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.
Original language | English (US) |
---|---|
Pages (from-to) | 1233-1238 |
Number of pages | 6 |
Journal | Nature genetics |
Volume | 46 |
Issue number | 11 |
DOIs | |
State | Published - Nov 5 2014 |
ASJC Scopus subject areas
- Genetics
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Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma. / 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.; Slager, Susan L.; Wu, Xifeng; De Sanjose, Silvia; Smedby, Karin E.; Salles, Gilles; Skibola, Christine F.; Rothman, Nathaniel; Chanock, Stephen J.
In: Nature genetics, Vol. 46, No. 11, 05.11.2014, p. 1233-1238.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma
AU - Cerhan, James R.
AU - Berndt, Sonja I.
AU - Vijai, Joseph
AU - Ghesquières, Hervé
AU - McKay, James
AU - Wang, Sophia S.
AU - Wang, Zhaoming
AU - Yeager, Meredith
AU - Conde, Lucia
AU - De Bakker, Paul I.W.
AU - Nieters, Alexandra
AU - Cox, David
AU - Burdett, Laurie
AU - Monnereau, Alain
AU - Flowers, Christopher R.
AU - De Roos, Anneclaire J.
AU - Brooks-Wilson, Angela R.
AU - Lan, Qing
AU - Severi, Gianluca
AU - Melbye, Mads
AU - Gu, Jian
AU - Jackson, Rebecca D.
AU - Kane, Eleanor
AU - Teras, Lauren R.
AU - Purdue, Mark P.
AU - Vajdic, Claire M.
AU - Spinelli, John J.
AU - Giles, Graham G.
AU - Albanes, Demetrius
AU - Kelly, Rachel S.
AU - Zucca, Mariagrazia
AU - Bertrand, Kimberly A.
AU - Zeleniuch-Jacquotte, Anne
AU - Lawrence, Charles
AU - Hutchinson, Amy
AU - Zhi, Degui
AU - Habermann, Thomas M.
AU - Link, Brian K.
AU - Novak, Anne J.
AU - Dogan, Ahmet
AU - Asmann, Yan W.
AU - Liebow, Mark
AU - Thompson, Carrie A.
AU - Ansell, Stephen M.
AU - Witzig, Thomas E.
AU - Weiner, George J.
AU - Veron, Amelie S.
AU - Zelenika, Diana
AU - Tilly, Hervé
AU - Haioun, Corinne
AU - Molina, Thierry Jo
AU - Hjalgrim, Henrik
AU - Glimelius, Bengt
AU - Adami, Hans Olov
AU - Bracci, Paige M.
AU - Riby, Jacques
AU - Smith, Martyn T.
AU - Holly, Elizabeth A.
AU - Cozen, Wendy
AU - Hartge, Patricia
AU - Morton, Lindsay M.
AU - Severson, Richard K.
AU - Tinker, Lesley F.
AU - North, Kari E.
AU - Becker, Nikolaus
AU - Benavente, Yolanda
AU - Boffetta, Paolo
AU - Brennan, Paul
AU - Foretova, Lenka
AU - Maynadie, Marc
AU - Staines, Anthony
AU - Lightfoot, Tracy
AU - Crouch, Simon
AU - Smith, Alex
AU - Roman, Eve
AU - Diver, W. Ryan
AU - Offit, Kenneth
AU - Zelenetz, Andrew
AU - Klein, Robert J.
AU - Villano, Danylo J.
AU - Zheng, Tongzhang
AU - Zhang, Yawei
AU - Holford, Theodore R.
AU - Kricker, Anne
AU - Turner, Jenny
AU - Southey, Melissa C.
AU - Clavel, Jacqueline
AU - Virtamo, Jarmo
AU - Weinstein, Stephanie
AU - Riboli, Elio
AU - Vineis, Paolo
AU - Kaaks, Rudolph
AU - Trichopoulos, Dimitrios
AU - Vermeulen, Roel C.H.
AU - Boeing, Heiner
AU - Tjonneland, Anne
AU - Angelucci, Emanuele
AU - Di Lollo, Simonetta
AU - Rais, Marco
AU - Birmann, Brenda M.
AU - Laden, Francine
AU - Giovannucci, Edward
AU - Kraft, Peter
AU - Huang, Jinyan
AU - Ma, Baoshan
AU - Ye, Yuanqing
AU - Chiu, Brian C.H.
AU - Sampson, Joshua
AU - Liang, Liming
AU - Park, Ju Hyun
AU - Chung, Charles C.
AU - Weisenburger, Dennis D.
AU - Chatterjee, Nilanjan
AU - Fraumeni, Joseph F.
AU - Slager, Susan L.
AU - Wu, Xifeng
AU - De Sanjose, Silvia
AU - Smedby, Karin E.
AU - Salles, Gilles
AU - Skibola, Christine F.
AU - Rothman, Nathaniel
AU - Chanock, Stephen J.
N1 - Funding Information: We thank C. Allmer, E. Angelucci, A. Bigelow, S. Buehler, K. Butterbach, A. Chabrier, J.M. Conners, M. Corines, M. Cornelis, K. Corsano, H. Dykes, L. Ershler, A. Gabbas, R.P. Gallagher, R.D. Gascoyne, P. Hui, L. Irish, L. Jacobus, L. Klareskog, A.S. Lai, J. Lunde, M. McAdams, R. Montalvan, L. Padyukov, M. Rais, T. Rattle, L. Rigacci, K. Snyder, G. Specchia, M. Stagner, G. Thomas, C. Tornow, G. Wood and M. Yang. The overall GWAS project was supported by the Intramural Program of the US National Institutes of Health/National Cancer Institute. A list of support provided to individual studies appears in the Supplementary Note. Publisher Copyright: © 2014 Nature America, Inc. All rights reserved.
PY - 2014/11/5
Y1 - 2014/11/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84908886283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908886283&partnerID=8YFLogxK
U2 - 10.1038/ng.3105
DO - 10.1038/ng.3105
M3 - Article
C2 - 25261932
AN - SCOPUS:84908886283
VL - 46
SP - 1233
EP - 1238
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 11
ER -