Nasopharyngeal carcinoma risk prediction via salivary detection of host and Epstein-Barr virus genetic variants
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Qian Cui1, Fu-Tuo Feng1, Miao Xu1, Wen-Sheng Liu1, You-Yuan Yao1, Shang-Hang Xie1, Xi-Zhao Li1, Zu-Lu Ye1, Qi-Sheng Feng1, Li-Zhen Chen1, Jin-Xin Bei1, Lin Feng1, Qi-Hong Huang5, Wei-Hua Jia1, Su-Mei Cao1, Ellen T. Chang4, Weimin Ye1,2, Hans-Olov Adami2,3 and Yi-Xin Zeng1
1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China
2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
3Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
4Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA
5Sihui Cancer Institute, Sihui, Guangdong, P. R. China
Yi-Xin Zeng, email: firstname.lastname@example.org
Hans-Olov Adami, email: email@example.com
Keywords: nasopharyngeal carcinoma, saliva, case-control, risk prediction
Received: April 16, 2016 Accepted: June 30, 2016 Published: August 09, 2016
Genetic susceptibility and Epstein-Barr virus (EBV) infection are important etiological factors in nasopharyngeal carcinoma (NPC). In this study, in southern China, where NPC is endemic, a single nucleotide polymorphism (SNP) in the EBV-encoded RPMS1 gene (locus 155391: G > A [G155391A]) and seven host SNPs (rs1412829, rs28421666, rs2860580, rs2894207, rs31489, rs6774494, and rs9510787) were confirmed to be significantly associated with NPC risk in 50 NPC cases versus 54 hospital-based controls with throat washing specimens and 1925 NPC cases versus 1947 hospital-based controls with buffy coat samples, respectively. We established a strategy to detect the NPC-associated EBV and host SNPs using saliva samples in a single test that is convenient, noninvasive, and cost-effective and displays good compliance. The potential utility of this strategy was tested by applying a risk prediction model integrating these EBV and host genetic variants to a population-based case-control study comprising 1026 incident NPC cases and 1148 controls. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve of the NPC risk prediction model of 0.74 (95% CI: 0.71−0.76). Net reclassification improvement (NRI) analysis showed that inclusion of the EBV SNP significantly improved the discrimination ability of the model (NRI = 0.30, P < 0.001), suggesting the promising value of EBV characteristics for identifying high-risk NPC individuals in endemic areas. Taken together, we developed a promising NPC risk prediction model via noninvasive saliva sampling. This approach might serve as a convenient and effective method for screening the population with high-risk of NPC.
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