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.

项目总结/摘要 普通人群长期接触低剂量的有毒金属，包括铅、镉和 锰，从受污染的食物和饮用水是广泛的在美国，与非洲 美国人比他们的白色同行更暴露。这种暴露的种族差异可能有助于 非洲裔美国人所经历的疾病负担不平等，包括子宫内膜异位症的发展， 纤维瘤这些平滑肌子宫肿瘤的发展超过80%的非洲裔美国妇女的年龄 50并与大量发病率相关。这种疾病的风险因素很少被确定， 易于干预，激发了调查环境因素作用的需要。此外，鉴于 避免暴露于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，参与身体对这些化学物质的吸收 对预防至关重要。然而，很少有人对这些因素进行人体研究， 影响有毒金属的摄取和吸收，特别是在育龄妇女中， 其中铁、锌和钙的饮食摄入量不足，月经失血是 缺铁的主要原因此外，先前对金属和子宫肌瘤的人体研究已经产生了 矛盾的结果，可能是由于所采用的研究设计的限制。其中的核心假设 建议是：1）饮食中铁、钙和锌的摄入量以及 大量月经出血会消耗铁储存，增加身体对铅，镉和 锰在妇女中，和2）这些有毒金属增加子宫肌瘤的风险，因为诱变和 在体内和体外表现出的激素作用。为了验证这些假设，拟议的研究将建立在 一个由近1,700名年轻的非裔美国妇女组成的队列，使用数据和存档的生物样本 来自环境，生活方式和肌瘤研究（SELF），一项为期5年的肌瘤前瞻性研究，由 国家环境健康科学研究所（ZIAES 049013，D. Baird，主要研究者）。 将对入组时存档的全血样本进行铅、镉和锰分析并储存 将测量血清样品的身体铁储存、铁蛋白和转铁蛋白受体的生物标志物。这些 生物标志物数据将与关于饮食摄入和大量月经出血的问卷调查数据相关联， 在5年内每20个月收集一次关于肌瘤的超声数据，以实现以下目标：1） 确定膳食中必需营养素铁、钙和锌的摄入不足的程度， 与铅、镉和锰的血液浓度改变有关; 2）确定 体内铁储存量低、月经大量出血与铅、镉和锰之间的关系 浓度;和3）确定血铅，镉和锰之间的关联 入组时的浓度和5年内子宫肌瘤的发病率。 本NIH独立之路中提出的研究和伴随的职业发展计划 奖项申请将允许厄普森博士实现她的长期职业目标作为一个护士科学家回答 将妇女生殖健康和环境健康领域联系起来的重要研究问题， 最终为可行的干预措施提供信息，以改善育龄妇女的健康。K99的指导- 该奖项的第一阶段将在国家研究所的校内研究计划内进行。 环境健康科学是环境健康研究的先锋。厄普森医生会 接受Donna Baird博士，Janet Hall和Erik Tokar的指导，他们是子宫肌瘤领域的著名学者 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米歇尔·门德斯博士组成的咨询委员会提供， 伊丽莎白·科温博士，她在R 01 granitary和学术求职过程中有专业知识， 一位著名的护士科学家指导部分将辅之以结构化培训 活动，包括课程作业，指导阅读，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，这将促进 过渡到独立。从提供这种指导和完成结构化培训 活动，厄普森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K99和R 00阶段进行新的研究。这 将允许厄普森博士贡献关键信息的行为和生物因素参与身体的 金属的摄取，以及进行有毒金属和子宫肌瘤风险的第一次前瞻性研究， R 00独立相位。开展这一创新研究和培训不仅将促进 作为一名护士科学家，候选人的独立研究生涯的成功启动，但将告知未来 干预措施，以防止不同的接触有毒金属，减少疾病的负担，并提高质量 生命，与国家护理研究所的研究重点相一致。