Risk Of Laryngeal Cancer Research Articles

Adherence to a low-fat dietary pattern reduces head and neck cancer risk: evidence from the PLCO trial

PurposeLow-fat dietary (LFD) pattern refers to a dietary structure with reduced fat intake. The aim was to investigate the association between LFD pattern and risk of head and neck cancer (HNC).MethodsData were derived from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. LFD score was used to assess adherence to an LFD pattern, with higher scores indicating greater adherence. Cox regression was used to evaluate the association between LFD score and risk of HNC and its subtypes. To visualize the trend in risk of HNC and its subtypes with changing LFD score, restricted cubic spline plots were utilized. A series of subgroup analyses were conducted to identify potential confounders. Sensitivity analyses were performed to assess the robustness of the results.ResultsAmong 98,459 participants of PLCO trial, 268 cases with HNC were identified during an average of 8.8 years of follow-up. In the fully adjusted model, participants in the highest compared with the lowest quartiles of LFD score had a lower risk of HNC (HR Q4 vs. Q1: 0.60; 95% CI: 0.40–0.90; P for trend = 0.026) and larynx cancer (HRQ4 vs. Q1: 0.46; 95% CI: 0.22–0.96; P for trend = 0.039). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of HNC and its subtypes (all P for nonlinearity > 0.05). The primary association remained robust in the sensitivity analysis.ConclusionOur findings suggest that adherence to an LFD pattern may lower the risk of HNC in the US population.

Cannabis Use and Head and Neck Cancer

Cannabis is the most commonly used illicit substance worldwide. Whether cannabis use is associated with head and neck cancer (HNC) is unclear. To assess the clinical association between cannabis use and HNC. This large multicenter cohort study used clinical records from a database that included 20 years of data (through April 2024) from 64 health care organizations. A database was searched for medical records for US adults with and without cannabis-related disorder who had recorded outpatient hospital clinic visits and no prior history of HNC. Propensity score matching was performed for demographic characteristics, alcohol-related disorders, and tobacco use. Subsequently, relative risks (RRs) were calculated to explore risk of HNC, including HNC subsites. This analysis was repeated among those younger than 60 years and 60 years or older. Cannabis-related disorder. Diagnosis of HNC and any HNC subsite. The cannabis-related disorder cohort included 116 076 individuals (51 646 women [44.5%]) with a mean (SD) age of 46.4 (16.8) years. The non-cannabis-related disorder cohort included 3 985 286 individuals (2 173 684 women [54.5%]) with a mean (SD) age of 60.8 (20.6) years. The rate of new HNC diagnosis in all sites was higher in the cannabis-related disorder cohort. After matching (n = 115 865 per group), patients with cannabis-related disorder had a higher risk of any HNC (RR, 3.49; 95% CI, 2.78-4.39) than those without HNC. A site-specific analysis yielded that those with cannabis-related disorder had a higher risk of oral (RR, 2.51; 95% CI, 1.81-3.47), oropharyngeal (RR, 4.90; 95% CI, 2.99-8.02), and laryngeal (RR, 8.39; 95% CI, 4.72-14.90) cancer. Results were consistent when stratifying by older and younger age group. This cohort study highlights an association between cannabis-related disorder and the development of HNC in adult patients. Given the limitations of the database, future research should examine the mechanism of this association and analyze dose response with strong controls to further support evidence of cannabis use as a risk factor for HNCs.

Deregulation of MMP-2 and MMP-9 in laryngeal cancer: A retrospective observational study.

Laryngeal carcinoma (LC) is reported to have a higher incidence rate among all types of head and neck cancers around the globe. Mechanisms resulting in the pathogenesis of LC are complicated due to involvement of invasion and metastasis and there is a need to understand this complicated multistep process. Numerous molecules including matrix metalloproteinases (MMPs) are involved in regulating metastatic mechanisms. Furthermore, activation and expression of different classes of MMPs have been observed in multiple pathological and physiological events including inflammation, invasion, and metastasis. Among all members of MMPs, matrix metalloproteinases-2 (MMP-2), and matrix metalloproteinases-9 (MMP-9) have been frequently reported to correlate with tumor pathogenesis. The present study is designed to check the involvement of MMP-2 and MMP-9 in LC pathogenesis. 184 laryngeal tumor samples along with adjacent uninvolved healthy sections were collected to check the expression deregulation of the above-mentioned gene in LC using real-time PCR and immunohistochemistry (IHC). Real-time PCR and IHC analyses showed the significant upregulation of MMP-2 (P < .0001) and MMP-9 (P < .0001) genes in laryngeal tumors compared to controls. Spearman correlation showed the positive correlation of expression deregulation of selected MMPs with advanced TNM stage [MMP-2, (P < .0001); MMP-9, P < .0001] and smoking status [MMP-2 (P < .0001); MMP-9 P < .0001] in laryngeal pathogenesis. Receiver operating curve (ROC) analysis showed the good diagnostic/prognostic value of said markers in laryngeal cancer patients. The present study showed that significant upregulation of selected MMPs was found associated with an increased risk of laryngeal cancer and can act as good diagnostic markers for the detection of said disease.

Role of multidetector computed tomography in assessment of laryngeal cancer: experiences from 31 cases

Aims. To compare the efficacy of computed tomography from endoscopic examination in diagnosing and staging laryngeal carcinoma. Methods. From February 2019 to July 2020, we conducted a retrospective study on patients with laryngeal carcinoma. After receiving a clinical diagnosis of laryngeal masses, patients underwent indirect laryngoscopy evaluation before being referred for computed tomography (CT) scans. A postimaging biopsy was undertaken via direct laryngoscopy. Imaging features of the tumor, such as size, level of invasion, and tumor staging, were analyzed. Results. The mean age was 61±11, with 90% of male patients. The risk of laryngeal cancer for those patients who were active smokers (93.5%) and alcohol consumers (67.7%). The most common symptom was hoarseness (93.5%). In CT image, more than half of the cancers were carcinoma of the glottis (29%) and two regions, supraglottis and glottis (22.6%), while the less common cancers were the subglottic (3.2%) and all three regions (9.7%) carcinoma, especially true vocal cord (67.7%) is the most common site starting carcinoma. The percentage of tumor spreading to paraglottic space and pre-epiglottic space was 50% and 30.6%, respectively. The most common stage of laryngeal cancer in CT was the T3 stage (35.5%). Compared to laryngoscopy, there is a weak agreement (Kappa=0.518) in staging in laryngeal cancer in CT. Conclusion. MDCT is better in staging of laryngeal cancer in the T3 and T4 stages as compared to laryngoscopy.

DIAPH2 gene polymorphisms and laryngeal cancer risk in men

BackgroundThe DIAPH2 gene is one of the genes commonly associated with laryngeal squamous cell carcinoma (LSCC). In our study, we considered the four polymorphisms of this gene, i.e. rs5920828, rs4322175, rs12851931 and rs5921830 as potential genetic risk factors for LSCC.MethodsWe determined the genotyping of the genetic variants of DIAPH2 in 230 male patients with histologically confirmed LSCC compared to the European population. Demographic and environmental exposure data of each subject were examined. To conduct the genetic tests, extraction of total DNA was performed. We genotyped all four variants in each patient and determined their frequencies.ResultsIn the case of the rs12851931 polymorphism in the DIAPH2 gene, a significant difference was observed in the distribution of the T stage depending on the polymorphism. Heterozygotes were more often associated with T2 stage, while homozygotes were more likely to have higher tumor stages. The rs12851931 homozygotes of DIAPH2 were statistically significantly more prevalent in smokers. The results suggested that rs12851931 polymorphism in DIAPH2 could increase the onset risk of LSCC.ConclusionsOur results provide further information on the role of the DIAPH2 gene in the pathogenesis of LSCC.

Study on the Association of XRCC1 Gene rs72484243 Polymorphisms with Increased Laryngeal Cancer Risk

Objective: To study the association of X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms with increased laryngeal cancer risk. Methods: A total of 120 individuals, comprising 60 patients with laryngeal squamous cell carcinoma (LSCC), and 60 healthy volunteers participated were selected. Blood samples were taken and analyzed, and 4 XRCC1 polymorphisms (rs145135970, rs1799780, rs25489, and rs72484243) were genotyped. Results: Gender, age, body mass index (BMI), and smoking habits were shown to be the high-risk factors for LSCC. Genotype and allele distributions for the 4 polymorphisms differed significantly between both groups (P &lt; 0.05). Furthermore, carriers with the rs72484243GTGT- allele exhibited an increased risk of LSCC relative to those who had the rs145135970 GTGTGTGTGTGTGT- allele, the rs1799780 G-A allele, or the rs25489 C-T allele, as determined by binary logistic regression analysis (OR = 2.74, 95% CI: 1.27–5.91, P = 0.01), after accounting for possible co-factors like sex, age, BMI, drinking and smoking behavior, and special diet requirements. In addition, a TA haplotype and a GTGTGTGTGTGTGTTG haplotype were linked to LSCC in Chinese populations in a haploid association study of 4 SNP loci in the XRCC1 gene (P = 0.05 OR = 1.36, 95% CI = 1.1228–1.6406). Conclusion: Genetic polymorphisms of the XRCC1 gene at the rs72484243 site were correlated with an elevated risk of LSCC among the Xinjiang population.

Combined PIK3CA and SOX2 Gene Amplification Predicts Laryngeal Cancer Risk beyond Histopathological Grading.

The PIK3CA and SOX2 genes map at 3q26, a chromosomal region frequently amplified in head and neck cancers, which is associated with poor prognosis. This study explores the clinical significance of PIK3CA and SOX2 gene amplification in early tumorigenesis. Gene copy number was analyzed by real-time PCR in 62 laryngeal precancerous lesions and correlated with histopathological grading and laryngeal cancer risk. Amplification of the SOX2 and PIK3CA genes was frequently detected in 19 (31%) and 32 (52%) laryngeal dysplasias, respectively, and co-amplification in 18 (29%) cases. The PIK3CA and SOX2 amplifications were predominant in high-grade dysplasias and significantly associated with laryngeal cancer risk beyond histological criteria. Multivariable Cox analysis further revealed PIK3CA gene amplification as an independent predictor of laryngeal cancer development. Interestingly, combined PIK3CA and SOX2 amplification allowed us to distinguish three cancer risk subgroups, and PIK3CA and SOX2 co-amplification was found the strongest predictor by ROC analysis. Our data demonstrate the clinical relevance of PIK3CA and SOX2 amplification in early laryngeal tumorigenesis. Remarkably, PIK3CA amplification was found to be an independent cancer predictor. Furthermore, combined PIK3CA and SOX2 amplification is emerging as a valuable and easy-to-implement tool for cancer risk assessment in patients with laryngeal precancerous lesions beyond current WHO histological grading.

Aspirin intake and head and neck cancer: A pooled analysis within the INHANCE consortium.

Aspirin intake might be inversely associated with head and neck cancer (HNC). Thus, we investigated this relationship within the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Four case-control studies within the INHANCE consortium were included (2024 cases, 4196 controls). Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression and subsequently pooled with DerSimonian-Laird random-effects model. Nonlinearity of the relationship between duration of intake and HNC was modeled with fractional polynomials. Aspirin was inversely associated with HNC overall (OR = 0.48; 95% CI: 0.26, 0.91). Results for laryngeal cancer were similar (OR = 0.54; 95% CI: 0.30, 0.96). Analysis on duration of intake confirmed findings for HNC overall, showing also inverse associations for oropharyngeal and laryngeal cancer. This study suggests that aspirin intake may reduce the risk of HNC, driven mainly by decreases in risk for laryngeal and oropharyngeal cancer.

The Combined Effects of Alcohol Consumption and Smoking on Cancer Risk by Exposure Level: A Systematic Review and Meta-Analysis.

Alcohol consumption is a major risk factor for cancer, and when combined with smoking, the risk increases. Nevertheless, few studies have comprehensively evaluated the combined effects of alcohol consumption and smoking on the risk of various cancer types. Therefore, to assess these effects, we conducted a systematic review and meta-analysis. We performed a systematic search of five literature databases, focusing on cohort and case-control studies. Considering exposure levels, we quantified the combined effects of alcohol consumption and smoking on cancer risk and assessed multiplicative interaction effects. Of 4,452 studies identified, 24 (4 cohort studies and 20 case-control studies) were included in the meta-analysis. We detected interaction effect of light alcohol and moderate smoking on head and neck cancer risk (relative risk [RR], 4.26; 95% confidence interval [CI], 2.50-7.26; I² = 65%). A synergistic interaction was observed in heavy alcohol and heavy smoking group (RR, 35.24; 95% CI, 23.17-53.58; I² = 69%). In more detailed cancer types, the interaction effect of heavy alcohol and heavy smoking was noticeable on oral (RR, 36.42; 95% CI, 24.62-53.87; I² = 46%) and laryngeal (RR, 38.75; 95% CI, 19.25-78.01; I² = 69%) cancer risk. Our study provided a comprehensive summary of the combined effects of alcohol consumption and smoking on cancers. As their consumption increased, the synergy effect became more pronounced, and the synergy effect was evident especially for head and neck cancer. These findings provide additional evidence for the combined effect of alcohol and smoking in alcohol guidelines for cancer prevention.

Cancer Risk According to Alcohol Consumption Trajectories: A Population-based Cohort Study of 2.8 Million Korean Men.

Alcohol drinking behaviors change temporally and can lead to changes in related cancer risks; previous studies have been unable to identify the association between the two using a single-measurement approach. Thus, this study aimed to investigate the association of drinking trajectories with the cancer risk in Korean men. A trajectory analysis using group-based trajectory modeling was performed on 2,839,332 men using data on alcohol drinking levels collected thrice during the Korean National Health Insurance Service's general health screening program conducted between 2002 and 2007. Cox proportional hazards regression was performed to evaluate the associations between drinking trajectories and cancer incidence, after adjustments for age, income, body mass index, smoking status, physical activity, family history of cancer, and comorbidities. During 10.5 years of follow-up, 189,617 cancer cases were recorded. Six trajectories were determined: non-drinking, light, moderate, decreasing-heavy, increasing-heavy, and steady-heavy. Light-to-heavy alcohol consumption increased the risk for all cancers combined in a dose-dependent manner (adjusted hazard ratio [aHR] 1.03; 95% confidence interval [CI], 1.02-1.05 for light drinking, aHR 1.06; 95% CI 1.05-1.08 for moderate drinking, aHR 1.19; 95% CI, 1.16-1.22 for decreasing-heavy drinking, aHR 1.23; 95% CI, 1.20-1.26 for increasing-heavy drinking, and aHR 1.33; 95% CI, 1.29-1.38 for steady-heavy drinking [P-trend <0.001]). Light-to-heavy alcohol consumption was linked to lip, oral cavity, pharyngeal, esophageal, colorectal, laryngeal, stomach, and gallbladder and biliary tract cancer risks, while heavy alcohol consumption was associated with hepatic, pancreatic, and lung cancer risks. An inverse association was observed for thyroid cancer. The cancer risks were lower for decreasing-heavy drinkers, compared to steady-heavy drinkers. No safe drinking limits were identified for cancer risks; reduction in heavy intake had protective effects.

Knowledge, attitudes, and willingness of community pharmacy staff in Mures County, Romania, to provide the brief advice to stop smoking: A cross-sectional study

Abstract Background and objective: Providing brief advice to stop smoking (BASS) can significantly increase motivation to quit, long-term smoking cessation rates, and substantially impact public health. The study aimed to evaluate knowledge, attitudes, and willingness of community pharmacy staff in Mures County, Romania, to provide BASS to smokers. Methods: The observational, cross-sectional study included a sample of 96 professionals working in community pharmacies in Mures County, Romania. Data were collected using an online questionnaire. Descriptive statistics were calculated. Results: Generally, more than 90% of the respondents acknowledged that smoking is addictive, represents a health hazard, and increases the risk of lung and laryngeal cancer, chronic obstructive pulmonary disease, heart attack, and stroke. Up to 70% of the respondents recognized the most common scientifically proven quit medications, such as nicotine replacement therapy, bupropion, and varenicline. Most pharmacists agreed that they should regularly ask the patients about their smoking status and encourage smokers to quit. They also declared they should receive continual education regarding quit services, medications, and techniques. BASS was credited with very high efficacy by 17.1%, high efficacy by 26.8%, and moderate efficacy by 46.3% of the respondents. The most common perceived barriers to providing BASS in community pharmacies were lack of demand from smokers (78.0%), lack of time (73.2%), and lack of educational materials (39.0%). About 70% of the pharmacists received no formal training regarding quit services, but more than 75% were interested in earning such a qualification. About 65% of the respondents estimated they could dedicate 10-15 minutes of their daily working time to provide BASS to interested customers. Conclusions: Overall, the study found an acceptable level of knowledge and willingness of the participants in offering BASS, suggesting that a program to provide BASS in Mures County community pharmacies may be feasible and useful.

Trend and projection of larynx cancer incidence and mortality in China from 1990 to 2044: A Bayesian age-period-cohort modeling study.

Larynx cancer is one of the most common cancers in head and neck, and imposes heavy burden on individual and societies. A comprehensive understanding of the burden of larynx cancer is necessary to improve prevention and control strategies. However, the secular trend of larynx cancer incidence and mortality in China remains unclear. The incidence and deaths rates of larynx cancer from 1990 to 2019 were collected from the Global Burden of Disease Study 2019 database. The temporal trend of larynx cancer was analyzed using a joinpoint regression model. The age-period-cohort model was used to explore the age, period, and cohort effects on larynx cancer and predict future trends up to 2044. From 1990 to 2019, the age-standardized incidence rate of larynx cancer in China increased by 1.3% (95% CI 1.1 to 1.5) in males, but decreased by 0.5% (95% CI -0.1 to 0) in females. The age-standardized mortality rate of larynx cancer in China decreased by 0.9% (95% CI -1.1 to -0.6) and 2.2% (95% CI -2.8 to -1.7) in males and females, respectively. Among the four risk factors, smoking and alcohol use contributed to a heavier burden compared to occupational exposure to asbestos and sulfuric acid with respect to mortality. Age effects showed that the incidence and deaths of larynx cancer were concentrated in people older than 50 years old. Period effects exerted the most significant effect on larynx cancer incidence for males. In terms of cohort effects, people born in the earlier cohorts presented a higher risk of larynx cancer compared with the later cohorts. From 2020 to 2044, the age-standardized incidence rates of larynx cancer continued to increase in males, whereas the age-standardized mortality rates continued to decrease in both males and females. The burden of larynx cancer in China has a significant gender difference. The age-standardized incidence rates will continue to increase in males up to 2044. The disease pattern and risk factors of larynx cancer should be comprehensively studied to promote the development of timely intervention measures and relieve the burden effectively.

Digit ratio (2D:4D), laryngeal cancer and vocal fold leukoplakia

BackgroundTo date, there are no studies that have analyzed the possible influence of exposure to prenatal sex hormones on the risk of laryngeal cancer (LC) and premalignant laryngeal lesion—vocal fold leukoplakia (VFL). Digit ratio (2D:4D) is suggested to be a proxy of prenatal sex hormone exposure.ObjectiveTo examine 2D:4D in patients with LC and clarify if it could add to the verified risk factors in estimating the overall risk of LC.Methods511 subjects participated in the study. The study group included 269 patients: with LC (N = 114, 64 men) and VFL (N = 155, 116 men). Controls included 242 healthy individuals (66.40 ± 4.50 years (106 men)).ResultsPredictive models estimating the risk of VFL and LC in women, based solely on predictors like smoking and alcohol consumption had a lower area under the ROC curve (AUC) than the model with left 2D:4D. AUC for the model estimating the likelihood of VFL increased from 0.83 to 0.85, and for LC from 0.76 to 0.79.ConclusionsLow left 2D:4D may be associated with an increased risk of developing leukoplakia and laryngeal cancer in women. In the case of laryngeal cancer, left 2D:4D may serve as additional variable (to other known risk factors, such as smoking and/or alcohol consumption), which can improve cancer risk prediction.

Association between long-term exposure to air pollution and the risk of incident laryngeal cancer: a longitudinal UK Biobank-based study

We assessed the association between long-term joint exposure to ambient air pollutants and the risk of laryngeal cancer and whether this risk was modified by genetic susceptibility. We used a multivariable Cox proportional hazards regression model to analyze data from UK Biobank to determine the relationship between long-term exposure to air pollutants–nitric oxide (NO), nitrogen dioxide (NO2), and 2.5-µm and 10-µm particulate matter (PM2.5 and PM10) and the risk of laryngeal cancer. In multivariable-adjusted models, in model 3 and compared with the participants with lower quintile scores for air pollution, the participants with the highest quintile scores for air pollution had a higher laryngeal cancer risk. The observed association was more pronounced among the participants who were female, were smokers, had a systolic blood pressure equal to or greater than 120 mmHg, and had diabetes. Compared with the participants with a low GRS and the lowest quintile score for air pollution exposure, those with an intermediate GRS and the highest quintile score for air pollution exposure had a higher risk of laryngeal cancer. Long-term exposure to NO2, NO, or PM2.5, individually or jointly, was associated with a risk of incident laryngeal cancer, especially in the participants with an intermediate GRS.

Intake of prebiotic fibers and the risk of laryngeal cancer: the PrebiotiCa study

PurposeTo evaluate whether the intake of specific fibers with prebiotic activity, e.g., inulin-type fructans (ITFs), fructo-oligosaccharides (FOSs), and galacto-oligosaccharides (GOSs), is associated with laryngeal cancer risk.MethodsWithin the PrebiotiCa study, we used data from a case–control study (Italy, 1992–2009) with 689 incident, histologically confirmed laryngeal cancer cases and 1605 controls. Six prebiotic molecules (ITFs, nystose [FOS], kestose [FOS], 1F-β-fructofuranosylnystose [FOS], raffinose [GOS] and stachyose [GOS]) were quantified in various foods via ad hoc conducted laboratory analyses. Subjects’ prebiotic fiber intake was calculated by multiplying food frequency questionnaire intake by the prebiotic content of each food item. The odds ratios (OR) of laryngeal cancer for prebiotic fiber intake were calculated using logistic regression models, including, among others, terms for tobacco, alcohol, and total energy intake.ResultsThe intakes of kestose, raffinose and stachyose were inversely associated with laryngeal cancer, with ORs for the highest versus the lowest quartile of 0.70 (95% confidence interval, CI 0.50–0.99) for kestose, 0.65 (95% CI 0.45–0.93) for raffinose and 0.61 (95% CI 0.45–0.83) for stachyose. ITFs, nystose and 1F-β-fructofuranosylnystose were not associated with laryngeal cancer risk. Current smokers and heavy drinkers with medium–low intakes of such prebiotic fibers had, respectively, an over 15-fold increased risk versus never smokers with medium–high intakes and a five to sevenfold increased risk versus never/moderate drinkers with medium–high intakes.ConclusionAlthough disentangling the effects of the various components of fiber-rich foods is complex, our results support a favorable role of selected prebiotic fibers on laryngeal cancers risk.

Tracheostomy dependence following “organ preservation” (chemo)radiation protocol for laryngeal and hypopharyngeal cancers

Patients receiving primary (chemo)radiotherapy for laryngeal or hypopharyngeal cancer risk developing severe laryngeal dysfunction and becoming tracheostomy dependent, detracting from the benefits of organ preservation. We aim to describe the airway outcomes for this cohort and identify risk factors for developing tracheostomy dependence. Patients with laryngeal or hypopharyngeal cancer who were recommended for and underwent primary (chemo)radiotherapy over a 6-year period were identified from a tertiary hospital Head and Neck cancer database. Patient, tumor, and treatment details were collected and analyzed. Of 166 patients, 18.7% (N=31) required tracheostomy insertion. Advanced tumor classification was the only significant predictor (p < 0.00001). Successful decannulation was observed in 12.9% (N=4). Decannulation was observably less successful with advanced tumors, bilateral vocal cord immobility, tracheostomies inserted under emergency conditions. We quantified tracheostomy insertion rates and dependence in patients undergoing "organ-preserving" (chemo)radiotherapy, to assist in the pre-treatment counseling of patients opting for this approach.

Evaluation of genetic and epigenetic changes of Tumor Necrosis Factor-Alpha gene in larynx cancer

BackgroundTumor Necrosis Factor-Alpha (TNF-α) is a proinflammatory cytokine that plays a role in inflammation, which is one of the hallmarks of cancer, and its polymorphic variants have been associated with disease risk in many cancers in the literature. The aim of this study was to investigate four different polymorphic variants, differential methylation and expression status of the TNF-α gene and to determine the associations between these variants and disease risk, and to evaluate the relationship between the results and clinical parameters. We purposed to investigate the genetic and epigenetic alterations of the TNF-α gene in larynx cancer (LC). Material and MethodsAfter isolation of DNA/RNA from whole blood, tumor and normal tissue, polymorphic variant alleles differrential expression and methylation levels were analyzed by RFLP, semiquantitative RT-PCR, and restriction enzyme digestion, respectively. TNF-α expression and methylation levels were calculated using BIO1D software. The frequencies of the variants c.–238 G>A (rs361525), c.–857 C>T (rs1799724), c.–863 C>A (rs1800630), and c.–1031 T > C (rs1799964) in the promoter region of TNF-α in LC Turkish patients and healthy individuals were examined using the De-Finetti case-control program. Haplotype frequencies and linkage disequilibrium were analyzed using the SNPStats program. ResultsThe frequency of genotype c.–1031 T > C was significantly lower in patients than in healthy individuals [TT vs TC: OR (%95CI) = 7.00 (1.75–27.93), p = 0.003, χ2 = 8.76]. The heterozygous variant of − 857 was associated with recurrence [T vs G: OR (%95CI) = 0.15 (0.02–0.95), p = 0.02, χ2 = 4.86]. For c.–238 G>A, c.–857 C>T, and c.–863 C>A, there was no statistically significant difference between the patient and healthy group in terms of disease risk. A significant association was found between c.–1031 T > C and disease risk of LC. Decreased expression was detected in 46% (23/50) and increased expression in 54% (27/50) of tumor tissue samples compared to the matched normal tissues of patients. Methylation-related loss of expression was detected in 53.3% (16/30) of patients. ConclusionOur study is the first investigating four different polymorphic regions of the TNF-α promoter region and the expression/methylation status of TNF-α in the same LC patient and healthy cohort. According to our results, the c.–1031 T > C variant was reported to be significantly associated with a reduced risk of LC. In addition, the TNF-α variant c. –857 C>T suggests that it may be a potential biomarker for predicting the recurrence of LC. An association between c. –857 C>T variant and methylation-based expression status was observed.

Do Polymorphisms of the TERT, GSTM1, and GSTT1 Genes Increase Laryngeal Cancer Susceptibility in Smokers of Romanian Descent?

Background and Objectives: The aim of this study was to investigate the association between smoking status and single-nucleotide polymorphism in candidate genes that had a known association with smoking-related tumors in previous studies and to explore their link to laryngeal cancer risk in a population of northern Romanian descent. The genes selected have key functions in xenobiotic metabolism (GSTs: the glutathione S-transferases family: GSTM1 and GSTT1) and chromosomal management (TERT). Materials and Methods: The genotype frequencies of TERTRs2736100 and the GST subfamilies (GSTM1 and GSTT1) were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The relationship between the polymorphisms and the risk of laryngeal cancer was analyzed in a retrospective case–control study of 92 laryngeal cancer cases and 101 controls, all of whom were smokers. Results: Subjects presenting the GSTT1-null variant had a two-fold increase in risk (OR = 2.05, 95% CI = 1.07–3.95, p = 0.02). While no individual risk was observed for the TERTRs2736100 polymorphism, stratification based on gender revealed a nine-fold increase in risk for carriers of the “C” allele in the heterozygote variant who were male (OR = 9, 65% CI = 3.51–26.51, p = 0.0000). Conclusions: The results showed that the GSTT1-null genotype and the mutant heterozygote variant of TERTRs2736100 genes may play a significant role in laryngeal cancer susceptibility in subjects of northern Romanian descent. There may be no association between the susceptibility to laryngeal carcinoma and the GSTM1 polymorphism. The results could not confirm the carcinogenic influence smoking has on laryngeal cancer development for the studied polymorphisms.

Evaluation of advanced protein oxidation and RAGE gene variants in the risk of laryngeal cancer

Laryngeal tumours with multifactorial etiopathogenesis constitute ∼1% of all body cancers. The imbalance between oxidative and antioxidative systems affects redox-homeostasis. The oxidative stress generated by the continuous formation of reactive oxygen species results in the oxidation of cellular molecules. The present study investigated the protein oxidation levels and the distribution of receptors for advanced glycation end products (RAGE) variants in the risk of laryngeal carcinoma (LC). RAGE gene polymorphisms were determined by restriction endonuclease-based assay in 120 controls and 120 LC patients. Spectrophotometric methods were used to determine oxidant and antioxidant parameters including protein-carbonyl-groups (PCO), advanced-oxidation-protein-products (AOPP), lipid-hydroperoxides (LPH), thiol-fractures, superoxide-dismutase (SOD) activity. The distributions of rs1800624 and rs2070600 genotypes differed non-significantly among the study groups, however, the rs2070600-Ser allele had a higher frequency among the patients. While rs1800624-A allele carriers had higher frequency of perineural and lymphatic invasion, rs2070600-Ser allele frequency was higher in advanced-stage patients and in patients with muscle and perineural invasion. PCO, AOPP, LPH levels, and SOD activity were significantly higher in the patients. According to AUCs all of them are of diagnostic importance, therefore, cut-off values were determined. The analysis of the combined effects of RAGE polymorphisms and the oxidative stress parameters showed that LPH, thiols, and SOD activity differ among RAGE variants. Our results suggest that high levels of serum PCO, AOPP, LPH, and SOD activity and rs2070600-Ser allele may have effects on LC risk individually and both polymorphisms of RAGE may affect the progression of the disease by interacting with the oxidant–antioxidant system.

Investigation of the Upper Respiratory Tract of a Male Smoker with Laryngeal Cancer by Inhaling Air Associated with Various Physical Activity Levels

Smokers are at a higher risk of laryngeal cancer, which is a type of head and neck cancer in which cancer cells proliferate and can metastasize to other tissues after a tumor has formed. Cigarette smoke greatly reduces the inhaled air quality and can also lead to laryngeal cancer. In this study, the upper airway of a 70-year-old smoker with laryngeal cancer was reconstructed by taking a CT scan using Mimics software. To solve the governing equations, computational fluid dynamics (CFD) with a pressure base approach was used with the help of Ansys 2021 R1 software. As a result, the maximum turbulence intensity occurred in the larynx. At 13 L/min, 55 L/min, and 100 L/min, the maximum turbulence intensity was 1.1, 3.5, and 6.1, respectively. The turbulence intensity in the respiratory system is crucial because it demonstrates the ability to transfer energy. The maximum wall shear stress (WSS) also occurred in the larynx. At 13 L/min, 55 L/min, and 100 L/min, the maximum WSS was 0.62 Pa, 5.4 Pa, and 12.4 Pa, respectively. The WSS index cannot be calculated in vivo and should be calculated in vitro. Excessive WSS in the epiglottis is inappropriate and can lead to an airway obstruction. Furthermore, real mathematical modeling outcomes provide an approach for future prevention, treatment, and management planning by forecasting the zones prone to an acceleration of disease progression. In this regard, accurate computational modeling leads to pre-visualization in surgical planning to define the best reformative techniques to determine the most probable patient condition consequences.