The main areas of research activity for 2002 can be briefly summarized as follows:

The NCI is sponsoring development of a national pediatric cancer registry and research network (the Children’s Cancer research Network, CCRN), and Drs. Buckley, Deapen and Bernstein at USC are playing key roles in the establishment of the registry. This resource is expected to provide the central focus for a broad range of research into the incidence and cause of childhood cancers in the U.S. and Canada. The first step towards establishment of the CCRN is to pilot test and implement a registration/consent protocol within the Children’s Oncology Group. The pilot study was completed in 2002 (under the direction of Dr Julie Ross, University of Minnesota, with Dr. Buckley involved as vice-chair of the committee). It was remarkably successful, with over 95% of parents giving permission for registration (including personal identifiers) and for future contact for participation in possible epidemiological studies. Following completion of the pilot, the proptocol was opened throughout the COG. The major contribution of USC investigators will be in the establishment of the CCRN registry, which will perform record linkage of COG and State Cancer Registry data. Since registrations in the State registries typically take 12-24 months to be completed and validated, it will be at least 12 months before data from COG can be record-linked to State data.

This study, described in the last report (Buckley, PI), is on-going. This project enrolls newly diagnosed cases for mother and father interviews; controls come from a random-digit-dialing procedure and also from a friend control. Cases and friend controls provide a pre-treatment blood sample that is being used to determine the frequency of aberrant VDJ-mediated mutations on peripheral lymphocytes. Accrual has been very slow, for reasons that are common to all COG epidemiological studies at this time. A primary motivation for the CCRN initiative (above) is to expedite epidemiological studies and to reduce the logistical impediments that currently hamper research.

Other COG related studies include a proposed case-control study of brain tumors (VanTornout and Buckley) and two studies being conducted out of the University of Minnesota (Julie Ross, P.I.) for which Dr. Buckley is a co-investigator (a case-control study of Downs syndrome/leukemia and an infant leukemia case/control study to examine the role of exposure to topoisomerase inhibitors), both of which ended in 2002 and are currently in data cleanup and analysis phases.

Dr. Preston-Martin's area of interest is childhood brain tumors. She continues to direct the analysis of data from a multi-national case-control study of brain tumors, including 1218 cases & 2223 controls at 9 centers.

Dr. Van Tornout’s research is focused on identification of polymorphisms that confer genetic susceptibility, and interactions with environmental risk factors, in childhood cancer. Current projects include studies of neuroblastoma, brain tumors, and Ewing’s sarcoma. An R01 application is currently in development for submission (Feb 1) to study selected metabolic polymorphisms in children with brain tumors where the involvement of MTHFR raises the intriguing possibility of a gene-environment interaction between this key enzyme of folate metabolism and level of folate intake during pregnancy. This project includes Dr. Gauderman, from the Biostatistics Core, as a co-investigator.

The causes of childhood cancer remain largely unknown. Members of the Childhood Cancer Core are conducting a broad range of studies aimed at identifying and characterizing environmental exposures that contribute to cancer risk, while at the same time using molecular tools to explore genetic factors and their interactions with the environment. Clearly, this research has the potential to have significant public health impact.

Highest priority continues to be the establishment of the Children’s Cancer Research Network. The cooperative group environment has become less and less conducive to epidemiological research, due to competing priorities and administrative overload within the group. The CCRN will provide a streamlined process to ascertain and enroll cases onto epidemiological and biology studies, and through linkage with State and Regional cancer registries will provide a population basis for future research.

In more general terms, the merit of a distinct Childhood Cancer Core within this center has been under discussion. Although the biological and epidemiological characteristics that are unique to cancers in children require approaches that may be different in many respects from epidemiological studies of adult cancer, there is also substantial overlap. Indeed, many of the investigators with an interest in childhood cancer also conduct research on adult cancer. Given the relatively small group of investigators making up the Childhood Cancer Core, an argument can be made for the amalgamation of the Childhood Cancer and Adult Cancer Cores into a single unit.

The studies that are currently accruing new patients ascertain their subjects through the Children’s Oncology Group. This is a national cooperative clinical trials group whose member institutions register, and treat, a very high percentage of all childhood cancer under age 14 in the United States. Thus the ethnic distribution of COG registered patients follows closely that of the U.S. population and epidemiological studies based on the COG patient population are similarly representative.