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

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.

SUBMITTER: Cerhan JR 

PROVIDER: S-EPMC4213349 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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

Cerhan James R JR   Berndt Sonja I SI   Vijai Joseph J   Ghesquières Hervé H   McKay James J   Wang Sophia S SS   Wang Zhaoming Z   Yeager Meredith M   Conde Lucia L   de Bakker Paul I W PI   Nieters Alexandra A   Cox David D   Burdett Laurie L   Monnereau Alain A   Flowers Christopher R CR   De Roos Anneclaire J AJ   Brooks-Wilson Angela R AR   Lan Qing Q   Severi Gianluca G   Melbye Mads M   Gu Jian J   Jackson Rebecca D RD   Kane Eleanor E   Teras Lauren R LR   Purdue Mark P MP   Vajdic Claire M CM   Spinelli John J JJ   Giles Graham G GG   Albanes Demetrius D   Kelly Rachel S RS   Zucca Mariagrazia M   Bertrand Kimberly A KA   Zeleniuch-Jacquotte Anne A   Lawrence Charles C   Hutchinson Amy A   Zhi Degui D   Habermann Thomas M TM   Link Brian K BK   Novak Anne J AJ   Dogan Ahmet A   Asmann Yan W YW   Liebow Mark M   Thompson Carrie A CA   Ansell Stephen M SM   Witzig Thomas E TE   Weiner George J GJ   Veron Amelie S AS   Zelenika Diana D   Tilly Hervé H   Haioun Corinne C   Molina Thierry Jo TJ   Hjalgrim Henrik H   Glimelius Bengt B   Adami Hans-Olov HO   Bracci Paige M PM   Riby Jacques J   Smith Martyn T MT   Holly Elizabeth A EA   Cozen Wendy W   Hartge Patricia P   Morton Lindsay M LM   Severson Richard K RK   Tinker Lesley F LF   North Kari E KE   Becker Nikolaus N   Benavente Yolanda Y   Boffetta Paolo P   Brennan Paul P   Foretova Lenka L   Maynadie Marc M   Staines Anthony A   Lightfoot Tracy T   Crouch Simon S   Smith Alex A   Roman Eve E   Diver W Ryan WR   Offit Kenneth K   Zelenetz Andrew A   Klein Robert J RJ   Villano Danylo J DJ   Zheng Tongzhang T   Zhang Yawei Y   Holford Theodore R TR   Kricker Anne A   Turner Jenny J   Southey Melissa C MC   Clavel Jacqueline J   Virtamo Jarmo J   Weinstein Stephanie S   Riboli Elio E   Vineis Paolo P   Kaaks Rudolph R   Trichopoulos Dimitrios D   Vermeulen Roel C H RC   Boeing Heiner H   Tjonneland Anne A   Angelucci Emanuele E   Di Lollo Simonetta S   Rais Marco M   Birmann Brenda M BM   Laden Francine F   Giovannucci Edward E   Kraft Peter P   Huang Jinyan J   Ma Baoshan B   Ye Yuanqing Y   Chiu Brian C H BC   Sampson Joshua J   Liang Liming L   Park Ju-Hyun JH   Chung Charles C CC   Weisenburger Dennis D DD   Chatterjee Nilanjan N   Fraumeni Joseph F JF   Slager Susan L SL   Wu Xifeng X   de Sanjose Silvia S   Smedby Karin E KE   Salles Gilles G   Skibola Christine F CF   Rothman Nathaniel N   Chanock Stephen J SJ  

Nature genetics 20140928 11

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 marke  ...[more]

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