Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

• Autoři: BERNDT Sonja I.; CAMP Nicola J.; SKIBOLA Christine F.; VIJAI Joseph; WANG Zhaoming; GU Jian; NIETERS Alexandra; KELLY Rachel S.; SMEDBY Karin E.; MONNEREAU Alain; COZEN Wendy; COX Angela; WANG Sophia S.; LAN Qing; TERAS Lauren R.; MACHADO Moara; YEAGER Meredith; BROOKS-WILSON Angela R.; HARTGE Patricia; PURDUE Mark P.; BIRMANN Brenda M.; VAJDIC Claire M.; COCCO Pierluigi; ZHANG Yawei; GILES Graham G.; ZELENIUCH-JACQUOTTE Anne; LAWRENCE Charles; MONTALVAN Rebecca; BURDETT Laurie; HUTCHINSON Amy; YE Yuanqing; CALL Timothy G.; SHANAFELT Tait D.; NOVAK Anne J.; KAY Neil E.; LIEBOW Mark; CUNNINGHAM Julie M.; ALLMER Cristine; HJALGRIM Henrik; ADAMI Hans-Olov; MELBYE Mads; GLIMELIUS Bengt; CHANG Ellen T.; GLENN Martha; CURTIN Karen; CANNON-ALBRIGHT Lisa A.; DIVER W. Ryan; LINK Brian K.; WEINER George J.; CONDE Lucia; BRACCI Paige M.; RIBY Jacques; ARNETT Donna K.; ZHI Degui; LEACH Justin M.; HOLLY Elizabeth A.; JACKSON Rebecca D.; TINKER Lesley F.; BENAVENTE Yolanda; SALA Núria; CASABONNE Delphine; BECKER Nikolaus; BOFFETTA Paolo; BRENNAN Paul; FORETOVÁ Lenka; MAYNADIE Marc; MCKAY James; STAINES Anthony; CHAFFEE Kari G.; ACHENBACH Sara J.; VACHON Celine M.; GOLDIN Lynn R.; STROM Sara S.; LEIS Jose F.; WEINBERG J. Brice; CAPORASO Neil E.; NORMAN Aaron D.; ROOS Anneclaire J De; MORTON Lindsay M.; SEVERSON Richard K.; RIBOLI Elio; VINEIS Paolo; KAAKS Rudolph; MASALA Giovanna; WEIDERPASS Elisabete; CHIRLAQUE María-Dolores; VERMEULEN Roel C. H.; TRAVIS Ruth C.; SOUTHEY Melissa C.; MILNE Roger L.; ALBANES Demetrius; VIRTAMO Jarmo; WEINSTEIN Stephanie; CLAVEL Jacqueline; ZHENG Tongzhang; HOLFORD Theodore R.; VILLANO Danylo J.; MARIA Ann; SPINELLI John J.; GASCOYNE Randy D.; CONNORS Joseph M.; BERTRAND Kimberly A.; GIOVANNUCCI Edward; KRAFT Peter; KRICKER Anne; TURNER Jenny; ENNAS Maria Grazia; FERRI Giovanni M.; MILIGI Lucia; LIANG Liming; MA Baoshan; HUANG Jinyan; CROUCH Simon; PARK Ju-Hyun; CHATTERJEE Nilanjan; NORTH Kari E.; SNOWDEN John A.; WRIGHT Josh; FRAUMENI Joseph F.; OFFIT Kenneth; WU Xifeng; SANJOSE Silvia de; CERHAN James R.; CHANOCK Stephen J.; ROTHMAN Nathaniel; SLAGER Susan L.
• Rok publikování: 2016
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: Nature Communications
• Fakulta / Pracoviště MU: Lékařská fakulta
• Doi: http://dx.doi.org/10.1038/ncomms10933
• Obor: Onkologie a hematologie
• Klíčová slova: TRANSCRIPTION FACTOR EOMESODERMIN; FAS GENE-MUTATIONS; SUSCEPTIBILITY LOCI; FOLLICULAR LYMPHOMA; RISK; VARIANTS; EXPRESSION; BANK1; PRIORITIZATION; CLASSIFICATION
• Popis: Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P = 2.55 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.