BRAIN NEOPLASMS, LEUKEMIA & PETROCHEMAL EXPOSURES

描述(改编自申请者摘要)：脑瘤和白血病 是美国最常见的儿童和青少年恶性肿瘤 关于遗传遗传易感性和环境的作用的信息 儿童和青少年肿瘤发展中的暴露是 缺乏。在台湾，四大石化产业分布在 高雄都会区。这些设施靠近居民区。 因为该地区的人口密度很高。数据表明， 环境中多环芳烃(PAH)和挥发物的浓度 石油化工行业周围的有机化合物(VOC)至少有10和 分别是美国工业化社区的2倍。 我们在高雄市进行的初步病例对照研究显示，杨 居住在附近3公里(公里)内的居民(&lt；30岁) 石化行业患脑肿瘤的人数增加了6.0倍，患脑肿瘤的人数增加了2.9 白血病的发病率增加了一倍。这项建议的目的是研究 接触空气污染物(多环芳烃和挥发性有机化合物)的关联性 石油化学工业，特定的遗传多态(P4501A1(MspI和外显子 7)和GSTMI&TL)，以及 高雄市儿童及青少年脑瘤及白血病的调查。 我们的假设是脑瘤和白血病的风险增加 在累积暴露于这些危险的患者中， 几个基因中可遗传的多态改变了这种联系。此外 环境和遗传因素与大脑的独立关联 肿瘤和白血病，我们假设有更大的风险相关 同时存在环境暴露和高风险 基因分型。我们还评估了父母基因多态在遗传多样性中的作用 他们的兄弟姐妹患上了癌症。这项拟议的研究使用了 环境分子流行病学方法，利用前瞻性 一组脑瘤和白血病受试者和一名 以人群为基础的病例对照设计。这项提议是对 国家研究理事会的建议，风险评估和公众 卫生政策特别重视对儿童的保护。

DESCRIPTION (Adapted from the Applicant's Abstract): Brain tumors and leukemia are the most common children and adolescent malignancies in the U.S. Adequate information on the role of inherited genetic susceptibility and environmental exposures in the development of neoplasms in children and adolescents is lacking. In Taiwan, four large petrochemical industries are located in Kaohsiung metropolitan area. These facilities are proximal to residential areas because of the high population density in the region. Data have shown that the concentrations of ambient polycyclic aromatic hydrocarbons (PAH) and volatile organic compounds (VOC) around the petrochemical industries are at least 10 and 2 times, respectively, higher than those in U.S. industrialized communities. Our preliminary case-control study in Kaohsiung metropolitan showed that young residents (< 30 yr) living within 3 kilometers (km) of the vicinity of petrochemical industries have a 6.0 fold increase in brain neoplasms and a 2.9 fold increase in leukemia. The purpose of this proposal is to examine the association of exposure to air contaminants (PAH & VOC) emitted from the petrochemical industries, specific genetic polymorphisms (P4501A1 (MspI & exon 7) and GSTMI & Tl) from study subjects and their parents, and the risks of brain tumors and leukemia among children and youths in metropolitan Kaohsiung. Our hypothesis is that there is an increase risk of brain tumors and leukemia in patients with higher cumulative exposure to these hazards, and that heritable polymorphisms in several genes modify this association. In addition to an independent association of environmental and genetic factors with brain neoplasm and leukemia, we hypothesize that there is greater risk associated with the presence of combined environmental exposure and the high risk genotype. We also assess the role of the parental genetic polymorphisms in the development of cancer in their sibling. This proposed study uses an environmental molecular epidemiologic approach, utilizing prospective enrollment of a cohort of brain tumor and leukemia subjects and a population-based case-control design. This proposal is responsive to the recommendation of the National Research Council that risk assessment and public health policy pay special attention to the protection of children.