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OBJECTIVES: Epstein-Barr virus (EBV) C promoter (Cp) hypermethylation, a crucial factor for EBV latent infection of nasopharyngeal epithelial cells, has been recognized as a promising biomarker for nasopharyngeal carcinoma (NPC) detection. In this study, we develop a novel EBV Cp methylation quantification (E-CpMQ) assay and evaluate its diagnostic performance for NPC detection. METHODS: A novel qPCR assay for simultaneous quantification of methylated- and unmethylated EBV Cp was developed by the combinational modification of MethyLight and QASM, with an innovative calibrator to improve the detection accuracy and consistency. The NP swab samples and synthetic standards were used for the analytical validation of the E-CpMQ. The diagnostic efficacy of the developed E-CpMQ assay was validated in 137 NPC patients and 137 non-NPC controls. RESULTS: The E-CpMQ assay can detect the EBV Cp methylation ratio in one reaction system under 10 copies with 100â¯% recognition specificity, which is highly correlated to pyrosequencing with a correlation coefficient over 0.99. The calibrated E-CpMQ assay reduces the coefficient of variation by an average of 55.5â¯% with a total variance of less than 0.06 units standard deviation (SD). Linear methylation ratio detection range from 4.76 to 99.01â¯%. The sensitivity and specificity of the E-CpMQ respectively are 96.4â¯% (95â¯% CI: 91.7-98.8â¯%), 89.8â¯% (95â¯% CI: 83.5-94.3â¯%). CONCLUSIONS: The developed E-CpMQ assay with a calibrator enables accurate and reproducible EBV Cp methylation ratio quantification and offers a sensitive, specific, cost-effective method for NPC early detection.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/genética , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/genética , ADN Viral/genética , Nasofaringe , Metilación de ADNRESUMEN
Previous studies have demonstrated strong associations between host genetic factors and Epstein-Barr virus (EBV) VCA-IgA with the risk of nasopharyngeal carcinoma (NPC). However, the specific interplay between host genetics and EBV VCA-IgA on NPC risk is not well understood. In this two-stage case-control study (N = 4804), we utilized interaction and mediation analysis to investigate the interplay between host genetics (genome-wide association study-derived polygenic risk score [PRS]) and EBV VCA-IgA antibody level in the NPC risk. We employed a four-way decomposition analysis to assess the extent to which the genetic effect on NPC risk is mediated by or interacts with EBV VCA-IgA. We consistently found a significant interaction between the PRS and EBV VCA-IgA on NPC risk (discovery population: synergy index [SI] = 2.39, 95% confidence interval [CI] = 1.85-3.10; replication population: SI = 3.10, 95% CI = 2.17-4.44; all pinteraction < 0.001). Moreover, the genetic variants included in the PRS demonstrated similar interactions with EBV VCA-IgA antibody. We also observed an obvious dose-response relationship between the PRS and EBV VCA-IgA antibody on NPC risk (all ptrend < 0.001). Furthermore, our decomposition analysis revealed that a substantial proportion (approximately 90%) of the genetic effects on NPC risk could be attributed to host genetic-EBV interaction, while the risk effects mediated by EBV VCA-IgA antibody were weak and statistically insignificant. Our study provides compelling evidence for an interaction between host genetics and EBV VCA-IgA antibody in the development of NPC. These findings emphasize the importance of implementing measures to control EBV infection as a crucial strategy for effectively preventing NPC, particularly in individuals at high genetic risk.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/genética , Neoplasias Nasofaríngeas/genética , Estudios de Casos y Controles , Estudio de Asociación del Genoma Completo , Anticuerpos Antivirales/genética , Proteínas de la Cápside/genética , Antígenos Virales/genética , Inmunoglobulina ARESUMEN
BACKGROUND: Epstein-Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV seropositives within an NPC screening program in China. METHODS: The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18â237 screened). Nasopharynx swabs were collected/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy/MRI) and medium-risk (those referred to accelerated screening) individuals. RESULTS: By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%-99.9%), with a referral rate of 63.4% (201/317, 95% CI, 57.8%-68.7%) and NPC detection rate among positives of 9.5% (19/201, 95% CI, 5.8%-14.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%). CONCLUSIONS: Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.
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Infecciones por Virus de Epstein-Barr , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Anticuerpos Antivirales , ADN , ADN Viral , Infecciones por Virus de Epstein-Barr/diagnóstico , Herpesvirus Humano 4/genética , Humanos , Inmunoglobulina A , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Nasofaringe , Reflejo , TriajeRESUMEN
Despite evidence suggesting the utility of Epstein-Barr virus (EBV) markers to stratify individuals with respect to nasopharyngeal carcinoma (NPC) risk in NPC high-risk regions, no validated NPC risk prediction model exists. We aimed to validate an EBV-based NPC risk score in an endemic population undergoing screening for NPC. This prospective study was embedded within an ongoing NPC screening trial in southern China initiated in 2008, with 51 235 adult participants. We assessed the score's discriminatory ability (area under the receiver-operator-characteristics curve, AUC). A new model incorporating the EBV score, sex and family history was developed using logistic regression and internally validated using cross-validation. AUCs were compared. We also calculated absolute NPC risk combining the risk score with population incidence and competing mortality data. A total of 151 NPC cases were detected in 2008 to 2016. The EBV-based score was highly discriminating, with AUC = 0.95 (95% CI = 0.93-0.97). For 90% specificity, the score had 87.4% sensitivity (95% CI = 81.0-92.3%). As specificity increased from 90% to 99%, the positive predictive value increased from 2.4% (95% CI = 1.9-3.0%) to 12.5% (9.9-15.5%). Correspondingly, the number of positive tests per detected NPC case decreased from 272 (95% CI = 255-290) to 50 (41-59). Combining the score with other risk factors (sex, first-degree family history of NPC) did not improve AUC. Men aged 55 to 59 years with the highest risk profile had the highest 5-year absolute NPC risk of 6.5%. We externally validated the discriminatory accuracy of a previously developed EBV score in a high-risk population. Adding nonviral risk factors did not improve NPC prediction.
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BACKGROUND: The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. METHODS: The authors conducted a population-based case-control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self-reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration-response relations. RESULTS: Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26-1.68), chemical vapors (OR, 1.37; 95% CI, 1.17-1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25-1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30-1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia. CONCLUSIONS: Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas. LAY SUMMARY: The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC. Duration-response trends were observed with increasing duration of exposure. These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high-incidence region.
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Neoplasias Nasofaríngeas , Exposición Profesional , Estudios de Casos y Controles , Humanos , Carcinoma Nasofaríngeo/epidemiología , Neoplasias Nasofaríngeas/epidemiología , Neoplasias Nasofaríngeas/etiología , Exposición Profesional/efectos adversos , Factores de RiesgoRESUMEN
BACKGROUND: Although stratifying individuals with respect to nasopharyngeal carcinoma (NPC) risk with Epstein-Barr virus-based markers is possible, the performance of diagnostic methods for detecting lesions among screen-positive individuals is poorly understood. METHODS: The authors prospectively evaluated 882 participants aged 30 to 70 years who were enrolled between October 2014 and November 2018 in an ongoing, population-based NPC screening program and had an elevated NPC risk. Participants were offered endoscopy and magnetic resonance imaging (MRI), and lesions were identified either by biopsy at a follow-up endoscopy or further contact and linkage to the local cancer registry through December 31, 2019. The diagnostic performance characteristics of endoscopy and MRI for NPC detection were investigated. RESULTS: Eighteen of 28 identified NPC cases were detected by both methods, 1 was detected by endoscopy alone, and 9 were detected by MRI alone. MRI had significantly higher sensitivity than endoscopy for NPC detection overall (96.4% vs 67.9%; Pdifference = .021) and for early-stage NPC (95.2% vs 57.1%; P = .021). The sensitivity of endoscopy was suggestively lower among participants who had previously been screened in comparison with those undergoing an initial screening (50.0% vs 81.2%; P = .11). The authors observed a higher overall referral rate by MRI versus endoscopy (17.3% vs 9.1%; P < .001). Cases missed by endoscopy had early-stage disease and were more commonly observed for tumors originating from the pharyngeal recess. CONCLUSIONS: MRI was more sensitive than endoscopy for NPC detection in the context of population screening but required the referral of a higher proportion of screen-positive individuals. The sensitivity of endoscopy was particularly low for individuals who had previously been screened.
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Carcinoma , Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Adulto , Anciano , Carcinoma/diagnóstico por imagen , Detección Precoz del Cáncer/métodos , Endoscopía/métodos , Endoscopía Gastrointestinal , Herpesvirus Humano 4 , Humanos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/patologíaRESUMEN
OBJECTIVE: Plasma Epstein-Barr virus (EBV) DNA is considered a biomarker for nasopharyngeal carcinoma (NPC). However, its long-term role in NPC development is unclear. MATERIALS AND METHODS: A total of 1363 participants seropositive for EBV VCA-IgA and EBNA1-IgA in a community-based NPC screening program in southern China were tested for plasma EBV DNA levels by real-time qPCR between 2008 and 2015. New NPC cases were confirmed by active follow-up approach and linkage to local cancer registry through the end of 2016. Cox proportional hazards regression analysis was performed to calculate the hazard ratios (HRs) for NPC risk with plasma EBV DNA. RESULTS: Thirty patients were newly diagnosed during a median 7.5 years follow-up. NPC incidence increased with the plasma EBV DNA load ranging from 281.46 to 10,074.47 per 100,000 person-years in participants with undetectable and ≥ 1000 copies/ml levels; the corresponding cumulative incidence rates were 1.73 and 50%. Furthermore, plasma EBV DNA loads conferred an independent risk for NPC development after adjustment for other risk factors, with HRs of 7.63 for > 3-999 copies/ml and 39.79 for ≥1000 copies/ml. However, the HRs decreased gradually after excluding NPC cases detected in the first 2 to 3 years and became statistically nonsignificant by excluding cases detected during the first 4 years. CONCLUSION: Elevated plasma EBV DNA can predict NPC risk over 3 years. Monitoring plasma EBV DNA can be used as a complementary approach to EBV serological antibody-based screening for NPC.
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Biomarcadores de Tumor/sangre , ADN Viral/sangre , Infecciones por Virus de Epstein-Barr/epidemiología , Carcinoma Nasofaríngeo/epidemiología , Neoplasias Nasofaríngeas/epidemiología , Adulto , Anciano , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , Proteínas de la Cápside/inmunología , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/virología , Femenino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/virología , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/virología , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Pruebas Serológicas/estadística & datos numéricosRESUMEN
PURPOSE: To compare the performance of three-level EuroQol five-dimensions (EQ-5D-3L) and five-level EuroQol five-dimensions (EQ-5D-5L) among common cancer patients in urban China. METHODS: A hospital-based cross-sectional survey was conducted in three provinces from 2016 to 2018 in urban China. Patients with breast cancer, colorectal cancer, or lung cancer were recruited to complete the EQ-5D-3L and EQ-5D-5L questionnaires. Response distribution, discriminatory power (indicator: Shannon index [H'] and Shannon evenness index [J']), ceiling effect (the proportion of full health state), convergent validity, and health-related quality of life (HRQoL) were compared between the two instruments. RESULTS: A total of 1802 cancer patients (breast cancer: 601, colorectal cancer: 601, lung cancer: 600) were included, with the mean age of 55.6 years. The average inconsistency rate was 4.4%. Compared with EQ-5D-3L (average: H' = 1.100, J' = 0.696), an improved discriminatory power was observed in EQ-5D-5L (H' = 1.473, J' = 0.932), especially contributing to anxiety/depression dimensions. The ceiling effect was diminished in EQ-5D-5L (26.5%) in comparison with EQ-5D-3L (34.5%) (p < 0.001), mainly reflected in the pain/discomfort and anxiety/depression dimensions. The overall utility score was 0.790 (95% CI 0.778-0.801) for EQ-5D-3L and 0.803 (0.790-0.816) for EQ-5D-5L (p < 0.001). A similar pattern was also observed in the detailed cancer-specific analysis. CONCLUSIONS: With greater discriminatory power, convergent validity and lower ceiling, EQ-5D-5L may be preferable to EQ-5D-3L for the assessment of HRQoL among cancer patients. However, higher utility scores derived form EQ-5D-5L may also lead to lower QALY gains than those of 3L potentially in cost-utility studies and underestimation in the burden of disease.
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Neoplasias/epidemiología , Psicometría/métodos , Calidad de Vida/psicología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Liquid biopsy is gaining increasing popularity in cancer screening and diagnosis. However, there is no relatively mature DNA isolation method or commercial kit available that is compatible with different LB sample types. This study developed a PAN-sample DNA isolation method (PAN method) for liquid biopsy samples. METHODS: The PAN method has two key steps, including biosample-specific pretreatments for various LB sample types and high concentration guanidine thiocyanate buffer for lysis and denaturation procedure. Subsequently, the performance of PAN method was validated by a series of molecular analyses. RESULTS: The PAN method was used to isolate DNA from multiple sample types related to LB, including plasma, serum, saliva, nasopharyngeal swab, and stool. All purified DNA products showed good quality and high quantity. Comparison of KRAS mutation analysis using DNA purified using PAN method versus QIAamp methods showed similar efficiency. Epstein-Barr virus DNA was detected via Q-PCR using DNA purified from serum, plasma, nasopharyngeal swab, and saliva samples collected from nasopharyngeal carcinoma patients. Similarly, methylation sequencing of swab and saliva samples revealed good coverage of target region and high methylation of HLA-DPB1 gene. Finally, 16S rDNA gene sequencing of saliva, swab, and stool samples successfully defines the relative abundance of microbial communities. CONCLUSIONS: This study developed and validated a PAN-sample DNA isolation method that can be used for different LB samples, which can be applied to molecular epidemiological research and other areas.
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ADN Viral/aislamiento & purificación , Infecciones por Virus de Epstein-Barr/diagnóstico , Heces/virología , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/diagnóstico , Saliva/virología , Manejo de Especímenes/métodos , Estudios de Casos y Controles , Metilación de ADN , ADN Viral/análisis , ADN Viral/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Cadenas beta de HLA-DP/análisis , Cadenas beta de HLA-DP/genética , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Biopsia Líquida , Neoplasias Nasofaríngeas/virología , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16SRESUMEN
Background: Oral Epstein-Barr virus (EBV) status reflects host EBV activity and potentially links to EBV-associated diseases, however, factors influencing oral EBV loads or reactivation, such as environmental exposures or host factors, are not fully understood. Methods: A 2-stage, multicenter, cross-sectional study of 6558 subjects from 21 administrative cities of southern China and 3 populations from representative geographical areas in China (referred to as the south, north, and northeastern populations) was performed. The relationships between demographical factors and environmental exposures to EBV loads were analyzed by logistic regression models. Results: Current smoking, with a dose-response effect, was found to be strongly associated with higher oral EBV loads in the pooled data, with an odds ratio of 1.58 (95% confidence interval, 1.39-1.79), as well as in each of the separate populations. The odds ratio increased to 3.06 when current smokers in southern China were compared to never smokers in northern China. Additionally, higher oral EBV loads tended to be detected in older participants, male participants, and participants in southern China. Conclusions: This study provided evidence linking the effect of host-environmental factors, particularly smoking, to oral EBV activity. It could strengthen our understanding of the possible causal roles of EBV-related diseases, which may help to prevent or mitigate EBV-associated diseases.
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ADN Viral , Demografía , Exposición a Riesgos Ambientales , Herpesvirus Humano 4/genética , Boca/virología , Adulto , Anciano , Anciano de 80 o más Años , China , Estudios Transversales , Infecciones por Virus de Epstein-Barr/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Población , Análisis de Regresión , Fumar , Carga Viral , Adulto JovenRESUMEN
In this paper, we aim to control and evaluate the quality of Liuwei Dihuang Concentrated Pill by using the model of fingerprint technique and "component structure" theory. Agilent 5 TC-C_(18) column(4.6 mm×250 mm,5 µm) was used, with 0.1% formic acid solution-acetonitrile as mobile phase at a flow rate of 1.0 mL·min~(-1). The column temperature was 30 â, with detection wavelength of 242 nm and the sample volume of 10 µL. The characteristic fingerprint of Liuwei Dihuang Concentrated Pill was established by high performance liquid chromatography(HPLC) for its quality control. Seventeen common peaks were identified, and the similarity was 0.550-0.997 in 29 batches of samples, indicating that the quality difference among batches of Liuwei Dihuang Concentrated Pills was significant. The structural characteristics of the Moutan Cortex components in Liuwei Dihuang Concentrated Pills were characterized. On this basis, combined with the structural characteristics of genuine components of Moutan Cortex, the structural characteristics of components in Liuwei Dihuang Concentrated Pills were further analyzed. The results showed that there were significant differences in the contents and quantity ratios of 9 representative components(components) of Moutan Cortex in Liuwei Dihuang Concentrated Pills from different manufacturers, indicating internal quality differences among different batches of products. The fingerprint technique and the "component structure" theory established by the above research provide an analytical method and a research foundation for the quality evaluation of Liuwei Dihuang Concentrated Pills.
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Medicamentos Herbarios Chinos , Cromatografía Líquida de Alta Presión , Control de CalidadRESUMEN
Guided by the theory of "component structure", we analyzed the structural characteristics of pharmacodynamical components in genuine Moutan Cortex. The compositions of organic small molecules were determined by high performance liquid chromatography(HPLC) for 20 batches of genuine Moutan Cortex and 12 batches of non-genuine Moutan Cortex. By means of similarity analysis, clustering analysis(CA), principal component analysis(PCA) and orthogonal partial least-squares discriminant analysis(OPLS-DA), the elements in structural characteristics of the pharmacodynamical components were extracted as follows: terpene glycosides components(oxidized paeoniflorin, paeoniflorin,galloyl paeoniflorin, benzoyloxy paeoniflorinand benzoyl paeoniflorin), tannin components(1,3,6-tri-O-galloside acyl glucose, pentagalloyl glucose), and phenolic acid components(methyl gallate, paeonol). The contents and quantity ratios of terpene glycoside component, tannin component and phenolic acid components in genuine Moutan Cortex were determined as 14.1, 12.5, 21.7 mg·g~(-1), 1.00â¶0.89â¶1.54. The contents and quantity ratios of the oxidized paeoniflorin, paeoniflorin and benzoylpaeoniflorin in the terpene glycoside components were characteristic and determined as 2.05, 7.05, 3.30 mg·g~(-1), 1.00â¶3.44â¶1.61. The unique structural characteristics of genuine Moutan Cortex provide scientific basis for the formulation of quality standards.
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Medicamentos Herbarios Chinos , Paeonia , Cromatografía Líquida de Alta Presión , Análisis de Componente PrincipalRESUMEN
BACKGROUND: An association between a nonmedicinal herbal diet and nasopharyngeal carcinoma (NPC) has often been hypothesized but never thoroughly investigated. METHODS: This study enrolled a total of 2469 patients with incident NPC and 2559 population controls from parts of Guangdong and Guangxi Provinces in southern China between 2010 and 2014. Questionnaire information was collected on the intake of traditional herbal tea and herbal soup as well as the specific herbal plants used in soups and other potentially confounding lifestyle factors. Multivariate logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the NPC risk in association with herbal tea and soup intake. RESULTS: Ever consumption of herbal tea was not associated with NPC risk (OR, 1.03; 95% CI, 0.91-1.17). An inverse association was observed for NPC among ever drinkers of herbal soup (OR, 0.78; 95% CI, 0.67-0.90) but without any monotonic trend with an increasing frequency or duration of herbal soup consumption. Inverse associations with NPC risk were detected with 9 herbal plants used in herbal soup, including Ziziphus jujuba, Fructus lycii, Codonopsis pilosula, Astragalus membranaceus, Semen coicis, Smilax glabra, Phaseolus calcaratus, Morinda officinalis, and Atractylodes macrocephala (OR range, 0.31-0.79). CONCLUSIONS: Consuming herbal soups including specific plants, but not herbal tea, was inversely associated with NPC. If replicated, these results might provide potential for NPC prevention in endemic areas.
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Dieta , Carcinoma Nasofaríngeo/epidemiología , Carcinoma Nasofaríngeo/etiología , Adulto , Anciano , Estudios de Casos y Controles , Susceptibilidad a Enfermedades , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Vigilancia de la Población , Factores de Riesgo , Adulto JovenRESUMEN
IgA antibodies targeting Epstein-Barr virus (EBV) have been proposed for screening for nasopharyngeal carcinoma (NPC). However, methods differ, and the antigens used in these assays differ considerably between laboratories. To enable formal comparisons across a range of established EBV serology assays, we created a panel of 66 pooled serum samples and 66 pooled plasma samples generated from individuals with a broad range of IgA antibody levels. Aliquots from these panels were distributed to six laboratories and were tested by 26 assays measuring antibodies against VCA, EBNA1, EA-EBNA1, Zta, or EAd antigens. We estimated the correlation between assay pairs using Spearman coefficients (continuous measures) and percentages of agreement (positive versus negative, using predefined positivity cutoffs by each assay developer/manufacturer). While strong correlations were observed between some assays, considerable differences were also noted, even for assays that targeted the same protein. For VCA-IgA assays in serum, two distinct clusters were identified, with a median Spearman coefficient of 0.41 (range, 0.20 to 0.66) across these two clusters. EBNA1-IgA assays in serum grouped into a single cluster with a median Spearman coefficient of 0.79 (range, 0.71 to 0.89). Percentages of agreement differed broadly for both VCA-IgA (12% to 98%) and EBNA1-IgA (29% to 95%) assays in serum. Moderate-to-strong correlations were observed across assays in serum that targeted other proteins (correlations ranged from 0.44 to 0.76). Similar results were noted for plasma. We conclude that standardization of EBV serology assays is needed to allow for comparability of results obtained in different translational research studies across laboratories and populations.
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Anticuerpos Antivirales/sangre , Técnicas de Laboratorio Clínico/normas , Infecciones por Virus de Epstein-Barr/diagnóstico , Laboratorios , Pruebas Serológicas/normas , Proteínas Virales/inmunología , Antígenos Virales/inmunología , Bancos de Muestras Biológicas , Proteínas de la Cápside/inmunología , Técnicas de Laboratorio Clínico/métodos , Antígenos Nucleares del Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4 , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Pruebas Serológicas/métodosRESUMEN
BACKGROUND: Chinese-style salted fish intake in early life is considered an established risk factor for nasopharyngeal carcinoma (NPC). However, results for adult intakes of salted fish and preserved foods are inconsistent. OBJECTIVE: The aim of this study was to ascertain the relations of Chinese-style hard and soft salted fish and preserved food intakes with NPC risk. METHODS: We conducted a population-based case-control study in southern China with 2554 NPC cases identified through a rapid case ascertainment system and 2648 healthy controls, frequency-matched on age, sex, and area. Subjects (aged 20-74 y) were interviewed via a food-frequency questionnaire, including information on portion size. Data were also collected on alcohol consumption and potential confounders. Food intake was grouped into 3-5 energy-adjusted intake levels during adulthood (10 y prior) and adolescence (16-18 y). For childhood (at age 10 y), intake frequency of selected food items was collected. Multivariate-adjusted ORs with 95% CIs were estimated via logistic regression. RESULTS: We found no association between NPC and intake of hard Chinese-style salted fish during adulthood, and an increased risk at the highest level of intake during adolescence (OR: 1.19; 95% CI: 1.03, 1.39). In contrast, we found a decreased risk for the middle intake level of soft salted fish during adulthood (OR: 0.68; 95% CI: 0.57, 0.81) and adolescence (OR: 0.71; 95% CI: 0.59, 0.85). Preserved foods showed contrasting risk profiles, e.g., the highest adult intake level of salted egg (OR: 1.51; 95% CI: 1.22, 1.87) and fermented black beans (OR: 0.67; 95% CI: 0.56, 0.80). Associations with NPC were weaker than previously reported, e.g., for weekly childhood intake of salted fish (OR: 1.56; 95% CI: 1.24, 1.97). CONCLUSIONS: Hard and soft salted fish have different risk profiles. Salted fish and other preserved foods were at most weak risk factors for NPC in all periods and may play a smaller role in NPC occurrence than previously thought.
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Productos Pesqueros/efectos adversos , Alimentos en Conserva/efectos adversos , Carcinoma Nasofaríngeo/etiología , Neoplasias Nasofaríngeas/etiología , Cloruro de Sodio Dietético/efectos adversos , Adolescente , Adulto , Anciano , Animales , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , RiesgoRESUMEN
Because persistent inflammation may render the nasopharyngeal mucosa susceptible to carcinogenesis, chronic ear-nose-throat (ENT) disease and its treatment might influence the risk of nasopharyngeal carcinoma (NPC). Existing evidence is, however, inconclusive and often based on methodologically suboptimal epidemiologic studies. In a population-based case-control study in southern China, we enrolled 2,532 persons with NPC and 2,597 controls, aged 20-74 years, from 2010 to 2014. Odds ratios were estimated for associations between NPC risk and history of ENT and related medications. Any history of chronic ENT disease was associated with a 34% increased risk of NPC. Similarly, use of nasal drops or aspirin was associated with approximately doubled risk of NPC. However, in secondary analyses restricted to chronic ENT diseases and related medication use at least 5 years prior to diagnosis/interview, most results were statistically nonsignificant, except a history of uncured ENT diseases, untreated nasal polyps, and earlier age at first diagnosis of ENT disease and first or most recent aspirin use. Overall, these findings suggest that ENT disease and related medication use are most likely early indications rather than causes of NPC, although the possibility of a modestly increased NPC risk associated with these diseases and related medications cannot be excluded.
Asunto(s)
Carcinoma Nasofaríngeo/epidemiología , Neoplasias Nasofaríngeas/epidemiología , Enfermedades Otorrinolaringológicas/complicaciones , Adulto , Anciano , Aspirina/efectos adversos , Estudios de Casos y Controles , China/epidemiología , Enfermedad Crónica , Femenino , Humanos , Modelos Logísticos , Masculino , Medicina Tradicional China/efectos adversos , Persona de Mediana Edad , Análisis Multivariante , Carcinoma Nasofaríngeo/etiología , Neoplasias Nasofaríngeas/etiología , Oportunidad Relativa , Enfermedades Otorrinolaringológicas/tratamiento farmacológico , Factores de Riesgo , Adulto JovenRESUMEN
The magnitude and patterns of associations between smoking and risk of nasopharyngeal carcinoma (NPC) in high-incidence regions remain uncertain. Associations with active and passive tobacco smoking were estimated using multivariate logistic regression in a population-based case-control study of 2,530 NPC cases and 2,595 controls in Guangdong and Guangxi, southern China, in 2010-2014. Among men, risk of NPC was significantly higher in current smokers compared with never smokers (odds ratio (OR) = 1.32, 95% confidence interval (CI): 1.14, 1.53) but not in former smokers (OR = 0.92, 95% CI: 0.73, 1.17). Risk increased with smoking intensity (per 10 cigarettes/day, OR = 1.09, 95% CI: 1.03, 1.16), smoking duration (per 10 years, OR = 1.11, 95% CI: 1.06, 1.16), and cumulative smoking (per 10 pack-years, OR = 1.08, 95% CI: 1.04, 1.12). Risk decreased with later age at smoking initiation (per year, OR = 0.97, 95% CI: 0.96, 0.98) but not greater time since smoking cessation. Exposures to passive smoking during childhood (OR = 1.24, 95% CI: 1.03, 1.48) and from a spouse during adulthood (OR = 1.30, 95% CI: 1.03, 1.63) were independently associated with increased NPC risk in never-smoking men and women, but exposure-response trends were not observed. In conclusion, active and passive tobacco smoking are associated with modestly increased risk of NPC in southern China; risk is highest among long-term smokers.
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Carcinoma/etiología , Neoplasias Nasofaríngeas/etiología , Fumar/efectos adversos , Contaminación por Humo de Tabaco/efectos adversos , Adulto , Anciano , Carcinoma/epidemiología , Estudios de Casos y Controles , China/epidemiología , Femenino , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/epidemiología , Oportunidad Relativa , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: To the authors' knowledge, no studies to date have explored familial risks of nasopharyngeal carcinoma (NPC) in detail and quantified its lifetime risk in high-incidence populations. METHODS: The authors conducted a population-based case-control study of 2499 NPC cases and 2576 controls randomly selected in southern China from 2010 through 2014. Unconditional logistic regression was used to estimate multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) associated with a family history of NPC. In addition, the authors compiled a reconstructed cohort comprising 40,781 first-degree relatives of cases and controls to calculate the lifetime cumulative risk of NPC. RESULTS: Individuals with a first-degree family history of NPC were found to be at a >4-fold risk of NPC (OR, 4.6; 95% CI, 3.5-6.1) compared with those without such a history, but had no excess risk of other malignancies. The excess risk was higher for a maternal than a paternal history and was slightly stronger for a sibling compared with a parental history, and for a sororal than a fraternal history. Among relatives of cases, the cumulative risk of NPC up to age 74 years was 3.7% (95% CI, 3.3%-4.2%), whereas that among relatives of controls was 0.9% (95% CI, 0.7%-1.2%). Cumulative risk was higher in siblings than in parents among relatives of cases, whereas no such difference was noted among relatives of controls. CONCLUSIONS: Individuals with a family history of NPC have a substantially higher risk of NPC. These relative and cumulative risk estimates can guide the development of strategies for early detection and clinical consultation in populations with a high incidence of NPC. Cancer 2017;123:2716-25. © 2017 American Cancer Society.
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Carcinoma/epidemiología , Neoplasias Nasofaríngeas/epidemiología , Adulto , Anciano , Carcinoma/genética , Estudios de Casos y Controles , China/epidemiología , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Humanos , Incidencia , Modelos Logísticos , Masculino , Anamnesis , Persona de Mediana Edad , Análisis Multivariante , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Oportunidad Relativa , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Adulto JovenRESUMEN
Acylglycerol kinase (AGK) has been reported to promote a malignant phenotype and enhance the development of cancer stem cells. However, the clinical value of AGK in cancer remains unclear. This study aimed to investigate the expression and clinicopathological significance of AGK in nasopharyngeal carcinoma (NPC). AGK was significantly upregulated in NPC cell lines and clinical specimens as indicated by real-time PCR and Western blotting. Among the AGK-positive cases, 52/114 (45.6 %) of the archived human NPC specimens expressed high levels of AGK. High expression of AGK was associated with significantly shorter overall and disease-free survival (P < 0.001 and P = 0.002; log-rank test) and was an independent prognostic factor for overall survival (P = 0.041; multivariate Cox analysis). High AGK expression was associated with lymph node metastasis (P < 0.001; chi-squared test) and was an independent predicted factor for lymph node metastasis in NPC (P = 0.032; multivariate logistic analysis). AGK is overexpressed and associated with disease progression and lymph node metastasis in NPC. AGK has potential as a novel prognostic factor for overall survival in NPC.
Asunto(s)
Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Neoplasias Nasofaríngeas/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Adulto , Western Blotting , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Modelos Logísticos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias Nasofaríngeas/enzimología , Neoplasias Nasofaríngeas/patología , Estadificación de Neoplasias , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia ArribaRESUMEN
INTRODUCTION: In the past several decades, declining incidences of nasopharyngeal carcinoma (NPC) have been observed in Chinese populations in Hong Kong, Taiwan, Los Angeles, and Singapore. A previous study indicated that the incidence of NPC in Sihui County, South China remained stable until 2002, but whether age, diagnosis period, and birth cohort affect the incidence of NPC remains unknown. METHODS: Age-standardized rates (ASRs) of NPC incidence based on the world standard population were examined in both males and females in Sihui County from 1987 to 2011. Joinpoint regression analysis was conducted to quantify the changes in incidence trends. A Poisson regression age-period-cohort model was used to assess the effects of age, diagnosis period, and birth cohort on the risk of NPC. RESULTS: The ASRs of NPC incidence during the study period were 30.29/100,000 for males and 13.09/100,000 for females. The incidence of NPC remained stable at a non-significant average annual percent change of 0.2% for males and -1.6% for females throughout the entire period. A significantly increased estimated annual percent change of 6.8% (95% confidence interval, 0.1%-14.0%) was observed from 2003 to 2009 for males. The relative risk of NPC increased with advancing age up to 50-59 and decreased at ages >60 years. The period effect curves on NPC were nearly flat for males and females. The birth cohort effect curve for males showed an increase from the 1922 cohort to the 1957 cohort and a decrease thereafter. In females, there was an undulating increase in the relative risk from the 1922 cohort to the 1972 cohort. CONCLUSIONS: The incidence trends for NPC remained generally stable in Sihui from 1987 to 2011, with an increase from 2003 to 2009. The relative risks of NPC increased in younger females.