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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：
9059082
负责人：
Jennifer Ann Rusiecki
金额：
$ 64.26万
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 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9059082
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 polybrominated diphenyl ether public health priorities repository residence sex sulfotransferase thyroid disruption 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，据报道，包括美国在内的世界许多地区甲状腺乳头状癌的发病率有所增加，但原因不明。新的证据表明，多溴二苯醚 (PBDE) 和其他多卤芳香烃 (PHAH)，包括多氯联苯 (PCB) 和有机氯农药，能够改变甲状腺激素稳态并导致甲状腺功能障碍。这些变化被怀疑导致甲状腺肿瘤发生。虽然动物研究提供了确凿的证据支持 PHAH 与甲状腺癌风险之间的联系，但尚未进行人体研究来检验这一新假设，即接触 PBDE 和其他 PHAH 会增加患乳头状甲状腺癌的风险。在这里，我们提出一项在大型美国军事队列中进行的病例对照研究，以检查 1) PBDE/PHAH 暴露与乳头状甲状腺癌风险之间的关联； 2) PBDE/PHAH 暴露与甲状腺激素紊乱之间的关联； 3）与PHAH环境暴露相关的甲状腺乳头状癌和甲状腺激素破坏的风险是否因编码参与PHAH和内源性甲状腺激素调节、代谢或功能活动的酶的主要基因的遗传多态性而变化。拟议的研究将使用国防部血清库 (DoDSR) 的预诊断血清进行，该库包含自 1989 年以来从超过 900 万人收集的超过 4400 万份血清样本。病例将通过中央军事肿瘤登记处确定。该研究将包括 800 例甲状腺乳头状癌病例，这些病例是在 2000 年至 2012 年间通过 DoDSR 中储存的诊断前血清诊断出来的。将根据年龄、性别和血清抽取日期将每个病例匹配一个对照。通过与军事医疗保健和行政数据库的链接，可以获得每个受试者的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将增进我们对甲状腺乳头状癌病因学的了解，而且还为监管这些化合物的生产和使用的政策制定者提供重要的科学证据，并将激发其他研究领域的兴趣，找出消除 PBDE 和其他 PHAH 现有来源的方法。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A case-control study of exposure to organophosphate flame retardants and risk of thyroid cancer in women.

DOI：
10.1186/s12885-018-4553-9
发表时间：
2018-06-05
期刊：
BMC cancer
影响因子：
3.8
作者：
Deziel NC;Yi H;Stapleton HM;Huang H;Zhao N;Zhang Y
通讯作者：
Zhang Y

Response to the commentary letter entitled 'Diagnostic radiography and thyroid cancer - causation or simply an association?' to our article entitled 'Diagnostic radiography exposure increases the risk for thyroid microcarcinoma: a population-based case-co

对题为“放射诊断与甲状腺癌——因果关系还是简单的关联？”的评论信的回应

DOI：
10.1097/cej.0000000000000206
发表时间：
2016
期刊：
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)
影响因子：
0
作者：
Zhang,Yawei;Huang,Huang;Sandler,Jason;Udelsman,Robert
通讯作者：
Udelsman,Robert

Germline Variants in DNA Repair Genes, Diagnostic Radiation, and Risk of Thyroid Cancer.

DNA 修复基因的种系变异、诊断放射和甲状腺癌的风险。