Agricultural exposure and risk of ovarian cancer in the AGRIculture and CANcer (AGRICAN) cohort.

BACKGROUND: Ovarian cancer is rare with a poor prognosis and few established risk factors. Hormones and reproductive factors significantly impact its development, suggesting a potential link with endocrine disrupters. METHODS: In the AGRICAN cohort, 59 391 female farmers completed data on lifelong agricultural exposures and reproductive life. Cox models with attained age as timescale (HR and 95% CI) were used. The role of hormonal factors as potential confounders was considered along with specific time windows for exposure (childhood, puberty and menopause). Female farmers were the reference group (for the principal analyses). RESULTS: Between enrolment (2005-2007) and the end of follow-up (31 December 2017), 262 incident ovarian cancers were identified. An increased risk was observed for females involved in pigs (HR=2.12 (95% CI 1.27 to 3.52)) including during puberty (HR=1.83 (95% CI 1.13 to 2.94)), fruit-growing (HR=2.17 (95% CI 1.09 to 4.30)) and potato seed treatment (HR=2.81 (95% CI 1.29 to 6.09)). Conversely, females born on farms growing grain cereals (HR=0.64 (95% CI 0.46 to 0.90)) or pig-breeding (HR=0.78 (95% CI 0.55 to 1.12)) presented a reduced risk of ovarian cancer. Triazine herbicide exposure was not associated with ovarian cancer. The effect of agricultural exposures remained unchanged in multivariate models considering contraception, parity, puberty age, menopause age and body mass index. CONCLUSION: This study is the first to assess the association between specific agricultural exposures and ovarian cancer comprehensively. Some of the positive associations observed suggest that some pesticide exposure (especially during puberty) could play a role in the development of ovarian cancer. On the other hand, agricultural exposure during early life could have a protective effect, as observed for lung cancer among farmers. Finally, we did not confirm the previous putative effect of exposure to triazine herbicides.

Herbicide exposure during occupational knapsack spraying in French gardeners and municipal workers.

CONTEXT: There is a lack of data on pesticide exposure levels during spraying with a knapsack, while it could have important implications for their users' health. METHODS: We assessed levels and determinants of exposure in 24 male private landscapers/gardeners and municipal workers in France in 2011. Actual dermal exposure to glyphosate was assessed with cotton undergarments and gloves, and a cotton coverall changed between mixing and spraying to assess the contribution of each phase and body area to overall contamination. A field monitor observed the whole workshift and filled in a standardized observation grid. RESULTS: The median actual contamination was 5,256 µg for the body, and 4,620 µg for hands. Spraying was more exposing than mixing/loading for all body parts except hands, which contributed to nearly 90% of body exposure during mixing/loading, and 30% during spraying, followed by back (14%). In the most exposed quartile, levels were close to some observations in agriculture. CONCLUSION: Our study provides new data on pesticide exposure levels of knapsack sprayer users; it should lead to a reinforced prevention, in order to make exposures as low as possible and lessen the risk of chronic diseases.

Exposure to pesticides and risk of Hodgkin lymphoma in an international consortium of agricultural cohorts (AGRICOH).

PURPOSE: Some pesticides may increase the risk of certain lymphoid malignancies, but few studies have examined Hodgkin lymphoma (HL). In this exploratory study, we examined associations between agricultural use of 22 individual active ingredients and 13 chemical groups and HL incidence. METHODS: We used data from three agricultural cohorts participating in the AGRICOH consortium: the French Agriculture and Cancer Cohort (2005-2009), Cancer in the Norwegian Agricultural Population (1993-2011), and the US Agricultural Health Study (1993-2011). Lifetime pesticide use was estimated from crop-exposure matrices or self-report. Cohort-specific covariate-adjusted overall and age-specific (< 40 or ≥ 40 years) hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression and combined using random effects meta-analysis. RESULTS: Among 316 270 farmers (75% male) accumulating 3 574 815 person-years at risk, 91 incident cases of HL occurred. We did not observe statistically significant associations for any of the active ingredients or chemical groups studied. The highest risks of HL overall were observed for the pyrethroids deltamethrin (meta-HR = 1.86, 95% CI 0.76-4.52) and esfenvalerate (1.86, 0.78-4.43), and inverse associations of similar magnitude were observed for parathion and glyphosate. Risk of HL at ≥ 40 years of age was highest for ever-use of dicamba (2.04, 0.93-4.50) and lowest for glyphosate (0.46, 0.20-1.07). CONCLUSION: We report the largest prospective investigation of these associations. Nonetheless, low statistical power, a mixture of histological subtypes and a lack of information on tumour EBV status complicate the interpretability of the results. Most HL cases occurred at older ages, thus we could not explore associations with adolescent or young adult HL. Furthermore, estimates may be attenuated due to non-differential exposure misclassification. Future work should aim to extend follow-up and refine both exposure and outcome classification.

A Multicenter Study to Assess a Systematic Screening of Occupational Exposures in Lung Cancer Patients.

Occupational lung cancer cases remain largely under-reported and under-compensated worldwide. In order to improve the detection and compensation of work-related lung cancers, we implemented a systematic screening of occupational exposures, combining a validated self-administered questionnaire to assess occupational exposures and a specialized occupational cancer consultation. After a pilot study, the present prospective, open-label, scale-up study aimed to assess this systematic screening of occupational exposures in lung cancer patients in five sites in France by associating university hospitals with cancer centers. Patients with lung cancer were sent a self-administered questionnaire to collect their job history and potential exposure to lung carcinogens. The questionnaire was assessed by a physician to determine if a specialized occupational cancer consultation was required. During the consultation, a physician assessed if the lung cancer was occupation-related and, if it was, delivered a medical certificate to claim for compensation. Patients were offered help from a social worker for the administrative procedure. Over 15 months, 1251 patients received the questionnaire and 462 returned it (37%). Among them, 176 patients (38.1%) were convened to the occupational cancer consultation and 150 patients attended the consultation. An exposure to occupational lung carcinogen was identified in 133 patients and a claim for compensation was judged possible for 90 patients. A medical certificate was delivered to 88 patients and 38 patients received compensation. Our national study demonstrated that a systematic screening of occupational exposures is feasible and will bring a significant contribution to improve the detection of occupational exposures in lung cancer patients.

Pesticide Exposure in Fruit-Growers: Comparing Levels and Determinants Assessed under Usual Conditions of Work (CANEPA Study) with Those Predicted by Registration Process (Agricultural Operator Exposure Model).

Knowledge of pesticide exposure levels in farmers is necessary for epidemiological studies and regulatory purposes. In the European pesticide registration process, operators' exposure is predicted using the Agricultural Operator Exposure Model (AOEM), created in 2014 by the European Food Safety Authority based on studies conducted by the pesticide industry. We compared operators' exposures during treatment days in the apple-growing industry under non-controlled working conditions and AOEM-predicted values. The dermal exposure of thirty French apple-growers from the CANEPA study when applying two fungicides was measured using body patches and cotton gloves. For each observation, the corresponding exposure was calculated by means of the AOEM, using data recorded about the operator, spraying equipment and personal protective equipment (PPE) used. A significant linear correlation was observed between calculated and measured daily exposures. The model overestimated the daily exposure approximately 4-fold and the exposure during application 10-fold. However, exposure was underestimated during mixing/loading for 70% of the observations when the operator wore PPE. The AOEM did not overestimate exposures in all circumstances, especially during mixing/loading, when operators handle concentrated products. The protection provided by PPE appeared to be overestimated. This could be due to the optimal working conditions under which the "industrial" studies are conducted, which may not be representative of real working conditions of operators in fruit-growing.

Colorectal cancer among farmers in the AGRICAN cohort study.

OBJECTIVES: Specific farming types and tasks have rarely been studied in relation to colorectal cancer (CRC). We evaluated associations between 5 types of livestock and 13 types of crops in relation to CRC and its subsites within the Agriculture and Cancer (AGRICAN) study. METHODS: AGRICAN cohort includes 181,842 agricultural workers living in 11 French geographical areas. Data on farming types and tasks was collected by self-administered questionnaires. We identified 2 609 CRC, 972 right colon, 689 left colon and 898 rectal incident cancer cases during follow-up from 2005 to 2015. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: Significantly increased CRC risk was observed for farmers producing horses (HR=1.18, 95% CI 1.06-1.31), sunflower (HR=1.23, 95% CI 1.03-1.45) and field vegetables (HR=1.18, 95% CI 1.02-1.36). Positive associations were also observed for pig, poultry and wheat/barley. Some associations were observed only for specific subsites: left colon cancer was associated with fruit growing (HR=1.36, 95% CI 1.09-1.70) and potato (HR=1.28, 95% CI 1.05-1.57). Tasks related to livestock (animal care, insecticide treatment, disinfection of milking equipment and building) or to crop (haymaking, sowing, pesticide treatment, seed treatment, harvesting) were also associated with CRC. Duration and size of farming types/task increased the risk for some of the associations. Analysis stratified by sex suggested an interaction with several farming types/task. CONCLUSIONS: The current study showed original and positive findings for several farming types and tasks and CRC risk, overall and by subsites.

Agricultural exposure and risk of soft tissue sarcomas and gastrointestinal stromal sarcoma in the AGRIculture and CANcer (AGRICAN) cohort.

Sarcomas are a heterogeneous group of tumors whose incidence is nearly 5 per 100 000 inhabitants in Europe. Their causes are poorly understood, although occupational exposures (especially farming and pesticides) are suspected. The AGRICAN cohort is a prospective study of 181 842 individuals enrolled in 2005 to 2007 who completed an enrolment questionnaire with data on lifelong agricultural exposure. Associations between agricultural exposure and sarcoma overall, gastrointestinal stromal tumors (GIST) and myomatous and fibrous sarcoma together, were analyzed with a Cox model. Until 2015, 188 incident cases of sarcoma were identified. Increased risks were observed (a) among cattle farmers working <10 years (HR<10years  = 2.45, 95% CI 1.36-4.43) and breeding ≥50 livestock (HR≥50animals  = 3.84, 95% CI 1.60-9.22), especially if involved in animal care and building disinfection, (b) in greenhouse production (HR = 1.82, 95% CI 1.01-3.30) and (c) in field-grown vegetable production (HR = 1.49, 95% CI 0.96-2.32). Concerning histological subtypes, GIST were positively associated with pesticide use in vineyards (HR = 2.24, 95% CI 0.95-5.30). For myomatous and fibrous sarcoma, the only increase was seen in field-grown vegetable production (HR = 2.37, 95% CI 1.16-4.85). In AGRICAN, the risk of sarcomas was increased in several farming activities with differences according to histological subtype.

Reliability of baseline self-reported information in the AGRICAN cohort.

PURPOSE: An important challenge in epidemiology is to ensure the reliability of collected data. Very few studies have been conducted in farming populations. We assessed the reliability of self-reported data on lifestyle, reproductive history, health and agricultural activities and tasks from the AGRICAN cohort. METHODS: Our analysis focused on 739 individuals from the 181,842 cohort members who completed the questionnaire twice between 2005 and 2007 with a median time interval of 452 days. Consistency in the responses to questionnaire items (lifestyle, health and agricultural activities including pesticide treatments) was assessed by the percentage of exact agreement (PA), Cohen's Kappa value (K) and the intraclass correlation coefficient (ICC). RESULTS: Agreement was substantial to almost perfect for education, smoking, reproductive history and most health indicators (K/ICC > 0.61). Agreement was moderate for alcohol consumption and fair for diet. Agreement was substantial for animal and crop farming activities and tasks such as pesticide use on crops and protective equipment use (PA 81-99%, K/ICC 0.61-0.96). Most tasks showed moderate to substantial agreement, except a few with low agreement. Substantial to perfect agreement was observed for the duration of tasks, based on exact years of beginning and ending. CONCLUSION: Farmers' answers appeared reliable for most occupational data, including data used to assess individual exposure to specific pesticides, and for most potential confounders.

Pesticide exposure of workers in apple growing in France.

OBJECTIVE: Although apple trees are heavily sprayed, few studies have assessed the pesticide exposure of operators and workers in apple orchards. However, these data are crucial for assessing the health impact of such exposures. The aim of this study was to measure pesticide exposure in apple growing according to tasks and body parts. METHODS: A non-controlled field study was conducted in apple orchards in 4 regions of France during the 2016 and 2017 treatment seasons. Workers' external contamination and their determinants were assessed over 156 working days corresponding to 30 treatment days, 68 re-entry days and 58 harvesting days. We measured pesticide dermal contamination during each task and made detailed observations of work characteristics throughout the day. Captan and dithianon were used as markers of exposure. RESULTS: The median dermal contamination per day was 5.50 mg of captan and 3.33 mg of dithianon for operators, 24.39 mg of captan and 1.84 mg of dithianon for re-entry workers, and 5.82 mg of captan and 0.74 mg of dithianon for harvesters. Thus, workers performing re-entry tasks, especially thinning and anti-hail net opening, presented higher contamination, either equal to or higher than in operators. For these last ones, mixing/loading and equipment cleaning were the most contaminating tasks. Most of the contamination was observed on workers' hands in all tasks, except for net-opening in which their heads accounted for the most daily contamination. CONCLUSIONS: This study highlights the importance of taking indirect exposures into account during re-entry work in apple growing.

Cancer incidence in agricultural workers: Findings from an international consortium of agricultural cohort studies (AGRICOH).

BACKGROUND: Agricultural work can expose workers to potentially hazardous agents including known and suspected carcinogens. This study aimed to evaluate cancer incidence in male and female agricultural workers in an international consortium, AGRICOH, relative to their respective general populations. METHODS: The analysis included eight cohorts that were linked to their respective cancer registries: France (AGRICAN: n = 128,101), the US (AHS: n = 51,165, MESA: n = 2,177), Norway (CNAP: n = 43,834), Australia (2 cohorts combined, Australian Pesticide Exposed Workers: n = 12,215 and Victorian Grain Farmers: n = 919), Republic of Korea (KMCC: n = 8,432), and Denmark (SUS: n = 1,899). For various cancer sites and all cancers combined, standardized incidence ratios (SIR) and 95% confidence intervals (CIs) were calculated for each cohort using national or regional rates as reference rates and were combined by random-effects meta-analysis. RESULTS: During nearly 2,800,000 person-years, a total of 23,188 cancers were observed. Elevated risks were observed for melanoma of the skin (number of cohorts = 3, meta-SIR = 1.18, CI: 1.01-1.38) and multiple myeloma (n = 4, meta-SIR = 1.27, CI: 1.04-1.54) in women and prostate cancer (n = 6, meta-SIR = 1.06, CI: 1.01-1.12), compared to the general population. In contrast, a deficit was observed for the incidence of several cancers, including cancers of the bladder, breast (female), colorectum, esophagus, larynx, lung, and pancreas and all cancers combined (n = 7, meta-SIR for all cancers combined = 0.83, 95% CI: 0.77-0.90). The direction of risk was largely consistent across cohorts although we observed large between-cohort variations in SIR for cancers of the liver and lung in men and women, and stomach, colorectum, and skin in men. CONCLUSION: The results suggest that agricultural workers have a lower risk of various cancers and an elevated risk of prostate cancer, multiple myeloma (female), and melanoma of skin (female) compared to the general population. Those differences and the between-cohort variations may be due to underlying differences in risk factors and warrant further investigation of agricultural exposures.

DNA damage in circulating leukocytes measured with the comet assay may predict the risk of death.

The comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Kaplan-Meier analysis indicated a worse overall survival in the medium and high tertile of DNA damage (p < 0.001). The effect of DNA damage on survival was modelled according to Cox proportional hazard regression model. The adjusted hazard ratio (HR) was 1.42 (1.06-1.90) for overall mortality, and 1.94 (1.04-3.59) for diseases of the circulatory system in subjects with the highest tertile of DNA damage. The findings of this study provide epidemiological evidence encouraging the implementation of the comet assay in preventive strategies for non-communicable diseases.

The hCOMET project: International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confounders.

The alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project - a COST Action launched in 2016 - represent a valuable tool to meet this challenge. The aims of hCOMET were to establish reference values for the level of DNA damage in humans, to investigate the effect of host factors, lifestyle and exposure to genotoxic agents, and to compare different sources of assay variability. A database of 19,320 subjects was generated, pooling data from 105 studies run by 44 laboratories in 26 countries between 1999 and 2019. A mixed random effect log-linear model, in parallel with a classic meta-analysis, was applied to take into account the extensive heterogeneity of data, due to descriptor, specimen and protocol variability. As a result of this analysis interquartile intervals of DNA strand breaks (which includes alkali-labile sites) were reported for tail intensity, tail length, and tail moment (comet assay descriptors). A small variation by age was reported in some datasets, suggesting higher DNA damage in oldest age-classes, while no effect could be shown for sex or smoking habit, although the lack of data on heavy smokers has still to be considered. Finally, highly significant differences in DNA damage were found for most exposures investigated in specific studies. In conclusion, these data, which confirm that DNA damage measured by the comet assay is an excellent biomarker of exposure in several conditions, may contribute to improving the quality of study design and to the standardization of results of the comet assay in human populations.

Agriculture Exposure and Time to Pregnancy Among Women Enrolled in the French Prospective Cohort AGRICAN.

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.

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.

Occupational exposure to unintentionally emitted nanoscale particles and risk of cancer: From lung to central nervous system - Results from three French case-control studies.

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 2029 lung cancer cases and 2591 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.

Residential proximity to power lines and risk of brain tumor in the general population.

The effect of ELF-MF on human health is still controversial, particularly as regards long-term health effects like cancer. The literature does suggest, however, that they could be involved in the occurrence of brain tumors, although results concerning residential exposure are scarce. Our objective was to investigate the association between residential proximity to power lines and brain tumors among adults in France by using a geographical information system.CERENAT is a population-based case-control study carried out in France in 2004-2006. We used geographical data sources on power line location to create exposure scores based on distance between residence and power lines, and on the number of lines near residences. Conditional logistic regression for matched sets was used to estimate Odds Ratios (ORs) and 95% confidence intervals (95%CI).We found significant associations between cumulated duration living at <50 m to high voltage lines and: i) all brain tumors (OR 2.94; 95%CI 1.28-6.75); ii) glioma (OR 4.96; 95%CI 1.56-15.77). Further investigations are needed, particularly to improve the quality and availability of geographical and technical data on power lines.

Differential Diagnosis of Epithelioid Malignant Mesothelioma With Lung and Breast Pleural Metastasis: A Systematic Review Compared With a Standardized Panel of Antibodies-A New Proposal That May Influence Pathologic Practice.

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.

Occupational exposure to pesticides and multiple myeloma in the AGRICAN cohort.

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 < 0.01) and (ii) using insecticides on animals (HR 1.48, 95% CI 1.11, 1.98), especially among horse farmers (≥ 10 years: HR 2.77, 95% CI 1.22-6.27, p for trend = 0.01). We also observed significant elevated risks with disinfectant use in animal barns. CONCLUSIONS: Findings support the role of pesticide use on crops and animals in the occurrence of MM risk in farmers.