1) To examine whether telomere length is associated with risk of glioma. Based on biological and genetic evidence, there is strong reason to believe that telomere maintenance is of importance in glioma etiology. Prior studies indicate that shorter telomere length is associated with various types of cancer. We will examine whether telomere length is associated with glioma risk in 515 cases and 796 controls. 2) To examine whether results concerning the relationship between telomere length and glioma risk are affected by study design (nested case-control versus hospital-based case-control). Most studies of glioma have used the retrospective case-control design. While this design is appropriate for genotyping studies, it is possible that telomere length is affected post-tumor, which would strongly argue for use of pre-diagnostic samples. By conducting parallel studies in a retrospective case-control study, as well as a cohort study, we will be able to examine whether the relationship between telomere length and glioma risk is affected by time of blood draw (pre-disease, or post-disease). 3) To explore if the relationship between telomere length and glioma is modified by single nucleotide polymorphisms in the TERT gene that are highly significantly associated with glioma. Samples from PLCO are already undergoing genotyping using the Illumina 660W-Quad human Beadchip, and we expect information on approximately 550,000 single nucleotide polymorphism markers, including TERT SNPs that have been shown to be highly significant in other studies. We will explore whether the relationship between telomere length and glioma risk is modified by the relevant polymorphisms in the TERT gene. If results from this exploratory aim are promising, we will propose to extend this aim in the future by including data from other studies belonging to the cohort consortium.

Peter Inskip (NCI, DCEG)
Sharon Savage (NCI, DCEG)
Preetha Rajaraman (NCI, DCEG)