Evolution of management strategies for cerebral gliomas: the effects of science and technology.

The evolution in the management of gliomas will require a new understanding of the factors that predispose patients to develop gliomas. Much of the past literature has involved a questionnaire-type strategy to accumulate data regarding previous exposures to various environmental factors. However, the field of epidemiology has evolved into a molecular based approach that assesses the exposure of a given agent with regard to its dose that would cause a biological effect, as well as the subsequent detection of that biological effect including molecular genetic aberrations that lead to altered gene structure and function. Ultimately, this produces the clinical correlate of a brain tumor and, subsequently, is what is known about progression markers based upon not only our understanding of genomics, but also proteomics and transcriptomics. One of the clues that we are taking from molecular epidemiology comes in the form of assessing genomic polymorphism of certain DNA-repair genes. Data from the San Francisco Bay area adult glioma study demonstrated that certain DNA-repair genes such as ERCC1 and ERCC2 have particular variant alleles that indicate a susceptibility to the development of gliomas (Dr. Margaret Wrensch, personal communication). In that study, patients were threefold more likely to develop a glioma than the control population when these variant alleles were identified in these two particular DNA-repair genes (Fig. 38.1). Thus, this is a clue that susceptibility of gliomagenesis can be determined based on the assessment of constitutive or germline single nucleotide polymorphism.