Department of Prevention Cancer Environment, Centre Léon Bérard, Lyon, France; Inserm UMR 1296 Radiations : Défense, Santé, Environnement, Lyon, France.
Department of Prevention Cancer Environment, Centre Léon Bérard, Lyon, France; Inserm UMR 1296 Radiations : Défense, Santé, Environnement, Lyon, France; Ecole Centrale de Lyon, INSA Lyon, Université Claude Bernard Lyon 1, Ecully, France.
Environ Int. 2021 Apr;149:106399. doi: 10.1016/j.envint.2021.106399. Epub 2021 Jan 24.
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), 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.
背景：苯并[a]芘（BaP）是有机物质不完全燃烧时形成的一种内分泌干扰污染物。它已被认为是一种生殖和发育毒物，然而，环境空气中 BaP 对乳腺癌（BC）的长期影响的流行病学证据有限。因此，我们评估了在法国 E3N 队列研究中，环境空气 BaP 暴露与 BC 的风险之间的关联，总体而言，以及根据绝经状态和分子亚型（雌激素受体阴性/阳性（ER-/ER+）和孕激素受体阴性/阳性（PR-/PR+））、BC 的分期和分化程度进行评估。
方法：在 5222 例新发 BC 病例和 5222 例匹配对照的嵌套病例对照研究中，每年的 BaP 暴露量使用化学传输模型（CHIMERE）进行估计，并根据参与者在 1990-2011 年随访期间的居住地址进行分配。多变量条件逻辑回归模型用于估计比值比（OR）和 95%置信区间（CI）。
结果：总体而言，累积空气 BaP 暴露与 BC 的总体风险显著相关，BaP 浓度水平每增加 1 个四分位距（IQR），OR=1.15（95%CI：1.04-1.27）。然而，按绝经状态，仅在经历绝经过渡的女性中仍存在显著的正相关关系（即，在纳入时为绝经前女性，在诊断时已绝经），每增加 1 IQR 的 OR=1.20（95%CI：1.03-1.40）。按激素受体状态，ER+、PR+和 ER+PR+BC 与 BaP 之间存在正相关关系，OR 分别为 1.17（95%CI：1.04-1.32）、1.16（95%CI：1.01-1.33）和 1.17（95%CI：1.01-1.36）。BaP 与 3 级 BC 之间也存在边缘正相关关系（每增加 1 IQR 的 OR=1.15（95%CI：0.99-1.34）。
结论：我们提供了累积 BaP 暴露与 BC 风险增加相关的证据，这与绝经状态、激素受体状态和 BC 的分化程度有关。我们的结果为先前的实验研究表明 BaP 的不良影响提供了进一步的流行病学证据。
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