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

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

doi:10.1038/ng.3105

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

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

School of Medicine

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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	https://doi.org/10.1038/ng.3105
State	Published - Nov 5 2014

ASJC Scopus subject areas

Genetics

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Cerhan, J. R., Berndt, S. I., Vijai, J., Ghesquières, H., McKay, J., Wang, S. S., Wang, Z., Yeager, M., Conde, L., De Bakker, P. I. W., Nieters, A., Cox, D., Burdett, L., Monnereau, A., Flowers, C. R., De Roos, A. J., Brooks-Wilson, A. R., Lan, Q., Severi, G., ... Chanock, S. J. (2014). Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma. Nature genetics, 46(11), 1233-1238. https://doi.org/10.1038/ng.3105

Cerhan, JR, Berndt, SI, Vijai, J, Ghesquières, H, McKay, J, Wang, SS, Wang, Z, Yeager, M, Conde, L, De Bakker, PIW, 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, RCH, 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, BCH, Sampson, J, Liang, L, Park, JH, Chung, CC, Weisenburger, DD, Chatterjee, N, Fraumeni, JF, Slager, SL, Wu, X, De Sanjose, S, Smedby, KE, Salles, G, Skibola, CF, Rothman, N & Chanock, SJ 2014, 'Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma', Nature genetics, vol. 46, no. 11, pp. 1233-1238. https://doi.org/10.1038/ng.3105

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title = "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.",

author = "Cerhan, {James R.} and Berndt, {Sonja I.} and Joseph Vijai and Herv{\'e} Ghesqui{\`e}res and James McKay and Wang, {Sophia S.} and Zhaoming Wang and Meredith Yeager and Lucia Conde and {De Bakker}, {Paul I.W.} and Alexandra Nieters and David Cox and Laurie Burdett and Alain Monnereau and Flowers, {Christopher R.} and {De Roos}, {Anneclaire J.} and Brooks-Wilson, {Angela R.} and Qing Lan and Gianluca Severi and Mads Melbye and Jian Gu and Jackson, {Rebecca D.} and Eleanor Kane and Teras, {Lauren R.} and Purdue, {Mark P.} and Vajdic, {Claire M.} and Spinelli, {John J.} and Giles, {Graham G.} and Demetrius Albanes and Kelly, {Rachel S.} and Mariagrazia Zucca and Bertrand, {Kimberly A.} and Anne Zeleniuch-Jacquotte and Charles Lawrence and Amy Hutchinson and Degui Zhi and Habermann, {Thomas M.} and Link, {Brian K.} and Novak, {Anne J.} and Ahmet Dogan and Asmann, {Yan W.} and Mark Liebow and Thompson, {Carrie A.} and Ansell, {Stephen M.} and Witzig, {Thomas E.} and Weiner, {George J.} and Veron, {Amelie S.} and Diana Zelenika and Herv{\'e} Tilly and Corinne Haioun and Molina, {Thierry Jo} and Henrik Hjalgrim and Bengt Glimelius and Adami, {Hans Olov} and Bracci, {Paige M.} and Jacques Riby and Smith, {Martyn T.} and Holly, {Elizabeth A.} and Wendy Cozen and Patricia Hartge and Morton, {Lindsay M.} and Severson, {Richard K.} and Tinker, {Lesley F.} and North, {Kari E.} and Nikolaus Becker and Yolanda Benavente and Paolo Boffetta and Paul Brennan and Lenka Foretova and Marc Maynadie and Anthony Staines and Tracy Lightfoot and Simon Crouch and Alex Smith and Eve Roman and Diver, {W. Ryan} and Kenneth Offit and Andrew Zelenetz and Klein, {Robert J.} and Villano, {Danylo J.} and Tongzhang Zheng and Yawei Zhang and Holford, {Theodore R.} and Anne Kricker and Jenny Turner and Southey, {Melissa C.} and Jacqueline Clavel and Jarmo Virtamo and Stephanie Weinstein and Elio Riboli and Paolo Vineis and Rudolph Kaaks and Dimitrios Trichopoulos and Vermeulen, {Roel C.H.} and Heiner Boeing and Anne Tjonneland and Emanuele Angelucci and {Di Lollo}, Simonetta and Marco Rais and Birmann, {Brenda M.} and Francine Laden and Edward Giovannucci and Peter Kraft and Jinyan Huang and Baoshan Ma and Yuanqing Ye and Chiu, {Brian C.H.} and Joshua Sampson and Liming Liang and Park, {Ju Hyun} and Chung, {Charles C.} and Weisenburger, {Dennis D.} and Nilanjan Chatterjee and Fraumeni, {Joseph F.} and Slager, {Susan L.} and Xifeng Wu and {De Sanjose}, Silvia and Smedby, {Karin E.} and Gilles Salles and Skibola, {Christine F.} and Nathaniel Rothman and Chanock, {Stephen J.}",

year = "2014",

month = nov,

day = "5",

doi = "10.1038/ng.3105",

language = "English (US)",

volume = "46",

pages = "1233--1238",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "11",

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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.

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.

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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

SN - 1061-4036

VL - 46

SP - 1233

EP - 1238

JO - Nature genetics

JF - Nature genetics

IS - 11

ER -

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

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