Longitudinal Assessment of Quality of Life in Nasopharyngeal Cancer Patients Treated with Intensity-Modulated Proton Therapy and Volumetric Modulated Arc Therapy at Different Time Points.

PURPOSE: This retrospective cohort study aims to compare the quality of life (QoL) in patients with nasopharyngeal cancer (NPC) treated with intensity-modulated proton therapy (IMPT) versus volumetric modulated arc therapy (VMAT) at different time points. MATERIALS AND METHODS: We conducted a longitudinal assessment of QoL on 287 newly diagnosed NPC patients (IMPT: 41 and VMAT: 246). We collected outcomes of global QoL, functional QoL, C30 symptoms, and HN35 symptoms from EORTC QLQ-C30 and QLQ-HN35 questionnaires at pre-radiotherapy, during radiotherapy (around 40 Gy), 3 months post radiotherapy, and 12-months post radiotherapy (RT). The generalized estimating equation was utilized to interpret the group effect, originating from inherent group differences; time effect, attributed to RT effects over time; and interaction of the group and time effect. RESULTS: IMPT demonstrated superior mean dose reductions in 12 of the 16 organs at risk compared to VMAT, including a significant (>50%) reduction in the oral cavity and larynx. Both groups exhibited improved scores of global QoL, functional QoL, and C30 symptoms at 12 months post RT compared to the pre-RT status. Regarding global QoL and C30 symptoms, there was no interaction effect of group over time. In contrast, significant interaction effects were observed on functional QoL (p = 0.040) and HN35 symptoms (p = 0.004) during RT, where IMPT created an average of 7.5 points higher functional QoL and 10.7 points lower HN35 symptoms than VMAT. CONCLUSIONS: Compared to VMAT, dose reduction attributed to IMPT could translate into better functional QoL and HN35 symptoms, but the effect is time dependent and exclusively observed during the RT phase.

Towards a replacement therapy for stimulant betel quid dependence: A proof of concept study.

Stimulant betel quid (SBQ) containing Piper betle leaf (L), green unripe Areca catechu nut (AN) and the alkalizing agent, slaked lime, is an addictive, carcinogenic stimulant, with no pharmacotherapy, chewed by millions of people in the Asia/Pacific region. We compared the in vivo physiological profile of chewing (1) non-stimulant P. betle leaf+AN (LAN), (2) SBQ utilizing slaked lime and (3) a novel SBQ utilizing Mg(OH)2 , as an alkalizing agent, by measuring physiological parameters of intoxication and these were correlated with in vitro levels of alkaloids measured by UHPLC-MS/MS. Chewing LAN, which contains high levels of arecoline, had no stimulatory physiological effect. Chewing SBQ containing slaked lime or novel SBQ containing Mg(OH)2 , induced equivalent stimulatory physiological responses. In vitro, slaked lime hydrolyzed muscarinic esters in LAN while Mg(OH)2 did not. The physiological stimulation induced by chewing both SBQ and the lack of physiology to chewing LAN can be explained by changes in lipid solubility of phytochemicals induced by mouth pH during chewing of basic SBQ or acidic LAN. Since antiquity people have added slaked lime to SBQ to enhance absorption of phyto-chemicals across oral membranes to stimulate physiology. The same physiological changes can be induced by substituting slaked lime for less physically and chemically destructive bases. If attitudes regarding SBQ dependence can advance towards the more progressive attitudes already used to help smokers quit tobacco, modern chemistry has the potential to make chewing SBQ safer and quitting programs may become more accessible and efficacious.

Linking metabolic syndrome with low bone mass through insights from BMI and health behaviors.

The objective of this study is to investigate the relationship between metabolic syndrome (MetS), and bone density in a 30- to 50-year-old Taiwanese population, and to explore the combined effects of BMI and health behaviors on this association. A total of 52,912 individuals aged 30-50 years from the Taiwan Biobank were included in this cross-sectional study. Bone density status was assessed using quantitative ultrasound (QUS). The joint effect was assessed by including an interaction term in the multi-logistic regression models to test the association between MetS, BMI, and bone density while controlling for potential confounders. MetS was associated with reduced bone density, with the risk of severe low bone density (SLBD) higher among BMI < 24 kg/m2 individuals with MetS (adjusted odds ratio [aOR] 1.5, 95% confidence interval [CI] 1.09-2.16), while the risk was not significant among BMI ≥ 24 kg/m2 individuals with MetS. Smoking, alcohol consumption, and lack of regular exercise among individuals with a BMI < 24 kg/m2 and MetS were associated with higher risk of severe low bone density (SLBD), the aORs (95%CI) were 2.9 (1.59-5.20), 2.1 (1.06-4.22), and 1.8 (1.24-2.54) respectively. Our study suggests that metabolic syndrome could increase the risk of severe low bone density, but this risk can be minimized through higher BMI, non-smoking, no alcohol consumption, and regular exercise. Conversely, smoking, alcohol consumption or lack of regular exercise may exacerbate the risk of severe low bone density. These findings highlight the importance of a multifactorial approach in managing bone healthcare.

Effects of DSM-5 Betel-Quid-Related Symptoms, Pathological Behaviors, and Use Disorder on Oral Squamous Cell Carcinoma Risk.

The neuroactive alkaloids in betel quid (BQ) can induce BQ addiction. We conducted a case-control study to investigate the effects of BQ-associated DSM-5 symptoms, pathological behaviors, and BQ use disorder (BUD) on oral squamous cell carcinoma (OSCC) risk. A total of 233 patients with newly diagnosed and histopathologically confirmed OSCC and 301 sex- and age-matched controls were included. BQ-related DSM-5 symptoms in the 12 months prior to disease onset were used to measure psychiatric characteristics and BUD. Compared with nonchewers, chewers with the symptoms of unsuccessful cutdown of BQ consumption, neglecting major roles, social or interpersonal problems, abandoning or limiting activities, hazardous use, and continued use despite the awareness of the dangers had a 54.8-, 49.3-, 49.9-, 40.4-, 86.2-, and 42.9-fold higher risk of developing OSCC, respectively. Mild-to-moderate and severe BUD were, respectively, associated with a 8.2-8.5- and 42.3-fold higher OSCC risk, compared with BQ nonuse. Risky BQ use of pathological behavior was associated with a 12.5-fold higher OSCC risk in chewers with no BUD or mild BUD and a 65.0-fold higher risk in chewers with moderate-to-severe BUD (p for risk heterogeneity between the two BUD groups, 0.041). In conclusion, BQ-associated DSM-5 symptoms, pathological behaviors, and BUD severity are associated with the impact of BQ chewing on OSCC development. The pathological behavior of risky BQ use enhances OSCC risk in chewers with moderate-to-severe BUD. Preventing BUD in new BQ users and treating BUD in chewers who already have the disorder are two priorities in areas where BQ chewing is prevalent.

Effectiveness of end-stage renal disease communication skills training for healthcare personnel: a single-center, single-blind, randomized study.

BACKGROUND: Given that the consequences of treatment decisions for end-stage renal disease (ESRD) patients are long-term and significant, good communication skills are indispensable for health care personnel (HCP) working in nephrology. However, HCP have busy schedules that make participation in face-to-face courses difficult. Thus, online curricula are a rising trend in medical education. This study aims to examine the effectiveness of online ESRD communication skills training (CST) concerning the truth-telling confidence and shared decision-making (SDM) ability of HCP. METHODS: For this single-center, single-blind study, 91 participants (nephrologists and nephrology nurses) were randomly assigned to two groups, the intervention group (IG) (n = 45) or the control group (CG) (n = 46), with the IG participating in ESRD CST and the CG receiving regular in-service training. Truth-telling confidence and SDM ability were measured before (T0), 2 weeks after (T1), and 4 weeks after (T2) the intervention. Group differences over the study period were analyzed by generalized estimating equations. RESULTS: IG participants exhibited significantly higher truth-telling confidence at T1 than did CG participants (t = 2.833, P = .006, Cohen's d = 0.59), while there were no significant intergroup differences in the confidence levels of participants in the two groups at T0 and T2. Concerning SDM ability, there were no significant intergroup differences at any of the three time points. However, IG participants had high levels of satisfaction (n = 43, 95%) and were willing to recommend ESRD CST to others (n = 41, 91.1%). CONCLUSIONS: ESRD CST enhanced short-term truth-telling confidence, though it is unclear whether this was due to CST content or the online delivery. However, during pandemics, when face-to-face training is unsuitable, online CST is an indispensable tool. Future CST intervention studies should carefully design interactive modules and control for method of instruction.

Betel Quid Dependence Effects on Working Memory and Remote Memory in Chewers with Concurrent Use of Cigarette and Alcohol.

OBJECTIVE: The current study asked whether BQ dependence level could affect working memory (WM) and remote memory for the chewers with concurrent use of cigarettes and alcohol, a common phenomenon in Taiwan. METHODS: The standardized neuropsychological tests (Wechsler Memory Scale III (WMS-III) and Remote Memory Test) were adopted to address the BQ chewers' verbal WM, spatial WM and remote memory. The Spatial Span Test and the Digit Span Test from WMS-III and the Remote Memory Test were adopted. The Betel Nut Dependency Scale (BNDS), the Fagerstrom Test for Nicotine Dependence (FTND), and the Alcohol Use Disorders Identification Test (AUDIT) were adopted to measure the dependence levels. RESULTS: The BQ dependence level and Last BQ did not affect spatial WM, verbal WM, and remote memory. Last Cigarette is critical in affecting WM; namely, longer interval led to worse performance. Finally, higher alcohol dependence level could lead to better remote memory. CONCLUSIONS: To our knowledge, there are no BQ studies addressing the effects of concurrent use of cigarettes and alcohol on memory. The current results suggest that cigarette smoking and alcohol drinking, rather than BQ chewing, are critical for memory performance.

Rapid green analytical methodology for simultaneous biomonitoring of five toxic areca nut alkaloids using UHPLC-MS/MS for predicting health hazardous risks.

Areca nut (AN) is a fundamental component of betel quid (BQ), an addictive and carcinogenic mixture chewed by hundreds of millions of people in India-Asia-Pacific. Chewing of BQ is associated with oral cancers due to specific carcinogenic alkaloids (arecaidine, guvacine, guvacoline, arecoline, N-Nitrosoguvacoline) in AN. To predict the hazardous health risks of short and long-term chewing of BQ, it is crucial to identify five toxic AN alkaloids in saliva and urine of BQ chewers. This study reports a green analytical methodology comprising in-syringe assisted vortex-induced salt-enhanced liquid-liquid microextraction coupled with ultra-HPLC-MS/MS for simultaneous biomonitoring of five AN alkaloids in saliva and urine. The analytical method validation results exhibited good linearities between 0.05 and 1000 ng mL-1 with r2 > 0.9930. The detection and quantification limits were between 0.01 and 1.5 and 0.05-5 ng mL-1. Relative recoveries ranged between 87.9% and 110.1% with RSD < 9.1% for saliva samples, 81.5-115.1% with RSD < 9.7% for urine samples. The results indicated the successful identification and real-time monitoring of concentrations of five target AN alkaloids in saliva and urine of BQ chewers and demonstrated the utility of this technique as an efficient analytical protocol for routine biomonitoring of levels of toxic AN alkaloids from BQ chewers and to predict the exposure level and its harmful health risk.

Quality of Life as a Mediator between Cancer Stage and Long-Term Mortality in Nasopharyngeal Cancer Patients Treated with Intensity-Modulated Radiotherapy.

BACKGROUND: Quality of life (QoL) attained before, during, or after treatments is recognized as a vital factor associated with therapeutic benefits in cancer patients. This nasopharyngeal cancer (NPC) patient longitudinal study assessed the relationship among QoL, cancer stage, and long-term mortality in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). PATIENTS AND METHODS: The European Organization for Research and Treatment of Cancer (EORTC) core QoL questionnaire (QLQ-C30) and the head and neck cancer-specific QoL questionnaire module (QLQ-HN35) were employed to evaluate four-dimensional QoL outcomes at five time points: pre- (n = 682), during (around 40 Gy) (n = 675), 3 months (n = 640), 1 year (n = 578) and 2 years post-IMRT (n = 505), respectively, for 682 newly diagnosed NPC patients treated between 2003 and 2017 at a single institute. The median followed-up time was 7.5 years, ranging from 0.3 to 16.1 years. Generalized estimating equations, multivariable proportional hazards models, and Baron and Kenny's method were used to assess the investigated effects. RESULTS: Advanced AJCC stage (III-IV) patients revealed a 2.26-fold (95% CI-1.56 to 3.27) higher covariate-adjusted mortality risk than early-stage (I-II) patients. Compared with during IMRT, advanced-stage patients had a significantly low global health QoL and a significantly high QoL-HN35 symptom by a large magnitude at pre-, 3 months, and 2 years post-IMRT. QoL scales at pre-IMRT, 1 year, and 2 years post-IMRT were significantly associated with mortality. The effect changes of mortality risk explained by global health QoL, QoL-C30, and QoL-HN35 symptom were 5.8-9.8% at pre-IMRT but at 2 years post-IMRT were 39.4-49.4% by global health QoL and QoL-HN35 symptoms. CONCLUSIONS: We concluded advanced cancer stage correlates with a long-term high mortality in NPC patients treated with IMRT and the association is partially intermediated by QoL at pre-IMRT and 2 years post-IMRT. Therefore, QoL-HN35 symptom and global health QoL-dependent medical support and care should be focused and tailored at 2 years post-IMRT.

Reduction in and Preventive Effects for Oral-Cancer Risk with Antidepressant Treatment.

Areca nut (AN) was identified as carcinogenic to humans. Around 600 million people globally use AN in some form, yet no effective therapeutic drug is available to overcome AN addiction. This preclinical study examines the effects of antidepressants on AN use with animal models. We produced AN powder and dissolved it into drinking water, training 55 C57BL/6 mice in free self-selection to drink AN water or normal water. Then, the mice were randomly divided into four groups. Selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants (TCAs) were given as three treatment groups and one placebo group for four weeks. In the follow-up period, the preference and amount of free selection of AN and normal water, and oral pathological change were evaluated. There was a significant decrease in preference for AN drinking during the first four weeks, and the 36th week after drug withdrawal in the MAOI and SSRI groups (all p < 0.05). The drug-reducing effect of AN water in the 1-4-week period was significant in the MAOI group (p < 0.0001) and was also significant in the 3-4-week period in the SSRI group (p = 0.03). The TCA group did not show a decrease effect. At the endpoint (60 weeks), oral mucosal fibrosis (OSF) levels and risk in the SSRI (p = 0.0081) and MAOI (p = 0.01) groups were significantly lower than those in the control group. Antidepressant drugs MAOIs and SSRIs could reduce the amount of AN use and decrease the early stage of oral fibrosis in mice, but SSRIs may need to be boosted again.

Cigarette Smoke Containing Acrolein Upregulates EGFR Signaling Contributing to Oral Tumorigenesis In Vitro and In Vivo.

Oral squamous cell carcinoma (OSCC) accounts for 80-90% of all intraoral malignant neoplasms. The single greatest risk factor for oral cancer is tobacco use, including cigarettes, cigars, chewing tobacco, and snuff. Aberrations of the epidermal growth factor receptor (EGFR) pathway features prominently in oral tumorigenesis and progression. It was shown that cigarette smoking (CS) is associated with worse prognosis in OSCC patients and overexpression of EGFR in tumor tissue. However, the mechanism by which cigarette smoking induced EGFR pathway activation remains to be fully elucidated. Acrolein, an IARC group 2A carcinogen, is a highly reactive aldehyde found in CS. Here we report that acrolein is capable of inducing tumorigenic transformation in normal human oral keratinocytes (NOK). The acrolein-transformed NOK cells showed EGFR copy number amplification, increased EGFR expression, and activation of downstream ERK and AKT signaling pathway. No p53 mutations were observed in acrolein-transformed NOK cells. Inhibiting EGFR pathway using an anti-EGFR antibody, cetuximab, inhibits tumor growth. Furthermore, by examining tissue sample from patients, we found an increased EGFR copy number was positively associated with acrolein-induced DNA damages in OSCC patients. Taken together, our results indicate that acrolein is important in tumorigenic transformation through amplification of EGFR and activating the downstream signaling pathway, contributing to oral carcinogenesis. This is the first study to provide molecular evidence showing that CS containing acrolein contributes to EGFR amplification in OSCC.

Characteristic-Grouped Adiposity Indicators for Identifying Metabolic Syndrome in Adolescents: Develop and Valid Risk Screening Tools Using Dual Population.

A simple, robust, and characterized adiposity indicator may be appropriate to be used as a risk screening tool for identifying metabolic syndrome (MetS) in adolescents. This study used dual adolescent populations to develop and validate efficient adiposity indicators from 12 characterized candidates for identifying MetS that may occur during the transition from adolescence to young adulthood. Data from the adolescent Nutrition and Health Survey in Taiwan (n = 1920, 12-18 years) and the multilevel Risk Profiles for adolescent MetS study (n = 2727, 12-16 years) were respectively used as training and validation datasets. The diagnostic criteria defined by the International Diabetes Federation for adolescents (IDF-adoMetS) and the Joint Interim Statement for adults (JIS-AdMetS) were employed to evaluate MetS. In the training dataset, principal component analysis converted 12 interrelated obesity indices into bodyfat-, lipid-, and body-shape-enhanced groups, with the first two characteristic-groups having a higher discriminatory capability in identifying IDF-adoMetS and JIS-AdMetS. In the validation dataset, abdominal volume index (AVI) among girls and waist circumference (WC) among boys were respectively validated to have a higher Youden's index (0.740-0.816 and 0.798-0.884) in identifying the two MetS. Every 7.4 and 4.3 positive tests of AVI (cutoff = 13.96) had an accurate IDF-adoMetS and JIS-AdMetS, respectively, and every 32.4 total tests of WC (cutoff = 90.5 cm) had a correct identification for the two MetS. This study stresses the discriminatory capability of bodyfat- and lipid-enhanced adiposity indicators for identifying MetS. AVI and WC were, respectively, supported as a risk screening tool for identifying female and male MetS as adolescents transition to adulthood.

Betel quid-associated cancer: Prevention strategies and targeted treatment.

Betel quid (BQ) and areca nut use are at risk of cancer. This review includes the latest evidence of carcinogenesis caused by BQ exposure, suggests possible prevention strategies. We conducted a systematic literature search in the PubMed and Web of Science databases to identify relevant articles published in the past 10 years according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Arecoline N-oxide, a metabolite of areca nut, is likely an initiator in carcinogenesis and is detoxified by N-acetylcysteine. Oral potentially malignant disorder and reactive oxygen species involved in carcinogenesis pathways may be treatable using antioxidants. Screening programs conducted by trained physicians are useful for identifying patients with early stages of oral cancer in high-risk groups. Anti-inflammatory medications may be used as chemopreventive agents in the disease-free stage after surgery. The association between survival and tumor somatic mutations in patients who chew BQ should be addressed in cancer studies. Current evidence on the natural course from BQ exposure to cancer occurrence and development provides information for developing primary, secondary, and tertiary prevention strategies against BQ-associated cancer at clinical or translational levels.

Antidepressant-induced reduction in betel-quid use in patients with depression: A pioneer clinical study.

Betel-quid is commonly used around the world and is listed as a Group I carcinogen. Prior research has suggested a possible association between antidepressants and betel-quid use. We aimed to clarify the effects of antidepressant therapy in betel-quid chewers in the population of patients with depression.We enrolled 204 patients with depressive disorders, collected their demographic information, and administered the Substance Use Severity Rating Scale for alcohol, cigarettes, and betel-quid and the Hamilton Depression Rating Scale. We compared betel-quid and non-betel-quid chewers and examined the effects of antidepressant therapy on betel-quid abstinence after previous exposure to betel-quid.Patients with depression were reported a higher prevalence of 26% betel-quid chewing habits and patients who chewed betel-quid showed more severe depressive symptoms. After antidepressant therapy, the addictiveness of betel-quid was significantly reduced by 4 times.This was a pioneering study showing that antidepressants could be a candidate for betel-quid cessation therapy. Future clinical trials are needed to verify their efficacy in reducing consumption for betel-quid addiction treatment.

A haplotype-specific linkage disequilibrium pattern of monoamine oxidase A gene associated with regular smoking in women.

BACKGROUND: Cigarette smoking in women is raising a public health problem. The X-linked monoamine oxidase A (MAOA) was considered as a susceptibility gene to substance abuse of tobacco, but the evolutionary effect of MAOA may lead to a positive or negative association between genetic variations and smoking development among study regions. METHODS: Based on linkage disequilibrium (LD), we performed a haplotype-based association to explore the effect of MAOA gene on women's smoking risk in a case-control study. RESULTS: Genotyped single nucleotide polymorphisms (SNPs) of MAOA gene, rs5953210G>A, rs2283725A>G and rs1137070T>C, were significantly associated with current smoking risk in women, and the increased level of plasma MAO-A activity was raised with per copy increment of risk allele in current smokers (P < .01). The haplotype patterns with minor haplotype frequency >.05 were constructed using the Expectation-Maximization algorithm, and the haplotype-specific A-G-C pattern raised the 2-fold risk to develop regular smoking (P = .0005). In the diplotype analysis based on X-inactivation mechanism relative to no and full dosage compensation, we showed that A-G-C haplotype not only increased regular smoking risk in a dose-dependent manner (Ptrend = .0011) but also contributed to smoking risk in the dosage compensation mechanism. Compared to non-smokers, the effect of A-G-C haplotype on random X-activation was associated with the raised MAO-A activity in women smokers (P < .05) although the lifetime cigarette consumption showed a difference that was not statistically significant. CONCLUSION: This study provides information on MAOA LD-based haplotype and diplotype patterns in women smoking.

Effectiveness of a health belief model intervention using a lay health advisor strategy on mouth self-examination and cancer screening in remote aboriginal communities: A randomized controlled trial.

OBJECTIVE: Oral cancers caused by chewing betel nuts have a poor prognosis. Using a lay health advisor (LHA) can increase access to health care among underprivileged populations. This study evaluated a health belief model (HBM) intervention using LHAs for oral cancer screening (OCS) and mouth self-examination (MSE) in remote aboriginal communities. METHODS: The participants were randomly assigned to intervention (IG; n = 171) and control groups (CG; n = 176). In the IG, participants received a three-chapter one-on-one teaching course from LHAs, whereas those in the CG received only a leaflet. RESULTS: The IG participants were 2.04 times more likely to conduct a monthly MSE than those in the CG (95% confidence interval: 1.31-3.17) and showed significantly higher self-efficacy levels toward OSC and MSE (ß = 0.53 and 0.44, effect size = 0.33 and 0.25, respectively) and a lower barrier level for OSC (ß = -1.81, effect size = -0.24). CONCLUSION: The LHA intervention had a significantly positive effect on MSE, strengthening self-efficacy and reducing barriers to OCS among aboriginal populations. PRACTICE IMPLICATIONS: The effectiveness of the clinical treatment of underprivileged group can be improved through early diagnosis, which can be achieved using LHAs to reduce barriers to OSC.

Betel quid containing safrole enhances metabolic activation of tobacco specific 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).

Cigarette smoking (CS) and betel quid (BQ) chewing are two known risk factors that have synergistic potential for the enhancing the development of oral squamous cell carcinoma (OSCC) in Taiwan. Most mutagens and carcinogens are metabolically activated by cytochrome P450 (CYP450) to exert their mutagenicity or carcinogenicity. Previous studies have shown that metabolic activation of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), by CYP2A6 activity determines NNK-induced carcinogenesis. In addition, safrole affects cytochrome P450 activity in rodents. However, the effect of BQ safrole on the metabolism of tobacco-specific NNK and its carcinogenicity remains elusive. This study demonstrates that safrole (1 mg/kg/d) induced CYP2A6 activity, reduced urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels, and increased NNK-induced DNA damage, including N7-methylguanine, 8-OH-deoxyguanosine and DNA strand breaks in a Syrian golden hamster model. Furthermore, altered NNK metabolism and increased NNK-induced DNA damage were also observed in healthy subjects with CS and BQ chewing histories compared to healthy subjects with CS histories. In conclusion, BQ containing safrole induced tobacco-specific NNK metabolic activation, resulting in higher NNK-induced genotoxicity. This study provides valuable insight into the synergistic mechanisms of CS- and BQ-induced OSCC.

Acrolein Is Involved in the Synergistic Potential of Cigarette Smoking- and Betel Quid Chewing-Related Human Oral Cancer.

BACKGROUND: Cigarette smoking (CS) and betel quid (BQ) chewing are two known risk factors and have synergistic potential for the development of oral squamous cell carcinoma (OSCC) in Taiwan. The p53 mutation characteristics in OSCC (G to A or G to T mutations) are similar to that of acrolein-induced DNA damage. Acrolein is a major cigarette-related carcinogen that preferentially causes p53 mutations and inhibits DNA repair function in lung cancer. We hypothesize that acrolein is associated with OSCC carcinogenesis. METHODS: A total of 97 patients with OSCC and 230 healthy subjects with CS and/or BQ chewing histories were recruited. Slot blot analysis of Acr-dG adducts, an indicator of acrolein-induced DNA damage in buccal DNA, and LC/MS-MS analysis of 3-HPMA levels, urinary Acr metabolites, were performed. RESULTS: Our results showed that the level of Acr-dG adducts in buccal cells was 1.4-fold higher in patients with OSCC than in healthy subjects with CS and/or BQ chewing histories (P < 0.001). In addition, in healthy subjects, CS and BQ chewing were associated with significantly higher levels of 3-HPMA, indicating that CS and BQ chewing promotes acrolein absorption. However, 3-HPMA levels in patients with OSCC were significantly lower than those in healthy subjects, indicating impaired acrolein metabolism. CONCLUSIONS: In this study, we provide a novel mechanism by which increased acrolein uptake and impaired metabolism may contribute to the synergistic potential of CS and BQ-induced OSCC. IMPACT: Elevated acrolein-induced DNA damage (Acr-dG adducts) detected in buccal swabs may serve as an early indicator to identify patients at risk of developing OSCC.

Clustering of Metabolic Risk Components and Associated Lifestyle Factors: A Nationwide Adolescent Study in Taiwan.

Clustering of metabolic syndrome (MetS) risk components in childhood has been linked to a higher risk of diabetes and cardiovascular diseases in adulthood. By using data from the 2010⁻2011 Nutrition and Health Survey in Taiwan, this study investigated epidemic patterns and correlates for the clustering of MetS risk components. A total of 1920 adolescents aged 12⁻18 years were included in this study. The MetS diagnostic criteria defined by the Taiwan Pediatric Association (TPA) and International Diabetes Federation (IDF) for adolescents and the criteria defined by the Joint Interim Statement for adults (JIS-Adult) were used to evaluate MetS and its abnormal components. The prevalence of TPA-, IDF-, and JIS-Adult-defined MetS was 4.1%, 3.0%, and 4.0%, with 22.1%, 19.3%, and 17.7%⁻18.1% of adolescents having high fasting glucose, low high-density lipoprotein cholesterol, and central obesity, respectively. A 0.4-to-0.5-fold decreased risk of having ≥2 MetS abnormal components was detected among adolescents who consumed ≥1 serving/week of dairy products and fresh fruits. Boys who consumed ≥7 drinks/week of soda and girls who consumed ≥7 drinks/week of tea had a 4.6- and 5.2-fold risk of MetS, respectively. In conclusion, our findings revealed significant dimensions of adolescent MetS, including detecting population-specific prevalent patterns for MetS risk components and their clustering, and emphasized on health promotion activities that reduce sugar-sweetened beverage intake.

Variants in FAT1 and COL9A1 genes in male population with or without substance use to assess the risk factors for oral malignancy.

A number of genetic variants were suggested to be associated with oral malignancy, few variants can be replicated. The aim of this study was to identify significant variants that enhanced personal risk prediction for oral malignancy. A total of 360 patients diagnosed with oral squamous cell carcinoma, 486 controls and 17 newly diagnosed patients with OPMD including leukoplakia or oral submucous fibrosis were recruited. Fifteen tagSNPs which were derived from somatic mutations were genotyped and examined in associations with the occurrence of oral malignancy. Environmental variables along with the SNPs data were used to developed risk predictive models for oral malignancy occurrence. The stepwise model analysis was conducted to fit the best model in an economically efficient way. Two tagSNPs, rs28647489 in FAT1 gene and rs550675 in COL9A1 gene, were significantly associated with the risk of oral malignancy. The sensitivity and specificity were 85.7% and 85.5%, respectively (area under the receiver operating characteristic curve (AUC) was 0.91) for predicting oral squamous cell carcinoma occurrence with the combined genetic variants, betel-quid, alcohol and age. The AUC for OPMD was only 0.69. The predictive probability of squamous cell carcinoma occurrence for genetic risk score without substance use increased from 10% up to 43%; with substance use increased from 73% up to 92%. Genetic variants with or without substance use may enhance risk prediction for oral malignancy occurrence in male population. The prediction model may be useful as a clinical index for oral malignancy occurrence and its risk assessments.

Changes in Trace Elements During Early Stages of Chronic Kidney Disease in Type 2 Diabetic Patients.

Trace elements can influence glucose metabolism and be related to oxidative stress in type 2 diabetes mellitus. Moreover, trace elements play important roles in the nephrotic complications of these patients. Nevertheless, few investigations have been made into the changes in the levels of trace elements in diabetic patients at various stages of chronic kidney disease (CKD). The aims of this present study were to determine the levels of some important trace elements in diabetic patients during the early stages of CKD and to identify the relationship between these elements and CKD progression in type 2 diabetic patients. One hundred and forty-eight type 2 diabetic patients with chronic kidney diseases were recruited into this study. The subjects were grouped into four stages (1, 2, 3a, 3b) of CKD, according to their urine protein levels and estimated glomerular filtration rates (eGFRs). The levels of serum zinc and iron exhibited a statistically significant decreasing trend (P trend = 0.032 and 0.047, respectively) from stage 1 to stage 3b after adjustment for age, gender, smoking, alcohol consumption, education, hypertension, and body mass index. The other tested elements, including copper, magnesium, selenium, chromium, and manganese, did not display any significant trends upon proceeding from stage 1 to stage 3b. Thus, serum zinc and iron appear to be useful markers when evaluating the early progression of CKD in type 2 diabetic patients.