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

Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma.
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全基因组关联研究确定了弥漫性大B细胞淋巴瘤的多个易感基因座。

DOI:
10.1038/ng.3105
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发表时间:
2014-11
期刊:
影响因子:
30.8
通讯作者:
Chanock SJ
Chanock SJ
中科院分区:
生物学1区
文献类型:
--
作者:
Cerhan JR;Berndt SI;Vijai J;Ghesquières H;McKay J;Wang SS;Wang Z;Yeager M;Conde L;de Bakker PI;Nieters A;Cox D;Burdett L;Monnereau A;Flowers CR;De Roos AJ;Brooks-Wilson AR;Lan Q;Severi G;Melbye M;Gu J;Jackson RD;Kane E;Teras LR;Purdue MP;Vajdic CM;Spinelli JJ;Giles GG;Albanes D;Kelly RS;Zucca M;Bertrand KA;Zeleniuch-Jacquotte A;Lawrence C;Hutchinson A;Zhi D;Habermann TM;Link BK;Novak AJ;Dogan A;Asmann YW;Liebow M;Thompson CA;Ansell SM;Witzig TE;Weiner GJ;Veron AS;Zelenika D;Tilly H;Haioun C;Molina TJ;Hjalgrim H;Glimelius B;Adami HO;Bracci PM;Riby J;Smith MT;Holly EA;Cozen W;Hartge P;Morton LM;Severson RK;Tinker LF;North KE;Becker N;Benavente Y;Boffetta P;Brennan P;Foretova L;Maynadie M;Staines A;Lightfoot T;Crouch S;Smith A;Roman E;Diver WR;Offit K;Zelenetz A;Klein RJ;Villano DJ;Zheng T;Zhang Y;Holford TR;Kricker A;Turner J;Southey MC;Clavel J;Virtamo J;Weinstein S;Riboli E;Vineis P;Kaaks R;Trichopoulos D;Vermeulen RC;Boeing H;Tjonneland A;Angelucci E;Di Lollo S;Rais M;Birmann BM;Laden F;Giovannucci E;Kraft P;Huang J;Ma B;Ye Y;Chiu BC;Sampson J;Liang L;Park JH;Chung CC;Weisenburger DD;Chatterjee N;Fraumeni JF Jr;Slager SL;Wu X;de Sanjose S;Smedby KE;Salles G;Skibola CF;Rothman N;Chanock SJ

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弥漫性大B细胞淋巴瘤(DLBCL)是最常见的淋巴瘤亚型,临床上具有侵袭性。为了确定DLBCL的遗传易感性位点,我们对3项新的全基因组关联研究(GWAS)和1项既往扫描进行了荟萃分析,共计3,857例欧洲血统病例和7,666例对照,并对1,359例病例和4,557例对照中的9个有希望的SNP进行了额外的基因分型。在我们的多阶段分析中,四个位点的五个独立SNP达到了全基因组显著性,标记为6p 25的rs 116446171。(EXOC 2;P= 2.33 × 10−21),rs 2523607在6p21.33(HLA-B;P= 2.40 × 10−10),2p23.3处rs79480871(NCOA 1;P= 4.23 × 10−8)和两个独立的SNP,rs 13255292和rs 4733601,在8q24.21(PVT 1;P= 9.98 × 10− 13和3.63 × 10−11)。这些数据为这种B细胞恶性肿瘤的遗传易感性提供了大量的新证据,并指出了DLBCL发病机制中涉及免疫识别和免疫功能的途径。
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 × 10−13and 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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