Incidence of uterine leiomyoma in relation to urinary concentrations of phthalate and phthalate alternative biomarkers: A prospective ultrasound study.
Incidence of uterine leiomyoma in relation to urinary concentrations of phthalate and phthalate alternative biomarkers: A prospective ultrasound study.
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子宫平滑肌瘤的发病率与邻苯二甲酸酯和邻苯二甲酸酯替代生物标志物的尿浓度相关：一项前瞻性超声研究。
DOI：
10.1016/j.envint.2020.106218
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发表时间：
2021-03
影响因子：
11.8
通讯作者：
Wise LA
中科院分区：
文献类型：
--
作者：
Fruh V;Claus Henn B;Weuve J;Wesselink AK;Orta OR;Heeren T;Hauser R;Calafat AM;Williams PL;Baird DD;Wise LA
大量研究表明，某些邻苯二甲酸盐对生殖有不利影响。然而，关于邻苯二甲酸酯与子宫平滑肌瘤（UL）发病率之间关系的文献有限且不一致，目前尚无前瞻性研究。我们检查了尿中邻苯二甲酸盐浓度和邻苯二甲酸盐替代生物标志物与UL发病率的关系。我们对环境、生活方式和肌瘤研究（SELF）的754名参与者进行了病例队列分析，这是一个2010-2012年招募的年龄在23-35岁的绝经前黑人女性的前瞻性队列。在基线、20个月和40个月收集的尿液中，我们量化了14种邻苯二甲酸酯和2种邻苯二甲酸酯替代品[1,2-环己烷二羧酸二异壬酯（DINCH）]的生物标志物。经阴道超声在基线和60个月随访期间每20个月确定一次UL。我们评估了单个生物标志物，邻苯二甲酸二（2-乙基己基）酯的摩尔总和[ΣDEHP]和抗雄激素生物标志物的效价加权总和[WΣAA]。我们使用Cox比例风险回归来估计生物标志物与UL发病率之间的校正风险比（hr）和95%置信区间（CIs）。然后，我们使用分位数g计算来检查多种邻苯二甲酸酯生物标志物与UL发病率的联合关联。大多数个体生物标志物与UL发病率呈弱至中度负相关。邻苯二甲酸单异丁酯（MiBP）和邻苯二甲酸单羟基异丁酯（MHiBP）浓度最高和最低四分位数的hr分别为0.74 （95% CI: 0.46, 1.17）和0.65 （95% CI: 0.41, 1.03）。在BMI≥30 kg/m2的女性中，特定邻苯二甲酸酯的负相关更强。比较可检测和不可检测的DINCH生物标志物浓度，环己烷-1,2-二羧酸单羟基异油基酯（MHNCH）的hr为0.96 (95% CI: 0.65, 1.41)，环己烷-1,2-二羧酸单羧基异油基酯（MCOCH）的hr为0.71 （95% CI: 0.41, 1.23）。对于ΣDEHP和邻苯二甲酸单（2-乙基己基）酯（MEHP）的DEHP代谢物，我们观察到弱至中度的正相关。ΣDEHP和MEHP的最高和最低四分位数的hr分别为1.12 （95% CI: 0.71, 1.76）和1.34 （95% CI: 0.84, 2.14）。在混合物分析中，邻苯二甲酸酯生物标志物浓度联合四分位数增加的HR为0.90 （95% CI: 0.73, 1.08）。在这项对育龄黑人妇女的前瞻性超声研究中，无论是单独还是联合，尿中邻苯二甲酸盐和DINCH生物标志物的浓度与UL的高风险没有明显的相关性。
Numerous studies suggest that some phthalates have adverse reproductive effects. However, literature on the association between phthalates and incidence of uterine leiomyomata (UL) is limited and inconsistent, with no existing prospective studies. We examined the association of urinary concentrations of phthalate and phthalate alternative biomarkers with UL incidence. We conducted a case-cohort analysis within a subgroup of 754 participants in the Study of the Environment, Lifestyle, and Fibroids (SELF), a prospective cohort of premenopausal Black women aged 23-35 years who were recruited during 2010-2012. We quantified fourteen phthalates and two phthalate alternative [1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH)] biomarkers in urine collected at baseline, 20 months, and 40 months. Transvaginal ultrasounds identified UL at baseline and every 20 months during 60 months of follow-up. We evaluated the individual biomarkers, molar sum of di(2-ethylhexyl) phthalate [ΣDEHP] and potency-weighted sum of anti-androgenic [WΣAA] biomarkers. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between biomarkers and UL incidence. We then used quantile g-computation to examine joint associations of multiple phthalate biomarkers with UL incidence. Most individual biomarkers showed weak-to-moderate inverse associations with UL incidence. HRs comparing highest vs. lowest quartiles of mono-isobutyl phthalate (MiBP) and mono-hydroxyisobutyl phthalate (MHiBP) concentrations were 0.74 (95% CI: 0.46, 1.17) and 0.65 (95% CI: 0.41, 1.03), respectively. Inverse associations for specific phthalates were stronger among women with BMI ≥30 kg/m2. HRs comparing detectable vs. nondetectable concentrations of DINCH biomarkers were 0.96 (95% CI: 0.65, 1.41) for cyclohexane-1,2-dicarboxylic acid mono hydroxyisononyl ester (MHNCH) and 0.71 (95% CI: 0.41, 1.23) for cyclohexane-1,2-dicarboxylic acid mono carboxyisoocytl ester (MCOCH). For ΣDEHP and the DEHP metabolite of mono(2-ethylhexyl) phthalate (MEHP), we observed weak-to-moderate positive associations. HRs comparing highest vs. lowest quartiles were 1.12 (95% CI: 0.71, 1.76) and 1.34 (95% CI: 0.84, 2.14) for ΣDEHP and MEHP, respectively. In the mixtures analysis, the HR for a joint quartile increase in phthalate biomarker concentrations was 0.90 (95% CI: 0.73, 1.08). In this prospective ultrasound study of reproductive-aged Black women, urinary concentrations of phthalate and DINCH biomarkers were not appreciably associated with higher risk of UL, either individually or jointly.
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DOI：
10.1038/s41370-019-0114-9
发表时间：
2020-01-01
影响因子：
4.5
作者：
Bethea, Traci N.;Wesselink, Amelia K.;Wise, Lauren A.
通讯作者：
Wise, Lauren A.
影响因子：
10.4
作者：
Blount BC;Silva MJ;Caudill SP;Needham LL;Pirkle JL;Sampson EJ;Lucier GW;Jackson RJ;Brock JW
通讯作者：
Brock JW
影响因子：
3
作者：
Crespo, J. E.;Balart, R.;Lopez, J.
通讯作者：
Lopez, J.
影响因子：
3.3
作者：
Bonilla, Edmundo;del Mazo, Jesus
通讯作者：
del Mazo, Jesus
影响因子：
3.6
作者：
Craig, Zelieann R.;Hannon, Patrick R.;Flaws, Jodi A.
通讯作者：
Flaws, Jodi A.