Child Health and Development Studies, Public Health Institute, Berkeley, CA, 94709, USA.
Department of Environmental Toxicology, College of Biological Sciences, Comprehensive Cancer Center, University of California, Davis, Davis, CA, 95616, USA.
J Expo Sci Environ Epidemiol. 2019 Apr;29(3):302-309. doi: 10.1038/s41370-018-0072-7. Epub 2018 Sep 17.
Many suspected breast cancer risk factors, including the pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE), are stored in fat where they could influence carcinogenesis. We tested the hypothesis that the relationship of DDT and DDE (DDTs) with adiposity is modified by disposition to develop breast cancer. We predicted that concentrations of serum DDTs would be inversely correlated with body mass index (BMI) during active exposure when DDTs move into the larger fat pool. We described this correlation at an average of 17 years before breast cancer was diagnosed, in a prospective nested case-control study in the Child Health and Development Studies. Women entered the study during pregnancy from 1959 to 1966 when DDT was in active use. In total, 133 breast cancer cases were diagnosed under the age of 50 as of 1998. Mean time to diagnosis was 17 years. In total, 133 controls were matched to cases on birth year. We observed the expected inverse correlation of serum DDTs with BMI only in women who remained cancer-free and not in women who ultimately developed breast cancer (p for interaction < 0.05). Findings suggest that vulnerability to breast cancer before the age of 50 may be associated with an uncoupling of the inverse correlation between BMI and serum DDTs. Investigation into mechanisms may eventually reveal early biomarkers of breast cancer risk.
许多疑似乳腺癌的风险因素，包括杀虫剂滴滴涕（DDT）及其代谢物滴滴涕（DDE），都储存在脂肪中，这些物质可能会影响致癌作用。我们检验了这样一个假设，即 DDT 和 DDE（DDTs）与肥胖的关系受到乳腺癌易感性的影响。我们预测，在 DDT 进入更大脂肪池的活跃暴露期间，血清 DDT 浓度与体重指数（BMI）呈负相关。在儿童健康与发展研究中的前瞻性嵌套病例对照研究中，我们在乳腺癌诊断前平均 17 年时描述了这种相关性。这些女性在 1959 年至 1966 年怀孕期间加入了研究，当时 DDT 正在被广泛使用。截至 1998 年，共有 133 名 50 岁以下的乳腺癌病例被确诊。平均诊断时间为 17 年。共有 133 名对照与病例按出生年份匹配。我们仅在未患癌症的女性中观察到血清 DDT 与 BMI 呈预期的负相关，而在最终患有乳腺癌的女性中则没有观察到这种相关性（p 值<0.05）。研究结果表明，50 岁以下乳腺癌的易感性可能与 BMI 和血清 DDT 之间的负相关关系的脱钩有关。对机制的研究最终可能会揭示乳腺癌风险的早期生物标志物。
