exudates and Nasopharyngeal-Carcinoma

Epstein-Barr virus (EBV) was the first herpesvirus associated to human malignancies. Despite the well-known association between EBV and malignancies, the prevalence of EBV infection in Malaysians with malignancies is unknown. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used to conduct a systematic review and meta- analysis of published data in this study. Studies reporting the occurrence of EBV infection in Malaysian malignancy patients were searched in electronic databases like PubMed, Scopus, ScienceDirect, and Google Scholar without year or language constraints. The study protocol was filed in PROSPERO (CRD42021273769). A total of 21 studies were included, with 1,036 EBV infection cases among 2,078 malignancy patients. The random-effects model was used to produce summary estimates. The pooled prevalence of EBV infection in Malaysians with malignancy was 36.3% (95% CI, 20.3 - 56.2). When the prevalence estimates were stratified by malignancy type, nasopharyngeal carcinoma has the highest prevalence (90.5%), followed by lymphoma (23.4%), and gastric carcinoma (10.0%). Male patients had a higher cases prevalence and most patients were above the age of 40. In Malaysia, many malignancies are increasingly linked to EBV infection. Screening for EBV infection in malignancy patients is therefore important to determine disease recurrence and metastases.

Topics: Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Malaysia; Male; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Prevalence

This analysis provides an epidemiological update for nasopharyngeal carcinomas the state of Sarawak and an analysis of the trend over a 20 years period.. Data between 1996 to 2015 from a population-based cancer registry in Sarawak Malaysia was analyzed. Crude incidence rates and age-standardized rates (ASR) were calculated and compared between ethnic groups and locations (administrative division) and Joinpoint regression analysis was done to analyze trends.. A total of 3643 cases of NPC were recorded with male to female ratio of 2.5:1. Annualised age-standardized incidence rates able 2) for men is 13.2 cases per 100,000 population (95% CI: 12.6, 13.7) and for women is 5.3 cases per 100,000 population (95% CI: 5.0, 5.6). The highest incidence rates were reported among the Bidayuh population and it ranks among the highest in the world. Trend analysis noted an overall reduction of cases, with a significant decrease between 1996 and 2003 (annual percentage reduction of incidence by 3.9%). Analysis of individual ethnic groups also shows a general reduction with exception of Iban males showing an average 5.48 per cent case increase between 2009 to 2015, though not statistically significant.. Comparing the incidences with other registries, the Bidayuh population in Sarawak remained among the highest in the world and warrants close attention for early screening and prevention strategies.

Topics: Ethnicity; Female; Humans; Malaysia; Male; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Plastic Surgery Procedures

The male predominance in the incidence of nasopharyngeal carcinoma (NPC) suggests the contribution of the X chromosome to the susceptibility of NPC. However, no X-linked susceptibility loci have been examined by genome-wide association studies (GWASs) for NPC by far.. To understand the contribution of the X chromosome in NPC susceptibility, we conducted an X chromosome-wide association analysis on 1615 NPC patients and 1025 healthy controls of Guangdong Chinese, followed by two validation analyses in Taiwan Chinese (n = 562) and Malaysian Chinese (n = 716).. Our finding reveals new susceptibility loci at the X chromosome conferring risk of NPC and supports the value of including the X chromosome in large-scale association studies.

Topics: Adult; Asian People; China; Chromosomes, Human, X; Female; Genetic Association Studies; Genetic Loci; Genetic Predisposition to Disease; Humans; Malaysia; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Polymorphism, Single Nucleotide; Sex Characteristics; Taiwan

8-oxoG, a common DNA lesion resulting from reactive oxygen species (ROS), has been shown to be associated with cancer initiation. hOGG1 DNA glycosylase is the primary enzyme responsible for excision of 8-oxoG through base excision repair (BER). Integrins are members of a family of cell surface receptors that mediate the cell-cell and extracellular matrix (ECM) interactions. Integrins are involved in almost every aspect of carcinogenesis, from cell differentiation, cell proliferation, metastasis to angiogenesis. Loss of ITGA2 expression was associated with enhanced tumor intravasation and metastasis of breast and colon cancer. XPD gene encodes DNA helicase enzyme that is involved in nucleotide excision repair (NER). It is shown in previous research that XPD homozygous wildtype Lys/Lys genotype was associated with higher odds of NPC.. We conducted a 1 to N case-control study involving 300 nasopharyngeal carcinoma (NPC) cases and 533 controls matched by age, gender and ethnicity to investigate the effect of hOGG1 Ser326Cys, ITGA2 C807T and XPD Lys751Gln polymorphisms on NPC risk. Linkage disequilibrium and haplotype analysis were conducted to explore the association of allele combinations with NPC risk. Restriction fragment length polymorphism (RFLP-PCR) was used for DNA genotyping.. No significant association was observed between hOGG1 Ser326Cys and ITGA2 C807T polymorphisms with NPC risk after adjustment for age, gender, ethnicity, cigarette smoking, alcohol and salted fish consumption. Lys/Lys genotype of XPD Lys751Gln polymorphism was associated with increased NPC risk (OR = 1.60, 95% CI = 1.06-2.43). Subjects with history of smoking (OR = 1.81, 95% CI = 1.26-2.60), and salted fish consumption before age of 10 (OR = 1.77, 95% CI = 1.30-2.42) were observed to have increased odds of NPC. The odds of developing NPC of CGC haplotype was significantly higher compared to reference AGC haplotype (OR = 2.20, 95% CI = 1.06-4.58).. The allele combination of CGC from hOGG1, ITGA2 and XPD polymorphisms was significantly associated with increased odds of NPC.

Topics: Carcinoma; DNA Glycosylases; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Haplotypes; Humans; Integrin alpha2; Linkage Disequilibrium; Malaysia; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Polymorphism, Single Nucleotide; Risk Factors; Xeroderma Pigmentosum Group D Protein

Nasopharyngeal carcinoma (NPC) exhibits a distinctive racial and geographic distribution. Many studies have reported varied significant prognostic factors affect the survival of NPC patients. Hence, this current study aimed to identify the prognostic factors of NPC patients registered in a tertiary referral hospital.. The records of one hundred and thirty-four NPC cases confirmed by histopathology in Hospital Universiti Sains Malaysia (USM) between 1st January 1998 and 31st December 2007 that fulfilled the inclusion and exclusion criteria were retrospectively reviewed. Simple and multiple Cox proportional hazard regression analyses were performed to determine the significant prognostic factors affect the survival of NPC patients.. The mean (SD) age of patients diagnosed with NPC was 48.12 (15.88) years with Malay was the largest ethnic group compared to other ethnicities. Most of patients had locally advanced stage IV (40.6%) and stage III (39.1%) of NPC. The overall median survival time of NPC patients was 31.30 months (95% CI 23.76, 38.84). The significant prognostic factors that influenced the survival of NPC patients were older age (HR 1.03, 95% CI 1.01, 1.04), metastases (HR 2.52, 95% CI 1.01, 6.28) and stage IV disease (HR 4.50, 95% CI 1.66, 9.88).. Older age, the presence of metastases and late stage are significant prognostic factors that influence the survival of NPC. Therefore, it is important to provide education to public and to raise awareness to diagnose NPC at an earlier stage and before the presence of metastases.

Topics: Adult; Carcinoma; Female; Humans; Malaysia; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Prognosis; Referral and Consultation; Retrospective Studies; Survival Rate; Tertiary Care Centers

Endoscopic endonasal nasopharyngectomy (EEN) has become increasingly used for recurrent nasopharyngeal carcinoma (rNPC) due to reduced functional and cosmetic morbidities compared to conventional external approach. Majority of the existing studies on EEN focused on patients with lower recurrent staging of rT1 and rT2. The aims of this study were to provide a preliminary report on the outcome of EEN performed in patients with advanced (rT3 and rT4) rNPC, and to determine the prognostic factors for patients' survival. All patients who underwent EEN for rNPC between January 2003 and December 2015 inclusive were analyzed. All surgeries were performed in University Malaya Medical Centre in Kuala Lumpur and Queen Elizabeth Hospital in Sabah, by a single surgeon. We reported the 2-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) and any related complications and significant prognostic factors. Fifteen patients with recurrent NPC (2 rT3 and 13 rT4 tumours) underwent EEN over the 13 years period. The mean age was 50.4 years (range 30-65) and the mean follow-up period was 28.7 months (range 9-81 weeks). The 2-year OS, DFS and DSS were 66.7 % (mean 19.4 months), 40 % (mean 15.7 months) and 73.3 % (mean 20.2 months), respectively. No severe operative complications were encountered. No independent prognostic factors for survival outcome were identified. This is the first preliminary report in English that exclusively looked at the use of EEN in advanced rT3 and rT4 NPCs, showing favourable patient outcome. However, further long-term follow-up of patients is required.

Topics: Adult; Carcinoma; Disease-Free Survival; Female; Follow-Up Studies; Humans; Malaysia; Male; Middle Aged; Nasal Surgical Procedures; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Natural Orifice Endoscopic Surgery; Neoplasm Recurrence, Local; Neoplasm Staging; Pharyngectomy; Postoperative Complications; Prognosis; Retrospective Studies

Nasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition.. A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124).. Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR) = 7.27; 95% CI = 2.96-17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75-10.11) overlapping MICA/HCP5/HCG26 genes.. Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asian People; Carcinoma; China; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 6; Cohort Studies; DNA Copy Number Variations; Female; Gene Frequency; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Malaysia; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Young Adult

Nasopharyngeal carcinoma (NPC) is an epithelial squamous cell carcinoma on the mucosal lining of the nasopharynx. The etiology of NPC remains elusive despite many reported studies. Most studies employ a single platform approach, neglecting the cumulative influence of both the genome and transcriptome toward NPC development. We aim to employ an integrated pathway approach to identify dysregulated pathways linked to NPC. Our approach combines imputation NPC GWAS data from a Malaysian cohort as well as published expression data GSE12452 from both NPC and non-NPC nasopharynx tissues. Pathway association for GWAS data was performed using MAGENTA while for expression data, GSA-SNP was used with gene p values derived from differential expression values from GEO2R. Our study identified NPC association in the gene ontology (GO) axonemal dynein complex pathway (pGWAS-GSEA  = 1.98 × 10(-2) ; pExpr-GSEA  = 1.27 × 10(-24) ; pBonf-Combined  = 4.15 × 10(-21) ). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (pAmpliSeq-GSEA  = 6.56 × 10(-4) ). Loss of function in the axonemal dynein complex causes impaired cilia function, leading to poor mucociliary clearance and subsequently upper or lower respiratory tract infection, the former of which includes the nasopharynx. Our approach illustrates the potential use of integrated pathway analysis in detecting gene sets involved in the development of NPC in the Malaysian cohort.

Topics: Carcinoma; Case-Control Studies; Cohort Studies; Dyneins; Female; Gene Expression Profiling; Genome-Wide Association Study; Humans; Malaysia; Male; Models, Genetic; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Polymorphism, Single Nucleotide; RNA, Neoplasm; Signal Transduction

Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein-Barr virus type 1 (EBV-1) infection. We carried out a genome-wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA-A to NPC with the strongest signal detected in rs3869062 (p = 1.73 × 10(-9)). HLA-A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (p(HLA-A-aa-site-99) = 3.79 × 10(-8), p(rs1136697) = 3.79 × 10(-8)) and T-cell receptor binding site (p(HLA-A-aa-site-145) = 1.41 × 10(-4), p(rs1059520) = 1.41 × 10(-4)) of the HLA-A. We also detected strong association signals in the 5'-UTR region with predicted active promoter states (p(rs41545520) = 7.91 × 10(-8)). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520-G correlated with reduced HLA-A expression. Multivariate logistic regression diminished the effects of HLA-A amino acid variants and SNPs, indicating a correlation with the effects of HLA-A*11:01, and to a lesser extent HLA-A*02:07. We report the strong genetic influence of HLA-A on NPC susceptibility in the Malaysian Chinese.

Topics: Amino Acids; Asian People; Carcinoma; Cohort Studies; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; HLA-A Antigens; Humans; Malaysia; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Polymorphism, Single Nucleotide

To evaluate the treatment outcome and major late complications of all patients with recurrent nasopharyngeal carcinoma (NPC) treated with intracavitary brachytherapy (ICBT) in Hospital Kuala Lumpur.. This retrospective study was conducted at the Department of Radiotherapy and Oncology, Hospital Kuala Lumpur, Malaysia. All patients with histologically confirmed recurrent NPC in the absence of distant metastasis treated in the period 1997-2010 were included in this study. These patients were treated with ICBT alone or in combination with external beam radiotherapy (EBRT). Treatment outcomes measured were local recurrence free survival (LRFS), disease free survival (DFS) and overall survival (OS).. Thirty three patients were eligible for this study. The median age at recurrence was 56 years with a median time to initial local recurrence of 27 months. Majority of patients were staged as rT1-2 (94%) or rN0 (82%). The proportion of patients categorised as stage III-IV at first local recurrence was only 9%. Twenty one patients received a combination of ICBT and external beam radiotherapy while 12 patients were treated with ICBT alone. Median interval of recurrence post re-irradiation was 32 months (range: 4-110 months). The median LRFS, DFS and OS were 30 months, 29 months and 36 months respectively. The 5 year LRFS, DFS and OS were 44.7%, 38.8% and 28.1% respectively. The N stage at recurrence was found to be a significant prognostic factor for LRFS and DFS after multivariate analysis. Major late complications occurred in 34.9% of our patients.. Our study shows ICBT was associated with a reasonable long term outcome in salvaging recurrent NPC although major complications remained a significant problem. The N stage at recurrence was a significant prognostic factor for both LRFS and DFS.

Topics: Adult; Aged; Aged, 80 and over; Brachytherapy; Carcinoma; Female; Follow-Up Studies; Humans; Malaysia; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; Neoplasm Staging; Retrospective Studies; Salvage Therapy; Survival Rate; Treatment Outcome

Nasopharyngeal carcinoma (NPC) is a solid tumor of the head and neck. Multimodal therapy is highly effective when NPC is detected early. However, due to the location of the tumor and the absence of clinical signs, early detection is difficult, making a biomarker for the early detection of NPC a priority. The dysregulation of small non-coding RNAs (miRNAs) during carcinogenesis is the focus of much current biomarker research. Herein, we examine several miRNA discovery methods using two sample matrices to identify circulating miRNAs (c-miRNAs) associated with NPC.. We tested two miRNA discovery workflows on two sample sources for miRNAs associated with NPC. In the first workflow, we assumed that NPC tumor tissue would be enriched for miRNAs, so we compared miRNA expression in FFPE from NPC cases and controls using microarray and RNA-Seq technologies. Candidate miRNAs from both technologies were verified by qPCR in FFPE and sera from an independent NPC sample set. In a second workflow, we directly interrogated NPC case and control sera by RNA-Seq for c-miRNAs associated with NPC, with candidate c-miRNAs verified by qPCR in the sera from the same independent NPC sample set.. Both microarray and RNA-Seq narrowed the miRNA signature to 1-5% of the known mature human miRNAs. Moreover, these two methods produced similar results when applied to the same sample type (FFPE), with RNA-Seq additionally indicating "unknown" miRNAs associated with NPC. However, we found different miRNA profiles in NPC sera compared to FFPE using RNA-Seq, with the few overlapping miRNAs found to be significantly up-regulated in FFPE significantly down-regulated in sera (and vice versa). Despite the different miRNA profiles found in FFPE and sera, both profiles strongly associated with NPC, providing two potential sources for biomarker signatures for NPC.. We determined that the direct interrogation of sera by RNA-Seq was the most informative method for identifying a c-miRNA signature associated with NPC. We also showed that there are different miRNA expression profiles associated with NPC for tumor tissue and sera. These results reflect on the methods and meaning of miRNA biomarkers for NPC in tissue and peripheral blood.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Case-Control Studies; Cluster Analysis; DNA, Complementary; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Herpesvirus 4, Human; Humans; Malaysia; Male; MicroRNAs; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Oligonucleotide Array Sequence Analysis; Paraffin Embedding; Real-Time Polymerase Chain Reaction; RNA, Neoplasm; RNA, Viral; Tissue Fixation

DNA repair pathways play a crucial role in maintaining the human genome. Previous studies associated DNA repair gene polymorphisms (XPD Lys751Gln, XRCC1 Arg280His and XRCC1 Arg399Gln) with nasopharyngeal carcinoma. These non-synonymous polymorphisms may alter DNA repair capacity and thus increase or decrease susceptibility. The present study aimed to determine the genotype distribution of XPD codon 751, XRCC1 codon 280 and codon 399 polymorphisms and haplotype associations among NPC cases and controls in the Malaysian population.. We selected 157 NPC cases and 136 controls from two hospitals in Kuala Lumpur, Malaysia for this study. The polymorphisms studied were genotyped by PCR-RFLP assay and allele and genotype frequencies, haplotype and linkage disequilibrium were determined using SNPstat software.. For the XPD Lys751Gln polymorphism, the frequency of the Lys allele was higher in cases than in controls (94.5% versus 85.0%). For the XRCC1 Arg280His polymorphism, the frequency of Arg allele was 90.0% and 89.0% in cases and controls, respectively and for XRCC1 Arg399Gln the frequency of the Arg allele was 72.0% and 72.8% in cases and controls respectively. All three polymorphisms were in linkage disequilibrium. The odds ratio from haplotype analysis for these three polymorphisms and their association with NPC was 1.93 (95%CI: 0.90-4.16) for haplotype CGC vs AGC allele combinations. The global haplotype association with NPC gave a p-value of 0.054.. Our study provides an estimate of allele and genotype frequencies of XRCC1Arg280His, XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms in the Malaysian population and showed no association with nasopharyngeal cancer.

Topics: Carcinoma; Case-Control Studies; DNA Repair; DNA-Binding Proteins; Genotype; Haplotypes; Humans; Incidence; Malaysia; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Risk Factors; X-ray Repair Cross Complementing Protein 1; Xeroderma Pigmentosum Group D Protein

Nasopharyngeal carcinoma (NPC) is the commonest radiocurable cancer in Malaysia. This study aimed to determine the treatment outcomes and late effects of radiotherapy for NPC patients treated in University Malaya Medical Centre (UMMC).. All newly diagnosed patients with NPC referred for treatment to the Oncology unit at UMMC from 2004-2008 were retrospectively analyzed. Treatment outcomes were 5 years overall survival (OS), disease free survival (DFS), cause-specific survival (CSS), loco- regional control (LRC) and radiotherapy-related late effects. The Kaplan-Meier method was used for survival analysis and differences in survival according to AJCC stage was compared using the log-rank test.. A total of 176 patients with newly diagnosed NPC were treated in UMMC during this period. Late presentation was common, with 33.5% presenting with T3-4 disease, 84.7% with N1-3 disease and 75.6% with AJCC stage 3-4 disease. Radical RT was given to 162 patients with 22.7% having RT alone and 69.3% having CCRT. The stipulated OTT was 7 weeks and 72.2% managed to complete their RT within this time period. Neoadjuvant chemotherapy was given to 14.8% while adjuvant chemotherapy was administered to 16.5%. The 5 years OS was 51.6% with a median follow up of 58 months. The 5 years OS according to stage were 81.8% for stage I, 77.9% for stage II, 47.4% for stage III and 25.9% for stage IV. The 5 years overall CSS, DFS and LRC were 54.4%, 48.4% and 70.6%, respectively. RT related late effects were documented in 80.2%. The commonest was xerostomia (66.7%). Other documented late effects were hearing deficit (17.3%), visual deficit (3.1%), neck stiffness (3.1%) , dysphagia (3.4%), cranial nerve palsy (2.5%), pneumonitis (0.6%) and hypothyroidism (1.2%).. The 5 years OS and LRC in this study are low compared to the latest studies especially those utilizing IMRT. Implementation of IMRT for NPC treatment should be strongly encouraged.

Topics: Adult; Aged; Carcinoma; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Malaysia; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Radiotherapy Dosage; Retrospective Studies; Survival Rate; Time Factors; Young Adult

Nasopharyngeal carcinoma (NPC) is a multifactorial and polygenic disease with high incidence in Asian countries. Epstein-Barr virus infection, environmental and genetic factors are believed to be involved in the tumorigenesis of NPC. The association of single nucleotide polymorphisms (SNPs) in LPLUNC1 and SPLUNC1 genes with NPC was investigated by performing a two-stage case control association study in a Malaysian Chinese population. The initial screening consisted of 81 NPC patients and 147 healthy controls while the replication study consisted of 366 NPC patients and 340 healthy controls. The combined analysis showed that a SNP (rs2752903) of SPLUNC1 was significantly associated with the risk of NPC (combined P = 0.00032, odds ratio = 1.62, 95% confidence interval = 1.25-2.11). In the subsequent dense fine mapping of SPLUNC1 locus, 36 SNPs in strong linkage disequilibrium with rs2752903 (r(2) ≥ 0.85) were associated with NPC susceptibility. Screening of these variants by electrophoretic mobility shift and luciferase reporter assays showed that rs1407019 located in intron 3 (r(2)  = 0.994 with rs2752903) caused allelic difference in the binding of specificity protein 1 (Sp1) transcription factor and affected luciferase activity. This SNP may consequently alter the expression of SPLUNC1 in the epithelial cells. In summary, our study suggested that rs1407019 in intronic enhancer of SPLUNC1 is associated with NPC susceptibility in which its A allele confers an increased risk of NPC in the Malaysian Chinese population.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asian People; Autoantigens; Carcinoma; Case-Control Studies; China; Electrophoretic Mobility Shift Assay; Fatty Acid-Binding Proteins; Female; Genetic Predisposition to Disease; Glycoproteins; Humans; Introns; Linkage Disequilibrium; Malaysia; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Odds Ratio; Phosphoproteins; Polymorphism, Single Nucleotide; Proteins; Random Allocation; Young Adult

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr Virus (EBV)-associated cancer that is the fifth most common cancer in Malaysia. Early and accurate diagnoses are critical for patient prognosis. Unfortunately, early detection of NPC is still a challenge and the cost of more accurate imaging protocols is prohibitive in developing countries like Malaysia.. To evaluate the clinical values of pre-treatment plasma EBV DNA levels in Malaysian NPC patients.. Plasma EBV DNA levels were measured by quantitative PCR (Q-PCR) in a large and multi-ethnic cohort of Malaysian patients with NPC (n=459) and 72 control subjects.. We show for the first time that, compared to controls, NPC patients with stage I disease had significantly higher levels of EBV DNA (p<0.001). Further, the median level of plasma EBV DNA in stage IV patients with distant metastasis was >9-fold higher than those without systemic spread (p=0.001), suggesting plasma EBV DNA measurement could aid in the diagnosis of metastatic disease in advanced cases. Further, using a cut-off value of 8000 copies/mL, we demonstrate that EBV DNA level is a strong predictor for overall survival of NPC patients.. Our data show that pre-treatment plasma EBV DNA is a potential biomarker for early stage and metastatic NPC. We conclude that the quantification of plasma EBV DNA is a useful tool in developing countries to stratify patients for MRI or PET/CT scans where such imaging protocol is not routinely applied.

Topics: Adolescent; Adult; Aged; Carcinoma; Case-Control Studies; DNA, Viral; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Kaplan-Meier Estimate; Malaysia; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Retrospective Studies; Statistics, Nonparametric

Nasopharyngeal carcinoma is the third most common cancer among men in Peninsular Malaysia. However, no information is available about the prognostic factors. The objective of this study was to identify factors with an influence on outcome in patients treated in Hospital Kuala Lumpur.. A total of 159 patients with non-metastatic nasopharyngeal carcinoma treated during 2002-2003 in Hospital Kuala Lumpur were included in this study. All received radiotherapy. Fifty three patients were treated with radiotherapy alone, while 106 patients received combination chemotherapy. Overall survival and local recurrence-free survival were analyzed using the Kaplan-Meier method and univariate analysis was performed using the log-rank test.. This study found out that 5-year overall survival and 5-year local recurrence-free survival rates were 58.6% and 54.2% respectively. The stage specific 5-year overall survival rates were: Stage I, 100%; Stage II; 93.3%, Stage III, 62.7%; Stage IVA, 42.2%; and Stage IVB, 40.6%. On univariate analysis, gender (p<0.05), T-classification (p<0.001), N-classification (p<0.05), stage (p<0.05) and cranial nerve involvement (p<0.001) were found to be significant prognostic factors for 5-year overall survival, while gender (p<0.05) and N-classification (p<0.05) were significant prognostic factors for 5-year local recurrence-free survival.. The overall survival rate of patients for this study was low. The patient factor that significantly affected 5-year overall survival was gender, while disease factors were stage, T-classification, N-classification and cranial nerve involvement.

Topics: Adolescent; Adult; Aged; Carcinoma; Carcinoma, Squamous Cell; Combined Modality Therapy; Cross-Sectional Studies; Disease-Free Survival; Female; Humans; Malaysia; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharynx; Neoplasm Recurrence, Local; Prognosis; Sex Factors; Survival Rate; Treatment Outcome; Young Adult

Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Malaysia, mainly occurring among the Chinese population. To detect common genetic alterations in NPC, we screened seven cases of NPC using the comparative genomic hybridization (CGH) technique. Before proceeding to the CGH technique, the tumors were first confirmed to consist of 75% tumor cells or more. In brief, the technique consists of binding tumor DNA with normal DNA and human Cot-1 DNA, which is then hybridized to normal metaphase spreads. The slides were then counterstained with 4,6 diamino-2-phenylindole (DAPI II) for detection. Analyses were performed using CGH software (Cytovision). We found genetic alterations in all seven NPC samples. The common chromosomal gains (57%, four cases) were found on chromosome arms 1q, 4p, 5, 7q, 11, 14p, 15q, 18p, and 21p, and common chromosomal losses (43%, three cases) were found on chromosome arm 16p. Our results showed chromosomal alterations in all seven NPC cases in the Malaysian population. This result provides the platform for further investigations to locate tumor suppressor genes and oncogenes at specific chromosomal regions in Malaysian NPC patients.

Topics: Adult; Aged; Carcinoma; Chromosome Mapping; Chromosomes; Comparative Genomic Hybridization; DNA, Neoplasm; Female; Humans; Malaysia; Male; Middle Aged; Models, Genetic; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms