Abstract
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.
Highlights
Hodgkin lymphoma is a cancer of the lymphatic system characterized by the presence of B-cell derived Hodgkin Reed– Sternberg (HRS) tumor cells [1]
Classical Hodgkin lymphoma is the major form and comprises four histologic subtypes of which the nodular sclerosis Hodgkin lymphoma (NSHL) subtype is most common followed by mixed cellularity Hodgkin lymphoma (MCHL)
We have identified a novel group of highly correlated genetic variants, located near the MHC class-II human leukocyte antigen (HLA)–DPB1 gene, which are associated with genetic susceptibility to Classical Hodgkin lymphoma (cHL)
Summary
Hodgkin lymphoma is a cancer of the lymphatic system characterized by the presence of B-cell derived Hodgkin Reed– Sternberg (HRS) tumor cells [1]. Hodgkin lymphoma is relatively rare, but contributes substantially to worldwide disease burden, totaling 66,000 new cases in 2012 and 25,000 deaths [2]. It affects mainly young adults ages 15 to 35 years and older adults ages 55 years and over. Clinical Epidemiology Unit, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden. A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein–Barr virus (EBV) status, within the MHC region
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