Clément Piel

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

Background and Aim Epidemiological studies have reported an increased risk of Parkinsons 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.

Allergic conditions and risk of glioma and meningioma in the CERENAT case-control study

Inverse association between allergic conditions and glioma risk has been consistently reported in epidemiological studies with little attention paid to potential environmental confounders; the association with meningioma risk is less consistent. We examined the association between allergy history and risk of glioma and meningioma in adults using data from the CERENAT (CEREbral tumors: a NATional study) multicenter case-control study carried out in 4 areas in France in 2004–2010. Participants’ histories of doctor-diagnosed allergic asthma, eczema, rhinitis/hay fever and other allergic conditions were collected at onset through a detailed questionnaire delivered in a face-to-face interview. Conditional logistic regression for matched sets was adjusted for participants’ educational level and mobile phone use. A total of 273 glioma cases, 218 meningioma cases and 982 matched controls selected from the local electoral rolls were analyzed. A significant inverse association was found between glioma and a history of any allergy (OR 0.52, 95% CI 0.36–0.75), with a dose–effect relationship with the number of allergic conditions reported (p-trend = 0.001) and a particularly strong association with hay fever/allergic rhinitis (OR 0.46, 95% CI 0.30–0.72). Interestingly, associations with glioma risk were more pronounced in women. For meningioma, no association was observed with overall or specific allergic conditions. Our findings confirmed the inverse association between allergic conditions and glioma risk but questioned the role of allergy in meningioma risk. Future research is needed to clarify the biological mechanism of overall allergy and allergic rhinitis on glioma and to confirm the different effect by gender.

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.

1185 Maternal cumulative exposure to extremely low frequency electromagnetic fields and pregnancy outcomes in the elfe cohort

Objectives To study the relations between maternal cumulative exposure to extremely low frequency electromagnetic fields (ELF MF) and the risk of moderate prematurity and small for gestational age within the birth cohort Elfe. Methods The Elfe study included 18,329 infants born at 33 weeks of amenorrhea or more in France in 2011 and was designed to follow children until 20 years of age. Gestational age and anthropometric data at birth was collected in medical records and small for gestational age was defined according to a French customised growth standard. During interviews, mothers were asked to report their job status during pregnancy. If employed, their occupation was coded according to the ISCO-88 classification and the date on which they stopped their work was recorded. Cumulative exposure to ELF MF during pregnancy was assessed, for both mothers who worked and those who didn’t work during pregnancy, using a recently updated job-exposure matrix (JEM). Cumulative exposure was considered as a categorical variable (<17.5, 17.5–23.8, 23.8–36.2, 36.2–61.6 or ≥61.6 µT-days), as a binary variable (<44.1 and ≥44.1 µT-days) and as a continuous variable. Associations were analysed by logistic regression, adjusting for mother’s lifestyle factors, sociodemographic characteristics and some mother’s medical history during and before pregnancy. Analyses were restricted to single births and to complete values for the pregnancy outcomes (n=16,733). Results Cumulative exposure was obtained for 96.0% of the mothers. Among them, 37.5% were classified in the 23.8–36.2 µT-days category, but high exposures were rare: 1.3% in the ≥61.6 µT-days category and 5.5% in the ≥44.1 µT-days category. No significant association was observed between maternal cumulative exposure and moderate prematurity and small for gestational age. Conclusion This large population-based study does not suggest that maternal exposure to ELF MF during pregnancy is highly associated with risk of moderate prematurity or small for gestational age.

Lung cancer risk and occupational exposures in crop farming: results from the AGRIculture and CANcer (AGRICAN) cohort

Objectives Farmers are considered at lower risk of lung cancer. However, specific tasks can expose them to hazardous air contaminants such as pesticides, diesel exhaust and mineral dust. This study aimed to assess the associations between various crops and related tasks and the risk of lung cancer, overall and by histological subtypes. Methods AGRIculture and CANcer is a prospective French cohort of individuals affiliated to the agricultural health insurance scheme. Incident lung cancers (n=897) were identified by cancer registries from enrolment (2005–2007) to 2013. Data on crop and livestock exposure during lifetime were obtained from the enrolment questionnaire. We used a Cox model with attained age as timescale, adjusted for gender, smoking history and exposure to cattle and horses. Effects of duration and surface were assessed and analyses stratified on gender and smoking status were performed. Results Winegrowers were at higher risk of adenocarcinoma (HR=1.27 (95% CI 0.94 to 1.72)). We also found an association between pea growing and small cell lung cancer: significant effect of duration (ptrend=0.04) and the suggestion of a surface–effect relationship (ptrend=0.06); increased risk (HR=2.38 (95% CI 1.07 to 5.28)) for pesticide users; and significant effect of duration (ptrend=0.01) for harvesters. The risk of squamous cell carcinoma was increased for sunflower growing (HR=1.59 (95% CI 0.97 to 2.62), fruit-tree pruning (HR=1.44 (95% CI 0.92 to 2.27)) and pesticide use on beets (HR=1.47 (95% CI 0.92 to 2.34)). Corn and/or wheat/barley growers were at lower risk of lung cancer. Conclusions Our results suggest associations between lung cancer and several crop-related tasks, even if we cannot rule out some chance findings due to multiple comparisons.

Maternal cumulative exposure to extremely low frequency electromagnetic fields and pregnancy outcomes in the Elfe cohort

OBJECTIVES To study the relations between maternal cumulative exposure to extremely low frequency electromagnetic fields (ELF EMF) and the risk of moderate prematurity and small for gestational age within the Elfe cohort. METHODS The Elfe study included 18,329 infants born at 33weeks of gestation or more in France in 2011 and was designed to follow the children until 20years of age. Gestational age and anthropometric data at birth were collected in medical records and small for gestational age was defined according to a French customized growth standard. During interviews, mothers were asked to report their job status during pregnancy. If employed, their occupation was coded according to the International Standard Classification of Occupations 1988 and the date on which they stopped their work was recorded. Cumulative exposure to ELF EMF during pregnancy was assessed, for both mothers who worked and those who did not during pregnancy, using a recently-updated job-exposure matrix (JEM). Cumulative exposure was considered as a categorical variable (<17.5, 17.5-23.8, 23.8-36.2, 36.2-61.6 or ≥61.6μT-days), a binary variable (<44.1 and ≥44.1μT-days) and a continuous variable. Associations were analyzed by logistic regression, adjusting for the mothers lifestyle factors, sociodemographic characteristics and some mothers medical history during and before pregnancy. Analyses were restricted to single births and to complete values for the pregnancy outcomes (n=16,733). RESULTS Cumulative exposure was obtained for 96.0% of the mothers. Among them, 37.5% were classified in the 23.8-36.2μT-days category, but high exposures were rare: 1.3% in the ≥61.6μT-days category and 5.5% in the ≥44.1μT-days category. No significant association was observed between maternal cumulative exposure and moderate prematurity and small for gestational age in this exposure range. CONCLUSION This large population-based study does not suggest that maternal exposure to ELF EMF during pregnancy is highly associated with risks of moderate prematurity or small for gestational age.

Occupational exposure to pesticides: development of a job-exposure matrix for use in population-based studies (PESTIPOP)

Occupational exposure to pesticides concerns a wide population of workers not only in agriculture. The reliability of self-reported information on pesticide use is questionable because of the diversity of use. The PESTIPOP job-exposure matrix has been designed to assess pesticide occupational exposure in the general population. The matrix is composed of two axes: the first axis corresponding to jobs (combinations of occupations and industries) and the second one to pesticide exposure. The estimated exposure metric is the probability of exposure coupled with a reliability assessment (low, medium or high). These metrics were defined by combining different sources: (1) an a priori expert assessment (Agricultural industry experts); (2) data from a multicenter case–control study on brain tumors in the general population (occupational history, specific questionnaires); and (3) an a posteriori expert assessment based on the data of a case–control study. So far, 2559 jobs have been identified and 209 (8%) were found to be exposed to pesticides. Jobs with agricultural exposure had a higher exposure probability than jobs with non-agricultural exposure (wood preservation, park maintenance, pest control). Indirect exposure was more frequent than direct exposure. The PESTIPOP matrix will be transcoded into international classifications for use in epidemiological studies.

1161 Central nervous system tumours and agricultural exposures in the prospective cohort agrican

Background Studies in farmers suggest a possible role of pesticides in the occurrence of Central Nervous System (CNS) tumours. However, scientific evidences are still insufficient because of methodological limits such as study designs, sample sizes or exposure assessments. We aimed to study the associations between occupational exposures to a range of farming activities and the incidence of primary CNS tumours, globally and by subtiles. Methods In the French prospective agricultural cohort AGRICAN, 181,842 participants completed the enrollment questionnaire over the period 2005–2011. Associations between exposures to 13 crops and 5 livestock and the risks of CNS tumours (identified through linkage to cancer registries) were estimated using Cox models with age as underlying timescale, adjusted on gender, professional status and educational level. Effects of specific tasks, duration and periods of exposure were also assessed. Results During a follow-up of 5.2 years in average, 273 incident cases of CNS tumours occurred, including 126 gliomas and 87 meningiomas. Analyses showed increased risks of CNS tumours that ranged from 10% to 85% with 11 of the 13 crops, significant in farmers growing peas and beets. Concerning gliomas, increases in risk were seen for all agricultural activities. A significant risk excess was observed in pesticide users (HR = 1.73; 95% CI: 1.05–2.84), especially in vine-growers performing treatments (HR = 1.86; 95% CI: 1.06–3.26). For meningiomas, significant positive associations were observed in sunflower growers, beet growers and hog raisers. A three-fold increased risk was seen in farmers using pesticides on potatoes (HR = 2.93; 95% CI: 1.15–7.47). Conclusion In the largest prospective agricultural cohort, we observed increased risks of CNS tumours among farmers. Even if we cannot completely rule out the contribution of other agricultural factors, pesticide exposures are our main hypothesis to explain these findings. Further analyses will explore the effects of some specific pesticides using the crop-exposure matrix PESTIMAT.