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

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妇女中最常见的癌症，并且难以预防。因此，迫切需要寻求发现潜在的新的可改变的危险因素。多种证据表明，镉是一种广泛存在的持久性重金属环境污染物，是乳腺组织中的致癌物，但需要更明确的流行病学调查。尽管已知在工业环境中与非常高水平的镉接触有关的致癌风险，但对终生接触低水平镉的致癌性知之甚少。体外实验和动物实验都表明，镉具有雌激素特性，这使得镉可能成为雌激素依赖性肿瘤（如乳腺癌）的危险因素。在之前的一项回顾性病例对照研究中，我们发现与高尿镉有关的乳腺癌风险增加了两倍以上，最近的另一项类似研究也支持这一结果。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，WHI是一项对绝经后妇女预防性健康实践的前瞻性队列研究。首先，我们将通过测量尿镉来评估镉暴露。大约10,000名WHI参与者在登记时捐献了尿液，截至2010年8月，这些女性中记录了567例浸润性乳腺癌病例。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系，将这些乳腺癌病例与大约1000名对照进行匹配。其次，我们将使用既定的方法来计算所有约161,000名WHI参与者（包括约7,000名诊断为浸润性乳腺癌的女性）的饮食镉暴露量，这些参与者完成了食物频率问卷调查，并估计浸润性乳腺癌与饮食镉暴露相关的危害。最后，为了这两个目的，我们将检查激素定义亚组的关联，以了解更多关于镉可能与乳腺癌风险相关的机制。由于大多数妇女通过食用在受污染土壤中生长的食物和吸烟而接触到镉，减少镉污染的战略可能为减少乳腺癌发病率提供机会。该研究的高效和强大的设计将及时提供有关无处不在的环境污染物对浸润性乳腺癌发病率的贡献的新信息。

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.