PHAHs and Thyroid Cancer Risk in DoDSR Cohort

描述(申请人提供)：在过去的几十年里，乳头状甲状腺癌的发病率在世界上许多地区都有增加的报道，包括美国，原因不明。新的证据表明，多溴联苯醚(PBDEs)和其他多卤代芳香烃(PHAHs)，包括多氯联苯(PCbs)和有机氯农药，能够改变甲状腺激素的动态平衡，导致甲状腺功能障碍。这些变化被怀疑是导致甲状腺肿瘤发生的原因。虽然动物研究已经提供了确凿的证据支持PHAHs和甲状腺癌风险之间的联系，但还没有进行人体研究来检验这一新的假设，即暴露于多溴二苯醚和其他PHAHs会增加乳头状甲状腺癌的风险。在这里，我们提出了一项嵌套在美国军队大型队列中的病例对照研究，以检查1)PBDE/PHAH暴露与乳头状甲状腺癌风险之间的关系；2)PBDE/PHAH暴露与甲状腺激素干扰之间的关联；以及3)与环境暴露PHAHs相关的乳头状甲状腺癌和甲状腺激素干扰的风险是否因编码参与PHAHs和内源性甲状腺激素的调节、代谢或功能活动的酶的主要基因的遗传多态而不同。这项拟议的研究将使用国防部血清库(DoDSR)的诊断前血清进行，该库包含自1989年以来从900多万人那里收集的4400万份血清样本。病例将通过一个集中的军事肿瘤登记来确定。这项研究将包括2000至2012年间被诊断为乳头状甲状腺癌的800例病例，诊断前血清储存在DoDSR中。每个病例将根据年龄、性别和血清采集日期匹配一个对照。关于潜在混杂因素的数据，包括年龄、体重和身高、性别和种族，将通过与军队医疗保健和行政数据库的链接，为每个受试者提供。这项研究的结果不仅将增进我们对乳头状甲状腺癌病因知之甚少的知识，还将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，并将启发其他研究领域找到消除现有多溴二苯醚和其他PHAHs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.