Cadmium Exposure and Risk of Breast Cancer in the Women's Health Initiative

妇女健康倡议中的镉暴露和乳腺癌风险

基本信息

批准号：
8471111
负责人：
POLLY A NEWCOMB
金额：
$ 27.17万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8471111
关键词：
Address Age at First Live Birth Agreement Animal Experiments Area Biological Assay Breast Breast Cancer Epidemiology Breast Cancer Risk Factor Cadmium Cancer Etiology Carcinogens Case-Control Studies Chemicals Cohort Studies Cross-Sectional Studies Data Diagnosis Diet Dietary Cadmium Disease Endocrine Disruptors Enrollment Environmental Exposure Environmental Pollutants Environmental Pollution Epidemiologic Studies Epidemiology Estrogen Receptors Estrogen receptor positive Estrogens Exposure to Food Frequencies Health Heavy Metals Hormonal In Vitro Incidence Investigation Learning Malignant - descriptor Mammary Gland Parenchyma Measurement Measures Mediating Methods Nested Case-Control Study Obesity Occupational Exposure Participant Pollution Population Population Study Postmenopause Prevention Prevention strategy Preventive Property Prospective Studies Questionnaires Research Research Design Retrospective Studies Risk Risk Factors Role Sample Size Sampling Soil Source Specimen Subgroup Testing Urine Woman Women&apos s Health Xeno Zinc base breast density cancer diagnosis cancer prevention cancer risk carcinogenesis carcinogenicity cigarette smoking cohort design environmental chemical food consumption hazard hormone therapy improved in vivo interest malignant breast neoplasm men modifiable risk non-smoking parity prevent prospective treatment effect tumor

项目摘要

DESCRIPTION (provided by applicant): Considerable advances have been made in breast cancer epidemiology, yet the disease remains the most commonly diagnosed cancer in US women and difficult to prevent. Therefore, it is imperative to pursue the discovery of potential new modifiable risk factors. Multiple lines of evidence suggest that cadmium, a widespread and persistent heavy metal environmental pollutant, is a carcinogen in breast tissue, but more definitive epidemiological investigation is required. In spite of the known carcinogenic risks associated with very high levels of cadmium exposure that occur in industrial settings, little is known about the carcinogenicity of low levels of cadmium exposure over a lifetime. Both in vitro and animal experiments show that cadmium has estrogenic properties, making cadmium a plausible risk factor for estrogen dependent tumors such as breast cancer. In a previous retrospective case#control study we found a more than two#fold increase in breast cancer risk associated with high urine cadmium, a result supported by a second recent similar study. We now propose to perform a more definitive test of this hypothesis within the Women's Health Initiative (WHI), a prospective cohort study of preventive health practices in postmenopausal women. First, we will assess cadmium exposure through measurement of urine cadmium. Approximately 10,000 participants in the WHI donated urine at enrollment, and 567 incident cases of invasive breast cancer were documented in these women through August 2010. We plan to evaluate the association between urine cadmium and breast cancer risk in a nested case#control study, matching these breast cancer cases with approximately 1,000 controls. Second, we will use established methods to calculate dietary exposure to cadmium among all ~161,000 WHI participants-including ~7,000 women diagnosed with invasive breast cancer-who completed food frequency questionnaires and estimate the hazard of invasive breast cancer associated with dietary cadmium exposure. Finally, for both of these aims we will examine associations in hormonally#defined subgroups to learn more about the mechanisms whereby cadmium may be associated with breast cancer risk. Because most women are exposed to cadmium through the consumption of foods grown in contaminated soils and through cigarette smoke, strategies that reduce cadmium pollution may present opportunities for reducing breast cancer incidence. The efficient and powerful design of the proposed study will provide timely new information on the contribution of a ubiquitous environmental contaminant to the incidence of invasive breast cancer.

描述（由申请人提供）：乳腺癌流行病学已经取得了相当大的进展，但该疾病仍然是美国女性中最常诊断出的癌症，并且难以预防。因此，当务之急是发现潜在的新的可改变的风险因素。多种证据表明，镉是一种广泛且持久的重金属环境污染物，是乳腺组织中的致癌物，但还需要更明确的流行病学调查。尽管已知工业环境中存在与高水平镉暴露相关的致癌风险，但人们对一生中低水平镉暴露的致癌性知之甚少。体外和动物实验均表明镉具有雌激素特性，这使得镉成为乳腺癌等雌激素依赖性肿瘤的合理危险因素。在之前的一项回顾性病例对照研究中，我们发现与高尿镉相关的乳腺癌风险增加了两倍多，这一结果得到了最近第二项类似研究的支持。我们现在建议在妇女健康倡议（WHI）中对这一假设进行更明确的检验，这是一项针对绝经后妇女预防性健康实践的前瞻性队列研究。首先，我们将通过测量尿液中的镉来评估镉的暴露情况。大约 10,000 名 WHI 参与者在入组时捐献了尿液，截至 2010 年 8 月，这些女性中记录了 567 起浸润性乳腺癌病例。我们计划在一项巢式病例对照研究中评估尿镉与乳腺癌风险之间的关联，将这些乳腺癌病例与大约 1,000 名对照者一起。其次，我们将使用既定方法计算所有约 161,000 名 WHI 参与者（包括约 7,000 名被诊断患有浸润性乳腺癌的女性）的膳食镉暴露量，这些参与者完成了食物频率调查问卷，并估计与膳食镉暴露相关的浸润性乳腺癌的危险。最后，为了这两个目标，我们将检查激素定义的亚组中的关联，以了解更多有关镉可能与乳腺癌风险相关的机制。由于大多数女性通过食用受污染土壤中种植的食物和吸烟而接触镉，因此减少镉污染的策略可能为降低乳腺癌发病率提供机会。该研究的高效而有力的设计将及时提供关于普遍存在的环境污染物对浸润性乳腺癌发病率的影响的新信息。