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.

项目摘要/摘要 一般人群长期暴露于低剂量的有毒金属，包括铅，镉和 锰，受污染的食物和饮用水在美国很普遍，非洲人 美国人比白人同行更暴露。暴露的这种种族差异可能会导致 非洲裔美国人承受的不平等疾病负担，包括子宫的发展 肌瘤。这些平滑肌子宫肿瘤在超过80％的非洲裔美国妇女中发展 50，与大量发病有关。几乎没有发现这种疾病的危险因素 适合干预，激发需要调查环境因素的作用的必要性。另外，给予 避免在环境中无处不在的有毒金属的困难，理解 行为和生物学因素，包括饮食和铁储存，参与人体吸收这些化学物质 对于预防至关重要。但是，关于这些因素的研究很少 影响有毒金属的摄取和吸收，尤其是在生殖年龄妇女中，大多数 其中的铁，锌和钙的饮食摄入量不足，而月经失血是一种 铁缺乏的主要贡献者。此外，先前对金属和子宫肌瘤的研究已经产生 矛盾的结果，可能是由于所采用的研究设计的局限性所致。其中的中心假设 提案是1）铁，钙和锌的饮食摄入中的常见缺陷以及 大量月经出血的铁储存量，增加了人体对铅的吸收，镉和 锰在女性中，2）这些有毒金属增加了子宫肌瘤风险，并且考虑到诱变和 激素作用在体内和体外表现出。为了检验这些假设，拟议的研究将基于 建立了近1,700名年轻的非洲裔美国妇女，使用数据和存档的生物样本组成 根据环境，生活方式和肌瘤（自我）的研究，这是一项针对肌瘤的前瞻性研究。 美国国家环境健康科学研究所（Ziaes049013，D。Baird，首席研究员）。 将分析纳入铅，镉和锰的归档全血样品，并存储 血清样品将用于体铁储存，铁蛋白和转铁蛋白受体的生物标志物。这些 生物标志物数据将链接到有关饮食摄入量和重量大量出血的问卷数据以及 在5年内每20个月收集一次的肌瘤的超声数据，以实现以下目的：1） 确定基本营养素铁，钙和锌的饮食摄入中缺乏的程度 与铅，镉和锰的血液浓度改变有关； 2）确定 低体铁储存，重月经和铅，镉和锰之间的关联 浓度； 3）确定血铅，镉和锰之间的关联 在5年内入学率和子宫肌瘤发病率时的浓度。 NIH独立途径提出的研究和随附的职业发展计划 奖励申请将使Upson博士能够实现她作为护士科学家的长期职业目标 重要的研究问题，弥合妇女生殖健康和环境健康领域 最终为可行的干预措施提供了改善生殖时代妇女健康状况的信息。 K99指导 - 该奖项的阶段将在国立国家研究所的壁内研究计划中进行 环境卫生科学，环境卫生研究的先锋研究所。 Upson博士Will 从博士那里获得指导。唐娜·贝尔德（Donna Baird），珍妮特·霍尔（Janet Hall）和埃里克·托卡（Erik Tokar），子宫肌瘤的著名学者 研究，生殖内分泌学和金属毒理学。其他指导将是 由她的咨询委员会提供，由营养流行病学专家Michelle Mendez博士组成， 伊丽莎白·科温（Elizabeth Corwin）博士，他在R01授予技巧和学术求职过程中具有专业知识 一位知名的护士科学家。指导组成部分将由结构化培训补充 包括课程工作，定向阅读，参加研讨会，研讨会和国家的活动 会议和职业发展活动，以解决专业成长的关键领域，以促进 过渡到独立。从提供这项指导和结构化培训的完成 活动，Upson博士将实现她的短期目标，其中包括获得毒理学的熟练程度， 生殖内分泌学和营养，并将这些知识融入她现有的护理知识 和流行病学技能设置，以便在奖项的K99和R00阶段进行新的研究。这 将允许Upson博士就人体所涉及的行为和生物学因素提供关键信息 还吸收金属，以对有毒金属和子宫肌瘤风险进行首次前瞻性研究 R00独立阶段。这项创新研究和培训的行为不仅会促进 成功启动了候选人作为护士科学家的独立研究职业，但将为未来提供信息 采取干预措施，以防止不同暴露于有毒金属，减轻疾病的负担并提高质量 生活，与国家护理研究所的研究重点保持一致。