Inter-rater reliability of occupational exposure assessment in a case-control study of female breast cancer.

The objective of this paper was to estimate the inter-rater reliability of expert assessments of occupational exposures. An inter-rater reliability sub-study was conducted within a population-based case-control study of postmenopausal breast cancer. Detailed information on lifetime occupational histories was obtained from participants and two industrial hygienists assigned exposures to 185 jobs using a checklist of 293 agents. Experts rated exposure for each job-agent combination according to exposure status (unexposed/exposed), confidence that the exposure occurred (possible/probable/definite), intensity (low/medium/high), and frequency (% time per week). The statistical unit of observation was each job-agent assessment (185 jobs × 293 agents = 54,205 assessments per expert). Crude agreement, Gwet AC1/2 statistics, and Cohen's Kappa were used to estimate inter-rater agreement for confidence and intensity; for frequency, the intra-class correlation coefficient (ICC) was used. The majority of job-agent combinations were evaluated by the two experts to be not exposed (crude agreement >98% of decisions). The degree of agreement between the experts for the confidence of exposure status was Gwet AC1/2 = 0.99 (95% CI: 0.99-0.99), and for intensity, a Gwet AC2 = 0.99 (95% CI: 0.99-0.99). For frequency, an ICC of 0.31 (95% CI: 0.26-0.35) was found. A sub-analysis restricted to job-agent combinations for which the two experts agreed on exposure status revealed a moderate agreement for confidence of exposure (Gwet AC2 = 0.66) and high agreement for intensity (Gwet AC2 = 0.96). For frequency, the ICC was 0.52 (95% CI: 0.47-0.57). A high level of inter-rater agreement was found for identifying exposures and for coding intensity, but agreement was lower for the coding of frequency of exposure.

Does substance use explain social differences in terms of depression? Findings from the Constances cohort.

BACKGROUND: The role of alcohol, tobacco and cannabis use in social differences in terms of depression is poorly understood. METHOD: We have applied mediation and moderated-mediation models stratified by gender to a population-based sample (N = 37,192) of French men and women from the Constances cohort with baseline and follow-up measures of depressive states. We have examined whether socioeconomic status (SES, measured by education and income) differences in the prevalence of depressive states may be explained by both differences in prevalence of substance use according to SES (mediating effects) and differential effects of substance use on depressive state according to SES (moderating effects). RESULTS: In the mediation models, substance use only explained 5.3% and 2.4% of the association between low education and depressive state in men and women respectively, and was not a significant mediator for income. Moderated mediation models showed robust moderation effects of education and income in both men and women. The association of tobacco use with depressive symptoms, which was the only substance for which a mediation effect remained and for which the moderation effect of SES was the strongest, was significantly higher in participants with low SES. LIMITATIONS: The partially cross-sectional nature of the data restricts the possibility of drawing causality with regards to associations between SES and substance use. CONCLUSION: Targeting substance use, particularly tobacco, can especially reduce depression risk in individuals of low SES.

Association between Hospitalization and Change of Frailty Status in the GAZEL Cohort.

OBJECTIVES: To assess the relationship between changes of frailty status and intervening hospitalizations, using information of the GAZEL cohort, matched with the data of the French National Health Data System. DESIGN: Observational cohort study. PARTICIPANTS: Community-dwelling adults of the GAZEL cohort (n = 12145; aged between 58 and 73 years in 2012). MEASUREMENTS: Frailty was determined with the Strawbridge questionnaire in 2012, 2013 and 2014. Data regarding hospitalizations (notably their number, length of stay, emergency department use, and main diagnosis) were collected from the French National Health Data System. The relationship between intervening hospitalizations and changes of frailty status over time was assessed with multivariate Markov models. RESULTS: The prevalence of frailty was 14% in 2012 and 2013 and 17% in 2014. A total of 2715 changes in frailty status were observed from 2012 to 2014. At least one hospitalization was recorded for 1453 people (12%) between the 2012 and 2013 questionnaires, and 1472 (13%) between the 2013 and 2014 questionnaires. No association was found between intervening hospitalizations and changes of frailty status (aHR 1.14 [0.97-1.35] for robust to frail transition and aHR 0.89 [0.73-1.08] for frail to robust transition). However, repeated hospitalizations, hospitalizations after emergency department use, surgery and several diagnosis groups were significantly associated with transitions towards frailty or its recovery. CONCLUSION: Hospitalizations encompass a wide range of clinical situations, some of them being associated with incident frailty. An early recognition of these situations could help to better prevent and manage frailty in the early old age.

Association Between Potentially Inappropriate Medications and Frailty in the Early Old Age: A Longitudinal Study in the GAZEL Cohort.

OBJECTIVES: High-risk prescribing can have deleterious effects on the health of older people. This study aimed to assess the role of inappropriate prescribing on changes in frailty status over 3 years of follow-up. DESIGN, SETTING: This is a prospective observational study nested in the GAZEL cohort. PARTICIPANTS: The study sample included 12,405 community-dwelling people aged 58 to 73 in 2012, and followed for 3 years. MEASUREMENT: Polypharmacy and potentially inappropriate medications (PIMs) were assessed from reimbursement data by the French National Health Insurance. Frailty was evaluated each year with the Strawbridge questionnaire. PIMs were defined according to the Laroche list plus additional criteria dealing with inappropriate prolonged use of medications. The relationship between PIMs and changes in frailty status (incident frailty and recovery) was analyzed with Markov multistate modeling. RESULTS: The prevalence of frailty increased from 14% in 2012 to 17% in 2014, whereas the frequency of PIMs was 29% in 2012 and 23% in 2014. Polypharmacy (5-9 drugs: aHR 1.31, 95% CI 1.14-1.50; and 10 drugs or more: aHR 1.57, 95% CI 1.28-1.92) and potentially inappropriate use of nonsteroidal anti-inflammatory drugs (aHR 1.33, 95% CI 1.04-1.71) were significantly associated with incident frailty, when the presence of at least 1 PIM presented a small association with the risk of becoming frail (aHR 1.15, 95% CI 1.01-1.32). CONCLUSIONS/IMPLICATIONS: This study brings new elements to our knowledge regarding the association between inappropriate prescribing and frailty in older adults, which support research development to alert on inappropriate prescribing and to improve drug prescribing among old people, especially with polypharmacy.

Recurrent hyperactive ESR1 fusion proteins in endocrine therapy-resistant breast cancer.

Background: Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. Patients and methods: To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287-395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high coverage (>5000×) genomic profiling of 62 cancer-related genes in 254 ctDNA samples. In addition to traditional gene fusion detection methods (i.e. discordant reads, split reads), ESR1 REs were detected from targeted sequencing data by applying a novel algorithm (copyshift) that identifies major copy number shifts at rearrangement hotspots. Results: We identify 88 ESR1 REs across 83 unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2 via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease and co-occur with known ESR1 missense alterations, suggestive of polyclonal resistance. Importantly, all fusions result from a breakpoint in or near ESR1 intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro characterization of three fusions reveals ligand-independence and hyperactivity dependent upon the 3' partner gene. Our lower-bound estimate of ESR1 fusions is at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at least 10× enriched. We postulate this enrichment may represent secondary resistance to more aggressive endocrine therapies applied to patients with ESR1 LBD missense alterations. Conclusions: Collectively, these data indicate that N-terminal ESR1 fusions involving exons 6-7 are a recurrent driver of endocrine therapy resistance and are impervious to ER-targeted therapies.

Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer.

BACKGROUND: Genomic changes that occur in breast cancer during the course of disease have been informed by sequencing of primary and metastatic tumor tissue. For patients with relapsed and metastatic disease, evolution of the breast cancer genome highlights the importance of using a recent sample for genomic profiling to guide clinical decision-making. Obtaining a metastatic tissue biopsy can be challenging, and analysis of circulating tumor DNA (ctDNA) from blood may provide a minimally invasive alternative. PATIENTS AND METHODS: Hybrid capture-based genomic profiling was carried out on ctDNA from 254 female patients with estrogen receptor-positive breast cancer. Peripheral blood samples were submitted by clinicians in the course of routine clinical care between May 2016 and March 2017. Sequencing of 62 genes was carried out to a median unique coverage depth of 7503×. Genomic alterations (GAs) in ctDNA were evaluated and compared with matched tissue samples and genomic datasets of tissue from breast cancer. RESULTS: At least 1 GA was reported in 78% of samples. Frequently altered genes were TP53 (38%), ESR1 (31%) and PIK3CA (31%). Temporally matched ctDNA and tissue samples were available for 14 patients; 89% of mutations detected in tissue were also detected in ctDNA. Diverse ESR1 GAs including mutation, rearrangement and amplification, were observed. Multiple concurrent ESR1 GAs were observed in 40% of ESR1-altered cases, suggesting polyclonal origin; ESR1 compound mutations were also observed in two cases. ESR1-altered cases harbored co-occurring GAs in PIK3CA (35%), FGFR1 (16%), ERBB2 (8%), BRCA1/2 (5%), and AKT1 (4%). CONCLUSIONS: GAs relevant to relapsed/metastatic breast cancer management were identified, including diverse ESR1 GAs. Genomic profiling of ctDNA demonstrated sensitive detection of mutations found in tissue. Detection of amplifications was associated with ctDNA fraction. Genomic profiling of ctDNA may provide a complementary and possibly alternative approach to tissue-based genomic testing for patients with estrogen receptor-positive metastatic breast cancer.

[The REDSIAM network]. / Le réseau REDSIAM (Réseau données Sniiram) ­ Spécial REDSIAM.

The French national health database (SNIIRAM) proved to be very useful for epidemiology, health economics, evaluation, surveillance or public health. However, it is a complex database requiring important resources and expertise for being used. The REDSIAM network has been set up for promoting the collaboration of teams working on the Sniiram. The main aim of REDSIAM is to develop and validate methods for analyzing the Sniiram database for research, surveillance, evaluation and public health purposes by sharing the knowledge and experience of specialized teams in the fields of diseases identification from the Sniiram data. The work conducted within the network is devoted to the development and the validation of algorithms using Sniiram data for identifying specific diseases. The REDSIAM governance includes the Steering Committee composed of the main organizations in charge of producing and using the Sniiram data, the Bureau and the Technical Committee. The network is organized in thematic working groups focused on specific pathological domains, and a charter defines the rules for participation in the network, the functioning of the thematic working groups, the rules for publishing and making available algorithms. The articles in this special issue of the journal present the first results of some of the thematic working groups.

Body mass index as a predictor of healthy and disease-free life expectancy between ages 50 and 75: a multicohort study.

BACKGROUND: While many studies have shown associations between obesity and increased risk of morbidity and mortality, little comparable information is available on how body mass index (BMI) impacts health expectancy. We examined associations of BMI with healthy and chronic disease-free life expectancy in four European cohort studies. METHODS: Data were drawn from repeated waves of cohort studies in England, Finland, France and Sweden. BMI was categorized into four groups from normal weight (18.5-24.9 kg m-2) to obesity class II (⩾35 kg m-2). Health expectancy was estimated with two health indicators: sub-optimal self-rated health and having a chronic disease (cardiovascular disease, cancer, respiratory disease and diabetes). Multistate life table models were used to estimate sex-specific healthy life expectancy and chronic disease-free life expectancy from ages 50 to 75 years for each BMI category. RESULTS: The proportion of life spent in good perceived health between ages 50 and 75 progressively decreased with increasing BMI from 81% in normal weight men and women to 53% in men and women with class II obesity which corresponds to an average 7-year difference in absolute terms. The proportion of life between ages 50 and 75 years without chronic diseases decreased from 62 and 65% in normal weight men and women and to 29 and 36% in men and women with class II obesity, respectively. This corresponds to an average 9 more years without chronic diseases in normal weight men and 7 more years in normal weight women between ages 50 and 75 years compared to class II obese men and women. No consistent differences were observed between cohorts. CONCLUSIONS: Excess BMI is associated with substantially shorter healthy and chronic disease-free life expectancy, suggesting that tackling obesity would increase years lived in good health in populations.

Yttrium-90 radioembolization for colorectal cancer liver metastases in KRAS wild-type and mutant patients: Clinical and ccfDNA studies.

Patients with unresectable, chemo-refractory colorectal cancer liver metastases (CRCLM) have limited local treatment options. We report our institutional experience on the efficacy of resin-based yttrium-90 (90Y) radioembolization for the treatment of CRCLM and our findings on associated circulating cell-free DNA (ccfDNA) studies. A total of 58 patients treated with 90Y for CRCLM at the Medstar Georgetown University Hospital had a median survival of 6 months [95% confidence interval (CI), 4.55­7.45 months] after treatment, with a 12-month survival rate of 33%. The median survival from treatment stratified by mutational status was longer in the wild-type (WT) as compared to the KRAS mutant patients at 7 vs. 5 months, but did not achieve statistical significance (p=0.059). Median tumor local control duration after 90Y treatment was 2 months (95% CI, 0.34­3.66 months) for the entire cohort and was longer in the WT vs. the mutant patients (2 vs. 1 month, respectively, p=0.088). Plasma was prospectively collected from a subset of 9 patients both before and after single lobe treatment, and ccfDNA concentration and fragmentation index (FI) were measured using quantitative PCR and atomic-force microscopy (AFM). In the WT and KRAS mutant patients, DNA FI was reduced from a median of 0.73-0.65 after treatment. A reduction in DNA FI after single lobe treatment was associated with an improved overall survival (p=0.046). Analysis by AFM of paired pre- and post-treatment samples from KRAS mutant and WT patients revealed a larger average decrease in fragment size in the WT patients (p=0.013). 90Y radioembolization extends local control for CRCLM, however, KRAS mutant tumors may be more radio-resistant to treatment. Changes in the FI of patients following treatment were noted and may be evaluated in a larger study for relevance as a biomarker of response.

Development of a job-task-exposure matrix to assess occupational exposure to disinfectants among US nurses.

OBJECTIVES: Occupational exposure to disinfectants is associated with work-related asthma, especially in healthcare workers. However, little is known about the specific products involved. To evaluate disinfectant exposures, we designed job-exposure (JEM) and job-task-exposure (JTEM) matrices, which are thought to be less prone to differential misclassification bias than self-reported exposure. We then compared the three assessment methods: self-reported exposure, JEM and JTEM. METHODS: Disinfectant use was assessed by an occupational questionnaire in 9073 US female registered nurses without asthma, aged 49-68 years, drawn from the Nurses' Health Study II. A JEM was created based on self-reported frequency of use (1-3, 4-7 days/week) of 7 disinfectants and sprays in 8 nursing jobs. We then created a JTEM combining jobs and disinfection tasks to further reduce misclassification. Exposure was evaluated in 3 classes (low, medium, high) using product-specific cut-offs (eg, <30%, 30-49.9%, ≥50%, respectively, for alcohol); the cut-offs were defined from the distribution of self-reported exposure per job/task. RESULTS: The most frequently reported disinfectants were alcohol (weekly use: 39%), bleach (22%) and sprays (20%). More nurses were classified as highly exposed by JTEM (alcohol 41%, sprays 41%, bleach 34%) than by JEM (21%, 30%, 26%, respectively). Agreement between JEM and JTEM was fair-to-moderate (κ 0.3-0.5) for most disinfectants. JEM and JTEM exposure estimates were heterogeneous in most nursing jobs, except in emergency room and education/administration. CONCLUSIONS: The JTEM may provide more accurate estimates than the JEM, especially for nursing jobs with heterogeneous tasks. Use of the JTEM is likely to reduce exposure misclassification.

Quantitative discrimination between oil and water in drilled bore cores via Fast-Neutron Resonance Transmission Radiography.

A novel method utilizing the Fast Neutron Resonance Transmission Radiography is proposed for non-destructive, quantitative determination of the weight percentages of oil and water in cores taken from subterranean or underwater geological formations. The ability of the method to distinguish water from oil stems from the unambiguously-specific energy dependence of the neutron cross-sections for the principal elemental constituents. Monte-Carlo simulations and initial results of experimental investigations indicate that the technique may provide a rapid, accurate and non-destructive method for quantitative evaluation of core fluids in thick intact cores, including those of tight shales for which the use of conventional core analytical approaches appears to be questionable.

[The opening of the French national health database: Opportunities and difficulties. The experience of the Gazel and Constances cohorts]. / L'ouverture du Système national d'information inter-régimes de l'assurance maladie (SNIIRAM) : des opportunités et des difficultés. L'expérience des cohortes Gazel et Constances.

BACKGROUND: In France, the national health database (SNIIRAM) is an administrative health database that collects data on hospitalizations and healthcare consumption for more than 60 million people. Although it does not record behavioral and environmental data, these data have a major interest for epidemiology, surveillance and public health. One of the most interesting uses of SNIIRAM is its linkage with surveys collecting data directly from persons. Access to the SNIIRAM data is currently relatively limited, but in the near future changes in regulations will largely facilitate open access. However, it is a huge and complex database and there are some important methodological and technical difficulties for using it due to its volume and architecture. METHODS: We are developing tools for facilitating the linkage of the Gazel and Constances cohorts to the SNIIRAM: interactive documentation on the SNIIRAM database, software for the verification of the completeness and validity of the data received from the SNIIRAM, methods for constructing indicators from the raw data in order to flag the presence of certain events (specific diagnosis, procedure, drug…), standard queries for producing a set of variables on a specific area (drugs, diagnoses during a hospital stay…). Moreover, the REDSIAM network recently set up aims to develop, evaluate and make available algorithms to identify pathologies in SNIIRAM. CONCLUSION: In order to fully benefit from the exceptional potential of the SNIIRAM database, it is essential to develop tools to facilitate its use.

Effect size for the main cognitive function determinants in a large cross-sectional study.

BACKGROUND AND PURPOSE: The aim of our study was to examine the effect sizes of different cognitive function determinants in middle and early old age. METHODS: Cognitive functions were assessed in 11 711 volunteers (45 to 75 years old), included in the French CONSTANCES cohort between January 2012 and May 2014, using the free and cued selective reminding test (FCSRT), verbal fluency tasks, digit-symbol substitution test (DSST) and trail making test (TMT), parts A and B. The effect sizes of socio-demographic (age, sex, education), lifestyle (alcohol, tobacco, physical activity), cardiovascular (diabetes, blood pressure) and psychological (depressive symptomatology) variables were computed as omega-squared coefficients (ω2 ; part of the variation of a neuropsychological score that is independently explained by a given variable). RESULTS: These sets of variables explained from R2 = 10% (semantic fluency) to R2 = 26% (DSST) of the total variance. In all tests, socio-demographic variables accounted for the greatest part of the explained variance. Age explained from ω2 = 0.5% (semantic fluency) to ω2 = 7.5% (DSST) of the total score variance, gender from ω2 = 5.2% (FCSRT) to a negligible part (semantic fluency or TMT) and education from ω2 = 7.2% (DSST) to ω2 = 1.4% (TMT-A). Behavioral, cardiovascular and psychological variables only slightly influenced the cognitive test results (all ω2 < 0.8%, most ω2 < 0.1%). CONCLUSION: Socio-demographic variables (age, gender and education) are the main variables associated with cognitive performance variations between 45 and 75 years of age in the general population.

Laser biospectroscopy and 5-ALA fluorescence navigation as a helpful tool in the meningioma resection.

5-aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PP IX), which possesses fluorescent properties and is more intensively accumulated in tumor cells than in normal tissue. Therefore, the use of 5-ALA in the surgical treatment of intracranial tumors, particularly gliomas, has gained popularity in the last years, whereas its use in other intracranial pathological entities including meningiomas has been reported occasionally. This study describes a series of 28 patients with intracranial meningiomas, who were administered 5-ALA for a better visualization of tumor boundaries. Twelve patients underwent also laser spectroscopic analysis in order to confirm the visual impression of tumor tissue visualization. Bone infiltration was readily demonstrated. In one case, the tumor recurrence could have been prevented by removal of a tumor remnant, which would possibly have been better recognized if spectroscopic analysis had been used. Fluorescent navigation (FN) is a useful method for maximizing the radicality of meningioma surgery, particularly if the tumor infiltrates the bone, the skull base, and/or the surrounding structures.

Lifestyle-related risk factors and trajectories of work disability over 5 years in employees with diabetes: findings from two prospective cohort studies.

AIMS: To examine work disability trajectories among employees with and without diabetes and identify lifestyle-related factors associated with these trajectories. METHODS: We assessed work disability using records of sickness absence and disability pension among participants with diabetes and age- sex-, socio-economic status- and marital status-matched controls in the Finnish Public Sector Study (1102 cases; 2204 controls) and the French GAZEL study (500 cases; 1000 controls), followed up for 5 years. Obesity, physical activity, smoking and alcohol consumption were assessed at baseline and the data analysed using group-based trajectory modelling. RESULTS: Five trajectories described work disability: 'no/very low disability' (41.1% among cases and 48.0% among controls); 'low-steady' (35.4 and 34.7%, respectively); 'high-steady' (13.6 and 12.1%, respectively); and two 'high-increasing' trajectories (10.0 and 5.2%, respectively). Diabetes was associated with a 'high-increasing' trajectory only (odds ratio 1.90, 95% CI 1.47-2.46). Obesity and low physical activity were similarly associated with high work disability in people with and without diabetes. Smoking was associated with 'high-increasing' trajectory in employees with diabetes (odds ratio 1.88, 95% CI 1.21-2.93) but not in those without diabetes (odds ratio 1.32, 95% CI 0.87-2.00). Diabetes was associated with having multiple ( ≥ 2) risk factors (21.1 vs. 11.4%) but the association between multiple risk factors and the 'high-increasing' trajectory was similar in both groups. CONCLUSIONS: The majority of employees with diabetes have low disability rates, although 10% are on a high and increasing disability trajectory. Lifestyle-related risk factors have similar associations with disability among employees with and without diabetes, except smoking which was only associated with poorer prognosis in diabetes.

Excess non-psychiatric hospitalizations among employees with mental disorders: a 10-year prospective study of the GAZEL cohort.

OBJECTIVE: To examine whether non-psychiatric hospitalizations rates were higher in those with mental disorders. METHOD: In a cohort of 15,811 employees, aged 35-50 years in 1989, mental disorder status was defined from 1989 to 2000. Hospitalizations for all-causes, myocardial infarction (MI), stroke, and cancer, were recorded yearly from 2001 to 2011. Negative binomial regression models were used to estimate hospitalization rates over the follow-up. RESULTS: After controlling for baseline sociodemographic factors, health-related behaviors, self-rated health, and self-reported medical conditions, participants with a mental disorder had significantly higher rates of all-cause hospitalization [incidence rate ratio, IRR=1.20 (95%, 1.14-1.26)], as well as hospitalization due to MI [IRR=1.44 (95%, 1.12-1.85)]. For stroke, the IRR did not reach statistical significance [IRR=1.37 (95%, 0.95-1.99)] and there was no association with cancer [IRR=1.01 (95%, 0.86-1.19)]. A similar trend was observed when mental disorders groups were considered (no mental disorder, depressive disorder, mental disorders due to psychoactive substance use, other mental disorders, mixed mental disorders, and severe mental disorder). CONCLUSION: In this prospective cohort of employees with stable employment as well as universal access to healthcare, we found participants with mental disorders to have higher rates of non-psychiatric hospitalizations.

[The French mesothelioma network from 1998 to 2013]. / Mésothéliome: les dispositifs en place en France « le réseau mésothéliome ¼ 1998-2013.

Mesothelioma is a rare disease less than 0.3% of cancers in France, very aggressive and resistant to the majority of conventional therapies. Asbestos exposure is nearly the only recognized cause of mesothelioma in men observed in 80% of case. In 1990, the projections based on mortality predicted a raise of incidence in mesothelioma for the next three decades. Nowadays, the diagnosis of this cancer is based on pathology, but the histological presentation frequently heterogeneous, is responsible for numerous pitfalls and major problems of early detection toward effective therapy. Facing such a diagnostic, epidemiological and medico-legal context, a national and international multidisciplinary network has been progressively set up in order to answer to epidemiological survey, translational or academic research questions. Moreover, in response to the action of the French Cancer Program (action 23.1) a network of pathologists was organized for expert pathological second opinion using a standardized procedure of certification for mesothelioma diagnosis. We describe the network organization and show the results during this last 15years period of time from 1998-2013. These results show the major impact on patient's management, and confirm the interest of this second opinion to provide accuracy of epidemiological data, quality of medico-legal acknowledgement and accuracy of clinical diagnostic for the benefit of patients. We also show the impact of these collaborative efforts for creating a high quality clinicobiological, epidemiological and therapeutic data collection for improvement of the knowledge of this dramatic disease.

Occupational and non-occupational attributable risk of asbestos exposure for malignant pleural mesothelioma.

OBJECTIVES: To estimate the proportion of pleural mesothelioma cases that can be attributed to asbestos exposure in France including non-occupational exposure. METHODS: A population-based case-control study including 437 incident cases and 874 controls was conducted from 1998 to 2002. Occupational and non-occupational asbestos exposure was assessed retrospectively by two expert hygienists. ORs of pleural mesothelioma for asbestos-exposed subjects compared to non-exposed subjects, and population-attributable risk (ARp) of asbestos exposure were estimated using a conditional logistic regression. RESULTS: A clear dose-response relationship was observed between occupational asbestos exposure and pleural mesothelioma (OR=4.0 (99% CI 1.9 to 8.3) for men exposed at less than 0.1 f/mL-year vs. 67.0 (99% CI 25.6 to 175.1) for men exposed at more than 10 f/mL-year). The occupational asbestos ARp was 83.1% (99% CI 74.5% to 91.7%) for men and 41.7% (99% CI 25.3% to 58.0%) for women. A higher risk of pleural mesothelioma was observed in subjects non-occupationally exposed to asbestos compared to those never exposed. The non-occupational asbestos ARp for these subjects was 20.0% (99% CI -33.5% to 73.5%) in men and 38.7% (99% CI 8.4% to 69.0%) in women. When considering all kinds of asbestos exposure, ARp was 87.3% (99% CI 78.9% to 95.7%) for men and 64.8% (99% CI 45.4% to 84.3%) for women. CONCLUSIONS: Our study suggests that the overall ARp in women is largely driven by non-occupational asbestos exposure arguing for the strong impact of such exposure in pleural mesothelioma occurrence. Considering the difficulty in assessing domestic or environmental asbestos exposure, this could explain the observed difference in ARp between men and women.