PHAHs and Thyroid Cancer Risk in DoDSR Cohort

描述（由申请人提供）：在过去的几十年里，包括美国在内的世界许多地方都报道了甲状腺乳头状癌发病率的增加，原因不明。越来越多的证据表明，多溴联苯醚（PBDEs）和其他多卤芳烃（PHAHs），包括多氯联苯（PCBs）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。这些变化被怀疑会导致甲状腺的肿瘤发生。虽然动物研究提供了确凿的证据支持多溴二苯醚和甲状腺癌风险之间的联系，但还没有进行人体研究来验证接触多溴二苯醚和其他多溴二苯醚会增加患乳头状甲状腺癌风险的新假设。在此，我们提出了一项在美国大型军事队列中嵌套的病例对照研究，以检验1)多溴二苯醚/多环芳烃暴露与甲状腺乳头状癌风险之间的关系；2)多溴二苯醚/多环芳烃暴露与甲状腺激素紊乱的关系；3)参与PHAHs和内源性甲状腺激素调控、代谢或功能活动的主要基因编码基因的遗传多态性是否与环境暴露相关的乳头状甲状腺癌和甲状腺激素紊乱的风险有关。拟议的研究将使用来自国防部血清库（DoDSR）的预诊断血清进行，该血清库包含自1989年以来从900多万人收集的4400多万份血清标本。病例将通过集中的军队肿瘤登记来确定。该研究将包括800例2000年至2012年间诊断出的乳头状甲状腺癌病例，这些病例的诊断前血清储存在DoDSR中。将根据年龄、性别和抽取血清的日期为每个病例匹配一名对照。每个受试者的潜在混杂因素数据，包括年龄、体重和身高、性别和种族，将通过与军事保健和行政数据库的联系获得。这项研究的结果不仅将促进我们对甲状腺乳头状癌病因的了解，而且还将为监管这些化合物的生产和使用的决策者提供重要的科学证据，并将激发其他研究领域寻找消除现有多溴二苯醚和其他多环芳烃来源的方法。

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. PUBLIC HEALTH RELEVANCE: The increasing incidence of papillary thyroid cancer, and increased human exposure to polybrominated diphenyl ethers (PBDEs) and other polyhalogenated aromatic hydrocarbons (PHAHs) among the general population, makes understanding the relationship between PBDEs and other PHAHs and risk of papillary thyroid cancer a public health priority.