Preoperative Serum Selenium Concentrations and Disease-Specific Survival in Patients With Oral Cancer: A Long-Term Follow-Up Study.

BACKGROUND: Serum selenium (Se) concentration has been reported to be associated with the incidence of oral cancer. The association between serum Se and long-term survival in oral cancer patients is still unclear. PURPOSE: The purpose of this study is to measure the association between serum Se and disease-specific survival (DSS). STUDY DESIGN, SETTING, AND SAMPLE: This was a single-center, prospective cohort study conducted at the First Affiliated Hospital of Fujian Medical University (Fujian Province, China) from September 2011 to December 2018. The inclusion criteria were patients with newly diagnosed primary oral cancer confirmed by histology. The exclusion criteria were patients with recurrent oral cancer or metastatic cancer. PREDICTOR VARIABLE: The predictor variable is the preoperative serum Se concentration measured using inductively coupled plasma-mass spectrometry. MAIN OUTCOME VARIABLE(S): The primary outcome variable is DSS calculated from the date of diagnosis to the date of death due to oral cancer or the end of follow-up, whichever occurred first. COVARIATES: The covariates were age, sex, occupation, education level, body mass index, surgery therapy, adjuvant therapy, tumor node metastasis stage, and pathological grading. ANALYSES: Kaplan-Meier survival analysis, Cox proportional hazards regression, and restricted cubic spline regression were utilized. P value < .05 was significant. RESULTS: The sample was composed of 235 subjects with a median age of 59 years (ranged from 20 to 80 years) and 142 (60.43%) were male. The median follow-up was 54.90 months (interquartile range: 35.47). Se levels were associated with DSS (unadjusted hazard ratio [HR] = 0.70; 95% confidence interval [CI]: 0.54-0.91) suggesting that higher levels of Se are associated with longer or improved DSS. After adjustment of age, sex, occupation, education level, residence, tumor node metastasis stage, pathological grading, surgery therapy, radiotherapy, and chemotherapy, patients with higher serum Se had a better DSS (aHR = 0.67; 95% CI: 0.49-0.92). Of note, we found that the association between serum Se and DSS was observed only in patients with radiotherapy (aHR = 0.49; 95% CI: 0.33-0.73). And the protective effect of radiotherapy on survival was only observed in patients with higher Se concentrations (aHR = 0.36; 95% CI: 0.20-0.63). Additionally, there was a multiplicative interaction between Se and radiotherapy on the prognosis of oral cancer patients (Pinteraction<0.01). CONCLUSION AND RELEVANCE: Our findings suggest that a high Se concentration might contribute to better DSS among oral cancer patients, and the effect may partly depend on radiotherapy treatment. Given these findings, additional research should focus on the role of Se in DSS among oral cancer patients and the interaction with radiotherapy.

Antitumor effect of toosendanin on oral squamous cell carcinoma via suppression of p-STAT3.

BACKGROUND: Toosendanin (TSN) exhibits potent antitumor activity against various tumor cell lines. However, its efficacy against oral squamous cell carcinoma (OSCC) remains unknown. Here, we investigated the effects of TSN on OSCC cells in vitro and verified them in vivo using a patient-derived xenograft (PDX) model. METHODS: The effect of TSN on OSCC cells was investigated by cytotoxicity assays and flow cytometry. The expression of proteins was detected by western blotting. An OSCC PDX model was constructed to further investigate the role of TSN in regulating the function of OSCC. RESULTS: The cell viability of CAL27 and HN6 cells decreased as the concentration of TSN increased within the experimental range. Compared with controls, TSN at lower doses inhibited cell proliferation and induced apoptosis through S-phase cell cycle arrest. TSN inhibited OSCC cell proliferation by downregulating the STAT3 pathway through the inhibition of STAT3 phosphorylation. After successful construction of the OSCC PDX model with high pathological homology to the primary tumor and treatment with an intraperitoneal injection of TSN, we showed that TSN significantly reduced the tumor size of the PDX model mice without obvious toxicity. CONCLUSIONS: Both in vitro and in vivo, TSN significantly inhibits the proliferation and promoted apoptosis of OSCC cells. Furthermore, TSN demonstrates potent inhibition of STAT3 phosphorylation, indicating its potential as a promising therapeutic agent for OSCC. Therefore, TSN holds great promise as a viable drug candidate for the treatment of OSCC.

Erythrocyte ω-3 polyunsaturated fatty acids are inversely associated with the risk of oral cancer: a case-control study.

OBJECTIVES: Evidence about ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and oral cancer risk were limited. We aimed to evaluate the association of erythrocyte ω-3 PUFAs with the risk of oral cancer in a population from China. METHODS: Erythrocyte ω-3 PUFAs of 236 oral cancer patients and 300 controls were determined by gas chromatography. Restricted cubic spline and logistic regression were used to analyze the association between erythrocyte ω-3 PUFAs and oral cancer risk. The crude and adjusted OR with 95% CI was calculated. Stratification analysis was performed to explore the potential interaction between ω-3 PUFAs and other traditional risk factors such as smoking and drinking. RESULTS: Eicosapentaenoic acids (EPA), docosahexaenoic acids (DHA) and ω-3 index were negatively but non-linearly related to risk of oral cancer as observed by restricted cubic spline. The adjusted OR of EPA, DHA, and ω-3 index were 0.52 (95% CI: 0.35-0.76), 0.19 (95% CI: 0.08-0.44), 0.20 (95% CI: 0.09-0.44), respectively. Stratification analysis showed that the adverse correlation between EPA and oral cancer was only significant in the non-smoking group, while the adverse correlation of ɑ-linolenic acid (ALA), EPA, and DHA were only significant in the non-drinking group. General multiplicative interactions were observed between ω-3 PUFAs and smoking or drinking. CONCLUSIONS: Adverse but non-linear associations were observed between erythrocyte EPA, DHA, ω-3 index, and oral cancer risk. Additionally, there were multiplicative interactions between ω-3 PUFAs and other behavior factors such as smoking and drinking. The protective effect of ω-3 PUFAs maybe more significant in the non-smoking or non-drinking population.

Nutritional assessment and prognosis of oral cancer patients: a large-scale prospective study.

BACKGROUND: To evaluate and compare the prognostic performance of four nutritional indicators body mass index (BMI), serum albumin (ALB), prognostic nutritional index (PNI) and nutritional risk index (NRI) in oral cancer patients, and to predict the response to chemotherapy in patients with different nutritional status. METHODS: This prospective study which involved 1395 oral cancer patients was conducted in Fujian, China from September 2007 to November 2018. The BMI, PNI and NRI were calculated according to the following formulas: BMI = weight / height2 (kg/m2), PNI = albumin (g/l) + 0.005 × lymphocyte (count/µl) and NRI = (1.519 × albumin, g/l) + (41.7× present/ideal body weight), respectively. The univariate and multivariate Cox proportional hazards models were used to compare the prognostic value of BMI, ALB, PNI and NRI in overall survival (OS) in oral cancer. RESULTS: Patients with BMI < 18.5 kg/m2 (VS 18.5 kg/m2 ≤ BMI < 24 kg/m2) had a poor survival outcome (HR = 1.585; 95% CI: 1.207-2.082 ). ALB, PNI, NRI were inversely correlated with OS of oral cancer (HR = 0.716; 95% CI: 0.575-0.891; HR = 0.793; 95% CI: 0.633-0.992; HR = 0.588; 95% CI: 0.469-0.738, respectively). In addition, the prognostic predictive performance of NRI was superior to BMI or ALB or PNI. Interestingly, compared with patients with better nutritional status, chemotherapy was significantly associated with poorer OS in malnourished oral cancer patients. CONCLUSIONS: BMI, ALB, PNI and NRI are of prognostic value in patients with oral cancer and the prognostic performance of NRI was superior to BMI or ALB or PNI. Malnutrition (BMI < 18.5 kg/m2 or ALB< 40 g/l or PNI < 49.3 or NRI < 97.5) could predict an unfavorable response to chemotherapy in oral cancer patients.

Independent and joint effects of tea and milk consumption on oral cancer among non-smokers and non-drinkers: a case-control study in China.

This study aims to evaluate the independent and joint effects of tea and milk consumption on oral cancer risk among non-smokers and non-drinkers (NS/ND). A hospital-based case-control study was performed in Fujian, China. 421 cases and frequency-matched 1398 controls were included without tobacco smoking and alcohol drinking habits. Unconditional logistic regression model was used to assess the relationship of tea and milk consumption with oral cancer risk. Tea and milk consumption were significantly associated with decreased risk of oral cancer, the adjusted odds ratios (aORs) were 0.73 (95% CI: 0.54-0.97) and 0.69 (95% CI: 0.55-0.88), respectively. According to subgroup analysis, the inverse associations between tea consumption and oral cancer risk were only observed among the elders (>60 years) and urban residents. While the protect effect of milk drinking was more obvious in males, normal body mass index population (18.5-23.9), urban residents and those age ≤ 60 years. Additionally, a significantly multiplicative interaction between tea and milk consumption was observed for oral cancer risk (P = 0.001). The present study is the first to simultaneously assess the association of tea consumption and milk drinking with oral cancer risk. The results suggest that tea and milk consumption are independent protective factors for oral cancer among NS/ND, with a joint effect between them.

Passive smoking and cooking oil fumes (COF) may modify the association between tea consumption and oral cancer in Chinese women.

PURPOSE: To evaluate the confounding effects of passive smoking and COF exposure on association between tea and oral cancer in Chinese women. METHODS: A case-control study including 207 female oral cancer cases and 480 age-matched controls was performed in Fujian, China. Data were collected with a structured questionnaire by face-to-face interviews. The effects of tea consumption on oral cancer were, respectively, adjusted for Model-1 and Model-2 using logistic regression analysis. Model-1 did not adjusted for passive smoking and COF; Model-2 included the variables in Model-1, passive smoking and COF. RESULTS: Tea consumption was associated with a decreased risk of oral cancer in females: The OR was 0.498 (95 % CI 0.312-0.795) for Model-1 and 0.565 (95 % CI 0.352-0.907) for Model-2. The ORs for all the categories of tea consumption estimated by Model-2 were slightly higher than Model-1. When stratified by passive smoking, the statistically significant association between tea drinking and oral cancer was only emerged in non-passive smoking women. Stratification by COF found tea drinking was still associated with a decreased risk of oral cancer for women who have light-COF exposure, but an increased risk for those who subjected to heavy exposure. A negative, multiplicative interaction was found between tea consumption and COF exposure for oral cancer, but not found between tea consumption and passive smoking. CONCLUSIONS: Tea consumption reduces the risk of oral cancer in Chinese women, but this effect is modified by the carcinogenic effects of passive smoking and COF exposure.

[Effect of tea on oral cancer in nonsmokers and nondrinkers: a case-control study].

UNLABELLED: OBJECTIVE To investigate the effect of tea on oral cancer in nonsmokers and nondrinkers. METHODS: A case-control study were performed between September 2010 and January 2015 including 203 oral cancer cases in nonsmokers and nondrinkers with pathologically confirmed and 572 community controls. The related information included socio-demographic characteristics, detailed information on tobacco smoking and alcohol and tea consumption, personal medical history, family history of cancer, and occupational history were collected from all subjects. Unconditional logistic regression analysis was used to calculate the odds ratios (OR) and 95% confidence intervals (95% CI) to examine the effect of tea on oral cancer and to assess multiplicative interactions between tea and passive smoking. We also stratified by age, sex, residence, and passive smoking to explore possible difference in association between subgroups. Additive interactions between tea and passive smoking were assessed using relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: Compared with non-tea drinkers, tea consumption (OR = 0.52, 95% CI: 0.34-0.81), age of tea drinking initiation (years) ≥ 18 (OR = 0.54, 95% CI: 0.34-0.85), duration of tea consumption (years) < 20 (OR = 0.49, 95% CI: 0.27-0.90), duration of tea consumption (years) ≥ 20 (OR = 0.55, 95% CI: 0.32-0.95), average daily tea consumed < 700 ml (OR = 0.52, 95% CI: 0.32-0.86), moderate concentration of tea consumed (OR = 0.56, 95% CI: 0.32-0.96), weak concentration of tea consumed (OR = 0.35, 95% CI: 0.16-0.77), drinking green-tea (OR = 0.48, 95% CI: 0.28-0.82) and drinking moderate temperature of tea (OR = 0.55, 95% CI: 0.31-0.98) could reduce the risk of oral cancer; Stratified analysis indicated the protective effects of tea drinking on female (OR = 0.53, 95% CI: 0.30-0.94), age < 60 years old (OR = 0.53, 95% CI: 0.29-0.97), live in the urban (OR = 0.38, 95% CI: 0.20-0.69) and no passive smoking (OR = 0.47, 95% CI: 0.25-0.86) population with nonsmoking and nondrinking was more obvious; Crossover analysis showed tea and passive smoking did not exist multiplication interaction relationship (OR = 0.95, 95% CI: 0.41-2.20) and addition interaction relationship (RERI = -0.15, 95% CI: -0.92-0.62;AP = -0.16, 95% CI: -1.06-0.73; SI = -0.18, 95% CI: -1.44-0.87). CONCLUSION: Tea consumption, age of tea drinking initiation, duration of tea consumption, average daily tea consumed, concentration of tea consumed, types of tea and temperature of tea might have impact on the incidence of oral cancer in nonsmokers and nondrinkers to a certain extent.