Grandmaternal Perinatal Serum DDT in Relation to Granddaughter Early Menarche and Adult Obesity: Three Generations in the Child Health and Development Studies Cohort.
Grandmaternal Perinatal Serum DDT in Relation to Granddaughter Early Menarche and Adult Obesity: Three Generations in the Child Health and Development Studies Cohort.
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DOI：
10.1158/1055-9965.epi-20-1456
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发表时间：
2021-08
期刊：
影响因子：
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通讯作者：
Cohn BA
中科院分区：
文献类型：
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作者：
Cirillo PM;La Merrill MA;Krigbaum NY;Cohn BA
在先前出版物中的儿童健康与发展研究多代队列中，怀孕期间或怀孕后的血清滴滴涕与母亲的乳腺癌（F0）以及成年女儿的乳腺癌、乳房X光密度和肥胖（F1）相关。在这里，我们研究了 F0 围产期血清 DDT 与孙女 (F2) 测量的中位年龄 26 岁时的肥胖和自我报告的初潮年龄之间的关系。 F2 体重、身高和腰围由经过培训的检查员测量。在存档的 F0 围产期血清中测量了 o,p'-DDT、p,p'-DDT 和 p,p'-DDE。 F0 DDT 与 F2 结果的关联（考虑到 F1 特征）是在对数线性模型中估计的，该模型针对 F0 和 F1 体重指数 (BMI)、种族和初潮时间进行了调整（N = 258 个肥胖三联体；N = 235 个初潮早期三联体）。估计了 F0 BMI 和 DDT 之间的相互作用。在正常体重 F0 (70%) 中，F0 o,p'-DDT 与 F2 肥胖相关（比值比，OR，2.6；95% 置信区间 (CI)，1.3, 6.7，三分位数 3 比 1），但在超重和肥胖 F0 中不相关（p 交互作用 = 0.03），独立于其他 DDT。 F0 o,p’-DDT 也与 F2 初潮早期相关（OR，2.1；95% CI，1.1，3.9，三分位数 3 比 1），并且这种关联并未因 F0 BMI 改变。几十年前就被禁止的祖先接触环境化学物质可能会影响初潮提前和肥胖的发展，而这些都是乳腺癌和心脏代谢疾病的既定危险因素。年轻女性对祖先环境暴露反应的可操作生物标志物的发现可能为乳腺癌的预防提供机会。
Serum DDTs during or just after pregnancy were associated with breast cancer in mothers (F0), and with breast cancer, mammographic density and obesity in adult daughters (F1) in the Child Health and Development Studies multi-generational cohort in prior publications. Here we investigate F0 perinatal serum DDT associations with granddaughters’(F2) measured obesity at a median age of 26 and self-reported age at menarche. F2 weight, height and waist circumference were measured by trained examiners. o,p’-DDT, p,p’-DDT and p,p’-DDE were measured in archived F0 perinatal serum. F0 DDT associations with F2 outcomes, accounting for F1 characteristics, were estimated in log-linear models adjusted for F0 and F1 body mass index (BMI), race, and menarche timing (N=258 triads for obesity; N=235 triads for early menarche). Interactions between F0 BMI and DDTs were estimated. F0 o,p’-DDT was associated with F2 obesity (Odds ratio, OR, 2.6; 95% Confidence Interval (CI), 1.3, 6.7, tertile 3 vs. 1), among normal weight F0 (70%), but not among overweight and obese F0 (p-interaction=0.03), independent of other DDTs. F0 o,p’-DDT was also associated with F2 early menarche (OR, 2.1; 95% CI, 1.1, 3.9, tertile 3 vs. 1) and this association was not modified by F0 BMI. Ancestral exposure to environmental chemicals, banned decades ago, may influence the development of earlier menarche and obesity, which are established risk factors for breast cancer and cardiometabolic diseases. Discovery of actionable biomarkers of response to ancestral environmental exposures in young women may provide opportunities for breast cancer prevention.