Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma.
James R CerhanSonja I BerndtJoseph VijaiHervé GhesquièresJames McKaySophia S WangZhaoming WangMeredith YeagerLucia CondePaul I W de BakkerAlexandra NietersDavid CoxLaurie BurdettAlain MonnereauChristopher R FlowersAnneclaire J De RoosAngela R Brooks-WilsonQing LanGianluca SeveriMads MelbyeJian GuRebecca D JacksonEleanor KaneLauren R TerasMark P PurdueClaire M VajdicJohn J SpinelliGraham G GilesDemetrius AlbanesRachel S KellyMariagrazia ZuccaKimberly A BertrandAnne Zeleniuch-JacquotteCharles LawrenceAmy HutchinsonDegui ZhiThomas M HabermannBrian K LinkAnne J NovakAhmet DoganYan W AsmannMark LiebowCarrie A ThompsonStephen M AnsellThomas E WitzigGeorge J WeinerAmelie S VeronDiana ZelenikaHervé TillyCorinne HaiounThierry Jo MolinaHenrik HjalgrimBengt GlimeliusHans-Olov AdamiPaige M BracciJacques RibyMartyn T SmithElizabeth A HollyWendy CozenPatricia HartgeLindsay M MortonRichard K SeversonLesley F TinkerKari E NorthNikolaus BeckerYolanda BenaventePaolo BoffettaPaul BrennanLenka ForetovaMarc MaynadieAnthony StainesTracy LightfootSimon CrouchAlex SmithEve RomanW Ryan DiverKenneth OffitAndrew ZelenetzRobert J KleinDanylo J VillanoTongzhang ZhengYawei ZhangTheodore R HolfordAnne KrickerJenny TurnerMelissa C SoutheyJacqueline ClavelJarmo VirtamoStephanie WeinsteinElio RiboliPaolo VineisRudolph KaaksDimitrios TrichopoulosRoel C H VermeulenHeiner BoeingAnne TjonnelandEmanuele AngelucciSimonetta Di LolloMarco RaisBrenda M BirmannFrancine LadenEdward GiovannucciPeter KraftJinyan HuangBaoshan MaYuanqing YeBrian C H ChiuJoshua SampsonLiming LiangJu-Hyun ParkCharles C ChungDennis D WeisenburgerNilanjan ChatterjeeJoseph F FraumeniSusan L SlagerXifeng WuSilvia de SanjoseKarin E SmedbyGilles SallesChristine F SkibolaNathaniel RothmanStephen J ChanockPublished in: Nature genetics (2014)
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.