The Childhood Leukemia International Consortium

Background: Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemia (ALL) and 17% are acute myeloid leukemia (AML). Childhood leukemia shows further diversity based on cytogenetic and molecular characteristics, which may relate to distinct etiologies. Case-control studies conducted worldwide, particularly of ALL, have collected a wealth of data on potential risk factors and in some studies, biospecimens. There is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood ALL. The risk of childhood leukemia, like other complex diseases, is likely to be influenced both by independent and interactive effects of genes and environmental exposures. While some studies have analyzed the role of genetic variants, few have been sufficiently powered to investigate gene-environment interactions. Objectives: The Childhood Leukemia International Consortium (CLIC) was established in 2007 to promote investigations of rarer exposures, gene-environment interactions and subtype-specific associations through the pooling of data from independent studies. Methods: By September 2012, CLIC included 22 studies (recruitment period: 1962-present) from 12 countries, totaling approximately 31. 000 cases and 50. 000 controls. Of these, 19 case-control studies have collected detailed epidemiologic data, and DNA samples have been collected from children and child-parent trios in 15 and 13 of these studies, respectively. Two registry-based studies and one study comprising hospital records routinely obtained at birth and/or diagnosis have limited interview data or biospecimens. Conclusions: CLIC provides a unique opportunity to fill gaps in knowledge about the role of environmental and genetic risk factors, critical windows of exposure, the effects of gene-environment interactions and associations among specific leukemia subtypes in different ethnic groups. © 2013 Elsevier Ltd

Capturing complexity in how configurations of firm Internal Orientations impact corporate social performance outcomes: Breaking from the dominant logic of symmetric-variable to asymmetric-case-based theory and testing

This study exemplifies how an asymmetric and case based (configurational) research approach (using fuzzy state logic and complexity theory) is useful for conceptualization and explanation of complex topics and heterogeneous outcomes. The study here analyses the recipes (condition combinations) for Internal Orientation constructs (IO: strategic intent, CSP management, strategic orientation and industrial standards) among multi-national companies (MNCs) indicating “high” levels of corporate social performance (CSP) and the “United Nations Principles for Responsible Investment” (UNPRI) ESG factor framework (Environment, Social-human rights, and Governance) – separately and as a whole. The study applies a mixed methods research design and includes comparing ESG with financial performance across a “Top-100 Sustainable Companies Index” (n?=?82 of MNCs trading on the Swedish stock exchange). The study's findings support the core tenets of complexity theory; all four IO constructs affect a high E or S or G outcome but not all three outcomes in combination

The Glioma International Case-Control Study: A Report from the Genetic Epidemiology of Glioma International Consortium

Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen collection. To our knowledge, the GICC Study is the largest glioma study to date that includes collection of blood samples, which will allow for genetic analysis and interrogation of gene-environment interactions

Analysis of Up-Regulation of DNA-PKcs and Its Mechanism in Human Gliomas

OBJECTIVE To detect the differences in gene expression of nonhomologous end-joining pathway including Ku70, Ku80, ERCC4, lig4 and DNA-PKcs between human primary gliomas and normal brain tissues, and furthermore, to explore the underlying mechanism for the expression alteration. METHODS The expression levels of Ku70, Ku80, ERCC4, lig4 and DNA-PKcs in 36 specimens of glioma and 12 specimens of normal brain tissue were measured using SYBR green-based real-time quantitative PCR. Methylation of DNA-PKcs was detected through methylation-specifi c PCR (MSP). RESULTS There was no significant difference in expression of Ku70, Ku80, ERCC4 and lig4 between human primary gliomas and normal brain tissues (P < 0.05), while DNA-PKcs were significantly up-regulated (P = 0.002). The expression of DNA-PKcs was significantly higher in patients with grade III and IV diseases compared to patients with grade II disease or in normal brain tissues (P < 0.05). Moreover, glioma tissue showed weaker methylation than normal brain tissue. CONCLUSION The up-regulation of the DNA-PKcs may be associated with pathogenesis of glioma. Demethylation of DNA-PKcs promoter is an important reason for its up-regulation