Department of Occupational and Environmental Health, School of Public Health, Center for International Collaborative Research on Environment, Nutrition, and Public Health, Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin, 300070, China.
Department of Epidemiology and Biostatistics, Key Laboratory of Breast Cancer Prevention and Therapy in Ministry of Education, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
Environ Health. 2022 Sep 9;21(1):83. doi: 10.1186/s12940-022-00895-3.
Perfluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Recent studies have implicated exposure to PFASs as a risk factor for breast cancer in Europe and America. Little is known about the role of PFASs with respect to breast cancer in the Chinese population.
Participants who were initially diagnosed with breast cancer at Tianjin Medical University Cancer Institute and Hospital between 2012 and 2016 were recruited as cases. The controls were randomly selected from the participants with available blood samples in the Chinese National Breast Cancer Screening Program (CNBCSP) cohort. Ultimately, we enrolled 373 breast cancer patients and 657 controls. Plasma PFASs were measured by an ultra-performance liquid chromatography (UPLC) system coupled to a 5500 Q-Trap triple quadrupole mass spectrometer. A logistic regression model with least absolute shrinkage and selection operator (LASSO) regularization was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationships between PFASs and breast cancer. The three most predictive variables in the LASSO model were selected from 17 PFASs, which was based on the optimal penalty coefficient (λ = 0.0218) identified with the minimum criterion. Additionally, Bayesian kernel machine regression (BKMR) and quantile g-computation models were applied to evaluate the associations between separate and mixed exposure to PFASs and breast cancer.
Perfluorooctanesulfonic acid (PFOS) exhibited the highest concentration in both the cases and controls. Perfluorooctanoic acid (PFOA) and perfluoro-n-decanoic acid (PFDA) were positively associated with breast cancer, and perfluoro-n-tridecanoic acid (PFTrDA) was negatively associated with breast cancer according to both the continuous-PFASs and the quartile-PFASs logistic regression models. Of note, PFOA was associated with the occurrence of estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (OR = 1.47, 95% CI: 1.19, 1.80; OR = 1.36, 95% CI: 1.09, 1.69; OR = 1.62, 95% CI: 1.19, 2.21).
Overall, we observed that PFASs were associated with breast cancer in Chinese women. Prospective cohort studies and mechanistic experiments are warranted to elucidate whether these associations are causal.
全氟烷基物质（PFASs）是一大类合成化学品，其中一些是乳腺毒物和内分泌干扰物。最近的研究表明，接触 PFASs 是欧洲和美洲乳腺癌的一个风险因素。在中国人群中，关于 PFASs 与乳腺癌的关系知之甚少。
2012 年至 2016 年期间，在天津医科大学肿瘤医院初诊为乳腺癌的患者被招募为病例。对照组是从中国国家乳腺癌筛查计划（CNBCSP）队列中可获得血液样本的参与者中随机选择的。最终，我们纳入了 373 名乳腺癌患者和 657 名对照。通过超高效液相色谱（UPLC）系统与 5500 Q-Trap 三重四极杆质谱联用仪测量血浆 PFASs。使用最小绝对收缩和选择算子（LASSO）正则化的逻辑回归模型计算比值比（OR）和 95%置信区间（CI），以评估 PFASs 与乳腺癌之间的关系。在 LASSO 模型中，从 17 种 PFAS 中选择了 3 种最具预测性的变量，这是基于识别的最优惩罚系数（λ=0.0218）。此外，贝叶斯核机器回归（BKMR）和分位数 g 计算模型被应用于评估单独和混合暴露于 PFASs 与乳腺癌之间的关联。
在病例和对照组中，全氟辛烷磺酸（PFOS）的浓度最高。全氟辛酸（PFOA）和全氟壬酸（PFDA）与乳腺癌呈正相关，而全氟正十三烷酸（PFTrDA）与乳腺癌呈负相关，这两种模型均为连续 PFASs 和四分位 PFASs 逻辑回归模型。值得注意的是，PFOA 与雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体 2（HER2）阳性乳腺癌有关（OR=1.47，95%CI：1.19，1.80；OR=1.36，95%CI：1.09，1.69；OR=1.62，95%CI：1.19，2.21）。
总的来说，我们观察到 PFASs 与中国女性乳腺癌有关。需要前瞻性队列研究和机制实验来阐明这些关联是否具有因果关系。
