Association of DDX58 177 C > T polymorphism with decreased risk of Epstein–Barr virus-related nodular sclerosis classical Hodgkin lymphoma

Abstract

Classical Hodgkin lymphoma (cHL) is frequently related to Epstein–Barr virus (EBV) infection. Its malignant capacity is attributed to disruption of an EBV-host balance influenced by environmental and genetic drivers. EBV structures activate Type I interferon (IFN) pathway of the innate immunity, therefore, genetic polymorphisms could influence this response. We explored the impact of four single nucleotide polymorphisms (SNPs) on EBV-associated cHL susceptibility. Toll-like receptors 9 (TLR9_rs5743836), and 3 (TLR3_rs3775291), Interleukin-28B (IL28B_rs12979860), and DEAD-box polypeptide 58 (DDX58_rs10813831) were genotyped in 73 EBV-positive and 106 EBV-negative cHL patients and 396 controls. Only DDX58_rs10813831 T-allele was decreased among EBV-positive cHL compared to controls. A stratified analysis in EBV-positive cHL showed that the reduced rate was associated with younger age and nodular sclerosis. In conclusion, DDX58_rs10813831 T-allele may be associated with a reduced risk of nodular sclerosis EBV-related cHL, which suggests a role for RIG-I (retinoic acid-inducible gene I), encoded by DDX58, in these cases.

Keywords:

• Classical Hodgkin lymphoma
• DDX58
• EBV
• genetic susceptibility
• IFN pathway
• IL28B
• single nucleotide polymorphisms
• TLR-3
• TLR-9

Acknowledgements

We are indebted to all individuals who kindly donated blood or tissue samples, as well as to the Hospital Puerta de Hierro Blood Bank and Biobank staff. We are also grateful to Teresa Hernando who helped with the epidemiologic aspects of the work and to Dr Elvira Ramil from the Sequencing Core facility of the Instituto de Investigación Puerta de Hierro for excellent technical support.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.1080/10428194.2016.1190972.

Funding information

The authors were funded by the following institutions: NGL and PM, by grants from programs Miguel Servet and Joan Rodés, Fondo de Investigación Sanitaria [CP09/00182 (NGL) and JR14/0018 (PM)], respectively, and Instituto de Salud Carlos III (FEDER); JMV, by Fundación para la Investigación Biomédica Puerta de Hierro.