Phthalate Metabolites and Breast Cancer Risk in the Women's Health Initiative

妇女健康倡议中的邻苯二甲酸盐代谢物和乳腺癌风险

基本信息

批准号：
9054118
负责人：
Katherine Whitney Reeves
金额：
$ 50.03万
依托单位：
UNIVERSITY OF MASSACHUSETTS AMHERST
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-15 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9054118
关键词：
Address Advocacy Affect Age Biological Markers Body mass index Breast Breast Cancer Cell Breast Cancer Prevention Breast Cancer Risk Factor Breast Cancer cell line Case-Control Studies Characteristics Chemicals Chronic Cosmetics Data Diagnosis Diagnostic Dibutyl Phthalate Disease Endocrine disruption Equipment Estrogen Receptor Status Estrogen Receptors Excision Exogenous Hormone Therapy Exposure to Floor Health Hormone Receptor Hormones Human Human Milk In Vitro Individual Ingestion Laboratory Animal Models Link Malignant Neoplasms Mammary Gland Parenchyma Mammographic Density Manufacturer Name Measurable Measurement Measures Medical Medical Records Mono-S Parents Participant Pharmaceutical Preparations Plasticizers Population Postmenopause Prevalence Primary Prevention Property Prospective Studies Public Health Questionnaires Reporting Resources Retrospective Studies Risk Role Safety Sampling Specimen Subgroup Time Toy Urine Woman Women&apos s Health cancer risk cohort consumer product cost diethylphthalate follow-up hormone therapy malignant breast neoplasm medical supply phthalates prospective urinary

项目摘要

DESCRIPTION (provided by applicant): Mounting laboratory and animal model evidence supports the potentially carcinogenic effects of phthalates, chemicals used as plasticizers in a wide variety of consumer products (e.g. cosmetics, medications, vinyl flooring). Phthalate metabolites are measurable in nearly 100% of the U.S. population, though levels vary widely, and also have been reported in human breast milk. However, data on whether phthalates affect human breast cancer risk is lacking. Only one small retrospective case-control study exists, which reported a two-fold increase in breast cancer risk associated with urinary levels of mono-ethyl phthalate, yet either no association or an inverse association with other phthalate metabolites studied. Retrospective studies utilizing a single urine sample are poorly suited for addressing this important question, because 1) urinary phthalate metabolite levels measured after diagnosis may have been affected by phthalate exposure during treatment, and 2) a single measurement is unlikely to reflect longer-term exposures, which are of greater relevance to cancer risk. As a result, the impact of phthalate exposure on breast cancer risk remains poorly understood. Clarifying the effects of these common exposures will provide critical information for the millions of women concerned about their breast health. We propose a prospective study nested within the Women's Health Initiative (WHI) to evaluate associations between levels of eleven urinary phthalate metabolites and breast cancer risk. Prospectively collected urine samples from baseline and year 3 of follow-up are available on a sub-sample of WHI participants with year 1 urine samples also available on some participants. Extensive data from questionnaires and medical records, including known breast cancer risk factors, also are available on these participants. We will measure levels of eleven phthalate metabolites in repeated urine samples from 500 invasive breast cancer cases diagnosed after year 3 of follow-up and 1,000 healthy matched controls to address the following Specific Aims: 1) to determine if phthalate metabolite levels are associated with breast cancer risk, and 2) to evaluate if the associations between phthalate metabolite levels and breast cancer vary by: a) disease characteristics such as hormone receptor status; and b) personal factors including age, postmenopausal hormone therapy use, and body mass index. The stored repeat urine samples and vast accompanying data available within the prospective WHI cohort are a unique resource and provide an excellent opportunity to explore for the first time the role of phthalates in breast cancer risk. If a link between phthalates and breast cancer risk were observed, women could reduce their exposure to phthalate-containing consumer products as a means of primary prevention. Ultimately, understanding if exposure to phthalates affects breast cancer risk may motivate manufacturer, legislative, and advocacy efforts to remove phthalates from consumer products altogether.

描述（由适用提供）：安装实验室和动物模型证据支持邻苯二甲酸盐的潜在致癌作用，邻苯二甲酸盐，在各种消费产品中用作增塑的化学物质（例如化妆品，药物，乙烯基地板）。邻苯二甲酸酯代谢产物在几乎100％的美国人群中可以测量，尽管水平差异很大，并且在人类母乳中也有报道。但是，有关邻苯二甲酸盐是否影响人类乳腺癌风险的数据。仅存在一项小的回顾性病例对照研究，报告说，乳腺癌水平相关的乳腺癌风险增加了两倍，但与其他邻苯二甲酸酯代谢物工作室无关或与其他相关性相关。利用单个尿液样品的回顾性研究不适合解决这一重要问题，因为1）诊断后测得的尿邻苯二甲酸酯代谢物水平可能受到治疗过程中邻苯二甲酸盐暴露的影响，而2）单一测量不太可能反映与癌症风险相关的长期持续性。结果，邻苯二甲酸盐暴露对乳腺癌风险的影响仍然很少了解。阐明这些常见暴露的影响将为数百万关注其乳房健康的妇女提供关键信息。我们提出了一项嵌套在妇女健康计划（WHI）中的前瞻性研究，以评估11次尿邻苯二甲酸酯代谢产物和乳腺癌风险之间的关联。从基线和后续第3年收集的尿液样本可在WHI参与者的子样本中获得，其中1年的尿液样本也可供一些参与者提供。这些参与者也提供了来自问卷和病历的大量数据，包括已知的乳腺癌危险因素。我们将测量来自500例侵入性乳腺癌病例的反复尿液样本中的11种邻苯二甲酸酯代谢产物的水平，以解决以下特定目的：1）确定乳腺癌水平是否与乳腺癌的风险相关，以及2）是否与乳腺癌疾病之间的疾病相关。地位; b）个人因素，包括年龄，绝经后马酮治疗和体重指数。存储的重复尿液样本和潜在同类中的大量参与数据是一种独特的资源，并为邻苯二甲酸酯在乳房中的作用提供了绝佳的机会癌症风险。如果观察到邻苯二甲酸盐与乳腺癌风险之间的联系，妇女可以减少含邻苯二甲酸酯的消费产品的暴露，以此作为初级预防的一种手段。最终，了解邻苯二甲酸盐的暴露是否会影响乳腺癌的风险，可能会激发制造商，立法和倡导工作，以完全从消费产品中清除邻苯二甲酸盐。