Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region

• Published in: American journal of human genetics Vol. 95; no. 4; pp. 462 - 471
• Main Authors: Skibola, Christine F., Berndt, Sonja I., Vijai, Joseph, Conde, Lucia, Wang, Zhaoming, Yeager, Meredith, de Bakker, Paul I.W., Birmann, Brenda M., Vajdic, Claire M., Foo, Jia-Nee, Bracci, Paige M., Vermeulen, Roel C.H., Slager, Susan L., de Sanjose, Silvia, Linet, Martha S., Salles, Gilles, Lan, Qing, Severi, Gianluca, Hjalgrim, Henrik, Lightfoot, Tracy, Melbye, Mads, Gu, Jian, Ghesquières, Hervé, Link, Brian K., Morton, Lindsay M., Holly, Elizabeth A., Smith, Alex, Tinker, Lesley F., Teras, Lauren R., Kricker, Anne, Becker, Nikolaus, Zhang, Yawei, Giles, Graham G., Vineis, Paolo, Monnereau, Alain, Bertrand, Kimberly A., Albanes, Demetrius, Zeleniuch-Jacquotte, Anne, Gabbas, Attilio, Chung, Charles C., Burdett, Laurie, Hutchinson, Amy, Lawrence, Charles, Montalvan, Rebecca, Liang, Liming, Huang, Jinyan, Ma, Baoshan, Liu, Jianjun, Adami, Hans-Olov, Glimelius, Bengt, Ye, Yuanqing, Nowakowski, Grzegorz S., Thompson, Carrie A., Habermann, Thomas M., Novak, Anne J., Liebow, Mark, Witzig, Thomas E., Weiner, George J., Schenk, Maryjean, Hartge, Patricia, De Roos, Anneclaire J., Cozen, Wendy, Zhi, Degui, Akers, Nicholas K., Riby, Jacques, Smith, Martyn T., Lacher, Mortimer, Roman, Eve, Kane, Eleanor, Jackson, Rebecca D., North, Kari E., Diver, W. Ryan, Turner, Jenny, Armstrong, Bruce K., Benavente, Yolanda, Boffetta, Paolo, Foretova, Lenka, Maynadie, Marc, Staines, Anthony, McKay, James, Zheng, Tongzhang, Holford, Theodore R., Chamosa, Saioa, Kaaks, Rudolph, Kelly, Rachel S., Ohlsson, Bodil, Travis, Ruth C., Weiderpass, Elisabete, Clavel, Jacqueline, Giovannucci, Edward, Kraft, Peter, Mazza, Patrizio, Cocco, Pierluigi, Chiu, Brian C.H., Fraumeni, Joseph F., Offit, Kenneth, Wu, Xifeng, Cerhan, James R., Smedby, Karin E., Chanock, Stephen J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.10.2014; Cell Press; Elsevier
• Subjects: Alleles; Amino acids; Antigens; Basic Medicine; Biomarkers, Tumor - genetics; Case-Control Studies; Chromosomes, Human - genetics; Gene loci; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Genomics; Haplotypes - genetics; HLA Antigens - genetics; Humans; Leukocytes; Lymphoma; Lymphoma, Follicular - genetics; Medical and Health Sciences; Medical Genetics; Medical Genetics and Genomics (including Gene Therapy); Medicin och hälsovetenskap; Medicinsk genetik; Medicinsk genetik och genomik (Här ingår: Genterapi); Medicinska och farmaceutiska grundvetenskaper; Polymorphism, Single Nucleotide - genetics
• ISSN: 0002-9297; 1537-6605; 1537-6605
• DOI: 10.1016/j.ajhg.2014.09.004

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10−20) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10−11) near ETS1; 3q28 (rs6444305, p = 1.10 × 10−10) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10−10) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10−8) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10−67 to 2.67 × 10−70). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 × 10−16) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 × 10−9). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.