Five Gene Variations May Raise Risk of Brain Tumors

September 2009

Study Is First to Discover Glioma Risk Factors

Variations in five genes may raise a person's risk of developing glioma, the most prevalent type of brain tumor.

This study, the first to suggest risk factors for any type for glioma, was the largest to date of a rare cancer. The international research team, led by scientists at M. D. Anderson and the Institute of Cancer Research in the United Kingdom, reported its findings online in Nature Genetics.

Significance of study

"This is a groundbreaking study because it's the first time we've had a large enough sample to understand the genetic risk factors related to glioma, which opens the door to understanding a possible cause of these brain tumors," says co-senior author Melissa Bondy, Ph.D., professor in M. D. Anderson's Department of Epidemiology.

Bondy and colleagues expect their findings may eventually help identify people most at risk for the disease and provide potential targets for treatment or prevention.

Gliomas, deadly tumors that form in the supportive tissue of the brain and spine, account for about 80% of primary malignant brain tumors, with about 22,000 new cases and 13,000 deaths annually in the United States.

Research methods

Researchers analyzed 521,571 single nucleotide polymorphisms (SNPS), points in the genome known to vary from person to person, in:

1,878 glioma patients
3,670 people without glioma

They discovered 34 SNPS that were associated with glioma.

These 34 SNPS were analyzed in independent studies in Germany, France and Sweden that examined:

2,545 glioma patients
2,973 without glioma

Primary results

The SNPS associated with glioma were narrowed to 14, which were mapped to five genes. These gene variations raise a person's glioma risk by 18% to 36%.

The five genes identified, listed in descending order by their strongest effect, are:

CCDC26 on chromosome 8
TERT on chromosome 5
CDKN2A on chromosome 9
RTEL1 on chromosome 20
PHLDB1 on chromosome 11

Additional results

Risk escalates with the number of genes involved. People with eight or more of the 14 risk variations have a threefold risk of developing glioma.

What’s next?

Co-first author Sanjay Shete, Ph.D., associate professor in the Department of Epidemiology at M. D. Anderson, cautions it's too early to screen people for risk using these variations alone.

Additional research is needed on the genes involved and how variation affects their function and contributes to development of gliomas. And the disease is not solely genetic. A more comprehensive model that includes demographic and behavioral factors as well as environmental exposures is needed to identify those at risk.

Bondy will be principal investigator on a multicenter research project beginning next year that will examine 6,000 glioma patients and 6,000 people without glioma.

"We have only just begun to understand the causes of brain tumors,” she says. “Our findings give reasons for hope and an incentive for a more comprehensive investigation of what has been a mysterious disorder."

Adapted by Dawn Dorsey from an M. D. Anderson news release.