Urinary cadmium and risk of breast cancer

尿镉与乳腺癌风险

• 批准号: 8432616
• 负责人: Jaymie R Meliker
• 金额: $ 40.18万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8432616
• 关键词: Address; Area; Arsenic; Attention; Biochemical; Biological; Biological Markers; Blood; Blood specimen; Body Burden; Bone Diseases; Breast; Breast Cancer Risk Factor; Cadmium; Carcinogenesis Mechanism; Cardiovascular Diseases; Cells; Chronic; Cohort Studies; DNA Damage; DNA Methylation; Development; Disease; Elements; Endocrine; Endocrine disruption; Endometrial Carcinoma; Environment; Environmental Health; Environmental sludge; Epidemiologic Studies; Epidemiology; Epigenetic Process; Equus caballus; Exposure to; Fertilizers; Future; General Population; Health; Heavy Metals; Human; Impaired Renal Function; Incidence; Lead; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Mercury; Metallothionein; Metals; Molecular; New York; Osteoporosis; Outcome; Oxidative Stress; Parents; Periodontal Diseases; Persons; Physiological; Play; Population; Postmenopause; Predisposition; Process; Prospective Studies; Public Health; Regulation; Renal function; Reporting; Reproducibility; Research; Research Design; Risk; Risk Assessment; Role; Sampling; Science; Sewage; Soil; Source; Spottings; Testing; Tobacco; Toxicology; Urine; Variant; cancer risk; carcinogenesis; clinical application; cohort; design; diet and cancer; disorder prevention; epigenetic marker; experience; hazard; inorganic phosphate; insight; malignant breast neoplasm; never smoker; novel; parent project; peripheral blood; prognostic; prospective; public health relevance; reproductive; response; toxic metal; urinary; validation studies; zinc thionein

DESCRIPTION (provided by applicant): Cadmium is a heavy metal that occurs naturally in the environment. In addition to the natural levels in soil, increased application of phosphate fertilizers and sewage sludge to cropland beginning in the latter half of the late 20th century resulted in increased cadmium in foodstuffs and tobacco, earning it notoriety as "the Trojan horse of the green revolution". Historically, cadmium-health research has focused on health effects from high exposures occurring in small subpopulations. However, epidemiologic and mechanistic evidence accumulated during the past decade suggests widespread health risks from low-level, chronic exposure to cadmium, including endocrine disruption and increased risk for breast and endometrial cancer along with reproductive effects, osteoporosis, renal function, cardiovascular disease and periodontal disease. Importantly, the early epidemiologic and mechanistic evidence suggests that increased risk may be observed at levels of exposure common to 30-60% of the population, which emphasizes the need for focused research on the effects of low-level cadmium. This competitive revision application proposes the creation of a cadmium consortium that builds onto the parent project: a prospective case-cohort epidemiologic study designed to test the hypothesis that cadmium contributes to the high incidence of breast cancer in Western populations. The proposed consortium will enhance the parent project while providing novel findings in its own right, findings that will guide future studies and clinical application of risk assessment for cadmium exposure. One aim will investigate temporal variability in urinary cadmium levels. This biomarker has the promise of being a rare long-term indicator of decades-long exposure; however, validation studies in lower-exposure populations, such as those in the U.S., are necessary to assess whether a single spot urine sample is a stable, reproducible estimate of cadmium body burden. A second aim will develop molecular biomarkers to help identify biological endpoints of exposure and possible connections to the carcinogenic process, considering interplay between cadmium, zinc, and metallothionein. A third aim will investigate DNA methylation profiles and their association with breast cancer and cadmium, making this one of the first prospective studies of epigenetic markers and cancer, and one of the first to examine cadmium's role in epigenetic processes in a human population. This new consortium will bridge population-level and molecular efforts to bring novel insights to the understanding of health risks from cadmium, using advances in exposure science, epigenetics, biochemical analysis, and biomarkers. Of note, there is great potential for disease prevention, with more extensive regulation to avoid population exposure, because primary sources of exposure to cadmium for the general population, e.g., fertilizer, are already well recognized.

描述（由申请人提供）：镉是一种自然存在于环境中的重金属。除了土壤中的自然含量外，从20世纪下半叶开始，农田中磷肥和污水污泥的施用量增加，导致食品和烟草中的镉含量增加，从而赢得了“绿色革命特洛伊木马”的美誉。从历史上看，镉健康研究的重点是小群体中高剂量暴露对健康的影响。然而，过去十年积累的流行病学和机制证据表明，低水平的长期接触镉会带来广泛的健康风险，包括内分泌干扰和乳腺癌和子宫内膜癌风险增加，以及生殖影响、骨质疏松症、肾功能、心血管疾病和牙周病。重要的是，早期流行病学和机制证据表明，30-60% 人群普遍接触的风险可能会增加，这强调需要对低浓度镉的影响进行重点研究。该竞争性修订申请提议创建一个以母项目为基础的镉联盟：一项前瞻性病例队列流行病学研究，旨在检验镉导致西方人群乳腺癌高发的假设。拟议的联盟将增强母项目，同时提供本身的新颖发现，这些发现将指导镉暴露风险评估的未来研究和临床应用。目标之一是研究尿镉水平的时间变化。这种生物标志物有望成为数十年暴露的罕见长期指标。然而，有必要对低暴露人群（例如美国的人群）进行验证研究，以评估单点尿液样本是否可以稳定、可重复地估计人体镉负荷。第二个目标是开发分子生物标志物，以帮助识别暴露的生物终点以及与致癌过程的可能联系，考虑镉、锌和金属硫蛋白之间的相互作用。第三个目标是研究 DNA 甲基化谱及其与乳腺癌和镉的关联，使其成为第一个表观遗传标记和癌症的前瞻性研究之一，也是第一个研究镉在人类表观遗传过程中的作用的研究之一。这个新联盟将利用暴露科学、表观遗传学、生化分析和生物标志物方面的进步，将人口层面和分子层面的努力结合起来，为了解镉的健康风险带来新的见解。值得注意的是，通过更广泛的监管来避免人群接触镉，疾病预防具有巨大潜力，因为公众接触镉的主要来源（例如化肥）已得到充分认识。