Search

Introduction Agricultural work can expose workers to potentially hazardous agents including known and suspected carcinogens. Objectives We aimed to evaluate the cancer incidence in agricultural cohorts in an international consortium, AGRICOH, relative to the respective general populations. Methods For 24 cancer sites/types and all cancers combined, we estimated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) in eight cohorts that were linked to respective cancer registries: France (AGRICAN: n=128,101), the United States (AHS: n=51,165, MESA: n=2,177), Norway (CNAP: n=43,834), Australia (2 cohorts combined, Australian Pesticide Exposed Workers and Victorian Grain Farmers: n=13,134), Republic of Korea (KMCC: n=8,432), and Denmark (SUS: n=1,899). We then combined the SIR estimates across cohorts by random-effects meta-analysis. Results During nearly 2,800,000 person-years, 23,188 cancers were diagnosed. We observed an elevated risk for melanoma of the skin (number of cohorts included=3, meta-SIR=1.18, 95% CI: 1.01–1.38) and multiple myeloma in women (n=4, meta-SIR=1.27, 95% CI: 1.04–1.54) and prostate cancer (n=6, meta-SIR=1.06, 95% CI: 1.01–1.12) compared to the general population. For several cancer sites, including bladder, breast (female), colorectum, esophagus, larynx, lung, and pancreas and all cancers combined, the risk was lower in the agricultural cohorts than in the general population (n=7, sex-adjusted meta-SIR for all cancers combined=0.83, 95% CI: 0.77–0.90). The direction of risk was mostly consistent across cohorts while for some cancer sites, such as liver and lung in men and women, and stomach, colorectum, and skin in men, the SIR varied greatly across cohorts. Conclusion Our findings suggest that agricultural workers have a lower risk of various cancers and an elevated risk for prostate cancer, multiple myeloma (female), and melanoma of skin (female) compared to the general population. The observed excesses and deficits of cancer incidence in agricultural workers may be largely due to underlying differences in risk factors and warrant further investigation of specific agricultural exposures.

Introduction Many studies have shown a link between exposure to pesticides and a higher level of DNA damage. However, longitudinal studies are rare and little is known about long term DNA damage and cancer risk in exposed subjects. Objectives i) Quantify DNA damage for the women included in a French agricultural cohort at two time points, ii) study the relationship between DNA damage and agricultural tasks, and iii) between DNA damage and cancer incidence. Methods 320 female agricultural workers were enrolled from 1997 to 2000 and completed a face-to-face questionnaire. 245 gave a blood sample at enrolment (T0). Ten years later, 104 donated another sample (T10). Using the comet assay with an internal historical negative control, we quantified DNA damage in PBMC on 200 nuclei using a 4-category visual scoring system. Results At enrolment, there were no differences in DNA damage for farm owners/co-owners (n=135, 55%, p=0.84), or participants in livestock tasks within our study population (n=159, 65%, p=0.23). Pesticide exposure through application of anti-parasites to livestock (n=138, 56%, p=0.25) and disinfection of milking equipment (n=117, 48%, p=0.78) did not influence DNA damage. However, damage tended to be higher for those implicated in milking (n=109, 44%, p=0.18). Women who carried out administrative (n=180, 73%) and domestic tasks (n=213, 87%) tended to have lower damage scores (p=0.08 and p=0.07, respectively), as well as women who undertook other tasks had significantly lower damage (p=0.04) than those not involved. From enrolment to end of 2017, 37 incident cancer cases were diagnosed, of which 21 were breast cancer cases. No association was found between DNA damage and cancer incidence (p=0.45). Conclusion Occupational exposure in the agricultural field could be evaluated using the comet assay. Women’s involvement to tasks not related to farm upkeep show a lower level of DNA damage than those not undertaking these tasks.

Introduction Pesticide exposures increase the risk of chronic diseases in farmers. Knowledge of exposure levels are needed for epidemiological studies and for regulation. In pesticide registration process, operator’s exposure is predicted by the AOEM, set up in 2014 by the European Food Safety Authority, based on thirty studies conducted by the pesticide industry. To date, we are not aware of any field study comparing predicted data with those measured under real working conditions. Objective We aimed to compare operators’ exposures during treatment days in apple-growing under non-controlled conditions of work and values predicted by AOEM. Methods Thirty apple growers from the French CANEPA study, were observed applying two fungicides (captan/dithianon) in 2016–2017. Dermal exposure was measured by body patches and cotton gloves. Detailed parameters about the farm, operator, application day, spraying equipment and personal protective equipment (PPE) used were recorded. For each observation, the corresponding exposure was calculated by the AOEM, using these parameters. The relationship between measured and calculated exposures was studied by linear regression. Results Significant linear correlation was observed between calculated and measured daily exposures. Overall, the model overestimated daily exposure and exposure during application. However exposure was underestimated at mixing/loading in many observations, especially when the operator wore long working clothes or gloves. Conclusion The AOEM model did not appear conservative in the sense that it did not overestimate exposures in all circumstances. More specifically: 1) the overestimation at spraying appeared a consequence of the overestimation of daily treated area, 2) the protection provided by PPE appeared overestimated, 3) mixing/loading exposure, a phase in which operators are exposed to concentrated products, appeared underestimated. These discrepancies could be due to optimal working conditions (larger farms, newer equipment) under which industries’ studies are conducted that are not representative of operators’ actual working conditions in fruit growing.

Introduction Data on pesticide exposure during occupational knapsack spraying is scarce. Objective This field study assessed its levels and determinants. Methods Private landscapers/gardeners and municipal workers in the Normandy region, France, were enrolled between March and May 2011. They were equipped with cotton undergarments and gloves to assess actual dermal exposure to glyphosate, and with cotton coveralls separately for each phase to assess the contribution of mixing/loading and spraying and the distribution on 11 body areas. A field monitor observed the whole workshift and filled in a standardized observation grid. Respiratory samplings were also systematically performed, and additional surface wipes obtained from various equipment. Results Twenty-four workers were included, all men, with a median age of 40 years old, and a median experience in pesticide use of 14.5 years. The total work time varied between 110 and 360 min (median 210), and the number of mixing/loading-spraying cycles ranged from 1 to 8 (median 2). Spraying was more exposing than mixing/loading for all body parts except hands. Hands contributed to nearly 90% of body exposure during mixing/loading, and 30% during spraying, followed by back for spraying (14%). The median actual body contamination was 5,256 µg, with a median of 4,620 µg for hands. Dermal PPE use was associated with a decreased actual dermal exposure (estimate -0.81, p=0.001), and the number of mixing/spraying cycles with an increased exposure (more or less than 2 cycles: estimate 0.85, p=0.0006). Conclusion Given their large contribution to overall dermal exposure, caution should be paid to handwashing and common hygiene rules during knapsack spraying. To our knowledge, our study is the first to report a high contamination of the back during spraying.

Objectives In few retrospective studies, prolonged time-to-pregnancy (TTP) was observed for women exposed to pesticides especially in flower production. The present study investigated time-to-pregnancy in the AGRICAN cohort. Methods Analyses were performed on 616 women reporting a pregnancy (2005 to 2017), and data on agricultural activities performed before the last pregnancy was retrospectively collected. Fecundability odds ratios (fOR) were estimated using a discrete time analogue of Cox proportional hazard model adjusted on maternal and paternal age, body mass index (BMI), and alcohol consumption. Results A decrease in fecundability was non-significantly associated with farm work (adjusted fOR = 0.86; 95% confidence interval [CI]: 0.71 to 1.05). Decreases were also observed for nightwork (afOR = 0.75; 95% CI: 0.49 to 1.15) and exposure to vibrations (afOR = 0.68; 95% CI: 0.43 to 1.09). Conclusion Women working on a farm before conception appeared to experience a longer TTP. Negative associations were suggested for some agricultural activities and working conditions.

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, 0.94-2.24) and significantly trebled in open field agriculture (OR=3.58, 1.20-0.70). 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.

Context The greenspace sector includes a broad range of occupations: gardeners, landscapers, municipal workers, maintenance operators of public facilities, golf-course employees and other sports facilities, horticulturists, plant and tree nursery workers etc. The health impact of occupational pesticide exposure has mainly been studied among farmers. Other professionals such as greenspace workers are also extremely exposed, presenting specific exposure features (practices, types of pesticide used). The aim of this review was to summarize epidemiological literature that examine the relationship between pesticide exposure and the risk of cancer and long-term health effects in greenspace workers. Method Six main groups of greenspace workers were identified and examined through a systematic literature review based on PubMed and Scopus. The studies were then grouped according to their design, health outcomes and the type of population studied. Results Forty-four articles were selected among the 1679 identified. Fifteen studies were conducted exclusively among greenspace workers, while ten also studied these workers with other pesticide applicators. Six were cohorts from the general population in which greenspace workers were identified. Elevated risks were found in several studies for leukaemia, soft-tissue sarcoma, multiple myeloma, non-Hodgkin lymphoma and Parkinson's disease. Discussion The majority of studies used rough parameters for defining exposure such as job titles which could lead to the misclassification of exposure, with the risk of false or positive negative conclusions. Health outcomes were mainly collected through registries or death certificates, and information regarding potential confounders was often missing. Conclusion The review identified only 15 studies conducted exclusively among greenspace workers. Elevated risk was found for several sites of cancer and Parkinson's diseases. Further epidemiological research is needed, conducted specifically on these workers, to better characterize this population, its exposure to pesticides and the related health effects.

International audience; 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.

International audience; PURPOSE:Epidemiological studies have found an increased risk of multiple myeloma (MM) in farmers. Few studies have investigated the detailed circumstances of occupational pesticide exposure which could explain these increased risks (pesticide use on crops, seeds or on animals, contact with treated crops) and the role of other exposures. In the Agriculture and Cancer cohort (AGRICAN), we assessed the associations between MM and crop- or animal-related activities, with specific attention to pesticide exposure via use on animals and crops or contact with treated crops and to disinfectant exposure.METHODS:Analyses concerned 155,192 participants, including 269 incident MM identified by cancer registries from enrolment (2005-2007) to 2013. Cox models using attained age as time scale were run to calculate hazard ratios (HR) and 95% confidence intervals (CI).RESULTS:MM risk was increased in farmers (i) who started using pesticides on crops in the 1960s, especially among those applying pesticides on corn (≥ 20 years: HR 1.73, 95% CI 1.08, 2.78, p for trend

International audience; 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.

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.

Context.—Pleural mesothelioma is a rare cancer with an often-challenging diagnosis because of its potential to be a great mimicker of many other tumors. Among them, primary lung and breast cancers are the 2 main causes of pleural metastasis. The development and application of targeted therapeutic agents have made it even more important to achieve an accurate diagnosis. In this setting, international guidelines have recommended the use of 2 positive and 2 negative immunohistochemical biomarkers.Objectives.—To define the most highly specific and sensitive minimum set of antibodies for routine practice to use for the separation of epithelioid malignant mesothelioma from lung and breast metastasis and to determine the most relevant expression cutoff.Design.—To provide information at different levels of expression of 16 mesothelial and epithelial biomarkers, we performed a systematic review of articles published between 1979 and 2017, and we compared those data to results from the Mesothelioma Telepathology Network (MESOPATH) of the standardized panel used in routine practice database since 1998.Results.—Our results indicate that the following panel of markers—calretinin (poly)/thyroid transcription factor 1 (TTF-1; clone 8G7G3/1) and calretinin (poly)/estrogen receptor-α (ER-α; clone EP1)—should be recommended; ultimately, based on the MESOPATH database, we highlight their relevance which are the most sensitive and specific panel useful to the differential diagnosis at 10% cutoff.Conclusions.—Highlighted by their relevance in the large cohort reported, we recommend 2 useful panels to the differential diagnosis at 10% cutoff.

International audience; Objectives: Nanoscale particles (1-100 nm) can be of natural origin, and either intentionally or unintentionally produced by human activities. Toxicological data have suggested a possible carcinogenic effect of such particles. The aim of this study was to estimate the association between occupational exposure to nanoscale particles and risk of lung cancer, pleural mesothelioma and brain tumors in adults.Methods: Three French population-based case-control studies were analyzed: 1) the ICARE study including 2,029 lung cancer cases and 2,591 controls; 2) the PNSM study including 371 pleural mesothelioma cases and 730 controls and 3) the CERENAT study including 257 brain tumor cases and 511 controls. Occupational exposure to unintentionally emitted nanoscale particles (UNPs) was retrospectively assessed by a job exposure matrix providing a probability and a frequency of exposure.Results: In adjusted analyses among men, significant associations between occupational exposure to UNPs and lung cancer (OR=1.51; 95% CI: 1.22-1.86 and brain tumors (OR=1.69; 95% CI: 1.17-2.44) were observed. No increased OR was observed for pleural mesothelioma (OR=0.78; 95% CI: 0.46-1.33).Conclusion: This is the first study showing positive associations between occupational exposure to UNPs and increased risk of lung cancer and brain tumors. These preliminary results should encourage further epidemiological research.

Background: Diesel exhaust is a known lung carcinogen. Farmers use a variety of dieselized equipment and thus may be at increased risk of lung cancer, but farm exposures such as endotoxins may also be protective for lung cancer. Objectives: We evaluated the relative risk of incident lung cancer, including histological subtype, from enrollment (1993–1997) to 2010–2011 in relation to farm equipment use in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators and spouses in Iowa and North Carolina, USA. Methods: Farm equipment use was reported by 21,273 farmers and 29,840 spouses. Rate ratios (RRs) were estimated separately for farmers and spouses with Poisson regression models adjusted for smoking and other confounders. We conducted stratified analyses by exposure to animals or stored grain, a surrogate for endotoxin exposure. Results: Daily diesel tractor use (vs. no use) was positively associated with lung cancer in farmers (RR = 1.48; 95% CI: 0.87, 2.50; 35 exposed, 32 unexposed cases), particularly adenocarcinoma (RR = 3.39; 95% CI: 1.23, 9.33; 12 exposed, 7 unexposed cases). The association of adenocarcinoma with daily (vs. low/no) use of diesel tractors was stronger for farmers with no animal or stored grain exposures (RR = 6.23; 95% CI: 2.25, 17.25; 5 exposed, 18 unexposed cases) than among farmers with these exposures (RR = 1.19; 95% CI: 0.51, 2.79; 7 exposed, 27 unexposed cases) (p-interaction = 0.05). Conclusions: This study provides preliminary evidence of an increased risk of lung adenocarcinoma among daily drivers of diesel tractors and suggests that exposure to endotoxins may modify the impact of diesel exposure on lung cancer risk. Confirmation of these findings with more exposed cases and more detailed exposure information is warranted. Citation: Tual S, Silverman DT, Koutros S, Blair A, Sandler DP, Lebailly P, Andreotti G, Hoppin JA, Beane Freeman LE. 2016. Use of dieselized farm equipment and incident lung cancer: findings from the Agricultural Health Study Cohort. Environ Health Perspect 124:611–618; http://dx.doi.org/10.1289/ehp.1409238

Objectives Prostate cancer is one of the most frequent cancers among men worldwide. Its etiology is largely unknown, but an increased risk has been repeatedly observed among farmers. Our aim was to identify occupational risk factors for prostate cancer among farmers in the prospective cohort study AGRICAN. Methods Data on lifetime agricultural exposures (type of crops, livestock and tasks including pesticide use, re-entry and harvesting) were collected from the enrolment questionnaire. During the period from enrolment (2005–2007) to 31 December 2009, 1672 incident prostate cancers were identified. Hazard ratios (HR) were estimated using Cox regression analysis. Results We found an increased risk for cattle breeders using insecticides [HR 1.20, 95% confidence interval (95% CI) 1.01–1.42] with a significant dose–response relationship with number of cattle treated (P for trend 0.01). A dose–response relationship was also observed with the number of hogs (P for trend 0.06). We found an excess of prostate cancer risk among people involved in grassland activities, mainly in haymaking (HR 1.18, 95% CI 1.02–1.36). Pesticide use and harvesting among fruit growers were associated with an elevated prostate cancer risk, with a two-fold increased risk for the largest area. For potato and tobacco producers, an elevated prostate cancer risk was observed for almost all tasks, suggesting a link with pesticide exposure since all of them potentially involved pesticide exposure. Conclusions Our analysis suggests that the risk of prostate cancer is increased in several farming activities (cattle and hog breeding, grassland and fruit-growing) and for some tasks including pesticide use.

ObjectivesFarmers 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.MethodsAGRIculture 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.ResultsWinegrowers 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.ConclusionsOur results suggest associations between lung cancer and several crop-related tasks, even if we cannot rule out some chance findings due to multiple comparisons.

International audience; 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.

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.

Introduction Beyond pesticide exposure, farmers are likely to be exposed to several air pollutants. Some of them are of particular interest, either because of their known carcinogenic properties, for lung cancer (total dust, Diesel exhaust, crystalline silica,) or other cancer sites (mycotoxins) or because of a supposed protective effect on lung cancer risk (endotoxins). However, except for endotoxins, very few studies, assessed farmers’ exposure levels by individual samplings. Our study aims at describing the levels, and assessing the determinants, of agricultural exposure to these air pollutants. Methods We assessed French farmers’ individual exposure to several air contaminants: (1) inhalable endotoxins and mycotoxins during various tasks in several breedings (cattle, horse) and 3 crops (grassland, wheat/barley, peas); (2) respirable crystalline silica during harvesting of these 3 crops; (3) respirable elementary carbon during the use of Dieselized farm equipment. Inhalable dusts, up to 20 µ, were assessed in real time. Sampling was performed during the whole activity, and endotoxin exposure was also assessed for each task separately. Field monitors followed the farmers and collected detailed information on the activity. Results The field study is on-going, we already observed around 40 individual measurements in 20 different farms. The protocol was judged acceptable by the participants. Sampling duration ranges from 80 to 240 min, depending on the type of activity. First results from real-time dust measurements suggest a higher exposure during stables cleaning and mulching (mean concentration of inhalable dusts: 0.545 mg/m3). A total of several hundreds of measurements is expected in various types of farms and working conditions (number of animals, cultivated area, type of equipment). Discussion We hope our study will improve the assessment of occupational health hazards in agriculture, and thus primary prevention, by quantifying the levels of individual exposure to several air pollutants.

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

Introduction 2,6-Dinitroanilines included 15 herbicides, some of which are still used on a wide range of crops worldwide and in France, especially pendimethalin which was given special attention by the IARC. The aim of our analyses was to estimate the associations between LC and exposure to pendimethalin, benfluralin, butralin, ethalfluralin, nitralin, oryzalin, trifluralin -all once or still authorised in France-, in the French AGRIculture and CANcer (AGRICAN) cohort. Methods More than 1 80 000 people affiliated for at least 3 years to the agricultural health insurance scheme were enrolled between 2005 and 2007. A total of 563 incident LC were identified from enrollment to 2011. Data on crop exposure during lifetime (13 crops, specific tasks including pesticide use) were collected. The evaluation of potential exposure to each dinitroaniline relied on a specific crop-exposure matrix, PESTIMAT. Analyses were adjusted on smoking history, involvement in cattle and horse breeding, peas growing, exposure to farming activities during childhood. Results In the population, 16 533 people (11.2% of the cohort) were potentially exposed to one or more dinitroanillines. Pendimethalin and trifluralin were the most frequently used, but not associated to any increased risk of LC, nor was exposure to dinitroanillines in general. We observed an increased risk of adenocarcinoma for oryzalin exposure (HR=2.93[1.13–7.59], n=5 exposed cases), but with no linear effect with duration. Conclusion We did not found any increased risk of LC among pendimethalin users. Our results suggest a possible association of lung adenocarcinoma with oryzalin, currently authorised in France, especially on the vineyard.

International audience; IntroductionTo perform large scale metabolomic analyses, high throughput approaches are required. The direct introduction mass spectrometry (DIMS) approach appears to be very attractive to achieve this goal. However, processing DIMS data is still very challenging due to the large number of samples and the intrinsic complexity of the mass spectra.ObjectivesThe objective of this study is to develop a computational procedure, based on an innovative chemometric method, i.e. Independent component–discriminant analysis (IC–DA), for processing DIMS data.MethodMetabolomic fingerprints were obtained by direct introduction high resolution mass spectrometry (DI-HRMS) analysis of urine samples of subjects that had been professionally exposed to pesticides. Spectral data were processed using the developed IC–DA procedure. Results obtained from this method were compared to those obtained by the conventional Partial least squares–discriminant analysis (PLS–DA). For both the IC–DA and PLS–DA methods, a validation was performed based on a permutation test.ResultIC–DA results enabled a good detection of discriminant variables and a clear discrimination of control samples and exposure classes whereas a less striking discrimination was obtained with PLS–DA. Putative annotation of these variables was performed using metabolomic databases. Targeted correlation analysis was used for the detection of ions associated with the most discriminant variables, consolidating their identity assignment.ConclusionThis study demonstrated the efficiency of IC–DA to discriminate the different exposure groups. As well the improvement of high throughput metabolomic studies was provided by combining DI–HRMS with this new chemometric tool.

To elaborate and describe a large prospective agricultural cohort including males and females in France with various agricultural activities and to study causes of death. To date, few large prospective cohorts have been conducted among agricultural population. AGRIculture and CANcer cohort is a large prospective cohort of subjects in agriculture studying cancer among active and retired males and females, farm owners and workers, living in eleven areas of France with a population-based cancer registry. Enrollment was conducted from 2005 to 2007 with a postal questionnaire. In January 2008, 180,060 individuals (54 % males, 54 % farm owners, 50 % retired) were enrolled. Mortality was studied until December 2009 (605,956 person-years with standardized mortality ratio (SMR) by comparison with the general population of the areas. Over this period, 11,450 deaths 6,741 in men and 4,709 in women were observed, including 3,405 cancer-related deaths. SMRs were significantly reduced for global mortality (SMR = 0.68, 95 % CI 0.67–0.70 in males and SMR = 0.71, 95 % CI 0.69–0.73 in females) and for death by cancer (SMR = 0.67, 95 % CI 0.65, 0.70 in males and SMR = 0.76, 95 % C: 0.71, 0.80 in females). These results were mainly explained by less frequent smoking-related causes of death (lung cancer, cardiovascular diseases). Nonsignificant excesses of death were observed only for rheumatoid arthritis and arthrosis, suicides (in females), death for event of undetermined intent (in males) and breast cancer in male agricultural workers. These first results are the first ones obtained in France based on a large prospective agricultural cohort showing that farmers would be in healthier condition than the general population.

ContextExposure to inorganic arsenicals, including occupational use of pesticides, is carcinogenic to the lung (IARC group 1). However epidemiological data are scarce for agricultural exposures. This work assesses lung cancer (LC) risk, including duration-effect relationships, associated to arsenicals use in farming, by gender and histology.MethodsWe linked data from two French projects: (1) the Agriculture and Cancer (AGRICAN) cohort, a large prospective cohort of farmers and people affiliated to the French agricultural insurance scheme and (2) the Pesticide Matrix (PESTIMAT), a crop-exposure matrix. Incident lung cancer cases were collected and their histological subtype ascertained from cancer registries, from enrolment (2005–2007) to December 31 st 2013. The enrolment questionnaire included items on smoking history, and the involvement in 18 different breedings/crops and specific tasks, including pesticide application, with years of beginning and end. We performed Cox models, with age as timescale, adjusted on gender, smoking, and two activities found to be protective in previous analyses – cattle breeding and corn growing. The reference group included farmers having never applied any pesticide on any crop. We assessed risks for each inorganic compound (lead, sodium, aluminum, copper and calcium arsenate) and for overall exposure.ResultsNearly 10% (n=14 359 people) of the population was potentially exposed to arsenicals, in vineyard growing before 2001, or in fruit-tree or potato growing before 1973. We observed 98 incident LC among exposed people. Only women exhibited a higher risk of LC (HR 3.14 95% CI(1.42–6.96) for exposure to any compound, n=7 exposed cases, all adenocarcinomas), but with no duration-effect relationship. Risks were significantly elevated for lead, copper and sodium arsenate.ConclusionWe found an increased risk of LC, especially adenocarcinomas, among women. At this stage, exposure assessment was broad: the use of an exposure index, based on probability, frequency and intensity of use, will help refine the analyses.

BackgroundPesticide exposures are suspected to be implicated in the excess of Central Nervous System (CNS) tumors 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 and CANcer), we assessed the associations between potential exposures to carbamate insecticides and the incidence of CNS tumors, overall and by histological subtype.MethodsAGRICAN enrolled 181 842 participants involved in agriculture. Incident CNS tumors were identified by linkage with cancer registries from enrolment (2005–2007) 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 timescale, adjusting for gender, educational level and smoking.ResultsDuring a 6.9 year average follow-up, 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 insecticides and linear trends with duration of use of each carbamate. Considering tumor 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.ConclusionsFindings reinforce carcinogenicity evidence for already suspected active ingredients and draw attention to additional active ingredients, notably used on fruit trees, vineyards, potatoes and beets.

Few studies were performed to assess workers’ exposure to pesticides in orchards and even less during re-entry activities. However, nearly 40 pesticide treatments per year are carried out in apple-growing especially against fungal diseases, mainly scab. In order to characterize pesticide exposures of farmers in epidemiological studies, we performed a non-controlled field study in 3 regions of France (Normandy, South-West and Rhône-Alpes) in apple orchards during the 2016 and 2017 seasons. We observed the activity of the workers trying to disrupt it as little as possible. Workers’ external contamination and their determinants were assessed during 158 working days, corresponding to 31 treatment days (including mixing, spraying and equipment cleaning), 69 re-entry days (including apple hand-thinning, anti-hail net opening and closing tasks) and 58 harvesting days. We performed both detailed observations of work characteristics on the whole day (including an ergonomic approach) and pesticide measurements for dermal contamination during each task (following the OCDE guidelines). Potential dermal exposure was measured with cotton pads placed onto the skin (11 body areas), and cotton gloves or hand rinsing for each task. Captan and dithianon, fungicides representative of pesticide use in apple-growing, were used as markers for exposure. Relative contribution of the different body areas to total exposure was assessed. In addition, to investigate potential sources of contamination, we measured dislodgeable residues in the environment of the workers by analyzing leaf and fruit samples and surfaces of work equipment. Results indicated that workers’ dermal exposure was higher during re-entry tasks than treatments and harvests. The median dermal contamination during treatment was 4.03 mg of active ingredients per day, levels ranging from 0.95 mg to 64.19 mg. Most of the contamination was observed on the hands, especially during mixing. We will focus our presentation on levels and main determinants of pesticide exposure during treatment tasks.

PurposeIncreased risks of Non-Hodgkin’s Lymphomas (NHLs) have been reported among farmers in several meta-analyses, with exposure to pesticides as the main explanation. Few studies investigated associations by NHL subtypes and considering specific pesticides. From the French agricultural cohort AGRICAN, we assessed the role of benzimidazole fungicides use on NHL risk, overall and for multiple myeloma (MM), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL-SLL) and Diffuse Large B-cell Lymphoma (DLBCL).MethodsNearly 1 82 000 participants affiliated in a health assurance system reported in the enrollment questionnaire (2005–2007) lifetime pesticide use with start and end year on 13 crops and were followed until 2013. Using the crop-exposure matrix PESTIMAT, associations between NHLs and benzimidazole fungicides exposure (overall and for benomyl, carbendazim, fenzaflore, thiabendazole and thiophanate methyl) were estimated using Cox models.ResultsAfter exclusion of prevalent cases, individuals with incomplete agricultural profession history data or a zero tracking period, 1,133 NHL incident cases were identified from cancer registries (269 MM, 244 CLL-SLL, 190 DLBCL). Nearly 20% of participants were considered exposed (median duration from 7 to 20 years according to active ingredient). Increased NHL risk was observed with exposure to benzimidazole, overall, on any crops (NHL: HR=1.13, 95%CI=0.94–1.37, 150 cases, no duration relationship). Moreover, borderline positive associations were reported on specific crops: wheat/barley (NHL: HR=1.23, CLL-SLL: HR=1.42), beets (DLBCL, HR=2.19) and rape (DLBCL, 2.32). Significant increased risks were reported with MM for use of thiophanate-methyl on wheat/barley (HR=3.46, 23 exposed cases, no duration relationship) and with DLBCL for all 4 benzimidazole used on beets (HR from 2.34 to 2.57 and for the 2 used on rape (HR=2.39 and 2.46), although based on respectively 7 and 6 cases.ConclusionThese findings suggest positive associations between incidence of specific NHL subtypes, and exposure to benzimidazole as a chemical family or specific ingredients in this family.

Purpose Livestock farming has been recognized as a risk factor for chronic bronchitis (CB). The role of crop farming, however, has been less studied. We sought to assess the role of a large range of farming activities on the risk of CB in the French agricultural cohort AGRICAN (AGRIculture and CANcer). Methods Data on respiratory health and farming activities were collected by questionnaire from 2005 to 2007. Associations between farming activities and self-reported doctor's diagnosis of CB were estimated by a logistic regression adjusted for confounders. Results CB was reported by 1207 farmers (8.4%). Two farming activities were associated with CB: cattle raising (odds ratio [OR] 1.24, 95% confidence interval 1.03–1.48), and potato production (OR 1.33, 95% confidence interval 1.13–1.57). Associations were more pronounced in small-scale cattle raising and in large-scale potato production, in particular among the longest exposed workers (≥20 years). Pesticide poisoning and exposure to pesticides in potato farmers were significantly associated with CB risk (OR 1.64 and OR 1.63, respectively). Conclusions This analysis suggests that other agricultural settings not previously reported, such as potato production, may be a risk factor for CB. The nature and circumstances of exposure to hazardous agents need to be further explored.

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.

In his letter, Tomenson1 provides his opinion on the development and use of crop-exposure matrices (CEMs) in a pooling project within the AGRICOH consortium.2 Although overall his concerns repeat acknowledged limitations of the developed CEMs, discussed in detail in our paper, we disagree with his conclusion. Tomenson concludes that “it is difficult to see how the pooling project can be worthwhile unless the exposure measures are greatly improved.” Part of this conclusion is based on his interpretation of low agreement between self-reported pesticide use in the Agricultural Health Study (AHS) and exposure assigned to this population using two CEM approaches approximating methods developed …

Epidemiological studies have reported an increased risk of Parkinson’s disease (PD) in farmers, especially in those exposed to pesticides, but no clear conclusion can be drawn on the type of use, duration or latency associated with an effect. In the French prospective agricultural cohort AGRICAN, we assessed associations between agricultural and pesticide exposures, including their duration, and the risk of PD. Self-reported doctor-diagnosed PD and history of life-time exposure to 13 crops and 5 types of animals and pesticide use were collected at enrollment (2005–2011) among 181,842 participants affiliated to the French agriculture health assurance scheme (77% having worked on a farm, 23% who did not). Associations between agricultural/pesticide use and PD were estimated by logistic regression adjusted for sex, age, education, smoking status and alcohol consumption. PD was reported by 1 732 subjects (1.2%). Significant higher risk of PD was found for 3 types of animals (swine, horses, and poultry) and 7 crops (corn, peas, beet, rape, fruit-growing, potatoes and vegetables): odds ratios [OR] = 1.19 (horses) to 1.46 (peas). Pesticide exposure (E) was significantly associated with PD in all the animals and crops studied except tobacco (OR = 1.31 (cattle) to 1.83 (horses)) with a significant dose related-relationship with duration of exposure on cattle, swine, horses, poultry, vineyards and rape (P-trend

Introduction Even though some risk factors for breast cancer are well-established (reproductive history or lifestyle), they explain no more than 50% of cases. Occupational exposures, including farming, have been seldom studied and were based on small-scale studies. Our aim was to assess the association between farming activities and breast cancer in the AGRICAN cohort. Methods AGRICAN consisted of 181,842 participants affiliated to the French agricultural health insurance. Data on lifetime agricultural exposures (18 farming activities, up to 5 tasks) and living in a farm during first year of life were collected from the enrollment questionnaire (2005–2007). Hazard ratios were estimated using Cox regression analysis with age as time scale. Results From enrolment to 2011, 743 incident breast cancers were identified among 55,558 postmenopausal women (555 ductal and 99 lobular carcinoma) through linkage with cancer registries. We found an overall lower breast cancer risk among farmers (HR 0.81, 95% CI: 0.65–1.01) and cattle breeders, with a linear inverse relationship with duration (≥40 years HR 0.71, 95% CI: 0.52–0.95; p-trend Conclusion This work provides new results on associations between farming activities and breast cancer among postmenopausal women. It also emphasises the need to consider pesticide exposures during other tasks than application.

Occupational exposure to pesticides concerns a wide population of workers, not only in agriculture but in numerous other occupational industries, including gardeners/landscapers, pest killers, workers in wood industry. The reliability of self-reported information on lifelong use of pesticides is questionable because of the large range of molecules possibly used. So are biological measurements because of the short half-life of most pesticides. The PESTIPOP job-exposure matrix, which is under development, intends to estimate parameters of pesticide occupational exposure in the French general population. The current version of the matrix is composed of two axis: the first axis corresponding to occupations (combinations of jobs and industries classified according to the French classifications of the National Institute for Statistics and Economic Studies) and the second one to pesticide exposure (globally and in four categories: insecticides, herbicides, fungicides, others). The estimated exposure metric is the probability of exposure coupled with a reliability level (low, medium or high). These metrics were defined by combining different sources: i) an a priori expert assessment (panel of agricultural industry experts); ii) data collected in a multicentric case control study (596 cases and 1192 controls) on brain tumours in the general population (occupational history, specific questionnaires); iii) an a posteriori expert assessment by consensus among three experts, based on the data of the case control study. So far, 105 occupations (24 in agriculture) and 77 industries (14 in agriculture) were classified as exposed to pesticides, corresponding to 166 occupation-industry pairs. For example, youth workers in training centres had a probability of 33% to be exposed to insecticides and herbicides whereas teachers in nursery or primary schools had a probability of 25% to be exposed to insecticides according to the matrix. Transcoding into international classifications (ISOC, ISIC) will follow to allow comparison with international existing matrices.

Introduction Pesticide exposure, before and during the pregnancy, was described as dangerous for pregnancy and child development. Few studies investigated occupational pesticide exposure of women. The purpose of this study was to develop an untargeted approach to assess pesticide exposure of women of childbearing age, involved in agricultural activities and lived on farm. Methods Thirty-nine women, aged 50 years or less and included in a prospective cohort of farmers were interviewed twice, during enrollment (1997 to 2000) and at 10-years of follow-up (between 2007 and 2010). First morning urine and individual data, including agricultural activities and pesticide use on crops, cattle, inside livestock buildings or on courtyard, were collected at each timepoint. An upgradable list of 205 quantifiable pesticides (including 16 metabolites) was formulated. Urine samples were analysed by using HPLC – tandem mass spectrometry with limits of quantification between 0.01 and 0.5 µg/L. Results Almost all of women lived and worked on crop-livestock farms. Very few of them applied pesticide on crops but an half used herbicides on courtyard or insecticides on animal. Overall, 78 samples were analysed and 102 pesticides or metabolites were detected in at least one sample with a median of 9 molecules in samples at enrollment (min-max: 3–37) and at follow-up (1–57). Pentachlorophenol was detected in 75% of samples (median for contaminated samples: 0.582 and 0.506 µg/L at enrollment and at follow-up respectively). Four others pesticides were detected in more than 50% of samples at enrollment or at follow-up: Fluazifop-butyl (0.010 and 0.012 µg/L), Dinoterb (0.146 and 0.303 µg/L), Imazamethabenz-methyl (0.353 and 0.269 µg/L), and Hydroxyatrazine (0.034 and 0.0266 µg/L). Conclusion We detected, without significant change after 10 years, active ingredients rarely analysed in studies of women occupationally exposed and some of them have been described as potential endocrine disruptors.

Background Epidemiological studies have repeatedly found lower risks of lung cancer in farmers. Besides a lower prevalence of tobacco-smoking, exposure to endotoxins, which is highly present in animal farming, has been offered as an explanation. However, its role remains controversial. Little is known about the agricultural activities concerned. In the AGRICAN cohort, we assessed the relationship between animal farming and lung cancer by investigating the type of animals, tasks, timing of exposure and taking smoking history into account. Methods The AGRICAN cohort consisted of 170,834 participants affiliated to the French agricultural health insurance scheme. Linkage with cancer registries identified 487 incident lung cancers from enrolment (2005–2007) to 2011. The enrolment questionnaire provided detailed information on lifelong farming, including tasks performed with cattle, horses, pigs, poultry, sheep and/or goats with years of beginning and end, and exposure to a farm during the first year of life. Associations between lung cancer and exposure to animals were analysed using a Cox model with adjustment for smoking, using age as time scale. Results Risk in lung cancer (especially adenocarcinoma) was inversely associated with duration of occupational exposure to cattle (≥40 years: HR = 0.60, [95% CI=0.41–0.89], p–trend = 0.04) and horse (≥20 years: 0.64 [0.35–1.17], p–trend = 0.08), but not with poultry or pig farming. Lower lung cancer risk remained associated with long–term exposure to cattle, even 25 years after cessation of exposure. More pronounced decreased risks were observed among individuals who had cared for animals, undertaken milking and who had been exposed to cattle in infancy. Interpretation Our study provides strong evidence of an inverse association between cattle and horse farming, and lung cancer. Further research is warranted to identify the etiologic protective agents and biological mechanisms involved.

Objectives Animal farming entails a variety of exposures to infectious agents, endotoxins and pesticides, which may play a role in the aetiology of lympho-hematopoietic cancers. The aim of this investigation was to assess lymph-hematopoietic cancers risk in association with raising animals on farms. Method Self–reported animal production (cattle, hogs, sheep/goats, poultry) were collected in the US Agricultural Health Study, French Agriculture and Cancer Study, and Cancer in the Norwegian Agricultural Population cohorts. Associations with risk of lymph-hematopoietic cancers, including 18 cancer outcomes, were evaluated using Cox proportional hazard models, adjusted for sex, pesticides and other confounders. The referent category consisted of farmers who didn’t produce the animal species being evaluated. Cohort-specific hazard ratios (HR) were combined using random effects meta-analysis. Among 316,270 farmers, 3,282 lymph-hematopoietic cancers were diagnosed between 1993–2011. Results 60%, 35%, 33%, and 27%, of farmers raised cattle, hogs, poultry and sheep/goats, respectively, although the prevalence varied by cohort. Raising cattle was not associated with overall non-Hodgkin lymphoma (meta-HR=1.04; 95% Confidence Interval (CI): 0.93–1.16; I2 = 13%), but was associated with follicular lymphoma (meta-HR = 1.43; 95% CI: 1.02–2.01; I2 = 21%). The risk of myelodysplastic syndromes was significantly reduced in farmers who raised sheep/goats (meta-HR = 0.66; 95% CI: 0.46–0.95; I2 = 0%), as was the risk of „marginal-zone lymphoma among farmers who raised hogs (meta-HR = 0.57; 95% CI: 0.33–0.99; I2 = 0%), with the majority of exposed cases coming from two cohorts. We observed no meta-association between raising poultry and any lymph-hematopoietic cancer subtypes. It should be noted that differences in raising animals between countries and years might have influenced relevant exposures and therefore HR estimates for lymph-hematopoietic cancer sub-types might vary by cohort for specific animals. Conclusions This study suggests specificity of associations between specific animals raised and lymph-hematopoietic cancer sub-types. These associations will be investigated further considering number of animals raised and farmers producing single species.

Introduction Nanoscale particles (1-100 nm) may be naturally occurring; intentionally-produced for commercial purposes or unintentionally-produced by manufacturing processes or human activities. Toxicological data have suggested a possible carcinogenic effect of nanoscale particles and have shown that they have the ability to translocate into different organs including the brain. While epidemiological data on nanoscale particles are very scarce to date, there is some suggestion of their potential role in cancer (e.g. diesel exhaust emissions classified as carcinogenic for humans by IARC). The objective of this study was to estimate the association between occupational exposure to nanoscale particles and risk of brain tumour in adults. Methods The CERENAT study is a multicenter case-control study carried out in four districts of France between 2004 and 2006. From detailed occupational histories, occupational exposure to unintentionally-produced nanoscale particles was retrospectively assessed by the MatPUF job exposure matrix providing a probability and frequency of exposure for each combination occupation × industry according to international and national classifications. Conditional logistic regression was used to estimate ORs and 95% CIs. Results Overall, 596 brain tumour cases and 1192 matched controls were included in this study. Among men, a significant association between occupational exposure to nanoscale particles and brain tumour was observed (OR = 1.5; 95% CI: 1.1–2.2). This increased OR was essentially observed in the highest exposure categories (OR = 1.6; 95% CI: 1.1–2.4 for a total duration of exposure over 30 years) as well as for carbonaceous (OR = 1.5; 95% CI: 1.1–2.3) and HAP nanoscale particles (OR = 1.6; 95% CI: 1.1–2.4). Conclusion Even if these preliminary results should be confirmed by other analyses including the intensity of exposure (on-going work in a further version of the job-exposure matrix), these results should encourage further epidemiological research on nanoscale particles.