigned to 125 (7.0%) and 629 (35.2%) individuals and exposure outside agriculture to 146 (8.2%) individuals. For overall agricultural exposure, we observed no increase in risk for all brain tumors (OR 1.04, 0.69-1.57) and a slight increase for gliomas (OR 1.37, 0.79-2.39). Risks for gliomas were higher when considering agricultural exposure for more than 10 years (OR 2.22, 0.94-5.24) and significantly trebled in open field agriculture (OR 3.58, 1.20-10.70). Increases in risk were also observed in non-agricultural exposures, especially in green space workers who were directly exposed (OR 1.89, 0.82-4.39), and these were statistically significant for those exposed for over 10 years (OR 2.84, 1.15-6.99). DISCUSSION: These data support some previous findings regarding the potential role of occupational exposures to pesticides in CNS tumors, both inside and outside agriculture.

Increasing incidence of central nervous system (CNS) tumors (2000-2012): findings from a population based registry in Gironde (France).

BACKGROUND: Although some countries have observed a stabilization in the incidence of CNS, an increasing incidence has been reported from multiple studies. Recent observations point out to the heterogeneity of incidence trends according to histological subtypes, gender and age-groups. Using a high-quality regional CNS tumor registry, this article describes the trends of CNS tumor incidence for main histological subtypes, including benign and malignant tumors, in the French department of Gironde from 2000 to 2012. METHODS: Crude and age-standardized incidence rates were calculated globally, by histological subtypes, malignant status, gender and age groups. For trends, annual percent changes (APC) were obtained from a piecewise log-linear model. RESULTS: A total of 3515 CNS tumors was registered during the period. The incidence of overall CNS tumors was 19/100000 person-years (8.3/100000 for neuroepithelial tumors and 7.3/100000 for meningeal tumors). An increased incidence of overall CNS tumors was observed from 2000 to 2012 (APC = + 2.7%; 95%-confidence interval (CI): 1.8-3.7). This trend was mainly explained by an increase in the incidence of meningiomas over the period (APC = + 5.4%, 95%-CI: 3.8-7.0). The increased incidence rate of CNS tumors was more pronounced in female and in older patients even though the incidence rate increased in all age groups. CONCLUSIONS: Part of the temporal variation may be attributed to improvement in registration, diagnosis and clinical practices but also to changes in potential risk factors. Thus, etiological studies on CNS tumors are needed to clarify this rising trend.

Central nervous system tumors and agricultural exposures in the prospective cohort AGRICAN.

Studies in farmers suggest a possible role of pesticides in the occurrence of Central Nervous System (CNS) tumors but scientific evidence is still insufficient. Using data from the French prospective agricultural cohort AGRICAN (Agriculture & Cancer), we investigated the associations between exposure of farmers and pesticide users to various kinds of crops and animal farming and the incidence of CNS tumors, overall and by subtypes. Over the 2005-2007, 181,842 participants completed the enrollment questionnaire that collected a complete job calendar with lifetime history of farming types. Associations were estimated using proportional hazards models with age as underlying timescale. During a 5.2 years average follow-up, 273 incident cases of CNS tumors occurred, including 126 gliomas and 87 meningiomas. Analyses showed several increased risks of CNS tumors in farmers, especially in pesticide users (hazard ratio = 1.96; 95% confidence interval: 1.11-3.47). Associations varied with tumor subtypes and kinds of crop and animal farming. The main increases in risk were observed for meningiomas in pig farmers and in farmers growing sunflowers, beets and potatoes and for gliomas in farmers growing grasslands. In most cases, more pronounced risk excesses were observed among pesticide applicators. Even if we cannot completely rule out the contribution of other factors, pesticide exposures could be of primary concern to explain these findings.

Dietary and Alcohol Intake and Central Nervous System Tumors in Adults: Results of the CERENAT Multicenter Case-Control Study.

BACKGROUND: Little is known about the relationship between diet and central nervous system (CNS) tumors, especially in terms of their histological subtypes. This study investigated the overall associations between food groups, alcohol intake and CNS tumors, and in particular about the associations between neuroepithelial tumors and meningiomas. METHODS: Data were collected through the CERENAT (CEREbral tumors: a NATional study) case-control study conducted in France during the period 2004-2010. Data were available for 1,479 subjects (494 cases, including 201 neuroepithelial tumors, 193 meningiomas, 100 other CNS tumors, and their 985 matched controls). Conditional logistic regressions for matched sets were adjusted based on the participants' educational level, occupation, smoking status and frequency of food group consumption. RESULTS: A heavy consumption of grilled meat and poultry was associated with neuroepithelial tumors in a dose-related relationship (ORQ4vsQ1 = 3.72, 95% CI 1.62-8.52, p = 0.005). Higher fruit and vegetable intake was inversely associated with meningiomas (for fruits: ORQ4vsQ1 = 0.38, 95% CI 0.17-0.87, p = 0.06, for vegetables ORQ4vsQ1 = 0.26, 95% CI 0.11-0.62, p = 0.007). Consumption of alcohol on a daily basis was inversely associated with CNS tumors especially for meningiomas (ORQ4vsQ1 = 0.33, 95% CI 0.18-0.61, p = 0.001). CONCLUSIONS: Results obtained in terms of grilled meat, fruits and vegetables consumption were in line with those published in epidemiological literature. Contradictions in results between neuroepithelial tumors and meningiomas confirmed the need to analyze the effects of dietary factors on the basis of the histological subtypes of CNS tumors.

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

UNLABELLED: 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.

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.

Intergenerational Transmission of Parental Adverse Childhood Experiences and Children's Outcomes: A Scoping Review.

Adverse childhood experiences (ACEs) are among the leading environmental causes of morbidity and mortality. Extending research on within-generation effects, more recent scholarship has explored between-generation consequences of ACEs. Despite growing interest in the intergenerational effects of parents' ACEs on children's outcomes, this line of scholarship has yet to be coalesced into a comprehensive review. The current study is a scoping review on the intergenerational transmission of parental ACEs and children's outcomes. Ten databases such as PubMed, APA PsycArticles, and Social Work Abstracts were searched. To be included, empirical studies must have been published in English and analyzed associations between a cumulative measure of at least four parental ACEs and children's outcomes. Sixty-eight studies qualified for the review and, among these, 60 were published in the most recent 5 years (2018-2022). Fifty-one studies had sample sizes smaller than 500, and 55 focused on the effect of maternal ACEs. Nearly all studies demonstrated that parental ACEs could affect children's outcomes directly or indirectly via mechanisms like maternal mental health problems or parenting-related factors. By scoping the extant literature, this review advances the knowledge base regarding the intergenerational impacts of parental childhood trauma and children's outcomes. It also reveals methodological limitations that should be addressed in future research to strengthen causal inferences along with practical implications for interventions that aim to interrupt the intergenerational transmission of trauma.

Prenatal Exposure to Intimate Partner Violence and Child Developmental Outcomes: A Scoping Review Study.

Pregnant women face an increased risk of intimate partner violence (IPV). In addition to the risk of violence faced by women, there is a dual concern for risk of harm to the fetus. Expanding knowledge on childbirth outcomes, other domains of children's development have been examined in recent literature. Yet, there is limited comprehensive knowledge in the area. This scoping review study, informed by ecobiodevelopmental theory, mapped evidence associating prenatal IPV exposure and children's development. We searched eight databases, including PubMed, CINAHL, and ERIC. Thirty-one empirical studies published in English that associated prenatal IPV exposure and children's development were eligible for our review. Included studies were published between 2006 and 2022, with 39% published in the most recent 5 years. Eighteen studies had sample sizes smaller than 500, and 21 were atheoretical; six failed to consider covariates. Reviewed studies showed adverse effects of prenatal IPV exposure on psychological, behavioral, physical health, and physiological outcomes, either directly or indirectly via mechanisms such as maternal behavioral health. Due to inconsistency in results and a lack of empirical evidence, however, social and cognitive outcomes were identified as needing further research to enhance our understanding of the global and domain-specific effects of prenatal IPV exposure. Prospective longitudinal studies, driven by theories of causal mechanisms, which adjust for empirically qualified confounders, will be critical to inform practice and policy to promote healthy development of prenatally IPV-exposed children. Incorporating strengths/asset-focused outcomes and examining contextual factors and sex/gender specific effects may advance the knowledge in this area.

Occupational and residential exposure to electromagnetic fields and risk of brain tumors in adults: a case-control study in Gironde, France.

The etiology of brain tumors remains largely unknown. Among potential risk factors, exposure to electromagnetic fields is suspected. We analyzed the relationship between residential and occupational exposure to electromagnetic field and brain tumors in adults. A case-control study was carried out in southwestern France between May 1999 and April 2001. A total of 221 central nervous system tumors (105 gliomas, 67 meningiomas, 33 neurinomas and 16 others) and 442 individually age- and sex-matched controls selected from general population were included. Electromagnetic field exposure [extremely low frequency (ELF) and radiofrequency separately was assessed in occupational settings through expert judgement based on complete job calendar, and at home by assessing the distance to power lines with the help of a geographical information system. Confounders such as education, use of home pesticide, residency in a rural area and occupational exposure to chemicals were taken into account. Separate analyses were performed for gliomas, meningiomas and acoustic neurinomas. A nonsignificant increase in risk was found for occupational exposure to electromagnetic fields  [odds ratio (OR = 1.52, 0.92-2.51)]. This increase became significant for meningiomas, especially when considering ELF separately [OR = 3.02; 95 percent confidence interval (95% CI) =1.10-8.25]. The risk of meningioma was also higher in subjects living in the vicinity of power lines (<100 m), even if not significant (OR = 2.99, 95% CI 0.86-10.40). These data suggest that occupational or residential exposure to ELF may play a role in the occurrence of meningioma.

Neurobehavioral effects of long-term exposure to pesticides: results from the 4-year follow-up of the PHYTONER study.

OBJECTIVE: The aim of the PHYTONER study is to investigate the role of pesticides on neurobehavioral performances in French vineyard workers. METHODS: 929 workers affiliated to the health insurance system for farmers in the Bordeaux area of south-western France were enrolled in the study in 1997-1998. They were contacted for a first follow-up in 2001-2003. Participants completed a questionnaire and nine neurobehavioral tests. They were classified according to their life-long pesticide exposure, as directly exposed, indirectly exposed or non-exposed. Educational level, age, sex, alcohol consumption, smoking, psychotropic drug use and depressive symptoms were taken into account in the analysis. RESULTS: 614 subjects were available for investigation at follow-up. Follow-up analysis confirmed that the risk of obtaining a low performance on the tests was higher in exposed subjects, with ORs ranging from 1.35 to 5.60. Evolution of performances over the follow-up period demonstrated that exposed subjects had the worst decreases in performance. The risk of having a two-point lower score on the Mini-Mental State Examination was 2.15 (95% CI 1.18 to 3.94) in exposed subjects. CONCLUSION: These results suggest long-term cognitive effects of chronic exposure to pesticides and raise the issue of the risk of evolution towards dementia. The PHYTONER study is the first to provide prospective data on the natural history of neurological disorders associated with pesticide exposure.

Increased risk of central nervous system tumours with carbamate insecticide use in the prospective cohort AGRICAN.

BACKGROUND: Pesticide exposures are suspected to be implicated in the excess of central nervous system (CNS) tumours observed in farmers, but evidence concerning individual pesticides remains limited. Carbamate insecticides, used on a wide range of crops, have shown evidence of carcinogenicity in some experimental studies. In the cohort AGRICAN (AGRIculture & CANcer), we assessed the associations between potential exposures to carbamate insecticides and the incidence of CNS tumours, overall and by histological subtype. METHODS: AGRICAN enrolled 181 842 participants involved in agriculture. Incident CNS tumours were identified by linkage with cancer registries from enrolment (2005-07) until 2013. Carbamate exposure was assessed by combining information on lifetime periods of pesticide use on crop or livestock and the French crop-exposure matrix PESTIMAT, individually for each of the 19 carbamate insecticides registered in France since 1950. Associations were estimated using proportional hazards models with age as the underlying time scale, adjusting for gender, educational level and smoking. RESULTS: During a 6.9-year average follow-up, 381 incident cases of CNS tumours occurred, including 164 gliomas and 134 meningiomas. Analyses showed increased risks of CNS tumours with overall exposure to carbamate insecticides and linear trends with duration of use of each carbamate. Considering tumour subtypes, hazard ratios for gliomas ranged from 1.18 for thiofanox to 4.60 for formetanate, and for meningiomas from 1.51 for carbaryl to 3.67 for thiofanox. CONCLUSIONS: Findings reinforce carcinogenicity evidence for already suspected active ingredients and draw attention to additional active ingredients, notably used on fruit trees, vineyards, potatoes and beets.

Agricultural exposures to carbamate herbicides and fungicides and central nervous system tumour incidence in the cohort AGRICAN.

BACKGROUND: Pesticides exposures could be implicated in the excess of Central Nervous System (CNS) tumors observed in farmers, but evidence concerning individual pesticides remains limited. Carbamate derivative pesticides, including herbicides and fungicides (i.e. (thio/dithio)-carbamates), have shown evidence of carcinogenicity in experimental studies in animals. In the French AGRICAN cohort, we assessed the associations between potential exposures to carbamate herbicides and fungicides and the incidence of CNS tumors, overall and by histological subtype. METHODS: AGRICAN enrolled 181,842 participants involved in agriculture. Incident CNS tumors were identified by linkage with cancer registries from enrollment (2005-2007) until 2013. Individual exposures were assessed by combining information on lifetime periods of pesticide use on crops and the French crop-exposure matrix PESTIMAT, for each of the 14 carbamate and thiocarbamate herbicides and the 16 carbamate and dithiocarbamate fungicides registered in France since 1950. Associations were estimated using proportional hazard models with age as the underlying timescale, adjusting for gender, educational level and smoking. RESULTS: During an average follow-up of 6.9 years, 381 incident cases of CNS tumors occurred, including 164 gliomas and 134 meningiomas. Analyses showed increased risks of CNS tumors with overall exposure to carbamate fungicides (Hazard Ratio, HR = 1.88; 95% CI: 1.27-2.79) and, to a lesser extent, to carbamate herbicides (HR = 1.44; 95% CI: 0.94-2.22). Positive associations were observed with specific carbamates, including some fungicides (mancozeb, maneb, metiram) and herbicides (chlorpropham, propham, diallate) already suspected of being carcinogens in humans. CONCLUSIONS: Although some associations need to be corroborate in further studies and should be interpreted cautiously, these findings provide additional carcinogenicity evidence for several carbamate fungicides and herbicides.

Pesticide use in agriculture and Parkinson's disease in the AGRICAN cohort study.

Background and Aim: Epidemiological studies have reported an increased risk of Parkinson's disease (PD) in farmers exposed to pesticides, but no clear conclusion can be drawn on the type of pesticide and duration of use associated with an effect. In the French agricultural cohort AGRICAN, we assessed associations between PD and pesticide use according to the types of livestock and crops grown, including exposure to some active ingredients with duration of use. Methods: Self-reported PD and history of lifetime exposure to 13 crops and 5 types of animals and pesticide use were collected at enrolment (2005-07) among 181 842 participants. Exposure to selected active ingredients and duration of use lifelong were assessed with the crop-exposure matrix PESTIMAT. Associations between pesticide use and PD were estimated by logistic regression according to crops and livestock, adjusted for sex, age, educational level, smoking status and alcohol consumption. Results: PD was reported by 1732 subjects (1.2%) at enrolment in the cohort. Pesticide use lifelong was associated with an increased risk of PD in all types of activities [odds ratio (OR) = 1.31 (cattle) to 1.79 (peas), P < 0.05]. Rotenone, diquat, paraquat and several dithiocarbamates were associated with an increased risk of PD [OR = 1.31 (cuprobam) to 1.57 (rotenone)], especially in farmers with the longest exposure. Conclusions: Our work suggests that the risk of PD is increased in farmers exposed to pesticides on several French crops and livestock, and supports additional evidence of an association of PD with dithiocarbamate fungicides, rotenone and the herbicides diquat and paraquat.