Randomized double-blind, placebo-controlled trial evaluating oral glutamine on radiation-induced oral mucositis and dermatitis in head and neck cancer patients.

BACKGROUND: Glutamine is the primary fuel for the gastrointestinal epithelium and maintains the mucosal structure. Oncologists frequently encounter oral mucositis, which can cause unplanned breaks in radiotherapy (RT). OBJECTIVES: The aim of this study was to explore the association between oral glutamine and acute toxicities in patients with head and neck cancer undergoing RT. METHODS: This was a parallel, double-blind, randomized, placebo-controlled Phase III trial conducted in a university hospital. A central randomization center used computer-generated tables to allocate interventions to 71 patients with stages I-IV head and neck cancers. The patients, care providers, and investigators were blinded to the group assignment. Eligible patients received either oral glutamine (5 g glutamine and 10 g maltodextrin) or placebo (15 g maltodextrin) 3 times daily from 7 d before RT to 14 d after RT. The primary and secondary endpoints were radiation-induced oral mucositis and neck dermatitis, respectively. These were documented in agreement with the National Cancer Institute Common Terminology Criteria for Adverse Events version 3. RESULTS: The study included 64 patients (placebo n = 33; glutamine n = 31) who completed RT for the completers' analysis. Based on multivariate analysis, glutamine had no significant effect on the severity of oral mucositis (OR: 0.3; 95% CI: 0.05, 1.67; P = 0.169). Only the change in body mass index (BMI) was significant in both multivariate completers (OR: 0.41; 95% CI: 0.20, 0.84; P = 0.015) and per-protocol analysis (OR: 0.40; 95% CI: 0.20, 0.83; P = 0.014). No difference was found in the incidence and severity of neck dermatitis between the two arms. CONCLUSIONS: The decrease in BMI was strongly related to the severity of oral mucositis in the head and neck cancer patients under RT, but not to the use of glutamine. This trial was registered at clinicaltrials.gov as NCT03015077.

Effects of APE1 Asp148Glu polymorphisms on OPMD malignant transformation, and on susceptibility to and overall survival of oral cancer in Taiwan.

BACKGROUND: The associations between malignant transformation of oral potentially malignant disorders (OPMDs), oral cancer development and prognosis, and apurinic/apyrimidinic endonuclease 1 (APE1) functional polymorphisms are unclear. METHODS: Patients with OPMDs, patients with oral cancer, and healthy controls from the community were recruited to determine the effects of APE1 polymorphisms on malignant transformation, overall survival, and genetic susceptibility, respectively. RESULTS: The APE1 Asp148Glu polymorphisms significantly correlated with a high hazard ratio for OPMD malignant transformation (adjusted hazard ratio [AHR] = 2.29; 95% confidence interval [CI] = 1.44-3.74) and low overall survival in oral cancer patients (AHR = 1.71, 95% CI = 1.11-2.56) according to follow-up and survival analysis. However, APE1 polymorphisms did not significantly correlate with development of oral cancer in the case-control study and logistic regression analysis. CONCLUSIONS: These results indicate that APE1 Asp148Glu polymorphisms may have indirect roles in increasing the OPMD malignant transformation rate and in decreasing overall survival in oral cancer patients.

Evaluation of the mRNA expression levels of integrins α3, α5, ß1 and ß6 as tumor biomarkers of oral squamous cell carcinoma.

Integrin signaling may modulate several different functions involved in cell migration, invasion, proliferation and motility, and is a potential candidate biomarker for oral cancer. In the present study, a total of four integrin genes were evaluated as potential biomarkers of oral squamous cell carcinoma (OSCC). Gene expression was determined using the reverse transcription-quantitative polymerase chain reaction in 55 OSCC and 55 matched normal oral tissues. The performance of individual and combined biomarkers was analyzed by receiver operating characteristic (ROC) analysis based on the relative mRNA expression (OSCC vs. matched oral tissue from the tumor-free margin), which was calculated using the ΔΔCq value (ΔCq of OSCC-ΔCq of oral tissue from the tumor-free margin of the same patient). In the individual ROC analysis, the areas under the ROC curve (AUCs) of relative mRNA expression (ΔΔCq) of integrin subunit α3 (ITGA3), integrin subunit α5 (ITGA5), integrin subunit ß1 (ITGB1) and integrin subunit ß6 (ITGB6) in all tumor locations were 0.724, 0.698, 0.640 and 0.657, respectively. For locations 2 (tongue/mouth part) and 3 (edentulous ridge), their individual AUC values were 0.840, 0.765, 0.725 and 0.763, respectively. In the cumulative ROC analysis, ITGA3, ITGA5 and ITGB1 genes exhibited the highest combined AUC values (0.809 and 0.871 for all locations and locations 2 and 3 combined, respectively) compared with other biomarker combinations. In conclusion, the results of the present study identified that higher mRNA expressions of ITGA3, ITGA5, ITGB1 and ITGB6 genes are suitable for OSCC diagnosis biomarkers. Cumulative ROC analysis indicated an improved overall performance compared with the best individual integrin biomarker of OSCC.

Overexpression of sprouty2 in human oral squamous cell carcinogenesis.

OBJECTIVE: This study investigated SPRY2 expression in human oral potentially malignant disorders (OPMDs) and oral squamous cell carcinomas (OSCCs). METHODS: 75 OSCCs, 23 OPMDs with malignant transformation (MT), 17 OPMDs without MT, and eight normal oral mucosa (NOM) tissues were used for immunohistochemical staining; three OSCC tissues with normal tissue counterparts were used for western blotting. Three human oral cancer cell lines (OCCLs), an oral precancer cell line (DOK), and a NOM primary culture (NOMPC) were used for western blotting; OCCLs and NOMPC were employed for real-time quantitative reverse transcription-polymerase chain reaction. OCCLs were evaluated in terms of proliferation, migration, invasion and BRAF V600E point mutation assays. RESULTS: Significantly increased SPRY2 protein expression was observed in OSCCs as compared with NOM, and SPRY2 expression also differed between OSCC patients with and without lymph-node metastasis. SPRY2 protein and mRNA expressions were significantly enhanced as compared with NOMPC. Increased phospho-ERK expression was observed in OCCLs as compared with NOMPC. Significant decreases in the proliferation rate, degrees of migration and invasion were noted in OCCLs with SPRY2 siRNA transfection as compared with those without SPRY2 siRNA transfection. No BRAF V600E point mutation was observed for OCCLs as compared with NOMPC. A significantly increased SPRY2 protein level was noted in OPMDs with MT as compared to those without MT, and was also found in OPMDs with MT in comparison with NOM, as well as in DOK in comparison with NOMPC. CONCLUSIONS: Our results indicated that SPRY2 overexpression is associated with human oral squamous-cell carcinogenesis.

Endoscopic screening for synchronous esophageal neoplasia among patients with incident head and neck cancer: Prevalence, risk factors, and outcomes.

Esophageal squamous-cell neoplasia (ESCN) is a common second primary neoplasia found in patients with head-and-neck squamous-cell carcinoma (HNSCC). This study sought to identify the risk factors for synchronous ESCN and how they influence survival in HNSCC patient. Eight hundred and fifteen incident HNSCC patients were prospectively recruited for endoscopy screening for ESCN using white-light imaging, narrow-band imaging, Lugol chromoendoscopy, and pathological confirmation. Associated lifestyle and clinicopathological data were collected. The interquartile follow-up period cutoffs were 11.3, 20.5 and 34.9 months. 124 patients (15.2%) were diagnosed as having synchronous ESCN (66 low-grade dysplasia, 29 high-grade dysplasia, and 29 esophageal squamous-cell carcinoma). Consumption of alcohol, but not betel nut or cigarette, was significantly associated with the presence of synchronous ESCN (adjusted odds ratio [aOR] = 7.1 and 10.9 for former and current drinkers, respectively). There was an interaction between cumulative dose of alcohol consumption and alcohol flushing response on the development of ESCN. High-dose drinkers with flush response were 16.9 times more likely to have esophageal high-grade dysplasia/SCC than non-drinkers. Compared with oral cavity cancer patients, those with hypopharyngeal, laryngeal and oropharyngeal cancer were 6.8, 4.6 and 2.8 times more likely to have esophageal high-grade dysplasia/SCC. HNSCC patients with synchronous ESCN had lower overall survival than those without (p < 0.0001). In conclusion, surveillance of ESCN is strongly recommended for the high-risk subpopulation of HNSCC patients, especially drinkers who have a flush response to alcohol, and those with distant metastasis of index cancer and cancers in hypopharynx, oropharynx and larynx.

Oxidized low-density lipoprotein is a common risk factor for cardiovascular diseases and gastroenterological cancers via epigenomical regulation of microRNA-210.

Hyperlipidemia, including the oxidized low-density lipoprotein (oxLDL) accumulation, is a risk and highly associated with the development of cancers and cardiovascular diseases. microRNA-210 (miR-210), a hypoxia-responsive microRNA regulated by HIF-1α, has been implicated in cancer and cardiovascular disease formation. Furthermore, Bioinformatics analysis revealed that the promoter of the miR-210 gene contains CpG-rich regions. It is unclear whether miR-210 expression could be epigenetically regulated in these disease progresses. The study aimed to explore the relationships between lipid and miR-210 in the context of cardiovascular disease and gastrointestinal cancer. We demonstrated oxLDL can decrease methylation in the miR-210 promoter to up-regulate miR-210. HIF-1α can bind to miR-210 promoter, but this HIF-1α binding site can be blocked by methylation. We showed that subjects of carotid atherosclerosis, stroke patients and cancer patients had hypomethylation in the miR-210 promoter, especially the HIF-1α binding site. Furthermore, miR-210 can directly inhibit sprouty-related EVH1 domain 2 (SPRED2) expressions, and SPRED2 reduces cell migration via ERK/c-Fos/MMPs pathways. Increased miR-210 and reduced SPRED2 levels were found in aorta of mice under high-fat diet and tumor tissues, which implied that miR-210 can be an underlying mechanism to explain oxLDL as a common risk factor for cardiovascular disease and gastrointestinal cancer.

TGF-ß1 and IL-10 single nucleotide polymorphisms as risk factors for oral cancer in Taiwanese.

Cytokine production capacity varies among individuals and depends on cytokine gene polymorphisms. Transforming growth factor-beta 1 (TGF-ß1) plays a significant role in regulating the proliferation and apoptosis of epithelial cells. Interleukin 10 (IL-10) is an immunoregulatory cytokine with biological functions of anti-inflammation, immunosuppression, allergy, and anti-agenesis. The two cytokines are supposed to play an important role in carcinogenesis. The association between cytokine gene polymorphisms with oral cancer (OC) was investigated. We studied the association between the polymorphism in TGF-ß1 (G to C polymorphism at codon 25 <+915>) and IL-10 (-1082 G/A, -819 C/T, and -592 C/A) and the risk of OC in patients (n = 162) and healthy controls (n = 118) in Taiwan. All genotyping experiments were performed using the polymerase chain reaction sequence-specific primer (PCR-SSP) method. It was found that the codon 25 GC genotype of TGF-ß1 is significantly higher in frequency in patients with OC compared with a healthy control group (p < 0.0001). People with the GC genotype in codon 25 had an 11.09-fold increased risk of OC [odds ratio (OR) = 11.09; 95% confidence interval (CI) = 6.16-113.23]. IL-10 polymorphisms in -819 and -592 positions correlated with the risk of OC (p < 0.0001). The IL-10 -592 C allele-containing genotypes posed an increased risk of OC (OR = 1.79, 95% CI = 1.11-2.91). People with the CT genotype in IL-10 -819 had a 3.32-fold increased risk of OC (OR = 3.32; 95% CI = 1.64-6.94). The results suggest that polymorphisms in TGF-ß1 and IL-10 may have a significant influence on the development of OC.

Role of cytokine gene (interferon-γ, transforming growth factor-ß1, tumor necrosis factor-α, interleukin-6, and interleukin-10) polymorphisms in the risk of oral precancerous lesions in Taiwanese.

Oral squamous cell carcinoma can be preceded by some benign oral lesions with malignant potential, including leukoplakia, erythroplakia, oral lichen planus, and oral submucous fibrosis. There are different degrees of inflammatory cells infiltration in histopathology. Inflammatory cytokines may play a pathogenic role in the development of oral precancerous lesions (OPCLs). Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. We hypothesized that the risk of OPCLs might be associated with cytokine gene polymorphisms of interferon (IFN)-γ, transforming growth factor (TGF)-ß1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10. In the present study, 42 OPCL patients and 128 controls were analyzed for eight polymorphisms in five different cytokine genes [IFN-γ (+874 T/A), TGF-ß1 (codons 10 T/C and 25 G/C), TNF-α (-308 G/A), IL-6 (-174 G/C), and IL-10 (-1082 A/G, -819 T/C, and -592 A/C)]. Cytokine genotyping was determined by the polymerase chain reaction sequence-specific primer technique using commercial primers. Allele and genotype data were analyzed for significance of differences between cases and controls using the Chi-square (χ(2)) test. Two-sided p < 0.05 were considered to be statistically significant. A series of multivariate logistic regression models, adjusted for age, sex, betel quid chewing, alcohol consumption, and smoking, was constructed in order to access the contribution of homozygous or heterozygous variant genotypes of polymorphisms. The TNF-α (-308) polymorphism was significantly associated with OPCLs. There were significant differences in the distribution of AA, GA, and GG genotypes between OPCL patients and controls (p = 0.0004). Patients with the AA or GA genotype had a 3.63-fold increased risk of OPCLs. The TGF-ß1 (codon 10 and 25) polymorphism was also significantly associated with OPCLs (p < 0.001). The IL-6 polymorphism was significantly associated with OPCLs. There are significant differences in the distribution of CC, GC, and GG genotypes between OPCL patients and controls (p < 0.001). Patients with the CC or GC genotype had a 35- or 20.59-fold increased risk of OPCLs. There were no significant differences in the distribution of IL-10 and IFN-γ genotypes between different groups of control individuals and OPCL patients. The IL-6, TGF-ß1, and TNF-α gene polymorphisms may have a significant association with the development of OPCLs.

Malignant transformation in 5071 southern Taiwanese patients with potentially malignant oral mucosal disorders.

BACKGROUND: Oral cancers can be preceded by clinically evident oral potentially malignant disorders (OPMDs). The current study evaluated the rate and the time of malignant transformation in the various OPMDs in a cohort of patients from southern Taiwan. Parameters possibly indicative for malignant transformation of OPMDs, such as epidemiological and etiological factors, and clinical and histopathological features were also described. METHODS: We followed-up 5071 patients with OPMDs-epithelial dysplasia with oral submucous fibrosis, epithelial dysplasia with hyperkeratosis/epithelial hyperplasia, hyperkeratosis/epithelial hyperplasia, oral submucous fibrosis, lichen planus, and verrucous hyperplasia-between 2001 and 2010 for malignant transformation. RESULTS: Two hundred nineteen of these 5071 OPMD patients (202 men, 17 women; mean age: 51.25 years; range: 30-81 years) developed oral cancers (179 squamous cell carcinomas; 40 verrucous carcinomas) in the same sites as the initial lesions at least 6 months after their initial biopsies. The overall transformation rate was 4.32% (mean duration of transformation: 33.56 months; range: 6-67 months). Additionally, the mean time of malignant transformation was significantly shorter for lesions with than without epithelial dysplasia. The risk of malignant transformation was 1.89 times higher for epithelially dysplastic than non-dysplastic lesions. The anatomical site of OPMD and the presence of epithelial dysplasia were significantly associated with malignant transformation. The hazard rate ratio was 1.87 times larger for tongue lesions than for buccal lesions. CONCLUSION: Patients with OPMDs require long-term follow up.

Unintended avulsion of hypertrophic adenoids in posterior nasopharynx: a case report of a rare complication caused by nasotracheal intubation.

The enlarged adenoid serves as a mechanical obstacle on the nasopharynx to intricate nasotracheal intubation. No matter what video or direct laryngoscopic techniques are applied, nasotracheal tube navigation from the nasal valve area through the nasal cavity to the nasopharynx is always blind; trauma is not uncommon. Here we report a case of unintended avulsed adenoids that plugged the tube tip while the nasotracheal tube blindly navigated through the nasopharyngeal space. After failing to insert a bent tip of gum elastic bougie passing through the nasopharynx, an alternative method of NTI was performed by mounting the nasotracheal tube on a fiberoptic bronchoscope. The nasotracheal tube was successfully railroaded along the insertion tube of the fiberscope to the trachea.

Retrospective study of biopsied head and neck lesions in a cohort of referral Taiwanese patients.

INTRODUCTION: A study of the whole spectrum of biopsied head and neck (HN) diseases in Taiwan has not yet been performed. Therefore, the current study aimed to provide updated information about HN lesions in a cohort of referral Taiwanese patients for histopathological examination. METHODS: HN lesions (2000-2011) in patients with records of age, sex, and histological diagnoses were retrieved from the Oral Pathology Department of the institution. These lesions were classified into four main categories: tumor/tumor-like reactive lesions, cystic/pseudocystic lesions, inflammatory/infective lesions, and others/miscellaneous lesions. RESULTS: A total of 37,210 HN lesions were included in the current study. Most of these lesions were distributed in the group of tumor/tumor-like reactive lesions, followed by the groups of inflammatory/infective lesions, cystic/pseudocystic lesions, and others/miscellaneous lesions. Squamous cell carcinoma was the most common HN lesion, and was also the most frequent malignant lesion among the referral patients. CONCLUSION: It was worthy of note that squamous cell carcinoma and oral potentially malignant disorders comprised high percentages of all HN lesions for the present cohort of referral patients.

Induction chemotherapy with docetaxel, cisplatin and fluorouracil followed by surgery and concurrent chemoradiotherapy improves outcome of recurrent advanced head and neck squamous cell carcinoma.

BACKGROUND: Locally recurrent rate of advanced head and neck squamous cell carcinoma (HNSCC) still remains high and the treatment is controversial. PATIENTS AND METHODS: We retrospectively analyzed ninety-three patients with recurrent advanced oral cancer from 2009 to 2013. Sixty-four patients are in the docetaxel with cisplatin and 5'-fluorouracil (TPF) group and the remaining twenty-nine patients are in the cisplatin and 5'-fluorouracil (PF) group. RESULTS: The overall response rate was better in the TPF group (p=0.005) than the PF group. Patients who received induction chemotherapy, TPF, followed by surgery and concurrent chemoradiotherapy (CRT) had better overall survival (OS) (p=0.012) and progression-free survival (PFS) (p=0.038), while patients with prior intra-arterial-infusion-chemotherapy had an adverse impact on OS (p=0.039). CONCLUSION: We showed that induction chemotherapy with TPF, followed by surgery and consolidation CRT, is the ideal choice for recurrent advanced HNSCC with improving response rates and survival. However, prior intra-arterial-infusion-chemotherapy showed an adverse impact.

Comparison of 4% and 6% topical cocaine solutions for reduction of epistaxis induced by nasotracheal intubation.

BACKGROUND: Nasotracheal intubation (NTI) provides a good field for surgeons in patients undergoing oromaxillofacial surgery; however, NTI is often complicated by epistaxis. The aim of this study was to compare the efficacy of 4% and 6% topical cocaine solutions in reducing epistaxis during NTI. METHODS: A total of 79 patients (16-65 years old) undergoing oromaxillofacial surgery were randomly assigned to two groups treated with either 4% cocaine (n = 39) or 6% cocaine (n = 40). Topical cocaine (1 mL) was sprayed onto the selected nasal cavity prior to NTI. All intubations were performed by an expert anesthesiologist using a GlideScope. The incidence and severity of epistaxis was examined along the nasal cavity up to the nasopharynx using a fiber optic bronchoscope. The hemodynamic responses to stimuli during the peri-NTI period were also recorded. RESULTS: The incidence of epistaxis was 43.59% (17/39) in the 4% cocaine group and 50% (20/40) in the 6% cocaine group (p = 0.57). The severity of epistaxis did not differ between the two groups (p = 0.46). High resistance during NTI and epistaxis were closely correlated and the major bleeding sites were located at the nasopharynx. Compared with the 4% cocaine group, treatment with 6% cocaine resulted in a higher heart rate and mean arterial pressure (both p < 0.05). There was no statistically significance difference between the two groups with respect to the hemodynamic responses to NTI. CONCLUSION: The spraying of either 4% or 6% topical cocaine into the nasal cavity gives comparable effects for intubation-related epistaxis. However, 6% cocaine may increase the hemodynamic responses while being sprayed. Therefore spraying with 4% topical cocaine had advantages with respect to 6% cocaine and is recommended for use prior to NTI.

Interval between intra-arterial infusion chemotherapy and surgery for locally advanced oral squamous cell carcinoma: impacts on effectiveness of chemotherapy and on overall survival.

BACKGROUND: The interval between intra-arterial infusion chemotherapy (IAIC) and surgery was investigated in terms of its effects on survival in patients with locally advanced oral squamous cell carcinoma (OSCC). METHODS: This retrospective study analyzed 126 patients who had completed treatment modalities for stage IV OSCC. All patients were followed up for 3 years. Kaplan-Meier and Cox regression methods were used to determine how survival was affected by general factors, primary tumor volume, TNM stage, and duration of neoadjuvant chemotherapy. RESULTS: In 126 patients treated for locally advanced OSCC by preoperative induction IAIC using methotrexate, multivariate analysis of relevant prognostic factors showed that an IAIC duration longer than 90 days was significantly associated with poor prognosis (hazard ratio, 1.77; P = 0.0259). CONCLUSIONS: Duration of IAIC is a critical factor in the effectiveness of multimodal treatment for locally advanced OSCC. Limiting the induction course to 90 days improves overall survival.

Radiotherapy for a repeatedly recurrent ameloblastoma with malignant transformation.

BACKGROUND: The role of radiation therapy (RT) for ameloblastoma remains controversial and undetermined due to the rarity of the disease. METHODS: A case of repeatedly recurrent ameloblastoma with malignant transformation is presented. The clinical course and managements are described. RESULTS: The 63-year-old man had a recurrent ameloblastoma in the left mandible. Five years after the first surgical resection, he underwent 8 more rounds of surgical excision of the recurrent tumors. The malignant transformation occurred and the unresectable tumor invaded the masticator space, parapharyngeal space, and skull base. He received 3-dimensional conformal RT, at the dose of 66 Gray (Gy) in 33 fractions. The ulcerative exophytic mass had regressed gradually. After follow-up of 28 months, the tumor was well controlled. CONCLUSIONS: RT seems to be a feasible treatment option for recurrent ameloblastoma with malignant transformation.

A retrospective comparison of the location and diameter of the inferior alveolar canal at the mental foramen and length of the anterior loop between American and Taiwanese cohorts using CBCT.

PURPOSE: The aim was to retrospectively compare the measurements of the location and size of the inferior alveolar canal at the mental foramen and the length of the anterior loop between two cohorts of Americans and Taiwanese using cone-beam computed tomography (CBCT). METHODS: CBCT was performed with an I-CAT(®) Cone-Beam 3D Dental Imaging System and reconstructed into multiple-plane views to measure two populations. RESULTS: There was no statistically significant difference (P = 0.2681) in the distance from the mental foramen to the inferior border of the mandible (mandibular border height) between Americans (9.84 ± 2.01 mm) and Taiwanese (10.13 ± 1.66 mm). No significant difference was found (p = 0.1161) in the inferior alveolar canal diameter between these two cohorts (2.26 ± 0.67 and 2.13 ± 0.47 mm, respectively). However, the anterior loop length of Taiwanese (7.61 ± 1.81 mm) was significantly longer than that of Americans (6.22 ± 1.68 mm) (P < 0.0001). CONCLUSION: Our study indicated that (1) the location of mental foramen of Americans was closer to the inferior border of the mandible than Taiwanese; (2) the diameter of the inferior alveolar canal of Americans was larger than Taiwanese; (3) the anterior loop of Taiwanese was longer than Americans. These differences may be, at least partly, due to the racial influence and this information may possess potential valuable clinical relevance.

Evaluating the performance of fibronectin 1 (FN1), integrin α4ß1 (ITGA4), syndecan-2 (SDC2), and glycoprotein CD44 as the potential biomarkers of oral squamous cell carcinoma (OSCC).

OBJECTIVES: Some extracellular matrix genes as prognostic biomarkers for oral squamous cell carcinoma (OSCC) were evaluated. METHODS: We investigated gene expression of fibronectin 1 (FN1), integrin α4ß1 (ITGA4), syndecan-2 (SDC2), and glycoprotein CD44 in matched OSCC/margin tissues. RESULTS: Areas under receiver-operating characteristic curves (AUCs) of relative mRNA expression of FN1, ITGA4, SDC2, and CD44 were 0.700, 0.677, 0.513, and 0.549, respectively. For tongue/mouth floor and edentulous ridge, AUC for FN1 and ITGA4 were 0.827 and 0.725 and sensitivities/specificities were 80%/84% and 88%/52%, respectively. CONCLUSION: FN1 and ITGA4 are potential OSCC biomarkers for tongue/mouth floor and edentulous ridge.

The effect of CCND1 +870A>G and VEGF +936C>T polymorphisms on oral cancer development and disease-free survival in a Taiwan population.

The association between polymorphisms in vascular endothelial growth factor (VEGF) +936C>T and cyclin D1 (CCND1) +870A>G genes, oral cancer risk, and disease-free survival remains controversial. We found no association between polymorphisms in the CCND1 and VEGF genes and oral cancer development using multivariate logistic regression analysis. Clinical data indicated that the VEGF +936C>T polymorphisms were associated with larger tumor size and advanced cancer stage, but the χ(2) test did not show that CCND1 polymorphisms were associated with larger tumor size and advanced cancer stage. However, Cox proportional hazards model analysis showed no correlation between the VEGF +936C>T polymorphisms and poor disease-free survival. The CCND1 +870A>G polymorphisms (hazard ratio (HR)=1.62, 95% CI=1.10-2.46; adjusted HR=1.63, 95% CI=1.08-2.54) and larger tumor size were associated with poor 5-year disease-free survival by the log rank test and multivariate Cox proportional hazards model analysis. We hypothesized that polymorphisms in CCND1 +870A>G and VEGF +936C>T genes are not correlated with the development of oral cancer. We found the CCND1 +870G allele to be an independent risk factor for poor 5-year disease-free survival in oral cancer patients. VEGF +936C>T polymorphisms were not directly correlated with poor survival, but they might be associated with increased tumor size, which affected our disease-free survival results.