Brain tumors and leukemia are the most common malignancies among children and adolescents in the U.S. However, 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 the Kaohsiung metropolitan area. These facilities are in close proximity to residential areas, due to the high population density of the region. Data have shown that concentrations of ambient polycyclic aromatic hydrocarbons (PAH) and volatile organic compounds (VOC) around the petrochemical industries are at least 10 and 2 times higher, respectively, than those in industrialized communities in the U.S. Our preliminary case-control study in the Kaohsiung metropolitan area showed that young residents (age 30 and under) living within 3 kilometers 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 and VOC) emitted from the petrochemical industries; relevant genetic polymorphisms (P4501A1 (MspI & exon 7), GSTM1 & GSTT1, CYP2E1, and DNA repair genes (XRCC1 and ERCC2) from study subjects and their parents; and the risks of brain tumors and leukemia among children and youths in metropolitan Kaohsiung. We hypothesize an increased risk of brain tumors and leukemia in patients with higher cumulative exposure and the high-risk genotype. We also assess the role of the parental genetic polymorphisms in the development of cancer in their offspring. This 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.