Genome-wide association study of glioma and meta-analysis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-12

AUTHORS

Preetha Rajaraman, Beatrice S. Melin, Zhaoming Wang, Roberta McKean-Cowdin, Dominique S. Michaud, Sophia S. Wang, Melissa Bondy, Richard Houlston, Robert B. Jenkins, Margaret Wrensch, Meredith Yeager, Anders Ahlbom, Demetrius Albanes, Ulrika Andersson, Laura E. Beane Freeman, Julie E. Buring, Mary Ann Butler, Melissa Braganza, Tania Carreon, Maria Feychting, Sarah J. Fleming, Susan M. Gapstur, J. Michael Gaziano, Graham G. Giles, Goran Hallmans, Roger Henriksson, Judith Hoffman-Bolton, Peter D. Inskip, Christoffer Johansen, Cari M. Kitahara, Mark Lathrop, Chenwei Liu, Loic Le Marchand, Martha S. Linet, Stefan Lonn, Ulrike Peters, Mark P. Purdue, Nathaniel Rothman, Avima M. Ruder, Marc Sanson, Howard D. Sesso, Gianluca Severi, Xiao-Ou Shu, Matthias Simon, Meir Stampfer, Victoria L. Stevens, Kala Visvanathan, Emily White, Alicja Wolk, Anne Zeleniuch-Jacquotte, Wei Zheng, Paul Decker, Victor Enciso-Mora, Brooke Fridley, Yu-Tang Gao, Matthew Kosel, Daniel H. Lachance, Ching Lau, Terri Rice, Anthony Swerdlow, Joseph L. Wiemels, John K. Wiencke, Sanjay Shete, Yong-Bing Xiang, Yuanyuan Xiao, Robert N. Hoover, Joseph F. Fraumeni, Nilanjan Chatterjee, Patricia Hartge, Stephen J. Chanock

ABSTRACT

Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk. More... »

PAGES

1877-1888

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00439-012-1212-0

DOI

http://dx.doi.org/10.1007/s00439-012-1212-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1045225613

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22886559


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