HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes

Sophia S. Wang; Mary Carrington; Sonja I. Berndt; Susan L. Slager; Paige M. Bracci; Jenna Voutsinas; James R. Cerhan; Karin E. Smedby; Henrik Hjalgrim; Joseph Vijai; Lindsay M. Morton; Roel Vermeulen; Ora Paltiel; Claire M. Vajdic; Martha S. Linet; Alexandra Nieters; Silvia de Sanjose; Wendy Cozen; Elizabeth E. Brown; Jennifer Turner; John J. Spinelli; Tongzhang Zheng; Brenda M. Birmann; Christopher R. Flowers; Nikolaus Becker; Elizabeth A. Holly; Eleanor Kane; Dennis Weisenburger; Marc Maynadie; Pierluigi Cocco; Demetrius Albanes; Stephanie J. Weinstein; Lauren R. Teras; W. Ryan Diver; Stephanie J. Lax; Ruth C. Travis; Rudolph Kaaks; Elio Riboli; Yolanda Benavente; Paul Brennan; James McKay; Marie Hélène Delfau-Larue; Brian K. Link; Corrado Magnani; Maria Grazia Ennas; Giancarlo Latte; Andrew L. Feldman; Nicole Wong Doo; Graham G. Giles; Melissa C. Southey; Roger L. Milne; Kenneth Offit; Jacob Musinsky; Alan A. Arslan; Mark P. Purdue; Hans Olov Adami; Mads Melbye; Bengt Glimelius; Lucia Conde; Nicola J. Camp; Martha Glenn; Karen Curtin; Jacqueline Clavel; Alain Monnereau; David G. Cox; Hervé Ghesquières; Gilles Salles; Paulo Bofetta; Lenka Foretova; Anthony Staines; Scott Davis; Richard K. Severson; Qing Lan; Angela Brooks-Wilson; Martyn T. Smith; Eve Roman; Anne Kricker; Yawei Zhang; Peter Kraft; Stephen J. Chanock; Nathaniel Rothman; Patricia Hartge; Christine F. Skibola

doi:10.1158/0008-5472.CAN-17-2900

HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes

Sophia S. Wang
, Mary Carrington
, Sonja I. Berndt
, Susan L. Slager
, Paige M. Bracci
, Jenna Voutsinas
, James R. Cerhan
, Karin E. Smedby
, Henrik Hjalgrim
, Joseph Vijai
, Lindsay M. Morton
, Roel Vermeulen
, Ora Paltiel
, Claire M. Vajdic
, Martha S. Linet
, Alexandra Nieters
, Silvia de Sanjose
, Wendy Cozen
, Elizabeth E. Brown
, Jennifer Turner

John J. Spinelli, Tongzhang Zheng, Brenda M. Birmann, Christopher R. Flowers, Nikolaus Becker, Elizabeth A. Holly, Eleanor Kane, Dennis Weisenburger, Marc Maynadie, Pierluigi Cocco, Demetrius Albanes, Stephanie J. Weinstein, Lauren R. Teras, W. Ryan Diver, Stephanie J. Lax, Ruth C. Travis, Rudolph Kaaks, Elio Riboli, Yolanda Benavente, Paul Brennan, James McKay, Marie Hélène Delfau-Larue, Brian K. Link, Corrado Magnani, Maria Grazia Ennas, Giancarlo Latte, Andrew L. Feldman, Nicole Wong Doo, Graham G. Giles, Melissa C. Southey, Roger L. Milne, Kenneth Offit, Jacob Musinsky, Alan A. Arslan, Mark P. Purdue, Hans Olov Adami, Mads Melbye, Bengt Glimelius, Lucia Conde, Nicola J. Camp, Martha Glenn, Karen Curtin, Jacqueline Clavel, Alain Monnereau, David G. Cox, Hervé Ghesquières, Gilles Salles, Paulo Bofetta, Lenka Foretova, Anthony Staines, Scott Davis, Richard K. Severson, Qing Lan, Angela Brooks-Wilson, Martyn T. Smith, Eve Roman, Anne Kricker, Yawei Zhang, Peter Kraft, Stephen J. Chanock, Nathaniel Rothman, Patricia Hartge, Christine F. Skibola

Beckman Research Institute and the City of Hope
Leidos Inc
Massachusetts Institute of Technology
National Institutes of Health
Mayo Clinic Rochester, MN
University of California at San Francisco
Karolinska Institutet
Statens Serum Institut
Memorial Sloan-Kettering Cancer Center
Utrecht University
Hadassah University Medical Centre
University of New South Wales
University of Freiburg
Bellvitge Biomedical Research Institute
CIBER Epidemiología y Salud Pública (CIBERESP)
University of Southern California
University of Alabama at Birmingham
Macquarie University
Provincial Health Services Authority
University of British Columbia
Brown University
Harvard University
Emory University
German Cancer Research Center
University of York
City of Hope National Med Center
Université de Bourgogne
University of Cagliari
American Cancer Society
University of Oxford
Imperial College London
International Agency for Research on Cancer
Hôpital Henri Mondor
University of Iowa
University of Eastern Piedmont
ATS Sardegna - ASSL Nuoro
Cancer Council Victoria
University of Melbourne
Rishospitalet
New York University
Stanford University
Uppsala University
University College London
University of Utah
Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS)
Université Paris Cité
Institut national de la santé et de la recherche médicale
CNRS
Hospices civils de Lyon
Masaryk Memorial Cancer Institute
Dublin City University
University of Washington
Wayne State University
Simon Fraser University
University of California at Berkeley
The University of Sydney
Yale University

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma.

Original language	English
Pages (from-to)	4086-4096
Number of pages	11
Journal	Cancer Research
Volume	78
Issue number	14
DOIs	https://doi.org/10.1158/0008-5472.CAN-17-2900
State	Published - Jul 15 2018

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10.1158/0008-5472.CAN-17-2900

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Wang, S. S., Carrington, M., Berndt, S. I., Slager, S. L., Bracci, P. M., Voutsinas, J., Cerhan, J. R., Smedby, K. E., Hjalgrim, H., Vijai, J., Morton, L. M., Vermeulen, R., Paltiel, O., Vajdic, C. M., Linet, M. S., Nieters, A., de Sanjose, S., Cozen, W., Brown, E. E., ... Skibola, C. F. (2018). HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes. Cancer Research, 78(14), 4086-4096. https://doi.org/10.1158/0008-5472.CAN-17-2900

@article{41102a30d40e409cb090f850f28ac48a,

title = "HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes",

abstract = "A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of {"}heterozygote advantage{"} regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95\% CI = 1.06–1.60; OR MZL = 1.45, 95\% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95\% CI = 1.24–3.55; OR MZL = 2.10, 95\% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma.",

author = "Wang, \{Sophia S.\} and Mary Carrington and Berndt, \{Sonja I.\} and Slager, \{Susan L.\} and Bracci, \{Paige M.\} and Jenna Voutsinas and Cerhan, \{James R.\} and Smedby, \{Karin E.\} and Henrik Hjalgrim and Joseph Vijai and Morton, \{Lindsay M.\} and Roel Vermeulen and Ora Paltiel and Vajdic, \{Claire M.\} and Linet, \{Martha S.\} and Alexandra Nieters and \{de Sanjose\}, Silvia and Wendy Cozen and Brown, \{Elizabeth E.\} and Jennifer Turner and Spinelli, \{John J.\} and Tongzhang Zheng and Birmann, \{Brenda M.\} and Flowers, \{Christopher R.\} and Nikolaus Becker and Holly, \{Elizabeth A.\} and Eleanor Kane and Dennis Weisenburger and Marc Maynadie and Pierluigi Cocco and Demetrius Albanes and Weinstein, \{Stephanie J.\} and Teras, \{Lauren R.\} and Diver, \{W. Ryan\} and Lax, \{Stephanie J.\} and Travis, \{Ruth C.\} and Rudolph Kaaks and Elio Riboli and Yolanda Benavente and Paul Brennan and James McKay and Delfau-Larue, \{Marie H{\'e}l{\`e}ne\} and Link, \{Brian K.\} and Corrado Magnani and Ennas, \{Maria Grazia\} and Giancarlo Latte and Feldman, \{Andrew L.\} and Doo, \{Nicole Wong\} and Giles, \{Graham G.\} and Southey, \{Melissa C.\} and Milne, \{Roger L.\} and Kenneth Offit and Jacob Musinsky and Arslan, \{Alan A.\} and Purdue, \{Mark P.\} and Adami, \{Hans Olov\} and Mads Melbye and Bengt Glimelius and Lucia Conde and Camp, \{Nicola J.\} and Martha Glenn and Karen Curtin and Jacqueline Clavel and Alain Monnereau and Cox, \{David G.\} and Herv{\'e} Ghesqui{\`e}res and Gilles Salles and Paulo Bofetta and Lenka Foretova and Anthony Staines and Scott Davis and Severson, \{Richard K.\} and Qing Lan and Angela Brooks-Wilson and Smith, \{Martyn T.\} and Eve Roman and Anne Kricker and Yawei Zhang and Peter Kraft and Chanock, \{Stephen J.\} and Nathaniel Rothman and Patricia Hartge and Skibola, \{Christine F.\}",

note = "Publisher Copyright: {\textcopyright} 2018 American Association for Cancer Research.",

year = "2018",

month = jul,

day = "15",

doi = "10.1158/0008-5472.CAN-17-2900",

language = "English",

volume = "78",

pages = "4086--4096",

journal = "Cancer Research",

issn = "0008-5472",

number = "14",

}

Wang, SS, Carrington, M, Berndt, SI, Slager, SL, Bracci, PM, Voutsinas, J, Cerhan, JR, Smedby, KE, Hjalgrim, H, Vijai, J, Morton, LM, Vermeulen, R, Paltiel, O, Vajdic, CM, Linet, MS, Nieters, A, de Sanjose, S, Cozen, W, Brown, EE, Turner, J, Spinelli, JJ, Zheng, T, Birmann, BM, Flowers, CR, Becker, N, Holly, EA, Kane, E, Weisenburger, D, Maynadie, M, Cocco, P, Albanes, D, Weinstein, SJ, Teras, LR, Diver, WR, Lax, SJ, Travis, RC, Kaaks, R, Riboli, E, Benavente, Y, Brennan, P, McKay, J, Delfau-Larue, MH, Link, BK, Magnani, C, Ennas, MG, Latte, G, Feldman, AL, Doo, NW, Giles, GG, Southey, MC, Milne, RL, Offit, K, Musinsky, J, Arslan, AA, Purdue, MP, Adami, HO, Melbye, M, Glimelius, B, Conde, L, Camp, NJ, Glenn, M, Curtin, K, Clavel, J, Monnereau, A, Cox, DG, Ghesquières, H, Salles, G, Bofetta, P, Foretova, L, Staines, A, Davis, S, Severson, RK, Lan, Q, Brooks-Wilson, A, Smith, MT, Roman, E, Kricker, A, Zhang, Y, Kraft, P, Chanock, SJ, Rothman, N, Hartge, P & Skibola, CF 2018, 'HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes', Cancer Research, vol. 78, no. 14, pp. 4086-4096. https://doi.org/10.1158/0008-5472.CAN-17-2900

TY - JOUR

T1 - HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes

AU - Wang, Sophia S.

AU - Carrington, Mary

AU - Berndt, Sonja I.

AU - Slager, Susan L.

AU - Bracci, Paige M.

AU - Voutsinas, Jenna

AU - Cerhan, James R.

AU - Smedby, Karin E.

AU - Hjalgrim, Henrik

AU - Vijai, Joseph

AU - Morton, Lindsay M.

AU - Vermeulen, Roel

AU - Paltiel, Ora

AU - Vajdic, Claire M.

AU - Linet, Martha S.

AU - Nieters, Alexandra

AU - de Sanjose, Silvia

AU - Cozen, Wendy

AU - Brown, Elizabeth E.

AU - Turner, Jennifer

AU - Spinelli, John J.

AU - Zheng, Tongzhang

AU - Birmann, Brenda M.

AU - Flowers, Christopher R.

AU - Becker, Nikolaus

AU - Holly, Elizabeth A.

AU - Kane, Eleanor

AU - Weisenburger, Dennis

AU - Maynadie, Marc

AU - Cocco, Pierluigi

AU - Albanes, Demetrius

AU - Weinstein, Stephanie J.

AU - Teras, Lauren R.

AU - Diver, W. Ryan

AU - Lax, Stephanie J.

AU - Travis, Ruth C.

AU - Kaaks, Rudolph

AU - Riboli, Elio

AU - Benavente, Yolanda

AU - Brennan, Paul

AU - McKay, James

AU - Delfau-Larue, Marie Hélène

AU - Link, Brian K.

AU - Magnani, Corrado

AU - Ennas, Maria Grazia

AU - Latte, Giancarlo

AU - Feldman, Andrew L.

AU - Doo, Nicole Wong

AU - Giles, Graham G.

AU - Southey, Melissa C.

AU - Milne, Roger L.

AU - Offit, Kenneth

AU - Musinsky, Jacob

AU - Arslan, Alan A.

AU - Purdue, Mark P.

AU - Adami, Hans Olov

AU - Melbye, Mads

AU - Glimelius, Bengt

AU - Conde, Lucia

AU - Camp, Nicola J.

AU - Glenn, Martha

AU - Curtin, Karen

AU - Clavel, Jacqueline

AU - Monnereau, Alain

AU - Cox, David G.

AU - Ghesquières, Hervé

AU - Salles, Gilles

AU - Bofetta, Paulo

AU - Foretova, Lenka

AU - Staines, Anthony

AU - Davis, Scott

AU - Severson, Richard K.

AU - Lan, Qing

AU - Brooks-Wilson, Angela

AU - Smith, Martyn T.

AU - Roman, Eve

AU - Kricker, Anne

AU - Zhang, Yawei

AU - Kraft, Peter

AU - Chanock, Stephen J.

AU - Rothman, Nathaniel

AU - Hartge, Patricia

AU - Skibola, Christine F.

PY - 2018/7/15

Y1 - 2018/7/15

N2 - A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma.

AB - A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma.

UR - https://www.scopus.com/pages/publications/85050829279

U2 - 10.1158/0008-5472.CAN-17-2900

DO - 10.1158/0008-5472.CAN-17-2900

M3 - Article

C2 - 29735552

AN - SCOPUS:85050829279

SN - 0008-5472

VL - 78

SP - 4086

EP - 4096

JO - Cancer Research

JF - Cancer Research

IS - 14

ER -

HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes

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