Lower Nasopharyngeal Carcinoma Risk Research Articles

LncRNA FAS-AS1 upregulated by its genetic variation rs6586163 promotes cell apoptosis in nasopharyngeal carcinoma through regulating mitochondria function and Fas splicing

Nasopharyngeal carcinoma (NPC) is a common head and neck malignant with a high incidence in Southern China. Genetic aberrations play a vital role in the pathogenesis, progression and prognosis of NPC. In the present study, we elucidated the underlying mechanism of FAS-AS1 and its genetic variation rs6586163 in NPC. We demonstrated that FAS-AS1 rs6586163 variant genotype carriers were associated with lower risk of NPC (CC vs. AA, OR = 0.645, P = 0.006) and better overall survival (AC + CC vs. AA, HR = 0.667, P = 0.030). Mechanically, rs6586163 increased the transcriptional activity of FAS-AS1 and contributed to ectopic overexpression of FAS-AS1 in NPC. rs6586163 also exhibited an eQTL trait and the genes affected by rs6586163 were enriched in apoptosis related signaling pathway. FAS-AS1 was downregulated in NPC tissues and over-expression of FAS-AS1 was associated with early clinical stage and better short-term treatment efficacy for NPC patients. Overexpression of FAS-AS1 inhibited NPC cell viability and promoted cell apoptosis. GSEA analysis of RNA-seq data suggested FAS-AS1 participate in mitochondria regulation and mRNA alternative splicing. Transmission electron microscopic examination verified that the mitochondria was swelled, the mitochondrial cristae was fragmented or disappeared, and their structures were destroyed in FAS-AS1 overexpressed cells. Furthermore, we identified HSP90AA1, CS, BCL2L1, SOD2 and PPARGC1A as the top 5 hub genes of FAS-AS1 regulated genes involved in mitochondria function. We also proved FAS-AS1 could affect Fas splicing isoform sFas/mFas expression ratio, and apoptotic protein expression, thus leading to increased apoptosis. Our study provided the first evidence that FAS-AS1 and its genetic polymorphism rs6586163 triggered apoptosis in NPC, which might have a potential as new biomarkers for NPC susceptibility and prognosis.

Intake of Alcohol and Tea and Risk of Nasopharyngeal Carcinoma: A Population-Based Case-Control Study in Southern China.

The potential effect of alcohol or tea intake on the risk of nasopharyngeal carcinoma (NPC) remains controversial. In a population-based case-control study in southern China, we assessed alcohol or tea intake from 2,441 histopathologically confirmed NPC cases and 2,546 controls. We calculated mean daily ethanol (g/day) and tea intake (mL/day). Fully adjusted ORs with 95% confidence intervals (CI) were estimated using logistic regression; potential dose-response trends were evaluated using restricted cubic spline analysis. Compared with nondrinkers, no significantly increased NPC risk in men was observed among current alcohol drinkers overall (OR, 1.08; 95% CI, 0.93-1.25), nor among current heavy drinkers (OR for ≥90 g/day ethanol vs. none, 1.32; 95% CI, 0.95-1.84) or former alcohol drinkers. Current tea drinking was associated with a decreased NPC risk (OR, 0.73; 95% CI, 0.64-0.84). Compared with never drinkers, those with the low first three quintiles of mean daily current intake of tea were at significantly lower NPC risk (OR, 0.53, 0.68, and 0.65, respectively), but not significant for the next two quintiles. Current daily tea intake had a significant nonlinear dose-response relation with NPC risk. Our study suggests no significant association between alcohol and NPC risk. Tea drinking may moderately reduce NPC risk, but the lack of a monotonic dose-response association complicates causal inference. Tea drinking might be a healthy habit for preventing NPC. More studies on biological mechanisms that may link tea with NPC risk are needed.

High Levels of Antibody that Neutralize B-cell Infection of Epstein-Barr Virus and that Bind EBV gp350 Are Associated with a Lower Risk of Nasopharyngeal Carcinoma.

Elevated IgA antibodies indicative of ongoing exposure to Epstein-Barr virus (EBV) are high-risk biomarkers for nasopharyngeal carcinoma (NPC), an EBV-related epithelial tumor. However, protective biomarkers that limit exposure to the virus have not been defined. We evaluated whether antibodies that can neutralize EBV infection by targeting glycoproteins involved in viral cell entry, including EBV vaccine candidate glycoprotein 350 (gp350), were associated with lower NPC risk. In a prospective cohort of 2,557 individuals from 358 high-risk NPC multiplex families in Taiwan, we identified 21 incident NPC cases and 50 disease-free controls. To complement data from high-risk families, we further identified 30 prevalent NPC cases and 50 healthy controls from the general Taiwanese population. We quantified EBV-neutralizing antibody, antibodies against EBV glycoproteins involved in B-cell and epithelial cell entry, and anti-EBNA1 IgA, a high-risk NPC biomarker. EBV-neutralizing antibodies blocking B-cell infection and anti-gp350 antibodies were present at significantly higher levels in disease-free controls compared with incident NPC cases (P < 0.03). Family members with both low EBV-neutralizing potential and elevated EBNA1 IgA had a 7-fold increased risk of NPC (95% CI, 1.9-28.7). Neutralizing antibodies against epithelial cell infection did not differ between incident cases and disease-free controls. Anti-glycoprotein antibody levels measured at diagnosis (prevalent NPC) were significantly higher than levels measured prior to diagnosis (P < 0.01). Elevated titers of EBV-neutralizing antibody and anti-gp350 antibody were low-risk biomarkers for NPC. These data suggest that a vaccine that induces potent EBV gp350 and B-cell-neutralizing antibodies could reduce the risk of EBV-related cancers such as NPC. Clin Cancer Res; 22(14); 3451-7. ©2016 AACR.

Association of polymorphisms hOGGI rs1052133 and hMUTYH rs3219472 with risk of nasopharyngeal carcinoma in a Chinese population.

This case–control study investigates the possible relationships between the single-nucleotide polymorphisms rs1052133 in the human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene and rs3219472 in the human MutY glycosylase homologue (hMUTYH) gene and the risk of nasopharyngeal carcinoma (NPC). The two polymorphisms were genotyped in 488 unrelated NPC patients and 573 cancer-free controls. Genotype GG at rs1052133 was associated with significantly lower NPC risk than genotypes GC + CC (odds ratio [OR] 0.770, 95% confidence interval [CI] 0.595–0.996, P=0.012). In subgroup analyses, subjects with genotype GG at rs1052133 were at lower risk of NPC than those with GC or CC among individuals older than 40 years (OR 0.706, 95% CI 0.524–0.950), women (OR 0.571, 95% CI 0.337–0.968), and those with no smoking history (OR 0.634, 95% CI 0.463–0.868). No significant association was seen between polymorphisms at hMUTYH rs3219472 and the risk of NPC. However, gene–gene interaction analysis showed that subjects with genotype CC at rs1052133 and genotype AA at rs3219472 (CC/AA) were at 2.887-fold higher risk of NPC than those with GG/GG, 3.183-fold higher risk than those with GG/GA, and 3.392-fold higher risk than those with GG/AA. Our results suggest that hOGG1 rs1052133 polymorphism may play an important role in NPC pathogenesis, especially among women, >40 years old, and those with no smoking history. The hMUTYH rs3219472 polymorphism may interact with hOGG1 rs1052133 polymorphism to influence susceptibility to NPC.

Milk consumption in relation to incidence of nasopharyngeal carcinoma in 48 countries/regions.

BackgroundDecreasing trends of nasopharyngeal carcinoma (NPC) incidence have been consistently reported in endemic populations but the etiology of NPC remains unclear. The objective of our study was to assess the international and local (Hong Kong) correlations of milk and dairy products per capita consumption with NPC incidence.MethodsWe conducted an ecological study in 48 countries/regions. Age standardized incidence rates of NPC were obtained from the Cancer Incidence in Five Continents. Dairy product consumption and Human Development Index were obtained from the Food and Agriculture Organization of the United Nations and the United Nations Development Programme. Spearman correlation, multivariate analysis and time-lagged analysis were performed.ResultsThe negative correlations between milk consumption and decreased age standardized incidence rates of NPC were observed in the 48 countries/regions adjusting for Human Development Index in endemic countries/regions. In Hong Kong, multivariate analysis, after adjusting for other potential confounders, including salted fish, cigarette, vegetable consumption and socioeconomic status, showed consistently negative and significant correlations between milk consumption and NPC incidence (The strongest coefficient (β) was observed at 10-year lag in males [β = −0.439; P < 0.01] and in females [β = −0.258; P < 0.01]).ConclusionsOur study showed the correlations on milk consumption per capita and against lower risk of NPC in 48 countries/regions and in Hong Kong. These hypothesis-generating results could support further studies on individual exposures and the disease.

Folate, vitamin B6, vitamin B12 and methionine intakes and risk for nasopharyngeal carcinoma in Chinese adults: a matched case-control study.

Many studies have suggested that folate-related one-carbon metabolism-related nutrients may play a role in certain cancer risks, but few studies have assessed their associations with the risk for nasopharyngeal carcinoma (NPC). In this study, we investigated the association between four folate-related one-carbon metabolism-related nutrients (folate, vitamin B6, vitamin B12 and methionine) and NPC risk in Chinese adults. A total of 600 patients newly diagnosed (within 3 months) with NPC were individually matched with 600 hospital-based controls by age, sex and household type (urban v. rural). Folate, vitamin B6, vitamin B12 and methionine intakes were measured using a validated seventy-eight-item FFQ. A higher dietary folate or vitamin B6 intake was associated with a lower NPC risk after adjusting for potential confounders. The adjusted OR of NPC for quartiles 2-4 (v. 1) were 0·66 (95% CI 0·48, 0·91), 0·52 (95% CI 0·37, 0·74) and 0·34 (95% CI 0·23, 0·50) (P(trend)<0·001) for folate and 0·72 (95% CI 0·52, 1·00), 0·55 (95% CI 0·39, 0·78) and 0·44 (95% CI 0·30, 0·63) (P(trend)<0·001) for vitamin B6. No significant association with NPC risk was observed for dietary vitamin B12 or methionine intake. The risk for NPC with dietary folate intake was more evident in the participants who were not exposed to toxic substances than in those who were exposed (P(interaction)=0·014). This study suggests that dietary folate and vitamin B6 may be protective for NPC in a high-risk population.

Choline and betaine intakes are associated with reduced risk of nasopharyngeal carcinoma in adults: a case–control study

Background:Intakes of choline and betaine have been inversely related to the risk of various neoplasms, but scant data exist on nasopharyngeal carcinoma (NPC). We examined the association between consumption of choline and betaine and risk of NPC.Methods:We conducted a case–control study with 600 incident NPC patients and 600 controls 1 : 1 matched by age, sex and household type in Guangdong, China. Dietary intake was assessed by a food frequency questionnaire through face-to-face interview.Results:Intakes of total choline, betaine and choline+betaine were inversely related to NPC after adjustment for various lifestyle and dietary factors (all P-trend <0.001). Adjusted odds ratios (95% CI) for quartile 4 (vs quartile 1) were 0.42 (0.29, 0.61) for total choline, 0.50 (0.35, 0.72) for betaine and 0.44 (0.30, 0.64) for betaine+total choline. Regarding various sources of choline, lower NPC risk was associated with greater intakes of choline from phosphatidylcholine, free choline, glycerophosphocholine and phosphocholine, but not sphingomyelin.Conclusion:These findings are consistent with a beneficial effect of choline and betaine intakes on carcinogenesis.

Greater intake of fruit and vegetables is associated with lower risk of nasopharyngeal carcinoma in Chinese adults: a case–control study

The effect of fruit and vegetable intake on the risk of nasopharyngeal carcinoma (NPC) remains uncertain due to limited published evidence. We performed a matched case-control study to investigate the relationship between the intake of fruit and vegetables and the risk of NPC. Between July 2009 and March 2011, 600 (448 male, 152 female), NPC incident cases from a single hospital in Guangzhou, Guangdong Province, China, a high-incidence area, were enrolled in the study. 600 controls, matched by gender, age (± 3 years) and household type (urban/rural) were also enrolled. Face-to-face interviews were used to collect habitual dietary intakes and information on various covariates. Multivariate conditional logistic regression analyses showed significant, dose-dependent inverse associations between the intake of vegetables, fruit or a combination of the two and the risk of NPC, even after adjustments for social-economic status, body mass index, dietary factors and other potential covariates. The adjusted odds ratios (95% confidence intervals) for NPC in the top quartile of vegetable intake, fruit intake or a combination of the two, as compared to the lowest quartile, were 0.33 (0.22-0.50), 0.70 (0.47-1.04) and 0.37 (0.25-0.55), respectively. Dark green leafy vegetables, carrots, peppers and tomatoes, citrus fruit and pome fruit showed much more pronounced benefits with regards to NPC than other types of fruit and vegetables. Interaction analyses demonstrated that the effects of total combined vegetable and fruit intake were much more significant in subjects with a higher education level (p interaction: 0.027), and the benefits of fruit were observed in males, but not in females (p interaction: 0.088). Our findings suggest that a greater consumption of fruit and vegetables may lower the risk of NPC in Chinese adults.