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

• 批准号: 9237267
• 负责人: Katherine Whitney Reeves
• 金额: $ 55.19万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-15 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9237267
• 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; Diethylhexyl 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; 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' s Health; cancer risk; carcinogenicity; cohort; consumer product; cost; diethylphthalate; follow-up; hormone therapy; malignant breast neoplasm; medical supply; phthalates; prospective; public health relevance; urinary

 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（由申请人提供）：越来越多的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，邻苯二甲酸盐是多种消费品（例如化妆品、药物、乙烯基地板）中用作增塑剂的化学物质，其邻苯二甲酸盐代谢物的检测结果接近 100%。尽管含量差异很大，并且在人类母乳中也有报道，但有关邻苯二甲酸盐是否影响人类乳腺癌风险的数据尚不清楚。仅存在一项小型回顾性病例对照研究，该研究报告与尿中邻苯二甲酸单乙酯水平相关的乳腺癌风险增加两倍，但与所研究的其他邻苯二甲酸酯代谢物没有关联或呈负相关。单一尿液样本不太适合解决这个重要问题，因为 1) 诊断后测量的尿邻苯二甲酸酯代谢物水平可能受到治疗期间邻苯二甲酸酯暴露的影响，2) 单一测量不太可能反映与癌症风险更相关的长期接触，因此，人们对邻苯二甲酸盐接触对乳腺癌风险的影响仍知之甚少，而澄清这些常见接触的影响将为数百万人提供重要信息。我们建议在女性健康倡议 (WHI) 中进行一项前瞻性研究，以评估 11 种尿邻苯二甲酸盐代谢物水平与乳腺癌风险之间的关联，前瞻性收集基线和第 3 年的尿液样本。我们还可以对 WHI 参与者的子样本进行随访，还可以获取一些参与者的第一年尿液样本，包括已知的乳腺癌风险因素。随访第 3 年后诊断的 500 名浸润性乳腺癌病例和 1,000 名健康匹配对照的重复尿样中含有 11 种邻苯二甲酸盐代谢物，旨在实现以下具体目标：1) 确定邻苯二甲酸盐是否存在代谢物水平与乳腺癌风险相关，2) 评估邻苯二甲酸酯代谢物水平与乳腺癌之间的关联是否因以下因素而变化：a) 疾病特征，如激素受体状态；b) 个人因素，包括年龄、绝经后激素治疗的使用、前瞻性 WHI 队列中存储的重复尿液样本和大量随附数据是独特的资源，为首次探索邻苯二甲酸盐在乳房中的作用提供了绝佳的机会。 如果观察到邻苯二甲酸盐与乳腺癌风险之间存在联系，女性可以减少接触含邻苯二甲酸盐的消费品，作为一级预防的手段，最终，了解接触邻苯二甲酸盐是否会影响乳腺癌风险可能会促使制造商、立法机构、以及倡导从消费品中完全去除邻苯二甲酸盐的努力。

项目成果

Urinary concentrations of phthalate biomarkers and weight change among postmenopausal women: a prospective cohort study.

绝经后妇女尿液中邻苯二甲酸酯生物标志物浓度和体重变化：一项前瞻性队列研究。

• 发表时间: 2019
• 作者: Díaz Santana, Mary V;Hankinson, Susan E;Bigelow, Carol;Sturgeon, Susan R;Zoeller, R Thomas;Tinker, Lesley;Manson, Jo Ann E;Calafat, Antonia M;Meliker, Jaymie R;Reeves, Katherine W
• 通讯作者: Reeves, Katherine W

Urinary Phthalate Biomarkers and Bone Mineral Density in Postmenopausal Women.

绝经后妇女的尿液邻苯二甲酸盐生物标志物和骨矿物质密度。

• 发表时间: 2021
• 作者: Reeves, Katherine W;Vieyra, Gabriela;Grimes, Nydjie P;Meliker, Jaymie;Jackson, Rebecca D;Wactawski;Wallace, Robert;Zoeller, R Thomas;Bigelow, Carol;Hankinson, Susan E;Manson, JoAnn E;Cauley, Jane A;Calafat, Antonia M
• 通讯作者: Calafat, Antonia M

Urinary Phthalate Biomarker Concentrations and Postmenopausal Breast Cancer Risk.

尿邻苯二甲酸盐生物标志物浓度和绝经后乳腺癌风险。

• 发表时间: 2019-10-01
• 作者: Reeves, Katherine W;Díaz Santana, Mary;Manson, JoAnn E;Hankinson, Susan E;Zoeller, R Thomas;Bigelow, Carol;Sturgeon, Susan R;Spiegelman, Donna;Tinker, Lesley;Luo, Juhua;Chen, Bertha;Meliker, Jaymie;Bonner, Matthew R;Cote, Michele L;Cheng, Ti
• 通讯作者: Cheng, Ti

Biomarkers of phthalates and inflammation: Findings from a subgroup of Women's Health Initiative participants.

邻苯二甲酸盐和炎症的生物标志物：女性健康倡议参与者小组的发现。

• DOI: 10.1016/j.ijheh.2021.113743
• 发表时间: 2021-05
• 期刊: International journal of hygiene and environmental health
• 影响因子: 6
• 作者: Trim A;Hankinson SE;Liu S;Shadyab AH;Meliker J;Bao W;Luo J;Liu B;Manson JE;Tinker L;Bigelow C;Reeves KW
• 通讯作者: Reeves KW

Predictors of urinary phthalate biomarker concentrations in postmenopausal women.

绝经后妇女尿邻苯二甲酸酯生物标志物浓度的预测因子。

• 发表时间: 2019
• 影响因子: 8.3
• 作者: Reeves, Katherine W;Santana, Mary Díaz;Manson, JoAnn E;Hankinson, Susan E;Zoeller, R Thomas;Bigelow, Carol;Hou, Lifang;Wactawski;Liu, Simin;Tinker, Lesley;Calafat, Antonia M
• 通讯作者: Calafat, Antonia M