@article{5f2132a038484055b66345135f41bd55,
title = "Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility",
abstract = "The causes of glioblastoma and other gliomas remain obscure. To discover new candidate genes influencing glioma susceptibility, we conducted a principal component-adjusted genome-wide association study (GWAS) of 275,895 autosomal variants among 692 adult high-grade glioma cases (622 from the San Francisco Adult Glioma Study (AGS) and 70 from the Cancer Genome Atlas (TCGA)) and 3,992 controls (602 from AGS and 3,390 from Illumina iControlDB (iControls)). For replication, we analyzed the 13 SNPs with P< 10 -6 using independent data from 176 high-grade glioma cases and 174 controls from the Mayo Clinic. On 9p21, rs1412829 near CDKN2B had discovery P = 3.4 × 10 -8, replication P = 0.0038 and combined P = 1.85 × 10 -10. On 20q13.3, rs6010620 intronic to RTEL1 had discovery P = 1.5 × 10 -7, replication P = 0.00035 and combined P = 3.40 × 10 9. For both SNPs, the direction of association was the same in discovery and replication phases.",
author = "Margaret Wrensch and Jenkins, {Robert B.} and Chang, {Jeffrey S.} and Yeh, {Ru Fang} and Yuanyuan Xiao and Decker, {Paul A.} and Ballman, {Karla V.} and Mitchel Berger and Buckner, {Jan C.} and Susan Chang and Caterina Giannini and Chandralekha Halder and Kollmeyer, {Thomas M.} and Kosel, {Matthew L.} and Lachance, {Daniel H.} and Lucie McCoy and O'Neill, {Brian P.} and Joe Patoka and Pico, {Alexander R.} and Michael Prados and Charles Quesenberry and Terri Rice and Rynearson, {Amanda L.} and Ivan Smirnov and Tarik Tihan and Joe Wiemels and Ping Yang and Wiencke, {John K.}",
note = "Funding Information: Work at University of California, San Francisco (UCSF) has been supported by US National Institutes of Health grants R01CA52689 and UCSF Brain Tumor SPORE, P50CA097257, as well as by grants from the National Brain Tumor Foundation, the UCSF Lewis Chair in Brain Tumor Research and by donations from families and friends of J. Berardi, H. Glaser and E. Olsen. J.S.C. was also supported by a fellowship from the National Cancer Institute (grant R25 CA 112355). Work at the Mayo Clinic has been supported by the Mayo Clinic Brain Tumor SPORE (NIH P50 CA108961), the Mayo Clinic Comprehensive Cancer Center (P30 CA15083) and the Bernie and Edith Waterman Foundation. The San Francisco Adult Glioma Study thanks the Northern California Cancer Center for identifying glioma cases; we also thank K. Aldape for pathology review and the pathology departments of Alexian, Alta Bates, Brookside, California Pacific, Doctors Pinole, Eden, El Camino, Good Samaritan, Highland, John Muir, Kaiser Redwood City, Kaiser San Francisco, Kaiser Santa Teresa, Los Gatos, Los Medanos, Marin General, Merrithew, Mills Peninsula, Mt. Diablo Hospital, Mt. Zion, Naval Hospital, O{\textquoteright}Connor, Ralph K Davies, Saint Louise, San Francisco General, San Jose, San Leandro, San Mateo County, San Ramon Valley, Santa Clara Valley, Sequoia, Seton, St. Francis, St. Luke{\textquoteright}s, St. Rose, Stanford, Summit, UC San Francisco, Valley Livermore, Veterans Palo Alto, Veterans SF, and Washington Hospitals and Medical Centers for providing tumor specimens for review. Genotyping services for San Francisco study subjects were provided by deCODE Genetics, Iceland. The company provided SNP and normalized CNV data and technical support in data analysis, including conference call tutorials in the use of the Disease Miner Software. We thank B. Scheithauer and C. Gianinni for their careful histological review of all the primary high-grade gliomas collected at the Mayo Clinic for this study. The Mayo Clinic Comprehensive Cancer Center Biospecimens and Processing (TACMA), Gene Analysis, Biostatistics and Bioinformatics Shared Resources were essential for the success of this study. We also thank K. Kelsey for helpful suggestions on genotyping and interpretation of results, N. Risch for very helpful suggestions on this paper and S. Sen for helpful discussions and suggestions on statistical methods. Some computations were performed using the UCSF Biostatistics High Performance Computing System.",
year = "2009",
month = aug,
doi = "10.1038/ng.408",
language = "English (US)",
volume = "41",
pages = "905--908",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "8",
}