Exploring the relationship of Vitamin D and childhood brain tumors

描述(由申请人提供)：循环中低水平的维生素D[25-(OH)D]与各种成人发病癌症有关。然而，尽管有令人信服的实验和流行病学证据表明，在妊娠发育过程中维生素D减少可能是一个危险因素，特别是对儿童脑瘤(CBT)，但对儿童癌症的研究尚未进行。对于CBT来说，宫内发育期已被证明是暴露的关键时间窗口。作为新生儿筛查计划的一部分，收集和存档的新生儿干血斑(DBS)是检查与儿童癌症相关的诊断前25-(OH)D的独特资源，并允许关注维生素D在宫内时间段的影响。长期目标是了解CBT的发病机制，以便开发干预措施来减轻儿童中这种疾病的负担。这项应用的总体目标是朝着实现长期目标迈出的一步 学期目标是检查DBS中测量的新生儿25-(OH)D与CBT风险之间的关系。这项拟议研究的中心假设是，怀孕期间维生素D缺乏与CBT风险增加有关。这一假说将通过追求两个特定目标来检验：1)在250例儿童脑瘤病例和250例对照中，评估25-(OH)D(在DBS中作为妊娠循环维生素D水平的标志物)与CBT风险之间的关联；2)在探索性分析中，确定25-(OH)D与脑瘤风险的关联是否因性别、种族/民族、产前吸烟、母亲的SES、脑瘤组织学、出生体重、胎龄及出生月份和季节而不同。这项研究具有创新性，因为它将首次通过使用DBS中的测量作为子宫内维生素D水平的标记物来检查循环中的维生素D水平作为CBT风险的预测因素。拟议的研究具有重要意义，因为它有望提供有价值的数据，最终将导致有效的干预目标，以减轻CBT的发生。

DESCRIPTION (provided by applicant): Low circulating levels of vitamin D [25-(OH)D] have been associated with various adult onset cancers. However, studies of childhood cancer have not been conducted despite compelling experimental and epidemiologic evidence suggesting that reduced vitamin D during gestational development may be a risk factor, particularly for childhood brain tumors (CBT). For CBT, the in utero period of development has been shown to be a critical time window of exposure. Neonatal dried blood spots (DBS) collected and archived as part of newborn screening programs represent a unique resource for examining pre-diagnostic 25-(OH)D in relation to childhood cancers and allows for focus on the impact of vitamin D during the in utero time period. The long-term goal is to understand the pathogenesis of CBT so that interventions can be developed to reduce the burden of this disease among children. The overall objective for this application, which is a step toward attainment of the long term goal, is to examine the association between neonatal 25-(OH)D, as measured in DBS, with risk of CBT. The central hypothesis of the proposed study is that vitamin D deficiency during pregnancy is associated with increased risk of CBT. The hypothesis will be tested by pursuing two specific aims 1) Evaluate among 250 childhood brain tumor cases and 250 controls the association between 25-(OH)D, as measured in DBS as a marker of gestational circulating vitamin D levels, and the risk of CBT; 2) In exploratory analyses, determine if the association between 25-(OH)D and brain tumor risk differs by sex, race/ethnicity, prenatal smoking, maternal SES, brain tumor histology, birth weight, gestational age and month and season of birth. This study is innovative because it will, for the first time, examine circulating vitamin D levels as predictors of CBT risk by using measurements in DBS as markers of in utero vitamin D levels. The proposed research is significant because it is expected to provide valuable data that will ultimately lead to efficacious targets for interventions to mitigate the occurrence of CBT.