PMID- 38359790 OWN - NLM STAT- MEDLINE DCOM- 20240219 LR - 20240224 IS - 2666-979X (Electronic) IS - 2666-979X (Linking) VI - 4 IP - 2 DP - 2024 Feb 14 TI - Host genetic variants, Epstein-Barr virus subtypes, and the risk of nasopharyngeal carcinoma: Assessment of interaction and mediation. PG - 100474 LID - S2666-979X(23)00318-X [pii] LID - 10.1016/j.xgen.2023.100474 [doi] LID - 100474 AB - Epstein-Barr virus (EBV) and human leukocyte antigen (HLA) polymorphisms are well-known risk factors for nasopharyngeal carcinoma (NPC). However, the combined effects between HLA and EBV on the risk of NPC are unknown. We applied a causal inference framework to disentangle interaction and mediation effects between two host HLA SNPs, rs2860580 and rs2894207, and EBV variant 163364 with a population-based case-control study in NPC-endemic southern China. We discovered the strong interaction effects between the high-risk EBV subtype and both HLA SNPs on NPC risk (rs2860580, relative excess risk due to interaction [RERI] = 4.08, 95% confidence interval [CI] = 2.03-6.14; rs2894207, RERI = 3.37, 95% CI = 1.59-5.15), accounting for the majority of genetic risk effects. These results indicate that HLA genes and the high-risk EBV have joint effects on NPC risk. Prevention strategies targeting the high-risk EBV subtype would largely reduce NPC risk associated with EBV and host genetic susceptibility. CI - Copyright (c) 2024 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Xu, Miao AU - Xu M AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. FAU - Feng, Ruimei AU - Feng R AD - Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030012, Shanxi, China. FAU - Liu, Zhonghua AU - Liu Z AD - Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA. FAU - Zhou, Xiang AU - Zhou X AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China. FAU - Chen, Yanhong AU - Chen Y AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. FAU - Cao, Yulu AU - Cao Y AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. FAU - Valeri, Linda AU - Valeri L AD - Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. FAU - Li, Zilin AU - Li Z AD - Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; School of Mathematics and Statistics, Northeast Normal University, Changchun, China. FAU - Liu, Zhiwei AU - Liu Z AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. FAU - Cao, Su-Mei AU - Cao SM AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. FAU - Liu, Qing AU - Liu Q AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. FAU - Xie, Shang-Hang AU - Xie SH AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. FAU - Chang, Ellen T AU - Chang ET AD - Center for Health Sciences, Menlo Park, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA. FAU - Jia, Wei-Hua AU - Jia WH AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. FAU - Shen, Jincheng AU - Shen J AD - Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA. FAU - Yao, Youyuan AU - Yao Y AD - Department of Geriatric Oncology, Jiangsu Province Hospital, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China. FAU - Cai, Yong-Lin AU - Cai YL AD - Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, China. FAU - Zheng, Yuming AU - Zheng Y AD - Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, China. FAU - Zhang, Zhe AU - Zhang Z AD - Department of Otolaryngology/Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China. FAU - Huang, Guangwu AU - Huang G AD - Department of Otolaryngology/Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China. FAU - Ernberg, Ingemar AU - Ernberg I AD - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. FAU - Tang, Minzhong AU - Tang M AD - Department of Otolaryngology/Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China. FAU - Ye, Weimin AU - Ye W AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Health Statistics & Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China. Electronic address: ywm@fjmu.edu.cn. FAU - Adami, Hans-Olov AU - Adami HO AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Clinical Effectiveness Group, Institute of Health and Society, University of Oslo, Oslo, Norway. Electronic address: hadami@hsph.harvard.edu. FAU - Zeng, Yi-Xin AU - Zeng YX AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: zengyx@sysucc.org.cn. FAU - Lin, Xihong AU - Lin X AD - Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. Electronic address: xlin@hsph.harvard.edu. LA - eng PT - Journal Article DEP - 20240109 PL - United States TA - Cell Genom JT - Cell genomics JID - 9918284260106676 SB - IM MH - Humans MH - Nasopharyngeal Carcinoma/genetics MH - Herpesvirus 4, Human/genetics MH - *Epstein-Barr Virus Infections/genetics MH - *Nasopharyngeal Neoplasms/epidemiology MH - Case-Control Studies MH - Polymorphism, Single Nucleotide/genetics PMC - PMC10879020 OTO - NOTNLM OT - Epstein-Barr virus OT - HLA polymorphism OT - causal inference OT - genetic susceptibility to cancer OT - interaction OT - mediation OT - nasopharyngeal carcinoma COIS- Declaration of interests The authors declare no competing interests. EDAT- 2024/02/16 00:42 MHDA- 2024/02/19 06:42 PMCR- 2024/01/09 CRDT- 2024/02/15 18:21 PHST- 2023/03/30 00:00 [received] PHST- 2023/09/29 00:00 [revised] PHST- 2023/12/06 00:00 [accepted] PHST- 2024/02/19 06:42 [medline] PHST- 2024/02/16 00:42 [pubmed] PHST- 2024/02/15 18:21 [entrez] PHST- 2024/01/09 00:00 [pmc-release] AID - S2666-979X(23)00318-X [pii] AID - 100474 [pii] AID - 10.1016/j.xgen.2023.100474 [doi] PST - ppublish SO - Cell Genom. 2024 Feb 14;4(2):100474. doi: 10.1016/j.xgen.2023.100474. Epub 2024 Jan 9.