Extranodal natural killer T-cell lymphoma (NKTCL) is a type of cancer that occurs in the white blood cells. The cause of the disease typically involves Epstein-Barr virus infection and HLA-DPB1 variants, but any genetic associations are not yet known. The objective of this study is to identify the novel genetic variants affecting the risk of NKTCL.

This is a meta-analysis genome-wide association study that included a total of 1,417 patients of NKTCL and 20,402 controls derived from a discovery cohort of 700 cases with NKTCL and 7752 controls without NKTCL. Logistic regression and meta-analysis were performed to identify susceptibility loci. The primary outcome of the study was the genetic risk of NKTCL.

The genetic data and meta-analysis identified two novel loci associated with NKTCL: IL18RAP on 2q12.1 and HLA-DRB1 on 6p21.3. The research further confirmed the correlation of rs1420106 at the promoter of IL18RAP with rs13015714. It was also discovered that the rs1420106-A risk variant resulted in increased activity of the IL18RAP expression.

The research concluded that the development of NKTCL is possible as a result of inflammation and immune regulation through the IL18–IL18RAP axis and antigen presentation involving HLA-DRB1. This data can be used to identify potential therapeutic targets and people at a high risk of NKTCL.

Ref: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30799-5/fulltext