A Novel Risk Locus at 6p21.3 for Epstein–Barr Virus-Positive Hodgkin Lymphoma
Background: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein–Barr virus (EBV) status, particularly within the MHC region. Methods: We have conducted an SNP imputation study of the MHC region, considering tumor EBV status in 1,200...
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| Published in | Cancer epidemiology, biomarkers & prevention Vol. 24; no. 12; pp. 1838 - 1843 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier
01.12.2015
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1055-9965 0147-9571 1538-7755 1538-7755 |
| DOI | 10.1158/1055-9965.EPI-15-0534 |
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| Abstract | Background: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein–Barr virus (EBV) status, particularly within the MHC region.
Methods: We have conducted an SNP imputation study of the MHC region, considering tumor EBV status in 1,200 classical Hodgkin lymphoma (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. Although strongly associated with EBV-positive cHL [OR, 2.33; 95% confidence interval (CI), 1.83–2.97; P = 7 × 10–12], there was little evidence for association between rs6457715 and the EBV-negative subgroup of cHL (OR, 1.06; 95% CI, 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 histologic 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. Cancer Epidemiol Biomarkers Prev; 24(12); 1838–43. ©2015 AACR. |
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| AbstractList | BACKGROUNDA proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein-Barr virus (EBV) status, particularly within the MHC region.METHODSWe have conducted an SNP imputation study of the MHC region, considering tumor EBV status in 1,200 classical Hodgkin lymphoma (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.RESULTSWe identified and subsequently replicated a novel association between a common genetic variant rs6457715 and cHL. Although strongly associated with EBV-positive cHL [OR, 2.33; 95% confidence interval (CI), 1.83-2.97; P = 7 × 10(-12)], there was little evidence for association between rs6457715 and the EBV-negative subgroup of cHL (OR, 1.06; 95% CI, 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 histologic subtype of cHL.CONCLUSIONSrs6457715, located near the HLA-DPB1 gene, is associated with EBV-positive cHL and suggests this region as a novel susceptibility locus for cHL.IMPACTThis 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. BACKGROUND: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein-Barr virus (EBV) status, particularly within the MHC region. METHODS: We have conducted an SNP imputation study of the MHC region, considering tumor EBV status in 1,200 classical Hodgkin lymphoma (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. Although strongly associated with EBV-positive cHL [OR, 2.33; 95% confidence interval (CI), 1.83-2.97; P = 7 × 10(-12)], there was little evidence for association between rs6457715 and the EBV-negative subgroup of cHL (OR, 1.06; 95% CI, 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 histologic 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. Cancer Epidemiol Biomarkers Prev; 24(12); 1838-43. A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein-Barr virus (EBV) status, particularly within the MHC region. We have conducted an SNP imputation study of the MHC region, considering tumor EBV status in 1,200 classical Hodgkin lymphoma (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. We identified and subsequently replicated a novel association between a common genetic variant rs6457715 and cHL. Although strongly associated with EBV-positive cHL [OR, 2.33; 95% confidence interval (CI), 1.83-2.97; P = 7 × 10(-12)], there was little evidence for association between rs6457715 and the EBV-negative subgroup of cHL (OR, 1.06; 95% CI, 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 histologic subtype of cHL. rs6457715, located near the HLA-DPB1 gene, is associated with EBV-positive cHL and suggests this region as a novel susceptibility locus for cHL. 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. Background: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein-Barr virus (EBV) status, particularly within the MHC region. Methods: We have conducted an SNP imputation study of the MHC region, considering tumor EBV status in 1,200 classical Hodgkin lymphoma (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. Although strongly associated with EBV-positive cHL [OR, 2.33; 95% confidence interval (CI), 1.83-2.97; P = 7 x 10(-12)], there was little evidence for association between rs6457715 and the EBV-negative subgroup of cHL (OR, 1.06; 95% CI, 0.92-1.21), indicating that this association was specific to the EBV-positive subgroup (P-het < 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 histologic 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. Background: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein–Barr virus (EBV) status, particularly within the MHC region. Methods: We have conducted an SNP imputation study of the MHC region, considering tumor EBV status in 1,200 classical Hodgkin lymphoma (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. Although strongly associated with EBV-positive cHL [OR, 2.33; 95% confidence interval (CI), 1.83–2.97; P = 7 × 10–12], there was little evidence for association between rs6457715 and the EBV-negative subgroup of cHL (OR, 1.06; 95% CI, 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 histologic 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. Cancer Epidemiol Biomarkers Prev; 24(12); 1838–43. ©2015 AACR. |
| Author | van den Berg, Anke Becker, Nikolaus Staines, Anthony de Sanjosé, Silvia Nieters, Alexandra Kiemeney, Lambertus Hjalgrim, Henrik Cocco, Pierluigi Foll, Matthieu Lightfoot, Tracy Gaborieau, Valérie Delahaye-Sourdeix, Manon Smedby, Karin Ekstrom Melbye, Mads Jarrett, Ruth F. Glimelius, Ingrid Galan, Pilar Foretova, Lenka Maynadié, Marc Vatten, Lars J. Brennan, Paul McKay, James D. Lathrop, Mark Benavente, Yolanda Duell, Eric J. Veenstra, Rianne Urayama, Kevin Y. Roman, Eve Diepstra, Arjan Chabrier, Amelie |
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| Cites_doi | 10.1186/1471-2105-11-134 10.1038/ng.2354 10.1371/journal.pone.0002551 10.1182/blood.V83.6.1595.1595 10.1038/ng.696 10.1093/annonc/7.suppl_4.S5 10.1038/ng.2756 10.1182/blood-2007-05-086934 10.1093/jnci/djr516 10.1073/pnas.0915054107 10.1002/(SICI)1097-0215(19970207)70:4<375::AID-IJC1>3.0.CO;2-T 10.1182/blood-2011-03-339630 10.1038/ncomms3549 10.1038/nrc2542 10.1056/NEJMoa023141 10.1182/blood-2011-03-343921 10.1016/S0140-6736(05)66780-3 10.1002/gepi.20533 10.1371/journal.pcbi.1002877 |
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| Keywords | SUBTYPE DISEASE SUSCEPTIBILITY SEQUENCE INFECTIOUS-MONONUCLEOSIS EBV GENOME-WIDE ASSOCIATION |
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| Snippet | Background: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein–Barr virus (EBV) status,... A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein-Barr virus (EBV) status, particularly within... BACKGROUNDA proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein-Barr virus (EBV) status,... Background: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein-Barr virus (EBV) status,... BACKGROUND: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein-Barr virus (EBV) status,... |
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| SubjectTerms | Adolescent Adult Aged Aged, 80 and over Case-Control Studies Chromosomes, Human, Pair 6 Epstein-Barr Virus Infections - epidemiology Epstein-Barr Virus Infections - genetics Epstein-Barr Virus Infections - pathology Epstein-Barr Virus Infections - virology Female Genetic Predisposition to Disease Hodgkin Disease - epidemiology Hodgkin Disease - genetics Hodgkin Disease - pathology Hodgkin Disease - virology Human health and pathology Humans Life Sciences Major Histocompatibility Complex - genetics Male Middle Aged Netherlands - epidemiology Polymorphism, Single Nucleotide Scandinavian and Nordic Countries - epidemiology Young Adult |
| Title | A Novel Risk Locus at 6p21.3 for Epstein–Barr Virus-Positive Hodgkin Lymphoma |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/26404960 https://www.proquest.com/docview/1744664261 https://hal.inrae.fr/hal-02632507 https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-270351 http://kipublications.ki.se/Default.aspx?queryparsed=id:132541219 |
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