Genetic Locus of Natural Killer T-cell Lymphoma Risk Identified Interview with:
Jin-Xin BEI, Ph.D.
Principal Investigator
State Key Laboratory of Oncology in South China
Sun Yat-sen University Cancer Center
Guangzhou China What is the background for this study?

Response: Natural killer T-cell lymphoma (NKTCL) is a rare and aggressive malignancy with remarkable prevalence in Asian and Latin populations, suggesting that the heritable components contribute to the disease risk. Epstein-Barr virus (EBV) infection has been thought to be major factor associated with NKTCL, and EBV DNA load in plasma has been applied in clinical managements, including diagnosis, treatment response and prognosis. However, the genetic component leading to NKTCL predisposition has not been identified. What are the main findings?

Response: A genome-wide association study of NKTCL was conducted in Chinese population, by comparing genetic variations (SNP) between 189 NKTCL patients and 957 controls at genome-wide level. The most significant association of SNP rs9277378 with NKTCL was identified and replicated in another four independent sample collections, with 325 cases and 4865 controls. Meta-analysis revealed that each copy of the risk allele increases 1.84 fold of NKTCL risk. Moreover, the risk allele was in near-complete linkage disequilibrium with four aminoacid residues (Gly84-Gly85-Pro86-Met87) at the edge of the peptide-biding groove of HLA-DPB1. Conditional logistic regression analysis suggested that the four aminoacid residues could account for most of the association between the risk allele of rs9277378 and NKTCL risk. In addition, the study revealed that NKTCL, nasopharyngeal carcinoma, and other types of lymphomas, despite that they were thought to be EBV-related and have been associated with HLA variations, have distinct HLA signatures, suggesting that these diseases might have different molecular mechanisms of pathogenesis. What should readers take away from your report?

Response: Although this study discovered for the first time the genetic variations of HLA-DPB1 to be associated with NKTCL susceptibility, a small proportion of the disease heritability could be explained. Further genetic studies with larger sample size and sufficient statistical power are pending to uncover the other risk loci with moderate genetic effects. Moreover, it should be interesting to resolve the puzzle why different diseases of EBV-related have distinct HLA background, which might be helpful to understand EBV’s role in pathogenesis, either driver or passenger, as EBV infection is common in general population. Thank you for your contribution to the community.

Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study
Li, Zheng et al.
The Lancet Oncology , Volume 0 , Issue 0 ,
Published Online:25 July 2016

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on July 29, 2016 by Marie Benz MD FAAD