Occupational pesticide exposure, cancer and chronic neurological disorders: A systematic review of epidemiological studies in greenspace workers

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

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

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

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

BACKGROUND: 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. METHODS: The AGRICAN cohort is a prospective study of 181,842 individuals enrolled in 2005-2007 who completed an enrolment questionnaire with data on lifelong agricultural exposure. Associations between agricultural exposure and sarcoma overall, GIST (gastro-intestinal stromal tumors) and myomatous and fibrous sarcoma together, were analyzed with a Cox model. RESULTS: Until 2015, 188 incident cases of sarcoma were identified. Increased risks were observed (1) among cattle farmers working < 10 years (HR(<10years) =2.45, 95%CI 1.36-4.43) and breeding ≥ 50 livestock (HR(≥50 animals) =3.84, 95%CI 1.60-9.22), especially if involved in animal care and building disinfection, (2) in greenhouse production (HR=1.82, 95%CI 1.01-3.30), and (3) 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). CONCLUSION: In AGRICAN, the risk of sarcomas was increased in several farming activities with differences according to histological subtype

Int J Epidemiol

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

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old