Identification of Genetic Variants Associated With Extranodal Natural Killer T-Cell Lymphoma
In a genome-wide association study reported in The Lancet Oncology, Li et al identified genetic variants associated with the risk of nasal-type extranodal natural killer T-cell lymphoma (NKTCL). This rare aggressive malignancy is seen predominantly in Asian and Latin American populations; Epstein-Barr virus infection is a known risk factor.
Study Details
The study included 189 patients and 957 controls from Guangdong province, with validation in 4 independent case-control series, including 75 cases from Guangdong province and 296 controls from Hong Kong, 65 cases and 983 controls from Guangdong province, 125 cases and 1,110 controls from Beijing, and 60 cases and 2,476 controls from Singapore.
Significant Associations
Associations exceeding the genome-wide significance threshold of P < 5 × 10-8 were found at 51 single nucleotide polymorphisms mapped to the class II MHC (major histocompatibility complex) region on chromosome 6; rs9277378, which is located in HLA-DPB1, had the strongest association with NKTCL susceptibility (odds ratio [OR] = 1.84, 95% confidence interval [CI] = 1.61–2.11, in meta-analysis of entire dataset). Mapping across the class II MHC region indicated that the residues Gly84-Gly85-Pro86-Met87 in near-complete linkage disequilibrium at the edge of the peptide-binding groove of HLA-DPB1 could account for most of the association between the rs9277378*A risk allele and disease susceptibility (OR = 2.38, P for haplotype = 2.32 × 10-14). The association was independent from MHC associations with Epstein-Barr virus infection.
The investigators concluded: “To our knowledge, this is the first time that a genetic variant conferring an NKTCL risk is noted at genome-wide significance. This finding underlines the importance of HLA-DP antigen presentation in the pathogenesis of NKTCL.”
The study was funded by the Top-Notch Young Talents Program of China, Special Support Program of Guangdong, Specialized Research Fund for the Doctoral Program of Higher Education, Program for New Century Excellent Talents in University, National Medical Research Council of Singapore, Tanoto Foundation Professorship in Medical Oncology, New Century Foundation Limited, Ling Foundation, Singapore National Cancer Centre Research Fund, and the U.S National Institutes of Health.
Jin-Xin Bei, PhD, of Sun Yat-Sen University Cancer Center, Guangzhou, China, is the corresponding author of The Lancet Oncology article.
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