Interaction between ionising radiation and genetic susceptibility in the aetiology of childhood acute lymphoblastic leukaemia
Children with Cancer UK
Yale University
The aetiology of childhood acute lymphoblastic leukaemia (ALL) is largely unknown. Various studies have evaluated the role of ionising radiation and genetic susceptibility, but potential interaction between the two factors has rarely being examined. A major barrier to this type of research is the limited availability of both radiation and genetic data in existing studies. In the proposed project, we will leverage three studies from the Childhood Leukaemia International Consortium (CLIC), including the California Childhood Leukemia Study (CCLS), the Children’s Cancer Group (CCG) study of childhood ALL, and the Australian Study of Childhood ALL, to assess gene-radiation interaction in the aetiology of childhood ALL. Specifically, we will use the CCLS as the discovery/training dataset and the CCG and Australian studies as validation datasets. The CCLS has a case-control design (746 cases and 734 controls), while the CCG (n = 507) and Australian (n = 602) studies have a case-only design. All studies have collected very similar data on diagnostic X-rays that a child received before the diagnosis of ALL (and comparable date for controls), as well as whole-genome genotyping data. After conducting rigorous quality control, we will use both benchmark logistic-regression based analysis and more advanced regularization-based G-E interaction analysis methods recently developed by Co-Applicant Dr. S Ma’s group and others. With 2,589 subjects, the proposed project will provide an unprecedented opportunity to elucidate the potential aetiological role of gene-radiation interaction. Our findings will help clarify the biological pathways in leukemogenesis and identify children at high risk for ALL.
2.1 Biological and endogenous factors