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Abstract
To date, the only established model for assessing risk for nasopharyngeal carcinoma (NPC) relies on the sero-status of the Epstein-Barr virus (EBV). By contrast, the risk assessment models proposed here include environmental risk factors, family history of NPC, and information on genetic variants. The models were developed using epidemiological and genetic data from a large case-control study, which included 1,387 subjects with NPC and 1,459 controls of Cantonese origin. The predictive accuracy of the models were then assessed by calculating the area under the receiver-operating characteristic curves (AUC). To compare the discriminatory improvement of models with and without genetic information, we estimated the net reclassification improvement (NRI) and integrated discrimination index (IDI). Well-established environmental risk factors for NPC include consumption of salted fish and preserved vegetables and cigarette smoking (in pack years). The environmental model alone shows modest discriminatory ability (AUC = 0.68; 95% CI: 0.66, 0.70), which is only slightly increased by the addition of data on family history of NPC (AUC = 0.70; 95% CI: 0.68, 0.72). With the addition of data on genetic variants, however, our model’s discriminatory ability rises to 0.74 (95% CI: 0.72, 0.76). The improvements in NRI and IDI also suggest the potential usefulness of considering genetic variants when screening for NPC in endemic areas. If these findings are confirmed in larger cohort and population-based case-control studies, use of the new models to analyse data from NPC-endemic areas could well lead to earlier detection of NPC.
Highlights
In most parts of the world, nasopharyngeal carcinoma (NPC) occurs at an annual incidence rate of,1/100,000 [1,2], yet in South East Asia and Southern China, it is endemic
In an attempt to meet that need, this study introduces several NPC prediction models that are the first to take into account known environmental risk factors, family history of the disease, and a genetic risk score comprising seven high risk single-nucleotide polymorphisms (SNPs) identified from the southern Chinese genome-wide association studies (GWAS)
Association with NPC Risk While all seven SNPs identified in this case-control study are consistently associated with NPC risk, the most significant association occurs in SNPs: rs2860580 (OR = 1.82, 95% confidence intervals (CIs): 1.62, 2.05]), rs2894207 (OR = 1.67, 95% CI: 1.44, 1.95), and rs28421666 (OR = 1.46, 95% CI: 1.24, 1.71), located in the HLA region (Table 1)
Summary
In most parts of the world, nasopharyngeal carcinoma (NPC) occurs at an annual incidence rate of ,1/100,000 [1,2], yet in South East Asia and Southern China, it is endemic. NPC appears to be most widespread in central of Guangdong province, where the city of Sihui, for instance, shows incidence rates of 30.94/100,000 in males and 13.00/100,000 in females [3] In addition to this strikingly localized pattern of geographic distribution, NPC is known to cluster in families in diverse populations [4], suggesting that its etiology may involve distinct risk factors. One such factor, which has been consistently validated, is the widespread consumption of salted fish in endemic areas [5]. In order to capture inherited genetic susceptibilities as well as shared environmental and behavioral risk factors, we included data on family history of NPC in our predictive model
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