• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8059-8065
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• 2016

Nasopharyngeal carcinoma (NPC) is a common tumor in southern China and south-eastern Asia. Effective strategies for the prevention or screening of NPC are limited. Exploring effective biomarkers for the early diagnosis and prognosis of NPC continues to be a rigorous challenge. Evidence is accumulating that DNA methylation alterations are involved in the initiation and progression of NPC. Over the past few decades, aberrant DNA methylation in single or multiple tumor suppressor genes (TSGs) in various biologic samples have been described in NPC, which potentially represents useful biomarkers. Recently, large-scale DNA methylation analysis by genome-wide methylation platform provides a new way to identify candidate DNA methylated markers of NPC. This review summarizes the published research on the diagnostic and prognostic potential biomarkers of DNA methylation for NPC and discusses the current knowledge on DNA methylation as a biomarker for the early detection and monitoring of progression of NPC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.653-656
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• 2015

Background: Nasopharyngeal carcinoma (NPC) is an aggressive disease and tends to involve surrounding tissues, and biomarkers for better management are yet to be identified. Materials and Methods: One hundred and fifty tissue samples with NPC diagnosis were were investigated using pan cytokeratin (CK) and epithelial membrane protein 2 (EMP2) antibodies. Results: Immunohistochemical expression of CK was identified in 144/150 (96%) and of EMP2 in 120/150 (80%). Conclusions: There is a high loss of EMP2 in NPC, especially high grade examples. Loss of CK expression is also linked to high grade NPC types.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6455-6459
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• 2014

Background: Nasopharyngeal carcinoma (NPC) is the fourth most common cancer in Malaysia. The objective of this study was to determine the five-year survival rate and median survival time of NPC patients in Hospital Universiti Sains Malaysia (USM). Methods: One hundred and thirty four NPC cases confirmed by histopathology in Hospital USM between $1^{st}$ January 1998 and $31^{st}$ December 2007 that fulfilled the inclusion and exclusion criteria were retrospectively reviewed. Survival time of NPC patients were estimated by Kaplan-Meier survival analysis. Log-rank tests were performed to compare survival of cases among presenting symptoms, WHO type, TNM classification and treatment modalities. Results: The overall five-year survival rate of NPC patients was 38.0% (95% confidence interval (CI): 29.1, 46.9). The overall median survival time of NPC patients was 31.30 months (95%CI: 23.76, 38.84). The significant factors that altered the survival rate and time were age (p=0.041), cranial nerve involvement (p=0.012), stage (p=0.002), metastases (p=0.008) and treatment (p<0.001). Conclusion: The median survival of NPC patients is significantly longer for age ${\leq}50$ years, no cranial nerve involvement, and early stage and is dependent on treatment modalities.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2001-2006
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• 2014

The objective of this study was to investigate the diagnostic significance of EBV antibody combined detection for nasopharyngeal carcinoma (NPC) in a high incidence region of southern China. Two hundred and eleven untreated NPC patients, 203 non-NPC ENT patients, and 210 healthy controls were recruited for the study. The titers of VCA/IgA and EA/IgA were assessed by immunoenzyme assay, and the levels of Rta/IgG and EBNA1/IgA were determined by enzyme-linked immunosorbent assay. The levels of VCA/IgA, EA/IgA, Rta/IgG and EBNA1/IgA demonstrated no association with gender or age (p>0.05). The receiver operating characteristic curve and the area under the curve were used to evaluate the diagnostic value. The sensitivity of VCA/IgA (98.1%) and the specificity of EA/IgA (98.5%) were the highest. When a logistic regression model was used to combine the results from multiple antibodies to increase the accuracy, the combination of VCA/IgA+Rta/IgG, whose area under the curve was 0.99, had the highest diagnostic efficiency, and its sensitivity, specificity and Youden index were 94.8%, 98.0% and 0.93 respectively. The data suggest that the combination of VCA/IgA+Rta/IgG may be most suitable for NPC serodiagnosis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.165-171
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• 2013

The aim of the present study was to analyze the expression of FHIT and WWOX in nasopharyngeal carcinoma (NPC) and correlations with clinical pathologic features. mRNA expression of the FHIT and WWOX was assessed by real-time fluorescent relatively quantitative PCR in 61 NPC tissues and 45 non-cancerous nasopharyngeal tissues. As a result, mRNA expression levels of both FHIT and WWOX were significantly lower in NPC patients than in control samples (P=0.049 and 0.045, respectively). Moreover, the mRNA expression of both had an inverse relation with larger invasive range (P=0.035 and 0.048, respectively), poor histologic differentiation (P=0.012 and 0.016) and advanced clinical stage (P=0.026 and 0.038). Consistency was found between expression of FHIT and WWOX in the same NPC tissues (r=0.681, P=0.00). In conclusion, synergy between FHIT and WWOX may exist in the development of NPC so that the two factors may be considered as important genetic markers. Detecting the expression of FHIT and WWOX should provide clinically significant information relevatn to tumor diagnosis, progression and treatment modalities for NPC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5145-5151
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• 2013

Background: Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles. Aims: To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma. Materials and Methods: We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G) using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300 healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models. Results: After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02-3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantly increased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1-141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18-0.89) in the smoking group. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants, was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004). Conclusion: This is the first study to focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphism and NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1-141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BER genes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6315-6319
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• 2013

To study the differentiated expression of the proto-oncogene Pokemon in nasopharyngeal carcinoma (NPC) cell lines and tissues, mRNA and protein expression levels of CNE1, CNE2, CNE3 and C666-1 were detected separately by reverse transcription polymerase chain reaction (RT-PCR), real-time PCR and Western-blotting. The immortalized nasopharyngeal epithelial cell line NP69 was used as a control. The Pokemon protein expression level in biopsy specimens from chronic rhinitis patients and undifferentiated non keratinizing NPC patients was determined by Western-blotting and arranged from high to low: C666-1>CNE1>CNE2> CNE3>NP69. The Pokemon mRNA expression level was also arranged from high to low: CNE1>CNE2>NP69>C666-1>CNE3. Pokemon expression of NP69 and C666-1 obviously varied from mRNA to protein. The Pokemon protein level of NPC biopsy specimens was obviously higher than in chronic rhinitis. The data suggest that high Pokemon protein expression is closely associated with undifferentiated non-keratinizing NPC and may provide useful information for NPC molecular target therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2653-2657
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• 2015

Nasopharyngeal carcinoma (NPC) is the second most common neoplasm of head and neck in Tunisia. The distribution is bimodal with a first period occurrence between 15 and 20 years old and a second peak at around 50 years of age. Undifferentiated carcinoma of nasopharynx type III (UCNT) is the predominant histological type (93.4%). Data of cancer registry of North Tunisia confirmed that it is an intermediate risk area for NPC with overall ASRs of 3.6 and 1.6/100,000 respectively in males and females. This study aimed to present the evolution of incidence rate of nasopharyngeal carcinoma over a period of 12 years (1994-2006). Data of cancer registry of North Tunisia (NTCR), covering half of the Tunisian population, were used to determine evolution of NPC incidence, calculated by 5 year periods. The estimated annual percentage change (EAPC) was used as an estimate of the trend. To best summarize the behavior or the data trend across years, we used a join-point regression program. Between 1994 and 2006, we observed negative annual average change of standardized incidence in men and women (-3.3%and -2.7%) also for the standardized incidences which showed a rather important decline (26.4% in males and 22.3% in females). The truncated age standardized incidence rate of NPC in adults aged of 30 years old and more (N= 1209) decreased by -0.4% per year from 1994 to 2006 over time in north Tunisia dropping from 6.09 to 4.14 person-years. However, the rate was relatively stable during this period among youths aged 0-29 years (N= 233) in both sexes. NPC demonstrated a favorable evolution from 1994-2006 probably due to a improvement in socioeconomic conditions.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2283-2287
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• 2015

In order to explore the association between RASSF1A methylation and nasopharyngeal carcinoma (NPC) risk of Chinese, we carried out a meta-analysis with searches of PubMed, Web of Science, ProQest and Medline databases. Ultimately, 14 articles were identified and analysised using R Software (R version 3.1.2) including meta packages. Overall, we found a significant relationship between RASSF1A methylation and NPC risk (OR 30.7; 95 % CI, 16.71~56.23; z=11.0591; p<0.0001) in a fixed effects model and (OR 32.1; 95% CI, 14.27~72.01; z=8.3984; p<0.0001) in a random effects model pooled. In tissue and NP brushings groups, similar results were found. Hence, our study identified a strong association between RASSF1A methylation and NPC and highlighted a promising potential for RASSF1A methylation in NPC risk prediction of Chinese.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2495-2502
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• 2012

Nasopharyngeal carcinoma (NPC) is a disease with distinct ethnic and geographic distribution. The incidence of NPC in Chinese residing in Asia has declined over the last few decades, but NPC mortality trends in the entire Chinese population over time have not been systematically evaluated. In this study, we examined NPC mortality at the national level in China between 1973-2005. Mortality rates were derived from the databases of national retrospective surveys on cancer mortality conducted in the periods of 1973-1975, 1990-1992, and 2004-2005, respectively. NPC was classified according to the International classification of diseases. Age-adjusted mortality rates were calculated by direct standardization according to the world standard population. Trends in rates were evaluated by age, gender, geographic areas, and socioeconomic status. From 1973 to 2005, there was a general trend of decrease in NPC mortality in China, with higher rates in the south on a downward trend in the north. The age-standardized NPC mortality rates were 2.60 per 100,000 in 1973-1975, 1.94 per 100,000 in 1990-1992, and 1.30 per 100,000 in 2004-2005, respectively. The trend was similar in both men and women, in both urban and rural areas, but the declining rates in females were more remarkable than in males. The mortality rates were higher for the age groups above 50 years than those less than 50 years of age, both showing downward trend over 30-year period. In summary, the overall NPC mortality has consistently decreased in China over the past three decades, particularly in women and in old adults.