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Abstract Background Spatial inequalities in health result from different exposures to health risk factors according to the features of geographical contexts, in terms of physical environment, social deprivation, and health care accessibility. Using a common geographical referential, which combines indices measuring these contextual features, could improve the comparability of studies and the understanding of the spatial dimension of health inequalities. Methods We developed the Geographical Classification for Health studies (GeoClasH) to distinguish French municipalities according to their ability to influence health outcomes. Ten contextual scores measuring physical and social environment as well as spatial accessibility of health care have been computed and combined to classify French municipalities through a K-means clustering. Age-standardized mortality rates according to the clusters of this classification have been calculated to assess its effectiveness. Results Significant lower mortality rates compared to the mainland France population were found in the Wealthy Metropolitan Areas (SMR = 0.868, 95% CI 0.863–0.873) and in the Residential Outskirts (SMR = 0.971, 95% CI 0.964–0.978), while significant excess mortality were found for Precarious Population Districts (SMR = 1.037, 95% CI 1.035–1.039), Agricultural and Industrial Plains (SMR = 1.066, 95% CI 1.063–1.070) and Rural Margins (SMR = 1.042, 95% CI 1.037–1.047). Conclusions Our results evidence the comprehensive contribution of the geographical context in the constitution of health inequalities. To our knowledge, GeoClasH is the first nationwide classification that combines social, environmental and health care access scores at the municipality scale. It can therefore be used as a proxy to assess the geographical context of the individuals in public health studies.

Epidemiological studies on health effects of air pollution usually estimate exposure at the residential address. However, ignoring daily mobility patterns may lead to biased exposure estimates, as documented in previous exposure studies. To improve the reliable integration of exposure related to mobility patterns into epidemiological studies, we conducted a systematic review of studies across all continents that measured air pollution concentrations in various modes of transport using portable sensors. To compare personal exposure across different transport modes, specifically active versus motorized modes, we estimated pairwise exposure ratios using a Bayesian random-effects meta-analysis. Overall, we included measurements of six air pollutants (black carbon (BC), carbon monoxide (CO), nitrogen dioxide (NO 2 ), particulate matter (PM 10 , PM 2.5 ) and ultrafine particles (UFP)) for seven modes of transport (i.e., walking, cycling, bus, car, motorcycle, overground, underground) from 52 published studies. Compared to active modes, users of motorized modes were consistently the most exposed to gaseous pollutants (CO and NO 2 ). Cycling and walking were the most exposed to UFP compared to other modes. Active vs passive mode contrasts were mostly inconsistent for other particle metrics. Compared to active modes, bus users were consistently more exposed to PM 10 and PM 2.5 , while car users, on average, were less exposed than pedestrians. Rail modes experienced both some lower exposures (compared to cyclists for PM 10 and pedestrians for UFP) and higher exposures (compared to cyclist for PM 2.5 and BC). Ratios calculated for motorcycles should be considered carefully due to the small number of studies, mostly conducted in Asia. Computing exposure ratios overcomes the heterogeneity in pollutant levels that may exist between continents and countries. However, formulating ratios on a global scale remains challenging owing to the disparities in available data between countries., 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.)

Background: An increasing evidence links air pollution to breast cancer (BC) risk. Yet, pollutant exposure estimates at the workplace location in pollution exposure assessment have not been considered., Objectives: This study investigates the association between particulate matters (PM 2·5 , PM 10 ) and nitrogen dioxide (NO 2 ) atmospheric concentrations (1990-2011), at the women's residential and workplace locations, and BC risk., Methods: This case-control study of 2419 BC cases and 2984 controls, was nested in the French prospective E3N cohort. The annual mean PM 2·5 , PM 10 and NO 2 concentrations were estimated using a Land Use Regression model (50 m x 50 m resolution) and assigned to the women's geocoded residential and workplace locations, from cohort recruitment to their index date (date of case diagnosis). Odds ratios (OR) and 95 % confidence intervals (CI) were estimated using multivariate logistic regression models., Results: An increased BC risk was observed for a 10 µg/m 3 increase of the 1990-2011 average PM 2·5 concentration estimates (OR=1·28; CI 1·00, 1·63). An increased risk was suggested for a 10 µg/m 3 increase for PM 10 (OR=1·09; CI 0·92, 1·30) and NO 2 (OR=1·05; CI 0·97, 1·13). No effect modification by menopausal status, nor difference by hormone receptor status were observed., Discussion: This study is the first to estimate BC risk and long-term air pollutant exposure from both, residential and workplace location histories. Results suggest that residential PM 2·5 , PM 10 and NO 2 concentrations are strongly correlated with workplace ones, indicating that residential data may serve as proxy for overall exposure. Future studies should consider exposure during commuting., 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.)

Background: While genetic, hormonal, and lifestyle factors partially elucidate the incidence of breast cancer, emerging research has underscored the potential contribution of air pollution. Polychlorinated biphenyls (PCBs) and benzo[a]pyrene (BaP) are of particular concern due to endocrine-disrupting properties and their carcinogenetic effect., Objective: To identify distinct long term trajectories of exposure to PCB153 and BaP, and estimate their associations with breast cancer risk., Methods: We used data from the XENAIR case-control study, nested within the ongoing prospective French E3N cohort which enrolled 98,995 women aged 40-65 years in 1990-1991. Cases were incident cases of primary invasive breast cancer diagnosed from cohort entry to 2011. Controls were randomly selected by incidence density sampling, and individually matched to cases on delay since cohort entry, and date, age, department of residence, and menopausal status at cohort entry. Annual mean outdoor PCB153 and BaP concentrations at residential addresses from 1990 to 2011 were estimated using the CHIMERE chemistry-transport model. Latent class mixed models were used to identify profiles of exposure trajectories from cohort entry to the index date, and conditional logistic regression to estimate their association with the odds of breast cancer., Results: 5058 cases and 5059 controls contributed to the analysis. Five profiles of trajectories of PCB153 exposure were identified. The class with the highest PCB153 concentrations had a 69% increased odds of breast cancer compared to the class with the lowest concentrations (95% CI 1.08, 2.64), after adjustment for education and matching factors. The association between identified BaP trajectories and breast cancer was weaker and suffered from large CI., Conclusions: Our results support an association between long term exposure to PCB153 and the risk of breast cancer, and encourage further studies to account for lifetime exposure to persistent organic pollutants., (© 2024. The Author(s).)

Background: Human exposure to air pollution involves complex mixtures of multiple correlated air pollutants. To date, very few studies have assessed the combined effects of exposure to multiple air pollutants on breast cancer (BC) risk., Objectives: We aimed to assess the association between combined exposures to multiple air pollutants and breast cancer risk., Methods: The study was based on a case-control study nested within the French E3N cohort (5222 incident BC cases/5222 matched controls). For each woman, the average of the mean annual exposure to eight pollutants (benzo(a)oyrene, cadmium, dioxins, polychlorinated biphenyls (PCB153), nitrogen dioxide (NO 2 ), ozone, particulate matter and fine particles (PMs)) was estimated from cohort inclusion in 1990 to the index date. We used the Bayesian Profile Regression (BPR) model, which groups individuals according to their exposure and risk levels, and assigns a risk to each cluster identified. The model was adjusted on a combination of matching variables and confounders to better consider the design of the nested case-control study. Odds ratios (OR) and their 95 % credible intervals (CrI) were estimated., Results: Among the 21 clusters identified, the cluster characterised by low exposures to all pollutants, except ozone, was taken as reference. A consistent increase in BC risk compared to the reference cluster was observed for 3 clusters: cluster 9 (OR=1.61; CrI=1.13,2.26), cluster 16 (OR=1.59; CrI=1.10,2.30) and cluster 15 (OR=1.38; CrI=1.00,1.88) characterised by high levels of NO 2 , PMs and PCB153. The other clusters showed no consistent association with BC., Discussion: This is the first study assessing the effect of exposure to a mixture of eight air pollutants on BC risk, using the BPR approach. Overall, results showed evidence of a positive joint effect of exposure to high levels to most pollutants, particularly high for NO 2 , PMs and PCB153, on the risk of BC., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Outdoor exposure to particulate matter (PM 2.5 and PM 10 ) in urban areas can vary considerably depending on the mode of transport. This study aims to quantify this difference in exposure during daily travel, by carrying out a micro-sensor measurement campaign. The pollutant exposure was assessed simultaneously over predefined routes in order to allow comparison between different transport modes having the same starting and ending points. During the six-week measurement campaign, the average reference values for PM background concentrations were 13.72 and 17.92μg/m 3 for the PM 2.5 and PM 10 , respectively. The results revealed that the mode with the highest exposure to PM 2.5 adjusted to background concentration (PM 2.5Norm ) was the bus (1.65) followed by metro (1.51), walking (1.33), tramway (1.31), car (1.09) and finally the bike (1.06). For PM 10Norm , the tramway had the highest exposure (1.86), followed by walking (1.68), metro (1.65), bus (1.61), bike (1.43) and finally the car (1.39). The level of urbanization around the route and the presence of preferential lanes for public transportation influenced the concentration to which commuters were exposed. For the active modes (bike and walking), we observed frequent variations in concentrations during the trip, characterized by punctual peaks in concentration, depending on the local characteristics of road traffic and urban morphology. Fluctuations in particulate matter inside public transport vehicles were partly explained by the opening and closing of doors during stops, as well as the passenger flows, influencing the re-suspension of particles. The car was one of the least exposed modes overall, with the lowest concentration variability, although these concentrations can vary greatly depending on the ventilation parameters used. These results encourage measures to move the most exposed users away from road traffic, by developing a network of lanes entirely dedicated to cycling and walking, particularly in densely populated areas, as well as encouraging the renewal of motorized vehicles to use less polluting fuels with efficient ventilation systems., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.)

This article describes some of the key prevention services in the Leon Berard Comprehensive Cancer Center (CLB) Lyon, France, which are based on clinical prevention services, outreach activities, and collaboration with professional and territorial health communities. In addition, research is embedded at all stages of the prevention continuum, from understanding cancer causes through to the implementation of prevention interventions during and after cancer. Health promotion activities in the community and dedicated outpatient primary cancer prevention services for individuals at increased risk have been implemented. The CLB's experience illustrates how prevention can be integrated into the comprehensive mission of cancer centers, and how in turn, the cancer centers may contribute to bridging the current fragmentation between cancer care and the different components of primary, secondary, and tertiary prevention. With increasing cancer incidence, the shift toward integrated prevention-centered cancer care is not only key for improving population health, but this may also provide a response to the shortage of hospital staff and overcrowding in cancer services, as well as offer opportunities to reduce carbon emissions from cancer care., (©2024 The Authors; Published by the American Association for Cancer Research.)

Cancer Causes: WHAT LEVERS FOR PRIMARY PREVENTION? Facing the continuous increase in cancer incidence, mobilizing efficient levers to act upstream of the disease is a major public health issue. Accelerating the transfer into practice of the continuous enrichment of the understanding of the multifactorial causes of cancers constitutes a first lever of prevention. This also requires a strengthening of the involvement of all actors and stakeholders, beyond the health and medico-social sectors. In order to guide practices, this article reviews the proportion of cancers attributable to the main lifestyle and environmental factors and causes, provides an update on cancers linked to heredity and the French oncogenetic organisation, addresses the specific issue of work related exposures and occupational cancers, proposes a prioritization of actions to break with the current fragmentation of prevention, in particular through improving the articulation of population-based interventions with targeted and personalized approaches, and better considering individuals in their environments.

Background: Dioxins are a family of chemical molecules that are chlorinated, lipophilic, and bio-accumulative. They are thought to enhance the risk of non-lymphoma Hodgkin's due to their known carcinogenic properties (NHL). This is the first epidemiological research to investigate the relationship between repeated emissions of airborne dioxin exposure and the risk of NHL., Objective: A case-control study nested within the French E3N cohort of 98,995 women covered by the health insurance provider of the national education system evaluated the association between cumulative airborne dioxin exposure and NHL risk., Materials and Methods: NHL incident cases (368) and controls (368) were compared. Over the duration of the study, participants' residential histories and the locations of industrial sites were gathered (1990-2008). Using a Geographic Information System (GIS)-based exposure index, the cumulative exposure to airborne dioxins for each participant was calculated at the individual address level. The odds ratios (OR) and 95 % confidence intervals (CI) were calculated using multivariable conditional logistic regression models (CI)., Results: The log-transformed continuous cumulative dioxin exposure index was substantially correlated with the risk of NHL (OR1.2 (95 % CI 1.0,1.4) for an increase in log-TEQ/m 2 of 4.4, or one standard deviation). The combined chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) subtype was significantly associated with NHL histological subtypes (OR 1.6 (95 % CI 1.1,2.3))., Conclusion: The findings of this study demonstrate a significant positive correlation between cumulative airborne dioxin exposure and the risk of NHL in women, and more specifically, a significant positive association for the CLL & SLL subtype. These results help to support the attempts to reduce the exposure to dioxins in the air., 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 © 2023. Published by Elsevier B.V.)

Objectives: The etiology of testicular germ cell tumors (TGCT) is suspected to be related to prenatal environmental risk factors. Some solvents have potential endocrine disrupting or carcinogenic properties and may disrupt male genital development in utero. The aim of this study was to examine the association between parental occupational exposure to solvents and TGCT risk among their offspring., Methods: A French nationwide case-control study, TESTIS included 454 TGCT cases and 670 controls frequency-matched on region and 5-year age strata. Participants were interviewed via telephone and provided information on parental occupations at birth. Job-exposure matrices (JEM) developed in the French Matgéné program were used to assign exposure to five petroleum-based solvents, five solvents or groups of oxygenated solvents, and five chlorinated solvents. Odds ratios (OR) for TGCT and 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusting for TGCT risk factors., Results: Occupational exposure to at least one solvent during the year of their son's birth was 41% among fathers and 21% among mothers. Paternal exposure to at least one solvent showed OR 0.89 (95% CI 0.68-1.15). Exposure to perchloroethylene (OR 1.41, 95% CI 0.55-3.61), methylene chloride (OR 1.13, 95% CI 0.54-2.34) and diesel/kerosene/fuel oil (OR 1.17, 95% CI 0.80-1.73) disclosed OR >1 but with low precision. Our results suggest a possible modest increase in non-seminoma risk for sons whose fathers were highly exposed to trichloroethylene (OR 1.44, 95% CI 0.79-2.63). Maternal exposure to at least one solvent showed OR 0.90 (95% CI 0.65-1.24). When stratifying by birth year, men born in the 1970s experienced an increased TGCT risk following maternal exposure to fuels and petroleum-based solvents (OR 2.74, 95% CI 1.11-6.76)., Conclusion: Overall, no solid association was found between parental occupational exposure to solvents and TGCT risk. The association found with maternal occupational exposure to fuels and petroleum solvents among older men needs further investigation.

Objective: This study investigated the association between occupational asbestos exposure (OAE) and survival in patients with histologically confirmed lung cancer (LC)., Methods: This monocentric study was conducted in the Comprehensive Cancer Centre Léon Bérard, Lyon, France. A systematic screening has been in place since 2014 for occupational exposure to carcinogens using a self-assessment questionnaire sent to all patients newly diagnosed with histologically confirmed LC identified through the multidisciplinary LC board from 2014 to 2019. When the physician suspected a work-related exposure from the questionnaire including job history, an occupational cancer consultation was carried out to detail carcinogen exposures and assess if the LC was work-related. Demographics, clinical characteristics and survival data were extracted from medical records. The association between asbestos exposure and overall survival (hazard ratio and 95% confidence intervals) was estimated by Cox proportional hazards regression., Results: Overall, 702 patients were eligible to the present study, including 180 patients with OAE. In the crude analysis, LCs assessed as moderately or highly attributable to OAE were associated with decreased overall survival (HR = 1.32, 95 %CI 1.04-1.67) compared to LC without OAE or with a low degree of imputability to OAE (median follow-up 28.8 months). After adjustment for confounding (age at diagnosis, smoking status, stage, brain metastasis at diagnosis, and histology), the association of OAE with overall survival was no longer statistically significant (HR = 1.21, 95 %CI 0.94-1.56)., Conclusion: Overall survival in occupationally asbestos exposed LC patients may be decreased in comparison with non-exposed LC patients, warranting further investigations in larger studies., 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 © 2023 Elsevier B.V. All rights reserved.)

Occupational lung cancer cases remain largely under-reported and under-compensated worldwide. In order to improve the detection and compensation of work-related lung cancers, we implemented a systematic screening of occupational exposures, combining a validated self-administered questionnaire to assess occupational exposures and a specialized occupational cancer consultation. After a pilot study, the present prospective, open-label, scale-up study aimed to assess this systematic screening of occupational exposures in lung cancer patients in five sites in France by associating university hospitals with cancer centers. Patients with lung cancer were sent a self-administered questionnaire to collect their job history and potential exposure to lung carcinogens. The questionnaire was assessed by a physician to determine if a specialized occupational cancer consultation was required. During the consultation, a physician assessed if the lung cancer was occupation-related and, if it was, delivered a medical certificate to claim for compensation. Patients were offered help from a social worker for the administrative procedure. Over 15 months, 1251 patients received the questionnaire and 462 returned it (37%). Among them, 176 patients (38.1%) were convened to the occupational cancer consultation and 150 patients attended the consultation. An exposure to occupational lung carcinogen was identified in 133 patients and a claim for compensation was judged possible for 90 patients. A medical certificate was delivered to 88 patients and 38 patients received compensation. Our national study demonstrated that a systematic screening of occupational exposures is feasible and will bring a significant contribution to improve the detection of occupational exposures in lung cancer patients.

Current evidence of an association of breast cancer (BC) risk with air pollution exposure, in particular from traffic exhaust, remains inconclusive, and the exposure assessment methodologies are heterogeneous. This study aimed to conduct a systematic review and meta-analysis on the association between traffic-related air pollution (TRAP) and BC incidence (PROSPERO CRD42021286774). We systematically reviewed observational studies assessing exposure to TRAP and BC risk published until June 2022, available on Medline/PubMed and Web of Science databases. Studies using models for assessing exposure to traffic-related air pollutants or using exposure proxies (including traffic density, distance to road, etc.) were eligible for inclusion. A random-effects meta-analysis of studies investigating the association between NO 2 /NO x exposure and BC risk was conducted. Overall, 21 studies meeting the inclusion criteria were included (seven case-control, one nested case-control, 13 cohort studies); 13 studies (five case-control, eight cohort) provided data for inclusion in the meta-analyses. Individual studies provided little evidence of an association between TRAP and BC risk; exposure assessment methods and time periods of traffic emissions were different. The meta-estimate on NO 2 exposure indicated a positive association (pooled relative risk per 10 µg/m 3 of NO 2 : 1.015; 95% confidence interval, CI: 1.003; 1.028). No association between NO x exposure and BC was found (three studies). Although there was limited evidence of an association for TRAP estimated with proxies, the meta-analysis showed a significant association between NO 2 exposure, a common TRAP pollutant marker, and BC risk, yet with a small effect size. Our findings provide additional support for air pollution carcinogenicity.

Nitrogen dioxide (NO 2 ) is an important air pollutant due to its adverse effects on human health. Yet, current evidence on the association between NO 2 and the risk of breast cancer lacks consistency. In this study, we investigated the association between long-term exposure to NO 2 and breast cancer risk in the French E3N cohort study. Association of breast cancer risk with NO 2 exposure was assessed in a nested case-control study within the French E3N cohort including 5222 breast cancer cases identified over the 1990-2011 follow-up period and 5222 matched controls. Annual mean concentrations of NO 2 at participants' residential addresses for each year from recruitment 1990 through 2011, were estimated using a land use regression (LUR) model. Multivariable conditional logistic regression models were used to compute odds ratios (ORs) and their 95% confidence intervals (CIs). Additional analyses were performed using NO 2 concentrations estimated by CHIMERE, a chemistry transport model. Overall, the mean NO 2 exposure was associated with an increased risk of breast cancer. In all women, for each interquartile range (IQR) increase in NO 2 levels (LUR: 17.8 μg/m 3 ), the OR of the model adjusted for confounders was 1.09 (95% CI: 1.01-1.18). The corresponding OR in the fully adjusted model (additionally adjusted for established breast cancer risk factors) was 1.07 (95% CI: 0.98-1.15). By menopausal status, results for postmenopausal women were comparable to those for all women, while no association was observed among premenopausal women. By hormone receptor status, the OR of estrogen receptor positive breast cancer = 1.07 (95% CI: 0.97-1.19) in the fully adjusted model. Additional analyses using the CHIMERE model showed slight differences in ORs estimates. The results of this study indicate an increased risk of breast cancer associated with long-term exposure to NO 2 air pollution. Observing comparable effects of NO 2 exposure estimated by two different models, reinforces these findings., 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Testicular cancer is the most common cancer in young men. Its causes are largely unknown, although prenatal occupational and environmental exposures have been suggested. We investigated paternal occupational exposure to heavy metals and welding fumes and the risk of testicular germ cell tumors (TGCT) in their offspring. A total of 454 cases and 670 controls were included from a French nationwide case-control study. The INTEROCC job exposure matrix was used to assign occupational exposures (cadmium, chromium, iron, nickel, lead, and welding fumes) to the fathers' jobs. Odds ratios (ORs) for TGCT were estimated using conditional logistic regression models for frequency-matched sets. Three complementary analytical approaches were used: (1) single-agent analysis, (2) analysis by groups, and (3) principal component analysis (PCA). The proportion of paternal exposure to different heavy metals and welding fumes ranged from 0.7% (cadmium) to 11.3% (lead). Based on PCA, three principal components explained 93.5% of the cumulative variance. No associations were found between heavy metals or welding fumes and TGCT. In this study, paternal occupational exposure to heavy metals or welding fumes was not associated with TGCT development in their sons., Competing Interests: The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript.

In epidemiology, left-truncated data may bias exposure effect estimates. We analyzed the bias induced by left truncation in estimating breast cancer risk associated with exposure to airborne dioxins. Simulations were run with exposure estimates from a Geographic Information System (GIS)-based metric and considered two hypotheses for historical exposure, three scenarios for intra-individual correlation of annual exposures, and three exposure-effect models. For each correlation/model combination, 500 nested matched case-control studies were simulated and data fitted using a conditional logistic regression model. Bias magnitude was assessed by estimated odds-ratios (ORs) versus theoretical relative risks (TRRs) comparisons. With strong intra-individual correlation and continuous exposure, left truncation overestimated the Beta parameter associated with cumulative dioxin exposure. Versus a theoretical Beta of 4.17, the estimated mean Beta (5%; 95%) was 73.2 (67.7; 78.8) with left-truncated exposure and 4.37 (4.05; 4.66) with lifetime exposure. With exposure categorized in quintiles, the TRR was 2.0, the estimated OR Q5 vs. Q1 2.19 (2.04; 2.33) with truncated exposure versus 2.17 (2.02; 2.32) with lifetime exposure. However, the difference in exposure between Q5 and Q1 was 18× smaller with truncated data, indicating an important overestimation of the dose effect. No intra-individual correlation resulted in effect dilution and statistical power loss. Left truncation induced substantial bias in estimating breast cancer risk associated with exposure with continuous and categorical models. With strong intra-individual exposure correlation, both models detected associations, but categorical models provided better estimates of effect trends. This calls for careful consideration of left truncation-induced bias in interpreting environmental epidemiological data., (© 2021. Springer Nature B.V.)

Molecular studies suggest that cadmium due to its estrogenic properties, might play a role in breast cancer (BC) progression. However epidemiological evidence is limited. This study explored the association between long-term exposure to airborne cadmium and risk of BC by stage, grade of differentiation, and histological types at diagnosis. A nested case-control study of 4401 cases and 4401 matched controls was conducted within the French E3N cohort. A Geographic Information System (GIS)-based metric demonstrated to reliably characterize long-term environmental exposures was employed to evaluate airborne exposure to cadmium. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. There was no relationship between cadmium exposure and stage of BC. Also, no association between cadmium exposure and grade of differentiation of BC was observed. However, further analyses by histological type suggested a positive association between cadmium and risk of invasive tubular carcinoma (ITC) BC [OR Q5 vs Q1  = 3.4 (95% CI 1.1-10.7)]. The restricted cubic spline assessment suggested a dose-response relationship between cadmium and ITC BC subtype. Our results do not support the hypothesis that airborne cadmium exposure may play a role in advanced BC risk, but suggest that cadmium may be associated with an increased risk of ITC., (© 2021. The Author(s).)

Background: Although the genetic and hormonal risk factors of breast cancer are well identified, they cannot fully explain the occurrence of all cases. Epidemiological and experimental studies have suggested that exposure to environmental pollutants, especially those with potential estrogenic properties, as polychlorinated biphenyls (PCBs) may have a role in breast cancer development. Being the most abundantly detected in human tissues and in the environment, congener 153 (PCB153) is widely used in epidemiological studies as indicator for total PCBs exposure., Objectives: We aimed to estimate the association between cumulative atmospheric exposure to PCB153 and breast cancer risk., Methods: We conducted a case-control study of 5222 cases and 5222 matched controls nested within the French E3N cohort from 1990 to 2011. Annual atmospheric PCB153 concentrations were simulated with the deterministic chemistry-transport model (CHIMERE) and were assigned to women using their geocoded residential history. Their cumulative PCB153 exposure was calculated for each woman from their cohort inclusion to their index date. Breast cancer odds ratios (ORs) associated with cumulative PCB153 exposure and their 95% confidence intervals (95% CIs) were estimated using multivariate conditional logistic regression models., Results: Overall, our results showed a statistically significant linear increase in breast cancer risk related to cumulative atmospheric exposure to PCB153 as a continuous variable (adjusted OR = 1.19; 95% CI: 1.08-1.31, for an increment of one standard deviation among controls (55 pg/m 3 )). Among women who became postmenopausal during follow-up, the association remained statistically significant (adjusted OR = 1.23; 95% CI: 1.09-1.39). In analyses by hormone receptors status, the positive association remained significant only for ER-positive breast cancer (adjusted OR = 1.18; 95% CI: 1.05-1.33)., Discussion: This study is the first to have estimated the impact of atmospheric exposure to PCB153 on breast cancer risk. Our results showed a statistically significant increase in breast cancer risk, which may be limited to ER-positive breast cancer. These results warrant confirmation in further independent studies but raise the possibility that exposure to PCB153 increase breast cancer risk., (Copyright © 2021 Elsevier Inc. All rights reserved.)