INSERM UMR-S 1124, T3S, Toxicologie Environnementale, Cibles thérapeutiques, Signalisation cellulaire et Biomarqueurs, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Service de Chirurgie Cancérologique Gynécologique et du Sein, Paris, France; Université Paris Cité, 45 rue des Saints-Pères, 75006 Paris, France.
INSERM UMR-S 1124, T3S, Toxicologie Environnementale, Cibles thérapeutiques, Signalisation cellulaire et Biomarqueurs, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Service de Chirurgie Cancérologique Gynécologique et du Sein, Paris, France; Université Paris Cité, 45 rue des Saints-Pères, 75006 Paris, France.
Environ Int. 2022 Dec;170:107615. doi: 10.1016/j.envint.2022.107615. Epub 2022 Nov 3.
Breast cancer (BC) is frequent with a poor prognosis in case of metastasis. The role of the environment has been poorly evaluated in its progression. We searched to assess whether a mixture of pollutants could be responsible of BC aggressiveness.
Patients undergoing surgery for their BC were prospectively included in the METAPOP cohort. Forty-two POPs were extracted, among them 17 dioxins (PCDD/F), 16 polychlorobiphenyls (PCB), 8 polybromodiphenylethers (PBDE) and 2,2',4,4',5,5'-hexabromobiphenyl (PBB153) were measured in the adipose tissue surrounding the tumor. BC aggressiveness was defined using tumor size and metastasis (distant or lymph nodes). Two complementary models were used to evaluate the impact of the mixture of pollutants: the BKMR (Bayesian Kernel machine regression) and WQS (weighted quantile sum regression) models. The WQS estimates the weight (positive or negative) of a certain chemical based on its quantile and the BKMR model applies a kernel-based approach to estimate posterior inclusion probabilities. The sub-group of patients with a body mass index (BMI) > 22 kg/ m was also analyzed.
Ninety-one patients were included. Of these, 38 patients presented a metastasis, and the mean tumor size was 25.4 mm. The mean BMI was 24.5 kg/m (+/- 4.1). No statistical association was found in the general population. However, in patients with a BMI > 22 kg/ m, our mixture was positively associated with tumor size (OR: 9.73 95 %CI: 1.30-18.15) and metastasis (OR = 3.98 95 %CI = 1.09-17.53) using the WQS model. Moreover, using the BKMR model on chemical families, dioxin like chemicals and PCDD were associated with a higher risk of metastasis.
These novel findings identified a mixture associated with breast cancer aggressiveness in patients with a BMI > 22 kg/ m.
乳腺癌（BC）的发病率较高，转移后预后不良。环境在其进展中的作用尚未得到充分评估。我们试图评估污染物混合物是否会导致 BC 的侵袭性增加。
前瞻性地纳入 METAPOP 队列中接受手术治疗的 BC 患者。从脂肪组织中提取了 42 种持久性有机污染物（POPs），其中包括 17 种二恶英（PCDD/F）、16 种多氯联苯（PCB）、8 种多溴二苯醚（PBDE）和 2,2',4,4',5,5'-六溴联苯（PBB153）。根据肿瘤大小和转移（远处或淋巴结）定义 BC 的侵袭性。使用两种互补模型来评估污染物混合物的影响：BKMR（贝叶斯核机器回归）和 WQS（加权分位数和回归）模型。WQS 根据化学物质的分位数估计其权重（正或负），BKMR 模型应用基于核的方法估计后验包含概率。还分析了 BMI>22kg/m2的患者亚组。
共纳入 91 例患者。其中，38 例患者出现转移，肿瘤平均大小为 25.4mm。平均 BMI 为 24.5kg/m（+/-4.1）。在普通人群中未发现统计学关联。然而，在 BMI>22kg/m2的患者中，使用 WQS 模型，我们的混合物与肿瘤大小（OR：9.73，95%CI：1.30-18.15）和转移（OR=3.98，95%CI：1.09-17.53）呈正相关。此外，使用 BKMR 模型对化学家族进行分析，发现类似二恶英的化学物质和 PCDD 与转移风险增加相关。
这些新发现确定了一种与 BMI>22kg/m2的患者的乳腺癌侵袭性相关的混合物。
