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祖孙三代同堂:胎儿期及围生期外婆血清滴滴涕与外孙女初潮年龄及成年后肥胖的关系——儿童健康发展研究队列研究

Grandmaternal Perinatal Serum DDT in Relation to Granddaughter Early Menarche and Adult Obesity: Three Generations in the Child Health and Development Studies Cohort.

机构信息

Child Health and Development Studies of the Public Health Institute, Berkeley, California.

Department of Environmental Toxicology, University of California, Davis, Davis California.

出版信息

Cancer Epidemiol Biomarkers Prev. 2021 Aug;30(8):1480-1488. doi: 10.1158/1055-9965.EPI-20-1456. Epub 2021 Apr 14.

Abstract

BACKGROUND

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.

METHODS

F2 weight, height and waist circumference were measured by trained examiners. -DDT, -DDT and 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 ( = 258 triads for obesity; = 235 triads for early menarche). Interactions between F0 BMI and DDTs were estimated.

RESULTS

F0 -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 ( = 0.03), independent of other DDTs. F0 -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.

CONCLUSIONS

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.

IMPACT

Discovery of actionable biomarkers of response to ancestral environmental exposures in young women may provide opportunities for breast cancer prevention..

摘要

背景

在母亲(F0)怀孕期间或之后的血清滴滴涕(DDTs)与乳腺癌有关,在先前的出版物中,在儿童健康与发展研究多代队列中,血清 DDT 与成年女儿(F1)的乳腺癌、乳房 X 光密度和肥胖有关。在这里,我们研究了 F0 围产期血清 DDT 与孙女(F2)的肥胖之间的关联,孙女的肥胖是在 26 岁的中位数年龄和自述初潮年龄时测量的。

方法

由经过培训的检查人员测量 F2 的体重、身高和腰围。在存档的 F0 围产期血清中测量了 DDT、-DDT 和 DDE。在对数线性模型中,根据 F1 特征,估计了 F0 DDT 与 F2 结果的关联,该模型还调整了 F0 和 F1 的体重指数(BMI)、种族和初潮时间(=258 个三胞胎用于肥胖;=235 个三胞胎用于初潮早)。还估计了 F0 BMI 和 DDTs 之间的相互作用。

结果

F0- DDT 与 F2 肥胖相关(优势比[OR],2.6;95%置信区间[CI],1.3-6.7;第 3 三分位与第 1 三分位),在正常体重的 F0 中(70%),但在超重和肥胖的 F0 中(=0.03)不相关,这与其他 DDTs 无关。F0- DDT 还与 F2 初潮早相关(OR,2.1;95%CI,1.1-3.9,第 3 三分位与第 1 三分位),且这种关联不受 F0 BMI 的影响。

结论

几十年前被禁止的环境化学物质的祖先暴露可能会影响初潮早和肥胖的发展,而初潮早和肥胖是乳腺癌和心血管代谢疾病的既定风险因素。

意义

发现年轻女性对祖先环境暴露的反应的可操作生物标志物可能为乳腺癌预防提供机会。

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