Abstract
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.
Highlights
Nasopharyngeal carcinoma (NPC) is a malignancy associated with Epstein-Barr virus (EBV)
Based on genotyping for RPMS1 using nested polymerase chain reaction (PCR) and Sanger sequencing methods in study population 1, we found that the frequencies of G155391A were significantly higher in the 50 matched samples from nasopharyngeal carcinoma (NPC) patients (84% in tumor biopsy samples and 82% in tumor washing samples) than that in 54 healthy throat washing samples (39%) (Table 1)
The sex and age-adjusted odds ratio (OR) for NPC associated with the A vs. G genotype was 8.41 based on tumor biopsy samples, and 6.34 based on throat washing samples
Summary
Nasopharyngeal carcinoma (NPC) is a malignancy associated with Epstein-Barr virus (EBV). It is quite rare in most parts of the world, with incidence rates well below 1 per 100,000 person-years, but it is rather prevalent in southern China, southeast Asia and northern Africa [1]. It has a geographic distribution and strikingly high incidence in the Guangdong Province, southern China, with an incidence rates above 20 per 100,000. Prevention and early detection are key to reducing NPC burden
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