Study identifies specific genetic risk factors that increase susceptibility to gliomas

A massive new study involving blood samples from over 30,000 individuals has identified 13 new genetic risk factors for glioma, the most common type of malignant brain tumor in adults. The study, published in Nature Genetics, reveals specific differences in a person's DNA that increase susceptibility to glioma tumors, and for the first time allows doctors to distinguish between a person's risk of developing tumor subtypes including glioblastoma and non-glioblastoma. Together malignant brain tumors cause an estimated 13,000 deaths in the United States annually.

"Because of the large sample size used in this study, for the first time we were able to assess if genetic risk was different for glioblastoma versus non-glioblastoma. Indeed their genetic risk profiles are different," said Jill Barnholtz-Sloan, PhD, Sally S. Morley Designated Professor in Brain Tumor Research at the Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine. Barnholtz-Sloan served as local primary investigator in the study and helped lead the data management and data analysis alongside Case Western Reserve University School of Medicine Doctoral Student, Quinn Ostrom, MA, MPH, and Biostatistician, Yanwen Chen, PhD, MS.

The enormous study credits 63 authors across more than 20 institutions, including collaborators in Sweden, Denmark, United Kingdom, Germany, Canada, and Israel. Said Barnholtz-Sloan, "Gliomas, while the most common type of malignant brain tumor in adults, are very rare, hence multi-site collaborations are necessary in order to have scientifically valid sample sizes."

In the new study, Barnholtz-Sloan and the researchers provide a meta-analysis of multiple published genome-wide association studies, or GWASs, increasingly popular research tools that search DNA sequence data for regions associated with disease risk. The studies are exceptionally powerful, and able to pinpoint specific DNA sequence molecules, say a G, C, T, or A, that are altered in people with a particular disease as compared to people without that disease. Previous GWASs had identified 13 specific locations in DNA that increase a person's risk for developing glioma. The new study doubled this number, identifying an additional 13 novel locations—five for glioblastoma, and eight for non-glioblastoma.

Said Barnholtz-Sloan, "A meta-analysis was needed because we wanted to analyze data from the most studies possible." In total, the team analyzed data from 12,496 people with gliomas (6,191 glioblastomas and 5,819 non-glioblastomas) and 18,190 people without gliomas.

The newly identified genetic risk factors could help distinguish patients most at risk for developing each kind of glioma. Each tumor subtype is associated with a different prognosis, with the most common, glioblastoma, associated with a median survival rate of only 12-14 months, according to the American Brain Tumor Association. With information from the new study, doctors are better equipped to diagnose high-risk patients early, which could ultimately improve prognosis.