Open AccessProceedings Article
Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility
TLDR
Wrensch et al. as mentioned in this paper found that variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility and showed that the direction of association was the same in discovery and replication phases.Abstract:
LETTERS Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility Margaret Wrensch 1,2,12 , Robert B Jenkins 3,12 , Jeffrey S Chang 4,12 , Ru-Fang Yeh 4,12 , Yuanyuan Xiao 4 , Paul A Decker 5 , Karla V Ballman 5 , Mitchel Berger 1 , Jan C Buckner 6 , Susan Chang 1 , Caterina Giannini 3 , Chandralekha Halder 3 , Thomas M Kollmeyer 3 , Matthew L Kosel 5 , Daniel H LaChance 7 , Lucie McCoy 1 , Brian P O’Neill 7 , Joe Patoka 1 , Alexander R Pico 8 , Michael Prados 1 , Charles Quesenberry 9 , Terri Rice 1 , Amanda L Rynearson 3 , Ivan Smirnov 1 , Tarik Tihan 10 , Joe Wiemels 2,4 , Ping Yang 11,13 & John K Wiencke 1,2,13 The causes of glioblastoma and other gliomas remain obscure 1,2 To discover new candidate genes influencing glioma susceptibility, we conducted a principal component– adjusted 3 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)) 4 and 3,992 controls (602 from AGS and 3,390 from Illumina iControlDB (iControls)) For replication, we analyzed the 13 SNPs with P o 10 A6 using independent data from 176 high-grade glioma cases and 174 controls from the Mayo Clinic On 9p21, rs1412829 near CDKN2B had discovery P ¼ 34 Â 10 A8 , replication P ¼ 00038 and combined P ¼ 185 Â 10 A10 On 20q133, rs6010620 intronic to RTEL1 had discovery P ¼ 15 Â 10 A7 , replication P ¼ 000035 and combined P ¼ 340 Â 10 A9 For both SNPs, the direction of association was the same in discovery and replication phases Subject characteristics, including participation rates for the discovery GWAS and replication phases, are listed in Supplementary Table 1a,b The distribution of P values from the principal component–adjusted logistic regression additive model across the genome for high-grade glioma cases versus controls (Fig 1) suggests potentially meaningful associations for several SNPs on chromosomes 1, 5, 9, 11 and 20 Supplementary Table 2 summarizes results for the 13 SNPs with P o 10 A6 for association with high-grade glioma in discovery data along with results from replication data; SNPs with Hardy-Weinberg P o 10 A5 in controls or with 45% missing data in any case or control group were excluded Three of these 13 SNPs (rs1412829 on 9p21, and rs6010620 and rs4809324 intronic to RTEL1 on 20q133) had significant association with high-grade glioma risk in the discovery phase (principal component analysis P o 18 Â 10 A7 ), were inde- pendent risk predictors in a multivariable analysis of 13 top hits, and were replicated in the Mayo Clinic dataset (Table 1) As shown in Table 1 and Supplementary Table 2, the minor allele frequencies for the three SNPs consistently differed in the same direction between high-grade glioma cases and controls regardless of data source (AGS, TCGA, iControls or Mayo Clinic) Supplementary Table 3 shows results from the multivariable model of discovery data that included all 13 SNPs (four from the 9p21 region, three in RTEL1, plus six others in other locations) Eight SNPs, including one in the 9p21 region and two intronic to RTEL1, remained independently associated with high- grade glioma risk after adjustment for other SNPs This was expected given the strong linkage disequilibrium (LD) evident for the four 9p21 SNPs and two of the three RTEL1 SNPs (Supplementary Table 4) In discovery data, only the interaction between chromosome 9p21 SNP rs1412829 and TERT SNP rs2736100 on chromosome 5 was statistically significant with Wald test P ¼ 0019 (see Supplementary P value Chromosome © 2009 Nature America, Inc All rights reserved Figure 1 Distribution of P values from principal component–adjusted logistic regression additive model across the genome for high-grade glioma cases versus controls The 13 SNPs with P o 10 A6 are shown in red 1 Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA 2 Institute of Human Genetics, University of California, San Francisco, San Francisco, California, USA 3 Department of Experimental Pathology, Mayo Clinic, Rochester, Minnesota, USA 4 Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA 5 Division of Biostatistics, 6 Department of Oncology and 7 Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA 8 Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, San Francisco, California, USA 9 Division of Research, Kaiser Permanente, Oakland, California, USA 10 Department of Pathology, University of California, San Francisco, San Francisco, California, USA 11 Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, USA 12 These authors contributed equally to this work 13 These authors jointly directed the work Correspondence should be addressed to MW (margaretwrensch@ucsfedu) Received 13 March; accepted 1 June; published online 5 July 2009; doi:101038/ng408 NATURE GENETICS ADVANCE ONLINE PUBLICATIONread more
Citations
More filters
Journal ArticleDOI
The epidemiology of glioma in adults: a "state of the science" review.
Quinn T. Ostrom,Luc Bauchet,Faith G. Davis,Isabelle Deltour,James L. Fisher,Chelsea Eastman Langer,Melike Pekmezci,Judith A. Schwartzbaum,Michelle C. Turner,Kyle M. Walsh,Margaret Wrensch,Jill S. Barnholtz-Sloan +11 more
TL;DR: A “state of the science” review of current research into causes and risk factors for gliomas in adults is provided.
Journal ArticleDOI
Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors
Jeanette E. Eckel-Passow,Daniel H. Lachance,Annette M. Molinaro,Kyle M. Walsh,Paul A. Decker,Hugues Sicotte,Melike Pekmezci,Terri Rice,Matt L. Kosel,Ivan Smirnov,Gobinda Sarkar,Alissa Caron,Thomas M. Kollmeyer,Corinne Praska,Anisha R. Chada,Chandralekha Halder,Helen M. Hansen,Lucie McCoy,Paige M. Bracci,Roxanne Marshall,Shichun Zheng,Gerald F. Reis,Alexander R. Pico,Brian P. O'Neill,Jan C. Buckner,Caterina Giannini,Jason T. Huse,Arie Perry,Tarik Tihan,Mitchell S. Berger,Susan M. Chang,Michael D. Prados,Joseph L. Wiemels,John K. Wiencke,Margaret Wrensch,Robert B. Jenkins +35 more
TL;DR: The five glioma molecular groups had different ages at onset, overall survival, and associations with germline variants, which implies that they are characterized by distinct mechanisms of pathogenesis.
Journal ArticleDOI
Epidemiologic and Molecular Prognostic Review of Glioblastoma
Jigisha P. Thakkar,Therese A. Dolecek,Craig Horbinski,Quinn T. Ostrom,Donita Lightner,Jill S. Barnholtz-Sloan,John L. Villano +6 more
TL;DR: The current epidemiology of GBM is reported with new data from the Central Brain Tumor Registry of the United States 2006 to 2010 as well as demonstrate and discuss trends in incidence and survival.
Journal ArticleDOI
Expression of Linear and Novel Circular Forms of an INK4/ARF-Associated Non-Coding RNA Correlates with Atherosclerosis Risk
TL;DR: The results identify novel circular RNA products emanating from the ANRIL locus and suggest causal variants at 9p21.3 regulate INK4/ARF expression and ASVD risk by modulating ANRil expression and/or structure.
Journal ArticleDOI
Genetics of adult glioma
TL;DR: The discovery of two separate molecular subtypes within the glioma classification that appear to correlate with biological etiology, prognosis, and response to therapy suggests that molecular genetic tests are and will be useful, beyond classical histology, for the clinical classification of gliomas.
References
More filters
Journal ArticleDOI
DNA helicases and their roles in cancer
TL;DR: The seminal roles of helicases in the DNA damage and replication stress responses, as well as DNA repair pathways, validate their vital importance in cancer biology and suggest their potential values as targets in anti-cancer therapy.
Genetic Variants of VEGF (rs201963 and rs3025039) and KDR (rs7667298, rs2305948, and rs1870377) Are Associated with Glioma Risk in a Han Chinese Population:
Jiannan Zhang,Jian Yang,Yuqing Chen,Qin Mao,Shanquan Li,Wenhao Xiong,Yingying Lin,Jie Chen,Jianwei Ge +8 more
TL;DR: The haplotype analysis demonstrated that two SNPs of VEGF could elevate the susceptibility to a glioma in the homozygous model, and threeSNPs of KDR were assumed to be associated with an increased risk of aglioma.
Journal ArticleDOI
A genetic variant in the APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in a Chinese Han population.
Keke Zhou,Dezhi Hu,Juan Lu,Weiwei Fan,Hongliang Liu,Hongyan Chen,Gong Chen,Qingyi Wei,Guhong Du,Ying Mao,Daru Lu,Liangfu Zhou +11 more
TL;DR: The results suggest that a specific genetic variant located in the APE1/Ref-1 promoter may modulate risk of glioblastoma, but not for other histological gliomas.
A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer
Ali Amin Al Olama,Zsofia Kote-Jarai,Sonja I. Berndt,David V. Conti,Fredrick R. Schumacher,Ying Han,Sara Benlloch,Dennis J. Hazelett,Zhaoming Wang,Ed Saunders,Daniel Leongamornlert,Sara Lindström,Sara Jugurnauth-Little,Tokhir Dadaev,Malgorzata Tymrakiewicz,Daniel O. Stram,Kristin A. Rand,Peggy Wan,Alex Stram,Xin Sheng,Loreall Pooler,Karen Park,Lucy Xia,Jonathan Tyrer,Laurence N. Kolonel,Loic Le Marchand,Robert N. Hoover,Mitchell J. Machiela,Merideth Yeager,Laurie Burdette,Charles C. Chung,Amy K. Hutchinson,Kai Yu,Chee Goh,Mahbubl Ahmed,Koveela Govindasami,Michelle Guy,Teuvo L.J. Tammela,Anssi Auvinen,Tiina Wahlfors,Johanna Schleutker,Tapio Visakorpi,Katri A. Leinonen,Jianfeng Xu,Markus Aly,Jenny L Donovan,Ruth C. Travis,Timothy J. Key,Afshan Siddiq,Federico Canzian,Kay-Tee Khaw,Atsushi Takahashi,Michiaki Kubo,Paul D.P. Pharoah,Nora Pashayan,Maren Weischer,Børge G. Nordestgaard,Sune F. Nielsen,Peter Klarskov,Martin Andreas Røder,Peter Iversen,Stephen N. Thibodeau,Shannon K. McDonnell,Daniel J. Schaid,Janet L. Stanford,Janet L. Stanford,Suzanne Kolb,Sarah K. Holt,Beatrice S. Knudsen,Antonio Hurtado Coll,Susan M. Gapstur,W. Ryan Diver,Victoria L. Stevens,Christiane Maier,Manuel Luedeke,Kathleen Herkommer,Antje E. Rinckleb,Sara S. Strom,Curtis A. Pettaway,Edward D. Yeboah,Edward D. Yeboah,Yao Tettey,Yao Tettey,Richard B. Biritwum,Richard B. Biritwum,Andrew A. Adjei,Andrew A. Adjei,Evelyn Tay,Evelyn Tay,Ann Truelove,Shelley Niwa,Anand P. Chokkalingam,Lisa A. Cannon-Albright,Lisa A. Cannon-Albright,Cezary Cybulski,Dominika Wokołorczyk,Wojciech Kluźniak,Jong Y. Park,Thomas A. Sellers,Hui-Yi Lin,William B. Isaacs,Alan W. Partin,Hermann Brenner,Aida Karina Dieffenbach,Christa Stegmaier,Constance Chen,Edward Giovannucci,Jing Ma,Meir J. Stampfer,Kathryn L. Penney,Lorelei A. Mucci,Esther M. John,Esther M. John,Sue A. Ingles,Rick A. Kittles,Adam B. Murphy,Hardev Pandha,Agnieszka Michael,Andrzej M. Kierzek,William J. Blot,Lisa B. Signorello,Wei Zheng,Demetrius Albanes,Jarmo Virtamo,Stephanie J. Weinstein,Barbara Nemesure,John D. Carpten,Cristina Leske,Suh-Yuh Wu,Anselm Hennis,Anselm Hennis,Adam S. Kibel,Benjamin A. Rybicki,Christine Neslund-Dudas,Ann W. Hsing,Ann W. Hsing,Lisa Chu,Lisa Chu,Phyllis J. Goodman,Eric A. Klein,S. Lilly Zheng,Jyotsna Batra,Judith A. Clements,Amanda B. Spurdle,Manuel R. Teixeira,Manuel R. Teixeira,Paula Paulo,Sofia Maia,Chavdar Slavov,Radka Kaneva,Vanio Mitev,John S. Witte,Graham Casey,Elizabeth M. Gillanders,Daniella Seminara,Elio Riboli,Freddie C. Hamdy,Gerhard A. Coetzee,Qiyuan Li,Matthew L. Freedman,David J. Hunter,Kenneth Muir,Kenneth Muir,Henrik Grönberg,David E. Neal,David E. Neal,Melissa C. Southey,Graham G. Giles,Graham G. Giles,Gianluca Severi,Gianluca Severi,Michael B. Cook,Hidewaki Nakagawa,Fredrik Wiklund,Peter Kraft,Stephen J. Chanock,Brian E. Henderson,Douglas F. Easton,Rosalind A. Eeles,Christopher A. Haiman +179 more
TL;DR: This paper conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry.
Journal ArticleDOI
Association between GSTP1 Ile105Val polymorphism and glioma risk: A systematic review and meta-analysis
TL;DR: It is suggested that there is no association between GSTP1 Ile105Val polymorphism and glioma risk under recessive model, and more well-designed and larger studies are needed to further assess this association.
Related Papers (5)
Abstract B11: Replication of previously identified breast cancer susceptibility loci in a breast cancer case-control study on women of African ancestry
Yonglan Zheng,Dezheng Huo,Temidayo O. Ogundiran,Adeyinka G. Falusi,Oladosu Ojengbede,Clement Adebamowo,William J. Blot,Wei Zheng,Qiuyin Cai,Lisa B. Signorello,Katherine L. Nathanson,Susan M. Domchek,Timothy R. Rebbeck,Michael S. Simon,Anselm Hennis,Barbara Nemesure,Suh-Yuh Wu,M.C. Leske,Stefan Ambs,Abayomi Odetunde,Imaria Anetor,Stella Akinleye,Qun Niu,Jing Zhang,Anna Pluzhnikov,Anuar Konkashbaev,Lin Chen,Eric R. Gamazon,Younghee Lee,Nancy J. Cox,Olufunmilayo O. Olopade +30 more
Abstract LB-299: Genome wide association study of breast cancer in Latinas identifies protective variants of Indigenous American origin on 6q25
Laura Fejerman,Nasim Ahmadiyeh,Donglei Hu,Scott Huntsman,Kenneth B. Beckman,Jennifer L. Caswell,Esther M. John,Gabriela Torres-Mejía,Luis G. Carvajal-Carmona,Magdalena Echeverry,Anna Marie Tuazon,Carolina Ramirez,Christopher R. Gignoux,Celeste Eng,Esteban Gonzalez-Burchard,Brian E. Henderson,Loic Le Marchand,Eliseo J. Pérez-Stable,Christopher A. Haiman,Elad Ziv +19 more