An international consortium of researchers, including members from the Yale School of Public Health, has narrowed the search for the gene or genes associated with inherited susceptibility to a malignant brain cancer to a region on chromosome 17.
The online report in the journal Cancer Research involved analysis of the genotype or genetic makeup of 75 families in which there were two or more members who had had glioma—a common form of adult brain cancer and the most deadly. The extensive genetic analysis pointed to a particular region on chromosome 17 known as 17q12-21.3. The next step will be to sequence this region in family members with glioma, and in those without, in order to identify mutations or variants that might cause the disease.
“In this study, each of the research sites collected families with glioma, a difficult undertaking for such a lethal disease,” said Elizabeth Claus, a professor at the School of Public Health, a practicing neurosurgeon and one of the study’s authors. “The families were then genotyped using an approach similar to the genome-wide association studies.”
In addition to the U.S. families in the study, the researchers identified as many as 1,000 such families worldwide – the largest collection of families with a least two members who have had glioma in the world—and are continuing to enroll such families.
They plan to follow the families they have identified to determine how important this chromosome 17 region is in the risk of glioma. Already, one person who was believed unaffected by the disease in one family has developed glioma.
The group performed laboratory analyses to determine the genetic makeup of 46 families in the first phase of the study and 29 in the second, confirmatory phase. The researchers are part of the Genetic Epidemiology of Glioma International Consortium, which consists of 15 institutions in the United States, the United Kingdom, Sweden, Denmark and Israel.
Claus is also the principal investigator of the Meningioma Consortium, an effort to define risk factors for meningioma, another type of primary brain tumor that is common in adults.
Funding for the study came from the National Institutes of Health, the Brain Science Foundation, the American Brain Tumor Association, the National Brain Tumor Society and the Tug McGraw Foundation.