EPID-23UNDERSTANDING INHERITED GENETIC RISK OF ADULT GLIOMA - A REVIEW

Abstract

Over the past six years, researchers have made major progress identifying inherited genetic variation that increases risk for primary adult glioma. Ten independent inherited variants in eight chromosomal regions have been convincingly associated with increased risk for adult glioma. We present a meta-analysis of these findings. Although most of these variants increase relative risk of primary adult glioma by 20% to 40%, the TP53 variant rs78378222 confers a two-fold relative risk (i.e. 200%), and rs557505857 on chromosome 8 confers a six-fold relative risk of IDH mutated astrocytomas and oligodendroglial tumors (i.e. 600%). Even with a six-fold relative risk, we show that the lifetime risk of adult glioma is too low for screening for the high-risk variant on chromosome 8. Furthermore, we show variants associated with specific histologic types of glioma and with molecular groups of glioma defined by tumor IDH mutation, TERT promoter mutation and 1p/19q co-deletion.