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DNA variations linked to brain tumors

07.07.2009
Mayo Clinic researchers and colleagues at the University of California San Francisco (UCSF) have found a connection between DNA alterations on human chromosome 9 and aggressive brain cancer known as glioblastoma. The findings are reported in the current online issue of Nature Genetics.

The study, conducted with different patient populations at each institution, looked for genome-wide associations using individual patient data and information in the Cancer Genome Atlas. Researchers found that persons with the specific alterations -- also known as single nucleotide polymorphisms (SNPs) -- have a 50 percent higher relative risk of developing glioblastoma.

"This is not to cause those who possess these SNPs to worry about having CT scans every year," advised Robert Jenkins, M.D. Ph.D., genetics researcher and Mayo senior author of the study. He says an individual's environment also has much to do with their risk of cancer and that such external factors may need to be present to trigger onset of brain tumors, even for those with these SNPs. "Increased relative risk is just that -- relative." A normal person's risk of developing a glioblastoma is about 1 in 10,000. The risk is about 1 in 7,000 for a person carrying one of these SNPs.

Each year between 25,000 and 30,000 persons are diagnosed with glioblastomas -- one of the most aggressive forms of brain tumor. The causes are not clear and very few who are diagnosed live beyond five years.

How the Study was Conducted

To discover genes that might indicate an increased susceptibility to glioblastomas and other types of brain tumors, the investigators searched over 250,000 variants in 692 adult glioma patients (from the San Francisco Adult Glioma Study; 70 from the Cancer Genome Atlas) and compared them to 3992 controls (3390 from Illumina Control database and 602 from the Genome Atlas). The study was then replicated using independent data from 176 glioma patients and 174 controls from Mayo Clinic. Additional reports in the same issue of Nature Genetics further support the findings with independent replication studies.

"Replication is essential in genome wide association studies," says Dr. Jenkins. "Replication across independent patient populations is critical in establishing a real association between glioblastomas and the presence of these SNPs in the genome of patients with that type of brain tumor."

Researchers on the study include Karla Ballman, Ph.D., Jan Buckner, M.D., Paul Decker, Caterina Giannini, M.D., Ph.D., Chandralekha Halder, Thomas Kollmeyer, Matthew Kosel, Daniel LaChance, M.D., Brian O'Neill, M.D., Amanda Rynearson, and Ping Yang, M.D., Ph.D., all of Mayo Clinic; Margaret Wrensch, Ph.D., Jeffrey Chang, M.D., Ph.D., Ru-Fang Yeh, Ph.D., Yuanuan Xiao, Ph.D., Mitchel Berger, M.D., Susan Chang, M.D., Lucie McCoy, Joe Patoka, Alexander Pico, Michael Prados, M.D., Terri Rice, Ivan Smirnov, Tarik Tihan, M.D., Ph.D., Joe Wiemels, Ph.D., and John Wiencke, Ph.D., all of the University of California San Francisco; and Charles Quesenberry, Ph.D., of Kaiser Permanente, Oakland.

Research was supported by the National Institutes of Health and the National Cancer Institute (including the UCSF and Mayo Clinic Brain Tumor Specialized Programs of Research Excellence (SPOREs), the National Brain Tumor Foundation, the UCSF Lewis Chair in Brain Tumor Research, the Mayo Clinic Cancer Center, the families and friends of John Berardi, Helen Glaser and Elvera Olsen, and the Bernie and Edith Waterman Foundation.

About Mayo Clinic

Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. Doctors from every medical specialty work together to care for patients, joined by common systems and a philosophy of "the needs of the patient come first." More than 3,300 physicians, scientists and researchers and 46,000 allied health staff work at Mayo Clinic, which has sites in Rochester, Minn., Jacksonville, Fla., and Scottsdale/Phoenix, Ariz. Collectively, the three locations treat more than half a million people each year. To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. For information about research and education visit www.mayo.edu. MayoClinic.com (www.mayoclinic.com) is available as a resource for your health stories.

Robert Nellis | EurekAlert!
Further information:
http://www.mayo.edu

Further reports about: Brain Cancer DNA DNA replication Genetics Genom Nature Immunology UCSF brain tumor

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