Large-scale study finds genetic errors associated with brain cancer

Hundreds of thousands of people in the United States are living with a brain tumor. Gliomas are a particular category of malignant brain tumor that includes glioblastoma - a tumor with a low survival rate. New research uncovers genetic variants associated with an increased risk of glioma.

A new genetic study carried out by a team of international researchers from the United Kingdom, Europe, and the U.S. identifies 13 new genetic errors that correlate with a high risk of glioma. The findings were published in the journal Nature Genetics.

The National Brain Tumor Society estimate that 688,096 U.S. individuals have a brain tumor, and nearly 140,000 of these are malignant.

Brain tumors are quite aggressive and difficult to treat, with an average of only 34.4 percent of the patients surviving 5 years after their initial diagnosis.

Of the different types of brain tumor, glioma is the most common. It describes a type of tumor that grows from the brain's glial cells, which can be found around the neurons, supporting the nerve cells.

Across all brain tumors, gliomas account for approximately 27 percent and are estimated to cause 13,000 yearly cancer deaths in the U.S., according to research quoted in the new study. Gliomas are usually divided into glioblastomas (GBMs) and non-GBM tumors. Patients diagnosed with GBMs have a survival rate as low as 5 percent.

The authors of the new study note that little is known about the environmental factors that contribute to the risk of being diagnosed with glioma. The researchers set out to examine the genetic background for glioma risk.

Study doubles the number of genetic variants known to raise glioma risk

The team conducted two new genomic studies and added their findings to that of previously existing studies. The result was a meta-analysis of almost 12,500 people with glioma and more than 18,000 healthy, glioma-free controls.

Overall, the scientists identified 13 new genetic variants that raised the risk of glioma: five new loci were identified for GBM, and eight for non-GBM tumors. The study shows that these genetic errors impact various cell functions, including the genesis and division of neurons, cell cycle regulation, DNA repair, and the production of some proteins.

Additionally, the scientists examined how different genetic strands affect a person's chances of developing GBM and non-GBM tumors.

For instance, they found that the expression of the HEATR3 gene increases the risk of GBM by 18 percent, but it has a much lower impact on non-GBM risk.

Study co-leader Richard Houlston, professor of molecular and population genetics at the Institute of Cancer Research in London in the U.K., comments on the significance of these findings:

"The changes in the way we think about glioma could be quite fundamental," Prof. Houston explains. "So for example, what we thought of as two related subtypes of the disease turn out to have quite different genetic causes which may require different approaches to treatment."

Apart from the newly discovered genetic errors, the study also confirmed the role of other genes that have been previously identified and correlated with the risk of brain and other types of cancer.

Before the new study, the total number of genetic variants linked to glioma risk was 13. The new research doubles this number.

"It has been exciting to have been involved in such a gigantic study including cases of brain cancer from all over the world. We have uncovered a treasure trove of new information about the genetic causes of glioma brain cancers.

Understanding the genetics of glioma in such detail allows us to start thinking about ways of identifying people at high inherited risk, and will open up a search for new treatments that exploit our new knowledge of the biology of the disease."

Prof. Richard Houlston

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