Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.

Authors:
Silvia Bea, PhD
Silvia Bea, PhD
IDIBAPS
Genomic Alterations
Barcelona | Spain
Dr. Itziar Salaverria, PhD
Dr. Itziar Salaverria, PhD
Institut d'Investigacions Biomèdiques August Pi i Sunyer
Genetics, Molecular biology, Lymphoma, pediatric lymphoma
Barcelona | Spain
Sonja I Berndt Christine F Skibola Vijai Joseph Nicola J Camp Alexandra Nieters Zhaoming Wang Wendy Cozen Alain Monnereau Sophia S Wang Rachel S Kelly Qing Lan Lauren R Teras Nilanjan Chatterjee Charles C Chung Meredith Yeager Angela R Brooks-Wilson Patricia Hartge Mark P Purdue Brenda M Birmann Bruce K Armstrong Pierluigi Cocco Yawei Zhang Gianluca Severi Anne Zeleniuch-Jacquotte Charles Lawrence Laurie Burdette Jeffrey Yuenger Amy Hutchinson Kevin B Jacobs Timothy G Call Tait D Shanafelt Anne J Novak Neil E Kay Mark Liebow Alice H Wang Karin E Smedby Hans-Olov Adami Mads Melbye Bengt Glimelius Ellen T Chang Martha Glenn Karen Curtin Lisa A Cannon-Albright Brandt Jones W Ryan Diver Brian K Link George J Weiner Lucia Conde Paige M Bracci Jacques Riby Elizabeth A Holly Martyn T Smith Rebecca D Jackson Lesley F Tinker Yolanda Benavente Nikolaus Becker Paolo Boffetta Paul Brennan Lenka Foretova Marc Maynadie James McKay Anthony Staines Kari G Rabe Sara J Achenbach Celine M Vachon Lynn R Goldin Sara S Strom Mark C Lanasa Logan G Spector Jose F Leis Julie M Cunningham J Brice Weinberg Vicki A Morrison Neil E Caporaso Aaron D Norman Martha S Linet Anneclaire J De Roos Lindsay M Morton Richard K Severson Elio Riboli Paolo Vineis Rudolph Kaaks Dimitrios Trichopoulos Giovanna Masala Elisabete Weiderpass María-Dolores Chirlaque Roel C H Vermeulen Ruth C Travis Graham G Giles Demetrius Albanes Jarmo Virtamo Stephanie Weinstein Jacqueline Clavel Tongzhang Zheng Theodore R Holford Kenneth Offit Andrew Zelenetz Robert J Klein John J Spinelli Kimberly A Bertrand Francine Laden Edward Giovannucci Peter Kraft Anne Kricker Jenny Turner Claire M Vajdic Maria Grazia Ennas Giovanni M Ferri Lucia Miligi Liming Liang Joshua Sampson Simon Crouch Ju-Hyun Park Kari E North Angela Cox John A Snowden Josh Wright Angel Carracedo Carlos Lopez-Otin David Martin-Garcia Elias Campo Joseph F Fraumeni Silvia de Sanjose Henrik Hjalgrim James R Cerhan Stephen J Chanock Nathaniel Rothman Susan L Slager

Nat Genet 2013 Aug 16;45(8):868-76. Epub 2013 Jun 16.

Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), Bethesda, Maryland, USA.

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P=1.22×10(-14)), 18q21.33 (BCL2, P=7.76×10(-11)), 11p15.5 (C11orf21, P=2.15×10(-10)), 4q25 (LEF1, P=4.24×10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50×10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27×10(-8)), 18q21.32 (PMAIP1, P=2.51×10(-8)), 15q15.1 (BMF, P=2.71×10(-10)) and 2p22.2 (QPCT, P=1.68×10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08×10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

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http://dx.doi.org/10.1038/ng.2652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729927PMC
August 2013
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