RNA demethylase ALKBH5 regulates hypopharyngeal squamous cell carcinoma ferroptosis by posttranscriptionally activating NFE2L2/NRF2 in an m6 A-IGF2BP2-dependent manner.

BACKGROUND: Having emerged as the most abundant posttranscriptional internal mRNA modification in eukaryotes, N6-methyladenosine (m6 A) has attracted tremendous scientific interest in recent years. However, the functional importance of the m6 A methylation machinery in ferroptosis regulation in hypopharyngeal squamous cell carcinoma (HPSCC) remains unclear. METHODS: We herein performed bioinformatic analysis, cell biological analyses, transcriptome-wide m6 A sequencing (m6 A-seq, MeRIP-seq), RNA sequencing (RNA-seq), and RNA immunoprecipitation sequencing (RIP-seq), followed by m6 A dot blot, MeRIP-qPCR, RIP-qPCR, and dual-luciferase reporter assays. RESULTS: The results revealed that ALKBH5-mediated m6 A demethylation led to the posttranscriptional inhibition of NFE2L2/NRF2, which is crucial for the regulation of antioxidant molecules in cells, at two m6 A residues in the 3'-UTR. Knocking down ALKBH5 subsequently increased the expression of NFE2L2/NRF2 and increased the resistance of HPSCC cells to ferroptosis. In addition, m6 A-mediated NFE2L2/NRF2 stabilization was dependent on the m6 A reader IGF2BP2. We suggest that ALKBH5 dysregulates NFE2L2/NRF2 expression in HPSCC through an m6 A-IGF2BP2-dependent mechanism. CONCLUSION: Together, these results have revealed an association between the ALKBH5-NFE2L2/NRF2 axis and ferroptosis, providing insight into the functional importance of reversible mRNA m6 A methylation and its modulators in HPSCC.

Comprehensive analysis reveals COPB2 and RYK associated with tumor stages of larynx squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the highly aggressive malignancy types of head and neck squamous cell carcinomas; genes involved in the development of LSCC still need exploration. METHODS: We downloaded expression profiles of 96 (85 in advanced stage and 11 in early stage) LSCC patients from TCGA-HNSC. Function enrichment and protein-protein interactions of genes in significant modules were conducted. Univariate and multivariate Cox regression analyses were performed to explore potential prognostic biomarkers for LSCC. The expression levels of genes at different stages were compared and visualized via boxplots. Immune infiltration was examined by the CIBERSORTx web-based tool and depicted with ggplot2. Gene set enrichment analysis (GSEA) was utilized to analyze functional enrichment terms and pathways. Immunohistochemical staining (IHC) was used to verify the expression of genes in the LSCC samples. RESULTS: We identified 25 modules, including 3 modules significantly related to tumor stages of LSCC via weighted gene co-expression network analysis (WGCNA). UIMC1, NPM1, and DCTN4 in the module 'cyan', TARS in the module 'darkorange', and COPB2 and RYK in the module 'lightyellow' showed statistically significant relation to overall survival. The expression of COPB2, DCTN4, RYK, TARS, and UIMC1 indicated association with the change of fraction of immune cells in LSCC patients; two genes, COPB2 and RYK, indicated different expression in various tumor stages of LSCC. Finally, COPB2 and RYK showed high-expression in tumor tissues of advanced LSCC patients. CONCLUSIONS: Our study provided a potential perceptive in analyzing progression of LSCC cells and exploring prognostic genes.

The Role of Nasal Endoscopy in Allergic Rhinitis and House Dust Mite Sublingual Immunotherapy.

INTRODUCTION: While there exists considerable evidence for efficacy of sublingual immunotherapy (SLIT), its impact on the improvement of nasal signs in allergic rhinitis (AR) patients remains quite unclear. In this study, the endoscopic examination and the modified Lund-Kennedy (MLK) scoring system were performed to describe and evaluate the therapeutic effect of SLIT. METHODS: A total of 105 patients with AR induced by house dust mites were enrolled and treated with standardized Dermatophagoides farinae (D. farinae) drops for 1 year. The total nasal symptoms score (TNSS), total medication score (TMS), visual analog scale (VAS), and MLK scores were assessed at baseline and 6 and 12 months. The MLK score was also compared for its correlation with TNSS, TMS, and VAS. RESULTS: The TNSS, TMS, and VAS scores statistically decreased after SLIT compared to baseline (all p < 0.05). After 12 months of treatment, the rates of well-controlled, partial controlled, and uncontrolled AR patients were 42, 49.5, and 8.5%, respectively. The nasal endoscopy findings showed significant improvement in nasal signs, which mainly included color change of turbinate mucosa, reduction of nasal secretions, and improvement of nasal edema. A significant decrease was observed in MLK scores, and there was a positive correlation between MLK and VAS scores. CONCLUSIONS: In addition to commonly utilized subjective assessments (TMS, TNSS, and VAS), our results of endoscopic examination and the MLK scores consistently confirmed that SLIT is an effective therapeutic modality for AR patients. The MLK scores might be considered as an auxiliary tool to evaluate efficacy of SLIT in clinical practice and outcomes research.

LINC01433 targets miR-506-3p to promote the biological progress of nasopharyngeal carcinoma cells.

PURPOSE: The current study aimed to investigate the role of long intergenic noncoding 01433 (LINC01433) in the proliferation, migration and invasion of nasopharyngeal carcinoma (NPC). METHODS: Real-time quantitative PCR (RT-qPCR) was performed to determine the expressions of LINC01433 and miR-506-3p in NPC samples and cell lines. The effects of LINC01433 on cell proliferation, migration and invasion were measured by CCK-8, wound healing assay and Transwell, respectively. In addition, Pearson correlation analysis, starBase, RNA immunoprecipitation, luciferase assay, Western blot and functional experiments were conducted to detect and confirm the relationship between LINC01433 and miR-506-3p. RESULTS: LINC01433 level was noticeably elevated in NPC tissues and cell lines. As the expression of LINC01433 in 5-8F cells was the highest in NPC cell lines and the expression of LINC01433 in SUNE1 cells was the lowest, 5-8F and SUNE1 cells were therefore selected as the target cells for following experiments. Furthermore, miR-506-3p was predicted as the target of LINC01433, and the two were negatively correlated with each other. Interestingly, overexpression of LINC01433 promoted proliferation, migration and invasion of NPC cells, while miR-506-3p reversed such effects of LINC01433. Moreover, LINC01433 silencing had the opposite effects to LINC01433 overexpression. Furthermore, miR-506-3p overexpression inhibited the expressions of MMP2, N-cadherin, p-PI3K and p-Akt, and promoted the expressions of E-cadherin and TIMP-2, and partially reversed the role of LINC01433 in promoting cancer development. CONCLUSION: The current findings reveal that LINC01433 regulates NPC cell biological progress through miR-506-3p.

Administration of 1% topical voriconazole drops was effective and safe in the treatment of refractory otomycosis without tympanic membrane perforation.

BACKGROUND: Refractory otomycosis is a common condition that is difficult to treat. OBJECTIVES: This study aimed to evaluate the effectiveness of 1% topical voriconazole drops in the treatment of otomycosis. METHODS: This retrospective analysis was conducted from November 2017 to November 2019. Patients who had refractory otomycosis without tympanic membrane perforation confirmed by microbial culture and fluorescent staining were included in the study. All patients were treated with 1% topical voriconazole drops hourly at daytime for 2 weeks. Evaluation of effectiveness was conducted 1 month after the completion of topical voriconazole treatment. Before and after topical voriconazole treatment, hearing tests were performed in all patients. RESULTS: Fifty-five patients were included in this study. The reasons for refractoriness were resistant recurrence to imidazole drugs (50 cases, 90.9%) and difficulty in cleaning the external auditory canal (5 cases, 9.1%). The most common strain was Aspergillus terreus (50.9%), followed by Aspergillus flavus (29.1%), Aspergillus niger (10.9%), and Aspergillus fumigatus (9.1%). After 2 weeks of treatment with 1% topical voriconazole drops, otomycosis in all patients was resolved. There was no significant change in bone conduction before and after topical voriconazole treatment (paired t-test, P = 0.5023; linear correlation analysis, R2 = 0.98; equation, y = 1.003x-0.284). Adverse effects, such as blurred vision and phototoxicity, were not observed in any patient. CONCLUSIONS: Administration of 1% topical voriconazole drops was effective and safe in the treatment of refractory otomycosis without tympanic membrane perforation within 2 weeks.

Risk factors for residual dizziness in patients successfully treated for unilateral benign posterior semicircular canal paroxysmal positional vertigo.

OBJECTIVE: The risk factors for residual dizziness (RD) after successful treatment of benign paroxysmal positional vertigo (BPPV) are poorly characterized. We determined the risk factors for RD in patients with benign unilateral posterior semicircular canal paroxysmal positional vertigo (pc-BPPV) after successful treatment. METHODS: We conducted a prospective study of patients diagnosed with unilateral pc-BPPV between March 2015 and January 2017. Bone mineral density (BMD) was measured by dual-energy X-ray bone mineral densitometry. Participants underwent bithermal caloric testing (C-test) using videonystagmography and a canalith repositioning procedure (CRP). The occurrence of RD was the primary outcome. The participants underwent follow-up 1 week, 1 month, and 1 year after successful CRP, consisting of outpatient visits, questionnaires, and telephone interviews. RESULTS: We assessed 115 participants with unilateral pc-BPPV (31 men and 84 women) who were 53.2 ± 8.8 years old. RD occurred in 60 (52.2%) participants. The participants who experienced RD were older, had vertigo for longer before treatment, and were more likely to show a positive C-test and significant BMD loss. CONCLUSIONS: We found that a significant reduction in BMD (T-score < -1 standard deviation), a positive C-test, and older age are independently associated with RD in patients with pc-BPPV after successful CRP.

YTHDF1-enhanced iron metabolism depends on TFRC m6A methylation.

Background: Among head and neck squamous cell carcinomas (HNSCCs), hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis. Iron metabolism, which plays a crucial role in tumor progression, is mainly regulated by alterations to genes and post-transcriptional processes. The recent discovery of the N6-methyladenosine (m6A) modification has expanded the realm of previously undiscovered post-transcriptional gene regulation mechanisms in eukaryotes. Many studies have demonstrated that m6A methylation represents a distinct layer of epigenetic deregulation in carcinogenesis and tumor proliferation. However, the status of m6A modification and iron metabolism in HPSCC remains unknown. Methods: Bioinformatics analysis, sample analysis, and transcriptome sequencing were performed to evaluate the correlation between m6A modification and iron metabolism. Iron metabolic and cell biological analyses were conducted to evaluate the effect of the m6A reader YTHDF1 on HPSCC proliferation and iron metabolism. Transcriptome-wide m6A-seq and RIP-seq data were mapped to explore the molecular mechanism of YTHDF1 function in HPSCC. Results: YTHDF1 was found to be closely associated with ferritin levels and intratumoral iron concentrations in HPSCC patients at Sir Run Run Shaw Hospital. YTHDF1 induced-HPSCC tumorigenesis depends on iron metabolism in vivo in vitro. Mechanistically, YTHDF1 methyltransferase domain interacts with the 3'UTR and 5'UTR of TRFC mRNA, then further positively regulates translation of m6A-modified TFRC mRNA. Gain-of-function and loss-of-function analyses validated the finding showing that TFRC is a crucial target gene for YTHDF1-mediated increases in iron metabolism. Conclusion: YTHDF1 enhanced TFRC expression in HPSCC through an m6A-dependent mechanism. From a therapeutic perspective, targeting YTHDF1 and TFRC-mediated iron metabolism may be a promising strategy for HPSCC.

The effect of the standard length of the first prescription on the adherence to sublingual immunotherapy for patients with allergic rhinitis.

BACKGROUND: Poor adherence to sublingual immunotherapy (SLIT) has become a major cause of unsatisfactory clinical efficacy for patients with allergic rhinitis (AR). This study was designed to identify the effect of different first prescription lengths on the adherence to SLIT. METHODS: The clinical data of 306 patients with AR who started SLIT between January 2017 and June 2018 were retrospectively reviewed. Patients were divided into 3 groups according to the length of their first prescription (group A: less than 3 months, group B: 3 to 6 months, group C: more than 6 months). The numbers of adherent or nonadherent patients in each group and the main reasons of nonadherence were analyzed. RESULTS: Groups A, B, and C included 102, 161, and 43 patients, respectively. The average lengths of the first prescription for group A, B, and C were 62.52 ± 17.63, 102.21 ± 9.22, and 189.07 ± 17.97 days. There were significance differences among the 3 groups (p < 0.05). There were 42 (41.18%), 112 (69.57%), and 37 (86.05%) adherent patients in group A, B, and C. There were 60 (58.82%), 49 (30.43%), and 6 (13.95%) nonadherent patients in group A, B, and C. There were significant differences in the proportions of adherent and nonadherent patients among the 3 groups (p < 0.05). The following reasons were cited for nonadherence to SLIT: the long course of SLIT; inconvenience of getting the prescription; ineffectiveness; side effects; and other reasons. CONCLUSION: Under certain conditions, 6 months is recommended as the standard length for the first prescription, which can significantly improve adherence to SLIT in patients with AR.

Prognosis Value of Platelet Counts, Albumin and Neutrophil-Lymphocyte Ratio of Locoregional Recurrence in Patients with Operable Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Peripheral blood inflammation factor neutrophil-lymphocyte ratio (NLR), platelet count (PLT) and nutritional factor serum albumin (ALB) have been proposed as prognostic markers of head and neck squamous carcinoma cancer (HNSCC) in recent years. In the current study, nomogram predict models based on pre-treatment hematological parameters and a modified risk-stratified score system have been built. METHODS: A total of 197 patients with oropharyngeal, hypopharyngeal and laryngeal cancers receiving multimodality treatment between 2012 and 2014 were included. The pre-treatment ALB, neutrophil, lymphocyte and platelet count (PLT) were detected. Cancer-specific survival and locoregional recurrence (LRC) by 5 years' follow-up in the cases were obtained. To integrate clinical characteristics, we propose a modified risk-stratified score system. Kaplan-Meier method, proportional hazards COX model, logistic models were used to establish nomograms within external validation. RESULTS: Five-year LRC was decreased (p=0.004) for 140 patients with pre-treatment NLR <2.77. Five-year LRC and 5-year cancer-specific survival were decreased (p=0.031, p=0.021) with pre-treatment PLT ≥248×109/L. Comparison of univariate parametric models demonstrated that pre-treatment NLR evaluation and PLT>248×109/L were better among tested models. On Bayesian information criteria (BIC) analysis, the optimal prognostic model was then used to develop nomograms predicting 3- and 5-year LRC. The external validation of this predictive model was confirmed in 57 patients from another hospital. CONCLUSION: Pre-treatment NLR elevation and PLT>248×109/L are promising predictors of prognosis in patients with operable HNSCC. Nomograms based on the pre-treatment hematological markers and modified risk-stratified score system provide distinct risk stratifications. There results provided the feasibility of anti-inflammatory and antiplatelet treatments for HNSCC patients.

Low-Concentration PTX And RSL3 Inhibits Tumor Cell Growth Synergistically By Inducing Ferroptosis In Mutant p53 Hypopharyngeal Squamous Carcinoma.

INTRODUCTION: RSL3-induced ferroptosis is a cell death pathway dependent upon intracellular iron and is characterized by accumulation of lipid hydroperoxides. Glutaminolysis, a glutamine-fueled intracellular metabolic pathway, is an essential pathway of ferroptosis in cancer cells. Recent findings showed low-concentration paclitaxel (PTX) could inhibit cell death by upregulating p53 expression; downregulating glutaminolysis-related genes. METHODS: The therapeutic effect of RSL3 plus low-concentration PTX combination therapy was investigated in HPSCC cells harboring mutant p53 (mtp53). Relative cell viability, ferroptosis-specific lipid peroxidation and relevant protein expression were evaluated. RESULTS: We demonstrated that neither PTX nor RSL3 in low concentration caused significant cell death; however, the combination therapy is shown to induce ferroptosis and significant cell death in mtp53 HPSCC. We discovered that low-concentration PTX enhanced the RSL3-induced ferroptosis by upregulating mtp53 expression. Furthermore, mtp53-mediated transcriptional regulation of SLC7A11 could be the key determinant. DISCUSSION: Although gain-of-function of p53 variants remains to be characterized, our findings provide new insight into the synergistical cell death by regulating ferroptosis and p53.

Novel genetic alterations and their impact on target therapy response in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is highly variable by tumor site, histologic type, molecular characteristics, and clinical outcome. During recent years, emerging targeted therapies have been focused on driver genes. HNSCC involves several genetic alterations, such as co-occurrence, multiple feedback loops, and cross-talk communications. These different kinds of genetic alterations interact with each other and mediate targeted therapy response. In the current review, it is emphasized that future treatment strategy in HNSCC will not solely be based on "synthetic lethality" approaches directed against overactivated genes. More importantly, biologic, genetic, and epigenetic alterations of HNSCC will be taken into consideration to guide the therapy. The emerging genetic alterations in HNSCC and its effect on targeted therapy response are discussed in detail. Hopefully, novel combination regimens for the treatment of HNSCC can be developed.

Tanshinone IIA suppress the proliferation of HNE-1 nasopharyngeal carcinoma an in vitro study.

Nasopharyngeal carcinoma (NPC) at present is considered to be one of the fatal diseases detected commonly in the people belonging to Southeast Asia and southern China. According to the WHO reports among the detected cases of NPC worldwide, 80% are from China. The present study investigates the effect of tanshinone IIA on the migration and invasion potential of HNE-1NPC cells and studied the detailed mechanism involved. Effect of the tanshinone IIA on viability of the HNE-1NPC cells was analyzed by MTS assay. Cell matrigel invasion and wound-healing motility assays, respectively were used for the analysis of invasion and migration potential of HNE-1 cells. Tanshinone IIA inhibited the viability of HNE-1cells in a dose dependent manner. Migration and invasion potential of the tanshinone IIA treated cells was reduced significantly (P < 0.05) compared to the control cells after 48 h. Analysis of the proteins involved in migration and invasion revealed a significant decrease in the expression of matrix metalloproteinase (MMP)-2 and MMP-9 on treatment with tanshinone IIA. It also inhibited the p65 and p50 expression in the nuclear fractions of HNE-1 cells after 48 h. Thus, tanshinone IIA inhibits migration and invasion potential of the HNE-1NPC cells through reduction in the expression of matrix metalloproteinases. Therefore, tanshinone IIA can be used for the treatment of NPC.

Interleukin (IL)-21 promoter polymorphism increases the risk of thyroid cancer in Chinese population.

Polymorphisms in Interleukin (IL)-21 have been researched in several cancers, but the association between IL-21 polymorphisms and thyroid cancer remains unclarified. This case-control study explored the role of five tagSNPs (rs12508721C>T, rs907715G>A, rs13143866G>A, rs2221903A>G and rs4833837A>G) in IL-21 gene in thyroid cancer development. IL-21 genotypes were examined in 615 thyroid cancer patients and 600 controls in Chinese population, and the associations with the risk of thyroid cancer were estimated by logistic regression. Moreover, the potential role of rs12508721C>T in thyroid cancer was further explored by biochemical assays. Compared with the rs12508721CC genotype, CT genotype presented a significantly decreased risk of thyroid cancer (adjusted odds ratios [OR]=0.72; 95%CI=0.57-0.94), the TT carriers had a further decreased risk of thyroid cancer (OR=0.56; 95%CI=0.41-0.87). Furthermore, our quantitative real-time PCR and Enzyme-linked immunosorbent assay (ELISA) results demonstrated that the presence of rs12508721T allele led to more IL-21 expression. However, no significant difference was found in genotype frequencies for other four sites between cases and controls. These findings suggested that rs12508721 polymorphism in IL-21 might be a genetic modifier for the development of thyroid cancer.

Polymorphisms of CD44 gene and nasopharyngeal carcinoma susceptibility in a Chinese population.

As members of adhesion molecule families, CD44 transmembrane glycoproteins have been originally thought to be essential for the formation of multicellular organisms and soon recognised to be able to initiate metastatic spread of tumour cells. To investigate the association between CD44 polymorphisms and nasopharyngeal carcinoma (NPC), we carried out a two-stage case-control study in 906 patients and 943 healthy controls in Eastern populations. Five single nucleotide polymorphisms of CD44 (rs10836347C>T, rs13347C>T, rs1425802A>G, rs11821102G>A and rs713330T>C) with proper frequency were selected from the HapMap database and genotyped with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Compared with the most common rs13347CC genotype, CT+TT genotypes significantly increased individuals' susceptibility to NPC (odds ratio = 2.58, 95% confidence interval = 2.13-3.13). Furthermore, our transient transfection focusing on reporter gene expression modulated by CD44 3'UTR demonstrated that the presence of an rs13347T allele led to greater transcriptional activity than the C allele. Similarly, more CD44 expression was shown in rs13347T carriers than C carriers in our western blotting results. All these findings suggest that CD44 rs13347C>T polymorphism may affect NPC development by improving CD44 expression.

Tongue coblation via the ventral approach for obstructive sleep apnea-hypopnea syndrome surgery.

OBJECTIVES/HYPOTHESIS: To determine the safety and efficacy of tongue Coblation via the ventral approach in the treatment of hypopharyngeal obstruction for patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). STUDY DESIGN: Prospective case-control study. METHODS: Tongue Coblation was performed under local anesthesia in one session in 40 inpatients diagnosed with OSAHS with predominant hypopharyngeal obstruction after failed uvulopalatopharyngoplasty. In the ventral approach (n = 20), only one puncture point was applied at the center of lingual frenulum, and 12 radiofrequency volumetric tissue reduction (RFVTR) lesions were implanted in the tongue. In the dorsal approach (n = 20), eight RFVTR lesions were distributed on the tongue. Using portable polysomnography (PSG) and the Epworth sleepiness questionnaire (ESQ), we followed 36 patients for 1 year after the operation. Good outcome was defined as apnea-hypopnea index <20 or reduction >50%. RESULTS: In the ventral approach, total energy was accumulated to 23,000 J in 12 lesions, with postoperative pain 2-3 by visual analog scale (VAS). There was only one case of moderate venous bleeding and hematoma. The ESQ comparison indicated subjective improvements in patients, and PSG showed a curative effect in 11 of 19 (61.11%, eight of 19 success plus three of 19 responders), with a failure rate of eight of 19. By contrast, in the dorsal approach, total energy was 16,000 J, with postoperative pain 3-4 (VAS). Complications included mild to moderate tongue venous hematoma, severe infection of tongue, and temporary mild glossal deviation. A curative effect was seen in six of 17, with a failure rate of 11 of 17. CONCLUSIONS: Tongue Coblation via the ventral approach is an effective and safe technique to treat hypopharyngeal obstruction in OSAHS surgery.

The effects of functional polymorphisms in the TGFß1 gene on nasopharyngeal carcinoma susceptibility.

OBJECTIVE: Transforming growth factor ß1 (TGFß1) promotes tumor growth and metastasis in the later stage of cancer development. In this study, we explored whether TGFß1 polymorphisms were associated with increased risk of nasopharyngeal carcinoma (NPC) in a Chinese population. DESIGN: Case-control study. SETTING: Hospitals of the Department of Otorhinolaryngology-Head and Neck Surgery. SUBJECTS AND METHODS: Two single nucleotide polymorphisms of TGFß1 gene promoter -509C/T (rs1800469) and 869T/C (Leu 10 Pro, rs1800470) at exon 1 were analyzed in 522 NPC patients and 712 age- and sex-matched controls in a Chinese population, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Functional relevance of the polymorphism was determined by biochemical assays. RESULTS: The -509T allele carriers were associated with a significantly reduced risk of NPC as compared with the noncarriers (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.53-0.89 and OR, 0.50; 95% CI, 0.31-0.67, respectively). Moreover, -509C-containing TGFß1 promoter drove an ~1.7-fold increase in reporter expression, compared with the -509T-containing counterpart in both CNE-1 and CNE-2 cell lines. The TGFß1 -509 CC genotype carriers had a higher TGFß1 mRNA level than the TGFß1 -509TT genotype carriers did (P < .01). However, no significant association was observed between the 869T/C polymorphism and risk of NPC. CONCLUSION: These findings indicate that the -509C/T polymorphism in TGFß1 may play a vital role in mediating individual susceptibility to NPC.

Genetic polymorphisms of MDM2 and TP53 genes are associated with risk of nasopharyngeal carcinoma in a Chinese population.

BACKGROUND: The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies also revealed TP53 72Arg>Pro and MDM2 309T>G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and nasopharyngeal carcinoma (NPC) susceptibility has not been explored. METHODS: In this study, we performed a case-control study between 522 NPC patients and 722 healthy controls in a Chinese population by using PCR-RFLP. RESULTS: We found an increased NPC risk associated with the MDM2 GG (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 2.08-3.96) and TG (OR = 1.49, 95% CI = 1.16-2.06) genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 2.22, 95% CI = 1.58-3.10) compared to the Arg/Arg genotype. The gene-gene interaction of MDM2 and TP53 polymorphisms increased adult NPC risk in a more than multiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 7.75, 95% CI = 3.53-17.58). CONCLUSION: The findings suggest that polymorphisms of MDM2 and TP53 genes may be genetic modifier for developing NPC.