Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study

• Published in: The lancet oncology 2016-09, Vol.17 (9), p.1240-1247
• Main Authors: Li, Zheng, PhD, Xia, Yi, MD, Feng, Li-Na, MD, Chen, Jie-Rong, BSc, Li, Hong-Min, MD, Cui, Jing, PhD, Cai, Qing-Qing, Prof, Sim, Kar Seng, MS, Nairismägi, Maarja-Liisa, PhD, Laurensia, Yurike, BSc, Meah, Wee Yang, BSc, Liu, Wen-Sheng, MMS, Guo, Yun-Miao, PhD, Chen, Li-Zhen, ADN, Feng, Qi-Sheng, BSc, Pang, Chi Pui, DPhil, Chen, Li Jia, PhD, Chew, Soo Hong, Prof, Ebstein, Richard P, Prof, Foo, Jia Nee, PhD, Liu, Jianjun, Prof, Ha, Jeslin, BSc, Khoo, Lay Poh, BSc, Chin, Suk Teng, BSc, Zeng, Yi-Xin, Prof, Aung, Tin, Prof, Chowbay, Balram, Prof, Diong, Colin Phipps, MD, Zhang, Fen, MD, Liu, Yan-Hui, MD, Tang, Tiffany, MD, Tao, Miriam, MD, Quek, Richard, MD, Mohamad, Farid, MD, Tan, Soo Yong, Prof, Teh, Bin Tean, Prof, Ng, Siok Bian, FRCPA, Chng, Wee Joo, Prof, Ong, Choon Kiat, PhD, Okada, Yukinori, PhD, Raychaudhuri, Soumya, PhD, Lim, Soon Thye, MD, Tan, Wen, Prof, Peng, Rou-Jun, MD, Khor, Chiea Chuen, PhD, Bei, Jin-Xin, Prof
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigen presentation; Biomarkers, Tumor - genetics; Cancer; Case-Control Studies; China; Chromosome 6; Education; Epstein-Barr virus; Female; Follow-Up Studies; Gene mapping; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Haplotypes; Hematology, Oncology and Palliative Medicine; Hepatitis; Histocompatibility antigen HLA; Humans; Linkage disequilibrium; Lymphocytes T; Lymphoma; Lymphoma, Extranodal NK-T-Cell - genetics; Lymphoma, Extranodal NK-T-Cell - pathology; Major histocompatibility complex; Male; Malignancy; Medical research; Middle Aged; Natural killer cells; Neoplasm Staging; Pathogenesis; Peptides; Polymorphism, Single Nucleotide - genetics; Prognosis; Risk Factors; Single-nucleotide polymorphism; Studies; T cell receptors; T-cell lymphoma; Young Adult
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(16)30148-6

Summary 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