Receptor activities of persistent pollutant serum mixtures and breast cancer risk

Studies on associations between persistent organic pollutants (POPs) and breast cancer risk are inconclusive. The majority of studies have evaluated the effect of single compounds, without considering multiple exposures to and interactions between different POPs. The present study aimed at evaluating breast cancer risk related to combined effects of serum POP mixtures on cellular receptor functions. Data on breast cancer cases (n = 77) and controls (n = 84) were collected among Greenlandic Inuit women. Serum mixtures of lipophilic POPs (lipPOPs), perfluoroalkyl acids (PFAAs) and dioxin-like POPs were extracted. The effect of the mixture extracts on the estrogen receptor (ER), androgen receptor (AR) and aryl hydrocarbon receptor (AhR) was determined using cell culture reporter gene assays. The serum mixtures were analyzed alone and upon co-exposure with natural receptor ligands to determine agonistic and antagonistic/competitive activity. We found that the frequency of lipPOP mixtures eliciting no, decreasing, or agonizing xenoandrogenic effect differed by breast cancer status. Using lipPOP mixtures with no effect on AR as reference, the mixtures with decreasing effects reduced breast cancer risk (OR: 0.30 (0.12; 0.76)). The AhR-toxic equivalent of serum mixtures was significantly lower in cases than in controls, and a reduced breast cancer risk was found when comparing the third tertile to the first (OR: 0.34 (0.14; 0.83)). We found no association between the xenoestrogenic activities of lipPOPs or PFAAs and breast cancer risk. Serum lipPOP mixtures are hormone disruptive and may influence breast cancer risk, whereas PFAAs seem to influence breast cancer risk through other pathways.