BRAIN NEOPLASMS, LEUKEMIA & PETROCHEMAL EXPOSURES

描述（改编自申请人的摘要）：脑肿瘤和白血病 是美国最常见的儿童和青少年恶性肿瘤。 关于遗传易感性和环境因素作用的信息 儿童和青少年肿瘤发展中的暴露是 缺乏在台湾，四个大型石化工业位于 高雄都会区。这些设施靠近居民区 因为该地区人口密度高。数据均显示 环境中多环芳烃（PAH）和挥发性 石油化工行业周围的有机化合物（VOC）至少为10， 2倍，分别高于美国工业化社区。 我们在高雄都会区的初步病例对照研究显示， 居民（< 30岁）居住在3公里（公里）的附近 石油化工行业的脑肿瘤增加了6.0倍， 白血病的发病率增加了一倍这项建议的目的是审查 暴露于空气污染物（PAH和VOC）的关联 石油化工行业，特定的遗传多态性（P4501A1（MspI和外显子 7)和GSTMI & Tl），以及 脑肿瘤和白血病的儿童和青少年在大都会高雄。 我们的假设是， 在累积暴露于这些危害的患者中， 几个基因的遗传多态性改变了这种关联。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， 同时存在环境暴露和高风险 基因型我们还评估了父母的遗传多态性的作用， 癌症的发展在他们的兄弟姐妹。这项研究使用了一个 环境分子流行病学方法，利用前瞻性 招募一组脑肿瘤和白血病受试者， 基于人群的病例对照设计。这项建议是响应 国家研究理事会建议，风险评估和公众 卫生政策特别注意保护儿童。

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.