PHAHs and Thyroid Cancer Risk in DoDSR Cohort

DoDSR 队列中的 PHAH 和甲状腺癌风险

基本信息

批准号：
8663258
负责人：
Jennifer Ann Rusiecki
金额：
$ 66.33万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8663258
关键词：
Age Animals Area Aromatic Hydrocarbons CYP1A1 gene CYP1A2 gene CYP1B1 gene CYP2D6 gene CYP2E1 gene CYP3A4 gene CYP3A5 gene Chemicals Classification Code Data Department of Defense Diagnosis Diagnostic Dioxins Drug Metabolic Detoxication Environmental Exposure Enzymes Etiology Exposure to Family Fishes Functional disorder GSTM1 gene GSTP1 gene GSTT1 gene Gender General Population Genes Genetic Polymorphism Glucuronosyltransferase Glutathione S-Transferase Healthcare Height Homeostasis Human Incidence Iodide Peroxidase Joints Knowledge Lead Link Malignant neoplasm of thyroid Metabolism Military Personnel Nested Case-Control Study Occupational Papillary thyroid carcinoma Phase Policy Maker Polychlorinated Biphenyls Population Production Public Health Race Recording of previous events Regulation Reporting Research Risk Sampling Serum Services Solid Source Specimen Testing Thyroid Gland Thyroid Hormones UGT1A1 gene UGT1A8 UDP-glucuronosyltransferase United States Weight administrative database base bilirubin uridine-diphosphoglucuronosyl transferase 1A10 cancer risk case-based chemical group cohort exposed human population man monoamine-sulfating phenol sulfotransferase novel organochlorine pesticide phenyl ether public health priorities repository residence sex sulfotransferase tumor registry tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): During the past several decades, an increased incidence of papillary thyroid cancer has been reported in many parts of the world, including the United States, with unknown reasons. Emerging evidence indicates that polybrominated diphenyl ethers (PBDEs) and other polyhalogenated aromatic hydrocarbons (PHAHs), including polychlorinated biphenyls (PCBs) and organochlorine pesticides, are able to alter thyroid hormone homeostasis and cause thyroid dysfunction. These changes are suspected to lead to tumorigenesis of the thyroid gland. While animal studies have provided solid evidence in support of the link between PHAHs and thyroid cancer risk, no human studies have been conducted to test this novel hypothesis that exposure to PBDEs and other PHAHs increases the risk of papillary thyroid cancer. Here, we propose a case-control study nested in a large US military cohort to examine 1) the association between PBDE/PHAH exposure and papillary thyroid cancer risk; 2) the association between PBDE/PHAH exposure and thyroid hormone disruption; and 3) whether the risk of papillary thyroid cancer and thyroid hormone disruption associated with environmental exposure to PHAHs varies by genetic polymorphisms in major genes coding for enzymes involved in the regulation, metabolism, or functional activities of PHAHs and endogenous thyroid hormones. The proposed study will be conducted using PRE-DIAGNOSTIC sera from the Department of Defense Serum Repository (DoDSR), which contains over 44 million serum specimens collected from over 9 million people since 1989. Cases will be ascertained via a centralized military tumor registry. The study will include 800 incident cases of papillary thyroid cancer that were diagnosed between 2000 and 2012 with pre-diagnostic sera banked in the DoDSR. One control will be matched to each case based on age, gender, and the date of serum draw. Data on potential confounders, including age, weight and height, sex, and race, will be available for each subject through linkage with military healthcare and administrative databases. Results from the study will not only advance our knowledge of the poorly understood etiology of papillary thyroid cancer, but also provide important scientific evidence to policy makers who regulate the production and use of these compounds and will intrigue other research areas to figure out ways to eliminate the existing sources of PBDEs and other PHAHs.

描述（由申请人提供）：在过去的几十年中，在包括美国在内的许多地区，包括美国的许多地方都报道了乳头状甲状腺癌的发病率增加。新兴的证据表明，多溴二苯基醚（PBDES）和其他多面化芳香族烃（PHAH），包括多氯联苯二苯基（PCB）和有机氯农药，能够改变甲状腺激素的hormonostostisis并引起甲状腺甲状腺素抑制性甲状腺素。怀疑这些变化会导致甲状腺的肿瘤发生。尽管动物研究为支持PHAH与甲状腺癌风险之间的联系提供了可靠的证据，但尚未进行人类研究来检验这一新型假设，即暴露于PBDES和其他PHAH会增加甲状腺甲状腺甲状腺癌的风险。在这里，我们提出了一项嵌套在美国大型军事队列中的病例对照研究，以检查1）PBDE/PHAH暴露与甲状腺甲状腺癌风险之间的关联； 2）PBDE/PHAH暴露与甲状腺激素破坏之间的关联； 3）与对环境暴露有关的乳头状甲状腺癌和甲状腺激素破坏的风险是否会因遗传多态性而有所不同，该基因编码参与调节，代谢或甲状腺甲状腺内源性荷尔蒙的调节，代谢或功能活性的酶。拟议的研究将使用国防部血清存储库（DODSR）的诊断前血清进行，该血清库，其中包含自1989年以来从900万人收集的4400万种血清标本。将通过集中的军事肿瘤注册表来确定病例。该研究将包括800例在2000年至2012年间被诊断出的甲状腺乳头状甲状腺癌事件，并在DODSR中使用了诊断前血清。一个控件将根据年龄，性别和血清绘制日期与每种情况匹配。通过与军事医疗保健和行政数据库的联系，将为每个主题提供有关潜在混杂因素的数据，包括年龄，体重和身高，性别和种族。这项研究的结果不仅会促进我们对乳头状甲状腺癌的病因知之甚少的了解，而且还为调节这些化合物的生产和使用的决策者提供了重要的科学证据，并将兴趣其他研究领域，以找出消除现有的PBDES和其他PHAH来源的方法。