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脂肪组织中功能性多氯联苯与乳腺癌患者预后生物标志物的相关性。

Associations between functional polychlorinated biphenyls in adipose tissues and prognostic biomarkers of breast cancer patients.

机构信息

Department of Preventive Medicine, Shantou University Medical College, Shantou, 515041, Guangdong Province, China.

University of Medicine, Pharmacy, Science and Technology, Targu Mures, Romania.

出版信息

Environ Res. 2020 Jun;185:109441. doi: 10.1016/j.envres.2020.109441. Epub 2020 Mar 29.

DOI:10.1016/j.envres.2020.109441
PMID:32247153
Abstract

BACKGROUND

Exposure to polychlorinated biphenyls (PCBs) has been shown to influence expression of some biomarkers that are predictive/prognostic for breast cancer. Therefore, our study was conducted to further investigating associations of different functional PCBs in adipose tissue with breast cancer prognostic biomarkers.

METHODS

Two hundred and five breast cancer patients were recruited in Shantou, China. Breast adipose tissues were collected during their resection surgery and levels of 7 PCB congeners were analyzed by gas chromatography-mass spectrometry (GC-MS). The PCB congeners were divided into 4 groups according to structure-activity. Socio-demographic, clinical and pathological information were obtained from questionnaire and digital medical records. Odds ratios (ORs) for associations between prognostic biomarkers and PCB levels (tertile 3 [T3], tertile 2 [T2] vs. tertile 1) were estimated from logistic regression models.

RESULTS

Most PCB congeners were detectable, with a highest level (22.06 ng/g lipid) of PCB153. As for estrogenic PCBs, increased PCB52 exposure was positively associated with PR expression (OR = 2.36, P = 0.054), but higher PCB101 level was negatively associated with HER-2 (OR = 0.24, P = 0.029) and tumor size (OR = 0.43). Limited dioxin-like PCB138 exposure was positively associated with ER (OR = 3.23, OR = 3.77, P = 0.047) but negatively with Top-IIα expression (OR = 0.35, OR = 0.28, P = 0.080). Higher PCB153 (CYP inducer) level was negatively associated with ER (OR = 0.32, OR = 0.19, P = 0.038) but positively with Ki-67 expression (OR = 1.43, OR = 3.60, P = 0.055). Higher neurotoxic PCB28 was positively associated with HER-2 (OR = 5.43, P = 0.006) and tumor size (OR = 2.37). Moreover, total PCBs exposure was positively associated with VEGF-C (OR = 76.91, OR = 97.96, P = 0.041) and tumor metastasis (OR = 2.25).

CONCLUSIONS

Different functional PCB congeners have different associations (both positive and negative) with breast cancer prognostic biomarkers, as well as tumor classification stage. Therefore, the development and aggressiveness of breast cancer may depend upon exposure to specific structure-activity of PCBs.

摘要

背景

接触多氯联苯 (PCBs) 已被证明会影响某些对乳腺癌具有预测/预后价值的生物标志物的表达。因此,我们进行了这项研究,以进一步调查脂肪组织中不同功能的 PCBs 与乳腺癌预后生物标志物之间的关联。

方法

在中国汕头招募了 205 名乳腺癌患者。在他们的切除手术中采集乳腺脂肪组织,并通过气相色谱-质谱法 (GC-MS) 分析 7 种 PCB 同系物的水平。根据结构-活性将 PCB 同系物分为 4 组。从问卷调查和数字病历中获取社会人口统计学、临床和病理信息。使用逻辑回归模型估计预后生物标志物与 PCB 水平(三分位 3 [T3]、三分位 2 [T2] 与三分位 1)之间关联的比值比 (OR)。

结果

大多数 PCB 同系物均可检测到,其中 PCB153 的水平最高(22.06ng/g 脂质)。对于雌激素类 PCBs,较高的 PCB52 暴露与 PR 表达呈正相关(OR=2.36,P=0.054),但较高的 PCB101 水平与 HER-2(OR=0.24,P=0.029)和肿瘤大小(OR=0.43)呈负相关。有限的二恶英样 PCB138 暴露与 ER 呈正相关(OR=3.23,OR=3.77,P=0.047),但与 Top-IIα 表达呈负相关(OR=0.35,OR=0.28,P=0.080)。较高的 PCB153(CYP 诱导剂)水平与 ER 呈负相关(OR=0.32,OR=0.19,P=0.038),但与 Ki-67 表达呈正相关(OR=1.43,OR=3.60,P=0.055)。较高的神经毒性 PCB28 与 HER-2(OR=5.43,P=0.006)和肿瘤大小(OR=2.37)呈正相关。此外,总 PCBs 暴露与 VEGF-C(OR=76.91,OR=97.96,P=0.041)和肿瘤转移(OR=2.25)呈正相关。

结论

不同功能的 PCB 同系物与乳腺癌预后生物标志物以及肿瘤分类分期具有不同的关联(包括正相关和负相关)。因此,乳腺癌的发展和侵袭性可能取决于对特定结构-活性的 PCB 的暴露。

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