Cancer incidence in the AGRICAN cohort study (2005-2011).

BACKGROUND: Numerous studies have been conducted among farmers, but very few of them have involved large prospective cohorts, and few have included a significant proportion of women and farm workers. Our aim was to compare cancer incidence in the cohort (overall, by sex, and by work on farm, occupational status and pesticide use) within the general population. METHODS: More than 180,000 participants in the AGRICAN cohort were matched to cancer registries to identify cancer cases diagnosed from enrolment (2005-2007) to 31st December 2011. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (95%CIs). RESULTS: Over the period, 11,067 incident cancer cases were identified (7304 men and 3763 women). Overall cancer incidence did not differ between the cohort and the general population. Moreover, SIRs were significantly higher for prostate cancer (SIR=1.07, 95%CI 1.03-1.11) and non-Hodgkin lymphoma (SIR=1.09, 95%CI 1.01-1.18) among men, skin melanoma among women (SIR=1.23, 95%CI 1.05-1.43) and multiple myeloma (men: SIR=1.38, 95%CI 1.18-1.62; women: SIR=1.26, 95%CI 1.02-1.54). In contrast, SIRs were lower for upper aerodigestive tract and respiratory cancers. Increase in risk was greater in male farm workers for prostate and lip cancer, in female farm workers for skin melanoma, and in male farm owners for multiple myeloma. Moreover, incidence of multiple myeloma and skin melanoma was higher among male and female pesticide users respectively. CONCLUSION: We found a decreased incidence for tobacco-related cancers and an increased incidence of prostate cancers, skin melanoma and multiple myeloma. Specific subgroups had a higher cancer incidence related to occupational status and pesticide use

Exposure to Farm Animals and Risk of Lung Cancer in the AGRICAN Cohort.

Epidemiologic studies have found lower risks of lung cancer in farmers. However, little is known about the types of agricultural activities concerned. In the Agriculture and Cancer cohort, we assessed the relationship between animal farming and lung cancer by investigating the types of animals, tasks, and timing of exposure. Analyses included 170,834 participants from the Agriculture and Cancer (AGRICAN) cohort in France. Incident lung cancers were identified through linkage with cancer registries from enrollment (2005-2007) to 2011. A Cox model, adjusting for pack-years of cigarette smoking, was used to calculate hazard ratios and 95% confidence intervals. Lung cancer risk was inversely related to duration of exposure to cattle (≥40 years: hazard ratio = 0.60, 95% confidence interval: 0.41, 0.89; P for trend < 0.01) and to horse farming (≥20 years: hazard ratio = 0.64, 95% confidence interval: 0.35, 1.17; P for trend = 0.09), especially for adenocarcinomas, but not with poultry or pig farming. More pronounced decreased risks were reported among individuals who had cared for animals, undertaken milking, and who had been exposed to cattle in infancy. Our study provides strong evidence of an inverse association between lung cancer and cattle and horse farming. Further research is warranted to identify the etiologic protective agents and biological mechanisms

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

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

Activités agricoles et risque de cancers chez les affiliés du régime agricole -Résultats intermédiaires de l'étude AGRICAN (AGRIculture et CANcers)

Ce volume rassemble l'ensemble des travaux de recherche conduits dans le cadre des appels à projets soutenus par le plan Ecophyto, et présentés à l'occasion du colloque Ecophyto Recherche des 13 et 14 octobre 2015National audienceThe part of cancers attributable to occupational exposures represents at least 2 to 8 % of the mortality by cancer (that is 3 in 12,000 deaths a year in France). Literature on cancer risk among agricultural population is scarce in France although these exposures concern more than 1 million people and France is one of first user countries of pesticides in the World. Nevertheless, according to numerous studies led mainly among the North American and Scandinavian farmers, several cancers are morefrequent among farmers (hematological cancers, malignant melanoma, soft tissue sarcomas, prostate, stomach and brain cancer…), particularly among those exposed to pesticides. A very large cohort of farmers and agricultural workers is constituted since 2008. This cohort AGRICAN concerns departments having a cancer registry qualified by the National Committee of Registers, for an enrolment of more than 180,000 members of the agricultural health insurance (farm owners and farm workers mainly, active or retired). It makes of this cohort the vastest and the most varied in then populations and the agricultural activities concerned at the international level and one of the biggest cohort led in France. The first results in terms of mortality and incidence over the period between the enrolment (2005-2007) and the end of year 2011 confirm and strengthen the trends observed at the international level, worth knowing lower risks for smoking related cancers and increased risks for hematological cancers, cancers of the prostate, the lips and for the cutaneous melanomas. The first internal analyses on the most frequent cancers showed increased risks for prostate cancers among cattle breeders (in particular during the use of insecticides on animals), or of pigs or still during the realization of hays as well as during the direct or indirect pesticide exposure on various crops (wheat- barley, fruit growing, potatoes, tobacco) and more particularly to those having never worn protective gloves during the use of pesticides. Lung cancer was also increased among farmers involved in peas growing, especially during harvesting. Interestingly, our study provides evidence of strong andconsistent protective effect of cattle and horse farming on lung cancer, especially in individuals who cared or milked the animals, independently of smoking. The first phase of follow-up of the exposures in this cohort began in its active phase at the beginning of 2015 with the sending of self-administered questionnaires which will allow to update information on the occupational exposures and life habits.Collaborative works are in progress with several other agricultural cohorts at the international level within the framework of the international consortium of agricultural cohorts (AGRICOH), in particular, on the risk factors of hematological cancers (Norwegian and American cohorts) and on the matrix exposure on endotoxins (American, New Zealand cohorts).La part des cancers attribuable à des expositions professionnelles représenterait au minimum 2 à 8% de la mortalité par cancer (soit 3 à 12.000 décès par année en France). La population agricole a été très peu étudiée en France en particulier en termes de survenue de cancer bien que les expositions professionnelles en exploitation agricole concernent plus de 1 million de personnes et que la Francesoit un des premiers pays utilisateurs de pesticides au Monde. Pourtant, d’après de nombreuses études menées principalement chez les agriculteurs nord-américains et scandinaves, certains cancers (hémopathies malignes, cancers cutanés, sarcomes des tissus mous, cancer de la prostate, tumeurs cérébrales, cancers gastriques,…) sont retrouvés en excès dans cette profession et plus particulièrement chez les utilisateurs de pesticides. Une très vaste cohorte d’agriculteurs et de salariés agricoles est maintenant mise en place depuis 2008. Cette cohorte AGRICAN concerne des départements disposant d’un registre des cancers qualifié par le Comité National des Registres, pour une population incluse de plus de 180 000 affiliés du régimeagricole (chefs d’exploitation et ouvriers agricoles principalement, en activité ou retraités). Cela fait de cette cohorte la plus vaste et la plus variée dans les populations et les activités agricoles concernées au niveau international et une des plus grandes études de cohorte menée en France. Les premiers résultats en termes de mortalité et d’incidence sur la période entre l’inclusion (2005-2007) et la fin d’année 2011 confirment et renforcent les tendances observées au niveau international, à savoir desrisques plus faibles pour les cancers très liés au tabagisme et des risques augmentés pour des cancers hématologiques, de la prostate, des lèvres et pour les mélanomes cutanés. Les premières analyses internes sur les cancers les plus fréquents ont montré des risques augmentés de cancers de la prostate chez les éleveurs de bovins (notamment lors de l’utilisation d’insecticides sur animaux), ou de cochonsou encore lors de la réalisation des foins ainsi que lors de l’exposition directe ou indirecte aux pesticides sur différentes cultures (blé-orge, arboriculture, pommes de terre, tabac) et plus particulièrement chez ceux n’ayant jamais porté de gants de protection lors de l’utilisation de pesticides. De façon intéressante, notre étude fournit des éléments convaincants en faveur d’un fort effet protecteur de l’implication dans des élevages de bovins ou de chevaux sur le cancer du poumon, particulièrementchez les éleveurs impliqués dans l’alimentation ou la traite des vaches, et ceci en tenant compte du tabagisme. La première phase de suivi des expositions dans cette cohorte a débuté dans sa phase active en début 2015 par l’envoi d’auto-questionnaires de suivi qui permettront de mettre à jour des informations sur les expositions professionnelles et des habitudes de vie. Des travaux collaboratifs sont en cours avec plusieurs autres cohortes agricoles au niveau international dans le cadre du consortium international de cohortes agricoles (AGRICOH), notamment, sur les facteurs de risque de cancers hématologiques (cohortes norvégiennes et américaines), sur une matrice d’exposition aux endotoxines (cohortes américaines, néo-zélandaises…)

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

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

Retreatment With Sofosbuvir Plus Grazoprevir/Elbasvir Plus Ribavirin of Patients With Hepatitis C Virus Genotype 1 or 4 Who Previously Failed an NS5A- or NS3-Containing Regimen: The ANRS HC34 REVENGE Study

International audienceBackground: Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct-acting antiviral (DAA)–based regimens is commonly associated with emergence of resistance-associated substitutions (RASs). Retreatment of patients who failed prior DAAs remains challenging. The aim of this prospective and randomized study was to evaluate the efficacy (primary endpoint: SVR 12 weeks after end of treatment [SVR12]) and safety of sofosbuvir + grazoprevir/elbasvir + ribavirin for 16 or 24 weeks in patients who had failed to achieve SVR on previous NS5A- or NS3-based therapy and with evidence of RASs at failure.Methods: Patients were chronically infected with HCV genotype 1 or 4. Most of them had advanced fibrosis or compensated cirrhosis (liver stiffness 5.8–48.8 kPa).Results: All patients achieved HCV RNA below the lower limit of quantification (either target detected [unquantifiable] or target not detected) during treatment. SVR12 was achieved by 25 of 26 patients. The only patient who did not reach SVR was a patient who died, but HCV RNA was negative at this time (5 weeks after stopping treatment). No patient discontinued treatment because of adverse events or virological failure. Globally, treatment was well tolerated.Conclusions: Our findings support the concept of retreating with sofosbuvir + grazoprevir/elbasvir + ribavirin, for 16 weeks, genotype 1 or 4 DAA-experienced patients with proven NS5A or NS3 RASs

Int J Epidemiol

BACKGROUND: Pesticides are commonly used in agriculture, and previous studies endorsed the need to further investigate the possible association between their use and risk of lymphoid malignancies in agricultural workers. METHODS: We investigated the relationship of ever use of 14 selected pesticide chemical groups and 33 individual active chemical ingredients with non-Hodgkin lymphoid malignancies (NHL) overall or major subtypes, in a pooled analysis of three large agricultural worker cohorts. Pesticide use was derived from self-reported history of crops cultivated combined with crop-exposure matrices (France and Norway) or self-reported lifetime use of active ingredients (USA). Cox regression models were used to estimate cohort-specific hazard ratios (HRs) and 95% confidence intervals (CIs), which were combined using random effects meta-analysis to calculate meta-HRs. RESULTS: During follow-up, 2430 NHL cases were diagnosed in 316 270 farmers accruing 3 574 815 person-years under risk. Most meta-HRs suggested no association. Moderately elevated meta-HRs were seen for: NHL and ever use of terbufos (meta-HR = 1.18, 95% CI: 1.00-1.39); chronic lymphocytic leukaemia/small lymphocytic lymphoma and deltamethrin (1.48, 1.06-2.07); and diffuse large B-cell lymphoma and glyphosate (1.36, 1.00-1.85); as well as inverse associations of NHL with the broader groups of organochlorine insecticides (0.86, 0.74-0.99) and phenoxy herbicides (0.81, 0.67-0.98), but not with active ingredients within these groups, after adjusting for exposure to other pesticides. CONCLUSIONS: Associations of pesticides with NHL appear to be subtype- and chemical-specific. Non-differential exposure misclassification was an important limitation, showing the need for refinement of exposure estimates and exposure-response analyses