Trends in nasopharyngeal cancer mortality in the United States, 1999-2020.

OBJECTIVES: The incidence of nasopharyngeal cancer (NPC) has been declining in the United States (US) in recent years. However, little is known about the latest trends in NPC mortality in the US population. This study aimed to examine the trends in NPC mortality rate by age, sex, race and ethnicity and US Census Region from 1999 to 2020. METHODS: Mortality data were extracted from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (WONDER) database. Decedents whose cause of death was NPC were identified using the International Classification of Diseases Codes, 10th Revision: C11.0-C11.9. Trends in age adjusted mortality rates (AAMR) from NPC were assessed using a joinpoint regression model. Annual Percentage Changes (APC) and Average Annual Percentage Changes were examined overall and by age, sex, race and ethnicity and census region. RESULTS: From 1999 through 2020, a total of 14 534 NPC deaths were recorded in the US (AAMR = 0.2 per 100 000; 95% CI: 0.2, 0.2). Overall trends remained stationary throughout the study period. Since 2006, recent trends declined by 6.1% per year (95% CI: -8.4, -3.7) among Non-Hispanic Whites, and by 2.7% per year among Non-Hispanic Blacks, Asians/Pacific Islanders and Hispanics. Trends either stabilized or declined by sex, age and US Census Region. Similar results were obtained when the analysis was restricted to decedents aged 65 years and above. CONCLUSIONS: Stationary or declining trends in NPC mortality could be due to the falling incidence of the disease and/or advances in medical diagnosis and treatment. Considering the enigmatic nature of NPC, future studies should explore the genetic and sociodemographic factors associated with the trends reported in this study.

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

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

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

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

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

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

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

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

The contribution of interleukin-8 genotypes and expression to nasopharyngeal cancer susceptibility in Taiwan.

The incidence rate of nasopharyngeal cancer (nasopharyngeal carcinoma [NPC]) is much higher in Southeast Asia than in western countries. Interleukin-8 (IL-8), a chemokine produced by macrophages, epithelial cells, airway smooth muscle cells, and endothelial cells, is an important immuno-mediator in the development and progression of many types of cancer. Genetic variations in IL-8 have been associated with the risks of NPC and other cancers. In the current study, we evaluated the role of IL-8 in NPC at the levels of DNA, RNA, and protein in a Taiwanese population. First, in a case-control study, 176 NPC patients and 352 cancer-free controls were genotyped, and the associations of IL-8 T - 251A, C + 781T, C + 1633T, and A + 2767T polymorphisms with NPC risk were evaluated. Second, the NPC tissue samples were assessed for their IL-8 mRNA and protein expression by real-time quantitative reverse transcription polymerase chain reaction (PCR) and Western blotting, respectively. Regarding the IL-8 promoter T - 251A, the TA and AA genotypes were associated with significantly decreased risks of NPC compared with the wild-type TT genotype (adjusted odds ratio = 0.61 and 0.52, 95% confidence interval = 0.47-0.93 and 0.37-0.91, P = .0415 and .0289, respectively). The mRNA and protein expression levels for NPC tissues revealed no significant associations among the 20 NPC samples with different genotypes. These findings suggest that IL-8 may play an important role in the carcinogenesis of NPC in Taiwan.

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

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

Significant association of the cytokine variants with head and neck cancer risk: evidence from meta-analysis.

AIM: To evaluate the possible relevance of the IL-18-137 G>C (rs187238), IL-18-607 C>A (rs1946518) and IL-4-590 C>T (rs2243250) polymorphisms to the genetic susceptibility of head and neck cancer. METHODS: Data were retrieved from PubMed, EMBASE, Web of Science and CNKI databases, and the results were independently analysed by two reviewers using Stata 14.0 software. RESULTS: After searching for and assessing the literature, a total of thirteen studies involving 2,959 patients newly diagnosed as head and neck cancer and 3,622 controls from healthy donors were analysed. The results suggested that a strong relationship between patients and healthy controls was observed in the IL-18-137 G>C polymorphism in consistence with the result (CC vs. GG + GC: OR = 1.63, P = 0.004; CC vs. GG: OR = 1.82, P = 0.001). When stratified by cancer type, ethnicity and the source of control samples, significant and elevated risks were obtained in the genetic susceptibility to Asian patients with NPC in all genetic models and in those studies using the PCR-RFLP test method. In addition, comparable results were obtained for the IL-18-607 C>A polymorphism, especially for Asian patients with NPC. CONCLUSIONS: It should be a potential association between IL-18 variants and nasopharyngeal carcinoma. Furthermore, IL-18 gene variants might be considered as a critical role in predicting the occurrence of nasopharyngeal carcinoma in Asian population. However, the IL-4-590 C>T polymorphism does not influence the development of head and neck cancer.

Impact of marital status at diagnosis on survival and its change over time between 1973 and 2012 in patients with nasopharyngeal carcinoma: a propensity score-matched analysis.

The impact of marital status at diagnosis on survival outcomes and its change over time in patients with nasopharyngeal carcinoma (NPC) are unclear. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with NPC in the United States from 1973 to 2012. A primary comparison (married vs. unmarried) was implemented with 1:1 propensity score matching. Secondary comparisons were performed individually between three unmarried subgroups (single, separated/divorced, widowed) and married group. The effect of marital status on cause-specific survival (CSS) and overall survival (OS) were evaluated using univariate/multivariate analysis. Moreover, we investigated the change over time (1973-2012) in the effect of marital status on NPC survival. Married patients had better 5-year CSS/OS than unmarried patients (61.1% vs. 52.6%, P < 0.001; 55.6% vs. 45.3%, P < 0.001, respectively). In multivariate analysis, unmarried patients had significantly poorer CSS/OS than married patients (adjusted hazard ratio [aHR] = 1.35, P < 0.001; aHR = 1.40, P < 0.001, respectively). The survival benefit of being married was only detected in non-Hispanic white and Chinese American patients. Single, separated/divorced, and widowed patients had significantly poorer CSS/OS than married patients (aHR = 1.37 and 1.37; 1.46 and 1.42; 1.43 and 1.48, respectively; all P < 0.001). The change over time in the effect of marital status on survival was more stable in male than female. The strength of the negative effect of separated/divorced and widowed status showed a downward and upward trend, respectively. Gender difference in the adverse effect of single status on NPC survival became smaller over time. Only non-Hispanic white and Chinese American patients with NPC obtain survival benefits from married status. Single and widowed patients are regarded as high-risk population.

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

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

Association of Single-Nucleotide Polymorphisms in DC-SIGN with Nasopharyngeal Carcinoma Susceptibility.

The aim of this study was to explore potential relationships of four single-nucleotide polymorphisms (SNPs) in the gene encoding dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) with risk of nasopharyngeal carcinoma (NPC). The DC-SIGN SNPs rs7252229, rs4804803, rs2287886, and rs735240 were genotyped in 477 unrelated NPC patients and 561 cancer-free controls. At rs7252229, risk of NPC was significantly lower in individuals with GC (odds ratio [OR] 0.076, 95% confidence interval [CI] 0.008-0.690), GG (OR 0.056, 95%CI 0.006-0.487), or GC + GG (OR 0.059, 95%CI 0.007-0.515) than in individuals with the CC genotype, after adjusting for age, gender, smoking history, and EBV-VCA-IgA status. At rs4804803, risk of NPC was significantly higher in individuals with the genotype GG than in those with the genotype AA (adjusted OR 9.038, 95%CI 1.708-47.822). At rs735240, risk of NPC did not change significantly with genotypes AG, GG, or AG + GG after adjusting for age, gender, and smoking history. However, when data were also adjusted for EBV-VCA-IgA status, three genotypes emerged as associated with significantly higher risk of NPC than the AA genotype: AG (OR 2.976, 95%CI 1.123-7.888), GG (OR 3.314, 95%CI 1.274-8.622), or GG + AG (OR 3.191, 95%CI 1.237-8.230). Our results suggest that DC-SIGN SNPs rs7252229, rs4804803, and rs735240 may influence NPC risk in the Chinese population. The mechanisms mediating this risk require a further study.

The prognostic role of sex, race, and human papillomavirus in oropharyngeal and nonoropharyngeal head and neck squamous cell cancer.

BACKGROUND: Human papillomavirus (HPV) is a well-established prognostic marker for oropharyngeal squamous cell cancer (OPSCC). Because of the limited numbers of women and nonwhites in studies to date, sex and racial/ethnic differences in prognosis have not been well explored. In this study, survival differences were explored by the tumor HPV status among 1) patients with OPSCCs by sex and race and 2) patients with nonoropharyngeal (non-OP) head and neck squamous cell cancers (HNSCCs). METHODS: This retrospective, multi-institution study included OPSCCs and non-OP HNSCCs of the oral cavity, larynx, and nasopharynx diagnosed from 1995 to 2012. Race/ethnicity was categorized as white non-Hispanic, black non-Hispanic, Asian non-Hispanic, and Hispanic of any race. Tumors were centrally tested for p16 overexpression and the presence of HPV by HPV16 DNA and high-risk HPV E6/E7 messenger RNA in situ hybridization. Kaplan-Meier and Cox proportional hazards models were used to evaluate overall survival (OS). RESULTS: The study population included 239 patients with OPSCC and 621 patients with non-OP HNSCC with a median follow-up time of 3.5 years. After adjustments for the tumor HPV status, age, current tobacco use, and stage, the risk of death was lower for women versus men with OPSCC (adjusted hazard ratio, 0.55; P = .04). The results were similar with p16. In contrast, for non-OP HNSCCs, HPV positivity, p16 positivity, and sex were not associated with OS. CONCLUSIONS: For OPSCC, there are differences in survival by sex, even after the tumor HPV status has been taken into account. For non-OP HNSCC, the HPV status and the p16 status are not of prognostic significance. Cancer 2017;123:1566-1575. © 2017 American Cancer Society.

Racial and Ethnic Disparities in Nasopharyngeal Cancer Survival in the United States.

Objective To determine whether patient race and ethnicity affect nasopharyngeal cancer survival. Study Design Retrospective database analysis. Setting National Cancer Institute's SEER database (Surveillance, Epidemiology, and End Results), 1988-2010. Subjects and Methods Nasopharyngeal carcinoma cases were extracted according to site codes and histology recode-broad groupings. The cohort of 5427 patients was used to calculate disease-specific survival in regard to race and ethnicity. Extracted data were further analyzed through direct comparisons and multivariable Cox regression models controlling for patient, tumor, and treatment characteristics. Results Unadjusted survival curves for all nasopharyngeal carcinomas considered together showed a statistically significant better disease-specific survival for the African American race ( P = .02) and Asian ethnicity ( P = .01) relative to Caucasian patients. The survival advantage for both these groups was eliminated after controlling for the age and sex of the patients. Conclusion African American and Asian patients with nasopharyngeal cancer have better disease-specific survival as compared with Caucasian patients, while Hispanic ethnicity has no effect relative to Caucasians. This disparity is accounted for by diagnosis at an older age in Caucasian patients but remains poorly explained in regard to Hispanic patients.

HLA-DRB1 allele polymorphism and nasopharyngeal carcinoma risk: a meta-analysis.

The human leukocyte antigens (HLA) DRB1 polymorphism has been implicated in susceptibility to nasopharyngeal carcinoma (NPC). However, the results are inconsistent. The aim of this meta-analysis is to evaluate the association between the HLA-DRB1 polymorphisms and NPC risk. All eligible case-control studies published up to June 17, 2015 were identified by searching PubMed, Web of Science, CNKI, Wanfang, and Weipu databases. The NPC risk associated with the HLA-DRB1 polymorphism was estimated for each study by odds ratios (OR) together with its 95 % confidence interval (CI), respectively. Twelve studies with 1152 cases and 1600 controls were included. Overall, a significant positively association between the HLA-DRB1*03, *08, *09, and *10 alleles polymorphism and NPC risk were found (OR = 1.55, 95 % CI 1.30-1.86; OR = 1.44, 95 % CI 1.08-1.92; OR = 1.33, 95 % CI 1.06-1.67; OR = 1.82, 95 % CI 1.02-3.26, respectively), and the HLA-DRB1*01, *11, and *12 alleles were negatively associated with NPC risk (OR = 0.55, 95 % CI 0.39-0.78; OR = 0.62, 95 % CI 0.42-0.91; OR = 0.62, 95 % CI 0.47-0.81, respectively), but we failed to detect any association between other alleles and NPC risk. When stratified by ethnicity, similar results were observed among Asians for HLA-DRB1*03, *08, *09, *11, and *12 alleles and Tunisians for HLA-DRB1*01, *03, and *11 alleles; However, no significant association among Caucasians was observed. This meta-analysis suggests that the HLA-DRB1*03, *08, *09, and *10 alleles polymorphism contributed to the susceptibility of NPC, whereas HLA-DRB1*11 and *12 alleles polymorphism may be an important protective factor for NPC, especially of Asian populations.

Risk of nasopharyngeal carcinoma penetrates across immigrant generations: A migrant cohort study of 2.3 million Jewish Israeli adolescents.

Nasopharyngeal cancer (NPC) incidence varies widely across geographic regions and ethnic groups. We conducted a large-scale migrant cohort study to assess origin and migrant generation as predictors of NPC, controlling for possible confounders. Data on 2.3 million Jewish Israeli adolescents, who underwent a compulsory general health examination at ages 16-19 between the years 1967 and 2011 were linked to the Israel National Cancer Registry to obtain incident NPC up to 2012. Cox proportional hazards were used to model time to event. During 46.5 million person-years of follow-up, 276 incident cases were identified. Origin was a strong independent predictor of NPC with high rates for first generation North African born (adjusted HR 5.52; 95% CI 2.43-12.52; p < 0.000044) and Asian born (adjusted HR 3.79; 95% CI 1.43-10.00; p = 0.007) compared to European-born, adjusted for sex, year of birth, residential socio-economic position, years of education, rural residence, body mass index and height. The magnitude of the associations was similar in the Israeli-born of North African and Asian origin, with these second and third generation immigrants showing elevated HRs (adjusted HR 6.09; 95% CI 2.81-13.20; p = 4.72.10-6 and 3.86; 95% CI 1.77-8.41; p = 0.00067, respectively). These findings suggest a strong genetic predisposition and/or efficient cultural transmission of environmental exposures in the etiology of NPC.

CYP2E1 polymorphisms and nasopharyngeal carcinoma risk: a meta-analysis.

The cytochrome P450 2E1 (CYP2E1) polymorphisms have been implicated in susceptibility to nasopharyngeal carcinoma (NPC). However, the results are inconsistent. The aim of this meta-analysis is to evaluate the association between the CYP2E1 polymorphisms and NPC risk. All eligible case-control studies published up to April 4, 2016 were identified by searching PubMed, Web of Science, CNKI, Wanfang and Weipu databases. The NPC risk associated with the CYP2E1 polymorphism was estimated for each study by odds ratios (OR) together with its 95 % confidence interval (CI), respectively. Seven case-control studies were included. Of those, there were seven studies (1302 cases and 1319 controls) for RsaI/PstI polymorphism and three studies (732 cases and 642 controls) for DraI polymorphism. Overall, a significant association was found for RsaI/PstI polymorphism under recessive and homozygote comparison models (OR = 2.72, 95 % CI 1.73-4.25; OR = 2.64, 95 % CI 1.68-4.16, respectively), while there was no significant association for RsaI/PstI polymorphism under other two genetic models. When stratified by ethnicity, similar results were observed between them. As for DraI polymorphism, we also observed a significant association under recessive and homozygote comparison models, but not for the other two models. This meta-analysis suggests that the CYP2E1 polymorphisms contributed to the susceptibility of NPC, especially in Asian populations.

A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

Common variations in TERT-CLPTM1L locus are reproducibly associated with the risk of nasopharyngeal carcinoma in Chinese populations.

Associations between single nucleotide polymorphisms (SNPs) at 5p15 (TERT-CLPTM1L) and multiple cancer types have been reported. We examined whether polymorphisms in the TERT-CLPTM1L locus were related to the risk of developing nasopharyngeal carcinoma (NPC) among Chinese populations. In the first stage, 26 tag SNPs were genotyped in a Guangxi population (855 patients and 1036 controls). In the second stage, the SNPs, which showed significant association, were further genotyped in a Guangdong population (997 patients and 972 controls). Functional analyses were conducted to verify the biological relevance of the associated polymorphism. In the 1st stage, four SNPs (rs2736098, rs2735845, rs402710, and rs401681) were significantly associated with the risk of developing NPC. After the 2nd stage validation, rs2735845 and rs401681 were independently associated with the risk of developing NPC in the additive model (rs2735845, OR = 1.19, 95% CI = 1.04-1.37, P = 0.011; rs401681, OR = 0.85, 95% CI = 0.74-0.99, P = 0.034). Furthermore, we observed higher CLPTM1L messenger RNA levels in fetal mesenchymal stem cells from the rs2735845 G allele carriers compared with that from non-carriers. In addition, using an immunohistochemistry assay, we observed higher TERT and CLPTM1L levels in NPC tissues compared with that in non-cancerous nasopharyngeal tissues. Our findings suggest that polymorphisms in the TERT-CLPTM1L locus may play a role in mediating the susceptibility to NPC in Chinese populations.

Asian Versus Non-Asian Outcomes in Nasopharyngeal Carcinoma: A North American Population-based Analysis.

OBJECTIVES: The effect of ethnicity on nasopharyngeal cancer (NPC) outcomes is unclear. This retrospective analysis examines survival and the impact of concurrent chemoradiation (chemoRT) among Asian and non-Asian patients. METHODS: Subjects included 380 consecutive patients with NPC treated at a Canadian institution from 2000 to 2009. Five-year Kaplan-Meier progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were compared between Asian (n=279) and non-Asian (n=101) subjects. Multivariable analysis was performed using Cox regression modeling. Two-variable interaction terms with concurrent chemoRT were used to examine whether concurrent chemoRT conferred different effects among subgroups. RESULTS: Asian subjects presented with earlier stage (P=0.005), were younger, had better performance status, and were less likely smokers (all P<0.001). Survival among Asian versus non-Asian subjects with stage I/II NPC were: PFS 68% versus 59% (P=0.04), DSS 87% versus 77% (P=0.08), and OS 84% versus 74% (P=0.003). Corresponding rates with stage III/IVA/IVB disease were PFS 49% versus 42% (P=0.12), DSS 72% versus 46% (P=0.001), and OS 70% versus 44% (P<0.001). On multivariable analysis, Asian ethnicity, age below 65 years, ECOG performance status 0-1, early stage, staging MRI use, and concurrent chemoRT were associated with improved DSS and OS (P<0.05). On testing interactions with concurrent chemoRT, Asian versus non-Asian ethnicity was significant (hazard ratio 3.9), suggesting that concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects. CONCLUSIONS: In this population-based study, Asian ethnicity was associated with improved DSS and OS. Concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects.

[Association of RTN4 gene rs2864052 and rs6545468 with the susceptibility of nasopharyngeal carcinoma in Guangxi Zhuang population].

Objective:To study the relationship of the polymorphism of RTN4 gene rs2864052 and rs6545468 and haplotype with the susceptibility of nasopharyngeal carcinoma in Guangxi Zhuang population. Method:The polymorphism of Nogo gene (rs2864052,rs6545468) and haplotype were analyzed using the method of single-base extension PCR and DNA sequencing in 282 cases of nasopharyngeal carcinoma (NPC) and 199 healthy persons (control group) in Guangxi Zhuang Autonomous Region. Result:There were no differences between the NPC's patients and controls in the genotype and allele frequencies of RTN4 gene rs2864052 site,or rs6545468 site. The frequency of AG haplotype in the NPC's patients was significantly lower than in the controls(P=0.004, OR=0.14,95%CI=0.31-0.68). Conclusion:The haplotype AG of RTN4 gene rs2864052 and rs6545468 sites may reduce the risk of nasopharyngeal carcinoma in Guangxi Zhuang population.