A novel risk locus at 6p21.3 for Epstein-Barr virus positive Hodgkin lymphoma

Manon Delahaye-Sourdeix; Kevin Y Urayama; Valérie Gaborieau; Rianne Veenstra; Matthieu Foll; Amelie Chabrier; Yolanda Benavente; Alexandra Nieters; Nikolaus Becker; Lenka Foretova; Marc Maynadie; Anthony Staines; Karin Ekström Smedby; Ingrid Glimelius; Tracy Lightfoot; Pierluigi Cocco; Pilar Galan; Lars J Vatten; Eric J Duell; Lambertus Kiemeney; Eve Roman; Silvia de Sanjose; Mark Lathrop; Mads Melbye; Paul Brennan; Arjan Diepstra; Anke van den Berg; Henrik Hjalgrim; Ruth F Jarrett; James D McKay

doi:10.1158/1055-9965.EPI-15-0534

A novel risk locus at 6p21.3 for Epstein-Barr virus positive Hodgkin lymphoma

Manon Delahaye-Sourdeix, Kevin Y Urayama, Valérie Gaborieau, Rianne Veenstra, Matthieu Foll, Amelie Chabrier, Yolanda Benavente, Alexandra Nieters, Nikolaus Becker, Lenka Foretova, Marc Maynadie, Anthony Staines, Karin Ekström Smedby, Ingrid Glimelius, Tracy Lightfoot, Pierluigi Cocco, Pilar Galan, Lars J Vatten, Eric J Duell, Lambertus KiemeneyEve Roman, Silvia de Sanjose, Mark Lathrop, Mads Melbye, Paul Brennan, Arjan Diepstra, Anke van den Berg, Henrik Hjalgrim, Ruth F Jarrett, James D McKay

Health Sciences

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

Abstract

BACKGROUND: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma (HL) differ by the tumor's Epstein-Barr virus (EBV) status, particularly within the major histocompatibility complex (MHC) region.

METHODS: We have conducted a single nucleotide polymorphism (SNP) imputation study of the MHC region, considering tumor EBV status in 1,200 classical HL (cHL) cases and 5,726 control subjects of European origin. Notable findings were genotyped in an independent study population of 468 cHL cases and 551 controls.

RESULTS: We identified and subsequently replicated a novel association between a common genetic variant rs6457715 and cHL. While strongly associated with EBV-positive cHL (OR=2.33 [1.83 - 2.97] P=7x10-12)), there was little evidence for association between rs6457715 and the EBV negative subgroup of HL (OR=1.06 [0.92 - 1.21]), indicating that this association was specific to the EBV positive subgroup (Phet< P=10-8). Furthermore, the association was limited to EBV-positive cHL subgroups within mixed cell (MCHL) and nodular sclerosis subtypes (NSHL), suggesting that the association is independent of histological subtype of cHL.

CONCLUSIONS: rs6457715, located near the HLA-DPB1 gene, is associated with EBV positive cHL and suggests this region as a novel susceptibility locus for cHL.

IMPACT: This expands the number of genetic variants that are associated with cHL, and provides additional evidence for a critical and specific role of EBV in the etiology of this disease.

Original language	English
Journal	Cancer Epidemiology Biomarkers & Prevention
DOIs	https://doi.org/10.1158/1055-9965.EPI-15-0534
Publication status	Published - 24 Sept 2015

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10.1158/1055-9965.EPI-15-0534

http://cebp.aacrjournals.org/content/early/2015/09/24/1055-9965.EPI-15-0534

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Delahaye-Sourdeix, M., Urayama, K. Y., Gaborieau, V., Veenstra, R., Foll, M., Chabrier, A., Benavente, Y., Nieters, A., Becker, N., Foretova, L., Maynadie, M., Staines, A., Ekström Smedby, K., Glimelius, I., Lightfoot, T., Cocco, P., Galan, P., Vatten, L. J., Duell, E. J., ... McKay, J. D. (2015). A novel risk locus at 6p21.3 for Epstein-Barr virus positive Hodgkin lymphoma. Cancer Epidemiology Biomarkers & Prevention. https://doi.org/10.1158/1055-9965.EPI-15-0534

@article{7a20cf9a126447a0afd2bc8729987f78,

title = "A novel risk locus at 6p21.3 for Epstein-Barr virus positive Hodgkin lymphoma",

abstract = "BACKGROUND: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma (HL) differ by the tumor's Epstein-Barr virus (EBV) status, particularly within the major histocompatibility complex (MHC) region.METHODS: We have conducted a single nucleotide polymorphism (SNP) imputation study of the MHC region, considering tumor EBV status in 1,200 classical HL (cHL) cases and 5,726 control subjects of European origin. Notable findings were genotyped in an independent study population of 468 cHL cases and 551 controls.RESULTS: We identified and subsequently replicated a novel association between a common genetic variant rs6457715 and cHL. While strongly associated with EBV-positive cHL (OR=2.33 [1.83 - 2.97] P=7x10-12)), there was little evidence for association between rs6457715 and the EBV negative subgroup of HL (OR=1.06 [0.92 - 1.21]), indicating that this association was specific to the EBV positive subgroup (Phet< P=10-8). Furthermore, the association was limited to EBV-positive cHL subgroups within mixed cell (MCHL) and nodular sclerosis subtypes (NSHL), suggesting that the association is independent of histological subtype of cHL.CONCLUSIONS: rs6457715, located near the HLA-DPB1 gene, is associated with EBV positive cHL and suggests this region as a novel susceptibility locus for cHL.IMPACT: This expands the number of genetic variants that are associated with cHL, and provides additional evidence for a critical and specific role of EBV in the etiology of this disease.",

author = "Manon Delahaye-Sourdeix and Urayama, {Kevin Y} and Val{\'e}rie Gaborieau and Rianne Veenstra and Matthieu Foll and Amelie Chabrier and Yolanda Benavente and Alexandra Nieters and Nikolaus Becker and Lenka Foretova and Marc Maynadie and Anthony Staines and {Ekstr{\"o}m Smedby}, Karin and Ingrid Glimelius and Tracy Lightfoot and Pierluigi Cocco and Pilar Galan and Vatten, {Lars J} and Duell, {Eric J} and Lambertus Kiemeney and Eve Roman and {de Sanjose}, Silvia and Mark Lathrop and Mads Melbye and Paul Brennan and Arjan Diepstra and {van den Berg}, Anke and Henrik Hjalgrim and Jarrett, {Ruth F} and McKay, {James D}",

note = "Copyright {\textcopyright} 2015, American Association for Cancer Research.",

year = "2015",

month = sep,

day = "24",

doi = "10.1158/1055-9965.EPI-15-0534",

language = "English",

journal = "Cancer Epidemiology Biomarkers & Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

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Delahaye-Sourdeix, M, Urayama, KY, Gaborieau, V, Veenstra, R, Foll, M, Chabrier, A, Benavente, Y, Nieters, A, Becker, N, Foretova, L, Maynadie, M, Staines, A, Ekström Smedby, K, Glimelius, I, Lightfoot, T, Cocco, P, Galan, P, Vatten, LJ, Duell, EJ, Kiemeney, L, Roman, E, de Sanjose, S, Lathrop, M, Melbye, M, Brennan, P, Diepstra, A, van den Berg, A, Hjalgrim, H, Jarrett, RF & McKay, JD 2015, 'A novel risk locus at 6p21.3 for Epstein-Barr virus positive Hodgkin lymphoma', Cancer Epidemiology Biomarkers & Prevention. https://doi.org/10.1158/1055-9965.EPI-15-0534

TY - JOUR

T1 - A novel risk locus at 6p21.3 for Epstein-Barr virus positive Hodgkin lymphoma

AU - Delahaye-Sourdeix, Manon

AU - Urayama, Kevin Y

AU - Gaborieau, Valérie

AU - Veenstra, Rianne

AU - Foll, Matthieu

AU - Chabrier, Amelie

AU - Benavente, Yolanda

AU - Nieters, Alexandra

AU - Becker, Nikolaus

AU - Foretova, Lenka

AU - Maynadie, Marc

AU - Staines, Anthony

AU - Ekström Smedby, Karin

AU - Glimelius, Ingrid

AU - Lightfoot, Tracy

AU - Cocco, Pierluigi

AU - Galan, Pilar

AU - Vatten, Lars J

AU - Duell, Eric J

AU - Kiemeney, Lambertus

AU - Roman, Eve

AU - de Sanjose, Silvia

AU - Lathrop, Mark

AU - Melbye, Mads

AU - Brennan, Paul

AU - Diepstra, Arjan

AU - van den Berg, Anke

AU - Hjalgrim, Henrik

AU - Jarrett, Ruth F

AU - McKay, James D

PY - 2015/9/24

Y1 - 2015/9/24

N2 - BACKGROUND: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma (HL) differ by the tumor's Epstein-Barr virus (EBV) status, particularly within the major histocompatibility complex (MHC) region.METHODS: We have conducted a single nucleotide polymorphism (SNP) imputation study of the MHC region, considering tumor EBV status in 1,200 classical HL (cHL) cases and 5,726 control subjects of European origin. Notable findings were genotyped in an independent study population of 468 cHL cases and 551 controls.RESULTS: We identified and subsequently replicated a novel association between a common genetic variant rs6457715 and cHL. While strongly associated with EBV-positive cHL (OR=2.33 [1.83 - 2.97] P=7x10-12)), there was little evidence for association between rs6457715 and the EBV negative subgroup of HL (OR=1.06 [0.92 - 1.21]), indicating that this association was specific to the EBV positive subgroup (Phet< P=10-8). Furthermore, the association was limited to EBV-positive cHL subgroups within mixed cell (MCHL) and nodular sclerosis subtypes (NSHL), suggesting that the association is independent of histological subtype of cHL.CONCLUSIONS: rs6457715, located near the HLA-DPB1 gene, is associated with EBV positive cHL and suggests this region as a novel susceptibility locus for cHL.IMPACT: This expands the number of genetic variants that are associated with cHL, and provides additional evidence for a critical and specific role of EBV in the etiology of this disease.

AB - BACKGROUND: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma (HL) differ by the tumor's Epstein-Barr virus (EBV) status, particularly within the major histocompatibility complex (MHC) region.METHODS: We have conducted a single nucleotide polymorphism (SNP) imputation study of the MHC region, considering tumor EBV status in 1,200 classical HL (cHL) cases and 5,726 control subjects of European origin. Notable findings were genotyped in an independent study population of 468 cHL cases and 551 controls.RESULTS: We identified and subsequently replicated a novel association between a common genetic variant rs6457715 and cHL. While strongly associated with EBV-positive cHL (OR=2.33 [1.83 - 2.97] P=7x10-12)), there was little evidence for association between rs6457715 and the EBV negative subgroup of HL (OR=1.06 [0.92 - 1.21]), indicating that this association was specific to the EBV positive subgroup (Phet< P=10-8). Furthermore, the association was limited to EBV-positive cHL subgroups within mixed cell (MCHL) and nodular sclerosis subtypes (NSHL), suggesting that the association is independent of histological subtype of cHL.CONCLUSIONS: rs6457715, located near the HLA-DPB1 gene, is associated with EBV positive cHL and suggests this region as a novel susceptibility locus for cHL.IMPACT: This expands the number of genetic variants that are associated with cHL, and provides additional evidence for a critical and specific role of EBV in the etiology of this disease.

U2 - 10.1158/1055-9965.EPI-15-0534

DO - 10.1158/1055-9965.EPI-15-0534

M3 - Article

C2 - 26404960

SN - 1055-9965

JO - Cancer Epidemiology Biomarkers & Prevention

JF - Cancer Epidemiology Biomarkers & Prevention

ER -