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

2013; Nature Portfolio; Volume: 45; Issue: 8 Linguagem: Inglês

10.1038/ng.2652

1546-1718

Sonja I. Berndt, Christine F. Skibola, Joseph Vijai, Nicola J. Camp, Alexandra Nieters, Zhaoming Wang, Wendy Cozen, Alain Monnereau, Sophia Wang, Rachel S. Kelly, Qing Lan, Lauren R. Teras, Nilanjan Chatterjee, Charles C. Chung, Meredith Yeager, Angela 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 Cannon‐Albright, Brandt Jones, W. Ryan Diver, Brian K. Link, George J. Weiner, Lucía 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 Foretová, Marc Maynadié, 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, José 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 Ríboli, Paolo Vineis, Rudolph Kaaks, Dimitrios Trichopoulos, Giovanna Masala, Elisabete Weiderpass, María‐Dolores Chirlaque, Roel Vermeulen, Ruth C. Travis, Graham G. Giles, Demetrius Albanes, Jarmo Virtamo, Stephanie J. Weinstein, Jacqueline Clavel, Tongzhang Zheng, Theodore R. Holford, Kenneth Offit, Andrew D. Zelenetz, Robert J. Klein, John J. Spinelli, Kimberly A. Bertrand, Francine Laden, Edward Giovannucci, Peter Kraft, Anne Kricker, Jennifer Turner, Claire M. Vajdic, Maria Grazia Ennas, Giovanni Maria Ferri, Lucia Miligi, Liming Liang, Joshua N. Sampson, Simon Crouch, Ju‐Hyun Park, Kari E. North, Angela Cox, John A. Snowden, Josh Wright, Ángel Carracedo, Carlos López‐Otín, Sı́lvia Beà, Itziar Salaverría, David Martin‐García, Elı́as Campo, Joseph F. Fraumeni, Sílvia de Sanjosé, Henrik Hjalgrim, James R. Cerhan, Stephen J. Chanock, Nathaniel Rothman, Susan L. Slager,

Genetic factors in colorectal cancer

Susan Slager and colleagues report a meta-analysis of genome-wide association studies for chronic lymphocytic leukemia (CLL). They identify nine loci newly associated with CLL. 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.