Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, 650 Charles E. Young Drive South, Los Angeles, CA 90025, USA.
Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, 650 Charles E. Young Drive South, Los Angeles, CA 90025, USA; Cancer Epidemiology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI 96813, USA.
Environ Int. 2022 Dec;170:107586. doi: 10.1016/j.envint.2022.107586. Epub 2022 Oct 19.
Epidemiologic evidence suggests that environmental factors acting as endocrine disrupting chemicals (EDCs) are associated with mammographic breast density and the risk of breast cancer. Exposure to EDCs during puberty, a period of rapid breast development, may affect susceptibility to breast carcinogenesis.
In a cohort of 366 Chilean adolescents from the Growth and Obesity Cohort Study, we evaluated the relation between urinary concentrations of 15 suspected EDC biomarkers across three pubertal time points (Tanner breast stage 1 (B1), 4 (B4), and 1-year post-menarche) and breast fibroglandular volume (FGV; percent FGV [%FGV] and absolute FGV [aFGV]) and total breast volume (tBV) at 2-years post-menarche. We used linear mixed models to test differences in creatinine-corrected EDC biomarker concentrations at B4 and 1-year post-menarche compared to B1 and calculated intraclass correlation coefficients (ICC) of EDC concentrations across time points to appraise the consistency of measurements. We fit multivariable generalized estimating equations (GEEs) to evaluate windows of susceptibility for the association between log-transformed EDCs and log-transformed breast outcomes. GEEs were adjusted for age, body fat percentage, total caloric intake, and maternal education.
Urinary EDC biomarker concentrations highly varied across pubertal time points (ICC range 0.01-0.30). For 12 EDCs, biomarker concentrations decreased over time. Triclosan measured at 1-year post-menarche was inversely associated with %FGV at 2-years post-menarche (β = -0.025, 95 % confidence interval = -0.041, -0.008). Mono(2-ethyl-5-carboxypentyl) phthalate and the sum of di(2-ethylhexyl) phthalate metabolite concentrations at B4 were positively associated with aFGV and tBV at 2-years post-menarche. No measured phenols were associated with aFGV and tBV, while no measured parabens were associated with %FGV and aFGV.
Our study suggests relatively high variability in EDC biomarker concentrations across the peripubertal time period. We also found evidence to suggest that there may be pubertal windows of susceptibility to select EDCs for the association with adolescent breast density.
流行病学证据表明，作为内分泌干扰物（EDCs）的环境因素与乳腺密度和乳腺癌风险有关。青春期是乳腺快速发育的时期，在此期间接触 EDC 可能会影响乳腺癌发生的易感性。
在智利生长和肥胖队列研究的 366 名青少年队列中，我们评估了 15 种疑似 EDC 生物标志物在三个青春期时间点（乳房 1 期（B1）、4 期（B4）和月经初潮后 1 年）的尿浓度与月经初潮后 2 年时乳腺纤维腺体体积（FGV；FGV 百分比[%FGV]和绝对 FGV[aFGV]）和总乳腺体积（tBV）之间的关系。我们使用线性混合模型比较 B4 和月经初潮后 1 年时与 B1 时的肌酐校正 EDC 生物标志物浓度，并计算 EDC 浓度随时间的内类相关系数（ICC），以评估测量的一致性。我们拟合多变量广义估计方程（GEE）来评估 EDC 与乳腺结果的对数转换之间关联的易感窗口。GEE 调整了年龄、体脂肪百分比、总热量摄入和母亲教育。
尿液 EDC 生物标志物浓度在青春期时间点差异很大（ICC 范围为 0.01-0.30）。对于 12 种 EDC，生物标志物浓度随时间下降。月经初潮后 1 年时测量的三氯生与月经初潮后 2 年时的%FGV 呈负相关（β=-0.025，95%置信区间=-0.041，-0.008）。B4 时的单（2-乙基-5-羧基戊基）邻苯二甲酸酯和二（2-乙基己基）邻苯二甲酸代谢物浓度总和与月经初潮后 2 年时的 aFGV 和 tBV 呈正相关。测量的酚类物质与 aFGV 和 tBV 无关，而测量的对羟基苯甲酸酯与%FGV 和 aFGV 无关。
我们的研究表明，在青春期期间，EDC 生物标志物浓度存在相对较高的变异性。我们还发现有证据表明，青春期可能存在对某些 EDC 与青少年乳腺密度关联的易感性窗口。
