An international consortium led by Baylor College of Medicine and The University of Texas MD Anderson Cancer Center has narrowed the search for the gene or genes associated with inherited susceptibility to glioma, a deadly form of brain cancer, to a region on chromosome 17.
The report online 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 – the most common form of adult brain cancer and one of the most deadly.
In total, the researchers led by Dr. Melissa Bondy, associate director for prevention and population science in the NCI-designated Dan L Duncan Cancer Center at BCM and Dr. Sanjay Shete, professor in the Department of Epidemiology at MD Anderson, determined the genotype or genetic makeup of 46 families in the first phase of the study and 29 in the second, confirmatory phase. Bondy and Shete 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.
Hunting for mutations
Their analysis of the massive amounts of data pointed to a particular region on chromosome 17 called 17q12-21.3. The next step will be to sequence the region in family members with glioma, and in those without, seeking to find mutations that could cause disease.
"Previous studies have shown that inherited susceptibility plays a role in glioma," said Bondy, a corresponding author of the study. "First-degree relatives show a two-fold increased risk of the disease."
"In this study, we collected a significant family history of the disease," said Shete, also a corresponding author of the study. "We genotyped them using an approach similar to the genome-wide association studies." Much of that laboratory work, looking for single nucleotide polymorphisms (or SNPs that represent a single nucleotide change in the genetic sequence) was done by Dr. Ching C. Lau, associate professor of pediatrics at BCM and a member of the Texas Children’s Cancer Center.
They plan to follow the families they have identified to determine how important this region is in the risk of glioma. Already, one person who was believed unaffected by the disease in one family has developed glioma.
In addition to the U.S. families in this study, the group has identified as many as 1,000 such families worldwide – the largest collection of families with a least two family members who have had glioma in the world. Only about five percent of glioma patients have a family history of the disease, said Shete. Only five to nine percent of the cases of glioma have a familial predisposition for the disease.
The sequencing effort designed to identify mutations associated with the disease will be possible because of funds from the Robert and Janice McNair Foundation, said Bondy, who is the newest BCM McNair Scholar in breast cancer.
Funding for this study came from the National Institutes of Health, the American Brain Tumor Association, the National Brain Tumor Society and the Tug McGraw Foundation. For more information on the consortium, please go to Gliogene.
Others who took part in this study include Robert K. Yu, Georgina N. Armstrong, and Yanhong Liu of MD Anderson; Eastwood Hon-Chiu Leung, Caleb Davis, Rita Cheng of the Dan L Duncan Cancer Center at BCM; Richard S. Houlston and Fay J Hosking of the Institute of Cancer Research, Sutton, United Kingdom; Elizabeth B. Claus of the Yale University School of Medicine, New Haven, Conn., and the Brigham and Women’s Hospital, Boston, Mass.; Jill Barnholtz-Sloan of the Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio; Rose Lai of the Neurological Institute of Columbia University, New York; Dora Il’yasova and Joellen Schildkraut of Duke University Medical Center, Durham, N.C.; Siegal Sadetzki of the Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Christoffer Johansen of the Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; Jonine L. Bernstein and Sara H of Memorial Sloan-Kettering Cancer Center, New York; Robert B. Jenkins and Ping Yang of Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minn.; Beatrice S. Melin and Roger Henriksson of Umeå University, Umeå ,Sweden; Nicholas A. Vick of Evanston Kellogg Cancer Care Center North Shore University Health System, Evanston, Ill.; Margaret Wrensch of University of California, San Francisco; and Bridget J. McCarthy and Faith G. Davis of University of Illinois at Chicago.