Pharyngeal Cancer Research Articles

СANCER INCIDENCE IN UKRAINE: TRENDS IN 2010-2019 AND THE IMPACT OF COVID-19 PANDEMIC.

In 2020, a sharp decrease in the number of new cancer cases was registered in Ukraine in the setting of the quarantine restrictions due to the COVID-19 pandemic, which contrasted with the previous trends. To study trends of cancer incidence rates in Ukraine in the recent decade and to assess the impact of COVID-19 pandemic on cancer detection in 2020. Records on cancer cases diagnosed during 2010-2020 (n = 1,498,911) from the database of the National Cancer Registry of Ukraine were used; the data being submitted early in 2022. Trends of the age-standardized incidence rates in 2010-2019 were estimated by the Joinpoint Regression Program. During 2010-2019, the incidence rates increased (p < 0.05) for colon, prostate, and pharyngeal cancers in males and for colon, thyroid, and pancreas in females with the rates of other prevalent cancers being stable or decreasing (lung and larynx in males, cervix and rectum in females, stomach in both genders); the incidence increased mainly at the expense of the population aged 60-74 years. A significant decrease in cancer incidence was in males aged 40-59 years. In 2020, the serious negative impact of COVID-19 outbreak on the timely detection of cancer occurred in all adult age groups of the Ukrainian population and involved all the most common cancers. The most pronounced diminution of the incidence rate was observed for non-melanoma skin cancers (by 35.9%- 37.9%); the decrements of the rates for other prevalent cancers varied from -23.0% (prostate gland) to -9.7% (pharynx) in males and from -21.2% (kidney) to -9.1% (pancreas) in females, the greatest ones being in the population aged 75+. The sharp drop of the cancer incidence rates registered in Ukraine 2020 is evidently the result of the limited access to healthcare facilities as well as the reduced oncological alertness of the population due to the predominant focus on COVID-19 during the pandemic. However, it is not a manifestation of a decrease in cancer incidence as such. In the following years, this may increase the proportion of advanced-stage diagnoses, the load on the cancer care system, and cancer mortality in the Ukrainian population. An evaluation of the short-termand long-term effects of the COVID-19 pandemic on the cancer burden in Ukraine requires further monitoring.

An Updated Evaluation of Atrazine-Cancer Incidence Associations among Pesticide Applicators in the Agricultural Health Study Cohort.

Atrazine is a common agricultural herbicide in the United States. Few epidemiologic studies have evaluated cancer risks. Previous analyses within the Agricultural Health Study (AHS) have found some evidence of associations with cancer at some sites. We updated exposure information, incident cases, and follow-up time to assess the associations between atrazine use and cancer at specific sites in the AHS. Information about lifetime pesticide use was reported at enrollment (1993-1997) and follow-up (1999-2005). Among 53,562 pesticide applicators in North Carolina and Iowa, we identified 8,915 incident cases through cancer registry linkages through 2014 (North Carolina)/2017 (Iowa). We used Poisson regression to evaluate the association between ever/never and intensity-weighted lifetime days of atrazine use and incident cancer risk controlling for several confounders. We also evaluated lagged exposures and age-stratified risk. Approximately 71.2% of applicators reported ever using atrazine, which was associated with lung cancer [; 95% confidence interval (CI): 1.04, 1.46]. Aggressive prostate cancer risk was increased in the highest quartile (; 95% CI: 0.95, 1.52; ), particularly among those years old (; 95% CI: 1.61, 5.75; ; ). Among applicators years of age, ever-atrazine use was associated with non-Hodgkin lymphoma (NHL) (; 95% CI: 1.10, 5.38; ). For soft tissue sarcoma, there was an elevated risk in the highest tertile of exposure (: 2.54; 95% CI: 0.97, 6.62; ). In analyses with exposure lagged by 25 years, there was an elevated risk of pharyngeal (; 95% CI: 1.45, 6.36; ) and kidney (; 95% CI: 1.15, 2.29; ) cancers. We observed suggestive associations with some malignancies in overall, age-specific, and lagged analyses. Associations with aggressive prostate cancer and NHL were apparent among those diagnosed at younger ages and with cancers of the pharynx and kidney, and soft tissue sarcomas were observed in lagged analyses. Further work is needed to confirm these observed associations and elucidate potential underlying mechanisms. https://doi.org/10.1289/EHP13684.

Oral streptococci S. anginosus and S. mitis induce distinct morphological, inflammatory, and metabolic signatures in macrophages.

Oral streptococci, key players in oral biofilm formation, are implicated in oral dysbiosis and various clinical conditions, including dental caries, gingivitis, periodontal disease, and oral cancer. Specifically, Streptococcus anginosus is associated with esophageal, gastric, and pharyngeal cancers, while Streptococcus mitis is linked to oral cancer. However, no study has investigated the mechanistic links between these Streptococcus species and cancer-related inflammatory responses. As an initial step, we probed the innate immune response triggered by S. anginosus and S. mitis in RAW264.7 macrophages. These bacteria exerted time- and dose-dependent effects on macrophage morphology without affecting cell viability. Compared with untreated macrophages, macrophages infected with S. anginosus exhibited a robust proinflammatory response characterized by significantly increased levels of inflammatory cytokines and mediators, including TNF, IL-6, IL-1β, NOS2, and COX2, accompanied by enhanced NF-κB activation. In contrast, S. mitis-infected macrophages failed to elicit a robust inflammatory response. Seahorse Xfe96 analysis revealed an increased extracellular acidification rate in macrophages infected with S. anginosus compared with S. mitis. At the 24-h time point, the presence of S. anginosus led to reduced extracellular itaconate, while S. mitis triggered increased itaconate levels, highlighting distinct metabolic profiles in macrophages during infection in contrast to aconitate decarboxylase expression observed at the 6-h time point. This initial investigation highlights how S. anginosus and S. mitis, two Gram-positive bacteria from the same genus, can prompt distinct immune responses and metabolic shifts in macrophages during infection.IMPORTANCEThe surge in head and neck cancer cases among individuals devoid of typical risk factors such as Human Papilloma Virus (HPV) infection and tobacco and alcohol use sparks an argumentative discussion around the emerging role of oral microbiota as a novel risk factor in oral squamous cell carcinoma (OSCC). While substantial research has dissected the gut microbiome's influence on physiology, the oral microbiome, notably oral streptococci, has been underappreciated during mucosal immunopathogenesis. Streptococcus anginosus, a viridans streptococci group, has been linked to abscess formation and an elevated presence in esophageal cancer and OSCC. The current study aims to probe the innate immune response to S. anginosus compared with the early colonizer Streptococcus mitis as an important first step toward understanding the impact of distinct oral Streptococcus species on the host immune response, which is an understudied determinant of OSCC development and progression.

Safety and outcome of three-dimensional transoral videolaryngoscopic surgery.

Transoral videolaryngoscopic surgery (TOVS) is widely used in Japan, and conventional two-dimensional (2D) endoscopic methods have been established. Three-dimensional (3D) endoscopic surgery offers superior distance perception because it provides stereoscopic views. Recently, we have developed 3D endoscopy for TOVS (3D TOVS). This study included 46 patients with pharyngeal cancer who underwent 3D TOVS. The perioperative complications and survival curves were retrospectively analyzed. One patient with oropharyngeal cancer who underwent neck dissection and transoral resection simultaneously experienced postoperative hemorrhage of the neck. Another patient with oropharyngeal cancer underwent hemostasis for postoperative pharyngeal hemorrhage. There was one case of aspiration pneumonia. One patient developed cervical lymph node recurrence; however, there was no local recurrence or primary mortality. The 2-year overall survival, disease-specific survival, local control rates, locoregional control rate, and invasive disease-free survival were 90.9%, 100%, 100%, 97.4%, and 79.9%, respectively. Three-dimensional endoscopy can be safely applied to TOVS.

Cone-beam computed tomography-guided online adaptive radiotherapy for pharyngeal cancer with whole neck irradiation: dose-volume histogram analysis between adapted and scheduled plans.

The present study aimed to evaluate whether an adapted plan with Ethos™ could be used for pharyngeal cancer. Ten patients with pharyngeal cancer who underwent chemoradiotherapy with available daily cone-beam computed tomography (CBCT) data were included. Simulated treatments were generated on the Ethos™ treatment emulator using CBCTs every four to five fractions for two plans: adapted and scheduled. The simulated treatments were divided into three groups: early (first-second week), middle (third-fourth week), and late (fifth-seventh week) periods. Dose-volume histogram parameters were compared for each period between the adapted and scheduled plans in terms of the planning target volume (PTV) (D98%, D95%, D50% and D2%), spinal cord (Dmax and D1cc), brainstem (Dmax) and ipsilateral and contralateral parotid glands (Dmedian and Dmean). The PTV D98%, D95% and D2% of the adapted plan were significantly higher than those of the scheduled plans in all periods, except for D98% in the late period. The adapted plan significantly reduced the spinal cord Dmax and D1cc compared with the scheduled plan in all periods. Ipsilateral and contralateral parotid glands Dmean of the adapted plan were lower than those of scheduled plan in the late period. In conclusion, the present study revealed that the adapted plans could maintain PTV coverage while reducing the doses to organs at risk in each period compared with scheduled plans.

Air pollution is associated with increased incidence-rate of head and neck cancers: A nationally representative ecological study

IntroductionEarly studies show conflicting findings regarding particulate matter ≤ 2.5 μm in diameter (PM2.5) exposure and development of head and neck cancers (HNC). We analyzed the relationship between PM2.5 exposure and various types of HNC in a nationally representative ecological sample. MethodsWe determined HNC incidence in 608 US counties from 2011 to 2019 using the Surveillance, Epidemiology and End Results (SEER) Program from the National Cancer Institute. We also collected information on sociodemographic factors from SEER and data on smoking and alcohol intake from CDC data frames (county level). PM2.5 exposure levels were estimated using satellite and meteorological data via previously validated general additive models. Flexible semi-nonparametric regression models were used to test the relationship between PM2.5 exposure levels and HNC incidence, adjusting for demographics, socioeconomic factors, and comorbidity. ResultsIncreased PM2.5 exposure levels were associated with higher incidence-rates of oral cavity and pharyngeal cancers controlling for confounders in our primary analyses (IRR = 1.04, 95 % CI 1.01, 1.07, p = 0.02 per 1 μg/m3 increase in PM2.5). This relationship was maintained after adjusting for multiple testing (Holm s method, p = 0.04) and in ordinary least squares (OLS) regression (β = 0.17, 95 % CI 0.01, 0.57, p = 0.01). Increased exposure was also associated with other HNC: esophagus (IRR = 1.06, 95 % CI 1.01, 1.11, p = 0.02), lip (IRR = 1.16, 95 % CI 1.03, 1.31, p = 0.01), tonsil (IRR = 1.10, 95 % CI 1.03, 1.16, p < 0.01). However, these relationships were not maintained in secondary analyses. ConclusionsThis nationally representative ecological study shows that increased levels of air pollution are associated with increased incidence of overall oral cavity and pharyngeal cancers in the US.

Socio -Cultural Elements in the Songs of Bishnu Prasad Rabha: A Retrospective

Bishnu Prasad Rabha has been an accomplished musician, creative writer, acclaimed master of fine arts, social activist and politician. His contribution to Assamese social and cultural life is great. When we talk about modern Assamese music, we need to mention the name of the musician par excellence Bishnu Prasad Rabha. His contribution to modern Assamese lyrical literature is great. Bishnu Prasad Rabha was a profound composer and musician of his times. He has numerous songs to his credit which speak of the aspirations of the Assamese community at large. Whether be it a romantic song or a patriotic song yet unique quality of the composer Bishnu Prasad Rabha was always there. He was born to Sardar Bahadur Gopal Chandra Rabha, an efficient officer under the Governor of Bengal. He was honoured with Order of Merit of the British empire. Bishnu Prasad’s mother was Gethi Rabha. He was born as the eighth child on 31st January, 1909 at Dhaka. Gopal Chandra Rabha was a great lover of music. Music sessions were held at his residence where the little Bishnu Prasad got acquainted with all the stalwarts of music in Bengal. Unfortunately, his father Gopal Chandra met an untimely death and the family fell into adversity. His widow Gethi along with her children took shelter at their own house in Tezpur. Bishnu Prasad resumed his studies in Tezpur He continued with his other co-curricular activities as well. It is no easy task to assess the worth of the multi -talented personality of Bishnu Prasad Rabha. In his lifetime he was a live legend. Music, fine arts, theatre performance, creative writing, politics, creating social awareness- he explored in all these diverse fields and won accolades for his exceptional contribution. His physical contribution towards the greater Assamese society came to a stop on 20th June, 1969 due to throat cancer. But the grand legacy of his craftsmanship lives on. In this Paper an attempt has been made to assess the socio-cultural elements present in his songs.

The Causal Relationship between PCSK9 Inhibitors and Malignant Tumors: A Mendelian Randomization Study Based on Drug Targeting.

Objective: This study explores the potential causal association between proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and tumor development using Mendelian randomization (MR) based on drug targets. Methods: Instrumental variables within ±100 kb of the PCSK9 gene locus, impacting low-density lipoprotein cholesterol (LDL-C), were utilized for MR analysis. Coronary heart disease (CHD) served as a positive control to validate the causal relationship between PCSK9 inhibitors and various cancers. We employed reverse MR to address the reverse causation concerns. Data from positive controls and tumors were sourced from OpenGWAS. Results: MR analysis suggested a negative causal relationship between PCSK9 inhibitors and both breast and lung cancers (95%CIBreast cancer 0.81~0.99, p = 2.25 × 10-2; 95%CILung cancer 0.65~0.94, p = 2.55 × 10-3). In contrast, a positive causal link was observed with gastric, hepatic, and oral pharyngeal cancers and cervical intraepithelial neoplasia (95%CIGastric cancer 1.14~1.75, p = 1.88 × 10-2; 95%CIHepatic cancer 1.46~2.53, p = 1.16 × 10-2; 95%CIOral cavity and pharyngeal cancer 4.49~6.33, p = 3.36 × 10-4; 95%CICarcinoma in situ of cervix uteri 4.56~7.12, p = 6.91 × 10-3), without heterogeneity or pleiotropy (p > 0.05). Sensitivity analyses confirmed these findings. The results of MR of drug targets suggested no causal relationship between PCSK9 inhibitors and bladder cancer, thyroid cancer, pancreatic cancer, colorectal cancer, malignant neoplasms of the kidney (except for renal pelvis tumors), malignant neoplasms of the brain, and malignant neoplasms of the esophagus (p > 0.05). Reverse MR helped mitigate reverse causation effects. Conclusions: The study indicates a divergent causal relationship of PCSK9 inhibitors with certain cancers. While negatively associated with breast and lung cancers, a positive causal association was observed with gastric, hepatic, oral cavity, and pharyngeal cancers and cervical carcinoma in situ. No causal links were found with bladder, thyroid, pancreatic, colorectal, certain kidney, brain, and esophageal cancers.

Genetically predicted circulating levels of cytokines and the risk of oral cavity and pharyngeal cancer: a bidirectional mendelian-randomization study.

Background: Epidemiological research has established associations between various inflammatory cytokines and the occurrence of oral cancer and oropharyngeal cancer (OCPC). We performed a Mendelian randomization (MR) analysis to systematically investigate the causal relationship between inflammatory cytokines and OCPC. Methods: We performed a bidirectional two-sample MR analysis using OCPC from 12 studies (6,034 cases and 6,585 controls) and genome-wide association study (GWAS) results for 41 serum cytokines from 8,293 Finns, respectively. Inverse variance weighting was used as the primary MR method and four additional MR methods (MR Egger, Weighted median, Simple mode, Weighted mode) were used to examine genetic associations between inflammatory traits and OCPC, and Cochran's Q test, MR-Egger intercept, leave-one-out analysis, funnel plot, and multivariate MR (MVMR) analysis were used to assess the MR results. Results: The results suggested a potential association between high gene expression of Macrophage inflammatory protein-1α (MIP1α/CCL3) and an increased risk of OCPC (Odds Ratio (OR): 1.71, 95% Confidence Interval (CI): 1.09-2.68, p = 0.019). Increasing the expression levels of the interleukin-7 (IL-7) gene by 1 standard deviation reduced the risk of OCPC (OR: 0.64, 95%CI: 0.48-0.86, p = 0.003). In addition, multivariate Mendelian randomization analysis also showed the same results (MIP1α/CCL3, OR: 1.002, 95% CI: 0.919-1.092, p = 0.044; IL-7, OR: 0.997, 95% CI: 0.994-0.999, p = 0.011). Conversely, there was a positive correlation between genetic susceptibility to OCPC and an increase in Interleukin-4 (IL-4) (OR: 1.04, 95%CI: 1.00-1.08, p = 0.027). Conclusion: Our study systematically assessed the association between inflammatory cytokines and the risk of OCPC. We identified two upstream regulatory factors (IL-7 and CCL3) and one downstream effector factor (IL-4) that were associated with OCPC, offering potential avenues for the development of novel treatments.

Head and Neck Cancer Incidence in the United States Before and During the COVID-19 Pandemic

Research about population-level changes in the incidence and stage of head and neck cancer (HNC) associated with the COVID-19 pandemic is sparse. To examine the change in localized vs advanced HNC incidence rates before and during the first year of the pandemic. In this cross-sectional study of patients in the US diagnosed with HNC from 2017 to 2020, the estimated number with cancer of the oral cavity and pharynx (floor of mouth; gum and other mouth; lip; oropharynx and tonsil; and tongue) and larynx were identified from the SEER cancer registry. Subgroup analyses were stratified by race and ethnicity, age, and sex. Data were analyzed after the latest update in April 2023. The COVID-19 pandemic in 2020. The primary outcomes were the annual incidence rates per 100 000 people for localized HNC (includes both localized and regional stages) and advanced HNC (distant stage) and weighted average annual percentage change from 2019 to 2020. Secondary outcomes included annual percentage change for 2017 to 2018 and 2018 to 2019, which provided context for comparison. An estimated 21 664 patients (15 341 [71%] male; 10 726 [50%] ≥65 years) were diagnosed with oral cavity and pharynx cancer in 2019 in the US, compared with 20 390 (4355 [70%] male; 10 393 [51%] ≥65 years) in 2020. Overall, the HNC incidence rate per 100 000 people declined from 11.6 cases in 2019 to 10.8 in 2020. The incidence rate of localized cancer declined to 8.8 cases (-7.9% [95% CI, -7.5 to -8.2]) from 2019 to 2020. The localized cancer incidence during the first year of the pandemic decreased the most among male patients (-9.3% [95% CI, -9.2 to -9.5]), Hispanic patients (-12.9% [95% CI, -12.9 to -13.0]), and individuals with larynx cancer (-14.3% [95% CI, -13.6 to -15.0]). No change in the overall incidence rate was found for advanced HNC. In this cross-sectional study, the incidence of localized HNC declined during the first year of the pandemic. A subsequent increase in advanced-stage diagnoses may be observed in later years.

Promoter DNA methylation patterns in oral, laryngeal and oropharyngeal anatomical regions are associated with tumor differentiation, nodal involvement and survival.

Differentially methylated regions (DMRs) can be used as head and neck squamous cell carcinoma (HNSCC) diagnostic, prognostic and therapeutic targets in precision medicine workflows. DNA from 21 HNSCC and 10 healthy oral tissue samples was hybridized to a genome-wide tiling array to identify DMRs in a discovery cohort. Downstream analyses identified differences in promoter DNA methylation patterns in oral, laryngeal and oropharyngeal anatomical regions associated with tumor differentiation, nodal involvement and survival. Genome-wide DMR analysis showed 2,565 DMRs common to the three subsites. A total of 738 DMRs were unique to laryngeal cancer (n=7), 889 DMRs were unique to oral cavity cancer (n=10) and 363 DMRs were unique to pharyngeal cancer (n=6). Based on the genome-wide analysis and a Gene Ontology analysis, 10 candidate genes were selected to test for prognostic value and association with clinicopathological features. TIMP3 was associated with tumor differentiation in oral cavity cancer (P=0.039), DAPK1 was associated with nodal involvement in pharyngeal cancer (P=0.017) and PAX1 was associated with tumor differentiation in laryngeal cancer (P=0.040). A total of five candidate genes were selected, DAPK1, CDH1, PAX1, CALCA and TIMP3, for a prevalence study in a larger validation cohort: Oral cavity cancer samples (n=42), pharyngeal cancer tissues (n=25) and laryngeal cancer samples (n=52). PAX1 hypermethylation differed across HNSCC anatomic subsites (P=0.029), and was predominantly detected in laryngeal cancer. Kaplan-Meier survival analysis (P=0.043) and Cox regression analysis of overall survival (P=0.001) showed that DAPK1 methylation is associated with better prognosis in HNSCC. The findings of the present study showed that the HNSCC subsites oral cavity, pharynx and larynx display substantial differences in aberrant DNA methylation patterns, which may serve as prognostic biomarkers and therapeutic targets.

Tobacco- and alcohol-attributable burden of early-onset lip, oral cavity, and pharyngeal cancer in 204 countries and territories from 1990 to 2019, with projections to 2040.

Rising trends in early-onset Lip and oral cavity cancer (LOC) and Other pharyngeal cancer (OPC) burden had been observed. This study aimed to evaluate the burdens of LOC and OPC attributable to tobacco and alcohol in young adults aged 15-49 years from 1990 to 2040. Tobacco- and alcohol-attributable death and disability-adjusted life years (DALYs) for LOC and OPC and the corresponding population-attributable fraction were obtained from Global Burden of Disease Study 2019 for individuals aged 15-49 years. Estimated annual percent change was calculated to quantify the temporal trend of disease burden between 1990 and 2019. The Bayesian age-period-cohort model was used to predict the age-standardized mortality rate from 2020 to 2040. In 2019, an estimated 16,887 deaths and 799,495 DALYs for tobacco- and alcohol-attributable early-onset LOC, and 8,402 deaths and 386,418 DALYs for early-onset OPC attributable to tobacco and alcohol were reported globally. Despite the global decrease in age-standardized mortality and DALYs rates of tobacco- and alcohol-attributable LOC and OPC in young adults aged 15-49 years between 1990 and 2019, certain regions experienced increases, such as regions of Asia, Eastern Europe, and Western Sub-Saharan Africa. Moreover, a growing age-standardized mortality in individuals aged <34 years was found. The socio-demographic index level was positively associated with a faster reduction of early-onset LOC and OPC DALYs attributable to alcohol use and smoking, except for that due to chewing tobacco. Furthermore, projections have also indicated an expected increase in the age-standardized mortality for tobacco- and alcohol-attributable early-onset LOC and OPC. Significant regional and demographic disparities in tobacco and alcohol-related early-onset LOC and OPC burden and their attributable proportion highlight a need for tailored age- and region-appropriate interventions to reduce the future LOC and OPC burden among young adults.

Survival in oral and pharyngeal cancers is catching up with laryngeal cancer in the NORDIC countries through a halfcentury.

Cancers of the head and neck (HN) are heterogeneous tumors with incidence rates varying globally. In Northern Europe oral and oropharyngeal cancers are the most common individual types. Survival for HN varies by individual tumor type but for most of them survival trends are not well known over extended periods of time. Data for a retrospective survival study were obtained for Danish, Finnish, Norwegian, and Swedish patients from the NORDCAN database from 1971 to 2020. Relative 1- and 5-year survival rates and 5/1-year conditional survival for years 2-5 were calculated. Both 1- and 5-year survival improved for all HN cancers but only marginally for laryngeal cancer. For the other cancers a 50-year increase in 5-year survival was about 30% units for nasopharyngeal and oropharyngeal cancers, 20% units for oral cancer and somewhat less for hypopharyngeal cancer. 5-year survival reached about 65% for all HN cancers, except for hypopharyngeal cancer (30%). Human papilloma virus infection is becoming a dominant risk factor for the rapidly increasing oropharyngeal cancer, the prevention of which needs to emphasize oral sex as a route of infection.

Prevalence of Current Areca Nut Use and Its Associated Factors among Bhutanese Aged 15-69 Years: Analysis of the Nationally Representative STEPS Survey 2019.

Areca nut (AN) use receives less global attention than tobacco use. Studies have linked AN consumption to a range of adverse health effects, including oral cavity and pharyngeal cancers, periodontal diseases, cardiovascular diseases, diabetes, hypertension, and addiction. The masticatory use of AN is rampant in Bhutan. There is a paucity of local evidence and limited empirical studies to understand the factors associated with current AN use in Bhutan. This analysis uses secondary data from the Bhutan STEPS Survey 2019 that included 5575 participants aged 15-69 years, selected using multistage stratified cluster sampling. The outcome variable of interest was current AN use. Weighted analysis was done to calculate the prevalence of AN use. Factors associated with AN use were assessed using multivariable logistic regression models. The prevalence of current AN use was 56.82% (95% confidence interval [CI]: 54.27-59.33). A significantly higher prevalence of 63.58% (95% CI: 60.58-66.48) was found in the age group of 25-39 years. Tobacco users were 17% more likely to use AN as compared to those who do not consume tobacco (adjusted odds ratio: 1.17, 95% CI: 1.08-1.26). Current alcohol consumers were 45% more likely to consume AN as compared to lifetime alcohol abstainers. Age, alcohol use, and tobacco use were associated with current AN use in Bhutan. There is a need to regulate access to AN while targeting young and middle-aged individuals with public health and behavioral interventions.

The causal association between artificial sweeteners and the risk of cancer: a Mendelian randomization study.

Artificial sweeteners (ASs) have been widely added to food and beverages because of their properties of low calories and sweet taste. However, whether the consumption of ASs is causally associated with cancer risk is not clear. Here, we utilized the two-sample Mendelian randomization (MR) method to study the potential causal association. Genetic variants like single-nucleotide polymorphisms (SNPs) associated with exposure (AS consumption) were extracted from a genome-wide association study (GWAS) database including 64 949 Europeans and the influence of confounding was removed. The outcome was from 98 GWAS data and included several types of cancers like lung cancer, colorectal cancer, stomach cancer, breast cancer, and so on. The exposure-outcome SNPs were harmonized and then MR analysis was performed. The inverse-variance weighted (IVW) with random effects was used as the main analytical method accompanied by four complementary methods: MR Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses consisted of heterogeneity, pleiotropy, and leave-one-out analysis. Our results demonstrated that ASs added to coffee had a positive association with high-grade and low-grade serous ovarian cancer; ASs added to tea had a positive association with oral cavity and pharyngeal cancers, but a negative association with malignant neoplasm of the bronchus and lungs. No other cancers had a genetic causal association with AS consumption. Our MR study revealed that AS consumption had no genetic causal association with major cancers. Larger MR studies or RCTs are needed to investigate small effects and support this conclusion.

Prognosis of South Asian Buccal Mucosa Cancer Patients in the United States: Association of Race with Overall Survival.

Squamous Cell Carcinoma (SCC) of the buccal mucosa and gingiva accounts for approximately 10% of oral and pharyngeal cancers diagnosed in the United States each year, with a disproportionally higher incidence in individuals of South Asian descent. However, little has been documented regarding trends pertaining to overall survival. Thus, this research serves to identify predictors of survival and determine if overall survival (OS) differs for South Asians compared to other races once they develop non-metastatic buccal mucosa or gingiva squamous cell carcinoma. A population-based, cohort study of patients registered in the National Cancer Database® (NCDB) between the years 2004-2016 was performed. Kaplan-Meyer Survival Curves were executed to examine overall survival, while univariable (UVA) and multivariable analysis (MVA) was performed to determine the effect of multiple variables on OS. South Asians had longer median OS at 88.7 months, compared to 58.6 months and 38.3 months for Caucasians and African Americans respectively (p<0.001). In UVA, race was highly significant, but when the cohort was selected to include only those who had undergone surgical resection, no statistically significant difference remained. On MVA, lack of surgery, older age, higher grade, higher T and N stage, use of chemotherapy, higher comorbidity scores were associated with worse OS, but race was not significant. South Asians in the US with non-metastatic buccal mucosa or gingiva SCC have better OS compared to Caucasians or African Americans, likely due to younger age at diagnosis (median 59 vs. 71 and 62 years old) and more frequent surgical resection (75% vs. 72% and 64%). In MVA, South Asians have similar OS as Caucasians.

Late-Stage Oral Cancer Detection After California and Illinois Restored Medicaid Dental Benefits.

Previous research found an association between California's Medicaid dental coverage and oral cancer detection. However, this relationship has yet to be explored in other states or by subgroup populations. In addition to controlling for sociodemographic and tumor characteristics, this study implemented a traditional difference-in-differences design to compare distant-stage diagnosis trends in states restoring Medicaid dental benefits (California [CA] and Illinois [IL]) with trends in states with constant Medicaid dental benefits. This retrospective, observational study analyzed oral cavity and pharynx cancer case data from The Surveillance, Epidemiology, and End Results program (2004-2017). The outcome was a binary variable indicating whether a patient was diagnosed at a distant stage. Subgroup analyses were conducted by state, race/ethnic group, sex, age, and county-level household income. The sample included 109,997 adults diagnosed with cancer of the oral cavity and pharynx. Restoring Medicaid dental benefits was associated with a statistically significant 2.7%-point decline in the probability of a distant-stage oral cancer diagnosis. This estimate represented a 14% relative change from baseline rates. Results were consistent for CA and IL and by county-level median income. Estimates were significantly larger for adults under age 65, males, and adults identifying as Hispanic; non-Hispanic Black; American Indian; or Asian American or Pacific Islander. Restoring Medicaid dental coverage improved early detection in both CA and IL, with the greatest reductions in distant-stage diagnoses occurring in younger adults, males, and minoritized racial/ethnic groups. Future research should investigate whether earlier detection reduces oral cancer mortality disparities.

The Relationship Between Annual Airborne Pollen Levels and the Occurrence of Uterine Cancer, Cervical Cancer, Corpus Uteri Cancer, Prostate Cancer, Bladder Cancer, Stomach Cancer, Cancer of the Gallbladder and Bile Ducts, Malignant Lymphoma, and Cancer of Oral and Pharyngeal, and Laryngeal Cancer: A Retrospective Study Based on The National Registry Database of Cancer Incidence In Japan, 1975–2015

Background: In Japan, pollen counts increased between 1977 and 1987, including three peaks (1978- 1980, 1982, 1984-1986) coinciding with triphasic Kawasaki disease (KD) outbreaks. Epidemiological findings have been extensively accumulated that KD since 2003 and, from 2018 related specific intractable diseases such as systemic vasculitis, collagen diseases, inflammatory bowel diseases, idiopathic dilated cardiomyopathy and further from 2019 various cancers such as lung, breast, pancreatic, skin and kidney cancers may be correlated to pollen exposure (PE). Methods and results: To elucidate the effects of PE on occurrence of other cancers, we evaluated the annual occurrence of disorders in relation to pollen counts using data from a national database. Specifically, we evaluated the occurrence of uterine cancer, cervical cancer, corpus uteri cancer, prostate cancer, bladder cancer, stomach cancer, cancer of gallbladder and bile ducts (GBB), malignant lymphoma (ML), oral and pharyngeal cancer (o-phar. cancers), laryngeal cancer. During 1975–2015, the 1978-80 and 1984-1986 peaks of pollen scatter was the earliest big peaks with which simultaneous increase in occurrence of uterine, cervical, bladder, stomach, GBB, o-phar. cancers and laryngeal cancers. Furthermore, simultaneous outbreaks of each cancer coincided with subsequent ten peaks of pollen scatter till 2015. Our results showed statistically significant correlations for o-phar cancers, laryngeal, prostate and stomach cancers between the annual number of newly registered patients (nRPs) in the patient-registry year and annual pollen levels in the same patient-registry year. Significant correlations were also shown between the number of nRPs in the patient-registry year and annual pollen levels measured 1 year (GBB), 2 years (prostate), 3 years (corpus uteri, stomach, ML), 5 years (uterine), 6 years (uterine, corpus uteri, prostate, bladder, GBB), 7 years (o-phar, laryngeal) and, 9 and 16 years (cervical) before the patient-registry year. Conclusion: We assume that cumulative effects of PE in many cases within about 6 years and more before the diagnosis of cancers might possibly trigger onset of cancers when cumulative effects of PE as environmental stress overwhelmed immunoreactive threshold. The authors would like to discuss the triggering effect of PE (the action of PE to induce a carcinogenic state in humans) on humans as a compromised host, in the preliminary stages of cancer development, in which human papillomavirus is thought to be involved in the pathogenesis.

Risk of Parkinson's disease-related death in cancer survivors: A population-based study in Japan

BackgroundThe risk of Parkinson's disease (PD)-related death in patients with cancer largely unexplored. MethodsWe analyzed data from the Neoplasms ANd other causes of DEath (NANDE) study, which investigates the causes of death in patients with cancer in Japan. Standardized mortality ratios (SMRs) were calculated to compare the risk of PD-related deaths in patients with cancer to that of the general population. Poisson regression models were employed to estimate the relative risk of PD-related death in the subgroups. ResultsThe cohort included 548,485 patients with cancer, yielding 2,047,398 person-years at risk from 1995 to 2013. During the study period, 242,250 patients died and 145 deaths were attributable to PD. The SMR for PD-related death was 2.34 (95% confidence interval [CI]: 1.99–2.75). Patients who were diagnosed with cancer before 70 years of age had a high SMR (>5) for PD-related deaths. The SMR of patients with mouth-to-stomach cancers (lip, oral cavity, pharynx, esophagus, and stomach cancers) was 3.72 (95% CI: 2.84–4.86), while that of those with other cancers was 1.93 (95% CI: 1.57–2.37). The multivariate Poisson regression model revealed that patients with mouth-to-stomach cancers were more likely to die of PD than those without (relative risk 2.07, 95 % CI; 1.46–2.93). ConclusionsPatients with cancer are at a high risk of PD-related death; particularly, mouth-to-stomach cancers and potentially obstructing medication for PD are attributable to a high mortality risk. Careful management, including adequate PD treatment, would benefit cancer survivors with PD and reduce the risk of PD-related death.

Guvacoline in betel nuts directly binds to and inhibits AChE activity, lowering ACh levels released by neurons

This paper investigates guvacoline, a compound found in betel nut, and its activity on acetylcholine level. Betel nuts are the chewable seeds of plant used in Chinese traditional medicine. It is commonly used all over southern Asia and the east African seaboard, being the fourth most commonly used drug in the world. It is known for being carcinogenic for throat cancer. Immediate symptoms of betel nut chewing indicate activation of the parasympathetic system, in which acetylcholine and acetylcholinesterase is involved. This paper predicts that guvacoline, found in areca nuts, increases free acetylcholine levels released from neurons by allosterically binding to acetylcholinesterase inhibiting it.