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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 working10 years (HR

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.

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; BACKGROUND:Medical care in rectal cancer is subject to social inequality. According to the last French guidelines, a 1-cm distal margin below the lower pole of the rectal tumor is now considered sufficient. This extends the limits of the current sphincter preservation gold standard. Like for other innovative technics, the dissemination of such technics is often subject to social and geographical inequalities. The objective was to analyze whether sphincter preservation in rectal cancer is subject to social or geographical inequality.METHODS:The odds of sphincter preservation was modeled by logistic regression among the 1453 patients in the Calvados digestive cancer registry between 1 January 1997 and 31 December 2015 by examining some of the variables that could influence it: social inequalities and geographical remoteness, sex, age, and stage.RESULTS:A total of 69.4% of the population received sphincter preservation. Patients in the more deprived quintiles had a significantly higher probability of having sphincter amputation (odds ratio (OR) = 1.469 (1.046-2.064)). This result was no longer significant after adjustment on stage and travel time. There was a dose-effect pattern of geographical remoteness on likelihood of sphincter preservation with a progressive increase in OR between patients living the nearest and the furthest from the reference center (p-trend = 0.0178).CONCLUSION:This study shows that the probability of receiving sphincter preservation is influenced by the social environment and strongly influenced by remoteness. Although management guidelines have had a huge impact on the rates of sphincter preservation, they have not reduced the influence of the social and geographical environment on sphincter preservation.

Background With the rising number of rectal cancer survivors, more patients with sphincter-preserving surgery are having to live with a potentially impaired quality of life. The survey aimed to assess bowel and genitourinary sequelae and their impact on quality of life in an unselected registry-based population of rectal cancer survivors. Methods This cross-sectional cohort survey (registered at ClinicalTrials.gov ; ID: NCT03459235 ) included patients with rectal cancer who underwent curative surgery with sphincter-preserving surgery from January 1, 2007 to January 31, 2015. Patients with recurrent disease, intestinal stoma, or cognitive disorders were excluded. Validated scoring system included the Urinary Symptom Profile in women and the International Prostate Symptom Score in men for urinary function, International Index for Erectile Function 5 in men and Female Sexual Function Index in women for sexual function, and Core 30/ Colo Rectal 29 questionnaires for quality of life and Low Anterior Resection Syndrome score for bowel function. The impact of functional sequelae on global quality of life was evaluated by multiple linear regression. Results Responders (45.3%, 92/203 patients) and nonresponders were comparable according to sex, age, tumor stage, and neoadjuvant chemoradiation. With a mean follow-up of 6.5 years, 65.2% of the rectal cancer survivors had bowel dysfunction, of whom 41.3% experienced major Low Anterior Resection Syndrome and 80% of rectal cancer survivors experienced genitourinary dysfunction. In multiple linear regression, poor bowel function was a significant predictor of global quality of life in men (P = .04) and women (P = .0003). Conclusion This survey highlights the importance of sexual and bowel dysfunction in rectal cancer survivors and the strong correlation between high Low Anterior Resection Syndrome score and inferior quality of life. Further studies are needed to improve knowledge on how to predict bowel dysfunction and how to best support patients with bowel dysfunction.

Pesticides exposures could be implicated in the excess of Central Nervous System (CNS) tumors observed in farmers, but evidence concerning individual pesticides remains limited. Carbamate derivative pesticides, including herbicides and fungicides (i.e. (thio/dithio)-carbamates), have shown evidence of carcinogenicity in experimental studies in animals. In the French AGRICAN cohort, we assessed the associations between potential exposures to carbamate herbicides and fungicides and the incidence of CNS tumors, overall and by histological subtype.AGRICAN enrolled 181,842 participants involved in agriculture. Incident CNS tumors were identified by linkage with cancer registries from enrollment (2005-2007) until 2013. Individual exposures were assessed by combining information on lifetime periods of pesticide use on crops and the French crop-exposure matrix PESTIMAT, for each of the 14 carbamate and thiocarbamate herbicides and the 16 carbamate and dithiocarbamate fungicides registered in France since 1950. Associations were estimated using proportional hazard models with age as the underlying timescale, adjusting for gender, educational level and smoking.During an average follow-up of 6.9 years, 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 fungicides (Hazard Ratio, HR = 1.88; 95% CI: 1.27-2.79) and, to a lesser extent, to carbamate herbicides (HR = 1.44; 95% CI: 0.94-2.22). Positive associations were observed with specific carbamates, including some fungicides (mancozeb, maneb, metiram) and herbicides (chlorpropham, propham, diallate) already suspected of being carcinogens in humans.Although some associations need to be corroborate in further studies and should be interpreted cautiously, these findings provide additional carcinogenicity evidence for several carbamate fungicides and herbicides.

Introduction Les sarcomes sont un groupe de tumeurs tres heterogene et complexe, leur taux d’incidence en Europe est d’environ 5 pour 100 000 habitants et leur etiologie est encore inconnue et peu etudiee. Quelques facteurs de risques professionnels sont suspectes de jouer un role dans leur developpement, en particulier les pesticides. Notre objectif est d’etudier les associations entre activites et tâches professionnelles agricoles et la survenue de sarcomes. Materiel et methodes Nos analyses s’appuient sur les donnees de la cohorte prospective AGRICAN. Entre 2005 et 2007, 181 842 individus ont ete inclus, et ont rempli un questionnaire d’inclusion retracant leur histoire professionnelle et leurs expositions agricoles. Entre l’inclusion et 2013 nous avons identifie 156 cas de sarcomes incidents, dont 33 cas de GIST (tumeurs stromales gastro-intestinales) et 38 cas de myosarcomes ou fibrosarcomes. Les associations ont ete etudiees grâce a un modele de Cox avec l’âge comme echelle de temps. Resultats Plus de la moitie de notre population d’etude etait composee d’hommes (55,87 %). L’âge median a l’inclusion etait de 67 ans. Les analyses ont montre plusieurs augmentations de risque pour le sarcome. Pour les personnes faisant de l’elevage bovin pendant moins de dix ans (HR = 2,43 [1,25–4,75]), et en particulier ceux avec plus de 50 bovins (HR = 3,85 [1,40–10,61]). Mais egalement des elevations de risque non significatives, pour les eleveurs de plus de 45 volailles (HR = 1,70 [0,91–3,15]) et pour ceux utilisant des insecticides sur les volailles (HR = 1,54 [0,85–2,80]). Pour les cultures, une augmentation de risque a ete trouvee pour la culture legumiere en plein champ (HR = 1,62 [1,01–2,60]) et la culture sous serres (HR = 2,23 [1,22–4,07]). Pour les analyses par sous type, aucune association n’a pu etre mise en evidence avec les GIST. Neanmoins, malgre des effectifs faibles, des associations positives ont ete trouvees entre les myosarcomes et fibrosarcomes et certaines activites, telle que la culture legumiere en plein champ (HR = 8,75 [1,95–39,3]). Conclusions Diverses associations ont ete mises en evidence entre certains elevages (bovins, volaille) et cultures (culture legumiere, culture sous serres) et la survenue de sarcomes. Mais egalement pour les sous-types histologiques des myosarcomes et fibrosarcomes (culture legumiere), malgre de tres faibles effectifs. Enfin, notre etude apporte de nouvelles connaissances sur l’exposition professionnelle agricole et le risque de sarcome dans un contexte tres peu documente dans la litterature.

PurposeSeveral studies and meta-analyses demonstrated that farmers have an excess risk of Non-Hodgkin Lymphomas (NHL), including Multiple Myeloma (MM). It has been suggested that pesticides could explain these results. Therefore circumstances of pesticide exposures (on crops, seeds or animals) and other farming tasks need to be explored in relation to NHL risk overall and major subtypes. From the large cohort of French farmers AGRICAN, we assessed the risk of NHL by subtypes (1) compared to the general population and (2) among farmers to identify the farm activities and tasks linked to NHLs subtypes.MethodsAGRICAN cohort enrolled more than 1 80 000 adults registered with the Mutualité Sociale Agricole, from 11 areas. Incident NHLs cases were identified by individual cross linkage with cancer registries from enrolment (2005–2007) to 2013. Lifetime work on 13 crops and 5 types of animals and the tasks performed (with duration and size information) were collected by enrollment questionnaire. Standardized incidence ratios (SIR) were calculated. Associations between NHLs and crops, animals and specific tasks were analyzed using Cox models.Results1,133 NHL incident cases were identified (269 MM, 244 chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL-SLL), and 190 diffuse large B-cell lymphoma (DLBCL)). Increased risks were observed for NHL overall and MM (SIR=1.05, and SIR=1.23, respectively). Positive associations were observed with exposure to pesticides i) on crops: DLBCL (grassland), MM (corn, wheat/barley and potato), CLL-SLL (corn, wheat/barley and vineyard) and DLBCL (tobacco), ii) in seed treatment: in CLL-SLL (sunflower, wheat/barley) and in MM (wheat/barley, corn) and iii) for use on animals (MM). Other tasks were linked to NHL risk: hay making (LDGCB) and harvesting corn (MM) and wheat/barley (CLL-SLL).ConclusionOur results supports the role of pesticide exposure on NHL risk, not only on crops. Moreover, specific associations according to NHLs subtypes were observed.

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.

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.