Causation and Etiological Studies
Based on studies begun in the 1960s by Dr. Darell Bigner, a case-control epidemiological and molecular epidemiological study are being conducted to assess the contributions of animal neurocarcinogen exposure and of glutathione S-transferase, cytochrome P-450, and DNA repair genes and their polymorphisms to the development and genetic susceptibility of brain tumors. Moreover, the effect of the above gene polymorphisms on treatment outcome and toxicity is also being assessed.
Preliminary evaluation of the glutathione S-transferase gene polymorphisms from over 400 brain tumor patients indicate a moderate to large effect for glutathione S-transferase 1 in some brain tumor subtypes. The completed study will obtain data on approximately 1,000 brain tumor cases and friend controls with approximately 430 glioblastoma multiforme cases, 300 lower grade astrocytoma cases, 100 oligodendrogliomas, and 150 meningiomas. This number of cases will be required to evaluate the investigators’ hypotheses with reasonable power for relative risk previously reported for glutathione S-transferase 1.
All study subjects will be asked to complete a web-based, self-administered, or telephone-based questionnaire for exposure assessment and dietary assessment, and to provide blood and/or buccal samples for DNA analysis. Research nurses at the Duke Comprehensive Cancer Center (DCCC) and the Evanston Hospital, Northwestern Comprehensive Cancer Center, will recruit approximately 1,000 recently diagnosed cases over the next four-year period. An equal number of friend controls will be identified by asking brain tumor patients to identify five friend controls of the same age, gender, and race, following which research staff will distribute packets of information to those friend controls. The protocol will be completed at a clinic appointment or by using a distance-based protocol. Medical records for cases will be reviewed to obtain clinical and treatment information for survival and toxicity analysis. Linkage with the National Death Index will obtain vital statistics for up to three years of followup time to assess outcomes.
Study coordination and survey data management will be completed at the University of Illinois in Chicago (UIC), with molecular analyses being conducted at the DCCC under the auspices of Dr. Francis Ali-Osman. DCCC will facilitate neuropathology review, provide management support and some local data collection, and store the remaining specimens in the central repository of the Brain Tumor Center Tissue Bank. Data analysis files will be compiled at Duke and distributed to the other investigators. Statistical analyses will use conditional logistic regression models appropriate for data analysis.
It is anticipated that this study will provide definitive information on the potential role, if any, of established animal neurocarcinogens such as acrylonitrile, acrylamide, ethylene oxide, glycidol, and hydrazines and other documented or highly suspect animal neurocarcinogens. Moreover, the role, if any, of polymorphisms in genes responsible for metabolism of potential carcinogens and chemotherapeutic agents and DNA repair genes will be determined both for potential susceptibility to the animal neurocarcinogens and for their influence on treatment toxicity and outcomes.