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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.)

Background: Benzo[a]pyrene (BaP) is an endocrine-disrupting pollutant formed during incomplete combustion of organic materials. It has been recognized as a reproductive and developmental toxicant, however epidemiological evidence of the long-term effect of ambient air BaP on breast cancer (BC) is limited. Thus we evaluated associations between ambient air BaP exposure and risk of BC, overall and according to menopausal status and molecular subtypes (estrogen receptor negative/positive (ER-/ER+) and progesterone receptor negative/positive (PR-/PR+)), stage and grade of differentiation of BC in the French E3N cohort study., Methods: Within a nested case-control study of 5222 incident BC cases and 5222 matched controls, annual BaP exposure was estimated using a chemistry-transport model (CHIMERE) and was assigned to the geocoded residential addresses of participants for each year during the 1990-2011 follow-up period. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Overall, cumulative airborne BaP exposure was significantly associated with the overall risk of BC, for each 1 interquartile range (IQR) increase in the concentration levels of BaP (1.42 ng/m 3 ), the OR = 1.15 (95% CI: 1.04-1.27). However, by menopausal status, the significant positive association remained only in women who underwent menopausal transition (i.e. premenopausal women at inclusion who became postmenopausal at diagnosis), OR per 1 IQR = 1.20 (95% CI: 1.03-1.40). By hormone receptor status, positive associations were observed for ER+, PR + and ER + PR + BC, with ORs = 1.17 (95% CI: 1.04-1.32), 1.16 (95% CI: 1.01-1.33), and 1.17 (95% CI: 1.01-1.36) per 1 IQR, respectively. There was also a borderline positive association between BaP and grade 3 BC (OR per 1 IQR = 1.15 (95% CI: 0.99-1.34)., Conclusions: We provide evidence of increased risk of BC associated with cumulative BaP exposure, which varied according to menopausal status, hormone receptor status, and grade of differentiation of BC. Our results add further epidemiological evidence to the previous experimental studies suggesting the adverse effects of BaP., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)