Cancer susceptibility variants and the risk of adult glioma in a US case-control study

被引：69

作者：

Egan, Kathleen M. ^{[1
]}

Thompson, Reid C. ^{[2
]}

Nabors, L. B. ^{[3
]}

Olson, Jeffrey J. ^{[4
]}

Brat, Daniel J. ^{[5
]}

LaRocca, Renato V.

Brem, Steven

Moots, Paul L.

Madden, Melissa H. ^{[1
]}

Browning, James E. ^{[1
]}

Chen, Y. Ann ^{[1
]}

机构：

[1] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol & Genet, Tampa, FL 33612 USA

[2] Vanderbilt Univ, Med Ctr, Dept Neurol Surg, Nashville, TN 37232 USA

[3] Univ Alabama Birmingham, Neurooncol Program, Birmingham, AL 35294 USA

[4] Emory Sch Med, Dept Neurosurg, Atlanta, GA 30322 USA

[5] Emory Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA

来源：

JOURNAL OF NEURO-ONCOLOGY | 2011年 / 104卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Genotype; Glioma; Susceptibility; Single nucleotide polymorphism; GENOME-WIDE ASSOCIATION; LOCI;

D O I：

10.1007/s11060-010-0506-0

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Malignant gliomas are the most common and deadly brain tumors. Although their etiology remains elusive, recent studies have narrowed the search for genetic loci that influence risk. We examined variants implicated in recent cancer genome-wide association studies (GWAS) for associations with glioma risk in a US case-control study. Cases were identified from neurosurgical and neuro-oncology clinics at major academic centers in the Southeastern US. Controls were identified from the community or were friends or other associates of cases. We examined a total of 191 susceptibility variants in genes identified in published cancer GWAS including glioma. A total of 639 glioma cases and 649 controls, all Caucasian, were included in analysis. Cases were enrolled a median of 1 month following diagnosis. Among glioma GWAS-identified variants, we detected associations in CDKN2B, RTEL1, TERT and PHLDB1, whereas we did not find overall associations for CCDC26. Results showed clear heterogeneity according to histologic subtypes of glioma, with TERT and RTEL variants a feature of astrocytic tumors and glioblastoma (GBM), CCDC26 and PHLDB1 variants a feature of astrocytic and oligodendroglial tumors, and CDKN2B variants most prominent in GBM. No examined variant in other cancer GWAS was found to be related to risk after adjustment for multiple comparisons. These results suggest that GWAS-identified SNPs in glioma mark different molecular etiologies in glioma. Stratification by broad histological subgroups may shed light on molecular mechanisms and assist in the discovery of novel loci in future studies of genetic susceptibility variants in glioma.

引用

页码：535 / 542

页数：8

共 21 条

[1] CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[2] The INTERPHONE study:: design, epidemiological methods, and description of the study population [J].

Cardis, Elisabeth ;

Richardson, Lesley ;

Deltour, Isabelle ;

Armstrong, Bruce ;

Feychting, Maria ;

Johansen, Christoffer ;

Kilkenny, Monique ;

McKinney, Patricia ;

Modan, Baruch ;

Sadetzki, Siegal ;

Schuez, Joachim ;

Swerdlow, Anthony ;

Vrijheid, Martine ;

Auvinen, Anssi ;

Berg, Gabriele ;

Blettner, Maria ;

Bowman, Joseph ;

Brown, Julianne ;

Chetrit, Angela ;

Christensen, Helle Collatz ;

Cook, Angus ;

Hepworth, Sarah ;

Giles, Graham ;

Hours, Martine ;

Iavarone, Ivano ;

Jarus-Hakak, Avital ;

Klaeboe, Lars ;

Krewski, Daniel ;

Lagorio, Susanna ;

Loenn, Stefan ;

Mann, Simon ;

McBride, Mary ;

Muir, Kenneth ;

Nadon, Louise ;

Parent, Marie-Elise ;

Pearce, Neil ;

Salminen, Tiina ;

Schoemaker, Minouk ;

Schlehofer, Brigitte ;

Siemiatycki, Jack ;

Taki, Masao ;

Takebayashi, Toru ;

Tynes, Tore ;

van Tongeren, Martie ;

Vecchia, Paolo ;

Wiart, Joe ;

Woodward, Alistair ;

Yamaguchi, Naohito .

EUROPEAN JOURNAL OF EPIDEMIOLOGY, 2007, 22 (09) :647-664

[3] Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].

Chin, L. ;

Meyerson, M. ;

Aldape, K. ;

Bigner, D. ;

Mikkelsen, T. ;

VandenBerg, S. ;

Kahn, A. ;

Penny, R. ;

Ferguson, M. L. ;

Gerhard, D. S. ;

Getz, G. ;

Brennan, C. ;

Taylor, B. S. ;

Winckler, W. ;

Park, P. ;

Ladanyi, M. ;

Hoadley, K. A. ;

Verhaak, R. G. W. ;

Hayes, D. N. ;

Spellman, Paul T. ;

Absher, D. ;

Weir, B. A. ;

Ding, L. ;

Wheeler, D. ;

Lawrence, M. S. ;

Cibulskis, K. ;

Mardis, E. ;

Zhang, Jinghui ;

Wilson, R. K. ;

Donehower, L. ;

Wheeler, D. A. ;

Purdom, E. ;

Wallis, J. ;

Laird, P. W. ;

Herman, J. G. ;

Schuebel, K. E. ;

Weisenberger, D. J. ;

Baylin, S. B. ;

Schultz, N. ;

Yao, Jun ;

Wiedemeyer, R. ;

Weinstein, J. ;

Sander, C. ;

Gibbs, R. A. ;

Gray, J. ;

Kucherlapati, R. ;

Lander, E. S. ;

Myers, R. M. ;

Perou, C. M. ;

McLendon, Roger .

NATURE, 2008, 455 (7216) :1061-1068

[4] Brain cancer mortality in the United States, 1986 to 1995: A geographic analysis [J].

Fang, ZX ;

Kulldorff, M ;

Gregorio, DI .

NEURO-ONCOLOGY, 2004, 6 (03) :179-187

[5] Molecular Epidemiology of Primary Brain Tumors [J].

Gu, Jun ;

Liu, Yanhong ;

Kyritsis, Athanassios P. ;

Bondy, Melissa L. .

NEUROTHERAPEUTICS, 2009, 6 (03) :427-435

[6] Potential etiologic and functional implications of genome-wide association loci for human diseases and traits [J].

Hindorff, Lucia A. ;

Sethupathy, Praveen ;

Junkins, Heather A. ;

Ramos, Erin M. ;

Mehta, Jayashri P. ;

Collins, Francis S. ;

Manolio, Teri A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (23) :9362-9367

[7] A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer [J].

Hunter, David J. ;

Kraft, Peter ;

Jacobs, Kevin B. ;

Cox, David G. ;

Yeager, Meredith ;

Hankinson, Susan E. ;

Wacholder, Sholom ;

Wang, Zhaoming ;

Welch, Robert ;

Hutchinson, Amy ;

Wang, Junwen ;

Yu, Kai ;

Chatterjee, Nilanjan ;

Orr, Nick ;

Willett, Walter C. ;

Colditz, Graham A. ;

Ziegler, Regina G. ;

Berg, Christine D. ;

Buys, Saundra S. ;

McCarty, Catherine A. ;

Feigelson, Heather Spencer ;

Calle, Eugenia E. ;

Thun, Michael J. ;

Hayes, Richard B. ;

Tucker, Margaret ;

Gerhard, Daniela S. ;

Fraumeni, Joseph F., Jr. ;

Hoover, Robert N. ;

Thomas, Gilles ;

Chanock, Stephen J. .

NATURE GENETICS, 2007, 39 (07) :870-874

[8] Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma [J].

Huse, Jason T. ;

Holland, Eric C. .

NATURE REVIEWS CANCER, 2010, 10 (05) :319-331

[9] A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma [J].

Landi, Maria Teresa ;

Chatterjee, Nilanjan ;

Yu, Kai ;

Goldin, Lynn R. ;

Goldstein, Alisa M. ;

Rotunno, Melissa ;

Mirabello, Lisa ;

Jacobs, Kevin ;

Wheeler, William ;

Yeager, Meredith ;

Bergen, Andrew W. ;

Li, Qizhai ;

Consonni, Dario ;

Pesatori, Angela C. ;

Wacholder, Sholom ;

Thun, Michael ;

Diver, Ryan ;

Oken, Martin ;

Virtamo, Jarmo ;

Albanes, Demetrius ;

Wang, Zhaoming ;

Burdette, Laurie ;

Doheny, Kimberly F. ;

Pugh, Elizabeth W. ;

Laurie, Cathy ;

Brennan, Paul ;

Hung, Rayjean ;

Gaborieau, Valerie ;

McKay, James D. ;

Lathrop, Mark ;

McLaughlin, John ;

Wang, Ying ;

Tsao, Ming-Sound ;

Spitz, Margaret R. ;

Wang, Yufei ;

Krokan, Hans ;

Vatten, Lars ;

Skorpen, Frank ;

Arnesen, Egil ;

Benhamou, Simone ;

Bouchard, Christine ;

Metsapalu, Andres ;

Vooder, Tonu ;

Nelis, Mari ;

Vaelk, Kristian ;

Field, John K. ;

Chen, Chu ;

Goodman, Gary ;

Sulem, Patrick ;

Thorleifsson, Gudmar .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 85 (05) :679-691

[10]

LIU H, 2010, PROSTATE IN PRESS

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