Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

全基因组关联研究鉴定出弥漫性大B细胞淋巴瘤的多个易感基因位点

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作者：Cerhan,James R,Berndt,Sonja I,Vijai,Joseph,Ghesquières,Hervé,McKay,James,Wang,Sophia S,Wang,Zhaoming,Yeager,Meredith,Conde,Lucia,de Bakker,Paul I W,Nieters,Alexandra,Cox,David,Burdett,Laurie,Monnereau,Alain,Flowers,Christopher R,De Roos,Anneclaire J,Brooks-Wilson,Angela R,Lan,Qing,Severi,Gianluca,Melbye,Mads,Gu,Jian,Jackson,Rebecca D,Kane,Eleanor,Teras,Lauren R,Purdue,Mark P,Vajdic,Claire M,Spinelli,John J,Giles,Graham G,Albanes,Demetrius,Kelly,Rachel S,Zucca,Mariagrazia,Bertrand,Kimberly A,Zeleniuch-Jacquotte,Anne,Lawrence,Charles,Hutchinson,Amy,Zhi,Degui,Habermann,Thomas M,Link,Brian K,Novak,Anne J,Dogan,Ahmet,Asmann,Yan W,Liebow,Mark,Thompson,Carrie A,Ansell,Stephen M,Witzig,Thomas E,Weiner,George J,Veron,Amelie S,Zelenika,Diana,Tilly,Hervé,Haioun,Corinne,Molina,Thierry Jo,Hjalgrim,Henrik,Glimelius,Bengt,Adami,Hans-Olov,Bracci,Paige M,Riby,Jacques,Smith,Martyn T,Holly,Elizabeth A,Cozen,Wendy,Hartge,Patricia,Morton,Lindsay M,Severson,Richard K,Tinker,Lesley F,North,Kari E,Becker,Nikolaus,Benavente,Yolanda,Boffetta,Paolo,Brennan,Paul,Foretova,Lenka,Maynadie,Marc,Staines,Anthony,Lightfoot,Tracy,Crouch,Simon,Smith,Alex,Roman,Eve,Diver,W Ryan,Offit,Kenneth,Zelenetz,Andrew,Klein,Robert J,Villano,Danylo J,Zheng,Tongzhang,Zhang,Yawei,Holford,Theodore R,Kricker,Anne,Turner,Jenny,Southey,Melissa C,Clavel,Jacqueline,Virtamo,Jarmo,Weinstein,Stephanie,Riboli,Elio,Vineis,Paolo,Kaaks,Rudolph,Trichopoulos,Dimitrios,Vermeulen,Roel C H,Boeing,Heiner,Tjonneland,Anne,Angelucci,Emanuele,Di Lollo,Simonetta,Rais,Marco,Birmann,Brenda M,Laden,Francine,Giovannucci,Edward,Kraft,Peter,Huang,Jinyan,Ma,Baoshan,Ye,Yuanqing,Chiu,Brian C H,Sampson,Joshua,Liang,Liming,Park,Ju-Hyun,Chung,Charles C,Weisenburger,Dennis D,Chatterjee,Nilanjan,Fraumeni,Joseph F Jr,Slager,Susan L,Wu,Xifeng,de Sanjose,Silvia,Smedby,Karin E,Salles,Gilles,Skibola,Christine F,Rothman,Nathaniel,Chanock,Stephen J
期刊：Nature Genetics影响因子：29.000
时间：2014起止号：2014 Nov;46(11):1233-8
doi：10.1038/ng.3105研究方向： 细胞生物学、免疫/内分泌
疾病类型： 淋巴瘤细胞类型： B细胞

Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.

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