Project 1: Childhood Leukemia International Consortium Studies

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PROJECT SUMMARY (See instructions): Leukemia is the most common cancer in children under 15 years of age. Despite years of research, the causes of childhood leukemia (CL) remain elusive. Due to their well-characterized carcinogenicity and toxicity, parental tobacco smoking and home pesticide exposures are frequently studied in CL. Though some studies have suggested a link between CL and parental tobacco smoking or home pesticides exposure, no definite conclusion can be reached due to inconsistent results likely resulted from problems associated with small sample size in individual studies. To overcome the limitations associated with the small sample size of individual studies, the proposed study will pool data (N~8000 cases and 18000 controls) from 14 case-control studies from 10 countries within the Childhood Leukemia International Consortium (CLIC) to: 1) conduct descriptive analyses to assess geographical differences in the frequency of leukemia subtypes; 2) assess the association between maternal/paternal smoking or home pesticide exposures and CL during different time periods (prenatal, during pregnancy, and postnatal) stratified by histologic, immunophenotypic. and cytogenetic subtypes; 3) examine the influence of genetic variation on the association between parental smoking or home pesticide exposures and CL by histologic, immunophenotypic and cytogenetic subtypes; and 4) maintain the CLIC website (http://clic.berkeley.edu) to facilitate communication among CLIC members and outside communities. Interview-based exposure data on parental smoking and home pesticides will be standardized across studies. Genetic data will be ascertained from 8 of the 14 studies focusing on 12 polymorphisms of seven xenobiotic metabolizing (CYP1A1, GSTM1, GSTTI, GSTPl, NQ01, and EPHX1) and drug transporter genes (MDR). In addition, availability and quality assessment of cytogenetic data will be conducted to facilitate subtype analyses. A two-stage data pooling method will be used to combine data across studies to account for study-specific covariates and inter-study heterogeneity. The proposed analyses will enhance our understanding of the roles of parental tobacco smoking and home pesticide exposure etiology of childhood leukemia. This will have important implications for prevention of CL.