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

Delahaye-Sourdeix, M. et al. (2015) A novel risk locus at 6p21.3 for Epstein-Barr virus-positive Hodgkin lymphoma. Cancer Epidemiology, Biomarkers and Prevention, 24(12), pp. 1838-1843. (doi:10.1158/1055-9965.EPI-15-0534) (PMID:26404960)

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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.

Item Type:Articles (Other)
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jarrett, Professor Ruth
Authors: Delahaye-Sourdeix, M., Urayama, K. Y., Gaborieau, V., Veenstra, R., Foll, M., Chabrier, A., Benavente, Y., Nieters, A., Becker, N., Foretova, L., Maynadié, M., Staines, A., Smedby, K. E., Glimelius, I., Lightfoot, T., Cocco, P., Galan, P., Vatten, L. J., Duell, E. J., Kiemeney, L., Roman, E., de Sanjosé, S., Lathrop, M., Melbye, M., Brennan, P., Diepstra, A., van den Berg, A., Hjalgrim, H., Jarrett, R. F., and McKay, J. D.
Subjects:R Medicine > RB Pathology
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Cancer Epidemiology, Biomarkers and Prevention
Journal Abbr.:Cancer Epidemiol. Biomarkers Prev.
Publisher:American Association for Cancer Research
ISSN:1055-9965
ISSN (Online):1538-7755
Published Online:24 September 2015

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
409572Investigation of the pathogenesis of Hodgkin lymphomaRuth JarrettBloodwise (BLOODWIS)08031MVLS III - CENTRE FOR VIRUS RESEARCH
409571Investigation of the pathogenesis of Hodgkin lymphomaRuth JarrettBloodwise (BLOODWIS)05045MVLS III - CENTRE FOR VIRUS RESEARCH