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- Title
Total Effective Xenoestrogen Burden in Serum Samples and Risk of Endometrial Cancer in the Spanish Screenwide Case-Control Study.
- Authors
Costas, Laura; Frias-Gomez, Jon; Peinado, Francisco M.; Manuel Molina-Molina, Jose; Peremiquel-Trillas, Paula; Paytubi, Sonia; Crous-Bou, Marta; de Francisco, Javier; Caño, Victor; Benavente, Yolanda; Pelegrina, Beatriz; Manuel Martínez, José; Pineda, Marta; Brunet, Joan; Matias-Guiu, Xavier; de Sanjosé, Silvia; Ponce, Jordi; Olea, Nicolás; Alemany, Laia; Fernández, Mariana F.
- Abstract
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 and the 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 hormones and more polar xenoestrogens (TEXB-ß) 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. RESULTS: Median TEXB-a and TEXB-ß levels for cases (0.30 and 1.25 Eeq pM/mL, respectively) and controls (0.42 and 1.28 Eeq pM/mL, respectively) did not significantly differ (??=0.653 and 0.933, respectively). An inverted-U risk trend across serum TEXB-a and TEXB-ß 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 [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-ß], whereas no significant associations were observed between the third category of exposure and the first [OR = 1.22 (95% CI: 0.64, 2.31) for TEXB-a, and OR=1.58 (95% CI: 0.75, 3.33) for TEXB-ß]. In mutually adjusted models for TEXB-a and TEXB-ß levels, the association of TEXB-a with endometrial cancer risk was attenuated [OR=1.45 (95% CI: 0.61, 3.47) for the second category of exposure], as well as estimates for TEXB-ß (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 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.
- Subjects
RISK assessment; HIGH performance liquid chromatography; IN vitro studies; PEARSON correlation (Statistics); HORMONES; BODY mass index; LOGISTIC regression analysis; ESTROGEN; MULTIVARIATE analysis; DECISION making; CHI-squared test; MANN Whitney U Test; DESCRIPTIVE statistics; ENDOMETRIAL tumors; ODDS ratio; HALOCARBONS; POLLUTANTS; STATISTICS; CASE studies; BIOLOGICAL assay; CONFIDENCE intervals; PUBLIC health; HORMONE-dependent tumors; DISEASE risk factors
- Publication
Environmental Health Perspectives, 2024, Vol 132, Issue 2, p027012-1
- ISSN
0091-6765
- Publication type
Article
- DOI
10.1289/EHP13202