Influence of Diet, Iron Stores, and Toxic Metals on Uptakes and Effects on Uterine Fibroid Risk in African American Women

饮食、铁储备和有毒金属对非裔美国女性摄取和子宫肌瘤风险的影响

• 批准号: 9912867
• 负责人: Kristen Upson
• 金额: $ 24.63万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-10 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9912867
• 关键词: Address; Adult; Adverse effects; Advisory Committees; African American; Age; Archives; Area; Award; Behavioral; Biological Factors; Biological Markers; Blood specimen; Cadmium; Calcium; Chemicals; Chronic; Communities; Complement; Corwin; DNA Sequence Alteration; Data; Development; Development Plans; Diet; Dietary Zinc; Dietary intake; Discipline of Nursing; Disease; Distress; Dose; Educational workshop; Enrollment; Environment; Environmental Health; Environmental Risk Factor; Epidemiology; Event; Exhibits; Exposure to; Ferritin; Fibroid Tumor; Food; Food Contamination; Frequencies; Functional disorder; Funding; Future; General Population; Goals; Growth; Health; Hemorrhage; Hormonal; Human; In Vitro; Incidence; Institutes; Intervention; Intestinal Absorption; Intestines; Intramural Research Program; Iron; Knowledge; Lead; Life Style; Link; Manganese; Measures; Medical; Mentors; Mentorship; Metal exposure; Metals; Michigan; Morbidity - disease rate; National Institute of Environmental Health Sciences; National Institute of Nursing Research; Nurses; Nutrient; Occupations; Ovarian; Pathway interactions; Phase; Population; Prevention; Principal Investigator; Process; Prospective Studies; Public Health; Quality of life; Questionnaires; Race; Reading; Reproductive Endocrinology; Reproductive Health; Reproductive History; Research; Research Design; Research Priority; Research Training; Risk; Risk Factors; Role; Sampling; Scientist; Serum; Smooth Muscle; Smooth Muscle Tumor; Steroids; Structure; TFRC gene; Testing; Toxic effect; Toxicology; Training; Training Activity; Ultrasonography; United States; United States National Institutes of Health; Uterine Fibroids; Uterine Neoplasms; Visit; Whole Blood; Woman; Zinc; absorption; base; behavioral study; blood Pb concentration; blood lead; burden of illness; career; career development; cohort; contaminated drinking water; data archive; drinking water; early onset; experience; ferritin receptor; hormonal signals; improved; in vivo; innovation; iron absorption; iron deficiency; lead exposure; meetings; novel; nutrition; nutritional epidemiology; prevent; prospective; racial disparity; reproductive; skills; toxic metal; tumor growth; tumorigenesis; uptake

PROJECT SUMMARY/ABSTRACT Chronic exposure of the general population to low-doses of toxic metals, including lead, cadmium, and manganese, from contaminated food and drinking water is widespread in the United States, with African Americans being more exposed than their white counterparts. This racial disparity in exposure may contribute to the unequal burden of disease experienced by African Americans, including the development of uterine fibroids. These smooth muscle uterine tumors develop in more than 80% of African American women by age 50 and are associated with substantial morbidity. Few risk factors for this disease have been identified that are amenable to intervention, motivating the need to investigate the role of environmental factors. In addition, given the difficulty in avoiding exposure to toxic metals that are ubiquitous in the environment, understanding behavioral and biologic factors, including diet and iron stores, involved in the body's uptake of these chemicals is critical for prevention. However, few human studies have been conducted on these factors that may influence the uptake and absorption of toxic metals, particularly among reproductive-age women, the majority of whom have inadequate dietary intakes of iron, zinc, and calcium, and for whom menstrual blood loss is a major contributor to iron deficiency. In addition, prior human studies of metals and uterine fibroids have yielded contradictory results, likely due to the limitations of the study designs employed. The central hypotheses in this proposal are that 1) common deficiencies in the dietary intake of iron, calcium, and zinc as well as the depletion of iron stores from heavy menstrual bleeding, increase the body's uptake of lead, cadmium and manganese in women, and 2) these toxic metals increase uterine fibroid risk given the mutagenic and hormonal actions exhibited in vivo and in vitro. To test these hypotheses, the proposed research will build on an established cohort of nearly 1,700 young, African American women using data and archived biosamples from the Study of Environment, Lifestyle & Fibroids (SELF), a 5-year prospective study of fibroids funded by the National Institute of Environmental Health Sciences (ZIAES049013, D. Baird, Principal Investigator). Archived whole blood samples from enrollment will be analyzed for lead, cadmium, and manganese and stored serum samples will be measured for biomarkers of body iron stores, ferritin and transferrin receptor. These biomarker data will be linked to questionnaire data on dietary intake and heavy menstrual bleeding as well as to ultrasound data on fibroids collected every 20 months over 5 years to accomplish the following aims: 1) to determine the extent to which deficiencies in dietary intake of essential nutrients iron, calcium, and zinc are associated with altered blood concentrations of lead, cadmium, and manganese; 2) to determine the associations between low body iron stores, heavy menstrual bleeding, and lead, cadmium, and manganese concentrations; and 3) to determine the associations between blood lead, cadmium, and manganese concentrations at enrollment and uterine fibroid incidence over a 5-year period. The research and accompanying career development plan proposed in this NIH Pathway to Independence Award application will allow Dr. Upson to achieve her long-term career goal as a nurse scientist to answer important research questions that bridge the fields of women's reproductive health and environmental health to ultimately inform feasible interventions to improve the health of reproductive-age women. The K99 mentored- phase of the award will take place within the Intramural Research Program at the National Institute of Environmental Health Sciences, an institute at the vanguard of environmental health research. Dr. Upson will receive mentorship from Drs. Donna Baird, Janet Hall, and Erik Tokar, eminent scholars in uterine fibroid research, reproductive endocrinology, and metals toxicology, respectively. Additional mentoring will be provided by her advisory committee consisting of Dr. Michelle Mendez, an expert in nutritional epidemiology, and Dr. Elizabeth Corwin, who has expertise in R01 grantsmanship and the academic job search process as an established nurse scientist. The mentorship component will be complemented by structured training activities, consisting of coursework, directed readings, attendance at workshops, seminars, and national meetings, and career development activities to address key areas of professional growth that will promote the transition to independence. From the provision of this mentorship and the completion of structured training activities, Dr. Upson will achieve her short-term goals which include gaining a proficiency in toxicology, reproductive endocrinology, and nutrition, and integrating this knowledge into her existing nursing knowledge and epidemiologic skill set so as to conduct novel research during the K99 and R00 phases of the award. This will allow Dr. Upson to contribute critical information on behavioral and biologic factors involved in the body's uptake of metals as well to conduct the first prospective study of toxic metals and uterine fibroid risk during the R00 independent phase. The conduct of this innovative research and training will not only facilitate the successful launch of the candidate's independent research career as a nurse scientist, but will inform future interventions to prevent disparate exposure to toxic metals, reduce the burden of disease, and improve quality of life, in alignment with the research priorities of the National Institute of Nursing Research.

项目概要/摘要 一般人群长期接触低剂量的有毒金属，包括铅、镉和 来自受污染食品和饮用水的锰在美国广泛存在，非洲 美国人比白人更容易受到影响。这种暴露的种族差异可能会导致 非裔美国人所经历的不平等的疾病负担，包括子宫发育 肌瘤。按年龄划分，超过 80% 的非洲裔美国女性都会患上这些平滑肌子宫肿瘤 50并且与大量发病率相关。已确定的这种疾病的危险因素很少 易于干预，激发了调查环境因素作用的需要。此外，鉴于 避免接触环境中普遍存在的有毒金属的困难，了解 行为和生物因素，包括饮食和铁储存，参与人体对这些化学物质的吸收 对于预防至关重要。然而，很少有人对这些因素进行人体研究，这些因素可能会导致 影响有毒金属的吸收和吸收，尤其是育龄妇女，大多数 其中铁、锌和钙的膳食摄入量不足，并且月经失血是一个严重问题 缺铁的主要因素。此外，先前对金属和子宫肌瘤的人体研究已经取得了成果 矛盾的结果，可能是由于所采用的研究设计的局限性。本文的中心假设 建议是：1）膳食中铁、钙和锌摄入量的常见缺乏以及 经血过多会导致铁储备耗尽，增加身体对铅、镉和 女性中的锰，2) 这些有毒金属会增加子宫肌瘤的风险，因为它们具有致突变性和致突变性。 在体内和体外表现出荷尔蒙作用。为了检验这些假设，拟议的研究将建立在 使用数据和存档的生物样本建立了一个由近 1,700 名年轻非裔美国女性组成的队列 来自环境、生活方式和肌瘤研究 (SELF)，这是一项由以下机构资助的为期 5 年的肌瘤前瞻性研究 国家环境健康科学研究所（ZIAES049013，D. Baird，首席研究员）。 将对登记时存档的全血样本进行铅、镉和锰分析并储存 将测量血清样本中体内铁储备、铁蛋白和转铁蛋白受体的生物标志物。这些 生物标志物数据将与饮食摄入量和月经出血量以及月经量的调查问卷数据相关联 5 年内每 20 个月收集一次肌瘤超声数据，以实现以下目标：1) 确定膳食中必需营养素铁、钙和锌摄入量的缺乏程度 与血液中铅、镉和锰浓度的改变有关； 2）确定 体内铁储存量低、经血过多与铅、镉和锰之间的关联 浓度； 3) 确定血铅、镉和锰之间的关联 入组时的浓度和五年内子宫肌瘤的发病率。 NIH 独立之路中提出的研究和相应的职业发展计划 奖项申请将使厄普森博士能够实现她作为护士科学家的长期职业目标 连接妇女生殖健康和环境健康领域的重要研究问题 最终为改善育龄妇女健康的可行干预措施提供信息。 K99 指导- 该奖项的阶段将在国家研究所的校内研究计划内进行 环境健康科学研究所，环境健康研究的先锋机构。厄普森博士将 接受博士的指导。唐娜·贝尔德 (Donna Baird)、珍妮特·霍尔 (Janet Hall) 和埃里克·托卡 (Erik Tokar)，子宫肌瘤领域的杰出学者 分别是研究、生殖内分泌学和金属毒理学。额外的指导将是 由营养流行病学专家 Michelle Mendez 博士组成的咨询委员会提供， 伊丽莎白·科温 (Elizabeth Corwin) 博士在 R01 资助和学术求职流程方面拥有丰富的专业知识 一位知名的护士科学家。指导部分将辅以结构化培训 活动，包括课程作业、定向阅读、参加讲习班、研讨会和国家 会议和职业发展活动，以解决专业发展的关键领域，从而促进 向独立过渡。从提供指导和完成结构化培训开始 通过这些活动，厄普森博士将实现她的短期目标，其中包括精通毒理学、 生殖内分泌学和营养学，并将这些知识整合到她现有的护理知识中 和流行病学技能，以便在该奖项的 K99 和 R00 阶段进行新颖的研究。这 将使厄普森博士能够提供有关人体的行为和生物因素的关键信息 金属的吸收，以及对有毒金属和子宫肌瘤风险进行首次前瞻性研究 R00独立相。这种创新研究和培训的进行不仅将促进 候选人作为护士科学家的独立研究生涯的成功启动，但将为未来提供信息 采取干预措施，防止不同程度地接触有毒金属、减轻疾病负担并提高质量 生命的一部分，与国家护理研究所的研究重点保持一致。