Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study
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...
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| creator | 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 |
| description | 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 |
| doi_str_mv | 10.1016/S1470-2045(16)30148-6 |
| format | Article |
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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<5 × 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=4·21 × 10−19 , odds ratio [OR] 1·84 [95% CI 1·61–2·11] 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 2·38, p value for haplotype 2·32 × 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).</description><identifier>ISSN: 1470-2045</identifier><identifier>EISSN: 1474-5488</identifier><identifier>DOI: 10.1016/S1470-2045(16)30148-6</identifier><identifier>PMID: 27470079</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>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</subject><ispartof>The lancet oncology, 2016-09, Vol.17 (9), p.1240-1247</ispartof><rights>Elsevier Ltd</rights><rights>2016 Elsevier Ltd</rights><rights>Copyright © 2016 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Sep 1, 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c635t-ab1c3735a84b6035ae4a4fb430debf636ff18d789a26426028b0ef9457fa376a3</citedby><cites>FETCH-LOGICAL-c635t-ab1c3735a84b6035ae4a4fb430debf636ff18d789a26426028b0ef9457fa376a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1470204516301486$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27470079$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Zheng, PhD</creatorcontrib><creatorcontrib>Xia, Yi, MD</creatorcontrib><creatorcontrib>Feng, Li-Na, MD</creatorcontrib><creatorcontrib>Chen, Jie-Rong, BSc</creatorcontrib><creatorcontrib>Li, Hong-Min, MD</creatorcontrib><creatorcontrib>Cui, Jing, PhD</creatorcontrib><creatorcontrib>Cai, Qing-Qing, Prof</creatorcontrib><creatorcontrib>Sim, Kar Seng, MS</creatorcontrib><creatorcontrib>Nairismägi, Maarja-Liisa, PhD</creatorcontrib><creatorcontrib>Laurensia, Yurike, BSc</creatorcontrib><creatorcontrib>Meah, Wee Yang, BSc</creatorcontrib><creatorcontrib>Liu, Wen-Sheng, MMS</creatorcontrib><creatorcontrib>Guo, Yun-Miao, PhD</creatorcontrib><creatorcontrib>Chen, Li-Zhen, ADN</creatorcontrib><creatorcontrib>Feng, Qi-Sheng, BSc</creatorcontrib><creatorcontrib>Pang, Chi Pui, DPhil</creatorcontrib><creatorcontrib>Chen, Li Jia, PhD</creatorcontrib><creatorcontrib>Chew, Soo Hong, Prof</creatorcontrib><creatorcontrib>Ebstein, Richard P, Prof</creatorcontrib><creatorcontrib>Foo, Jia Nee, PhD</creatorcontrib><creatorcontrib>Liu, Jianjun, Prof</creatorcontrib><creatorcontrib>Ha, Jeslin, BSc</creatorcontrib><creatorcontrib>Khoo, Lay Poh, BSc</creatorcontrib><creatorcontrib>Chin, Suk Teng, BSc</creatorcontrib><creatorcontrib>Zeng, Yi-Xin, Prof</creatorcontrib><creatorcontrib>Aung, Tin, Prof</creatorcontrib><creatorcontrib>Chowbay, Balram, Prof</creatorcontrib><creatorcontrib>Diong, Colin Phipps, MD</creatorcontrib><creatorcontrib>Zhang, Fen, MD</creatorcontrib><creatorcontrib>Liu, Yan-Hui, MD</creatorcontrib><creatorcontrib>Tang, Tiffany, MD</creatorcontrib><creatorcontrib>Tao, Miriam, MD</creatorcontrib><creatorcontrib>Quek, Richard, MD</creatorcontrib><creatorcontrib>Mohamad, Farid, MD</creatorcontrib><creatorcontrib>Tan, Soo Yong, Prof</creatorcontrib><creatorcontrib>Teh, Bin Tean, Prof</creatorcontrib><creatorcontrib>Ng, Siok Bian, FRCPA</creatorcontrib><creatorcontrib>Chng, Wee Joo, Prof</creatorcontrib><creatorcontrib>Ong, Choon Kiat, PhD</creatorcontrib><creatorcontrib>Okada, Yukinori, PhD</creatorcontrib><creatorcontrib>Raychaudhuri, Soumya, PhD</creatorcontrib><creatorcontrib>Lim, Soon Thye, MD</creatorcontrib><creatorcontrib>Tan, Wen, Prof</creatorcontrib><creatorcontrib>Peng, Rou-Jun, MD</creatorcontrib><creatorcontrib>Khor, Chiea Chuen, PhD</creatorcontrib><creatorcontrib>Bei, Jin-Xin, Prof</creatorcontrib><title>Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study</title><title>The lancet oncology</title><addtitle>Lancet Oncol</addtitle><description>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<5 × 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=4·21 × 10−19 , odds ratio [OR] 1·84 [95% CI 1·61–2·11] 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 2·38, p value for haplotype 2·32 × 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).</description><subject>Adult</subject><subject>Aged</subject><subject>Antigen presentation</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer</subject><subject>Case-Control Studies</subject><subject>China</subject><subject>Chromosome 6</subject><subject>Education</subject><subject>Epstein-Barr virus</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gene mapping</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Haplotypes</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Hepatitis</subject><subject>Histocompatibility antigen HLA</subject><subject>Humans</subject><subject>Linkage disequilibrium</subject><subject>Lymphocytes T</subject><subject>Lymphoma</subject><subject>Lymphoma, Extranodal NK-T-Cell - genetics</subject><subject>Lymphoma, Extranodal NK-T-Cell - pathology</subject><subject>Major histocompatibility complex</subject><subject>Male</subject><subject>Malignancy</subject><subject>Medical research</subject><subject>Middle Aged</subject><subject>Natural killer cells</subject><subject>Neoplasm Staging</subject><subject>Pathogenesis</subject><subject>Peptides</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Prognosis</subject><subject>Risk Factors</subject><subject>Single-nucleotide polymorphism</subject><subject>Studies</subject><subject>T cell receptors</subject><subject>T-cell lymphoma</subject><subject>Young Adult</subject><issn>1470-2045</issn><issn>1474-5488</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkUFvFSEUhYnR2Nr6EzQkbupiLMwwwLioMY1WkyYubDduCMPcaelj4BVm2r5_L_OmVtuNqwvc7x44HITeUPKBEsoPf1ImSFESVh9Q_r4ilMmCP0O7-ZgVNZPy-Xa9IDvoVUpXhFBBSf0S7ZQid4hodtGvE_AwWoOjTSscegx3Y9Q-dNphr8cp5rqyzkHEZ4UB57DbDOvLMOiPWOML8GGA4tZ2gHVKwVg92uBxGqdus49e9NoleH1f99D51y9nx9-K0x8n348_nxaGV_VY6JaaSlS1lqzlJFdgmvUtq0gHbc8r3vdUdkI2uuSs5KSULYG-YbXodSW4rvbQ0aK7ntoBOgM-O3BqHe2g40YFbdXjjreX6iLcKC4aUgqSBQ7uBWK4niCNarBp9qo9hCkpKstMMlnLjL57gl6FKfpsL1OUs2ykmQXrhTIxpBShf3gMJWpOT23TU3M0Ku-26Sme597-6-Rh6k9cGfi0AJD_88ZCVMlY8AY6G8GMqgv2v1ccPVEwznprtFvBBtJfNyqViiwiswblWwVe_Qa0V78d</recordid><startdate>20160901</startdate><enddate>20160901</enddate><creator>Li, Zheng, PhD</creator><creator>Xia, Yi, MD</creator><creator>Feng, Li-Na, MD</creator><creator>Chen, Jie-Rong, 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; 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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c635t-ab1c3735a84b6035ae4a4fb430debf636ff18d789a26426028b0ef9457fa376a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antigen presentation</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cancer</topic><topic>Case-Control Studies</topic><topic>China</topic><topic>Chromosome 6</topic><topic>Education</topic><topic>Epstein-Barr virus</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gene mapping</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Haplotypes</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Hepatitis</topic><topic>Histocompatibility antigen HLA</topic><topic>Humans</topic><topic>Linkage disequilibrium</topic><topic>Lymphocytes T</topic><topic>Lymphoma</topic><topic>Lymphoma, Extranodal NK-T-Cell - genetics</topic><topic>Lymphoma, Extranodal NK-T-Cell - pathology</topic><topic>Major histocompatibility complex</topic><topic>Male</topic><topic>Malignancy</topic><topic>Medical research</topic><topic>Middle Aged</topic><topic>Natural killer cells</topic><topic>Neoplasm Staging</topic><topic>Pathogenesis</topic><topic>Peptides</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Prognosis</topic><topic>Risk Factors</topic><topic>Single-nucleotide polymorphism</topic><topic>Studies</topic><topic>T cell receptors</topic><topic>T-cell lymphoma</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Zheng, PhD</creatorcontrib><creatorcontrib>Xia, Yi, MD</creatorcontrib><creatorcontrib>Feng, Li-Na, MD</creatorcontrib><creatorcontrib>Chen, Jie-Rong, BSc</creatorcontrib><creatorcontrib>Li, Hong-Min, MD</creatorcontrib><creatorcontrib>Cui, Jing, PhD</creatorcontrib><creatorcontrib>Cai, Qing-Qing, Prof</creatorcontrib><creatorcontrib>Sim, Kar Seng, MS</creatorcontrib><creatorcontrib>Nairismägi, Maarja-Liisa, PhD</creatorcontrib><creatorcontrib>Laurensia, Yurike, BSc</creatorcontrib><creatorcontrib>Meah, Wee Yang, BSc</creatorcontrib><creatorcontrib>Liu, Wen-Sheng, MMS</creatorcontrib><creatorcontrib>Guo, Yun-Miao, PhD</creatorcontrib><creatorcontrib>Chen, Li-Zhen, ADN</creatorcontrib><creatorcontrib>Feng, Qi-Sheng, BSc</creatorcontrib><creatorcontrib>Pang, Chi Pui, DPhil</creatorcontrib><creatorcontrib>Chen, Li Jia, PhD</creatorcontrib><creatorcontrib>Chew, Soo Hong, Prof</creatorcontrib><creatorcontrib>Ebstein, Richard P, Prof</creatorcontrib><creatorcontrib>Foo, Jia Nee, PhD</creatorcontrib><creatorcontrib>Liu, Jianjun, Prof</creatorcontrib><creatorcontrib>Ha, Jeslin, BSc</creatorcontrib><creatorcontrib>Khoo, Lay Poh, BSc</creatorcontrib><creatorcontrib>Chin, Suk Teng, BSc</creatorcontrib><creatorcontrib>Zeng, Yi-Xin, Prof</creatorcontrib><creatorcontrib>Aung, Tin, Prof</creatorcontrib><creatorcontrib>Chowbay, Balram, Prof</creatorcontrib><creatorcontrib>Diong, Colin Phipps, MD</creatorcontrib><creatorcontrib>Zhang, Fen, MD</creatorcontrib><creatorcontrib>Liu, Yan-Hui, MD</creatorcontrib><creatorcontrib>Tang, Tiffany, MD</creatorcontrib><creatorcontrib>Tao, Miriam, MD</creatorcontrib><creatorcontrib>Quek, Richard, MD</creatorcontrib><creatorcontrib>Mohamad, Farid, MD</creatorcontrib><creatorcontrib>Tan, Soo Yong, Prof</creatorcontrib><creatorcontrib>Teh, Bin Tean, Prof</creatorcontrib><creatorcontrib>Ng, Siok Bian, FRCPA</creatorcontrib><creatorcontrib>Chng, Wee Joo, Prof</creatorcontrib><creatorcontrib>Ong, Choon Kiat, PhD</creatorcontrib><creatorcontrib>Okada, Yukinori, PhD</creatorcontrib><creatorcontrib>Raychaudhuri, Soumya, PhD</creatorcontrib><creatorcontrib>Lim, Soon Thye, MD</creatorcontrib><creatorcontrib>Tan, Wen, Prof</creatorcontrib><creatorcontrib>Peng, Rou-Jun, MD</creatorcontrib><creatorcontrib>Khor, Chiea Chuen, PhD</creatorcontrib><creatorcontrib>Bei, Jin-Xin, Prof</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Pharma and Biotech Premium PRO</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Lancet Titles</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The lancet oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Zheng, PhD</au><au>Xia, Yi, MD</au><au>Feng, Li-Na, MD</au><au>Chen, Jie-Rong, BSc</au><au>Li, Hong-Min, MD</au><au>Cui, Jing, PhD</au><au>Cai, Qing-Qing, Prof</au><au>Sim, Kar Seng, MS</au><au>Nairismägi, Maarja-Liisa, PhD</au><au>Laurensia, Yurike, BSc</au><au>Meah, Wee Yang, BSc</au><au>Liu, Wen-Sheng, MMS</au><au>Guo, Yun-Miao, PhD</au><au>Chen, Li-Zhen, ADN</au><au>Feng, Qi-Sheng, BSc</au><au>Pang, Chi Pui, DPhil</au><au>Chen, Li Jia, PhD</au><au>Chew, Soo Hong, Prof</au><au>Ebstein, Richard P, Prof</au><au>Foo, Jia Nee, PhD</au><au>Liu, Jianjun, Prof</au><au>Ha, Jeslin, BSc</au><au>Khoo, Lay Poh, BSc</au><au>Chin, Suk Teng, BSc</au><au>Zeng, Yi-Xin, Prof</au><au>Aung, Tin, Prof</au><au>Chowbay, Balram, Prof</au><au>Diong, Colin Phipps, MD</au><au>Zhang, Fen, MD</au><au>Liu, Yan-Hui, MD</au><au>Tang, Tiffany, MD</au><au>Tao, Miriam, MD</au><au>Quek, Richard, MD</au><au>Mohamad, Farid, MD</au><au>Tan, Soo Yong, Prof</au><au>Teh, Bin Tean, Prof</au><au>Ng, Siok Bian, FRCPA</au><au>Chng, Wee Joo, Prof</au><au>Ong, Choon Kiat, PhD</au><au>Okada, Yukinori, PhD</au><au>Raychaudhuri, Soumya, PhD</au><au>Lim, Soon Thye, MD</au><au>Tan, Wen, Prof</au><au>Peng, Rou-Jun, MD</au><au>Khor, Chiea Chuen, PhD</au><au>Bei, Jin-Xin, Prof</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study</atitle><jtitle>The lancet oncology</jtitle><addtitle>Lancet Oncol</addtitle><date>2016-09-01</date><risdate>2016</risdate><volume>17</volume><issue>9</issue><spage>1240</spage><epage>1247</epage><pages>1240-1247</pages><issn>1470-2045</issn><eissn>1474-5488</eissn><abstract>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<5 × 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=4·21 × 10−19 , odds ratio [OR] 1·84 [95% CI 1·61–2·11] 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 2·38, p value for haplotype 2·32 × 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).</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>27470079</pmid><doi>10.1016/S1470-2045(16)30148-6</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1470-2045 |
| ispartof | The lancet oncology, 2016-09, Vol.17 (9), p.1240-1247 |
| issn | 1470-2045 1474-5488 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6790270 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| 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 |
| title | Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-16T08%3A13%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20risk%20of%20extranodal%20natural%20killer%20T-cell%20lymphoma:%20a%20genome-wide%20association%20study&rft.jtitle=The%20lancet%20oncology&rft.au=Li,%20Zheng,%20PhD&rft.date=2016-09-01&rft.volume=17&rft.issue=9&rft.spage=1240&rft.epage=1247&rft.pages=1240-1247&rft.issn=1470-2045&rft.eissn=1474-5488&rft_id=info:doi/10.1016/S1470-2045(16)30148-6&rft_dat=%3Cproquest_pubme%3E1827904858%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1816437390&rft_id=info:pmid/27470079&rft_els_id=S1470204516301486&rfr_iscdi=true |