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Purpose: Recent evidence suggests that plant-based diets may reduce the risk of breast cancer (BC). However, the macronutrient composition of plant-based diets and its potential impact on BC risk has not been well explored. This analysis investigated the association of macronutrient composition with BC risk across a spectrum of plant-based diet indexes using a multidimensional approach. Design: This study followed 64,655 participants from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) cohort from 1993 to 2014. Diets were evaluated using validated 208-item diet history questionnaires at baseline (1993) and follow-up (2005), to calculate adherence to the overall plant-based diet (PDI), healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI). The association of macronutrient composition with BC risk was assessed via generalized additive time-dependent Cox models across different levels of these indexes. Response surfaces were generated to visualize compositional associations at the 25th, 50th, and 75th percentile of each index (low, moderate, and high). Results: A total of 3,932 incident BC cases were identified during the 21-year follow-up. There was a significant association between macronutrient composition and BC risk for hPDI, uPDI, and PDI (all P < 0.001). Akaike information criterion favored the hPDI model for characterizing the association between macronutrients and BC. BC risk was highest for individuals with a lower hPDI score who also consumed a diet containing lower protein (10%), lower carbohydrate (35%), and higher fat (55%). The lowest risk of BC was observed in those with higher hPDI scores with the lowest intake of protein (10%). At higher PDI and uPDI, diets containing higher protein (30%) and fat (45%) had the highest BC risk. Conclusion: These results demonstrate a complex relationship between macronutrient composition, plant-based diet quality, and BC risk. Further research is needed to examine specific foods that may be driving these associations. Registry: The protocol is registered at clinicaltrials.gov as NCT03285230. [ABSTRACT FROM AUTHOR]

The individual results of SARS-CoV-2 serological tests measured after the first pandemic wave of 2020 cannot be directly interpreted as a probability of having been infected. Plus, these results are usually returned as a binary or ternary variable, relying on predefined cut-offs. We propose a Bayesian mixture model to estimate individual infection probabilities, based on 81,797 continuous anti-spike IgG tests from Euroimmun collected in France after the first wave. This approach used serological results as a continuous variable, and was therefore not based on diagnostic cut-offs. Cumulative incidence, which is necessary to compute infection probabilities, was estimated according to age and administrative region. In France, we found that a "negative" or a "positive" test, as classified by the manufacturer, could correspond to a probability of infection as high as 61.8% or as low as 67.7%, respectively. "Indeterminate" tests encompassed probabilities of infection ranging from 10.8 to 96.6%. Our model estimated tailored individual probabilities of SARS-CoV-2 infection based on age, region, and serological result. It can be applied in other contexts, if estimates of cumulative incidence are available. [ABSTRACT FROM AUTHOR]

Many dietary guidelines recommend restricting the consumption of processed red meat (PRM) in favour of healthier foods such as fish, to reduce the risk of chronic conditions such as hypertension and diabetes. The objective of this study was to estimate the potential effect of replacing PRM for fatty fish, lean fish, red meat, eggs, pulses, or vegetables, on the risk of incident hypertension and diabetes. This was a prospective study of women in the E3N cohort study. Cases of diabetes and hypertension were based on self-report, specific questionnaires, and drug reimbursements. In the main analysis, information on regular dietary intake was assessed with a single food history questionaire, and food substitutions were modelled using cox proportional hazard models. 95 % confidence intervals were generated via bootstrapping. 71 081 women free of diabetes and 45 771 women free of hypertension were followed for an average of 18·7 and 18·3 years, respectively. 2681 incident cases of diabetes and 12 327 incident cases of hypertension were identified. Relative to PRM, fatty fish was associated with a 15 % lower risk of diabetes (HR = 0·85, 95 CI (0·73, 0·97)) and hypertension (HR = 0 85 (0·79, 0·91)). Between 3 and 10 % lower risk of hypertension or diabetes was also observed when comparing PRM with vegetables, unprocessed red meat or pulses. Relative to PRM, alternative protein sources such as fatty fish, unprocessed red meat, vegetables or pulses was associated with a lower risk of hypertension and diabetes. [ABSTRACT FROM AUTHOR]

Purpose: Saturated fat has long been associated with cardiovascular disease in multiple prospective studies, and randomized controlled trials. Few studies have assessed the relative associations between saturated fat and other macronutrients with hypertension, a major risk factor for cardiovascular disease. The aim of this study was to assess the relative associations between saturated fat, other macronutrients such as monounsaturated and polyunsaturated fat, proteins, and carbohydrates, and incident hypertension in a large prospective cohort of French women. Methods: This study used data from the E3N cohort study, including participants free of hypertension at baseline. A food frequency questionnaire was used to determine dietary intakes of saturated fat (SFA), monounsaturated fat (MUFA), polyunsaturated fat (PUFA), animal protein (AP), vegetable protein (VP), carbohydrates (CH) and various foods. Cases of hypertension were based on self-report, validated by drug reimbursement data. Covariates were based on self-report. Cox proportional hazard models were used to estimate the relative associations between different macronutrients and hypertension risk, using the 'substitution' framework. Bootstrapping was used to generate 95% confidence intervals. Results: This study included 45,854 women free of hypertension at baseline. During 708,887 person-years of follow-up, 12,338 incident cases of hypertension were identified. Compared to saturated fat, higher consumption of all other macronutrients was associated with a lower risk of hypertension (HRMUFA = 0.74 [0.67: 0.81], HRPUFA = 0.84 [0.77: 0.92], HRCH = 0.83 [0.77: 0.88], HRAP = 0.91 [0.85: 0.97], HRVP = 0.93 [0.83: 1.03]). Conclusion: This study finds that relative to other macronutrients such as monounsaturated or polyunsaturated fat, higher intake of saturated fat is associated with a higher risk of hypertension among women. [ABSTRACT FROM AUTHOR]

Background: The interplay between age and symptoms intensity on antibody response to SARS-CoV-2 infection has not been studied in a general population setting. Methods: We explored the serologic profile of anti-SARS-CoV-2 antibodies after the first wave of the pandemic, by assessing IgG against the spike protein (ELISA-S), IgG against the nucleocapsid protein (ELISA-NP) and neutralizing antibodies (SN) in 82,126 adults from a French population-based multi-cohort study. Results: ELISA-S positivity was increased in 30- to 49-year-old adults (8.5%) compared to other age groups (5.6% in 20- to 29-year-olds, 2.8% in ≥ 50-year-olds). In the 3681 ELISA-S positive participants, ELISA-NP and SN positivity exhibited a U-shaped relationship with age, with a lower rate in 30- to 49-year-old adults, and was strongly associated with COVID-19-like symptoms. Conclusion: Our study confirms the independent role of age and symptoms on the serologic profile of anti-SARS-CoV-2 antibodies, but the non-linear relationship with age deserves further investigation. [ABSTRACT FROM AUTHOR]

Background: Nutritional factors are essential for the functioning of the immune system and could therefore play a role in COVID-19 but evidence is needed. Our objective was to study the associations between diet and the risk of SARS-CoV-2 infection in a large population-based sample. Methods: Our analyses were conducted in the French prospective NutriNet-Santé cohort study (2009--2020). Seroprevalence of anti-SARS-CoV-2 antibodies was assessed by ELISA on dried blood spots. Dietary intakes were derived from repeated 24 h dietary records (at least 6) in the two years preceding the start of the COVID-19 pandemic in France (February 2020). Multi-adjusted logistic regression models were computed. Results: A total of 7766 adults (70.3% women, mean age: 60.3 years) were included, among which 311 were positive for anti-SARS-CoV-2 antibodies. Dietary intakes of vitamin C (OR for 1 SD=0.86 (0.75--0.98), P=0.02), vitamin B9 (OR=0.84 (0.72--0.98), P=0.02), vitamin K (OR=0.86 (0.74--0.99), P=0.04), fibers (OR=0.84 (0.72--0.98), P=0.02), and fruit and vegetables (OR=0.85 (0.74--0.97), P=0.02) were associated to a decreased probability of SARS-CoV-2 infection while dietary intakes of calcium (OR=1.16 (1.01--1.35), P=0.04) and dairy products (OR=1.19 (1.06--1.33), P=0.002) associated to increased odds. No association was detected with other food groups or nutrients or with the overall diet quality. Conclusions: Higher dietary intakes of fruit and vegetables and, consistently, of vitamin C, folate, vitamin K and fibers were associated with a lower susceptibility to SARS-CoV-2 infection. Beyond its established role in the prevention of non-communicable diseases, diet could therefore also contribute to prevent some infectious diseases such as COVID-19. [ABSTRACT FROM AUTHOR]

Background: Significant differences in COVID-19 incidence by gender, class and race/ethnicity are recorded in many countries in the world. Lockdown measures, shown to be effective in reducing the number of new cases, may not have been effective in the same way for all, failing to protect the most vulnerable populations. This survey aims to assess social inequalities in the trends in COVID-19 infections following lockdown.Methods: A cross-sectional survey conducted among the general population in France in April 2020, during COVID-19 lockdown. Ten thousand one hundred one participants aged 18-64, from a national cohort who lived in the three metropolitan French regions most affected by the first wave of COVID-19. The main outcome was occurrence of possible COVID-19 symptoms, defined as the occurrence of sudden onset of cough, fever, dyspnea, ageusia and/or anosmia, that lasted more than 3 days in the 15 days before the survey. We used multinomial regression models to identify social and health factors related to possible COVID-19 before and during the lockdown.Results: In all, 1304 (13.0%; 95% CI: 12.0-14.0%) reported cases of possible COVID-19. The effect of lockdown on the occurrence of possible COVID-19 was different across social hierarchies. The most privileged class individuals saw a significant decline in possible COVID-19 infections between the period prior to lockdown and during the lockdown (from 8.8 to 4.3%, P = 0.0001) while the decline was less pronounced among working class individuals (6.9% before lockdown and 5.5% during lockdown, P = 0.03). This differential effect of lockdown remained significant after adjusting for other factors including history of chronic disease. The odds of being infected during lockdown as opposed to the prior period increased by 57% among working class individuals (OR = 1.57; 95% CI: 1.00-2.48). The same was true for those engaged in in-person professional activities during lockdown (OR = 1.53; 95% CI: 1.03-2.29).Conclusions: Lockdown was associated with social inequalities in the decline in COVID-19 infections, calling for the adoption of preventive policies to account for living and working conditions. Such adoptions are critical to reduce social inequalities related to COVID-19, as working-class individuals also have the highest COVID-19 related mortality, due to higher prevalence of comorbidities. [ABSTRACT FROM AUTHOR]

Background: Our main objectives were to estimate the incidence of illnesses presumably caused by SARS-CoV-2 infection during the lockdown period and to identify the associated risk factors.Methods: Participants from 3 adult cohorts in the general population in France were invited to participate in a survey on COVID-19. The main outcome was COVID-19-Like Symptoms (CLS), defined as a sudden onset of cough, fever, dyspnea, ageusia and/or anosmia, that lasted more than 3 days and occurred during the 17 days before the survey. We used delayed-entry Cox models to identify associated factors.Results: Between April 2, 2020 and May 12, 2020, 279,478 participants were invited, 116,903 validated the questionnaire and 106,848 were included in the analysis. Three thousand thirty-five cases of CLS were reported during 62,099 person-months of follow-up. The cumulative incidences of CLS were 6.2% (95% Confidence Interval (95%CI): 5.7%; 6.6%) on day 15 and 8.8% (95%CI 8.3%; 9.2%) on day 45 of lockdown. The risk of CLS was lower in older age groups and higher in French regions with a high prevalence of SARS-CoV-2 infection, in participants living in cities > 100,000 inhabitants (vs rural areas), when at least one child or adolescent was living in the same household, in overweight or obese people, and in people with chronic respiratory diseases, anxiety or depression or chronic diseases other than diabetes, cancer, hypertension or cardiovascular diseases.Conclusion: The incidence of CLS in the general population remained high during the first 2 weeks of lockdown, and decreased significantly thereafter. Modifiable and non-modifiable risk factors were identified. [ABSTRACT FROM AUTHOR]

Résumé: En France, comme au niveau mondial, l'incidence du cancer du sein a doublé en 30 ans. Outre le vieillissement de la population et les progrès du dépistage, les facteurs environnementaux à effet perturbateur endocrinien ont été suggérés pour expliquer cette augmentation. Parmi eux, on retrouve les dioxines, produites lors de la combustion de produits chlorés. L'objectif du projet GEO3N était d'étudier l'association entre l'exposition environnementale (alimentaire et atmosphérique) aux dioxines et le risque de cancer du sein dans la cohorte E3N (98 995 femmes adhérentes de la Mutuelle générale de l'Éducation nationale [MGEN], suivies depuis 1990). Aucune association statistiquement significative n'a été mise en évidence entre exposition alimentaire aux dioxines et risque de cancer du sein dans la cohorte E3N (n = 63 830 dont 3 465 cas de cancer du sein ; risque relatif [RR] = 0,94 ; intervalle de confiance à 95 % IC [IC 95 %] = 0,86-1,04 pour les plus exposées versus les moins exposées). Les expositions atmosphériques ont été estimées grâce à un indicateur spatialisé créé pour les besoins de l'étude. Il prend en compte : 1) les émissions de 2 620 sources industrielles identifiées et localisées sur le territoire français entre 1990 et 2008 ; 2) l'histoire résidentielle des sujets de la cohorte E3N (dont 78 % sont localisés à l'adresse) ; 3) des paramètres météorologiques ; 4) des paramètres techniques des sources. Cet outil a permis d'étudier l'exposition atmosphérique de 4 529 cas de cancer du sein et 4 529 témoins appariés. L'étude sur la région Rhône-Alpes (429 cas et 716 témoins appariés) n'a pas montré d'association statistiquement significative entre l'augmentation de l'exposition atmosphérique aux dioxines et le risque de cancer du sein. Les résultats de l'étude nationale (4 529 cas et 4 529 témoins appariés) sont en cours d'analyse. Les hypothèses fortes ainsi que les résultats d'études précédentes encouragent tout de même à étudier de manière plus large l'effet de la pollution atmosphérique sur le risque de cancer du sein. In France, breast cancer is the leading cause of death in women. Its incidence has doubled over the last 30 years. In addition to an aging population and more widespread breast cancer screening, the hypothesis of environmental factors with endocrine-disrupting properties has been suggested to explain the rise in breast cancer incidence. These factors include dioxins, which are released during combustion processes of chlorinated organic materials. The French E3N national cohort (98 995 women who have been followed up since 1990) offers the opportunity to study the impact of environmental exposure to dioxins on breast cancer risk while taking the residential history of its members and their individual breast cancer risk factors into account. The objective of the GEO3N project was to study the association between environmental exposure to dietary and airborne dioxins and breast cancer risk. We assessed the association between estimated dietary dioxin exposure and breast cancer risk in 63 830 women from the E3N cohort (including 3 465 women with breast cancer). No statistically significant association was observed. The dioxin-emitting industrial sources in mainland France between 1990 and 2008 were identified (N=2620). The residential history of the E3N participants was geocoded, and 78% were located at the address level. A spatialized indicator for airborne dioxin exposure was developed by using a Geographic Information System (GIS) that took into account major dioxin dispersion parameters. Breast cancer risk associated with airborne dioxin exposure was estimated in 4529 case women with breast cancer matched to 4529 control women without it. In the Rhône-Alpes region (429 breast cancer cases matched to 716 controls), no statistically significant association was observed between airborne dioxin exposure and breast cancer risk. Analyses are still ongoing at the national level. Strong biological hypothesis and results from previous studies support the utility of further investigation into the effect of pollution exposure on breast cancer risk. [ABSTRACT FROM AUTHOR]

Cadmium, due to its estrogen‐like activity, has been suspected to increase the risk of breast cancer; however, epidemiological studies have reported inconsistent findings. We conducted a case–control study (4,059 cases and 4,059 matched controls) nested within the E3N French cohort study to estimate the risk of breast cancer associated with long‐term exposure to airborne cadmium pollution, and its effect according to molecular subtype of breast cancer (estrogen receptor negative/positive [ER−/ER+] and progesterone receptor negative/positive [PR−/PR+]). Atmospheric exposure to cadmium was assessed using a Geographic Information System‐based metric, which included subject's residence‐to‐cadmium source distance, wind direction, exposure duration and stack height. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Overall, there was no significant association between cumulative dose of airborne cadmium exposure and the risk of overall, premenopausal and postmenopausal breast cancer. However, by ER and PR status, inverse associations were observed for ER− (ORQ5 vs. Q1 = 0.63; 95% CI: 0.41–0.95, ptrend = 0.043) and for ER−/PR− breast tumors (ORQ4 vs. Q1 = 0.62; 95% CI: 0.40–0.95, ORQ5 vs. Q1 = 0.68; 95% CI: 0.42–1.07, ptrend = 0.088). Our study provides no evidence of an association between exposure to cadmium and risk of breast cancer overall but suggests that cadmium might be related to a decreased risk of ER− and ER−/PR− breast tumors. These observations and other possible effects linked to hormone receptor status warrant further investigations. What's new? Cadmium is a common environmental contaminant that exerts estrogen‐like activity in human cells. While this activity suggests that cadmium might influence breast cancer risk, the relationship between cadmium exposure and breast cancer remains unclear. In this study, the authors employed a Geographic Information System (GIS)‐based metric to assess atmospheric cadmium exposure in women in France. No significant association was found between airborne cadmium and overall breast cancer risk. Risk varied, however, according to menopausal status and tumor hormone receptor status. Significant inverse associations were indicated for estrogen receptor‐negative breast cancers. Additional research is needed to assess cadmium exposure‐associated cancer risks. [ABSTRACT FROM AUTHOR]

Objective: To identify individual and contextual socio-economic factors associated with an increase in fruit and vegetable (F&V) consumption over a 12-year period and evaluate if some socio-economic factors were differentially associated with the change in consumption of some types of F&V.Design: Associations between increased F&V consumption and socio-economic factors were studied with multivariate logistic regression.Setting: E3N, a French prospective cohort study of 98 995 women.Subjects: E3N participants (n 58 193) with information on diet in 1993 and 2005, and numerous individual and contextual socio-economic factors available.Results: Associations between some individual socio-economic factors and changes in F&V consumption were observed. For instance, women who lived in a large household (>3 children v. no child) had higher probability of increasing their vegetable consumption (OR=1·33; 95 % CI 1·24, 1·42). This association was driven by higher consumption of courgette and raw cucumber. Living with a partner was associated with higher odds of increasing consumption of fruits (OR=1·07; 95 % CI 1·02, 1·13) such as pear, peach and grape.Conclusions: Certain individual socio-economic factors, but none of the contextual socio-economic factors examined, were associated with an increase in F&V consumption. Factors associated with an increase in total F&V consumption were not necessarily associated with an increase in fruit or vegetable consumption separately, or with an increase in each subtype of fruit or vegetable. Magnitudes of the different associations observed also differed when F&V were considered together, separately or by subtype. Increases in F&V consumption were mostly observed in women with high socio-economic position. To develop effective nutritional interventions and policies that take the socio-economic environment of individuals into account, we recommend future research to further focus on (i) pathways through which population characteristics might influence changes in F&V consumption and (ii) existing interactions between individual and contextual socio-economic factors. [ABSTRACT FROM AUTHOR]

Objective: To identify individual and contextual socio-economic factors associated with a healthy diet.Design: Dietary data from a large cohort study were used to derive two mutually exclusive dietary patterns through a latent class analysis. Associations between dietary patterns and socio-economic factors were studied with logistic regression.Setting: E3N, a French prospective cohort study composed of women recruited from a national health insurance plan covering people working in the national education system.Subjects: E3N participants (n 73 031) with dietary and socio-economic data available.Results: The 'Healthy' pattern was characterized by a large consumption of fruits and vegetables and the 'Less Healthy' pattern by a large consumption of pizza and processed meat. When all socio-economic factors were analysed together, all of the individual factors considered were associated with a healthy diet (e.g. women with three or more children were less likely to follow a healthy diet v. women with no children, OR (95 % CI): 0·70 (0·66, 0·75)) while the contextual factors associated with a healthy diet included the size of the agglomeration of residence and the area of birth and residence (e.g. women living in the West of France were less likely to follow a healthy diet v. those living in the South of France: 0·78 (0·72, 0·83)).Conclusions: We demonstrated that individual and contextual factors are both associated with diet. Rather than focusing only on individual factors, we recommend future studies or public health and nutritional strategies on diet to consider both types of factors. [ABSTRACT FROM AUTHOR]

In this exploratory study, we measured for the first-time human exposure to about 90 semi-volatile organic chemicals (SVOCs) in France and Italy using silicone wristbands. Participants in France (n = 40) and in Italy (n = 31) wore a silicone wristband for five days during 2018 and 2019. Samples were analyzed for 39 polybrominated diphenyl ethers (PBDEs), 10 novel brominated flame retardants (nBFRs), 25 organophosphate esters (OPEs), and 18 polycyclic aromatic hydrocarbons (PAHs). In both groups, the most commonly detected chemicals were BDE-209, BEHTBP, tris[(2R)-1-chloro-2-propyl] phosphate (TCIPP), and phenanthrene among PBDEs, nBFRs, OPEs, and PAHs, respectively. The concentrations of ∑ 39 PBDEs, ∑ 10 nBFRs, ∑ 25 OPEs, ∑ 18 PAHs, and of most individual chemicals were generally significantly higher in samples from France than in those from Italy, except for BDE-209 and TCIPP. On a broader scale, the chemical concentrations were generally significantly lower in this study than those measured in the United States in previous studies using the same type of wristbands. Efforts to standardize the protocols for the use of silicone wristbands are still needed but this study shows that wristbands are capable of capturing regional differences in human exposure to a large variety of SVOCs and, therefore, can be used as personal exposure monitor for studies with global coverage. Image 1 • Wristbands were used to evaluate human exposure to SVOCs in France and Italy. • BDE-209, BEHTBP, TCIPP, and phenanthrene were the most abundant chemicals. • The reported concentrations of SVOCs were significantly lower than that in USA. • SVOCs concentration and K oa were negatively and significantly correlated. Wristbands were used to evaluate human exposure to SVOCs in France and Italy. BDE-209, BEHTBP, TCIPP, and phenanthrene were the most abundant chemicals. The measured concentrations of SVOCs were significantly lower than that in the US. [ABSTRACT FROM AUTHOR]

Material conditions of lockdown and changes in regular functioning may have played a role on depressive manifestations. We aimed to examine the association between housing conditions and changes in professional activity and depression during the first COVID-19 outbreak in France. Participants of the CONSTANCES cohort were followed online. A first questionnaire covered the lockdown period (assessing housing conditions and changes in professional activity), and a second the post-lockdown period (assessing depression using the Center of Epidemiologic Studies Depression-Scale (CES-D)). Incident depression was also estimated (with a previous CES-D measure). Logistic regression models were applied. 22,042 participants (median age 46 years, 53.2 % women) were included and 20,534 had a previous CES-D measure. Depression was associated with female gender, lower household income and past history of depression. A negative gradient between the number of rooms and the likelihood of depression was consistently observed (OR = 1.55 95 % [1.19–2.00] for one room, OR = 0.76 [0.65–0.88] for seven rooms), while a U-shape relationship was observed with the number of people living together (OR = 1.62 [1.42–1.84] for living alone, OR = 1.44 [1.07–1.92] for six persons). These associations were also observed with incident depression. Changes in professional activity were associated with depression (Started distance working (OR = 1.33 [1.17–1.50]). Starting distance working was also associated with incident depression (OR = 1.27 [1.08–1.48]). A cross-sectional design was used. The consequences of lockdown on depression may vary depending on living conditions and changes in professional activity, including distance working. These results could help to better identify vulnerable people to promote mental health. • Housing conditions were associated with both prevalent and incident depression during the first COVID-19 related lockdown • A statistical gradient was observed between the number of rooms in the dwelling and the risk of depression • Changes in professional activity (such as starting distance working) were associated with prevalent and incident depression • Gender (women), lower household income and past history of depression were also associated with greater odds of depression [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer (BC) characteristics are known to influence patients survival. Social differences have been reported by previous studies for those characteristics but questions persist because of inconsistent conclusions. We aimed to investigate the impact of education on BC stage, grade, and hormone receptor (HR) status, while adjusting for potential confounders including a broad set of health behaviors, anthropometric measures, and reproductive factors., Methods: In the French E3N cohort, 5236 women developed a primary invasive BC for which there was available information on stage, grade, and HR status. No multivariate analyses was performed for BC stage based on the lack of association in bivariate analyses. Odds ratios and confidence intervals were estimated using multinomial logistic regression models for BC grade or binomial logistic regression models for HR status of BC., Results: Women with a lower education were diagnosed with higher grade BC compared to women with a higher education (1.32 [1.12; 1.57]). This association was slightly attenuated after adjustment for covariates independently and more strongly affected in the fully adjusted model (1.20 [0.99; 1.45]). A significant association was observed between lower education and HR- status of BC (1.20 [1.02; 1.42]) attenuated after adjustment for age at first childbirth (1.12 [0.95; 1.33])., Conclusion: In this cohort, education was associated with BC grade and HR status but not stage at diagnosis. The link between education and BC grade was not entirely explained by the different adjustments. A specific mechanism could be at play and deserves further investigations., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Context and Objectives: Persistent organic pollutants (POPs) are a group of organic chemical compounds potentially toxic to human health. The objectives of this study were 1) to describe the levels of POPs biomarkers in blood samples from French women collected during the 1990s and to compare them with levels measured in two more recent French studies, 2) to identify POPs exposure profiles, and 3) to explore their main determinants., Methods: 73 POPs biomarkers were measured in the blood of 468 women from the French E3N cohort (aged 45-73 years), collected between 1994 and 1999: 28 per- and polyfluoroalkyl substances, 27 organochlorine pesticides, 14 polychlorinated biphenyls and 4 polybrominated diphenyl ethers. POPs biomarker levels were described and compared with levels measured in two more recent French studies conducted by the French National Public Health Agency, the ENNS and Esteban studies. Principal component analysis was performed on POPs quantified in at least 75% of samples to identify the main exposure profiles. Linear regression models were used to estimate the associations between anthropometric, socio-demographic and lifestyle characteristics and exposure to these profiles., Results: Among the 73 biomarkers measured, 41 were quantified in more than 75% of samples. Levels of most pollutants that were also measured in the Esteban of ENNS studies have decreased over time. Six POPs exposure profiles were revealed, explaining 62.1% of the total variance. Most of the characteristics studied were associated with adherence to at least one of these profiles., Conclusion: This study highlighted that most of the pollutants for which a comparison was possible decreased over the 10 or 20 years following the E3N blood collection, and identified those which, on the contrary, tended to increase. The health effects of the profiles identified could be assessed in future studies. The determinants identified should be confirmed in larger populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Studies suggested that exposure to air pollutants, with endocrine disrupting (ED) properties, have a key role in breast cancer (BC) development. Although the population is exposed simultaneously to a mixture of multiple pollutants and ED pollutants may act via common biological mechanisms leading to synergic effects, epidemiological studies generally evaluate the effect of each pollutant separately. We aimed to assess the complex effect of exposure to a mixture of four xenoestrogen air pollutants (benzo-[a]-pyrene (BaP), cadmium, dioxin (2,3,7,8-Tétrachlorodibenzo-p-dioxin TCDD)), and polychlorinated biphenyl 153 (PCB153)) on the risk of BC, using three recent statistical methods, namely weighted quantile sum (WQS), quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR). The study was conducted on 5222 cases and 5222 matched controls nested within the French prospective E3N cohort initiated in 1990. Annual average exposure estimates to the pollutants were assessed using a chemistry transport model, at the participants' residence address between 1990 and 2011. We found a positive association between the WQS index of the joint effect and the risk of overall BC (adjusted odds ratio (OR) = 1.10, 95% confidence intervals (CI): 1.03-1.19). Similar results were found for QGC (OR = 1.11, 95%CI: 1.03-1.19). Despite the association did not reach statistical significance in the BKMR model, we observed an increasing trend between the joint effect of the four pollutants and the risk of BC, when fixing other chemicals at their median concentrations. BaP, cadmium and PCB153 also showed positive trends in the multi-pollutant mixture, while dioxin showed a modest inverse trend. Despite we found a clear evidence of a positive association between the joint exposure to pollutants and BC risk only from WQS and QGC regression, we observed a similar suggestive trend using BKMR. This study makes a major contribution to the understanding of the joint effects of air pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: Active smoking and the A blood group are associated with pancreatic adenocarcinoma (PC) risk. However, potential interactions between those risk factors and the role of passive smoking have been little investigated. We aimed to explore specific and joint associations of passive and active smoking, and effect modification by the ABO blood group in French women., Methods: The study included 96,594 women from the E3N prospective cohort, mean age: 49 years (SD 6.7). Information on active and passive smoking was reported at inclusion and throughout follow-up. Cases were classified according to the International Classification of Diseases 10. Associations with passive and active smoking and effect modification by the ABO blood group were investigated with multivariable Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI)., Results: During a 24-year median follow-up, 346 incident PC cases were identified. Current smoking compared with never and former smoking (HR 1.51 [95% CI 1.08-2.10]), and passive smoking in childhood compared with no childhood exposure (HR 1.47 [95% CI 1.08-2.00]) were associated with increased PC risk, but not passive exposure in adulthood (HR 1.16 [95% CI 0.91-1.47]). Exposure to both passive smoking in childhood and current smoking was associated with a stronger risk (HR 2.80 [95% CI 1.42-5.52]) than exposure to both current smoking and passive smoking only in adulthood (HR 1.68 [95% CI 1.10-2.57]) compared with neither passive nor active smoking. Associations between active smoking and PC risk were strongest in the O or B groups, while associations with passive smoking were strongest in the A or AB blood groups, but the interaction terms were not statistically significant., Conclusions: Both current smoking and passive smoking in childhood were associated with PC risk, with a maximal risk of current smokers exposed to passive smoking during childhood. Possible interactions between blood groups and active or passive smoking must be investigated in a larger series., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Importance: After an infection by SARS-CoV-2, many patients present with persistent physical symptoms that may impair their quality of life. Beliefs regarding the causes of these symptoms may influence their perception and promote maladaptive health behaviors., Objective: To examine the associations of self-reported COVID-19 infection and SARS-CoV-2 serology test results with persistent physical symptoms (eg, fatigue, breathlessness, or impaired attention) in the general population during the COVID-19 pandemic., Design, Setting, and Participants: Participants in this cross-sectional analysis were 26 823 individuals from the French population-based CONSTANCES cohort, included between 2012 and 2019, who took part in the nested SAPRIS and SAPRIS-SERO surveys. Between May and November 2020, an enzyme-linked immunosorbent assay was used to detect anti-SARS-CoV-2 antibodies. Between December 2020 and January 2021, the participants reported whether they believed they had experienced COVID-19 infection and had physical symptoms during the previous 4 weeks that had persisted for at least 8 weeks. Participants who reported having an initial COVID-19 infection only after completing the serology test were excluded., Main Outcomes and Measures: Logistic regressions for each persistent symptom as the outcome were computed in models including both self-reported COVID-19 infection and serology test results and adjusting for age, sex, income, and educational level., Results: Of 35 852 volunteers invited to participate in the study, 26 823 (74.8%) with complete data were included in the present study (mean [SD] age, 49.4 [12.9] years; 13 731 women [51.2%]). Self-reported infection was positively associated with persistent physical symptoms, with odds ratios ranging from 1.39 (95% CI, 1.03-1.86) to 16.37 (95% CI, 10.21-26.24) except for hearing impairment (odds ratio, 1.45; 95% CI, 0.82-2.55) and sleep problems (odds ratio, 1.14; 95% CI, 0.89-1.46). A serology test result positive for SARS-COV-2 was positively associated only with persistent anosmia (odds ratio, 2.72; 95% CI, 1.66-4.46), even when restricting the analyses to participants who attributed their symptoms to COVID-19 infection. Further adjusting for self-rated health or depressive symptoms yielded similar results. There was no significant interaction between belief and serology test results., Conclusions and Relevance: The findings of this cross-sectional analysis of a large, population-based French cohort suggest that persistent physical symptoms after COVID-19 infection may be associated more with the belief in having been infected with SARS-CoV-2 than with having laboratory-confirmed COVID-19 infection. Further research in this area should consider underlying mechanisms that may not be specific to the SARS-CoV-2 virus. A medical evaluation of these patients may be needed to prevent symptoms due to another disease being erroneously attributed to "long COVID."

Background: We aimed to estimate the seropositivity to anti-SARS-CoV-2 antibodies in May-June 2020 after the first lockdown period in adults living in three regions in France and to identify the associated risk factors., Methods: Between 4 May 2020 and 23 June 2020, 16 000 participants in a survey on COVID-19 from an existing consortium of three general adult population cohorts living in the Ile-de-France (IDF) or Grand Est (GE) (two regions with high rate of COVID-19) or in the Nouvelle-Aquitaine (NA) (with a low rate) were randomly selected to take a dried-blood spot for anti-SARS-CoV-2 antibodies assessment with three different serological methods (ClinicalTrial Identifier #NCT04392388). The primary outcome was a positive anti-SARS-CoV-2 ELISA IgG result against the spike protein of the virus (ELISA-S). Estimates were adjusted using sampling weights and post-stratification methods. Multiple imputation was used to infer the cumulative incidence of SARS-CoV-2 infection with adjustments for imperfect tests accuracies., Results: The analysis included 14 628 participants, 983 with a positive ELISA-S. The weighted estimates of seropositivity and cumulative incidence were 10.0% [95% confidence interval (CI): 9.1%, 10.9%] and 11.4% (95% CI: 10.1%, 12.8%) in IDF, 9.0% (95% CI: 7.7%, 10.2%) and 9.8% (95% CI: 8.1%, 11.8%) in GE and 3.1% (95% CI: 2.4%, 3.7%) and 2.9% (95% CI: 2.1%, 3.8%) in NA, respectively. Seropositivity was higher in younger participants [odds ratio (OR) = 1.84 (95% CI: 1.79, 6.09) in <40 vs 50-60 years old and OR = 0.56 (95% CI: 0.42, 0.74) in ≥70 vs 50-60 years old)] and when at least one child or adolescent lived in the same household [OR = 1.30 (95% CI: 1.11, 1.53)] and was lower in smokers compared with non-smokers [OR = 0.71 (95% CI: 0.57, 0.89)]., Conclusions: Seropositivity to anti-SARS-CoV-2 antibodies in the French adult population was ≤10% after the first wave. Modifiable and non-modifiable risk factors were identified., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Regional monitoring of the proportion of the population who have been infected by SARS-CoV-2 is important to guide local management of the epidemic, but is difficult in the absence of regular nationwide serosurveys. We aimed to estimate in near real time the proportion of adults who have been infected by SARS-CoV-2., Methods: In this modelling study, we developed a method to reconstruct the proportion of adults who have been infected by SARS-CoV-2 and the proportion of infections being detected, using the joint analysis of age-stratified seroprevalence, hospitalisation, and case data, with deconvolution methods. We developed our method on a dataset consisting of seroprevalence estimates from 9782 participants (aged ≥20 years) in the two worst affected regions of France in May, 2020, and applied our approach to the 13 French metropolitan regions over the period March, 2020, to January, 2021. We validated our method externally using data from a national seroprevalence study done between May and June, 2020., Findings: We estimate that 5·7% (95% CI 5·1-6·4) of adults in metropolitan France had been infected with SARS-CoV-2 by May 11, 2020. This proportion remained stable until August, 2020, and increased to 14·9% (13·2-16·9) by Jan 15, 2021. With 26·5% (23·4-29·8) of adult residents having been infected in Île-de-France (Paris region) compared with 5·1% (4·5-5·8) in Brittany by January, 2021, regional variations remained large (coefficient of variation [CV] 0·50) although less so than in May, 2020 (CV 0·74). The proportion infected was twice as high (20·4%, 15·6-26·3) in 20-49-year-olds than in individuals aged 50 years or older (9·7%, 6·9-14·1). 40·2% (34·3-46·3) of infections in adults were detected in June to August, 2020, compared with 49·3% (42·9-55·9) in November, 2020, to January, 2021. Our regional estimates of seroprevalence were strongly correlated with the external validation dataset (coefficient of correlation 0·89)., Interpretation: Our simple approach to estimate the proportion of adults that have been infected with SARS-CoV-2 can help to characterise the burden of SARS-CoV-2 infection, epidemic dynamics, and the performance of surveillance in different regions., Funding: EU RECOVER, Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Institut National de la Santé et de la Recherche Médicale (Inserm)., Competing Interests: Declaration of interests FC reports personal fees from Imaxio and Sanofi, outside of the submitted work. The other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aimed at estimating the SARS-CoV-2 infection hospitalization (IHR) and infection fatality ratios (IFR) in France., Patients and Methods: A serosurvey was conducted in 9782 subjects from the two French regions with the highest incidence of COVID-19 during the first wave of the pandemic and coupled with surveillance data., Results: IHR and IFR were 2.7% and 0.49% overall. Both were higher in men and increased exponentially with age. The relative risks of hospitalization and death were 2.1 (95% CI: 1.9-2.3) and 3.8 (2.4-4.2) per 10-year increase, meaning that IHR and IFR approximately doubled every 10 and 5 years, respectively. They were dramatically high in the very elderly (80-90 years: IHR: 26%, IFR: 9.2%), and also substantial in younger adults (40-50 years: IHR: 0.98%, IFR: 0.042%)., Conclusions: These findings support the need for comprehensive preventive measures to help reduce the spread of the virus, even in young or middle-aged adults., (© 2020 Elsevier Masson SAS. All rights reserved.)

Background: Perturbations in circulating metabolites prior to a breast cancer diagnosis are not well characterised. We aimed to gain more detailed knowledge to help understand and prevent the disease., Methods: Baseline plasma samples from 791 breast cancer cases and 791 matched controls from the E3N (EPIC-France) cohort were profiled by nuclear magnetic resonance (NMR)-based untargeted metabolomics. Partial least-squares discriminant analysis (PLS-DA) models were built from NMR profiles to predict disease outcome, and odds ratios and false discovery rate (FDR)-adjusted CIs were calculated for 43 identified metabolites by conditional logistic regression., Results: Breast cancer onset was predicted in the premenopausal subgroup with modest accuracy (AUC 0.61, 95% CI: 0.49-0.73), and 10 metabolites associated with risk, particularly histidine (OR = 1.70 per SD increase, FDR-adjusted CI 1.19-2.41), N-acetyl glycoproteins (OR = 1.53, FDR-adjusted CI 1.18-1.97), glycerol (OR = 1.55, FDR-adjusted CI 1.11-2.18) and ethanol (OR = 1.44, FDR-adjusted CI 1.05-1.97). No predictive capacity or significant metabolites were found overall or for postmenopausal women., Conclusions: Perturbed metabolism compared to controls was observed in premenopausal but not postmenopausal cases. Histidine and NAC have known involvement in inflammatory pathways, and the robust association of ethanol with risk suggests the involvement of alcohol intake.

Background: Epidemiologic evidence is insufficient to draw conclusions on the impact of low-dose aspirin use on breast cancer risk, and the potential impact of other antiplatelet drugs such as clopidogrel needs to be explored., Methods: We investigated the association between breast cancer risk and low-dose aspirin or clopidogrel use in the E3N cohort, which includes 98,995 women, with information on breast cancer risk factors collected from biennial questionnaires matched with drug reimbursement data available from 2004. Women with at least two reimbursements of the drug of interest in any previous 3-month period were considered "ever" exposed. Exposure was considered as time-varying and multivariable Cox regression models were used to estimate HRs of breast cancer., Results: Among 62,512 postmenopausal women followed during 9 years on average, 2,864 breast cancer cases were identified. Compared with never use, a transient higher breast cancer risk was observed during the third year of low-dose aspirin use [HR 2-≤3 years of use = 1.49 (1.08-2.07)], followed by a lower risk [HR 4+ years of use = 0.72 (0.52-0.99)]. Clopidogrel ever use was associated with a higher breast cancer risk [HR, 1.30 (1.02-1.68)], restricted to estrogen receptor negative (ER - ) tumors [HR ER + = 1.14 (0.83-1.57), HR ER - = 3.07 (1.64-5.76), P homogeneity = 0.01]., Conclusions: Low-dose aspirin was associated with a lower breast cancer risk only after several years of use, while ever use of clopidogrel was associated with a higher ER - breast cancer risk., Impact: Antiplatelet drugs are not good pharmacologic candidates for breast cancer prevention., (©2021 American Association for Cancer Research.)

To investigate whether risk factors for keratinocyte carcinomas (KCs), namely pigmentary traits and sun exposure, are associated with risk of non-Hodgkin's lymphomas (NHL) and chronic lymphocytic leukemia (CLL). E3N is a prospective cohort of French women aged 40-65 years at inclusion in 1990. Cancer data were collected at baseline and updated every 2-3 years. Hazard Ratios (HRs) and 95% confidence intervals (CIs) for associations between pigmentary traits and sun exposure, and risk of CLL/NHL were estimated using Cox models. With a median follow-up of 24 years, 622 incident cases of CLL/NHL were ascertained among the 92,097 included women. The presence of nevi was associated with CLL/NHL risk: HR for "many or very many nevi" relative to "no nevi": 1.56 [1.15; 2.11]. Such association with number of nevi appears to be mostly limited to risk of CLL: HR for "many or very many nevi": 3.00 [1.38; 6.52]; versus 1.32 [0.94; 1.84] for NHL. Women whose skin was highly sensitive to sunburn also had a higher risk of CLL: HR = 1.96 [1.21; 3.18], while no increase in risk of NHL was observed. Skin or hair color, number of freckles, and average daily ultraviolet (UV) dose during spring and summer in location of residence at birth or at inclusion (kJ/m 2 ) were not associated with CLL/NHL risk. Some pigmentary traits (presence of nevi and skin sensitivity), but not sun exposure, were associated with CLL/NHL. These observations suggest that CLL may share some constitutional risk factors with keratinocyte cancers., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Although anti-inflammatory agents could theoretically have anticancer properties, results from cohort studies on nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer (BC) risk are inconsistent., Methods: We investigated the association between NSAID use and BC incidence in the French E3N prospective cohort, which includes 98,995 women born between 1925 and 1950 and insured by a health insurance plan that covers mostly teachers. Self-reported information on lifestyle and medical history has been collected biennially by questionnaires and matched with data from a drug reimbursement database covering the period 2004-2014. Women who self-reported current NSAID use in the 2000 or 2002 questionnaires or with at least two reimbursements in any previous 3-month period were defined as exposed to NSAIDs. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for the association of NSAID use with BC risk., Results: In the current analysis, 62,512 postmenopausal women were followed between 2004 and 2014 (9 years on average, starting at a mean age of 63 years; 2864 incident BC). In multivariable models, there was no statistically significant association between NSAID use and BC risk [HR = 1.00 (0.92-1.08), compared with non-exposed women]. The NSAID-BC associations did not differ by NSAID types, BC subtypes, risk factors, and comorbidities, nor by duration and dose of use. However, a statistically significant interaction was observed by proton pump inhibitor (PPI) drug use (P interaction  = 0.01) whereby a decreased risk of BC with NSAID use was only observed among women who also used PPI before., Conclusion: Only women who used NSAIDs after having used PPI had a lower risk of BC. This result is novel and requires replication in other studies.

Background: Brominated flame retardants (BFRs) are lipophilic substances with endocrine-disrupting properties. To date, only few investigations, mainly retrospective case-control studies, have explored the link between internal levels of BFRs and the risk of breast cancer, leading to conflicting results. We investigated the associations between plasma concentrations of two main groups of BFRs, PBDEs (pentabromodiphenyl ethers) and PBBs (polybrominated biphenyls), and the risk of breast cancer in a nested case-control study., Methods: A total of 197 incident breast cancer cases and 197 controls with a blood sample collected in 1994-1999 were included. Plasma levels of PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, BDE153, BDE-154) and of PBB-153 were measured by gas chromatography coupled to high-resolution mass spectrometry. Conditional logistic regression models, adjusted for potential confounders, were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Women were aged 56 years on average at blood draw. All cases, except for one, were diagnosed after menopause, with an average age at diagnosis of 68 years. Overall, we found no evidence of an association between plasma levels of PBDEs and PBB-153 and postmenopausal breast cancer risk (log-concentrations of BFRs yielding non-statistically significant ORs of 0.87 to 1.07). The analysis showed a non-linear inverse association for BDE-100 and BDE-153 and postmenopausal breast cancer risk; nevertheless, these findings were statistically significant only when the exposure was modeled as ng/L plasma (third vs. first quintile: OR = 0.42, 95%CI = 0.19-0.93 and OR = 0.42, 95%CI = 0.18-0.98, respectively) and not when modeled as ng/gr of lipids (OR = 0.58, 95%CI = 0.27-1.25 and OR = 0.53, 95%CI = 0.25-1.17). These results were unchanged in stratified analyses by tumor hormone receptor expression or body mass index., Conclusions: Our results suggest no clear association between internal levels of PBDEs and PBB-153 and the risk of breast cancer in postmenopausal women. However, these findings need to be carefully interpreted, taking into account limitations due to the limited number of women included in the study, the lack of information concerning genetic susceptibility of cases, and the unavailability of exposure assessment during critical windows of susceptibility for breast cancer. More studies are warranted to further investigate the relationships between PBDE and PBB exposure and breast cancer risk.

Endocrine-disrupting chemicals are proposed to increase breast cancer (BC) incidence. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), two perfluorinated alkylated substances (PFASs), are suspected to be ubiquitously present in the blood of human population worldwide. We investigated the associations between serum concentrations of these substances and BC risk. Etude Epidémiologique auprès de femmes de l'Education Nationale is a cohort of 98,995 French women born in 1925-1950 and followed up since 1990. We sampled 194 BC cases and 194 controls from women with available blood samples. Serum concentrations of PFASs were measured by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Adjusted conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two sided. While PFASs concentrations were not associated with BC risk overall, we found positively linear associations between PFOS concentrations and the risk of ER+ (3rd quartile: OR = 2.22 [CI = 1.05-4.69]; 4th quartile: OR = 2.33 [CI = 1.11-4.90]); P trend = 0.04) and PR+ tumors (3rd quartile: OR = 2.47 [CI = 1.07-5.65]; 4th quartile: OR = 2.76 [CI = 1.21-6.30]; P trend = 0.02). When considering receptor-negative tumors, only the 2nd quartile of PFOS was associated with risk (ER-: OR = 15.40 [CI = 1.84-129.19]; PR-: OR = 3.47 [CI = 1.29-9.15]). While there was no association between PFOA and receptor-positive BC risk, the 2nd quartile of PFOA was positively associated with the risk of receptor-negative tumors (ER-: OR = 7.73 [CI = 1.46-41.08]; PR-: OR = 3.44 [CI = 1.30-9.10]). PFAS circulating levels were differentially associated with BC risk. While PFOS concentration was linearly associated with receptor-positive tumors, only low concentrations of PFOS and PFOA were associated with receptor-negative tumors. Our findings highlight the importance of considering exposure to PFASs as a potential risk factor for BC., (© 2019 UICC.)

Background: Dioxins, Group 1 carcinogens, are emitted by industrial chlorinated combustion processes and suspected to increase breast cancer risk through receptor-mediated pathways., Objectives: We estimated breast cancer risk associated with airborne dioxin exposure, using geographic information system (GIS) methods and historical exposure data., Methods: We designed a case-control study (429 breast cancer cases diagnosed between 1990 and 2008, matched to 716 controls) nested within the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort. Airborne dioxin exposure was assessed using a GIS-based metric including participants' residential history, technical characteristics of 222 dioxin sources, residential proximity to dioxin sources, exposure duration and wind direction. Odds ratios (OR) and 95% confidence intervals (CI) associated with quintiles of cumulative exposure were estimated using multivariate logistic regression models., Results: We observed no increased risk of breast cancer for higher dioxin exposure levels overall and according to hormone-receptor status. We however observed a statistically significant OR for Q2 versus Q1 overall (1.612, 95% CI: 1.042-2.493) and for estrogen-receptor (ER) positive breast cancer (1.843, 95% CI: 1.033-3.292)., Conclusions: Overall, as well as according to hormone-receptor status, no increased risk was observed for higher airborne dioxin exposure. The increased risk for low exposure levels might be compatible with non-monotonic dose-response relationship. Confirmation of our findings is required. Our GIS-based metric may provide an alternative in absence of ambient dioxin monitoring and may allow assessing exposure to other pollutants., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Dioxins are environmental and persistent organic carcinogens with endocrine disrupting properties. A positive association with several cancers, including risk of breast cancer has been suggested., Objectives: This study aimed to develop and assess performances of an exposure metric based on a Geographic Information System (GIS) through comparison with a validated dispersion model to estimate historical industrial dioxin exposure for its use in a case-control study nested within a prospective cohort., Methods: Industrial dioxin sources were inventoried over the whole French territory (n > 2500) and annual average releases were estimated between 1990 and 2008. In three selected areas (rural, urban and urban-costal), dioxin dispersion was modelled using SIRANE, an urban Gaussian model and exposure of the French E3N cohort participants was estimated. The GIS-based metric was developed, calibrated and compared to SIRANE results using a set of parameters (local meteorological data, characteristics of industrial sources, e.g. emission intensity and stack height), by calculating weighted kappa statistics (wκ) and coefficient of determination (R 2 ). Furthermore, as performance evaluation, the final GIS-based metric was tested to assess atmospheric exposure to cadmium., Results: The concordance between the GIS-based metric and the dispersion model for dioxin exposure estimate was strong (wκ median = 0.78 (1st quintile = 0.72, 3rd quintile =0.82) and R 2 median = 0.82 (1st quintile = 0.71, 3rd quintile = 0.87)). We observed similar performance for cadmium., Conclusions: Our study demonstrated the ability of the GIS-based metric to reliably characterize long-term environmental dioxin and cadmium exposures as well as the pertinence of using dispersion modelling to construct and calibrate the GIS-based metric.

Background: The gender switch in asthma incidence around puberty has been put forward to suggest a role of sex hormones in asthma. However, there are limited and inconsistent findings on change in asthma incidence with menopause. We aimed to investigate the associations between menopause and asthma incidence, and interactions with overweight/obesity., Methods: Asthma incidence was assessed in 67,872 women free of asthma at baseline (aged 41-68 years) and regularly followed up as a part of the French E3N cohort. Adjusted hazard ratios (aHR) were derived from Cox models considering age as the time-scale, menopausal status as a time-varying covariate and taking into account menopausal treatment., Results: During 843,243 person-years of follow-up, 1205 new-onset asthma cases were identified. Compared with pre-menopause, surgical menopause was associated with an increased risk of asthma onset (aHR = 1.33 [95%CI 1.01-1.75]) but no association was observed for natural menopause (aHR = 1.05 [0.84-1.32]). In women with natural menopause, a further analysis separating the transition through menopause and the later post-menopausal period did not show any change in asthma incidence with menopause in the total sample or in normal-weight women alone. However, in overweight/obese women, peri-menopausal and post-menopausal women had an increased risk of developing asthma compared with pre-menopausal women of the same age (aHR = 1.91 [1.00-3.66] and aHR = 2.08 [1.07-4.06] respectively)., Conclusion: Surgical menopause was associated with an increased risk of asthma onset. For natural menopause, no change in asthma incidence was observed in normal-weight women. However, overweight/obese women had an increased risk of developing asthma after natural menopause., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Many studies have demonstrated that lifestyle factors, including diet, may influence cancer survival. The number of cancer survivors is increasing worldwide and little is known about long-term diet changes in people who had cancer. We studied 53,981 women from the prospective E3N-EPIC cohort study with available dietary data in 1993 and 2005, among whom 4,619 had a cancer diagnosis inbetween (including n = 2,699 breast cancers). We evaluated the potential impact of a cancer diagnosis (comparing women with cancer to women with no cancer) on changes in FV consumption using multivariable linear regression models considering cancer site, stage at diagnosis and socioeconomic factors. Compared to women with no cancer, a statistically significant increase in FV consumption (β=+2.65%, [1.22-4.09]) was observed in women who had cancer, and this association appeared to be driven by breast cancer exclusively. The increase in FV consumption was larger in women who had an advanced stage of breast cancer (stages II-IV) (β=+7.23%, [3.92-10.5]) than in women with stages 0-I (β=+2.03%, [-0.20 to 4.26]). Women with no partner and no children were those having the highest increase in FV consumption (β=+18.71%, [6.51-30.91]). These changes were only observed in specific SE groups. When considering adherence to guidelines, the proportion of women who consumed less than 7.5 portions a day in 1993 and more in 2005 was greater in women with advanced breast cancer. More research is now needed to understand how the inequities we observed impact the long-term health after cancer., (© 2018 UICC.)

The incidence of type 2 diabetes (T2D) is steadily rising worldwide since the past 30 years. There is increasing interest in understanding the contribution of exposure to endocrine disrupting chemicals (EDCs) to T2D trend. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are stable, persistent, and bioaccumulative synthetic compounds, suspected to act as EDCs and for which the diet is the main route of exposure. We investigated associations between estimated dietary exposure to PFOS and PFOA and the risk of T2D in the large E3N prospective cohort study. Among 71 270 women included in this study, 2680 cases of incident type 2 diabetes were validated during follow-up (1993-2012). Dietary exposure was estimated combining dietary consumption data collected in E3N and food contamination data provided by ANSES in the 2nd French Total Diet Study. The estimated mean dietary exposure to PFOS and PFOA was 0.50 ng/kg body weight /day and 0.86 ng/kg body weight /day respectively. An inverse U-shape association was found when considering PFOA and T2D: women in the 4th, 5th, and 6th decile groups had a HR [95%CI] of 1.21 [1.06-1.46], 1.35 [1.15-1.59], and 1.33 [1.05-1.41], respectively, when compared to women of the 1st decile group, while the other decile groups were not associated to the risk of T2D. The positive association had the strongest effect size for non-obese women (body mass index (BMI) ≤25 kg/m 2 ). No association was found between dietary exposure to PFOS and T2D, except when considering only women with BMI≤25 kg/m2, in which a positive nonlinear association was observed (HR [95%CI] = 1.46 [1.09-1.96], 1.52 [1.09-2.11], and 1.44 [1.01-2.06] for the 6th, 8th, and 9th decile groups respectively). This is the first study to evaluate the association between dietary exposure to PFOA and PFOS and the risk of developing T2D in a large observational study with over 15 years of follow-up. The present study highlights the importance of studying the effects of EDCs in large epidemiological studies including not occupationally exposed populations, as well as the importance of considering exposure to PFOS and PFOA as a relevant risk factor for T2D., (Copyright © 2018. Published by Elsevier GmbH.)

Background: With population aging, further asthma research is needed in the elderly., Objective: We assessed the relevance of the controller-to-total asthma medication ratio and its fluctuations over time to identify participants with a subsequent risk of poor asthma-related outcomes among well-characterized elderly women., Methods: We studied 4,328 women with ever asthma (69.6 ± 6.1 years) from the Asthma-E3N study (Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale), which combined drug claims data since 2004 with prospective individual characteristics. The levels of the yearly controller-to-total asthma medication ratio from 2004 to 2011 were included in latent class analysis to identify groups of women characterized by specific long-term fluctuations of the ratio. Multiple regression models estimated the subsequent risk of uncontrolled asthma, asthma attacks, asthma exacerbations, and poor asthma-related quality of life associated with the level and the fluctuations of the ratio., Results: A short-term (12 months) ratio below 0.5 was associated with a higher risk of subsequent uncontrolled asthma, asthma attacks, asthma exacerbations (odds ratio [95% confidence interval (CI)] = 2.13 [1.41; 3.23], 1.51 [1.01; 2.26], and 2.18 [1.37; 3.44], respectively), and a lower total asthma quality of life questionnaire score (β [95% CI] = -0.49 [-0.68; -0.29]). The analysis of the long-term fluctuations of the ratio identified 5 profiles ("Never regular treatment," 53.2%; "Persistent high ratio," 21.8%; "Increasing ratio," 4.4%; "Initiating treatment," 8.8%; "Treatment discontinuation," 11.8%). The subsequent risk of poor asthma-related outcomes was significantly higher in profiles characterized by no or interrupted asthma maintenance therapy over time, compared with the "Persistent high ratio" group., Conclusions: The level and the long-term fluctuations of the controller-to-total asthma medication ratio predict poor asthma-related outcomes in elderly women., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: The solar wavelength involved in melanoma occurrence remains unknown. Sunburns and latitude gradient are indicators of greater exposure to the ultraviolet B radiation. We examined the associations between the components of holiday sun exposure with numbers of small (2-4.9 mm) and large nevi (> or = 5 mm) in young children., Methods: Information about each holiday period from birth to interview was recorded from parents of 628 6-7-year-old children in four European countries. Sun exposure was characterized using four different components: cumulative duration of holidays, number of holiday periods, sunburn episodes and latitude gradient between habitual living place and holiday places., Results: Individual susceptibility to sunlight, cumulative duration and number of holiday periods were moderately associated with increasing number of small but not of large nevi. The number of small nevi together with sunburn history and latitude gradient were strong predictors of large nevi number. In contrast, sunburn history and latitude gradient were not associated with small nevi., Conclusions: Exposure to high doses of ultraviolet B radiation would be implicated in the formation of large nevi, while solar radiation other than the ultraviolet B could be implicated in the development of small nevi in children. Given that numbers of large nevi are strong predictors of melanoma in children and adolescents, these results agree with the hypothesis that high ultraviolet B doses are needed for melanoma occurrence, but probably not for nevi formation.