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Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water. Chronic exposure has been associated with increased cancer risk despite inconclusive evidence, partly due to the challenges in long-term exposure assessment and potential exposure misclassification. We estimated concentrations of nitrate and THMs in drinking water using a public regulatory monitoring database (SISE-Eaux) for CONSTANCES, a French population-based prospective cohort. We obtained 26,322,366 measurements of drinking water parameters from 2000 to 2020. We excluded missing, implausible and duplicated measurements; we corrected or imputed missing geocodes of sampling locations; we calculated the annual median concentration of nitrate and THMs by surveillance area. To predict missing annual median concentrations, linear mixed models with random intercept using surveillance area as a clustering variable were developed for each region for nitrate and the four THM components (chloroform, chlorodibromomethane, bromodichloromethane and bromoform) separately. Concentrations in the nearest surveillance area from the household were merged per year among 75,462 participants with residential history geocoded for 2000-2020. Estimated concentrations resulting from this approach were compared with measured concentrations in 100 samples collected in Paris, Rennes and Saint-Brieuc in 2021. Median annual concentrations of total THMs and nitrate at study participants' homes for 2000-2020 were, respectively, 15.7 μg/l (IQR: 15.2) and 15.2 mg/l (IQR: 20.8). Among these, 35% were based on measurements for nitrate (16% for THMs), 44% (46%) were predicted using on linear mixed models, and 21% (38%) were based on distribution unit median values. Conditional R 2 predictive models ranged from 0.71 to 0.91 (median: 0.85) for nitrate, and from 0.48 to 0.80 for THMs (median: 0.68). These concentrations will allow future association analyses with risk of breast and colorectal cancer. Our cleaning process introduced here could be adapted to other large drinking water monitoring data., 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 Inc. All rights reserved.)

Research Question: Do heavy metals affect the risk of diminished ovarian reserve (DOR) in women of reproductive age?, Design: A total of 139 cases and 153 controls were included between 2016 and 2020. The participants were aged between 18 and 40 years and attended consultations for couple infertility in one of four fertility centres in western France. Cases of DOR were defined as women with an antral follicle count less than 7, anti-Müllerian hormone levels 1.1 ng/ml or less, or both. Controls were frequency matched on age groups and centres, and were women with normal ovarian reserve evaluations, no malformations and menstrual cycles between 26 and 35 days. Heavy metals (lead, mercury, cadmium and chromium) were measured in whole blood at inclusion. Single-exposure associations were examined with multivariable logistic regressions adjusted on potential confounders. Mixture effects were investigated with quantile g-computation and Bayesian kernel machine regression (BKMR)., Results: Chromium as a continuous exposure was significantly associated with DOR in unadjusted models (OR 2.07, 95% CI 1.04 to 4.13) but the association was no longer significant when confounders were controlled for (adjusted OR 2.75, 95% CI 0.88 to 8.60). Similarly, a statistically significant association was observed for the unadjusted second tercile of cadmium exposure (OR 1.87, 95% CI 1.06 to 3.30); however, this association was no longer statistically significant after adjustment. None of the other associations tested were statistically significant. Quantile g-computation and BKMR both yielded no significant change of risk of DOR for the mixture of metals, with no evidence of interaction., Conclusions: Weak signals that some heavy metals could be associated with DOR were detected. These findings should be replicated in other studies., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Associations of long-term exposure to air pollution and greenspace with health-related quality of life (HRQOL) are poorly studied and few studies have accounted for asthma-rhinitis status., Objective: To assess the associations of air pollution and greenspace with HRQOL and whether asthma and/or rhinitis modify these associations., Methods: The study was based on the participants in the second (2000-2002, n = 6542) and third (2011-2013, n = 3686) waves of the European Community Respiratory Health Survey (ECRHS) including 19 centres. The mean follow-up time was 11.3 years. HRQOL was assessed by the SF-36 Physical and Mental Component Summary scores (PCS and MCS). NO 2 , PM 2.5 and PM 10 annual concentrations were estimated at the residential address from existing land-use regression models. Greenspace around the residential address was estimated by the (i) mean of the Normalized Difference Vegetation Index (NDVI) and by the (ii) presence of green spaces within a 300 m buffer. Associations of each exposure variable with PCS and MCS were assessed by mixed linear regression models, accounting for the multicentre design and repeated data, and adjusting for potential confounders. Analyses were stratified by asthma-rhinitis status., Results: The mean (SD) age of the ECRHS-II and III participants was 43 (7.1) and 54 (7.2) years, respectively, and 48 % were men. Higher NO 2 , PM 2.5 and PM 10 concentrations were associated with lower MCS (regression coefficients [95%CI] for one unit increase in the inter-quartile range of exposures were -0.69 [-1.23; -0.15], -1.79 [-2.88; -0.70], -1.80 [-2.98; -0.62] respectively). Higher NDVI and presence of forests were associated with higher MCS. No consistent associations were observed for PCS. Similar association patterns were observed regardless of asthma-rhinitis status., Conclusion: European adults who resided at places with higher air pollution and lower greenspace were more likely to have lower mental component of HRQOL. Asthma or rhinitis status did not modify these associations., Competing Interests: Declaration of competing interest MJA holds investigator initiated grants for unrelated research from Pfizer, Boehringer-Ingelheim, Sanofi and GSK. He has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi. He has also received a speaker's fee from GSK., (Copyright © 2022. Published by Elsevier B.V.)

We conducted a systematic review and meta-analysis of the available literature on the association between greenspace exposure and all-sites and site-specific cancer incidence, prevalence, and mortality in adults. We searched PubMed, Scopus, and Web of Science for original articles published, without language restriction until September 2021. We assessed the risk of bias in each study and the overall quality of evidence for exposure-outcome pairs that were reported in two or more studies. Out of the 18 included studies, cross-sectional studies were the most common study design (n = 8), and most of the studies were conducted in Europe (n = 8). In terms of risk of bias, the majority of cohorts (four out of six) and case-control studies (three out of four) were of good or very good quality, and cross-sectional studies were mostly (five out of eight) of poor quality. Outcomes (incidence, prevalence, mortality) on different cancer sites were reported: lung cancer (n = 9), prostate cancer (n = 4), breast cancer (n = 4), skin cancer (n = 3), colorectal cancer (n = 2), all-sites cancer (n = 2), brain cancer (n = 1), mouth and throat cancer (n = 1), and esophageal cancer (n = 1). The meta-analyses for the breast, lung, and prostate cancer incidence did not show statistically significant associations (for example for breast cancer: hazard ratio = 0.83; 95% confidence interval: 0.47-1.48). For skin cancer, the available evidence suggests that greenspace could be a potential risk factor. For the other cancers, the evidence was non-conclusive. The overall quality of evidence of all of the exposure-outcome pairs was very low. Given the wide confidence interval of the pooled estimates and very low quality of evidence, the findings should be interpreted with caution. Future large and longitudinal studies are needed to assess the potential association of greenspace exposure with cancers, considering types and quality of greenspace, evaluation of cancer sub-types, and adjustment for a sufficient set of covariates., 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 Elsevier B.V. All rights reserved.)

We systematically reviewed the existing evidence (until end of November 2021) on the association between long-term exposure to greenspace and behavioral problems in children according to the PRISMA 2020. The review finally reached 29 relevant studies of which, 17 were cross-sectional, 11 were cohort, and one was a case-control. Most of the studies were conducted in Europe (n = 14), followed by the USA (n = 8), and mainly (n = 21) from 2015 onwards. The overall quality of the studies in terms of risk of bias was "fair" (mean quality score = 5.4 out of 9) according to the Newcastle-Ottawa Scale. Thirteen studies (45%) had good or very good quality in terms of risk of bias. The strength and difficulty questionnaire was the most common outcome assessment instrument. Exposure to the greenspace in the reviewed studies was characterized based on different indices (availability, accessibility, and quality), mostly at residential address locations. Association of exposure to different types of greenspace were reported for nine different behavioral outcomes including total behavioral difficulties (n = 16), attention deficit hyperactivity disorder (ADHD) symptoms and severity (n = 15), ADHD diagnosis (n = 10), conduct problems (n = 10), prosocial behavior (n = 10), emotional symptoms (n = 8), peer-relationship problems (n = 8), externalizing disorders (n = 6), and internalizing disorders (n = 5). Most of the reported associations (except for conduct problems) were suggestive of beneficial association of greenspace exposure with children's behaviors; however, the studies were heterogeneous in terms of their exposure indicators, study design, and the outcome definition., 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 B.V. All rights reserved.)

Background: Many studies investigated the relationship between outdoor fine particulate matter (PM 2.5 ) and cancer. While they generally indicated positive associations, results have not been fully consistent, possibly because of the diversity of methods used to assess exposure., Objectives: To investigate how using different PM 2.5 exposure assessment methods influences risk estimates in the large French general population-based Gazel cohort (20,625 participants at enrollment) with a 26-year follow-up with complete residential histories., Methods: We focused on two cancer incidence outcomes: all-sites combined and lung. We used two distinct exposure assessment methods: a western European land use regression (LUR), and a chemistry-dispersion model (Gazel-Air) for France, each with a time series ≥20-years annual concentrations. Spearman correlation coefficient between the two estimates of PM 2.5 was 0.71 across all person-years; the LUR tended to provide higher exposures. We used extended Cox models with attained age as time-scale and time-dependent cumulative exposures, adjusting for a set of confounders including sex and smoking, to derive hazard ratios (HRs) and their 95% confidence interval, implementing a 10-year lag between exposure and incidence/censoring., Results: We obtained similar two-piece linear associations for all-sites cancer (3711 cases), with a first slope of HRs of 1.53 (1.24-1.88) and 1.43 (1.19-1.73) for one IQR increase of cumulative PM 2.5 exposure for the LUR and the Gazel-Air models respectively, followed by a plateau at around 1.5 for both exposure assessments. For lung cancer (349 cases), the HRs from the two exposure models were less similar, with largely overlapping confidence limits., Conclusion: Our findings using long-term exposure estimates from two distinct exposure assessment methods corroborate the association between air pollution and cancer risk., 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 Elsevier B.V. All rights reserved.)

Background: Greenspace exposure has been suggested to be associated with a range of health outcomes. The available evidence on the association of this exposure with cancer is still very scarce and inconsistent., Objectives: We aimed to study the association between greenspace exposure and all-site and site-specific (prostate, breast, colorectal, bladder, lung, and malignant melanoma of skin) cancer incidence in the GAZEL cohort., Methods: This study was based on over 27 years of follow-up (1989-2016) of 19,408 participants across France. We assessed the residential greenspace exposure within several buffers as well as residential proximity to green spaces (agricultural, urban, and forests) in each follow-up. We used time-dependent Cox models, controlling for time-varying personal and area-level variables, with different lags between exposure and outcome. Additional analysis was conducted according to the urban-rural residence of the participants' over follow-up., Results: Over the 294,645 person-years of follow-up, we registered 4075 incident cases of cancer. We found an increase in the risk for all-sites cancer with an inter-quartile range increase of Normalized Difference in Vegetation Index across different buffers (hazard ratio (HR) of 1.08; 95% CI: 1.02, 1.14 for the 100 m buffer). We found a positive association of all-sites cancer with proximity to agricultural lands (HR: 1.03; 95% CI: 1.00, 1.05), and forests (HR:1.04; 95% CI: 1.00, 1.07), but not with urban green spaces. The cancer site-specific analyses suggested a protective role of greenspace for breast, lung, and colorectal cancers (e.g. breast cancer HR at 100 m buffer: 0.82; 95% CI: 0.69, 0.99). Non-significant associations were observed for prostate, bladder, and skin cancer. Stratified analyses based on urban, semi-urban, and rural classification did not suggest any differential pattern., Conclusion: We identified an increased risk of all-site cancer with increased greenspace and proximity to agricultural lands and forests; whereas potential protective role of greenspace for breast cancer., 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 © 2021 Elsevier B.V. All rights reserved.)

Satellite-derived (SAT) and chemical transport model (CTM) estimates of PM 2.5 and NO 2 are increasingly used in combination with Land Use Regression (LUR) models. We aimed to compare the contribution of SAT and CTM data to the performance of LUR PM 2.5 and NO 2 models for Europe. Four sets of models, all including local traffic and land use variables, were compared (LUR without SAT or CTM, with SAT only, with CTM only, and with both SAT and CTM). LUR models were developed using two monitoring data sets: PM 2.5 and NO 2 ground level measurements from the European Study of Cohorts for Air Pollution Effects (ESCAPE) and from the European AIRBASE network. LUR PM 2.5 models including SAT and SAT+CTM explained ~60% of spatial variation in measured PM 2.5 concentrations, substantially more than the LUR model without SAT and CTM (adjR 2 : 0.33-0.38). For NO 2 CTM improved prediction modestly (adjR 2 : 0.58) compared to models without SAT and CTM (adjR 2 : 0.47-0.51). Both monitoring networks are capable of producing models explaining the spatial variance over a large study area. SAT and CTM estimates of PM 2.5 and NO 2 significantly improved the performance of high spatial resolution LUR models at the European scale for use in large epidemiological studies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This study evaluated the associations between biological markers in the nitrate-nitrite-NO pathway and four environmental exposures among subjects examined in the second survey (2003-2007) of the French Epidemiological study on Genetics and Environment of Asthma (EGEA). Total nitrite and nitrate (NO(2)(-) /NO(3)(-)) levels were measured both in plasma and in exhaled breath condensate (EBC) in 949 adults. Smoking, diet and exposure to chlorine products were assessed using standardized questionnaires. Exposure to air pollutants was estimated by using geostatistical models. All estimates were obtained with generalized estimating equations for linear regression models. Median levels of NO(2)(-)/NO(3)(-) were 36.3 μM (1st-3rd quartile: 25.7, 51.1) in plasma and 2.0 μmol/mg proteins (1st-3rd quartile 0.9, 3.9) in EBC. After adjustment for asthma, age, sex and menopausal status, plasma NO(2)(-)/NO(3)(-) level increased with leafy vegetable consumption (above versus below median=0.04 (95%CI: 0.001, 0.07)) and decreased in smokers (versus non/ex-smokers=-0.08 (95%CI: -0.11, -0.04). EBC NO(2)(-)/NO(3)(-) level decreased in smokers (-0.08 (95%CI: -0.16, -0.001)) and with exposure to ambient O(3) concentration (above versus below median=-0.10 (95%CI: -0.17, -0.03)). Cured meat, chlorine products, PM(10) and NO(2) concentrations were not associated with NO(2)(-)/NO(3)(-) levels. Results suggest that potential modifiable environmental and behavioral risk factors may modify NO(2)(-)/NO(3)(-) levels in plasma and EBC according to the route of exposure., (Copyright © 2012 Elsevier Inc. All rights reserved.)