PHAHs and Thyroid Cancer Risk in DoDSR Cohort

描述（由申请人提供）：在过去的几十年中，世界上许多地方（包括美国）报告了乳头状甲状腺癌的发病率增加，原因不明。新出现的证据表明，多溴联苯醚（PBDE）和其他多卤代芳烃（PHAH），包括多氯联苯（PCB）和有机氯农药，能够改变甲状腺激素的体内平衡，导致甲状腺功能障碍。这些变化被怀疑会导致甲状腺肿瘤的发生。虽然动物研究提供了坚实的证据支持PHAH和甲状腺癌风险之间的联系，但尚未进行人体研究来验证这一新的假设，即接触多溴联苯醚和其他PHAH会增加甲状腺乳头状癌的风险。在这里，我们提出了一个病例对照研究嵌套在一个大型的美国军事队列检查1）之间的关联PBDE/PHAH暴露和甲状腺乳头状癌的风险; 2）之间的关联PBDE/PHAH暴露和甲状腺激素干扰;和3）与PHAH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是否因编码酶的主要基因的遗传多态性而异参与PHAH和内源性甲状腺激素的调节、代谢或功能活动。这项研究将使用来自国防部血清库（DoDSR）的预诊断血清进行，该库包含自1989年以来从900多万人中收集的4400多万份血清标本。病例将通过中央军事肿瘤登记处确定。该研究将包括2000年至2012年间诊断的800例甲状腺乳头状癌病例，这些病例使用DoDSR中储存的诊断前血清。根据年龄、性别和血清采集日期，将一个对照组与每例病例匹配。通过与军事医疗保健和行政数据库的链接，将获得每例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。这项研究的结果不仅将推进我们对乳头状甲状腺癌病因学知之甚少的知识，而且还为政策制定者提供了重要的科学证据，这些政策制定者规范了这些化合物的生产和使用，并将吸引其他研究领域找出消除PBDEs和其他PHAH的现有来源的方法。

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.