Urinary cadmium and risk of breast cancer

尿镉与乳腺癌风险

• 批准号: 8415525
• 负责人: Jaymie R Meliker
• 金额: $ 26.72万
• 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/8415525
• 关键词: Accounting; Address; Agreement; Apoptosis; Biological; Biological Availability; Biological Markers; Biometry; Breast; Breast Cancer Cell; Breast Cancer Risk Factor; Cadmium; Carcinogenesis Mechanism; Carcinogens; Cessation of life; Cohort Studies; Creatinine; DNA Repair; Data; Databases; Depressed mood; Developed Countries; Diagnosis; Diagnostic Neoplasm Staging; Diet; Dietary Zinc; Disease; Dose; Ductal; Educational Status; Endocrine; Enrollment; Environmental Carcinogens; Environmental Epidemiology; Environmental Exposure; Environmental Pollution; Environmental sludge; Epidemiologic Studies; Epidemiology; Epithelial Cells; Estrogen Antagonists; Estrogen Receptor 1; Estrogen Receptors; Estrogen receptor positive; Estrogens; Exercise; Exposure to; Female; Female Breast Carcinoma; Fertilizers; Food; Frequencies; Gene Activation; General Population; Half-Life; Health; Histology; Hormone replacement therapy; Hormones; Human; In Situ; In Vitro; Incidence; Individual; Intake; International; International Agency for Research on Cancer; Kidney; Laboratories; Light; Lobular; Lung; Malignant Neoplasms; Measures; Mediating; Metallothionein; Metals; Modification; Outcome; Participant; Play; Population; Postmenopause; Prevention; Prospective Studies; Questionnaires; Regulation; Reproductive History; Research Design; Risk; Risk Factors; Role; Sampling; Smoking; Smoking History; Smoking Status; Source; Specimen; Spottings; Time; Tobacco smoking; Trace metal; United States; United States Food and Drug Administration; Urine; Woman; Zinc; cancer diagnosis; cancer epidemiology; cancer risk; cigarette smoking; cohort; comparison group; design; diet and cancer; exposed human population; high risk; in vivo; inorganic phosphate; insight; malignant breast neoplasm; member; modifiable risk; nutritional epidemiology; prospective; public health relevance; research study; treatment effect; urinary

DESCRIPTION (provided by applicant): Environmental contaminants that mimic the effects of estrogen have been suggested to contribute to the high incidence of breast cancer in Western populations. In both in vitro and in vivo experiments, cadmium has been shown to possess potent estrogen-like activity, including proliferation of breast cancer cells, activation and increased expression of estrogen regulated genes, and activation of the estrogen receptor-1. Further, cadmium is classified as a known human carcinogen by the International Agency for Research on Cancer. This combination of estrogenic and carcinogenic activity makes cadmium a contaminant of particularly high concern for breast cancer. One modest-sized epidemiologic study suggests risk at cadmium exposure levels common to the upper quartile of the general population implying that cadmium may play a substantial role in breast cancer; however this study used urine cadmium collected after diagnosis. As a result, it has been questioned whether increased cadmium is a risk factor for breast cancer, or whether it reflects the effects of treatment or disease. In light of mechanistic and preliminary epidemiologic evidence supporting a cadmium-breast cancer relationship, this project aims to rigorously investigate the association between urinary cadmium levels collected prediagnostically and risk of breast cancer in a case-cohort study population from the Danish Diet Cancer and Health (DCH) prospective cohort. This is one of the few, if not only, cohorts in the world with adequate power for investigating breast cancer along with urine samples collected pre-diagnostically and available on all participants. Among the 57,053 members of the DCH cohort we will identify 900 cases of female breast cancer, and randomly select 900 women as a comparison group (sub-cohort) according to the efficient case-cohort design. Female population will be limited to those postmenopausal at baseline because most breast cancer cases occur in postmenopausal women. Urine samples will be analyzed for cadmium, other metals, and creatinine. This study will provide reliable and valuable insight into the hypothesized association between cadmium exposure in a general population and breast cancer and will assess whether zinc intake and smoking history modify these relationships. Analyses will also be stratified by ductal and lobular histology, in situ / invasive status, estrogen receptor positive, stage of cancer, along with other variables to investigate sensitivity of results and effect modification. The proposed study will address pressing questions posed by recent results and will overcome several methodological limitations of previous studies related to precision of the exposure assessment, study size, and possible bias in previous retrospective designs. If the study shows an association between urinary cadmium level and risk of breast cancer, there is great potential for prevention with more extensive regulation to avoid population exposure, since primary sources of general population exposure to cadmium are well recognized.

描述（由申请人提供）：表明雌激素作用的环境污染物已被提出有助于西方人群的乳腺癌的高发病率。在体外和体内实验中，镉已显示出具有有效的雌激素样活性，包括乳腺癌细胞的增殖，激活和雌激素调节基因的表达增加以及雌激素受体1的激活。此外，国际癌症研究机构将镉归为已知的人类致癌。雌激素和致癌活性的这种结合使镉成为人们特别关注乳腺癌的污染物。一项适中的流行病学研究表明，普通人群上四分位数常见的镉暴露水平的风险意味着镉可能在乳腺癌中起着重要作用。但是，这项研究使用了诊断后收集的尿液镉。结果，已经质疑增加镉是乳腺癌的危险因素，还是反映了治疗或疾病的影响。鉴于支持镉 - 胸癌关系的机械和初步的流行病学证据，该项目旨在严格研究从丹麦饮食癌和健康（DCH）前瞻性队列中的病例研究中收集的泌尿镉水平和乳腺癌的风险和乳腺癌的风险。这是世界上少数几个（即使是少数人），还具有足够的能力来研究乳腺癌，以及在所有参与者中收集的尿液样本，并为所有参与者提供。在DCH队列的57,053名成员中，我们将根据有效的病例 - 霍特设计确定900例女性乳腺癌，并随机选择900名女性作为比较组（亚科奥特）。女性人口将仅限于基线后的绝经后，因为大多数乳腺癌病例发生在绝经后妇女中。尿液样品将分析镉，其他金属和肌酐。这项研究将为普通人群与乳腺癌的镉暴露之间的假设关联提供可靠而有价值的见解，并评估锌摄入量和吸烟史是否会改变这些关系。分析还将通过导管和小叶组织学，原位 /侵入性状态，雌激素受体阳性，癌症的阶段以及其他变量来研究结果的敏感性和效果修饰。拟议的研究将解决最近结果提出的紧迫问题，并将克服与以前的回顾性设计相关的与暴露评估，研究规模和可能偏见有关的先前研究的几个方法学局限性。如果该研究表明尿镉水平与乳腺癌的风险之间存在关联，则有很大的预防潜力，并进行了更广泛的调节以避免人口暴露，因为普通人群暴露于镉的主要来源得到充分认可。