Risk Of NPC Research Articles

Diagnostic Value of DAPK Methylation for Nasopharyngeal Carcinoma: Meta-Analysis.

Methylation of DAPK has been reported to play a key role in the initiation and progression of nasopharyngeal cancer. However, there are differences between the studies on it. This meta-analysis was performed to evaluate the diagnostic value of DAPK promoter methylation for NPC. The study method involves the systematic research of eligible studies based on criteria. The frequency, odds ratios (OR), sensitivity as well as specificity with the corresponding 95% confidence intervals (CIs) were used to assess the effect sizes. A total of 13 studies, including 1048 NPC samples and 446 non-cancerous samples, were used for the meta-analysis. The overall frequencies of DAPK methylation were 56.94% and 9.28% in NPC samples and non-cancerous samples, respectively. The association between DAPK methylation and risk of NPC was also confirmed by calculating the OR value which was 13.13 (95%CI = 54.24-40.72) based on a random-effect model (Q = 64.74; p < 0.0001; I2 = 81.47% with 95%CI for I2 = 69.39-88.78). Additionally, the study results suggest that testing for DAPK methylation in tissue samples or brushing may provide a promising method for diagnosing NPC. This is the first meta-analysis that provided scientific evidence that methylation of the DAPK gene could serve as a potential biomarker for diagnosis, prognosis, and early screening of NPC patients.

Risk Factors Associated with Nasopharyngeal Cancer Incidences in Indonesia: A Systematic Review and Meta-Analysis.

To determine the risk factors associated the incidence of NPC, particularly in Indonesia. This systematic review and meta-analysis was conducted according to PRISMA statement. Database including PubMed, Scopus, Science Direct, Web of Science, and GARUDA were retrieved. Newcastle-Ottawa scale was used to assess the quality of published study and analyse the risk of bias of included study. Random-effect model and reported pooled Odds Ratio (OR) with 95%CI was carried out in our meta-analysis. A pooled of 7 studies were included in our study which included 764 participants. We found that female gender was not associated with the incidences of NPC (OR 1.45, 95% CI: 0.61-3.45, p=0.40), and smoking was highly increased the incidence of NPC (OR 4.39 95% CI (0.79-24.40), but not statistically significant (p=0.09). Furthermore, salted fish consumption and some HLA alleles were associated with increased risk. The incidence of NPC is not associated with female gender nor smoking habits. However, the risk of NPC is higher for those who consume salted fish and have some susceptible HLA alleles. Further investigations in larger studies are needed to confirm these findings.

Rare POLN mutations confer risk for familial nasopharyngeal carcinoma through weakened Epstein-Barr virus lytic replication.

SummaryBackgroundNasopharyngeal carcinoma (NPC) exhibits significant familial aggregation; however, its susceptibility genes are largely unknown. Thus, this study aimed to identify germline mutations that might contribute to the risk of familial NPC, and explore their biological functions.MethodsWhole-exome sequencing was performed in 13 NPC pedigrees with multiple cases. Mutations co-segregated with disease status were further validated in a cohort composed of 563 probands from independent families, 2,953 sporadic cases, and 3,175 healthy controls. Experimental studies were used to explore the functions of susceptibility genes and their disease-related mutations.FindingsThe three rare missense mutations in POLN (DNA polymerase nu) gene, P577L, R303Q, and F545C, were associated with familial NPC risk (5/576 [0·87%] in cases vs. 2/3374 [0·059%] in healthy controls with an adjusted OR of 44·84 [95% CI:3·91-514·34, p = 2·25 × 10−3]). POLN was involved in Epstein-Barr virus (EBV) lytic replication in NPC cells in vitro. POLN promoted viral DNA replication, immediate-early and late lytic gene expression, and progeny viral particle production, ultimately affecting the proliferation of host cells. The three mutations were located in two pivotal functional domains and were predicted to alter the protein stability of POLN in silico. Further assays demonstrated that POLN carrying any of the three mutations displayed reduced protein stability and decreased expression levels, thereby impairing its ability to promote complete EBV lytic replication and facilitate cell survival.InterpretationWe identified a susceptibility gene POLN for familial NPC and elucidated its function.FundingThis study was funded by the National Key Research and Development Program of China (2021YFC2500400); the National Key Research and Development Program of China (2020YFC1316902); the Basic and Applied Basic Research Foundation of Guangdong Province, China (2021B1515420007); the National Natural Science Foundation of China (81973131); the National Natural Science Foundation of China (82003520); the National Natural Science Foundation of China (81903395).

Incidence and mortality trends of nasopharynx cancer from 1990 to 2019 in China: an age-period-cohort analysis

BackgroundNasopharynx cancer (NPC) is a great health burden in China. This study explored the long-term trends of NPC incidence and mortality in China.MethodsWe retrospectively analyzed data from the Global Burden of Disease Study 2019 using an age-period-cohort framework.ResultsThe age-standardized incidence rate (ASIR) of NPC increased by 72.7% and age-standardized mortality rate (ASMR) of NPC decreased by 51.7% for both sexes between 1990 and 2019. For males, the local drift for incidence was higher than 0 (P < 0.05) in those aged 20 to 79 years. For females, the local drift was higher than 0 (P < 0.05) in those aged 30 to 59 years, and lower than 0 (P < 0.05) in those aged 65 to 84 years. The local drift for mortality rates were less than 0 (P < 0.05) in every age group for both sexes. The estimated period relative risks (RRs) for incidence of NPC were increased monotonically for males, and increased for females after 2000. The increasing trend of cohort RRs of incidence was ceased in recent birth cohorts. Both period and cohort effects of NPC mortality in China decreased monotonically.ConclusionsOver the last three decades, the ASMR and crude mortality rate (CMR) of NPC has decreased, but the ASIR and crude incidence rate (CIR) increased in China. Although the potential mortality risk of NPC decreased, the risk of NPC incidence was found to increase as the period move forward, and suggested that control and prevention efforts should be enhanced.

Association of Circulating Nutritional Markers, Diets, Lifestyles, Workplace and Environmental Exposures With Nasopharyngeal Carcinoma In Malaysia

Abstract Objectives This case-control study was conducted to determine the association between circulating nutritional markers, diet, lifestyle factors, workplace and environmental exposure with risk and survival of NPC in the search for markers to predict risk and prognosticate survival for this disease. Methods A total of 300 histologically confirmed NPC cases and 300 matched (age, gender, ethnicity) cancer-free controls were recruited from two local hospitals. An interviewer-administrated questionnaire was used to collect data. Anthropometry measurements were taken directly after interview. The fasting blood sample was collected by a trained and qualified paramedic from respective hospitals and analysed using relevant analysis in the laboratory. Clinical characteristics were obtained from patients’ medical records. Results Vigorous physical activity (AOR = 1.58, 95% CI = 1.09, 2.31), ex-smoking habit (AOR (quitted ≤ 2 years) = 4.69, 95% CI = 1.63, 13.5) and alcohol consumption (AOR (once a week) = 3.10, 95% CI = 1.22, 7.91) significantly increased the risk of NPC. A medium consumption of high-protein dietary pattern was protective against NPC risk (AOR (Q2 vs Q1) = 0.44, 95% CI = 0.25, 0.76), while a high consumption of high-salted and processed food dietary pattern increased the risk of NPC (AOR (Q4 vs. Q1) = 9.75, 95% CI = 4.66, 20.38). Workplace exposures to leather, cloth, textiles or carpet and dust, smoke, fumes or gases significantly increased the risk of NPC. Environmental exposure to disinfectants or biocides significantly increased the risk of NPC. The overall survival of NPC was 63.7% with 79.3% complete remission. Advanced NPC stage (AOR (Stage 4C) = 5.64, 95% CI = 1.13, 28.2), treatment with chemotherapy alone (AOR = 5.58, 95% CI = 2.30, 13.50) and low serum leptin level (AOR (Q1 vs. Q4) = 9.61, 95% CI = 3.36, 27.47) significantly increased risk of NPC mortality. Conclusions In conclusion, the generation of risk models in this study based on these factors would not only increase understanding of NPC aetiology, but could potentially contribute to planning and implementation of clinical and public health interventions. Funding Sources This study was funded by Science Fund, Ministry of Science, Technology, and Innovation, Malaysia.

Association of regenerating gene 1A single-nucleotide polymorphisms and nasopharyngeal carcinoma susceptibility in southern Chinese population

ObjectiveNasopharyngeal carcinoma (NPC) is a common malignancy in Southern China and Southeast Asia. Genetic susceptibility is a major contributing factor in determining the individual risk of NPC in these areas. To test the association between NPC and variants in regenerating gene 1A (REG1A), we conducted a hospital-based case–control study in a Cantonese-speaking population from Guangdong province.MethodsWe endeavored to determine whether genetic variants of the REG1A gene were associated with the risk of NPC amidst the Cantonese population in a hospital-based case–control study using polymerase chain reaction-restriction and direct sequencing analysis in 211 NPC patients and 150 healthy controls. The association between NPC risk and the 14C/T, 20C/T, 369G/T, 1201A/G, and 2922C/T polymorphisms was examined after adjustment for age and sex.ResultsWe found an increased risk of developing NPC in individuals with REG1A 2922C/T variant genotype (p = 0.003, OR 0.419, 95% CI 0.235–0.746), and after adjustment for sex and age (p = 0.003, OR 0.406, 95% CI 0.226–0.732). No association between other polymorphisms (14C/T, 20C/T, 369G/T, and 1201A/G) and the risk of NPC was observed, before or after adjustment for age and sex.ConclusionOur findings suggest that the REG1A 2922C/T polymorphism is associated with an increased risk of developing NPC in a Cantonese population from Guangdong province. Larger studies are required to confirm our findings and unravel the underlying mechanisms.

Increased risks between TLR2 (-196 to -174 ins/del) and TLR3 1377C>T variants and head and neck cancers in Tunisia.

IntroductionPrevious studies have highlighted the importance of polymorphisms of toll-like receptors (TLRs) in the pathogenesis of certain cancers, including head and neck cancers (HNC).Aim of the studyThe aim of this study was to evaluate the association of TLR2 (-196 to -174 ins/del) and TLR3 (1377 C>T) as potential risk factors for HNC in Tunisians.Material and methodsA case-control study including 246 HNC patients (174 nasopharyngeal carcinoma – NPC and 72 laryngeal cancer – LC) and 250 healthy controls. Genotyping was done by using PCR and PCR-RFLP methods.ResultsHigher minor allele frequencies of TLR2 (-196 to -174 ins/del) and TLR3 1377 C>T polymorphisms were seen in HNC, NPC, and LC compared to controls. In addition, higher increased HNC, NPC, and LC risk was associated with TLR2 ins/del and TLR2 del/del genotypes (p < 0.0001). Positive association with HNC, NPC, and LC risk was seen with TLR2 del-containing genotypes (ins/del + del/del) (p < 0.0001). The T/T genotype of TLR3 is associated with HNC, NPC, and LC susceptibility (p < 0.0001). Positive association with HNC and NPC risk was seen with TLR3 T allele carriers (C/T + T/T) (p < 0.0001). Increased frequency of T-ins, C-del, and T-del haplotypes was revealed in HNC and NPC cases than healthy controls; however, T-del was significantly higher in LC cases.ConclusionsOur results demonstrate an increased risk of HNC, NPC, and LC with TLR2 ins/del, TLR2 del/del, and TLR3 T/T genotypes. And positive association with T-ins, C-del, and T-del haplotypes with HNC and NPC and T-del haplotype with LC.

Reproductive history and risk of nasopharyngeal carcinoma: A population-based case–control study in southern China

ObjectsNasopharyngeal carcinoma (NPC) incidence exhibits a remarkable sex disparity, with higher risk among males. Whether this pattern can be partly explained by female reproductive history is unclear. MethodsA population-based case–control study of NPC was conducted in southern China between 2010 and 2014, including 674 histopathologically verified female NPC cases and 690 female controls randomly selected from population-based registries. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression after adjusting for potential confounders. ResultsWomen who had 3, 4, or ≥5 pregnancies compared with 2 pregnancies were at significantly increased risk for NPC (ORs 1.56, 1.45 and 1.88, respectively). History of deliveries was similarly associated with a greater risk of NPC. These positive associations were more prominent in women who were younger than 50 years, had less than 10 years of education, or were white-collar workers. Increasing time since menopause was associated with a diminished NPC risk (Ptrend = 0.010). Women more than 15 years after menopause had a 0.35-fold (95% CI: 0.16–0.75) NPC risk compared with those 0–3 years after menopause. ConclusionContrary to our hypothesis, a history of pregnancy or delivery increased the risk of NPC and the risk decreased with increasing time since menopause. However, the non-linear relationship and no consistent risk patterns across strata indicate that the observed associations are unlikely to be causal, and may at least partially be ascribed to residual confounding by socioeconomic factors.

No association of TNF-α-308G/A polymorphisms with head and neck cancer risk: A PRISMA-compliant meta-analysis.

Background:A number of studies had reported the association between tumor necrosis factor-alpha (TNF-α) gene polymorphisms and head and neck cancer (HNC) risk. However, the results remained controversial. Therefore, we performed a meta-analysis to derive a more precise evaluation of the association between TNF-α-308G/A polymorphism and overall HNC risk and evaluated influence of cancer types and ethnicities.Methods:A systematic literature search was performed using Pubmed, Embase, Cochrane Library, and Web of science. In total, we identified 15 studies including 2005 cancer cases and 2876 controls to evaluate the association of TNF-α-308G/A polymorphism with risk for HNC.Results:Overall, there was no significant association between TNF-α-308G/A polymorphism and the risk of HNC. Furthermore, subgroup analyses were performed according to the types of tumor and the ethnicities, we also found there was no significant association between TNF-α-308G/A polymorphism and the risk of NPC and OC, and European and Asian populations had no statistically significant difference in the relationship of TNF-α-308G/A polymorphism and HNC susceptibility.Conclusion:This meta-analysis indicates that the TNF-α-308G/A polymorphism is not associated with HNC risk. In the future, large and well-designed case-control studies are needed to validate our findings.

Associations of lifestyle and diet with the risk of nasopharyngeal carcinoma in Singapore: a case\u2013control study

BackgroundNasopharyngeal carcinoma (NPC) is a commonly diagnosed cancer in Southeast Asia. Many studies have examined the risk factors for NPC, yet the roles of some risk factors remain inconclusive. The purpose of this study was to examine associations between modifiable lifestyle factors and the risk of NPC in the Singaporean population.MethodsWe conducted a case–control study in Singapore with 300 patients and 310 controls who were recruited between 2008 and 2012. Each control was selected and individually matched to each patient based on sex, ethnicity, and age (±5 years). A total of 290 pairs of cases and controls were matched successfully. We examined lifestyle factors such as tobacco smoking, alcohol drinking, various salted and preserved food consumption, and weaning practices.ResultsAfter adjusting for covariates, multivariate analysis showed that those participants who were current smokers and had ever smoked tobacco had a higher risk of NPC than participants who had never smoked, with odds ratios (ORs) of 4.50 (95% confidence interval [CI] 2.58–7.86; P < 0.001) and 2.52 (95% CI 1.54–4.12; P < 0.001), respectively. Those who consumed salted vegetables at least once a week also showed a significantly increased risk of NPC than those who never or rarely consumed salted vegetables, with an OR of 4.18 (95% CI 1.69–10.38; P = 0.002).ConclusionSmoking (currently and ever-smoked) and consuming salted vegetables once a week or more were lifestyle risk factors for NPC, and changes of these factors for the better may reduce the risk of NPC.

Association of DNA Base-excision Repair XRCC1, OGG1 and APE1 Gene Polymorphisms with Nasopharyngeal Carcinoma Susceptibility in a Chinese Population

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. 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. 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. 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). 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.

Genetic Polymorphisms in Host Innate Immune Sensor Genes and the Risk of Nasopharyngeal Carcinoma in North Africa

Nasopharyngeal carcinoma (NPC) is a rare malignancy in most parts of the world. It is an Epstein-Barr virus−associated malignancy with an unusual racial and geographical distribution. The host innate immune sensor genes play an important role in infection recognition and immune response against viruses. Therefore, we examined the association between polymorphisms in genes within a group of pattern recognition receptors (including families of Toll-like receptors, C-type lectin receptors, and retinoic acid−inducible gene I−like receptors) and NPC susceptibility. Twenty-six single-nucleotide polymorphisms (SNPs) in five pattern-recognition genes were genotyped in 492 North African NPC cases and 373 frequency-matched controls. TLR3_rs3775291 was the most significantly associated SNP (odds ratio [OR] 1.49; 95% confidence interval [95% CI] 1.11−2.00; P = 0.008; dominant model). The analysis showed also that CD209_rs7248637 (OR 0.69; 95% CI 0.52−0.93; P = 0.02; dominant model) and DDX58_rs56309110 (OR 0.70; 95% CI 0.51−0.98; P = 0.04) were associated with the risk of NPC. An 18% increased risk per allele was observed for the five most significantly associated SNPs, TLR3_rs3775291, CD209_rs7248637, DDX58_rs56309110, CD209_rs4804800, and MBL2_rs10824792, (ptrend = 8.2 × 10−4). Our results suggest that genetic variation in pattern-recognition genes is associated with the risk of NPC. These preliminary findings require replication in larger studies.

Cyclin D1 G870A Polymorphism and Risk of Nasopharyngeal Carcinoma: A Meta-Analysis

Recently, there have been a number of studies on the association between cyclin D1 G870A polymorphism and nasopharyngeal carcinoma risk. However, the results of previous reports remain controversial and ambiguous. Thus, we performed a meta-analysis to explore more precisely the association between cyclin D1 G870A polymorphism and the risk of nasopharyngeal carcinoma. No significant association was found between cyclin D1 G870A polymorphism and nasopharyngeal carcinoma risk in total population analysis. In the subgroup meta-analysis by ethnicity, a negative association was shown in Caucasian subgroup, and no significant association in any genetic models among Asians was observed. In summary, positive results have been shown on the search for polymorphic variants influencing the risk of NPC. This meta-analysis provides evidence of the association between CCND1 G870A polymorphism and NPC risk, supporting the hypothesis that CCND1 870A allele probably acts as an important NPC protective factor in Caucasians but not in Asians. Since the results of our meta-analysis are preliminary and may be biased by the relatively small number of subjects, they still need to be validated by well-designed studies using larger samples in the future.

OP13 Nimotuzumab combined with radiotherapy for oesophageal carcinoma – A phase 2 clinical trial

Lys751Gln and nasopharyngeal carcinoma risk until now. The frequency of the XRCC1 codon 280 homozygous wild-type Arg/Arg genotype was 77.9% (88/113) in cases and 80.8% (105/130) in controls; the heterozygous Arg/His genotype was 21.3% (24/113) in cases and 18.5% (24/130) in controls; and the His/His genotype was 0.8% (1/113) in cases and 0.7% (1/130) in controls. For XRCC1 codon 280 polymorphisms, no significant association between Arg280His and risk of NPC was found (OR 1.30, 95% CI 0.66–2.57; p = 0.447). Interpretation: Risk of NPC was nearly two and a half times higher for individuals with the homozygous wild-type Lys/Lys genotype than for the heterozygous Lys/Gln genotype, adjusted for age, sex, and ethnicity. To our knowledge, there have been no documented reports of the association between XPDLys751Gln and nasopharyngeal carcinoma risk until now. Funding: Science Fund, Ministry of Science and Innovation, Malaysia. The authors declared no conflicts of interest.

Matrix metalloproteinase-1 (-1607) 1G/2G and -9 (–1562) C/T promoter polymorphisms: Susceptibility and prognostic implications in nasopharyngeal carcinomas

BackgroundMatrix metalloproteinases (MMPs) are proteolytic enzymes that play important roles in tumor invasion and metastasis by degrading extracellular matrix components. Genetic variations in promoter regions of MMP genes, affecting their expression, have been associated with susceptibility to cancers. The aim of this study was to investigate the susceptibility and prognostic implications of the MMP-1 (-1607) 1G/2G and MMP-9 (-1562) C/T polymorphisms in nasopharyngeal carcinomas. MethodsThe variation of the MMP-1 and MMP-9 promoter regions in 174 patients with NPC and 171 healthy control subjects was investigated. Association of the clinico-pathologic parameters and the genetic markers with the rates of the nasopharyngeal carcinoma-specific overall survival and the disease-free survival were assessed using univariate and multivariate analyses. ResultsNo association was found between genetic variation in MMP-9 and the risk of NPC occurrence. In contrast, a significantly increased risk of NPC was associated with the homozygous MMP-1 (-1607) 2G2G genotype (OR=2.27; p=0.02). A significant association was also found between the 2G2G genotype and the aggressive forms of NPC as defined by large tumor size (T3-T4), lymph node metastasis and advanced stages (III-IV) at the time of diagnosis. Moreover, an association was ascertained between the MMP-1 polymorphism and gender (OR=2.90; p=0.02). In univariate analysis, the MMP-1 (-1607) 2G allele showed a significant association with reduced disease-free survival for NPC patients (p=0.03). ConclusionsThe genetic variation in MMP-1 may represent a marker for the increased risk of nasopharyngeal carcinoma.

Polymorphisms of XRCC1 genes and risk of nasopharyngeal carcinoma in the Cantonese population

BackgroundNasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China. In addition to environmental factors such as Epstein-Barr virus infection and diet, genetic susceptibility has been reported to play a key role in the development of this disease. The x-ray repair cross-complementing group 1 (XRCC1) gene is important in DNA base excision repair. We hypothesized that two common single nucleotide polymorphisms of XRCC1 (codons 194 Arg→Trp and 399 Arg→Gln) are related to the risk of NPC and interact with tobacco smoking.MethodsWe sought to determine whether these genetic variants of the XRCC1 gene were associated with the risk of NPC among the Cantonese population in a hospital-based case control study using polymerase chain reaction-restriction fragment length polymorphism analysis. We conducted this study in 462 NPC patients and 511 healthy controls.ResultsAfter adjustment for sex and age, we found a reduced risk of developing NPC in individuals with the Trp194Trp genotype (OR = 0.48; 95% CI, 0.27–0.86) and the Arg194Trp genotype (OR = 0.79; 95% CI, 0.60–1.05) compared with those with the Arg194Arg genotype. Compared with those with the Arg399Arg genotype, the risk for NPC was not significantly different in individuals with the Arg399Gln genotype (OR = 0.82; 95% CI, 0.62–1.08) and the Gln399Gln genotype (OR = 1.20; 95% CI, 0.69–2.06). Further analyses stratified by gender and smoking status revealed a significantly reduced risk of NPC among males (OR = 0.32; 95% CI, 0.14–0.70) and smokers (OR = 0.34; 95% CI, 0.14–0.82) carrying the XRCC1 194Trp/Trp genotype compared with those carrying the Arg/Arg genotype. No association was observed between Arg399Gln variant genotypes and the risk of NPC combined with smoking and gender.ConclusionOur findings suggest that the XRCC1 Trp194Trp variant genotype is associated with a reduced risk of developing NPC in Cantonese population, particularly in males and smokers. Larger studies are needed to confirm our findings and unravel the underlying mechanisms.

Sequence Variants in Toll-Like Receptor 10 Are Associated with Nasopharyngeal Carcinoma Risk

Nasopharyngeal carcinoma (NPC) is a common malignancy in southern China and Southeast Asia. Genetic susceptibility is a major factor in determining the individual risk of NPC in these areas. To test the association between NPC and variants in Toll-like receptor 10 (TLR10), we conducted a hospital-based case-control study in a Cantonese-speaking population in Guangdong province. Seven single nucleotide polymorphisms in TLR10, selected with a tagging algorithm, were genotyped. When assessing each unique haplotype compared with the most common haplotype, "GAGTGAA," with the expectation-maximization algorithm in Haplo.stats, the risk of developing NPC was significantly elevated among men who carried the haplotype "GCGTGGC" (P = 0.005). After adjusting for age, gender, and VCA-IgA antibody titers, this association was more significant (P = 0.0007). To further assess the overall differences of haplotype frequency profiles between cases and healthy controls, the global score test, considering all haplotypes and adjusting for age, gender, and VCA-IgA antibody titers, gave a haplo score of 27.52 with P = 0.002. The haplotype specific odds ratio was 2.66 (confidence interval, 1.34-3.82) for GCGTGGC. We concluded that in this Cantonese population-based study, haplotype GCGTGGC with frequency of 11.4% in TLR10 was found to be associated with NPC and this association was statistically significant after adjusting for age, gender, and VCA-IgA antibody titers. It is possible that this is not a causal haplotype for NPC; rather, it is in strong linkage disequilibrium with a causal single nucleotide polymorphism in close proximity.

A Susceptibility Locus at Chromosome 3p21 Linked to Familial Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) poses one of the serious health problems in southern Chinese, with an incidence rate ranging from 15 to 50/100,000. Chromosome translocation t(1;3) and frequent loss of heterogeneity on short arms of chromosome 3 and 9 have been reported to be associated with NPC, and a genome-wide scan identified an NPC susceptibility locus on chromosome 4p15.1-q12 recently. In our study, we collected samples from 18 families at high risk of NPC from the Hunan province in southern China, genotyped with a panel of polymorphic markers on short arms of chromosomes 3, 9, and 4p15.1-q12. A locus on 3p21 was identified to link to NPC with a maximum logarithm of odds for linkage score of 4.18. Fine mapping located the locus to a 13.6-cM region on 3p21.31-21.2, where a tumor suppressor gene cluster resided. Our findings identified a novel locus for NPC and provided a map location for susceptibility genes candidates. In contrast to a recent study, no significant evidence for NPC linkage to chromosomes 4 and 9 was observed.

High Incidence of Nasopharyngeal Carcinoma in Native People of Sarawak, Borneo Island

Abstract Nasopharyngeal cancer (NPC) is generally a rare malignancy with a few well-known exceptions, notably South-East China. In this article, we describe evidence of a high risk of NPC in the population of Sarawak State, Malaysia, and particularly in one native ethnic group. Sarawak State is one of the two provinces of Malaysia located on the island of Borneo. The native population (71.6%) includes the Iban, Malay, Bidayuh, Melanau, and diverse smaller ethnic groups. The Chinese are the largest nonindigenous group (27.5%). We identified 392 newly diagnosed cases (292 males and 100 females) of NPC in 1996–1998 in Malaysian citizens, permanent residents of Sarawak. Age-standardized rates by sex and ethnic group were compared with the highest rates in the world. The age-adjusted rate (ASR) in Sarawak residents was 13.5/100,000 [95% confidence interval (CI) 12.2–15.0] and 6.2/100,000 (95% CI 5.7–6.7) in males and females, respectively. The risk in the Bidayuh people was 2.3-fold (M) and 1.9-fold (F) higher than the Sarawak average, and about 50% higher than that in Hong Kong—the highest recorded by any population-based registry for the same period. Local dietary habits, environmental exposures, and genetic susceptibility deserve investigation in this population.