UNASSIGNED: 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.
UNASSIGNED: The total effective xenoestrogen burden (TEXB) attributable to organohalogenated compounds (TEXB-α) and to endogenous hormones and more polar xenoestrogens (TEXB-β) 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.
UNASSIGNED: Median TEXB-α and TEXB-β 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 (p=0.653 and 0.933, respectively). An inverted-U risk trend across serum TEXB-α and TEXB-β 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-α, and OR=3.32 (95% CI: 1.62, 6.81) for TEXB-β], 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-α, and OR=1.58 (95% CI: 0.75, 3.33) for TEXB-β]. In mutually adjusted models for TEXB-α and TEXB-β levels, the association of TEXB-α 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-β (OR=2.68; 95% CI: 1.03, 6.99). Most of the individual halogenated contaminants showed no associations with both TEXB and endometrial cancer.
UNASSIGNED: 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.
■我们旨在评估全屏幕病例对照研究中血清样本中存在的异种雌激素混合物的联合雌激素活性与子宫内膜癌风险之间的关系。
■在156例患者的血清中评估了归因于有机卤代化合物(TEXB-α)以及内源性激素和更极性的异种雌激素(TEXB-β)的总有效异种雌激素负荷(TEXB)子宫内膜癌(病例)和150个对照通过高效液相色谱法进行化学提取和分离与E-SCREEN生物测定雌激素性。
■病例的TEXB-α和TEXB-β中位数水平(0.30和1.25eqpM/mL,分别)和对照(0.42和1.28EqpM/mL,分别)没有显着差异(分别为p=0.653和0.933)。在多变量调整模型中观察到血清TEXB-α和TEXB-β水平的倒U风险趋势:与最低暴露类别相比,第二类暴露呈正相关[比值比(OR)=2.11(95%CI:1.13,3.94)TEXB-α,TEXB-β]的OR=3.32(95%CI:1.62,6.81),而对于TEXB-α,第三类暴露和第一类暴露之间没有观察到显著关联[OR=1.22(95%CI:0.64,2.31),TEXB-β]的OR=1.58(95%CI:0.75,3.33)。在TEXB-α和TEXB-β水平的相互调整模型中,TEXB-α与子宫内膜癌风险的相关性减弱[第二类暴露的OR=1.45(95%CI:0.61,3.47)],以及TEXB-β的估计值(OR=2.68;95%CI:1.03,6.99)。大多数单独的卤化污染物与TEXB和子宫内膜癌没有相关性。
我们评估了血清总异种雌激素负荷与子宫内膜癌风险的关系,并发现在增加的暴露类别中呈倒U型风险趋势。使用人体样品进行体外生物测定可能会导致我们理解化学混合物对人体健康影响的负面影响的方式发生范式转变。从公共卫生的角度来看,这些结果与负责控制具有异种雌激素活性的化学品的生产和分配的决策者有关。https://doi.org/10.1289/EHP13202.