@article {1001661,
	title = {Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study},
	journal = {Lancet Oncol},
	volume = {17},
	number = {9},
	year = {2016},
	month = {2016 Sep},
	pages = {1240-7},
	abstract = {BACKGROUND: Extranodal natural killer T-cell lymphoma (NKTCL), nasal type, is a rare and aggressive malignancy that occurs predominantly in Asian and Latin American populations. Although Epstein-Barr virus infection is a known risk factor, other risk factors and the pathogenesis of NKTCL are not well understood. We aimed to identify common genetic variants affecting individual risk of NKTCL. METHODS: We did a genome-wide association study of 189 patients with extranodal NKTCL, nasal type (WHO classification criteria; cases) and 957 controls from Guangdong province, southern China. We validated our findings in four 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 1110 controls from Beijing (northern China), and 60 cases and 2476 controls from Singapore. We used imputation and conditional logistic regression analyses to fine-map the associations. We also did a meta-analysis of the replication series and of the entire dataset. FINDINGS: Associations exceeding the genome-wide significance threshold (p\&lt;5 {\texttimes} 10(-8)) were seen at 51 single-nucleotide polymorphisms (SNPs) mapping to the class II MHC region on chromosome 6, with rs9277378 (located in HLA-DPB1) having the strongest association with NKTCL susceptibility (p=4{\textperiodcentered}21 {\texttimes} 10(-19), odds ratio [OR] 1{\textperiodcentered}84 [95\% CI 1{\textperiodcentered}61-2{\textperiodcentered}11] in meta-analysis of entire dataset). Imputation-based fine-mapping across the class II MHC region suggests that four aminoacid 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 NKTCL susceptibility (OR 2{\textperiodcentered}38, p value for haplotype 2{\textperiodcentered}32 {\texttimes} 10(-14)). This association is distinct from MHC associations with Epstein-Barr virus infection. INTERPRETATION: 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. FUNDING: Top-Notch Young Talents Program of China, Special Support Program of Guangdong, Specialized Research Fund for the Doctoral Program of Higher Education (20110171120099), Program for New Century Excellent Talents in University (NCET-11-0529), National Medical Research Council of Singapore (TCR12DEC005), Tanoto Foundation Professorship in Medical Oncology, New Century Foundation Limited, Ling Foundation, Singapore National Cancer Centre Research Fund, and the US National Institutes of Health (1R01AR062886, 5U01GM092691-04, and 1R01AR063759-01A1).},
	keywords = {Adult, Aged, Biomarkers, Tumor, Case-Control Studies, China, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Lymphoma, Extranodal NK-T-Cell, Male, Middle Aged, Neoplasm Staging, Polymorphism, Single Nucleotide, Prognosis, Risk Factors, Young Adult},
	issn = {1474-5488},
	doi = {10.1016/S1470-2045(16)30148-6},
	url = {https://www.ncbi.nlm.nih.gov/pubmed/31879220},
	author = {Li, Zheng and Xia, Yi and Feng, Li-Na and Chen, Jie-Rong and Li, Hong-Min and Cui, Jing and Cai, Qing-Qing and Sim, Kar Seng and Nairism{\"a}gi, Maarja-Liisa and Laurensia, Yurike and Meah, Wee Yang and Liu, Wen-Sheng and Guo, Yun-Miao and Chen, Li-Zhen and Feng, Qi-Sheng and Pang, Chi Pui and Chen, Li Jia and Chew, Soo Hong and Ebstein, Richard P and Foo, Jia Nee and Liu, Jianjun and Ha, Jeslin and Khoo, Lay Poh and Chin, Suk Teng and Zeng, Yi-Xin and Aung, Tin and Chowbay, Balram and Diong, Colin Phipps and Zhang, Fen and Liu, Yan-Hui and Tang, Tiffany and Tao, Miriam and Quek, Richard and Mohamad, Farid and Tan, Soo Yong and Teh, Bin Tean and Ng, Siok Bian and Chng, Wee Joo and Ong, Choon Kiat and Okada, Yukinori and Raychaudhuri, Soumya and Lim, Soon Thye and Tan, Wen and Peng, Rou-Jun and Khor, Chiea Chuen and Bei, Jin-Xin}
}
