Risk Of Nasopharyngeal Carcinoma Research Articles

Genetic variations in CYP2A6, CYP2E1, GSTM1, GSTT1 genes and the risk of Nasopharyngeal carcinoma in North African population.

Nasopharyngeal carcinoma (NPC) is a multifactorial malignancy associated with both genetic and environmental factors. Polymorphic deletions of the phase I and phase II genes involved in the detoxification of potential carcinogens may be a risk factor for nasopharyngeal carcinoma. In this study, we investigated the relationship between CYP2E1 (rs3813867), CYP2A6, GSTM1(rs1183423000) and GSTT1(rs1601993659) gene variations and NPC risk in North African countries with the highest incidence of NPC (Morocco, Algeria and Tunisia). and the evaluation of the potential use of these variants as potential biomarkers for NPC management. A total of 600 NPC cases and 545 controls frequency-matched on ethnicity, sex, age and childhood household type, were recruited from three North African countries (Morocco, Algeria and Tunisia) and analysed. Genotyping of CYP2A6 and CYP2E1(rs3813867) was performed by polymerase chain reaction restriction (PCR)-fragment length polymorphism (RFLP) analysis and the GSTM1 (rs1183423000) and GSTT1(rs1601993659) genetic variations were evaluated using the PCR technique. The genotype distributions of CYP2E1(rs3813867), CYP2A6, GSTM1(rs1183423000) and GSTT1(rs1601993659) genotypes did not differ significantly among NPC cases and controls (p>0.05). Furthermore, our data did not reveal any association with smoking and the studied variants, even when the samples were stratified by the duration period of smoking. In this large studied North African population, our findings suggest that the functional CYP2E1, CYP2A6, GSTM1 and GSTT1 variations did not influence NPC susceptibility.

Effects of ambient temperature, relative humidity and absolute humidity on risk of nasopharyngeal carcinoma in China.

Nasopharyngeal carcinoma (NPC) has a unique geographic distribution. It is unknown whether meteorological factors are related to the incidence of NPC. To investigate the effect of ambient temperature, relative humidity (RH), and absolute humidity (AH) on the incidence of NPC, we collected the incidence rate of NPC in 2016 and meteorological data from 2006 to 2016 from 484 cities and counties across 31 provinces in China. Generalized additive models with quasi-Poisson regression and generalized linear models with natural cubic splines were employed respectively to elucidate the nonlinear relationships and specify the partial linear relationships. Subgroup and interactive analysis were also conducted. Temperature (R2 = 0.68, p < .001), RH (R2 = 0.47, p < .001), and AH (R2 = 0.70, p < .001) exhibited nonlinear correlations with NPC incidence rate. The risk of NPC incidence increased by 20.3% (95% confidence intervals [CI]: [18.9%, 21.7%]) per 1°C increase in temperature, by 6.3% (95% CI: [5.3%, 7.2%]) per 1% increase in RH, and by 32.2% (95% CI: [30.7%, 33.7%]) per 1 g/m3 increase in AH, between their the 25th and the 99th percentiles. In addition, the combination of low temperature and low RH was also related to increased risk (relative risk: 1.60, 95% CI: [1.18, 2.17]). Males and eastern or rural populations tended to be more vulnerable. In summary, this study suggests that ambient temperature, RH, and particularly AH are associated with the risk of NPC incidence.

Epidemiology of nasopharyngeal carcinoma: current insights and future outlook.

Nasopharyngeal carcinoma (NPC) is characterised by its remarkable geographical and ethnic distribution. The interplay between genetic susceptibility, environmental exposures, and Epstein-Barr virus (EBV) infections is indicated in the development of NPC. Exposure to tobacco smoking, dietary factors, and inhalants has been associated with the risk of NPC. Genetic association studies have revealed NPC-associated susceptibility loci, including genes involved in immune responses, xenobiotic metabolism, genome maintenance, and cell cycle regulation. EBV exposure timing and strain variation might play a role in its carcinogenicity, although further investigations are required. Other factors including medical history and oral hygiene have been implicated in NPC. Prevention strategies, including primary prevention and secondary prevention through early detection, are vital in reducing mortality and morbidity of NPC. The current review discusses the global and regional distribution of NPC incidences, the risk factors associated with NPC, and the public health implications of these insights. Future investigations should consider international, large-scale prospective studies to elucidate the mechanisms underlying NPC pathogenesis and develop individualized interventions for NPC.

200 cigarette smoking and risk of nasopharyngeal carcinoma

200 cigarette smoking and risk of nasopharyngeal carcinoma

Microbes translocation from oral cavity to nasopharyngeal carcinoma in patients.

The presence of oral microbes in extra-oral sites is linked to gastrointestinal cancers. However, their potential ectopically colonization in the nasopharynx and impact on local cancer development remains uncertain. Our study involving paired nasopharyngeal-oral microbial samples from nasopharyngeal carcinoma (NPC) patients and controls unveils an aberrant oral-to-nasopharyngeal microbial translocation associated with increased NPC risk (OR = 4.51, P = 0.012). Thirteen species are classified as oral-translocated and enriched in NPC patients. Among these, Fusobacterium nucleatum and Prevotella intermedia are validated through culturomics and clonal strain identification. Nasopharyngeal biopsy meta-transcriptomes confirm these microbes within tumors, influencing local microenvironment and cytokine response. These microbes correlate significantly with the Epstein-Barr virus(EBV) loads in the nasopharynx, exhibiting an increased dose-response relationship. Collectively, our study identifies oral microbes migrating to the nasopharynx, infiltrating tumors, impacting microenvironments and linking with EBV infection. These results enhance our understanding of abnormal microbial communication and their roles in carcinogenesis.

Impact of toll-like receptor 4 variations on nasopharyngeal carcinoma risk and survival in tunisian population.

The Toll-like receptor 4 (TLR4), an important member of the host's innate immune response, is coded by a polymorphic gene. This polymorphism could be a predisposing factor for NasoPharyngeal Carcinoma (NPC). To determine the association between TLR4 gene polymorphisms and the susceptibility to NPC in a cohort of Tunisian affected patients. Genomic DNAs from 245 unrelated patients affected by undifferentiated carcinoma type (UCNT) and 264 unrelated healthy controls were genotyped for the five single nucleotides polymorphisms (SNPs) of TLR4 locus (4434 A>G (rs1927914),7263 G>C (rs10759932), 6134 A>G(rs4986790), 8851C>T (rs 4986791), 5272 T>C(rs11536889), +8469 T>C (rs11536891)) by Taqman® 5'-nuclease assay. Among all polymorphisms studied, only the rs4986790 G and rs4986791 T alleles were significantly more prevalent in patients' group than controls (45% vs. 38%; p=0.03; pc=0.06) and increased the risk of the NPC (OR=1.3, 95% CI=1.01-1.69). Also, we found that the frequency of the rs4986790 AA and rs4986791 TT genotypes was significantly higher in controls than in patients (25.7% vs 37%; p=0.006, pc=0.02) and conferred a protector factor in NPC (OR= 0.59, 95% CI= 0.39-0.87). Further, based on the Kaplan-Meier survival curve we observed also the positive effect ofrs1927914 AA genotype on a prognostic of NPC (p=0.006; pc=0.01). Our study demonstrated that impaired production of TLR4 seems to be a risk factor of NPC development but functional studies are needed to confirm these findings. As to rs1927914 AA appears to be a good biomarker for better survival in a patient with NPC.

Serum 25-Hydroxyvitamin D Is Inversely Associated with Nasopharyngeal Carcinoma: A Hospital-Based Matched Case-Control Study in Malaysia.

Serum 25(OH)D deficiency consistently demonstrated molecular mechanisms through which chronic inflammation is associated with the risk of nasopharyngeal carcinoma (NPC). This study aimed to determine the association between serum 25(OH)D and NPC. A matched case-control study was conducted at two local hospitals. A total of 300 histologically confirmed NPC cases were matched with controls for age, gender, and ethnicity, and assessed for vitamin D status and other nutritional factors. Mean Vitamin D concentration was significantly lower among cases compared to controls (63.17 ± 19.15 nmol/L and 67.34 ± 23.06 nmol/L) (t = -2.41, p = 0.016). Multiple conditional logistic regression analysis indicated that higher levels of serum 25(OH)D were associated with reduced odds of NPC (AOR = 0.73, 95% CI = 0.57-0.94, p = 0.016) controlling for confounders including BMI, physical activity, smoking status, alcohol consumption, consumption of food high in vitamin D, salted fish consumption, and family history of NPC. There was a significant association between inadequate serum 25(OH)D status with accumulation of four risk factors and increased odds of getting NPC using polynomial regression analysis. Increased NPC odds ratios were observed after sequential accumulation of additional risk factors with the presence of inadequate serum 25(OH)D status (OR = 0.54, 95% CI = 0.27, 4.77, p = 0.322, OR = 1.04, 95% CI = 0.64, 1.72, p = 0.267, OR = 1.15, 95% CI = 0.73, 1.80, p = 0.067, OR = 1.93, 95% CI = 1.13, 3.31, p = 0.022, and OR = 5.55, 95% CI = 1.67, 10.3, p < 0.001 respectively). Future research in Malaysia should involve both prospective cohort studies and randomized controlled trials to confirm and further clarify the role of vitamin D in NPC outcomes.

Host genetic variants, Epstein-Barr virus subtypes, and the risk of nasopharyngeal carcinoma: Assessment of interaction and mediation

Epstein-Barr virus (EBV) and human leukocyte antigen (HLA) polymorphisms are well-known risk factors for nasopharyngeal carcinoma (NPC). However, the combined effects between HLA and EBV on the risk of NPC are unknown. We applied a causal inference framework to disentangle interaction and mediation effects between two host HLA SNPs, rs2860580 and rs2894207, and EBV variant 163364 with a population-based case-control study in NPC-endemic southern China. We discovered the strong interaction effects between the high-risk EBV subtype and both HLA SNPs on NPC risk (rs2860580, relative excess risk due to interaction [RERI]= 4.08, 95% confidence interval [CI]= 2.03-6.14; rs2894207, RERI= 3.37, 95% CI= 1.59-5.15), accounting for the majority of genetic risk effects. These results indicate that HLA genes and the high-risk EBV have joint effects on NPC risk. Prevention strategies targeting the high-risk EBV subtype would largely reduce NPC risk associated with EBV and host genetic susceptibility.

The interaction and mediation effects between the host genetic factors and Epstein-Barr virus VCA-IgA in the risk of nasopharyngeal carcinoma.

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.

Oral fungal profiling and risk of nasopharyngeal carcinoma: a population-based case-control study

Dysbiosis of the oral mycobiome has been linked to some diseases, including cancers. However, the role of oral fungal communities in nasopharyngeal carcinoma (NPC) carcinogenesis has not previously been investigated. We characterized the oral salivary fungal mycobiome in 476 untreated incident NPC patients and 537 population-based controls using fungal internal transcribed spacer (ITS)-2 sequencing. The relationship between oral fungal mycobiome and the risk of NPC was assessed through bioinformatic and biostatistical analyses. We found that lower fungal alpha diversity was associated with an increased odds of NPC [lower vs. higher: observed features (adjusted odds ratio [OR]=5.81, 95% confidence interval [CI]=3.60-9.38); Simpson diversity (1.53, 1.03-2.29); Shannon diversity (2.03, 1.35-3.04)]. We also observed a significant difference in global fungal community patterns between cases and controls based on Bray-Curtis dissimilarity (P<0.001). Carriage of oral fungal species, specifically, Saccharomyces cerevisiae, Candida tropicalis, Lodderomyces elongisporus, Candida albicans, and Fusarium poae, was associated with significantly higher odds of NPC, with ORs ranging from 1.56 to 4.66. Individuals with both low fungal and low bacterial alpha diversity had a profoundly elevated risk of NPC. Our results suggest that dysbiosis in the oral mycobiome, characterized by a loss of fungal community diversity and overgrowth of several fungal organisms, is associated with a substantially increased risk of NPC. This work was funded by the US National Institutes of Health, the Swedish Research Council, the High-level Talents Research Start-up Project of Fujian Medical University, and the China Scholarship Council.

Matted Lymph Nodes on MRI in Nasopharyngeal Carcinoma: Prognostic Factor and Potential Indication for Induction Chemotherapy Benefits.

Lymph node characteristics markedly affect nasopharyngeal carcinoma (NPC) prognosis. Matted node (MN), an important characteristic for lymph node, lacks explored MRI-based prognostic implications. Investigate MRI-determined MNs' prognostic value in NPC, including 5-year overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), progression-free survival (PFS), and its role in induction chemotherapy (IC). Retrospective cohort survival study. Seven hundred ninety-two patients with non-metastatic NPC (female: 27.3%, >45-year old: 50.1%) confirmed by biopsy. 5-T/3.0-T, T1-, T2- and post-contrast T1-weighted fast spin echo sequences acquired. MNs were defined as ≥3 nodes abutting with intervening fat plane replaced by extracapsular nodal spread (ENS). Patients were observed every 3 months for 2 years and every 6 months for 5 years using MRI. Follow-up extended from treatment initiation to death or final follow-up. MNs were evaluated by three radiologists with inter-reader reliability calculated. A 1:1 matched-pair method compared survival differences between MN-positive patients with or without IC. Primary endpoints (OS, DMFS, LRFS, PFS) were calculated from therapy initiation to respective event. Kappa values assessed inter-reader reliability. Correlation between MN, ENS, and LNN was studied through Spearman's correlation coefficient. Clinical characteristics were calculated via Fisher's exact, Chi-squared, and Student's t-test. Kaplan-Meier curves and log-rank tests analyzed all time-to-event data. Confounding factors were included in Multivariable Cox proportional hazard models to identify independent prognostic factors. P-values <0.05 were considered statistically significant. MNs incidence was 24.6%. MNs independently associated with decreased 5-year OS, DMFS, and PFS; not LRFS (P = 0.252). MN-positive patients gained significant survival benefit from IC in 5-year OS (88.4% vs. 66.0%) and PFS (76.4% vs. 53.5%), but not DMFS (83.1% vs. 69.9%, P = 0.145) or LRFS (89.9% vs. 77.8%, P = 0.140). MNs may independently stratify NPC risk and offer survival benefit from IC. 3 TECHNICAL EFFICACY: Stage 2.

EBV-IgA antibody responses in endemic and nonendemic populations with nasopharyngeal carcinoma: tumour marker prognostication study and a cross-sectional study.

Nasopharyngeal carcinoma (NPC) is the most prevalent head and neck cancer in Indonesia, with 100% Epstein-Barr virus (EBV) infection in tumor cells. NPC is rare in the Netherlands. The involvement of EBV in NPC pathogenesis is reflected by early onset aberrant IgA antibody responses to various EBV proteins. Screening for elevated EBV-IgA levels is proposed for NPC risk assessment in endemic countries but is poorly studied in nonendemic regions. This study analyzed the overall diversity (immunoblot) as well as the prevalence and normalized levels of IgA responses to immunodominant peptide epitopes of EBV proteins VCA P18, EBNA 1, and Zebra (Zta) (N-terminus, P 125, P 130, full-length recombinant Zebra) in Indonesian (n=50) and Dutch (n=50) patients with NPC. The results confirmed that elevated levels of IgA-VCA P18 and IgA-EBNA 1 were found in both NPC populations, but that IgA-Zta was more variable. IgA-Zta responses were more pronounced in Indonesian NPC cases, reflecting more frequent EBV reactivation overall. IgA-VCA P18 and IgA-EBNA are independent tumor markers and are both necessary for NPC risk assessment. Overall, these results confirmed the diagnostic benefit of combined IgA-VCA P18/-EBNA 1 testing for NPC risk assessment in endemic and nonendemic populations.

Changing patterns of nasopharyngeal carcinoma incidence in Hong Kong: a 30-year analysis and future projections

BackgroundThis study aims to evaluate the relationship between age, period, and birth cohort with the incidence trends of Nasopharyngeal Carcinoma (NPC) in Hong Kong, make projections through 2030 and parse the drivers of the incidence.MethodsUsing data from the Hong Kong Cancer Registry, we used an age-period-cohort model to uniquely estimate age, period, and cohort effects on NPC incidence trends and make projections. We further assessed the drivers of NPC incidence using a validated decomposition algorithm.ResultsFrom 1991 to 2020, crude and age-standardized incidence rates of NPC decreased significantly. The net drifts showed significant downward trends for both sexes, and local drift declined in all age groups. Period and cohort rate ratios revealed monotonic declining patterns for both sexes. Projections suggested that NPC incidence will continue to decline. Population decomposition showed that while population growth and ageing have led to an increase in NPC cases, epidemiologic changes offset these increases, resulting in an encouraging downward trend in the incidence and new NPC cases in Hong Kong.ConclusionsThe period and cohort risk of NPC in Hong Kong decreased, and epidemiologic changes offset the contribution of demographic factors, resulting in a continued decline in NPC incidence and cases.

Associations between serum trace elements and the risk of nasopharyngeal carcinoma: a multi-center case-control study in Guangdong Province, southern China.

Associations between trace elements and nasopharyngeal carcinoma (NPC) have been speculated but not thoroughly examined. This study registered a total of 225 newly diagnosed patients with NPC and 225 healthy controls matched by sex and age from three municipal hospitals in Guangdong Province, southern China between 2011 and 2015. Information was collected by questionnaire on the demographic characteristics and other possibly confounding lifestyle factors. Eight trace elements and the level of Epstein-Barr virus (EBV) antibody were measured in casual (spot) serum specimens by inductively coupled plasma-mass spectrometry (ICP-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. Restricted cubic splines and conditional logistic regression were applied to assess the relationship between trace elements and NPC risk through single-and multiple-elements models. Serum levels of chromium (Cr), cobalt (Co), nickel (Ni), arsenic (As), strontium (Sr) and molybdenum (Mo) were not associated with NPC risk. Manganese (Mn) and cadmium (Cd) were positively associated with NPC risk in both single-and multiple-element models, with ORs of the highest tertile compared with the reference categories 3.90 (95% CI, 1.27 to 7.34) for Mn and 2.30 (95% CI, 1.26 to 3.38) for Cd. Restricted cubic splines showed that there was a linear increasing trend between Mn and NPC risk, while for Cd there was a J-type correlation. Serum levels of Cd and Mn was positively related with NPC risk. Prospective researches on the associations of the two trace elements with NPC ought to be taken into account within the future.

High-throughput identification of regulatory elements and functional assays to uncover susceptibility genes for nasopharyngeal carcinoma

Large-scale genetic association studies have identified multiple susceptibility loci for nasopharyngeal carcinoma (NPC), but the underlying biological mechanisms remain to be explored. To gain insights into the genetic etiology of NPC, we conducted a follow-up study encompassing 6,907 cases and 10,472 controls and identified two additional NPC susceptibility loci, 9q22.33 (rs1867277; OR= 0.74, 95% CI= 0.68-0.81, p= 3.08×10-11) and 17q12 (rs226241; OR= 1.42, 95% CI= 1.26-1.60, p= 1.62×10-8). The two additional loci, together with two previously reported genome-wide significant loci, 5p15.33 and 9p21.3, were investigated by high-throughput sequencing for chromatin accessibility, histone modification, and promoter capture Hi-C (PCHi-C) profiling. Using luciferase reporter assays and CRISPR interference (CRISPRi) to validate the functional profiling, we identified PHF2 at locus 9q22.33 as a susceptibility gene. PHF2 encodes a histone demethylase and acts as a tumor suppressor. The risk alleles of the functional SNPs reduced the expression of the target gene PHF2 by inhibiting the enhancer activity of its long-range (4.3 Mb) cis-regulatory element, which promoted proliferation of NPC cells. In addition, we identified CDKN2B-AS1 as a susceptibility gene at locus 9p21.3, and the NPC risk allele of the functional SNP rs2069418 promoted the expression of CDKN2B-AS1 by increasing its enhancer activity. The overexpression of CDKN2B-AS1 facilitated proliferation of NPC cells. In summary, we identified functional SNPs and NPC susceptibility genes, which provides additional explanations for the genetic association signals and helps to uncover the underlying genetic etiology of NPC development.

Non-Homologous End-Joining Pathway Genotypes Significantly Associated with Nasopharyngeal Carcinoma Susceptibility.

Defects in the non-homologous end-joining (NHEJ) DNA repair pathway lead to genomic instability and carcinogenesis. However, the roles of individual NHEJ genes in nasopharyngeal carcinoma (NPC) etiology are not well-understood. The aim of this study was to assess the contribution of NHEJ genotypes, including XRCC4 (rs6869366, rs3734091, rs28360071, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and Ligase4 rs1805388, to NPC risk, with 208 NPC patients and 416 controls. Genotype-phenotype correlations were also investigated by measuring mRNA and protein expression in adjacent normal tissues and assessing the NHEJ repair capacity in blood lymphocytes from 43 NPC patients. The results showed significant differences in the distributions of variant genotypes at XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 between the cases and controls. The variant genotypes of these three polymorphisms were associated with significantly increased NPC risks. NPC patients with the risk genotypes at XRCC6 rs2267437 had significantly reduced expression levels of both mRNA and protein, as well as a lower NHEJ repair capacity, than those with the wild-type genotype. In conclusion, XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 in the NHEJ pathway were associated with NPC susceptibility. XRCC6 rs2267437 can modulate mRNA and protein expression and the NHEJ repair capacity.

Peptidome-wide association analysis of Epstein-Barr virus identifies epitope repertoires associated with nasopharyngeal carcinoma.

Human leukocyte antigen (HLA) molecules are essential for presenting Epstein-Barr virus (EBV) antigens and are closely related to nasopharyngeal carcinoma (NPC). This study aims to systematically investigate the association between HLA-bound EBV peptides and NPC risk through in silico HLA-peptide binding prediction. A total of 455 NPC patients and 463 healthy individuals in NPC endemic areas were recruited, and HLA-target sequencing was performed. HLA-peptide binding prediction for EBV, followed by peptidome-wide logistic regression and motif analysis, was applied. Binding affinity changes for EBV peptides carrying high-risk mutations were analyzed. We found that NPC-associated EBV peptides were significantly enriched in immunogenic proteins and core linkage disequilibrium (LD) proteins related to evolution, especially those binding HLA-A alleles (p = 3.10 × 10-4 for immunogenic proteins and p = 8.10 × 10-5 for core LD proteins related to evolution). These peptides were clustered and showed binding motifs of HLA supertypes, among which supertype A02 presented an NPC-risk effect (padj = 3.77 × 10-4 ) and supertype A03 presented an NPC-protective effect (padj = 4.89 × 10-4 ). Moreover, a decreased binding affinity toward risk HLA supertype A02 was observed for the peptide carrying the NPC-risk mutation BNRF1 V1222I (p = 0.0078), and an increased binding affinity toward protective HLA supertype A03 was observed for the peptide carrying the NPC-risk mutation BALF2 I613V (p = 0.022). This study revealed the distinct preference of EBV peptides for binding HLA supertypes, which may contribute to shaping EBV population structure and be involved in NPC development.

Feature Reviews of the Molecular Mechanisms of Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is rare in most parts of the world but endemic in southern Asia. Here, we describe the molecular abnormalities in NPC and point out potential molecular mechanisms for future therapy. This article provides a brief up-to-date review focusing on the molecular pathways of NPC, which may improve our knowledge of this disease, and we also highlight some issues for further research. In brief, some heritable genes are related to NPC; therefore, people with a family history of NPC have an increased risk of this disease. Carcinogenic substances and Epstein-Barr virus (EBV) exposure both contribute to tumorigenesis through the accumulation of multiple genomic changes. In recent years, salted fish intake has decreased the impact on NPC, which implies that changing exposure to carcinogens can modify the risk of NPC. Eradication of cancer-associated viruses potentially eradicates cancer, and EBV vaccines might also prevent this disease in the future. Screening patients by using an EBV antibody is feasible in the high-risk group; plasma EBV DNA measurement could also be conducted for screening, prognosis, and monitoring of this disease. Understanding the molecular mechanisms of NPC can further provide novel information for health promotion, disease screening, and precision cancer treatment.

LncRNA FAS-AS1 upregulated by its genetic variation rs6586163 promotes cell apoptosis in nasopharyngeal carcinoma through regulating mitochondria function and Fas splicing

Nasopharyngeal carcinoma (NPC) is a common head and neck malignant with a high incidence in Southern China. Genetic aberrations play a vital role in the pathogenesis, progression and prognosis of NPC. In the present study, we elucidated the underlying mechanism of FAS-AS1 and its genetic variation rs6586163 in NPC. We demonstrated that FAS-AS1 rs6586163 variant genotype carriers were associated with lower risk of NPC (CC vs. AA, OR = 0.645, P = 0.006) and better overall survival (AC + CC vs. AA, HR = 0.667, P = 0.030). Mechanically, rs6586163 increased the transcriptional activity of FAS-AS1 and contributed to ectopic overexpression of FAS-AS1 in NPC. rs6586163 also exhibited an eQTL trait and the genes affected by rs6586163 were enriched in apoptosis related signaling pathway. FAS-AS1 was downregulated in NPC tissues and over-expression of FAS-AS1 was associated with early clinical stage and better short-term treatment efficacy for NPC patients. Overexpression of FAS-AS1 inhibited NPC cell viability and promoted cell apoptosis. GSEA analysis of RNA-seq data suggested FAS-AS1 participate in mitochondria regulation and mRNA alternative splicing. Transmission electron microscopic examination verified that the mitochondria was swelled, the mitochondrial cristae was fragmented or disappeared, and their structures were destroyed in FAS-AS1 overexpressed cells. Furthermore, we identified HSP90AA1, CS, BCL2L1, SOD2 and PPARGC1A as the top 5 hub genes of FAS-AS1 regulated genes involved in mitochondria function. We also proved FAS-AS1 could affect Fas splicing isoform sFas/mFas expression ratio, and apoptotic protein expression, thus leading to increased apoptosis. Our study provided the first evidence that FAS-AS1 and its genetic polymorphism rs6586163 triggered apoptosis in NPC, which might have a potential as new biomarkers for NPC susceptibility and prognosis.

The Oral Microbiome as Mediator between Oral Hygiene and Its Impact on Nasopharyngeal Carcinoma

Oral hygiene and the alteration of the oral microbiome have been linked to nasopharyngeal carcinoma (NPC). This study aimed to investigate whether the oral microbiome plays a mediating role in the relationship between oral hygiene and NPC, and identify differential microbial taxonomies that potentially mediated this association. We conducted a case-control study that involved 218 NPC patients and 192 healthy controls. The 16S rRNA gene sequencing of the V4 region was performed to evaluate the composition of the oral microbiome. Mediation analysis was applied to explore the relationship among oral hygiene, the oral microbiome and NPC. We found that dental fillings and poor oral hygiene score were associated with increased risks of NPC (OR = 2.51 (1.52-4.25) and OR = 1.54 (1.02-2.33)). Mediation analysis indicated that dental fillings increased the risk of NPC by altering the abundance of Erysipelotrichales, Erysipelotrichaceae, Solobacterium and Leptotrichia wadei. In addition, Leptotrichia wadei also mediated the association between oral hygiene score and the risk of NPC. Our study confirmed that poor oral hygiene increased the risk of NPC, which was partly mediated by the oral microbiome. These findings might help us to understand the potential mechanism of oral hygiene influencing the risk of NPC via the microbiome.