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

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_T2 = 2.36, P_trend = 0.054), but higher PCB101 level was negatively associated with HER-2 (OR_T3 = 0.24, P_trend = 0.029) and tumor size (OR = 0.43). Limited dioxin-like PCB138 exposure was positively associated with ER (OR_T2 = 3.23, OR_T3 = 3.77, P_trend = 0.047) but negatively with Top-IIα expression (OR_T2 = 0.35, OR_T3 = 0.28, P_trend = 0.080). Higher PCB153 (CYP inducer) level was negatively associated with ER (OR_T2 = 0.32, OR_T3 = 0.19, P_trend = 0.038) but positively with Ki-67 expression (OR_T2 = 1.43, OR_T3 = 3.60, P_trend = 0.055). Higher neurotoxic PCB28 was positively associated with HER-2 (OR_T3 = 5.43, P_trend = 0.006) and tumor size (OR = 2.37). Moreover, total PCBs exposure was positively associated with VEGF-C (OR_T2 = 76.91, OR_T3 = 97.96, P_trend = 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.

Keywords: Breast cancer; Estrogen receptor (ER); Human epidermal growth factor receptor-2 (HER-2); Ki-67; Polychlorinated biphenyls (PCBs); Progesterone receptor (PR); Prognostic biomarkers; Topoisomerase-IIα (Top-IIα); Vascular endothelial growth factor-c (VEGF-C).