• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6005-6010
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• 2012

Background: Nasopharyngeal carcinoma (NPC) is endemic in Southern Chinese and Southeast Asian populations. Geographical and ethnic clustering of the cancer is due to genetic, environmental, and lifestyle risk factors. This case-control study aimed to identify or confirm both genetic and non-genetic risk factors for NPC in one of the endemic countries, Malaysia. Materials and Methods: A panel of 768 single-nucleotide polymorphisms (SNPs) previously associated with various cancers and known non-genetic risk factors for NPC were selected and analyzed for their associations with NPC in a case-control study. Results: Statistical analysis identified 40 SNPs associated with NPC risk in our population, including 5 documented previously by genome-wide association studies (GWAS) and other case-control studies; the associations of the remaining 35 SNPs with NPC were novel. In addition, consistent with previous studies, exposure to occupational hazards, overconsumption of salt-cured foods, red meat, as well as low intake of fruits and vegetables were also associated with NPC risk. Conclusions: In short, this study confirmed and/or identified genetic, environmental and dietary risk factors associated with NPC susceptibility in a Southeast Asian population.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2805-2809
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• 2013

Objective: This study aimed at investigating whether the orphan nuclear receptor NR4A2 is significantly associated with clinicopathologic features and overall survival of patients with nasopharyngeal carcinoma (NPC). Methods: Immunohistochemistry was performed to determine NR4A2 protein expression in 84 NPC tissues and 20 non-cancerous nasopharyngeal (NP) tissues. The prognostic significance of NR4A2 protein expression was evaluated using Cox proportional hazards regression models and Kaplan-Meier survival analysis. Results: We did not find a significant association between total NR4A2 expression and clinicopathological variables in 84 patients with NPC. However, we observed that high cytoplasmic expression of NR4A2 was significantly associated with tumor size (T classification) (P = 0.006), lymph node metastasis (N classification) (P = 0.002) and clinical stage (P = 0.017). Patients with higher cytoplasmic NR4A2 expression had a significantly lower survival rate than those with lower cytoplasmic NR4A2 expression (P = 0.004). Multivariate Cox regression analysis analysis suggested that the level of cytoplasmic NR4A2 expression was an independent prognostic indicator for overall survival of patients with NPC (P = 0.033). Conclusions: High cytoplasmic expression of NR4A2 is a potential unfavorable prognostic factor for patients with NPC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9899-9903
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• 2014

Nasopharyngeal carcinoma (NPC) is an uncommon disease in most countries but occurs with much greater frequency in southern China. This study aimed to examine the secular trends of NPC in urban Guangzhou over the time period of 2000-2011 using data from the Guangzhou Cancer Registry. Age-adjusted annual incidence rates of NPC were calculated by the direct method using the WHO World Standard Population (1960) as the reference. The average annual percentage change (AAPC) was used as an estimate of the trend. A total of 7,532 new cases of NPC and 3,449 related deaths were registered. In both genders, the peak incidence occurred in the 50- to 59-year age group, and this age distribution pattern remained similar throughout. The AAPC in NPC incidence rates was -3.26% (95% CI: -5.4%--1.1) for males and -5.74% (95% CI: -8.9%--2.5) for females, resulting in a total decrease of 39.3% (from 22.14 to 13.44 per 100,000 population) for males and 48.6% (from 10.1 to 5.18 per 100,000 population) for females over this 12-year period. The AAPCs in NPC mortality rates were -4.62% (95%CI: -3.5%--5.7) for males and -6.75% (95% CI: -5.2%--8.3) for females, resulting in a total decrease of -46.1% (from 12.1 to 6.54 per 100,000 population) for males and 51.7% (from 4.14 to 2.00 per 100,000 population) for females. The age-adjusted incidence and mortality rates of NPC declined during 2000-2011 in urban Guangzhou but remained high. Future efforts to improve prevention, early detection and treatment strategies are needed.

• Asian Pacific Journal of Cancer Prevention
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• 제17권6호
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• pp.2811-2819
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• 2016

Multiple genetic and environmental factors have been reported to play key role in the development of nasopharyngeal carcinoma (NPC). Here, we investigated interactions of XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms and environmental factors in modulating susceptibility to NPC in Northeast India. One-hundred NPC patients, 90 first-degree relatives of patients and 120 controls were enrolled in the study. XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms were determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis. The XRCC1 Gln/Gln genotype showed increased risk (OR=2.76; P<0.024) of NPC. However, individuals with both XRCC1 and XRCC2 polymorphic variants had 3.2 fold elevated risk (P<0.041). An enhanced risk of NPC was also observed in smoked meat (OR=4.07; P=0.004) and fermented fish consumers (OR=4.34, P=0.001), and tobacco-betel quid chewers (OR=7.00; P=0.0001) carrying XRCC1 polymorphic variants. However, smokers carrying defective XRCC1 gene showed the highest risk (OR = 7.47; P<0.0001). On MDR analysis, the best model for NPC risk was the five-factor model combination of XRCC1 variant genotype, fermented fish, smoked meat, smoking and chewing (CVC=10/10; TBA=0.636; P<0.0001); whereas in interaction entropy graphs, smoked meat and tobacco chewing showed synergistic interactions with XRCC1. These findings suggest that interaction of genetic and environmental factors might increase susceptibility to NPC in Northeast Indian populations.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5533-5537
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• 2013

MicroRNA-10b (miR-10b) has been reported to play an important role in some types of cancer, but the effects and possible mechanisms of action of miR-10b in the metastasis of nasopharyngeal carcinoma cells (NPC) have not been explored. The aim of the present study was to investigate the function of miR-10b in nasopharyngeal carcinoma and to determine the molecular mechanisms underlying its action. The MTT assay was used to assess proliferation of CNE-2Z cells. Wound healing and transwell migration assays were applied to assess cell migration and invasion, while and expression of E-cadherin and MMP-9 were detected using Western blot analysis. Real-time PCR was employed to detect the expression of genes related to migration and invasion and the $2^{-{\Delta}{\Delta}Ct}$ method was used to calculate the degree of expression. MTT assay showed the expression of miR-10b to have no effect on the proliferation of NPC cell lines. The wound healing assay showed that miR-10b mimics promoted the mobility and invasion of NPC cell lines. Inhibitors of miR-10b reduced the ability of NPC cell lines to migrate and invade. In addition, the expression of genes related to migration and invasion, such as E-cadherin, vimentin, and MMP-9, were confirmed to be different in the CNE-2Z NPC cell line transfected with miR-10b mimics and with miR-10b inhibitors. In the present study, miR-10b was found to upregulate the expression of MMP-9 and knockdown of miR-10b was found to significantly downregulate the expression of E-cadherin. On the whole, these results showed that miR-10b plays an important role in the invasion and metastasis of NPC cells.

• BMB Reports
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• 제52권3호
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• pp.208-213
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• 2019

Chemoresistance is the primary obstacle in the treatment of locally advanced and metastatic nasopharyngeal carcinoma (NPC). Recent evidence suggests that the transcription factor forkhead box M1 (FoxM1) is involved in chemoresistance. Our group previously confirmed that FoxM1 is overexpressed in NPC. In this study, we investigated the role of FoxM1 in cisplatin resistance of the cell lines 5-8F and HONE-1 and explored its possible mechanism. Our results showed that FoxM1 and NBS1 were both overexpressed in NPC tissues based on data from the GSE cohort (GSE12452). Then, we measured FoxM1 levels in NPC cells and found FoxM1 was overexpressed in NPC cell lines and could be stimulated by cisplatin. MTT and clonogenic assays, flow cytometry, ${\gamma}H2AX$ immunofluorescence, qRT-PCR, and western blotting revealed that downregulation of FoxM1 sensitized NPC cells to cisplatin and reduced the repair of cisplatin-induced DNA double-strand breaks via inhibition of the MRN (MRE11-RAD50-NBS1)-ATM axis, which might be related to the ability of FoxM1 to regulate NBS1. Subsequently, we demonstrated that enhanced sensitivity of FoxM1 knockdown cells could be reduced by overexpression of NBS1. Taken together, our data demonstrate that downregulation of FoxM1 could improve the sensitivity of NPC cells to cisplatin through inhibition of MRN-ATM-mediated DNA repair, which could be related to FoxM1-dependent regulation of NBS1.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3547-3553
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• 2014

Background: The prognostic value of serum alkaline phosphatase (S-ALP) has not been fully validated for nasopharyngeal carcinoma (NPC). Materials and Methods: S-ALP levels were measured in 601 patients newly diagnosed with NPC before radical treatment, and possible associations of these levels with 5-year overall survival (OS) and tumor-free survival (TFS) were explored using univariate and multivariate analyses. Results: Elevated pretreatment S-ALP (>85 U/L) was significantly less frequent among patients classified as T1+2 or stage I+II than among those classified as T3+4 or stage III+IV. Multivariate analysis showed that elevated pretreatment S-ALP (>85 U/L), age, T classification and N stage were independent predictors of poor OS and TFS. Conclusions: Pretreatment S-ALP may be a reliable biomarker to evaluate the long-term prognosis of patients with NPC.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4927-4935
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• 2015

Northeastern India is a major nasopharyngeal carcinoma (NPC) high risk-area although the rest of the country has very low incidence. A case-control study of 105 NPC cases and 115 controls was conducted to identify the potential risk factors for NPC development in this region. Information was collected by interviewer about socio-demographic characteristics, cigarette smoking, alcohol consumption, dietary history, occupational history, and a family history of cancer. Epstein-Barr viral load was assayed from the blood DNA by real time PCR. Associations between GSTs genotypes, cytochrome P450 family including CYP1A1, CYP2E1 and CYP2A6 polymorphisms and susceptibility to relationship between the diseases were studied using PCR-RFLP assay. Results indicate that Epstein-Barr virus load was significantly higher in patients compared to controls (p<0.0001). Furthermore, concentration of blood EBV-DNA was significantly higher in advanced stage disease (Stage III and IV) than in early stage disease (Stage I and II) (p<0.05). Presence of CYP2A6 variants that reduced the enzyme activity was significantly less frequent in cases than controls. Smoked meat consumption, exposure to smoke, living in poorly ventilated house and alcohol consumption were associated with NPC development among the population of Northeastern India. Thus, overall our study revealed that EBV viral load and genetic polymorphism of CYP2A6 along with living practices which include smoked meat consumption, exposure to smoke, living in poorly ventilated houses and alcohol consumption are the potential risk factors of NPC in north eastern region of India. Understanding of the risk factors and their role in the etiology of NPC are helpful forpreventive measures and screening.

• 대한두경부종양학회지
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• 제28권1호
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• pp.3-7
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• 2012

Background and Objectives : Nasopharyngeal carcinoma(NPC) shows a distinct geographic and demographic distribution with high incidences in Chinese and Southeast Asians. Current WHO classification divides NPC into nonkeratinizing carcinoma(NKC)(differentiated and undifferentiated subtypes), keratinizing squamous cell carcinoma(KSCC), and basaloid squamous cell carcinoma(BSCC). Relative frequency of histologic subtypes of NPC is known to vary according to the incidence of NPC. Korea is one of the low-incidence countries according to the GLOBOCAN 2008 database by IARC. The aim of this study is to assess the histopathologic types and EBV status of NPC of Koreans. Materials and Methods : We reviewed and reclassified 168 cases of NPC(132 males and 36 females) diagnosed from January 1996 through July 2006. In situ hybridization for EBV-encoded early RNA(EBER) was performed on 146 cases and the results were compared among different histologic types, genders, and age and stage groups. Results : NKC, undifferentiated subtype(NKC-U) was identified in 106 cases(63.1%) and differentiated subtype(NKC-D) in 49 cases(29.2%). Remaining 13 cases(7.7%) were classified as KSCC. NKC and NKC-U were more common in females than in males. EBV prevalence was higher in NKC than in KSCC(NKC-U, 90% ;, NKC-D, 84.1% ; KSCC, 7.7%) and more common in younger age(${\leq}40$) than older age(>40) group. Conclusion : Histologic type distribution and EBV prevalence of NPC in Korean patients corresponded to that of intermediate incidence area. Pathogenesis of nasopharyngeal KSCC is assumed to be different from that of NKC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9797-9800
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• 2014

Background: Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and Southeast Asia. Alu elements are among the most prevalent repetitive sequences and constitute 11% of the human genome. Although Alu methylation has been evaluated in many types of cancer, few studies have examined the levels of this modification in serum from NPC patients. Objective: To compare the Alu methylation levels and patterns between serum from NPC patients and normal controls. Materials and Methods: Sera from 50 NPC patients and 140 controls were examined. Quantitative combined bisulfite restriction analysis-Alu (qCOBRA-Alu) was applied to measure Alu methylation levels and characterize Alu methylation patterns. Amplified products were classified into four patterns according to the methylation status of 2 CpG sites: hypermethylated (methylation at both loci), partially methylated (methylation of either of the two loci), and hypomethylated (unmethylated at both loci). Results: A comparison of normal control sera with NPC sera revealed that the latter presented a significantly lower methylation level (p=0.0002) and a significantly higher percentage of hypomethylated loci (p=0.0002). The sensitivity of the higher percentage of Alu hypomethyted loci for distinguishing NPC patients from normal controls was 96%. Conclusions: Alu elements in the circulating DNA of NPC patients are hypomethylated. Moreover, Alu hypomethylated loci may represent a potential biomarker for NPC screening.