Cancers Of Upper Aerodigestive Tract Research Articles

Application of Multilayer Evidence for Annotation of C-Terminal BRCA2 Variants.

Simple SummaryThe potential pathogenic role of germline BRCA2 c.9976A>T and c.10095delinsGAATTATATCT was evaluated in hereditary breast and ovarian cancer (HBOC) patients by investigating 2491 probands and verified in an independent cohort of 122,209 patients. Although the c.10095delinsGAATTATATCT variant was more prevalent among patients compared to control populations, no increased risk for cancer was found. No association between c.9976A>T and clinicopathological parameters or elevated risk for HBOC cases was detected. However, lung cancer was more prevalent in families carrying c.9976A>T compared to pathogenic BRCA1/BRCA2 carrier families. An increased frequency of pancreatic cancer was found in families where c.9976A>T occurred together with other pathogenic BRCA1 variants. The C-terminal stop codon variants showed no association with other pathogenic BRCA2 variants. No loss of heterozygosity (LOH) in tumor tissue and no allelic imbalance in RNA level were confirmed. The c.9976A>T variant may be considered as a potential risk for lung cancer, and a potential modifying factor in pancreatic cancer when it occurs along with the pathogenic BRCA1 variant, although this observation should be validated in a larger sample cohort.The clinical relevance of the BRCA2 C-terminal stop codon variants is controversial. The pathogenic role of the germline BRCA2 c.9976A>T and c.10095delinsGAATTATATCT variants in hereditary breast and ovarian cancer (HBOC) patients was evaluated. An association with clinicopathological parameters was performed in 2491 independent probands diagnosed with HBOC and in 122,209 cancer patients reported earlier. Loss-of-heterozygosity (LOH) in tumor samples and allelic imbalance in RNA extracted from peripheral blood cells were investigated. Neither c.10095delinsGAATTATATCT or c.9976A>T variants showed significant association with clinicopathological parameters or elevated risk for HBOC-associated tumors. Lung cancer was more prevalent in families carrying the c.9976A>T variant compared to pathogenic BRCA1 or BRCA2 carrier families. An increased prevalence of pancreatic cancer was found in families where c.9976A>T occurred together with other pathogenic BRCA1 variants. An increased risk for familial pancreatic, lung and upper aero-digestive tract cancers was confirmed in the validation set. Regarding BRCA2 C-terminal variants, no linkage with other pathogenic BRCA2 variants, no LOH in tumor tissue and no allelic imbalance in RNA level were confirmed. The c.9976A>T variant may be considered as a potential risk for lung cancer, and a potential modifying factor in pancreatic cancer when it occurs along with the pathogenic BRCA1 variant, although this observation should be validated in a larger sample cohort.

Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation.

Diagnosed in more than 90% of cervical cancers, the fourth deadliest cancer in women, human papillomavirus (HPV) is currently the most common pathogen responsible for female cancers. Moreover, HPV infection is associated with many other diseases, including cutaneous and anogenital warts, and genital and upper aerodigestive tract cancers. The incidence and prevalence of these pathologies vary considerably depending on factors including HPV genotype, regional conditions, the study population, and the anatomical site sampled. Recently, features of the cervicovaginal microbiota are found to be associated with the incidence of HPV-related diseases, presenting a novel approach to identify high-risk women through both blood and cervical samples. Overall, the HPV repartition data show that HPV infection and related diseases are more prevalent in developing countries. Moreover, the available (2-, 4-, and 9-valent) vaccines based on virus-like particles, despite their proven effectiveness and safety, present some limitations in terms of system development cost, transport cold chain, and oncogenic HPV variants. In addition, vaccination programs face some challenges, leading to a considerable burden of HPV infection and related diseases. Therefore, even though the new (9-valent) vaccine seems promising, next-generation vaccines as well as awareness programs associated with HPV vaccination and budget reinforcements for immunization are needed.

Computer vision techniques for Upper Aero-Digestive Tract tumor grading classification – Addressing pathological challenges

5• A novel hybrid FR-PSO based SVM model is proposed for Upper Aero Digestive Tract Cancer grading classification . 5• Morphological analysis of benign and malignant tumours is carried out using image processing techniques . 5• Finding inter cellular Bridges to find the dysplasia type of tumours in UADT. 5• A Force Reconstructed PSO technique is used to fine-tune the SVM hyper plane for multiple class grading classification. Oral cancer is one of the common cancer types which scales higher in death rate every year. The connectivity of two different cavities like oral cavity and nasal cavity is known as Upper Aero-Digestive Tract (UADT). Both oral and nasal cavities consist of thirteen connecting sites from mouth to upper stomach. The traditional pathological analysis like manual microscopic review brings out major intra and interobserver variability problem. A new automated system is proposed using computer vision techniques to focus and analyse major pathological problems like intra and interobserver variability problem and mis-classification of dysplasia type of tumours. The morphological behaviour of biopsy tissue samples are analysed digitally with different sites of UADT and different cancerous and non-cancerous stages. The proposed technique will play a major role in assisting the manual pathology procedure for analysing the morphology of dysplasia type of tumours and classification of tumour gradings. A method is proposed which integrates an alternate process to find the morphology of dysplasia type tumours using different image processing techniques. A state-of-the-art Force Reconstructed Particle Swarm Optimization Based SVM is proposed for UADT oral cancer classification for ten different oral cavity sites. The proposed classification technique achieved 94 % accuracy.

Toothbrushing frequency and gastric and upper aerodigestive tract cancer risk: A meta-analysis.

Results of epidemiological studies evaluating the association between toothbrushing and gastric and upper aerodigestive tract (UADT) cancer risk showed inconsistent results. The purpose of this study was to evaluate the association between toothbrushing and gastric and UADT cancer risk and quantify the dose-response association between them. We searched the PubMed, EMBASE and Cochrane Library databases to identify relevant studies on toothbrushing and gastric and UADT cancer risk. Statistical analyses were performed using STATA 12.0 software. A total of 30 studies of involving 1194017 participants met eligibility criteria and were included in the meta-analysis. Meta-analysis using a random-effect model showed that the high frequency of toothbrushing was associated with significantly reduced risk of gastric and UADT cancers (OR: 0.55, 95% CI 0.46-0.64, P<.05). Our dose-response analysis presented that every increased toothbrushing per day might reduce oral cavity cancer risk by 6%, pharyngeal cancer risk by 11%, laryngeal cancer risk by 3%, oesophageal cancer risk by 6% and gastric cancer risk by 4%. This meta-analysis suggested the negative relationship between frequency of toothbrushing and risk of gastric and UADT cancers. Toothbrushing may be a protective factor for gastric and UADT cancers. However, this association must be further validated through large prospective studies.

Papillomaviruses and Upper Aero Digestive Tract Cancers in Cameroon. A Prospective Study

Papillomaviruses and Upper Aero Digestive Tract Cancers in Cameroon. A Prospective Study

Prognosis and Survival of Nasopharyngeal Cancer in Cameroon

Background: Nasopharyngeal carcinoma (NPC) is an entity belonging to up-per aerodigestive tract Cancers. NPC is more widespread in Southern China and South East Asia. In our country, it is the leading cause of head and neck cancers. Its prognosis remains bleak because of the late stage at diagnostic. Objectives: The objectives of this study were to determine the prognostic fac-tors and survival rate of patients with nasopharyngeal cancer in six reference hospitals in Cameroon. Material and Methods: It was a retrospective analytic study, conducted from January 2009 to December 2018. It was conducted in oncology, surgery and Ear Nose and Throat (ENT) units of six reference hos-pitals. Data from 114 files meeting the inclusion were collected. We have drawn survival curves and determined the different survival probabilities with the help of Kaplan-Meier Method. The different survival curves were compared using the Log-Rank Test (P < 0.05), variables that were statistically associated with the 5% cut off were introduced into the Cox regression model for multivariate analysis, thus allowing us to bring out the prognostic factors significantly associated with survival. Results: The mean age at the time of diagnosis of the 114 patients recruited was 45.30 ± 17.14 years. The predominant histological type was the UCNT (Undifferentiated Carcinoma of the NasoPharynx) representing 84.2%. According to the WHO classification, 2 patients were classified as stage I (1.8%), 33 as stage II (28.9%), 42 as stage III (36.8%), 25 as stage IV A (21.9%) and 12 as stage IV B (10.5%). At the end of the survival assessment period, 34 patients were dead and 73 patients (64%) were still alive. The median overall survival was 44 months. The overall survival rates at one, two, three, and four years were 80%; 74%; 68%; 44%, respectively. The prognostic factors associated with poor survival were: late consultation time of more than 12 months, N3 lymph node involvement, 3 and 4 advanced clinical stages. Conclusion: The study showed a low survival, with a median overall survival of 44 months. The overall survival rates at one, two, three, and four years were 80%; 74%; 68%; 44% respectively. The prognostic factors associated with poor survival were late consultation time of more than 12 months, N3 lymph Node involvement, 3 and 4 advanced clinical stages. In order to improve this survival, it is recommended that special emphasis be placed on early detection.

Inclusion of a gene-environment interaction between alcohol consumption and the aldehyde dehydrogenase 2 genotype in a risk prediction model for upper aerodigestive tract cancer in Japanese men.

The well‐known gene‐environment interaction between alcohol consumption and aldehyde dehydrogenase 2 (ALDH2) genotype in upper aerodigestive tract cancer risk may improve our ability to identify high‐risk subjects. Here, we developed and validated risk prediction models for this cancer in Japanese men and evaluated whether adding the gene‐environment interaction to the model improved the predictive performance. We developed two case‐cohort datasets in the Japan Public Health Center‐based Prospective Study: one from subjects in the baseline survey for model development (108 cases and 4049 subcohort subjects) and the second from subjects in the 5‐year follow‐up survey for model validation (31 cases and 1527 subcohort subjects). We developed an environmental model including age, smoking status, and alcohol consumption, and a gene‐environment interaction model including age, smoking status, and the combination of alcohol consumption and the ALDH2 genotype. We found a statistically significant gene‐environment interaction for alcohol consumption and the ALDH2 genotype. The c‐index for the gene‐environment interaction model (0.71) was slightly higher than that for the environmental model (0.67). The values of integrated discrimination improvement and net reclassification improvement for the gene‐environment interaction model were also slightly higher than those for the environmental model. Goodness‐of‐fit tests suggested that the models were well calibrated. Results from external model validation by the 5‐year follow‐up survey were consistent with those from the model development by the baseline survey. The addition of a gene‐environment interaction to a lifestyle‐based model might improve the performance to estimate the probability of developing upper aerodigestive tract cancer for Japanese men.

Upper Aero Digestive Tract Cancer: A Detailed Exploration Using Computer Vision Techniques

Upper Aero Digestive Tract Cancer: A Detailed Exploration Using Computer Vision Techniques

Hypertension is associated with oral, laryngeal, and esophageal cancer: a nationwide population-based study

Several studies have reported an association between hypertension and upper aerodigestive tract cancer, but no large-scale, population-based studies have been conducted to confirm this.The aim of this study was to explore the association between hypertension and risk of upper aerodigestive tract cancer in Koreans. Participants who underwent a national health screening examination from January 1 to December 31, 2009 (n = 9,746,606) were enrolled. We assessed the development of oral, laryngeal, or esophageal cancer until 2016 using records from the Korean Health Insurance claims database during the study period. During the seven-year follow-up period, 6,062, 2,658, and 4,752 subjects were newly diagnosed with oral, laryngeal, and esophageal cancer, respectively. Participants with metabolic syndrome had the highest risk of developing oral cancer (hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.03–1.16), laryngeal cancer (HR 1.27, 95% CI 1.17–1.38), and esophageal cancer (HR 1.11, 95% CI 1.04–1.19). Hypertension was a remarkable risk factor for each cancer (HR 1.11, 95% CI 1.04–1.17 for oral cancer; HR 1.23, 95% CI 1.13–1.33 for laryngeal cancer; HR 1.25, 95% CI 1.18–1.33 for esophageal cancer) after adjusting for age and other variables including gender, smoking status, alcohol intake, exercise, body mass index, and diabetes. Patients with untreated hypertension were at highest risk of developing oral cancer (HR 1.15; 95% CI 1.05–1.26), laryngeal cancer (HR 1.25; 95% CI 1.09–1.44), and esophageal cancer (HR 1.47; 95% CI 1.33–1.63) after adjusting for confounders. Hypertension was associated with the risk of oral, laryngeal, and esophageal cancer, despite of the lack of detailed biochemical information including the cancer cell types (squamous cell carcinoma or adenocarcinoma), cancer stage, physical findings and other medical history. Further studies are warranted to determine the reasons for this association and to establish effective interventions in this vulnerable population.

Abstract B129: Does insurance status explain the racial disparity in survival outcome seen in upper aerodigestive tract cancers in the United States?

Abstract Upper Aerodigestive tract (UADT) cancers are primarily squamous cell carcinomas that affect the oral cavity (hard palate, front 2/3 of tongue, gums, mucosal lining of lips and cheeks, and the floor of the mouth), oropharynx (base of the tongue, soft palate, and tonsils), hypopharynx, larynx (epiglottis and vocal cords), and the upper third of the esophagus with a five-year survival rate of 65.3% for oral cavity and pharyngeal cancers. If the cancer is detected during the localized stage, the survival rate improves to 84.4% (SEER 18 2009-2015).There have been several risk factors implicated in the pathogenesis of UADT cancers such as, male gender, smoking, alcohol use, and infection with human papilloma virus (HPV) for oropharyngeal cancers. The current literature suggests that regardless of stage people of African descent have a lower incidence of UADT cancers, but higher mortality rates compared to Caucasians. There are many proposed explanations for this paradoxical trend seen in African Americans. However, there is a paucity of research addressing this problem. We seek to understand if socioeconomic status is the underlying factor driving this disparity. We analyzed de-identified data collected from the Surveillance, Epidemiology, and End Results (SEER) program for 114,510 UADT cancer patients diagnosed from 2007-2016. We hypothesized that people who were uninsured or on Medicaid would have a life expectancy that was significantly reduced compared to those that had private insurance or Medicare regardless of race, tumor grade, gender or site of the cancer. Our study design is retrospective cohort. Our multivariate analysis model utilizes survival analysis techniques such as Kaplan-Meier survival, hazard curves and proportional hazards regression to analyze the survival time of our patients as a function of demographic and clinical variables. Survival months ranged from 0 to 119 months, with 25,122 patients experiencing death due to UADT cancers. The proportional hazards regression revealed that across all insurance groups (Insured, Uninsured, Medicaid, and Unknown) the survival time for Non-Hispanic Black People was significantly reduced compared to the other race/ethnicities (Asians, Caucasians, Hispanics (all races)) with Non-Hispanic Caucasians having the highest survival rate. Determining that the racial disparity exists regardless of insurance status, tumor grade, gender, and site of cancer can guide future researchers to focus on biological differences or other factors such as lack of access to care that underlie disease survival for UADT cancers. Citation Format: Joycemary G Amponsem, Dana Marshall, Derek Wilus, Mohammad Tabatabai. Does insurance status explain the racial disparity in survival outcome seen in upper aerodigestive tract cancers in the United States? [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B129.

Comparison of tobacco-specific nitrosamine levelsin smokeless tobacco products: High levels in products from Bangladesh.

Bangladesh exhibits the second highest rate of smokeless tobacco (SLT) product usage in the world, and this has been associated with the high upper aerodigestive tract cancer incidence in this country. The goal of the present study was to examine the levels of the highly carcinogenic tobacco-specific nitrosamines (TSNAs) in Bangladeshi SLT products and compare these levels to that observed in SLT brands from southeast Asia and the USA. The levels of TSNAs and nicotine were determined by LC-MS/MS in twenty-eight SLT brands and several tobacco additives from Bangladesh, as well as several SLT brands from India, Pakistan and the USA. The levels of N-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosoanatabine (NAT) and N-nitrosoanabasine (NAB) in Bangladeshi SLT brands ranged from 1.1–59, 0.15–34, 0.79–45, and 0.037–13 μg/g SLT powder, respectively. The mean levels of the highly carcinogenic TSNAs (NNN+NNK) were 7.4-, 2.4-, and 63-fold higher in Bangladeshi SLT products as compared to SLT brands from the USA, India and Pakistan, respectively; these trends were also observed for NAT and NAB. Similar mean levels of nicotine were observed in the Bangladeshi brands (31 mg/g powder) versus brands from the USA (25 mg/g powder) and India (20 mg/g powder); they were 3-fold higher than brands from Pakistan (10 mg/g powder). Gul SLT brands exhibited the highest pH and the highest levels of unprotonated nicotine. The high levels of TSNAs in Bangladeshi SLT brands may be an important factor contributing to the high rates of upper aerodigestive tract cancer in Bangladesh.

Meta-analysis of the association between dietary inflammatory index (DII) and upper aerodigestive tract cancer risk.

Background:Epidemiological studies have reported an inconsistent relationship between dietary inflammatory index (DII) and upper aerodigestive tract (UADT) cancer risk. However, no systematic review or meta-analysis has been reported up to now. To quantify the association between DII and UADT cancer risk, we performed this meta-analysis.Methods:The PubMed, EMBASE, Web of Science and Cochrane Library database were searched for relevant studies from inception December 2018. All case-control studies investigating the association between DII and UADT cancer risk were selected.Results:A total of 9 case-control studies were identified, involving 13,714 participants. The adjusted pooled OR of UADT cancer for the highest (the most pro-inflammatory diet) vs lowest (the most anti-inflammatory diet) DII categories were 2.27 (95% CI: 1.89–2.73). Subgroup analysis showed that individuals with the highest category of DII score were independently associated with esophagus cancer (OR = 2.53, 95% CI: 1.74–3.68), oral cavity cancer (OR = 2.23, 95% CI: 1.73–2.86), pharyngeal cancer (OR = 2.02, 95% CI: 1.54–2.64), and laryngeal cancer (OR = 2.05, 95% CI: 0.85–4.93).Conclusion:This meta-analysis suggested that the most pro-inflammatory diets (the highest DII scores) are associated with increased UADT cancer risk. However, the association between DII and laryngeal cancer risk need to be further investigated.

High TLR4 expression predicts a poor prognosis after esophagectomy for advanced thoracic esophageal squamous cell carcinoma.

Poor oral health is an independent risk factor for upper aerodigestive tract cancers, including esophageal squamous cell carcinoma (ESCC). The pattern recognition receptor Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide in the cell walls of Gram-negative periodontal pathogens associated with the development and progression of ESCC. It is, therefore, plausible that TLR4 plays a crucial role in the pathogenesis of ESCC. We used an ESCC tissue microarray to confirm expression of TLR4 in patients with ESCC and to determine whether TLR4 expression status correlates with the clinicopathological features of these patients or their prognosis after esophagectomy. We also tested whether the combined expression statuses of TLR4 and TLR3 better correlate with prognosis in these patients than either parameter alone. Clinical ESCC samples from all 177 patients tested showed expression of TLR4. Moreover, high TLR4 expression (3 + and 2 +) correlated with poorer 5-year overall survival after esophagectomy than lower TLR4 expression (1 +) (p = 0.0491). Patients showing high TLR4 expression tended to have a poorer prognosis whether treated with surgery alone or with surgery and adjuvant chemotherapy. Univariate and multivariate analyses showed TLR4 expression status to be an independent prognostic factor affecting 5-year overall survival. Patients exhibiting high TLR4 expression with low TLR3 expression had a much poorer prognosis than other patients (p = < 0.0001). High TLR4 expression predicts a poor prognosis in advanced thoracic ESCC patients after esophagectomy.

Association between dietary inflammatory index and upper aerodigestive tract cancer risk: A systematic review and dose-response meta-analysis.

The relationship between dietary inflammatory index (DII) and upper aerodigestive tract (UADT) cancer risk have been investigated in a growing number of epidemiological studies. However, their findings were inconsistent, and no systematic review or meta-analysis has been conducted up to now. This meta-analysis was carried out to examine potential dose-response relationship between DII score and UADT cancer risk. A systematic search was conducted for relevant studies in PubMed and Web of Science up to March 28, 2019. Categorical meta-analysis as well as linear and non-linear dose-response meta-analysis were performed to evaluate association between DII and UADT cancer risk. Nine case-control studies with a total of 4138 cases and 15,326 healthy controls were eligible in the present meta-analysis. The pooled odds ratios (ORs) of UADT cancer risk were 2.07 [95% confidence interval (CI): 1.82, 2.35] for the highest DII score compared with the lowest and 1.53 (95% CI: 1.39, 1.69) for higher DII score compared with lower score, respectively. Furthermore, a one-unit increment in DII score was associated with an increased risk of 18% for UADT cancers (OR: 1.18; 95% CI: 1.15, 1.21). An upward trend towards a positive association between elevated DII score and UADT cancer risk was also observed in non-linear dose-response meta-analysis. The present meta-analysis provides evidence of highly pro-inflammatory diets that might increase risk of UADT cancers. Therefore, reducing pro-inflammatory components in diets should be considered to prevent and control UADT cancers.

Periodontitis, oral hygiene habits, and risk of upper aerodigestive tract cancers: a case-control study in Maharashtra, India.

Chronic destructive periodontitis, a cause of systemic inflammation, affects some 10% to 15% of adults across the globe, with severity of disease increasing with age. The aim of this study was to explore the relationship between periodontitis and oral hygiene habits and upper aerodigestive tract(UADT) cancers. We conducted a case-control study, which included 240 UADT cancer cases and 240 controls matched by gender and age (±5years) from 2 different hospitals in Pune, India.In-person interviews and intraoral examinations were conducted for all patients. Severe periodontitis and greater than 5 missing teeth were associated with a significant risk of UADT cancers (adjusted odds ratio [OR] 2.25, 95% confidence interval [CI] 1.12-4.91; adjusted OR 3.28, 95% CI 1.95-5.49). Among the self-reported oral hygiene habits, dental checkups only at the time of pain was associated with an elevated risk for UADT cancers (adjusted OR 4.12; 95% CI 2.63-6.47). Topical application of mishri (black powder obtained by roasting and grinding tobacco) on gums (adjusted OR 3.06; 95% CI 1.75-5.35) and toothbrushing frequency less than once daily; (adjusted OR 2.09; 95% CI 1.27-3.45) were also associated with an elevated risk. Furthermore, the habit of ever chewing tobacco was associated with an elevated risk of severe periodontitis. Severe periodontitis is associated with an elevated risk for UADT cancers, and tobacco chewing strengthens this association in this population.

Smokeless Tobacco Use, Cigarette Smoking, and Upper Aerodigestive Tract Cancers: A Case-Control Study in the Batna Region, Algeria, 2008-2011.

Background:A significant proportion of the Algerian population uses tobacco products and is at risk of developing tobacco-associated cancers.Aims:This case-control study reports on the association between tobacco use and the occurrence of upper aerodigestive tract (UADT) cancers in Batna, Algeria.Methods:Incident primary UADT cancer cases in residents of Batna in 2008-2011 were identified using the regional tumor registry. One hospital and 1 population control were matched to each case by sex, year of birth, and residence. Information on tobacco use was collected, and odds ratios (ORs) were obtained using conditional logistic regression also after sex stratification.Results:The study included 192 cases (80%) of the 241 primary UADT cancer cases identified and 384 controls. Males represented 76.6% of cancer cases. Cancers of the nasopharynx (48%) and the larynx (26%) were the most common types. Ever use of smokeless tobacco (ST) (OR = 1.0; 95% confidence interval [CI]: 0.6-1.5) or current ST use (OR = 1.1; 95% CI: 0.6-1.7) was not associated with overall risk of UADT cancers. Associations with cancers of the nasopharynx (OR = 1.5; 95% CI: 0.5-4.6) and oral cavity/oropharynx (OR = 3.0; 95% CI: 0.8-11.8) were found when comparing use of ST only to no consumption of any tobacco. Cigarette smoking was associated with an increase in the overall risk of UADT cancers, with a 3-fold increase in the risk of laryngeal cancer when comparing smoking only to no consumption of any tobacco (OR = 3.3; 95% CI: 1.0-11.5). Associations for smokers who also consumed ST differed by cancer site.Conclusion:In this study from Algeria dominated by male cases and by cancer in the nasopharynx, cigarette smoking but not ST was associated with UADT cancer. Analyses by anatomical site and using as reference never use of any type of tobacco suggested few associations with ST but of lower precision.

Increased risk of head and neck cancer in Agent Orange exposed Vietnam Era veterans

ImportanceUnited States military personnel during the Vietnam Era were potentially exposed to Agent Orange, a known carcinogen. The link between Agent Orange and head and neck cancers is largely unknown; laryngeal cancer is currently the only subsite with sufficient evidence of an Agent Orange association. ObjectiveWe aim to determine the relationship between Agent Orange exposure and the incidence of head and neck cancers in Vietnam Era veterans as well as any relationship with head and neck cancer survival. Materials and methodsThe present study utilizes the Veterans Affairs Corporate Data Warehouse (VA CDW) to identify Vietnam Era veterans, their Agent Orange exposure status, limited demographic data, presence of head and neck cancer, and survival data. ResultsOf 8,877,971 Vietnam Era veterans, 22% self-reported exposure to Agent Orange, and 54,717 had a diagnosis of head and neck cancer. Agent Orange exposure significantly predicted upper aerodigestive tract carcinoma, with a relative risk (RR) of 1.10. On subsite analysis, Agent Orange exposure (as well as race, gender, and substance use) was significantly associated with oropharyngeal (RR 1.16), nasopharyngeal (RR 1.22), laryngeal (1.11), and thyroid (1.24) cancers. Agent Orange exposure was associated with improved 10-year overall survival in upper aerodigestive tract cancer patients. Conclusions and RelevanceSelf-reported Agent Orange exposure correlated with increased risks of oropharyngeal, nasopharyngeal, laryngeal, and thyroid cancers, and predicted improved survival in upper aerodigestive tract cancer patients. These findings broaden our understanding of the risks of Agent Orange exposure.

Egg Consumption and Risk of Upper Aero-Digestive Tract Cancers: A Systematic Review and Meta-Analysis of Observational Studies

Limited data are available that summarize the relation between egg intake and the risk of upper aero-digestive tract (UADT) cancers. This systematic review and meta-analysis was conducted to investigate the association between egg intake and the risk of UADT cancers. Medline/PubMed, ISI web of knowledge, EMBASE, Scopus, and Google Scholar were searched using relevant keywords. Observational studies conducted on humans investigating the association between egg consumption and the risk of UADT cancers were included. Overall, 38 studies with a total of 164,241 subjects (27, 025 cases) were included. Based on 40 effect sizes from 32 case-control studies, we found a 42% increased risk of UADT cancers among those with the highest egg consumption (ranging from ≥1 meal/d to ≥1 time/mo among studies) compared to those with the lowest intake (ranging from 0-20g/d to never consumed among studies) (overall OR: 1.42; 95% CI: 1.19, 1.68; P<0.001). However, this association was only evident in hospital-based case-control (HCC) studies (OR=1.50; 95% CI: 1.34, 1.68; P<0.001 for 'oropharyngeal and laryngeal cancer' and OR: 1.27; 95% CI: 1.08, 1.50; P=0.004 for esophageal cancer) and not in population-based case-control (PCC) studies (OR=1.25; 95% CI: 0.59, 2.67; P=0.56 for 'oropharyngeal and laryngeal cancer' and OR: 1.29; 95% CI: 0.92, 1.81; P=0.13 for esophageal cancer). In addition, the association was not significant in prospective cohort studies (overall OR: 0.86; 95% CI: 0.71, 1.04; P=0.11). Considering individual cancers, a positive association was observed between the highest egg consumption, compared with the lowest, and risk of oropharyngeal (OR: 1.88; 95% CI: 1.61, 2.20; P<0.001), laryngeal (OR: 1.83; 95% CI: 1.45, 2.32; P<0.001), oral & pharyngeal & laryngeal (OR: 1.37; 95% CI: 1.12, 1.67; P<0.001), and esophageal cancers (OR: 1.28; 95% CI: 1.10,1.48; P=0.001). We also found an inverse association between egg intake and the risk of oral cancer (OR: 0.78; 95% CI: 0.62, 0.99; P=0.04). In conclusion, high egg consumption (ranging from ≥1 meal/d to ≥1 time/mo among studies) was associated with increased risk of UADT cancers only in HCC studies but not in PCC or prospective cohort studies. PROSPERO registration number: CRD42018102619.

Evaluation of Low-Level Laser Therapy Efficacy in Pain Management of Grade 2 Oral Mucositis Induced by Radiotherapy or Chemoradiotherapy: a Phase II Randomized Study in Patients With Upper Aerodigestive Tract Cancer

Evaluation of Low-Level Laser Therapy Efficacy in Pain Management of Grade 2 Oral Mucositis Induced by Radiotherapy or Chemoradiotherapy: a Phase II Randomized Study in Patients With Upper Aerodigestive Tract Cancer

Identification of acrolein metabolites in human buccal cells, blood, and urine after consumption of commercial fried food.

ScopeAcrolein is a highly electrophilic α,β‐unsaturated aldehyde and is associated with human diseases. It is formed by Maillard reaction during food processing and could be detected in the emissions of overheated cooking oils. Consequently, humans are at risk of acrolein exposure through consumption of such prepared food.Methods and resultsWe conducted three human studies that healthy subjects (21–30 years) were served fried foods including fried chicken and French fries from three commercial fast food restaurants. Acrolein‐related metabolites including urinary 3‐hydroxypropyl mercapturic acid (3‐HPMA), serum acrolein‐protein conjugates (Acr‐FDP), and buccal acrolein‐induced DNA damages (Acr‐dG adducts) along with GSH levels in serum or buccal cells were investigated for different times after consumption.ConclusionUrinary 3‐HPMA levels were increased after 2‐hr consumption of fried food with an elimination half‐life of 10 hr. In addition, increased Acr‐dG adducts in oral cavity were inversely correlated to buccal glutathione (GSH) levels after consumption. However, there was no significant change in systemic GSH levels or Acr‐FDP adducts in serum. These results indicate that exposure of acrolein from consuming fried food affects local oral cavity homeostasis. This may provide a possible link between intake of fried food and increased risk of upper aerodigestive tract cancers.