Single nucleotide polymorphisms within NFKBIA are associated with nasopharyngeal carcinoma susceptibility in Chinese Han population.

Genes involved in latent membrane protein 1 (LMP1) signaling pathways have been suggested to play an important role in nasopharyngeal carcinogenesis. We investigated potentially functional genetic variants associated with the risk of nasopharyngeal carcinoma (NPC) in genes involved in the LMP1 signaling pathway. Altogether, 73 single nucleotide polymorphisms (SNPs) with MAF ≥ 10% were located within the regions of interest of the four genes TRAF3, NFKBIA, CHUK and MAP2K4. From these, 10 SNPs were selected for genotyping based on LD (r2 ≥ 0.80) in a hospital-based case-control study of 332 NPC cases and 585 healthy controls from the Chinese Han population. Minor allele carriers of the promoter SNP rs2233409 in NFKBIA, had an increased risk of NPC (AA vs GG: OR 7.14, 95%CI, 1.08-34.18, P = 0.04, dominant model). Based on the results, we concluded that rs2233409 polymorphism in NFKBIA may be moderately associated with the risk of NPC. Further studies with larger independent samples and functional analysis are needed to verify our results.

A functional variant in CHK1 contributes to increased risk of nasopharyngeal carcinoma in a Han Chinese population.

DNA damage checkpoints act as a supervisor by preventing the course of cell cycle upon DNA damage and keeping the steadiness of genome. Checkpoint kinase 1 (CHK1) cannot be ignore in the etiology of numerous human cancers including nasopharyngeal cancer (NPC). To discuss genetic polymorphisms of CHK1 rs492510 in the occurrence of NPC was our objective. Rs492510 polymorphism of CHK1 was genotyped in 684 patients with NPC and 823 cancer-free controls. We utilize logistic regression models to appraise the correlation of rs492510 and susceptibility of NPC. Comparative expression level about CHK1 in nasopharyngeal carcinoma tissues were determined by real-time polymerase chain reaction. And we made use of Dual-Luciferase Reporter Assay to assess the transcriptional ability of CHK1 with different rs492510 allele. Adjusting multivariate logistic regression based on age, sex, body mass index, smoking, and drinking status showed that CHK1 rs492510 GA + GG genotype carriers presented prominent higher risk in NPC (odds ratio = 1.376, 95% confidence interval: 1.087-1.742; P = .008). As a consequence, we revealed that CHK1 relative expression levels in NPC tissues was higher than rhinitis tissues. Besides, the expressions of CHK1 in rs492510 GA genotype carriers were higher compared with people in AA genotype. The G allele of rs492510 generated remarkable higher transcription activity of CHK1 vs A allele by luciferase reporter assay. Our study considered that single nucleotide polymorphism rs492510 could increase transcription activity of CHK1 with the functionality, contributing to the susceptibility of NPC.

The racial disparity of nasopharyngeal carcinoma based on the database analysis.

OBJECTIVE: To investigate whether the racial/ethnical disparity of nasopharyngeal carcinoma exists among the four major ethical groups in the United States named Asians, Caucasians, African Americans and Hispanics between the years of 1973 to 2013 using the Surveillance, Epidemiology, and End Result (SEER) database. METHODS: The National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database from 1973 to 2013 was utilized in this study to calculate survival trends for the four main ethical groups in the United States. The cases of nasopharyngeal carcinoma were extracted based on the SEER code cs0204schema. Death due to the diagnosed nasopharyngeal cancer was considered to be the event of interest, and death due to other causes was treated as the censoring events. Kaplan-Meier model was adopted to estimate survival outcomes; the Cox proportional hazards model was employed to do the hazard ratios (HR) estimation. RESULTS: A total of 8068 eligible patients of nasopharyngeal carcinoma were identified. The cohort was composed of 40.69% Caucasians, 11.34% African Americans, 40.16% Asians and 7.81% Hispanics. According to the multivariate Cox regression analysis, Asians had a better survival prognosis against Caucasians (HR: 0.74, 95% CI: 0.65-0.84, P < 0.001). African Americans showed marginal worse survival prognosis compared with Caucasians (HR: 1.26, 95% CI: 1.07-1.49, P < 0.005). There was no significant difference between Hispanics and Caucasians (HR: 1.13, 95% CI: 0.92-1.39, P = 0.261). CONCLUSION: Asians showed a disease specific survival advantage over Caucasians, African Americans and Hispanics, which was independent of sex, age at diagnosis, grade, TNM staging and treatment strategy.

Does East meet West? Towards a unified vision of the management of Nasopharyngeal carcinoma.

Nasopharyngeal cancer (NPC) is notable for its wide geographic variation, with incidences as high as 30 in 100,000 in endemic regions but < 1 in 100,000 worldwide. This review aims to identify areas where there could be differences in prognosis, management or outcomes among countries with high or low incidence of NPC. The incidence has generally declined both in endemic and non-endemic regions throughout the years, which may be attributed to the decrease in exposure to risk factors such as early exposure to salted fish and smoking. Ethnicity has an impact both on incidence and prognosis, with Southeast Asians having the highest incidence but also better survival. Concurrent chemoradiotherapy, with or without adjuvant and/or induction chemotherapy, is the standard of care for locoregionally advanced disease, as reflected in clinical practice guidelines. Despite improvements in management, a proportion of patients relapse. Salvage treatment is associated with significant morbidity due to the critical location of the nasopharynx and the toxicities of initial therapy. Clinical expertise is paramount, but is easier to attain in endemic regions and high volume centers where enrollment of patients in clinical trials is more feasible. Collaboration between low and high incidence countries and between low and high volume facilities is key to improving NPC prognosis worldwide.

Survival differences in nasopharyngeal carcinoma among racial and ethnic minority groups in the United States: A retrospective cohort study.

OBJECTIVE: The literature on nasopharyngeal carcinoma survival in the United States has focused mostly on Whites or Asians and not much is known about survivorship in other minority racial and ethnic groups. We aimed to determine the disease-specific survival rate and prognostic factors for nasopharyngeal carcinoma survival across the minority United States population. DESIGN: A retrospective cohort study. SETTING: The Surveillance, Epidemiology and End Results (SEER) 13 database from 1992 to 2014 was queried for adult cases of nasopharyngeal carcinoma (n = 2549). PARTICIPANTS: Eligible cases were Blacks, Hispanics, Asians/Pacific Islanders, American Indians/Alaska Natives; White patients were excluded. MAIN OUTCOMES MEASURE: A multivariable competing risk survival analysis yielded hazard ratios (HR) for competing mortality and was used to identify independent prognostic factors for survival. RESULTS: Non-Hispanic American Indians/Alaska Natives consistently had the worst cause-specific survival of any group and that non-Hispanic Asians/Pacific Islanders consistently had the best survival (P < 0.001). Even after adjusting for other poor prognostic factors in the study, including older age, keratinising histology, and lack of radiation treatment, non-Hispanic American Indians/Alaska Natives had more than double hazards of death from nasopharyngeal cancer compared with non-Hispanic Asians/Pacific Islanders (aHR = 2.63, 95% CI 1.67, 4.13). CONCLUSIONS: There are disparities in nasopharyngeal carcinoma survival among racial and ethnic minority groups in the United States, with American Indians/Alaskan Natives faring worst. It is critical that future research focuses on nasopharyngeal carcinoma among this population to improve survivorship and mitigate cancer-related health disparities.

Neutrophil-lymphocyte ratios in the prognostication of primary non-metastatic nasopharyngeal carcinoma / Neutrophil-lymphocyte ratios in the prognostication of primary non-metastatic nasopharyngeal carcinoma

Abstract Introduction: Nasopharyngeal carcinoma is a geographically and racially variable disease which has a high incidence in Malaysia. Based on current concepts in tumour related inflammation the inflammatory marker, neutrophil-lymphocyte ratio was tested to find its relationship with prognosis in nasopharyngeal carcinoma. Objective: To investigate the effect of the neutrophil-lymphocyte ratio on prognosis in non-metastatic primary nasopharyngeal carcinoma patients and to further refine the cut off between high and low neutrophil-lymphocyte ratio values. Methods: The medical charts of patients with histologically confirmed nasopharyngeal carcinoma from 1st January 2005 until 31st December 2009 were reviewed retrospectively and theneutrophil-lymphocyte ratio was calculated to see if there was any association between their higher values with higher failure rates. Results: Records of 98 patients (n = 98) were retrieved and reviewed. Only neutrophil-lymphocyte ratio (p = 0.004) and tumor node metastasis staging (p = 0.002) were significantly different between recurrent and non-recurrent groups, with the neutrophil-lymphocyte ratio being independent of tumor node metastasis staging (p = 0.007). Treatment failure was significantly higher in the high neutrophil-lymphocyte ratio group (p = 0.001). Disease free survival was also significantly higher in this group (p = 0.000077). Conclusion: High neutrophil-lymphocyte ratio values are associated with higher rates of recurrence and worse disease free survival in non-metastatic nasopharyngeal carcinoma patients undergoing primary curative treatment.

Resumo: Introdução: O carcinoma de nasofaringe é uma doença variável geográfica e etnicamente, com alta incidência na Malásia. Baseado em conceitos atuais sobre inflamação relacionada a tumores, o marcador inflamatório relação neutrófilos/linfócitos foi testado para verificar sua relação com o prognóstico dessa condição clínica. Objetivo: Investigar o efeito do marcador neutrófilos/linfócitos no prognóstico de pacientes com primários não metastáticos de nasofaringe e refinar o ponto de corte entre valores altos e baixos da relação neutrófilos/linfócitos. Método: Os prontuários médicos dos pacientes com carcinoma de nasofaringe confirmado histologicamente de 1º de janeiro de 2005 até 31 de dezembro de 2009 foram revisados retrospectivamente e a relação neutrófilos/linfócitos foi calculada para verificar se havia alguma associação entre valores maiores e aumento na taxa de falha de tratamento. Resultados: Os dados de 98 pacientes (n = 98) foram revisados. Apenas a relação neutrófilos/linfócitos (p = 0,004) e o estadiamento TNM (p = 0,002) foram significantemente diferentes entre os grupos recorrentes e os não recorrentes, a relação neutrófilos/linfócitos foi independente do estadiamento TNM (p = 0,007). A falha de tratamento foi significantemente maior no grupo com relação neutrófilos/linfócitos alta (p = 0,001). A sobrevida livre de doença também foi significantemente maior nesse grupo (p = 0,000077). Conclusão: Os altos valores da relação neutrófilos/linfócitos estão associados a maiores taxas de recorrência e menor tempo de sobrevida livre de doença em pacientes com carcinomas não metastáticos de nasofaringe submetidos a tratamento curativo primário.

Decreased macrophage inflammatory protein (MIP)-1α and MIP-1ß increase the risk of developing nasopharyngeal carcinoma.

BACKGROUND: The association of circulating inflammation markers with nasopharyngeal carcinoma (NPC) is still largely unclear. This study aimed to comprehensively explore the relationship between circulating cytokine levels and the subsequent risk of NPC with a two-stage epidemiologic study in southern China. METHODS: The serum levels of 33 inflammatory cytokines were first measured in a hospital-based case-control study (150 NPC patients and 150 controls) using multiplex assay platforms. Marker levels were categorized into two or more groups based on the proportion of sample measurements that was above the lower limit of detection. Odds ratios (ORs) and 95% confidence intervals (CIs) relating the serum marker concentration to the risk of NPC were computed by multivariable logistic regression models. The associations were validated in 60 patients with NPC and 120 controls in a subsequent nested case-control study within a NPC screening trial. Potential interactions between serum cytokines and Epstein-Barr virus (EBV) relating to the risk of NPC were assessed using a likelihood ratio test. RESULTS: The levels of serum macrophage inflammatory protein (MIP)-1α and MIP-1ß in the highest categories were associated with a decreased risk of NPC in both the case-control study (MIP-1α: OR = 0.49, 95% CI = 0.26-0.95; MIP-1ß: OR = 0.47, 95% CI = 0.22-1.00) and the nested case-control study (MIP-1α: OR = 0.13, 95% CI = 0.03-0.62; MIP-1ß: OR = 0.20, 95% CI = 0.04-0.94), compared with those in the lowest categories. Furthermore, individuals with lower levels of these two cytokine markers who were EBV seropositive presented with a largely higher risk of NPC compared with patients with higher levels who were EBV seronegative in both the case-control study (MIP-1α: OR = 16.28, 95% CI = 7.11-37.23; MIP-1ß: OR = 12.86, 95% CI = 5.9-28.05) and the nested case-control study (MIP-1α: OR = 86.12, 95% CI = 10.58-701.03; MIP-1ß: OR = 115.44, 95% CI = 13.92-957.73). CONCLUSIONS: Decreased preclinical MIP-1α and MIP-1ß levels might be associated with a subsequently increased risk of NPC. More mechanistic studies are required to fully understand this finding.

Neutrophil-lymphocyte ratios in the prognostication of primary non-metastatic nasopharyngeal carcinoma.

INTRODUCTION: Nasopharyngeal carcinoma is a geographically and racially variable disease which has a high incidence in Malaysia. Based on current concepts in tumour related inflammation the inflammatory marker, neutrophil-lymphocyte ratio was tested to find its relationship with prognosis in nasopharyngeal carcinoma. OBJECTIVE: To investigate the effect of the neutrophil-lymphocyte ratio on prognosis in non-metastatic primary nasopharyngeal carcinoma patients and to further refine the cut off between high and low neutrophil-lymphocyte ratio values. METHODS: The medical charts of patients with histologically confirmed nasopharyngeal carcinoma from 1st January 2005 until 31st December 2009 were reviewed retrospectively and theneutrophil-lymphocyte ratio was calculated to see if there was any association between their higher values with higher failure rates. RESULTS: Records of 98 patients (n=98) were retrieved and reviewed. Only neutrophil-lymphocyte ratio (p=0.004) and tumor node metastasis staging (p=0.002) were significantly different between recurrent and non-recurrent groups, with the neutrophil-lymphocyte ratio being independent of tumor node metastasis staging (p=0.007). Treatment failure was significantly higher in the high neutrophil-lymphocyte ratio group (p=0.001). Disease free survival was also significantly higher in this group (p=0.000077). CONCLUSION: High neutrophil-lymphocyte ratio values are associated with higher rates of recurrence and worse disease free survival in non-metastatic nasopharyngeal carcinoma patients undergoing primary curative treatment.

Higher incidence of nasopharyngeal carcinoma in some regions in the world confers for interplay between genetic factors and external stimuli.

Nasopharyngeal carcinoma (NPC) is a rare variety of head and neck cancers. The risk factors include three major causes: genetic factors, viral infection, and environmental and dietary factors. The types of NPC show strong ethnic and geographic variations. The keratinizing and non-keratinizing types are prevalent in the lower incidence regions like North America and Europe; whereas the undifferentiated type is mostly found in the regions with higher incidences like China, North Africa, Arctic, and Nagaland of North-East India. These suggest a possible major role of the internal genetic factors for generation and promotion of this disease. Viral infections might accelerate the process of carcinogenesis by helping in cellular proliferation and loss of apoptosis. Diet and other environmental factors promote these neoplastic processes and further progression of the disease occurs.