Total Effective Xenoestrogen Burden in Serum Samples and Risk of Endometrial Cancer in the Spanish Screenwide Case–Control Study
Menée à l'aide d'échantillons sanguins prélevés chez 150 témoins et 156 patientes atteintes d'un cancer de l'endomètre, cette étude analyse l'association entre l'activité oestrogénique liée aux polluants environnementaux et le risque de développer la maladie
BACKGROUND: 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. OBJECTIVE: We aimed to assess the relationship between the combined estrogenic activity of mixtures of xenoestrogens present in serum samples andthe risk of endometrial cancer in the Screenwide case–control study. METHODS: The total effective xenoestrogen burden (TEXB) attributable to organohalogenated compounds (TEXB-a) and to endogenous hormonesand more polar xenoestrogens (TEXB-b) was assessed in serum from 156 patients with endometrial cancer (cases) and 150 controls by combiningchemical extraction and separation by high-performance liquid chromatography with the E-SCREEN bioassay for estrogenicity. RESULTS: Median TEXB-aand TEXB-blevels for cases (0.30 and 1:25 Eeq pM=mL, respectively) and controls (0.42 and 1:28 Eeq pM=mL, respec-tively) did not significantly differ (p=0:653 and 0.933, respectively). An inverted-U risk trend across serum TEXB-aand TEXB-blevels wasobserved in multivariate adjusted models: Positive associations were observed for the second category of exposure in comparison to the lowest cate-gory of exposure [odds ratio(OR)=2:11 (95% CI: 1.13, 3.94) for TEXB-a, and OR = 3:32 (95% CI: 1.62, 6.81) for TEXB-b], whereas no significantassociations were observed between the third category of exposure and thefirst [OR = 1:22 (95% CI: 0.64, 2.31) for TEXB-a, and OR = 1:58 (95%CI: 0.75, 3.33) for TEXB-b]. In mutually adjusted models for TEXB-aand TEXB-blevels, the association of TEXB-awith endometrial cancer riskwas attenuated [OR = 1:45 (95% CI: 0.61, 3.47) for the second category of exposure], as well as estimates for TEXB-b(OR = 2:68; 95% CI: 1.03,6.99). Most of the individual halogenated contaminants showed no associations with both TEXB and endometrial cancer. CONCLUSIONS: We evaluated serum total xenoestrogen burden in relation to endometrial cancer risk and found an inverted-U risk trend across increas-ing categories of exposure. The use ofin vitrobioassays with human samples may lead to a paradigm shift in the way we understand the negativeimpact of chemical mixtures on human health effects. These results are relevant from a public health perspective and for decision-makers in charge ofcontrolling the production and distribution of chemicals with xenoestrogenic activity.