Total Effective Xenoestrogen Burden in Serum Samples and Risk of Endometrial Cancer in the Spanish Screenwide...

Endometrial cancer is a hormone-dependent cancer, and estrogens play a relevant role in its etiology. However, little is known about the effects of environmental pollutants that act as xenoestrogens or that influence estrogenic activity through different pathways.

We aimed to assess the relationship between the combined estrogenic activity of mixtures of xenoestrogens present in serum samples and the risk of endometrial cancer in the Screenwide case-control study.

The total effective xenoestrogen burden (TEXB) attributable to organohalogenated compounds ($\text{TEXB-}\alpha$) and to endogenous hormones and more polar xenoestrogens ($\text{TEXB-}\beta$) was assessed in serum from 156 patients with endometrial cancer (cases) and 150 controls by combining chemical extraction and separation by high-performance liquid chromatography with the E-SCREEN bioassay for estrogenicity.

Median $\text{TEXB-}\alpha$ and $\text{TEXB-}\beta$ levels for cases (0.30 and $1.25\text{\hspace{0.17em}Eeq pM}/\mathrm{mL}$, respectively) and controls (0.42 and $1.28\text{\hspace{0.17em}Eeq pM}/\mathrm{mL}$, respectively) did not significantly differ ($p=0.653$ and 0.933, respectively). An inverted-U risk trend across serum $\text{TEXB-}\alpha$ and $\text{TEXB-}\beta$ levels was observed in multivariate adjusted models: Positive associations were observed for the second category of exposure in comparison to the lowest category of exposure [$\text{odds ratio\hspace{0.17em}}\left(\text{OR}\right)=2.11$ (95% CI: 1.13, 3.94) for $\text{TEXB-}\alpha$, and $\text{OR}=3.32$ (95% CI: 1.62, 6.81) for $\text{TEXB-}\beta$], whereas no significant associations were observed between the third category of exposure and the first [$\text{OR}=1.22$ (95% CI: 0.64, 2.31) for $\text{TEXB-}\alpha$, and $\text{OR}=1.58$ (95% CI: 0.75, 3.33) for $\text{TEXB-}\beta$]. In mutually adjusted models for $\text{TEXB-}\alpha$ and $\text{TEXB-}\beta$ levels, the association of $\text{TEXB-}\alpha$ with endometrial cancer risk was attenuated [$\text{OR}=1.45$ (95% CI: 0.61, 3.47) for the second category of exposure], as well as estimates for $\text{TEXB-}\beta$ ($\text{OR}=2.68$; 95% CI: 1.03, 6.99). Most of the individual halogenated contaminants showed no associations with both TEXB and endometrial cancer.

We evaluated serum total xenoestrogen burden in relation to endometrial cancer risk and found an inverted-U risk trend across increasing categories of exposure. The use of in vitro bioassays with human samples may lead to a paradigm shift in the way we understand the negative impact of chemical mixtures on human health effects. These results are relevant from a public health perspective and for decision-makers in charge of controlling the production and distribution of chemicals with xenoestrogenic activity. https://doi.org/10.1289/EHP13202.