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The aim of this study was to analyse the impact of adjuvant trastuzumab on fatigue, emotional status, and quality of personal and work life of patients treated for localised breast cancer.In a prospective setting, we recruited age-matched localised breast cancer patients, treated by adjuvant chemotherapy with (group 1) or without IV trastuzumab (group 2), between September 2011 and May 2014. Patients completed questionnaires on quality of life (FACT-G, FACT-B), fatigue (FACIT-F, ICQ), anxiety-depression (HADS), and work life (dedicated self-questionnaire) at inclusion then at 3, 6, 9, and 15 months.We included 35 patients in each group. No significant difference was found between the two groups concerning return to work, fatigue, and quality of life scores at each phase of the study. In total, 39 patients (72.2%) reported having returned to work at T15, with no significant difference between the two groups (p = 0.53). Significantly higher scores for'helplessness' outcomes were observed in group 1, 9, and 15 months (6.138 and 5.731; p = 0.047 and 0.048, respectively). Patients in group 1 reported higher score of anxiety-depression than group 2 at 3 months (p = 0.027) then no significant difference was observed at the other times of the study.Trastuzumab does not appear to affect fatigue and return to work in patients with localised breast cancer. The emotional well-being could be affected in patients treated by trastuzumab, with a more pronounced 'helplessness' feeling which could be more related to the additional follow-up imposed by the prescription of trastuzumab.

Background: The National Lung Screening Trial (NLST) and NELSON study opened the debate on the relevance of lung cancer (LC) screening in subjects exposed to occupational respiratory carcinogens. This analysis reported the incremental cost-effectiveness ratios (ICER) of an organized LC screening program for an asbestos-exposed population. Methods: Using Markov modelization, individuals with asbestos exposure were either monitored without intervention or annual low-dose thoracic computed-tomography (LDTCT) scan LC screening. LC incidence came from a prospective observational cohort of subjects with occupational asbestos exposure. The intervention parameters were those of the NLST study. Utilities and LC-management costs came from published reports. A sensitivity analysis evaluated different screening strategies. Results: The respective quality-adjusted life year (QALY) gain, supplementary costs and ICER [95% confidence interval] were: 0.040 [0.010–0.065] QALY, 6900 [3700–11,800] € and 170,000 [75,000–645,000] €/QALY for all asbestos-exposed subjects; and 0.144 [0.071–0.216] QALY, 13,000 [5700–26,800] € and 90,000 [35,000–276,000] €/QALY for smokers with high exposure. When screening was based on biennial LDTCT scans, the ICER was 45,000 [95% CI: 15,000–116,000] €/QALY. Conclusions: Compared to the usual ICER thresholds, biennial LDTCT scan LC screening for smokers with high occupational exposure to asbestos is acceptable and preferable to annual scans.

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.

International audience; OBJECTIVE: This study aimed to develop and validate an automated artificial intelligence (AI)-driven quantification of pleural plaques in a population of retired workers previously occupationally exposed to asbestos. METHODS: CT scans of former workers previously occupationally exposed to asbestos who participated in the multicenter APEXS (Asbestos PostExposure Survey) study were collected retrospectively between 2010 and 2017 during the second and the third rounds of the survey. A hundred and forty-one participants with pleural plaques identified by expert radiologists at the 2nd and the 3rd CT screenings were included. Maximum Intensity Projection (MIP) with 5 mm thickness was used to reduce the number of CT slices for manual delineation. A Deep Learning AI algorithm using 2D-convolutional neural networks was trained with 8280 images from 138 CT scans of 69 participants for the semantic labeling of Pleural Plaques (PP). In all, 2160 CT images from 36 CT scans of 18 participants were used for AI testing versus ground-truth labels (GT). The clinical validity of the method was evaluated longitudinally in 54 participants with pleural plaques. RESULTS: The concordance correlation coefficient (CCC) between AI-driven and GT was almost perfect (>0.98) for the volume extent of both PP and calcified PP. The 2D pixel similarity overlap of AI versus GT was good (DICE = 0.63) for PP, whether they were calcified or not, and very good (DICE = 0.82) for calcified PP. A longitudinal comparison of the volumetric extent of PP showed a significant increase in PP volumes (p < 0.001) between the 2nd and the 3rd CT screenings with an average delay of 5 years. CONCLUSIONS: AI allows a fully automated volumetric quantification of pleural plaques showing volumetric progression of PP over a five-year period. The reproducible PP volume evaluation may enable further investigations for the comprehension of the unclear relationships between pleural plaques and both respiratory function and occurrence of thoracic malignancy.

BackgroundOccupational asbestos exposure is associated with pleural plaques (PP), a benign disease often seen as a marker of past exposure to asbestos and lung cancer. The association between these two diseases has not been formally proved, the aim of this study was to evaluate this association in the asbestos-related disease cohort (ARDCO) cohort.MethodsARDCO is a French multicentric cohort including workers formerly occupationally exposed to asbestos from 2003 to 2005. CT scan was performed to diagnose PP with double reading and lung cancer (incidence and mortality) was followed through health insurance data and death certificates. Cox models were used to estimate the association between PP and lung cancer adjusting for occupational asbestos exposure (represented by cumulative exposure index, time since first exposure and time since last exposure) and smoking status.ResultsA total of 176 cases (of 5050 subjects) and 88 deaths (of 4938 subjects) of lung cancer were recorded. Smoking status was identified as an effect modifier. Lung cancer incidence and mortality were significantly associated with PP only in non-smokers, respectively, HR=3.13 (95% CI 1.04 to 9.35) and HR=16.83 (95% CI 1.87 to 151.24) after adjustment for age, occupational asbestos exposure and smoking status.ConclusionsARDCO study was the first to study this association considering equal asbestos exposure, and more specifically, our study is the first to test smoking as an effect modifier, so comparison with scientific literature is difficult. Our results seem to consolidate the hypothesis that PP may be an independent risk factor for lung cancer but they must be interpreted with caution.

ObjectivesThe aim of this study was to analyse, within a French cohort of workers previously occupationally exposed to asbestos, incidence and mortality from various sites of head and neck cancers (larynx excluded) and to examine the potential link of these cancers with pleural plaques.MethodsA 10-year follow-up study was conducted in the 13 481 male subjects included in the cohort between October 2003 and December 2005. Asbestos exposure was assessed by industrial hygienist analysis of a standardised questionnaire. The final cumulative exposure index (CEI; in equivalent fibres.years/mL) for each subject was calculated as the sum of each employment period’s four-level CEI. The number of head and neck cancers recorded by the National Health Insurance fund was collected in order to conduct an incidence study. Complementary analysis was restricted to men who had performed at least one chest CT scan (N=4804). A mortality study was also conducted. We used a Cox model with age as the time axis variable adjusted for smoking, time since first exposure, CEI of exposure to asbestos and pleural plaques on CT scans.ResultsWe reported a significant dose–response relationship between CEI of exposure to asbestos and head and neck cancers after exclusion of laryngeal cancers, in the mortality study (HR 1.03, 95% CI (1.01 to 1.06) for an increase of 10 f.years/mL) and a close to significant dose–response relationship in the incidence study (HR 1.02, 95% CI (1.00 to 1.04) for an increase of 10 f.years/mL). No statistically significant association between pleural plaques and head and neck cancer incidence was observed.ConclusionsThis large-scale study suggests a relationship between asbestos exposure and head and neck cancers, after exclusion of laryngeal cancers, regardless of whether associated pleural plaques were present.

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

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.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).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.Farmers' answers appeared reliable for most occupational data, including data used to assess individual exposure to specific pesticides, and for most potential confounders.

Objective The aim of this study was to describe return to work determinants in patients with haematological malignancy. Results This medico-social pilot study included patients with haematological malignancy in the département of Calvados, aged 18 to 55 years, diagnosed between 1st January and 31st December 2010 and alive at 1st January 2015. Patients were identified via consultation of the Lower Normandy haematological malignancy Registry. They completed a specially developed self-questionnaire, in addition to validated questionnaires for anxiety-depression, quality of life and fatigue. Of the patients contacted, 50% accepted to participate. The mean age at diagnosis was 49.8 years, and the majority of patients (79.2%) was professionally active at the time of diagnosis. Only 64.9% of subjects had stopped work due to illness. The psychological impact (demonstrated anxiety) was significantly greater in men (p = 0.01). The majority of subjects returned to work after treatment (80.7%) and among them, the mean duration of absence from work was 16.1 months. Only 52.6% of subjects had informed their occupational physician and 56.7% had benefited from a pre-return visit.

Objective The aim of this study was to describe return to work determinants in patients with haematological malignancy.Results This medico-social pilot study included patients with haematological malignancy in the département of Calvados, aged 18 to 55 years, diagnosed between 1st January and 31st December 2010 and alive at 1st January 2015. Patients were identified via consultation of the Lower Normandy haematological malignancy Registry. They completed a specially developed self-questionnaire, in addition to validated questionnaires for anxiety-depression, quality of life and fatigue. Of the patients contacted, 50% accepted to participate. The mean age at diagnosis was 49.8 years, and the majority of patients (79.2%) was professionally active at the time of diagnosis. Only 64.9% of subjects had stopped work due to illness. The psychological impact (demonstrated anxiety) was significantly greater in men (p=0.01). The majority of subjects returned to work after treatment (80.7%) and among them, the mean duration of absence from work was 16.1 months. Only 52.6% of subjects had informed their occupational physician and 56.7% had benefited from a pre-return visit.The satisfactory response rate obtained is promising for the extension of the present project as a prospective multicentric study.

Objective: the aim of this study was to evaluate the association between interstitial lung abnormalities, asbestos exposure and age in a population of retired workers previously occupationally exposed to asbestos. Methods: previously occupationally exposed former workers to asbestos eligible for a survey conducted between 2003 and 2005 in four regions of France, underwent chest CT examinations and pulmonary function testing. Industrial hygienists evaluated asbestos exposure and calculated for each subject a cumulative exposure index (CEI) to asbestos. Smoking status information was also collected in this second round of screening. Expert radiologists performed blinded independent double reading of chest CT-scans and classified interstitial lung abnormalities into: no abnormality, minor interstitial findings, interstitial findings inconsistent with UIP, possible or definite UIP. In addition, emphysema was assessed visually (none, minor: emphysema &lt, 25%, moderate: between 25 and 50% and severe: &gt, 50% of the lung). Logistic regression models adjusted for age and smoking were used to assess the relationship between interstitial lung abnormalities and occupational asbestos exposure. Results: the study population consisted of 2157 male subjects. Interstitial lung abnormalities were present in 365 (16.7%) and emphysema in 444 (20.4%). Significant positive association was found between definite or possible UIP pattern and age (OR adjusted =1.08 (95% CI: 1.02–1.13)). No association was found between interstitial abnormalities and CEI or the level of asbestos exposure. Conclusion: presence of interstitial abnormalities at HRCT was associated to aging but not to cumulative exposure index in this cohort of former workers previously occupationally exposed to asbestos.

International audience; BackgroundThe objective of the study was to compare the prevalence of occupational exposure to asbestos and crystalline silica according to histological types of lung cancer and age at diagnosis.MethodsCaProMat study is a pooled case‐only study conducted between 1996 and 2011. The current study consisted of 6521 lung cancer cases. Occupational exposure to asbestos and crystalline silica was assessed by two Job‐Exposure Matrices. A weighted prevalence of exposure was derived and compared according to histological types and age at diagnosis.ResultsThere was no difference of weighted prevalence of exposure to asbestos and crystalline silica according to histological types of lung cancer. There was a statistically significant difference of weighted prevalence of exposure to asbestos and crystalline silica according to age at diagnosis.ConclusionsDue to the limited clinical importance of the difference, neither the histological type, nor the age at diagnosis can be used as an indicator for the occupational exposure to asbestos or crystalline silica.

Objectives The aim of this study was to assess the effect modification of the association between tobacco smoking and phenotypes of lung cancer (histological type, tumor location, and age at diagnosis) by occupational exposure to asbestos or to crystalline silica. Materials and methods The CaProMat study is a pooled case-only study including 7256 male lung cancer cases recruited between 1996 and 2011 in France and Canada. Two job-exposure matrices (JEMs) were used to assess occupational exposure to asbestos and crystalline silica. Statistical interactions between tobacco smoking and occupational exposure to asbestos or crystalline silica were assessed using unconditional logistic regression models for histological type and tumor location and linear regression models for age at diagnosis. Results Tobacco smoking was associated with squamous cell carcinoma and small cell carcinomas as well as an earlier age at diagnosis. Additional exposure to either asbestos or crystalline silica did not modify the effect of tobacco smoking for either histological type or age at diagnosis. Neither tobacco smoking nor occupational exposure to asbestos or crystalline silica influenced tumor location. Conclusions Tobacco smoking was the main factor related to histological type and age at diagnosis. Those associations were not modified by occupational exposure to asbestos or crystalline silica.

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.

Background Peritoneal malignant mesothelioma is a rare disease for which few population-based studies are available. The aim of this study was to describe the evolution of the incidence and survival of peritoneal malignant mesothelioma in France between 1989 and 2015, using data derived from the French network of cancer registries. Methods Age world-standardized incidence rates and overall survival were calculated using data from 16 French cancer registries. Log-linear Poisson regression analysis was used to estimate the average annual percentage change in incidence rates. Overall survival was performed using age-adjusted Cox proportional hazards model. Results In French men, the incidence has increased quietly over the reporting period from 0.07 to 0.10 with a maximum of 0.16 per 100,000 persons-years in 2001–2003. For women, the increase in incidence has been lower than for men over the period 1989–2015, ranging from 0.04 to 0.11. A better prognosis was associated with a diagnosis made after 2000 (HR = 1.76; p = 0.013), the epithelioid histological type (p = 0.003), and the fact of being a woman, which has a 5-year risk of death half that of men (HR = 0.55; p = 0.001), regardless of age, diagnosis period or histology. Conclusion Our results are similar to those currently available for other countries. In France, peritoneal mesothelioma remains a rare and fatal cancer with a small increase in the incidence rate since 1989 and a median survival of 1 year; it seemed to develop equally in women and men over this period of time.

IntroductionGuidelines concerning the follow-up of subjects occupationally exposed to lung carcinogens, published in France in 2015, recommended the setting up of a trial of low-dose chest CT lung cancer screening in subjects at high risk of lung cancer.ObjectiveTo evaluate the organisation of low-dose chest CT lung cancer screening in subjects occupationally exposed to lung carcinogens and at high risk of lung cancer.Methods and analysisThis trial will be conducted in eight French departments by six specialised reference centres (SRCs) in occupational health. In view of the exploratory nature of this trial, it is proposed to test initially the feasibility and acceptability over the first 2 years in only two SRCs then in four other SRCs to evaluate the organisation. The target population is current or former smokers with more than 30 pack-years (who have quit smoking for less than 15 years), currently or previously exposed to International Agency for Research on Cancer group 1 lung carcinogens, and between the ages of 55 and 74 years. The trial will be conducted in the following steps: (1) identification of subjects by a screening invitation letter; (2) evaluation of occupational exposure to lung carcinogens; (3) evaluation of the lung cancer risk level and verification of eligibility; (4) screening procedure: annual chest CT scans performed by specialised centres and (5) follow-up of CT scan abnormalities.Ethics and disseminationThis protocol study has been approved by the French Committee for the Protection of Persons. The results from this study will be submitted to peer-reviewed journals and reported at suitable national and international meetings.Trial registration numberNCT03562052; Pre-results.

As pleural plaque has been reported as a risk factor in the occurrence of lung cancer and mesothelioma, a reproducible and precise method of measurement of pleural plaque volume (PPV) is needed to further describe these relationships. The aim of the study was to assess the reproducibility of a 3-dimensional computed tomography (3D-CT) volumetric analysis of PPV in patients with occupational exposure to asbestos.A total of 28 patients were retrospectively randomly selected from the multicenter APEXS (Asbestos Post Exposure Survey) study, which was held between 2003 and 2005. All patients underwent a 3D-CT scan. Two readers specialized in chest radiology completed the 3D semiautomated quantification of lung volume using dedicated software. They also had to categorize the visual extent of pleural plaque in terms of thickness and circumference. Reproducibility of the continuous PPV variable was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Reproducibility of categorical variables was assessed using the κ test.Intraobserver reproducibility of PPV was almost perfect (ICC=0.98 [95% interval: 0.97-0.99]), and interobserver reproducibility was very good (ICC=0.93 [0.88-0.97]). At Bland-Altman analysis, the mean differences were 0.1 (limit of agreement: -11.0 to 11.2) and 3.7 cc (-17.8 to 25.2), respectively. Visual analysis of both plaque in terms of thickness and circumference were fair to moderate, with κ values ranging from 0.30 to 0.60.3D semiautomatic quantification of PPV is feasible and reproducible using CT in patients with occupational exposure to asbestos. PPV measurement may be useful to correlate with other asbestos-related disease outcomes and prognosis.

Introduction Les Resultats de l’etude NLST aux Etats-Unis et de l’etude NELSON en Europe ont ouvert le debat sur l’opportunite d’un depistage du cancer broncho-pulmonaire (CBP) chez des patients exposes a des carcinogenes respiratoires [1] , [2] . L’objectif de cette analyse est d’evaluer l’impact medico-economique, en France, de la mise en place d’un programme de depistage du CBP dans une cohorte de sujets exposes a l’amiante. Methodes L’analyse est basee sur une modelisation MCMC (Monte Carlo Markok Chain) permettant d’etablir le rapport cout utilite de la mise en place d’un depistage annuel du CBP par tomodensitometrie thoracique chez des sujets fumeurs et exposes fortement a l’amiante. Les donnees utilisees dans la modelisation sont l’incidence de CBP dans la cohorte francaise ARDCO (cohorte multiregionale de sujets exposes a l’amiante avec suivi longitudinal depuis 2002), et leurs consommations de soins, les parametres d’intervention sont issus de l’etude NLST. Les donnees d’utilites et de couts de prise en charge des CBP diagnostiques sont issues de la litterature. Une analyse de sensibilite a permis d’evaluer differentes strategies de depistage selon l’intervalle entre les scanners et la population cible. Resultats La mise en place d’un depistage annuel par TDM thoracique chez les sujets fumeurs et exposes fortement a l’amiante permet un gain de QALY de 0.041 par personne [IC 95 % 0.028–0.052] pour un cout de 6208 € par personne [IC 95 % 4536€–7904€], soit un ratio cout-utilite differentiel de 93 020 €/QALY [IC 95 % 51 898€–170 492€]. Lorsque le depistage repose sur un scanner tous les 2 ans, le rapport cout-utilite est plus favorable: 40 938 €/QALY [IC 95 % 22 440€–65 364€]. Conclusion Au regard des seuils habituels pour une intervention de sante, un depistage du CBP par TDM thoracique tous les 2 ans est acceptable et preferable a un depistage annuel dans cette population.

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.

Introduction Les lymphomes non hodgkiniens (LNH), les myelomes multiples (MM) et les leucemies lymphoides chroniques (LLC), hemopathies malignes derivees de la lignee lymphoide, sont des maladies frequentes et dont l’incidence est en augmentation. Ces affections sont possiblement en rapport avec une exposition environnementale et/ou professionnelle, avec de nombreux agents etiologiques suspectes. Le programme Rhelypro, soutenu par l’Anses, a pour but le reperage des expositions professionnelles aux cancerogenes consideres comme certains ou probables apres analyse des donnees de la litterature chez tous les patients ayant un diagnostic incident de LNH, MM, LLC, a partir d’un questionnaire specifique mis en place pour ce programme. Methode Il s’agit d’une etude multicentrique incluant 7 centres de consultation de pathologies professionnelles de Creteil, Paris - F.-Widal, Bordeaux, Caen, Lille, Toulouse, de juillet 2017 a avril 2019. Tous les cas incidents de LNH, MM et LLC, ont beneficie d’un questionnaire de reperage elabore collectivement par les equipes de pathologies professionnelles impliquees, et permettant de lister les principales situations d’exposition aux agents cancerogenes probables ou certains du Centre international de recherche sur le cancer (CIRC) pour lesquels un exces de LNH, MM ou LLC a ete rapporte. Un questionnaire professionnel classique etait ensuite utilise, suivie d’une expertise en pathologie professionnelle. L’acceptabilite du questionnaire par les patients, le nombre de sujets faisant l’objet d’une proposition de declaration de maladie professionnelle et l’identification du type de secteurs d’activites et de postes de travail concernes pour chaque nuisance ont ete evalues. Resultats La population d’etude est constituee de 205 patients avec un âge moyen de 60 ans. Les 3 nuisances les plus souvent retenues sont les solvants organiques (hors trichloroethylene, benzene et dichloromethane), le benzene et les pesticides. Des expositions professionnelles ont ete retenues pour 21 % des sujets d’apres l’expertise finale et ont conduit a proposer une demande de reconnaissance de maladie professionnelle. La sensibilite du questionnaire de reperage etait de 92 % et sa specificite de 83 % par rapport au questionnaire de pathologie professionnelle suivi d’expertise. Conclusion Le questionnaire de reperage propose parait avoir des performances (sensibilite, specificite) satisfaisantes, incitant a l’utiliser dans les services d’hematologie en routine pour les cas incidents de LNH. En cas de reponse positive, une expertise complementaire peut etre proposee en pathologie professionnelle dans le cadre du Reseau national de vigilance et de prevention des pathologies professionnelles.

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.

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.

Contexte L’association eventuelle entre l’exposition professionnelle a l’amiante et le cancer de l’œsophage demeure actuellement controversee, comme en temoigne l’evaluation du Centre international de recherche sur le cancer (CIRC) realisee en 2012. La question du lien eventuel entre ce cancer et l’exposition a l’amiante est cependant tres importante, tant en matiere de surveillance medicale des sujets exposes, qu’en matiere de reparation medico-legale des patients presentant ce type de pathologie. Objectif L’objectif de notre etude est d’analyser l’incidence et la mortalite par cancer de l’œsophage dans une cohorte de sujets ayant ete exposes professionnellement a l’amiante (cohorte ARDCo : « Asbestos-Related Diseases Cohort »). Methode Un suivi sur 10 ans de 14 515 hommes inclus dans le programme ARDCo entre octobre 2003 et decembre 2005 a ete realise. L’exposition a l’amiante a ete analysee par des hygienistes industriels a partir des donnees issues d’un questionnaire standardise adresse aux sujets eligibles. Les variables utilisees pour caracteriser cette exposition a l’amiante ont associe : la duree d’exposition a l’amiante, un indice d’exposition cumulee a l’amiante (IEC) et la latence (delai entre le debut de l’exposition et l’apparition des premiers symptomes de la maladie). Une analyse statistique des associations entre les variables d’exposition a l’amiante et, d’une part, l’incidence du cancer de l’œsophage et, d’autre part, la mortalite par cancer de l’œsophage, a ete realisee a l’aide d’un modele de Cox, avec ajustement sur le statut tabagique, la latence et l’IEC (exprime en Ln (IEC + 1)). Resultats Nous avons mis en evidence une relation dose-effet significative entre l’IEC a l’amiante et le cancer de l’œsophage, a la fois en incidence et en mortalite. Conclusion Cette vaste etude est en faveur d’une relation entre l’exposition a l’amiante et le cancer de l’œsophage.

Introduction L’exposition a l’amiante est largement decrite comme facteur de risque du cancer du larynx dans la litterature et classe par le CIRC comme cancerogene de groupe 1 depuis 2009. Toutefois, il n’existe en France aucun tableau de reconnaissance de maladie professionnelle pour cette pathologie dans le regime general ou agricole. D’autres facteurs de risque professionnels sont suspectes (brouillards d’acide fort inorganiques, hydrocarbures aromatiques polycycliques). L’action 12.4 du plan cancer 2014–2019 vise l’amelioration des connaissances en cancerologie professionnelle et ceci en exploitant notamment les donnees du reseau national de vigilance et de prevention des pathologies professionnelles (rnv3p) dans ce domaine. L’objectif de cette etude est une description des situations professionnelles a risque de cancer de larynx recenses dans le rnv3p de 2001 a 2016. Methodes Une extraction des cas de cancer du larynx (Codes CIM-10 C32 et D02.0) entre 2001 et 2016 dans la base du rnv3p a ete realisee. Les parametres etudies sont les donnees demographiques, les expositions professionnelles, le poste de travail, le secteur d’activite. Nous avons conserve pour notre etude les cas de cancer du larynx dont l’exposition est consideree par le medecin expert comme en lien direct avec la pathologie, c’est-a-dire avec une imputabilite moyenne (directe mais non essentielle) ou forte (directe et essentielle). Une analyse des commentaires saisis pour chacun des dossiers a ete realisee. Resultats Entre 2011 et 2016, 244 de probleme de sante (PST) de cancers du larynx ont ete enregistres dans la base du rnv3p. Parmi eux, 147 ont ete conclus comme d’origine professionnelle dont 87 juges par le medecin expert avec une imputabilite moyenne ou forte. Cette population est exclusivement masculine, avec un âge median de 59 ans. Sur 97 expositions professionnelles retrouvees parmi ces 87 dossiers, 78 concernent l’amiante. Les secteurs d’activite les plus representes correspondent a ceux des travaux de construction specialises (14 dossiers) et de la metallurgie (7 dossiers). Pour 60 cas sur les 87 etudies, une declaration de maladie professionnelle a ete conseillee au patient. Discussion L’exposition a l’amiante est la situation professionnelle a risque la plus decrite dans les cas de cancer du larynx recenses au sein de la base de 2001 a 2016. Cela apporte un element supplementaire quant a l’implication de l’amiante dans la cancerogenicite pour le larynx. Une reflexion sur la mise en place d’un nouveau tableau de maladie professionnelle paraitrait legitime de ce point de vue.

Contexte En 2015, des recommandations labellisees par la Haute Autorite de sante et l’institut national du cancer preconisaient la mise en place d’une experimentation sur le depistage du cancer bronchopulmonaire (CBP) chez les sujets exposes professionnellement a des agents cancerogenes pulmonaires par scanner thoracique. Objectif principal Evaluer la faisabilite d’un depistage du CBP chez des sujets exposes ou ayant ete expose professionnellement a des agents cancerogenes pulmonaires par scanner thoracique basse dose sans injection de produit de contraste. Methodes Seront inclus dans cette etudes des sujets a haut risque de CBP tel que defini dans la recommandation : sujets fumeurs âges de 55 a 74 ans, exposes ou ayant ete exposes a des cancerogenes pulmonaires certains selon le centre international de recherche sur le cancer (CIRC). L’etude se deroulera dans six centres specialises de reference (CSR). Compte tenu de la complexite du dispositif, il est propose dans un premier temps de tester la faisabilite et l’acceptabilite du dispositif de maniere sequentielle, les deux premieres annees (24 mois) sur deux CSR « Phase 1 : 2018–2020 ». Il est prevu d’etendre aux autres CSR apres deux ans « Phase 2 : 2020–2026 ». L’experimentation s’effectuera en plusieurs etapes : – reperage des sujets exposes ou ayant ete exposes professionnellement a des agents cancerogenes sur le poumon ; – evaluation des expositions professionnelles aux cancerogenes pulmonaires ; – evaluation du niveau de risque de CBP et verification de l’eligibilite ; – mise en œuvre du depistage, la realisation des scanners thoraciques sera effectuee par des centres specialises en imagerie thoracique ; – suivi pneumo-oncologique en cas de mise en evidence d’anomalies suspectes de CBP. Le critere d’evaluation principal est pour la phase 1 (2018–2020) : le taux de participation qui sera mesure par la proportion de sujets realisant le scanner thoracique basse dose parmi les sujets repondants eligibles et pour la phase 2 (2020–2026) : l’evaluation de l’impact du depistage du CBP mesure par des indicateurs de qualite des examens et des indicateurs de suivi. Retombees attendues Cette etude de faisabilite doit permettre d’apporter des elements essentiels avant d’envisager une generalisation au niveau national notamment en termes d’acceptabilite et de realisation pratique dans des centres specialises. Cette thematique correspond a une attente sociale forte (le champ des risques professionnels et des affections susceptibles d’en decouler).

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.

Resume Introduction Le syndrome d’Erasmus se definit comme l’association d’une sclerodermie systemique et d’une exposition a la silice. Observation Nous en rapportons un cas chez un foreur-artificier en carrieres de roches massives, expose a la silice et aux derives nitres contenus dans les explosifs. Conclusion La physiopathologie et les etiologies de la sclerodermie systemique sont encore imparfaitement connues mais il s’avere que le monoxyde d’azote, libere notamment lors de la metabolisation des derives nitres, est aussi implique dans la genese de la maladie : il semble donc licite de s’interroger sur les consequences d’une co-exposition au monoxyde d’azote non maitrisee et non quantifiee sur l’etat vasculaire, deja degrade par la sclerodermie. Plus largement, notre observation souligne l’importance d’un recueil soigneux et exhaustif des expositions professionnelles pour les patients atteints de sclerodermie systemique.

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.

Background: The relationships between asbestos exposure and colorectal cancer remain controversial. Objectives: We examined the association between asbestos exposure and colorectal cancer incidence. Methods: Volunteer retired workers previously exposed to asbestos were invited to participate in the French ARDCo screening program between 2003 and 2005. Additional data on risk factors for colorectal cancer were collected from the ARDCo-Nut subsample of 3,769 participants in 2011. Cases of colon and rectal cancer were ascertained each year through 2014 based on eligibility for free medical care following a cancer diagnosis. Survival regression based on the Cox model was used to estimate the relative risk of colon and rectal cancer separately, in relation to the time since first exposure (TSFE) and cumulative exposure index (CEI) to asbestos, and with adjustment for smoking in the overall cohort and for smoking, and certain risk factors for these cancers in the ARDCo-Nut subsample. Results: Mean follow-up was 10.2 years among 14,515 men, including 181 colon cancer and 62 rectal cancer cases (41 and 17, respectively, in the ARDCo-Nut subsample). In the overall cohort, after adjusting for smoking, colon cancer was significantly associated with cumulative exposure (HR = 1.14; 95% CI: 1.04, 1.26 for a 1-unit increase in ln-CEI) and ≥ 20–40 years since first exposure (HR = 4.67; 95% CI: 1.92, 11.46 vs. 0–20 years TSFE), and inversely associated with 60 years TSFE (HR = 0.26; 95% CI: 0.10, 0.70). Although rectal cancer was also associated with TSFE 20–40 years (HR = 4.57; 95% CI: 1.14, 18.27), it was not associated with ln-CEI, but these findings must be interpreted cautiously due to the small number of cases. Conclusions: Our findings provide support for an association between occupational exposure to asbestos and colon cancer incidence in men. Citation: Paris C, Thaon I, Hérin F, Clin B, Lacourt A, Luc A, Coureau G, Brochard P, Chamming’s S, Gislard A, Galan P, Hercberg S, Wild P, Pairon JC, Andujar P. 2017. Occupational asbestos exposure and incidence of colon and rectal cancers in French men: the Asbestos-Related Diseases Cohort (ARDCo-Nut). Environ Health Perspect 125:409–415; http://dx.doi.org/10.1289/EHP153

International audience; BACKGROUND:Our study aimed at analyzing incidence and mortality from esophageal cancer within a cohort of workers with previous occupational asbestos exposure (ARDCo Program).METHODS:A 10-year follow-up study was conducted in the 14 515 male subjects included in this program between October 2003 and December 2005. Follow-up began when exposure stopped. Asbestos exposure was analyzed by industrial hygienists using data from a standardized questionnaire. The Cox model was used, with age as the time axis variable adjusted for smoking, time since first exposure (TSFE) and cumulative exposure index (CEI) of exposure to asbestos.RESULTS:We reported a significant dose-response relationship between CEI of exposure to asbestos and esophageal cancer, in both incidence (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.00-1.58), and mortality (HR 1.40, [95%CI 1.12-1.75]).CONCLUSIONS:This large-scale study suggests the existence of a relationship between asbestos exposure and cancer of the esophagus.

Objectives To investigate inter-reader agreement for the detection of pleural and parenchymal abnormalities using CT in a large cross-sectional study comprising information on individual cumulative exposure to asbestos. Methods The project was approved by the hospital ethics committee, and all patients received information on the study and gave their written informed consent. In 5511 CT scans performed in a cohort of retired workers previously exposed to asbestos and volunteering to participate in a multiregional survey programme (Asbestos Related Diseases Cohort, ARDCO), double randomised standardised readings, triple in case of disagreement, were performed by seven trained expert radiologists specialised in thoracic imaging and blind to the initial interpretation. Inter-reader agreement was evaluated by calculating the κ-weighted coefficient between pairs of expert readers and results of routine practice and final diagnosis after expert reading. Results κ-Weighted coefficients between trained experts ranged from 0.28 to 0.52 (fair to good), 0.59 to 0.86 (good to excellent) and 0.11 to 0.66 (poor to good) for the diagnosis of asbestosis, pleural plaques and fibrosis of the visceral pleura, respectively. κ-Weighted coefficients between results of routine practice and final diagnosis after expert reading were 0.13 (poor), 0.53 (moderate) and 0.11 (poor) for the diagnosis of asbestosis, pleural plaques and fibrosis of the visceral pleura, respectively. Conclusions Interpretation of benign asbestos-related thoracic abnormalities requires standardisation of the reading and trained readers, particularly for participants asking for compensation, and with a view to the longitudinal survey of asbestos-exposed workers.

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.

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.

Background The association between pleural plaques and pleural mesothelioma remains controversial. The present study was designed to examine the association between pleural plaques on computed tomography (CT) scan and the risk of pleural mesothelioma in a follow-up study of asbestos-exposed workers. Methods Retired or unemployed workers previously occupationally exposed to asbestos were invited to participate in a screening program for asbestos-related diseases, including CT scan, organized between October 2003 and December 2005 in four regions in France. Randomized, independent, double reading of CT scans by a panel of seven chest radiologists focused on benign asbestos-related abnormalities. A 7-year follow-up study was conducted in the 5287 male subjects for whom chest CT scan was available. Annual determination of the number of subjects eligible for free medical care because of pleural mesothelioma was carried out. Diagnosis certification was obtained from the French mesothelioma panel of pathologists. Survival regression based on the Cox model was used to estimate the risk of pleural mesothelioma associated with pleural plaques, with age as the main time variable and time-varying exposure variables, namely duration of exposure, time since first exposure, and cumulative exposure index to asbestos. All statistical tests were two-sided. Results A total of 17 incident cases of pleural mesothelioma were diagnosed. A statistically significant association was observed between mesothelioma and pleural plaques (unadjusted hazard ratio (HR) = 8.9, 95% confidence interval [CI] = 3.0 to 26.5; adjusted HR = 6.8, 95% CI = 2.2 to 21.4 after adjustment for time since first exposure and cumulative exposure index to asbestos). Conclusion The presence of pleural plaques may be an independent risk factor for pleural mesothelioma.

Background Underreporting of occupational diseases related to asbestos exposure remains a matter of concern in France. The aim of this study was to evaluate the number of claims for compensation for asbestos-related non-malignant pulmonary or pleural occupational disease in subjects having undergone a chest CT-scan in a multiregional screening programme. Methods Among the 5444 voluntary retired asbestos-exposed subjects recruited in four regions between 2003 and 2005 who had undergone a chest CT-scan, the number of claims for compensation for an asbestos-related pulmonary or pleural benign disease was analysed in 2006 and 2010. Results Following CT-scan screening, 17.2% of participants were acknowledged as presenting with an asbestos-related non-malignant occupational disease, essentially pleural plaques, by the French National Health Insurance fund. Underreporting decreased as duration of follow-up after CT-scan increased. Nevertheless, 4 years after CT-scan, underreporting was still as high as 36% for subjects identified as presenting with pleural plaques. Mean duration between the date of CT-scan and the date of recognition as occupational disease was 7.4 months, shorter in cases where screening was coordinated by specialized centres. Conclusion A plan of action for an easier claiming process for compensation of asbestos-related diseases is desired. This could probably be obtained through improved sensitization of physicians engaged in the follow-up of asbestos-exposed subjects, and by standardization of the interpretation and reporting of asbestos-related abnormalities observed on chest CT-scans.

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.

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.

Introduction Certain digestive cancers, especially colorectal cancer, may be related to asbestos exposure. The aim of our study was to estimate the incidence of digestive cancers within a cohort of asbestos plant workers. Methods Our study was based on a retrospective cohort of 2,024 male and female workers occupationally exposed to asbestos, in the Calvados departement (France). Data on the cases of digestive cancers were collected thanks to the Calvados’ digestive cancer registry. For each localization, the observed number of cancers was calculated from 1st January 1978 to 31st December 2009 and compared with the expected number among the local general population, using Standardised Incidence Ratios (SIR). Asbestos exposure was assessed for each subject, using the company’s specific job exposure matrix, and according to three indicators: duration of exposure, Cumulative Exposure Index (CEI), mean atmospheric level. Results One hundred and nineteen cases of digestive cancers were observed, for an expected number of 77 (SIR = 1.54 [1.28; 1.85]). A significant excess of risk was observed for peritoneal mesothelioma, especially in women (SIR = 43.0 [13.9; 100]). Significantly elevated SIR were also observed among men for: all digestive cancers, even when excluding peritoneal mesothelioma (SIR = 1.50 [1.23; 1.82]); esophageal cancer in general (SIR = 1.67 [1.08; 2.47]) and among those with CEI above 80 fibres/ml.years (SIR = 1.90 [1.16; 2.94]); liver cancer (SIR = 1.85 [1.09; 2.92]). Concerning colorectal cancer, a significant excess of risk was observed for men with exposure duration above 25 years (SIR = 1.75 [1.05; 2.73]). Conclusions Our results are in favour of a link between long-duration asbestos exposure and colorectal cancer in men, which is consistent with most of the literature. They also suggest a relationship between asbestos exposure and cancer of the oesophagus in men. Finally, there might be an association with small intestine and liver cancers in men.

For lung cancer, there is evidence of a joint effect between smoking and asbestos. However, little is known about a possible joint effect between asbestos and other inorganic particles. The objective was to study the association between lung cancer and occupational asbestos exposure in the abscence or presence of additional exposure to inorganic particles. A 12-year follow-up study was conducted to analyse lung cancer incidence in a cohort of 13,814 retired workers previously exposed to asbestos and volunteering to participate in a multiregional survey program (Asbestos Related Diseases Cohort, ARDCO) from October 2003 and December 2005. From complete work histories, occupational exposure to asbestos, mineral wools, refractory ceramic fibers, crystalline silica and cement dust were assessed by job-exposure matrices. Association between lung cancer and occupational asbestos exposure was estimated by Cox model, adjusted for smoking, in the presence or absence of additional exposure to inorganic particles. At the end of follow-up (April 2015), 364 incident lung cancer cases were diagnosed. The association between lung cancer and asbestos exposure was statistically significant (HR=2.3 [95% CI=1.0-5.4]), but it seemed increased in the presence of additional exposure to mineral wools (HR=3.1 [95% CI=1.4-7.2]). However, at equal asbestos exposure level, the association was no longer different in the presence of additional exposure to mineral wools. Other inorganic particles did not modify the association between asbestos and lung cancer. Mineral wools may modify the association between lung cancer and asbestos. However, subjects exposed to both factors seemed also to be more exposed to asbestos.

Introduction Epidemiologic studies have found lower risks of lung cancer (LC), partly due to a lower prevalence of smoking, and with increasing evidence of potential protection in some animal farmers. However, farmers are also exposed to some hazardous air contaminants (pesticides, diesel exhaust, mineral dust). In the prospective cohort AGRICAN, we assessed associations between several crop-related activities and tasks and LC risk, including adenocarcinomas (ADC), squamous cell carcinomas (SqCC) and small cell carcinomas (SmCC). Methods AGRICAN includes French individuals affiliated to the agricultural health insurance scheme. Incident LC were identified by linkage with cancer registries from enrolment (2005–2007) to 2011. Data on crop exposure during lifetime (13 crops and from 2 to 5 specific tasks) were obtained from the enrolment questionnaire. Analyses were performed using a Cox model, with attained age as time scale, adjusted for gender, smoking history and exposure to potential protective activities – cattle and horses. Results Among the 148,046 subjects, 487 incident LC were identified. Higher risks were observed in pea growers, especially in those who harvested, (harvesting: HR = 1.43[0.99–2.06], with a significant relationship with duration of exposure (p-trend for duration = 0.06)), for all subtypes except ADC. Increased risks were also observed among (i) farmers growing vegetables (HR = 1.26[0.93–1.72]), (ii) vine-growers (ADC: HR = 1.37[0.97–1.93]), especially in those performing re-entry tasks (ADC: HR 1.40 [0.96–2.04]) and harvesting (ADC: HR = 1.37[0.95–1.95]); (iii) pesticide users on beets (SqCC: HR = 1.88[1.13–3.11]) and (iv) farmers who treated rape seeds (SqCC: HR = 2.55[1.17–5.53]). No significant relationship was observed with duration for any of these activities and tasks. Conclusions We found positive associations between LC risk and several crop-related tasks including pesticide exposure (application in fields or on seeds, re-entry tasks) or not like peas harvesting.

Introduction Farming and pesticide use have been repeatedly and consistently associated with prostate cancer risk but analysis on the role of specific active ingredients remain scarce and results inconclusive. We assessed associations between occupational exposure to specific organochlorines and prostate cancer in the agricultural cohort AGRICAN. Methods The AGRICAN cohort consisted of 181,842 participants, affiliated for at least 3 years to the French agricultural health insurance. Data on pesticide use on 6 crops, including years of beginning and ending, were collected from the enrolment questionnaire. Exposure to organochlorine insecticides and duration of exposure between 1950 and 2010 was assessed with the help of a crop-exposure matrix (PESTIMAT). Associations with prostate cancer were estimated using a Cox regression analysis with attained age as time scale. Results From enrolment (2005–2007) to 2009, 1 672 incident prostate cancer cases among 98,974 male participants were identified through linkage with cancer registries. A nearly significant increase in prostate cancer risk was observed when considering organochlorines as a group (HR 1.15, 95% CI: 0.99–1.32; 463 cases) with no linear relationship with duration of exposure. A significant association was observed for eight individual organochlorine pesticides (out of 18) and a significant relationship with duration of exposure was observed for 6 of them (aldrin, chlordane, dieldrin, DDD, toxaphene and HCH). When adjusting for exposure to the 5 other organochlorines, a greater prostate cancer risk remained among men with the highest duration of exposure to HCH and DDD. Conclusions Our study provides new results concerning the association between pesticide exposure and prostate cancer, especially for two organochlorines: DDD (a DDT metabolite) and HCH (a mix of isomers including γ-HCH also called lindane).

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 far...

Introduction: Farming and pesticide use have been repeatedly and consistently associated with prostate cancer risk but analysis on the role of specific active ingredients remain scarce and results ...

Contexte Dans les suites de la conference de consensus de 1999 sur le suivi medical des personnes ayant ete exposees a l’amiante, un programme experimental multiregional a ete mis en place, avec constitution de la cohorte asbestos-related diseases cohort (ARDCO). Objectif Ce travail etudie l’association entre plaques pleurales identifiees sur examen tomodensitometrique (TDM) du thorax et risque de mesotheliome ou de deces par cancer du poumon. Methodes Entre 2003 et 2005, des sujets retraites, anterieurement exposes a l’amiante et relevant du RGSS ont ete invites a participer a un programme de depistage dans les regions Aquitaine, Haute et Basse Normandie et Rhone-Alpes. Un index d’exposition cumule (IEC) a l’amiante a ete calcule pour chaque individu a partir d’un questionnaire professionnel standardise. Les examens TDM thoraciques ont ete relus par des experts radiologues, afin de determiner notamment l’existence d’anomalies pleurales liees a l’amiante (donnees disponibles chez plus de 5000 sujets). Les cas de mesotheliome incidents ont ete reperes a partir des demandes de prise en charge en ALD ou en maladie professionnelle (MP) aupres de la Securite sociale, avec sollicitation du College des anatomopathologistes specialises (MESOPATH) pour confirmer le diagnostic. Pour l’etude des CBP, une etude de mortalite a ete realisee avec obtention des causes de deces jusqu’au 31-12-2010 aupres du service CepiDc de l’Inserm. L’analyse statistique s’appuie sur une analyse de survie basee sur un modele de Cox, l’âge etant la variable principale. Resultats Chez les hommes, l’etude d’incidence (donnees ALD-MP) a retrouve une association significative entre la presence de plaques pleurales sur le TDM et le risque de developper un mesotheliome (hazard ratio [HR] ajuste sur l’IEC a l’amiante et la latence : 6,8 [IC 95 % : 2,2–21,4] pour les plaques pleurales typiques). L’etude de mortalite a identifie une association significative entre plaques pleurales et mortalite par cancer du poumon (HR ajuste sur le tabac et l’IEC a l’amiante : 2,41 [IC 95 % : 1,21–4,85]). Conclusion La presence de plaques pleurales apparait etre un facteur de risque independant pour la survenue du mesotheliome pleural et pour le risque de deces par cancer du poumon chez des sujets ayant ete exposes a l’amiante.