Pesticide Use & Breast Cancer Risk in Large Cohort of Female Agriculture Workers

描述(由申请人提供)： 摘要农药在乳腺癌病因学中的可能作用在很大程度上仍未得到解决，并继续引起公众的严重关注。这在一定程度上是由于重要的局限性和/或先前流行病学研究的狭隘重点。这项拟议研究的长期目标是确定与个别农药相关的癌症风险，以便更好地为公共政策和个人决策提供信息。该应用程序的目的是在一群高度暴露的女性中，特别是NIH管理的农业健康研究队列中的配偶，确定与个别农药相关的乳腺癌风险是否增加。NIH管理的农业健康研究队列是一个特征良好的、前瞻性的、多州的队列，包括大约51,000名男性农民和32,000名妻子。这是一个很好的实现这一目标的人群，因为它的规模大，随访率高，并且可以获得详细的杀虫剂使用、职业、人口、生活方式、体力活动、饮食和生育史信息，这些信息是在20世纪90年代中期注册时和在为期5年的后续访谈中从农民及其妻子那里收集的。重要的是，这个队列中最常用的几种杀虫剂现在或曾经被普通公众广泛使用。中心假设是，在动物身上或在体外被认为是乳腺癌致癌物的农药，或者在流行病学研究中以前与乳腺癌有关的农药，将与如此高度暴露的女性人群的乳腺癌风险有关。这一假设将通过两个具体目标进行检验：1)确定与使用特定农药有关的任何恶性乳腺癌风险增加；以及2)确定与农业社区经常发现的非特定农药暴露来源有关的任何恶性乳腺癌风险增加。在第一个目标下，将检查与使用个别杀虫剂有关的乳腺癌风险。妇女和其丈夫的使用将被分开考虑，以说明由此产生的接触的性质和程度的不同。在第二个目标下，乳腺癌风险将与增加一般接触杀虫剂机会的因素有关，包括饮用可能受到污染的井水、洗涤在使用杀虫剂期间穿的衣服，以及将杀虫剂储存在家中或家附近。分析将基于登记时没有癌症病史的31,531名妇女，估计到2006年，通过基于人口的癌症登记确定的乳腺癌病例为805例。将使用两次访谈(仅在诊断前)的数据，通过包括全队列的COX比例风险模型，以及按绝经状态和居住状态分别估计相对风险。潜在的混杂因素，包括人口、生活方式、饮食和生殖因素，将被考虑在内。这项拟议的研究提供了一个不同寻常的机会，以成本和时间高效的方式调查单独的杀虫剂对乳腺癌风险的影响。这项研究意义重大，因为它有望促进我们对个别农药在乳腺癌病因学中的作用的理解，并以一种以前不可能做到的方法严格地做到这一点。 公共卫生相关性： 项目简介鉴于通过饮食、职业、居住和其他途径接触杀虫剂的无处不在的情况，这一研究领域具有潜在的重要公共卫生影响。动物研究和非常有限的流行病学研究表明，某些常用的杀虫剂可能是乳腺癌的危险因素。然而，这种对人类的风险仍然未知或高度不确定。拟议的研究将有助于解决我们知识中的这些重要差距，并有助于为政策制定者和个人之间关于这些化学品的风险和好处的辩论提供信息。

DESCRIPTION (provided by applicant): ABSTRACT The possible role of pesticides in the etiology of breast cancer remains largely unresolved and continues to be a cause of serious concern in the general public. This is due in part to important limitations and/or the narrow focus of previous epidemiologic studies. The long-term goal of the proposed study is to identify the cancer risks associated with individual pesticides in order to better inform public policy and individual decision-making. The objective of this application is to identify any elevated risk of breast cancer associated with individual pesticides among a cohort of highly exposed women, specifically spouses in the NIH-administered Agricultural Health Study cohort, a well-characterized, prospective, multi-state cohort that includes approximately 51,000 male farmers and 32,000 wives. This is an excellent population in which to address this objective because of its large size, high rate of follow-up, and availability of detailed pesticide use, occupational, demographic, lifestyle, physical activity, dietary, and reproductive history information collected from both the farmers and their wives at enrollment in the mid-1990s and again in a 5-year follow-up interview. Importantly, several of the most commonly used pesticides in this cohort are or were widely used by the general public. The central hypothesis is that pesticides implicated as mammary carcinogens in animals or in vitro or previously linked to breast cancer in epidemiologic studies will be associated with breast cancer risk in such a highly exposed population of women. This hypothesis will be tested via two specific aims: 1) Identify any increased risk of malignant breast cancer associated with use of specific pesticides; and 2) Identify any increased risk of malignant breast cancer related to sources of non-specific pesticide exposure often found in agricultural communities. Under the first aim, breast cancer risk will be examined in relation to use of individual pesticides. Use by the woman and her husband will be considered separately to account for differences in the nature and extent of resulting exposure. Under the second aim, breast cancer risk will be investigated in relation to factors that increase opportunity for exposure to pesticides generally, including consumption of potentially contaminated well water, washing of clothes worn during pesticide application, and storage of pesticides in or near the home. Analyses will be based on the 31,531 women with no history of cancer at enrollment, with an estimated 805 incident cases of breast cancer identified through 2006 via population-based cancer registries. Relative risks will be estimated using data from both interviews (pre-diagnostic only), via Cox proportional hazards models including the full cohort, as well as separately by menopausal status and state of residence. Potential confounders, including demographic, lifestyle, dietary, and reproductive factors, will be accounted for. The proposed study offers an unusual opportunity to investigate, in a cost- and time-efficient manner, the effects of individual pesticides on breast cancer risk. This research is significant because it is expected to advance our understanding of the role of individual pesticides in the etiology of breast cancer and to do so in a methodologically rigorous manner not previously possible. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE This area of research has potentially important public health implications, given the ubiquity of exposure to pesticides through diet, occupation, residential use, and other routes. Animal studies and very limited epidemiologic research suggest that certain commonly used pesticides may be risk factors for breast cancer. However, this risk in humans remains unknown or highly uncertain. The proposed study will help address these important gaps in our knowledge and help to inform the debate among policy makers and individuals concerning the risks and benefits of these chemicals.