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; Mads Melbye

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 TurnerJohn 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, Mads Melbye

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

29 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Cancer Research
Vol/bind	78
Udgave nummer	14
Sider (fra-til)	4086-4096
Antal sider	11
ISSN	0008-5472
DOI	https://doi.org/10.1158/0008-5472.CAN-17-2900
Status	Udgivet - 2018

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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., ... Melbye, M. (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

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 & Melbye, M 2018, 'HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes', Cancer Research, bind 78, nr. 14, s. 4086-4096. https://doi.org/10.1158/0008-5472.CAN-17-2900

@article{cce4698c3a2146e297a9986e0f799efa,

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 Mads Melbye",

year = "2018",

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

language = "English",

volume = "78",

pages = "4086--4096",

journal = "Cancer Research",

issn = "0008-5472",

publisher = "American Association for Cancer Research",

number = "14",

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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 - Melbye, Mads

PY - 2018

Y1 - 2018

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.

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

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

M3 - Journal article

C2 - 29735552

AN - SCOPUS:85050829279

SN - 0008-5472

VL - 78

SP - 4086

EP - 4096

JO - Cancer Research

JF - Cancer Research

IS - 14

ER -