Current Research Highlights
Below are highlights of research reported by grantees supported by the Epidemiology and Genetics Research Program (EGRP). The featured research was nominated by extramural investigators and selected by EGRP Program Staff based on scientific merit, innovation, and/or potential public health impact.
Brain Cancer
Genetic Variants Associated With Increased Glioma Risk
Margaret Wrensch,
M.P.H., Ph.D.
Melissa Bondy,
Ph.D.
Common genetic variations may increase a person’s risk of developing brain cancer, and it is now possible to identify these potential risk factors. In two genome-wide association studies (GWAS), investigators independently discovered and validated a number of inherited genetic variants linked to glioma, the most common form of brain cancer. The findings, published in the August 2009 issue of Nature Genetics, mark the first time a link has been established between common, low-penetrance genetic variants and this highly lethal and little understood cancer. The findings could provide clues for investigating the inherited component of disease risk.
Margaret Wrensch, M.P.H., Ph.D., of the University of California, San Francisco, and colleagues identified loci associated with elevated risk for high-grade glioma on a region of 9p21 near CDKN2B and on a region of 20q13.3 that maps to the RTEL1 gene. RTEL1 also contained a gene variant that appears to have a protective effect against developing glioma.
Melissa Bondy, Ph.D., and colleagues from The University of Texas M.D. Anderson Cancer Center, and investigators from the Institute of Cancer Research in the United Kingdom, identified 14 variants associated with glioma risk, including two of the same variants on 9p21 and 20q13.3 identified by Wrensch et al. The top “hits” in this study pointed to five risk loci, including the following genes: CDKN2A-CDKN2B, TERT, CCDC26, PHLDB1, and RTEL1.
These studies, remarkable for their large sample sizes, open the door to advancing our understanding of the etiology of brain cancer. In addition, the same issue of Nature Genetics featured three studies that implicate other variants on 9p21 in the risk of melanoma and basal cell carcinoma.
This research was funded in part by EGRP grants to Drs. Bondy and Wrensch.
Wrensch M, Jenkins RB, Chang JS, Yeh RF, Xiao Y, Decker PA, Ballman KV, Berger M, Buckner JC, Chang S, Giannini C, Halder C, Kollmeyer TM, Kosel ML, Lachance DH, McCoy L, O'Neill BP, Patoka J, Pico AR, Prados M, Quesenberry C, Rice T, Rynearson AL, Smirnov I, Tihan T, Wiemels J, Yang P, Wiencke JK. Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet. 2009 Aug; 41(8): 905-8.
Shete S, Hosking FJ, Robertson LB, Dobbins SE, Sanson M, Malmer B, Simon M, Marie Y, Boisselier B, Delattre JY, Hoang-Xuan K, El Hallani S, Idbaih A, Zelenika D, Andersson U, Henriksson R, Bergenheim AT, Feychting M, Lönn S, Ahlbom A, Schramm J, Linnebank M, Hemminki K, Kumar R, Hepworth SJ, Price A, Armstrong G, Liu Y, Gu X, Yu R, Lau C, Schoemaker M, Muir K, Swerdlow A, Lathrop M, Bondy M, Houlston RS. Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet. 2009 Aug;41(8):899-904.
