Risk Of Oral Cavity Cancer Research Articles

Sugar-sweetened beverage intake and risk of oral cavity cancer: Results from 3 prospective US cohort studies.

10570 Background: Approximately 65% of adults in the US consume sugar-sweetened beverages (SSBs) daily, and consumption of SSBs substantially increased across successive birth cohorts in the US until 2000. Previous authors have identified an association between early-onset digestive tract cancers and SSBs. Recently, early-onset (<50 years) oral cavity squamous cell carcinoma has been observed in non-smoking, non-drinking individuals. The objective of this study was to investigate the association between SSBs and development of oral cavity cancer (OCC) in smokers, non-smokers, and those <50 years of age. Methods: We prospectively examined the association between SSB intake and OCC risk among 165,212 women in Nurses’ Health Study (NHS, 1986-2014) and Nurses’ Health Study II (NHSII, 1991-2015), and 45,790 men in the Health Professionals Follow-Up Study (HPFS, 1986-2014). All participants completed validated food frequency questionnaires (FFQs) every 4 years. Cox proportional hazards models adjusted for age, caloric intake, tobacco pack-years, alcohol intake, and BMI were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between SSB intake and OCC incidence. Results: We identified 129 incident OCC cases in NHS/NHSII over 36 years of follow-up and 99 cases in HPFS over 30 years of follow-up for HPFS. The mean age at study baseline was 44.4 years for NHS/NHSII and 54.1 years for HPFS. Notably, in the multivariable adjusted model, increasing SSB intake was associated with a higher risk of OCC only among female participants in NHS/NHSII. Specifically, those in the highest quartile of SSB intake had a 229% increased risk of OCC compared to the lowest quartile (95% CI 1.29-4.07, ptrend=0.04). In non- or light-drinkers (<5g/day) in NHS/NHSII, SSBs was associated with OCC (HR=2.58, 95% 1.16-5.70, ptrend=0.10, N=81 cases). However, in non- or light-smokers (<5 pack-years), SSB intake was not associated with risk of OCC, though power was limited due to low case numbers (HR=1.56, 95% 0.66-3.68, ptrend=0.45, N=64). In contrast, no association of SSB intake with OCC risk was observed in the male HPFS cohort, overall (N=99) or among non-smokers (N=44). Early-onset OCC (<50 years) was limited to 9 patients, and thus a subset analysis could not be performed. Conclusions: Higher SSB intake was associated with a higher risk of developing OCC in women, but not men, after controlling for known risk factors. Reduction of SSB consumption may serve as a potential strategy to address the increase in OCC observed in recent years.

Alzheimer's disease and oral manifestations: a bi-directional Mendelian randomization study.

Epidemiological studies have provided evidence suggesting an association between Alzheimer's disease (AD) and various oral manifestations. However, conflicting conclusions have been drawn, and whether a causal association truly exists remains unclear. In order to investigate the potential causal association between AD and prevalent oral diseases, we conducted a bi-directional two-sample Mendelian randomization analysis based on summary statistics from genome-wide association studies of AD (N = 63,926), as well as mouth ulcer (N = 461,103), oral cavity cancer (N = 4,151), and periodontal disease (N = 527,652). We identified that one standard increase in the risk of AD was causally associated with a reduced risk of oral cavity cancer (OR = 0.76, 95% CI: 0.63-0.92, p = 3.73 × 10-3). In the opposite direction, oral conditions were not causally associated with risk of AD. The present findings contributed to a better understanding of the correlation between AD and oral conditions, specifically oral cavity cancer. These results also identified new avenues for exploring the underlying mechanisms of oral cavity cancer.

The Risk of Oral Cancer and the High Consumption of Thermally Processed Meat Containing Mutagenic and Carcinogenic Compounds.

The International Agency for Research on Cancer has classified the consumption of heat-processed meat as a direct human carcinogen and the consumption of red meat as a probable carcinogen. Mutagenic and carcinogenic compounds present in meat dishes include, among others, polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HAAs). These compounds can cause the development of gastrointestinal cancer. Oral cancer is one of the world's research priorities due to the ever-increasing incidence rate. However, the effect of diet on oral cancer is still a poorly recognized issue. The aim of this study was to assess the relationship between the risk of oral cancer and dietary ingredients with a particular emphasis on red meat and thermally processed meat. This study was conducted among patients with oral cancer in 2022 and 2023. The shortened standardized Food Frequency Questionnaire (FFQ) and a multivariate regression statistical analysis were used. The high consumption of red meat in general and thermally processed meat, especially smoked, fried, roasted and boiled, increases the risk of oral cavity cancer. Limiting the consumption of meat products and modifying the methods of preparing meat dishes may reduce exposure to carcinogenic compounds from the diet and thus reduce the risk of developing oral cancer.

Inflammatory cytokines mediating the effect of oral lichen planus on oral cavity cancer risk: a univariable and multivariable mendelian randomization study

BackgroundWhile observational studies and experimental data suggest a link between oral lichen planus (OLP) and oral cavity cancer (OCC), the causal relationship and the role of inflammatory cytokines remain unclear.MethodsThis study employed a univariable and multivariable Mendelian Randomization (MR) analysis to investigate the causal relationship between OLP and the risk of OCC. Additionally, the potential role of inflammatory cytokines in modulating this association was explored. Instrumental variables were derived from genetic variants associated with OLP (n = 377,277) identified in Finngen R9 datasets, with 41 inflammatory cytokines as potential mediators, and OCC (n = 4,151) as the outcome variable. Analytical methods including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO were utilized to assess the causal links among OLP, inflammatory cytokines, and OCC risk. Multivariable MR (MVMR) was then applied to quantify the mediating effects of these cytokines in the relationship between OLP and increased OCC risk.ResultsMR analysis provided strong evidence of a causal relationship between OLP (OR = 1.417, 95% CI = 1.167–1.721, p < 0.001) and the risk of OCC. Furthermore, two inflammatory cytokines significantly influenced by OLP, IL-13 (OR = 1.088, 95% CI: 1.007–1.175, P = 0.032) and IL-9 (OR = 1.085, 95% CI: 1.005–1.171, P = 0.037), were identified. Subsequent analysis revealed a significant causal association only between IL-13 (OR = 1.408, 95% CI: 1.147–1.727, P = 0.001) and higher OCC risk, establishing it as a potential mediator. Further, MVMR analysis indicated that IL-13 (OR = 1.437, 95% CI = 1.139–1.815, P = 0.002) mediated the relationship between OLP and OCC, accounting for 8.13% of the mediation.ConclusionThis study not only elucidates the potential causal relationship between OLP and the risk of OCC but also highlights the pivotal mediating role of IL-13 in this association.

Delaying age at first sexual intercourse provides protection against oral cavity cancer: a mendelian randomization study.

To investigate whether age at first sexual intercourse could lead to any changes in the risk of oral cavity cancer. A two-sample mendelian randomization was conducted using genetic variants associated with age at first sexual intercourse in UK biobank as instrumental variables. Summary data of Northern American from a previous genome-wide association study aimed at oral cavity cancer was served as outcome. Three analytical methods: inverse variance-weighted, mendelian randomization Egger, and weighted median were used to perform the analysis, among which inverse variance-weighted was set as the primary method. Robustness of the results was assessed through Cochran Q test, mendelian randomization Egger intercept tests, MR PRESSO, leave one out analysis and funnel plot. The primary analysis provided substantial evidence of a positive causal relationship age at first sexual intercourse and the risk of oral cavity cancer (p = 0.0002), while a delayed age at first sexual intercourse would lead to a decreased risk of suffering oral cavity cancer (β = -1.013). The secondary outcomes confirmed the results (all β < 0) and all assessments supported the robustness, too (all p > 0.05). The study demonstrates that a delayed sexual debut would provide protection against OCC, thus education on delaying sexual intercourse should be recommended.

Association of gut microbiome and oral cavity cancer: A two sample mendelian randomization and case-control study

IntroductionConsidering the interconnectedness of the oral cavity and gut tract and the presence of abundant natural microbiota in both. We utilized Mendelian Randomization (MR) in a two-sample study to unveil the genetic causal impact of gut microbiota on the development of oral cavity cancer. Materials & methodsThe instrumental variables employed in this study consisted of single nucleotide polymorphisms (SNPs) that demonstrated a robust association with 211 distinct gut microbiota taxa, encompassing a sample size of 18,340 individuals. Our investigation sought to explore the potential causal relationship between these genetic variants and the incidence of oral cavity cancer. To accomplish this, we adopted a random effect inverse variance-weighted approach to analyze the causal effect. Additionally, sensitivity analyses were performed utilizing Cochran's Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests, to assess the robustness and validity of our findings. ResultsFive gut microbiota taxa (the family Prevotellaceae, the genus Alloprevotella, the genus Erysipelatoclostridium, the genus Parabacteroides, the genus Ruminococcus gauvreauii group) are predicted to play a causal role in promoting the initiation of the risk of oral cavity cancer. While the genus Christensenellaceae R 7 group, the genus Intestinimonas, the genus Ruminococcaceae, and the order Bacillales causally reduce the risk of oral cavity cancer. Furthermore, no significant evidence suggesting heterogeneity or pleiotropy was observed. DiscussionThe novel genetic causal effects of 211 gut microbiota taxa on oral cavity cancer are elucidated in this investigation, thus offering valuable insights for clinical interventions targeting oral cavity cancer.

Obesity and head and neck cancer risk: a mendelian randomization study

BackgroundObservational studies have reported controversial results on the association between obesity and head and neck cancer risk. This study aimed to perform a two-sample Mendelian randomization (MR) analysis to assess the causal association between obesity and head and neck cancer risk using publicly available genome-wide association studies (GWAS) summary statistics.MethodsSingle-nucleotide polymorphisms (SNPs) for obesity [body mass index (BMI), waist-to-hip ratio (WHR), whole body fat mass, lean body mass, and trunk fat mass] and head and neck cancer (total head and neck cancer, oral cavity cancer, oropharyngeal cancer, and oral cavity and oropharyngeal cancer) were retrieved from published GWASs and used as genetic instrumental variables. Five methods including inverse-variance-weighted (IVW), weighted-median, MR–Egger, weighted mode, and MR-PRESSO were used to obtain reliable results, and odds ratio with 95% confidence interval (CI) were calculated. Tests for horizontal pleiotropy, heterogeneity, and sensitivity were performed separately.ResultsGenetically predicted BMI was negatively associated with the risk of total head and neck cancer, which was significant in the IVW [OR (95%CI), 0.990 (0.984–0.996), P = 0.0005], weighted-median [OR (95%CI), 0.984 (0.975–0.993), P = 0.0009], and MR-PRESSO [OR (95%CI), 0.990 (0.984–0.995), P = 0.0004] analyses, but suggestive significant in the MR-Egger [OR (95%CI), 0.9980 (0.9968–0.9991), P < 0.001] and weighted mode [OR (95%CI), 0.9980 (0.9968–0.9991), P < 0.001] analyses. Similar, genetically predicted BMI adjust for smoking may also be negatively associated with the risk of total head and neck cancer (P < 0.05). Genetically predicted BMI may be negatively related to the risk of oral cavity cancer, oropharyngeal cancer, and oral cavity and oropharyngeal cancer (P < 0.05), but no causal association was observed for BMI adjust for smoking (P > 0.05). In addition, no causal associations were observed for other exposures and outcomes (all P > 0.05).ConclusionThis MR analysis supported the causal association of BMI-related obesity with decreased risk of total head and neck cancer. However, the effect estimates from the MR analysis were close to 1, suggesting a slight protective effect of BMI-related obesity on head and neck cancer risk.

Relationship between Menopausal Hormone Therapy and Oral Cancer: A Cohort Study Based on the Health Insurance Database in South Korea.

The association between the development of oral cavity cancer and sex hormones is unclear and inconsistent. This study aimed to evaluate the relationship between menopausal hormone therapy (MHT) and oral cavity cancer in menopausal women in Korea. In this retrospective cohort study, data were provided by the Korean National Health Insurance Service regarding a screening examination conducted from 1 January 2002 to 31 December 2019. Postmenopausal patients aged ≥40 years were considered, including 333,072 women in the MHT group and 847,558 women in the non-MHT group. Participants were divided into MHT types (tibolone, combined estrogen plus progestin by manufacturer, estrogen, combined estrogen plus progestin by physician, and topical estrogen), and the risk factors for oral cavity cancer development were analyzed. There was no significant association between smoking, alcohol consumption, age at menarche, and age at menopause with oral cavity cancer in postmenopausal women. However, the oral estrogen (hazard ratio [HR]: 1.633; 95% confidence interval [CI]: 1.35–1.976) and tibolone groups (HR: 1.633; 95% CI: 1.35–1.976) were associated with an elevated risk of oral cavity cancer. The results of this study suggest that MHT increases the risk of oral cavity cancer in postmenopausal women.

Association between oral cavity cancer and metabolic syndrome.

Few studies have been conducted on the association between oral cavity cancer and metabolic diseases. This study aimed to investigate the relationship between oral cavity cancer and metabolic diseases. This cohort study used the database of the Korean National Health Insurance Service, which contains medical data of 97% of the Korean population. Oral cavity cancer occurred in a total of 2718 patients. Metabolic syndrome was defined according to IDF criteria. The Cox proportional hazard regression model was used. The HR for oral cavity cancer in patients with metabolic syndrome was 1.113(95% CI 1.006-1.232), which was significantly higher than that in normal patients, especially in males (p = 0.0386). When the number of metabolic syndrome factors was ≥ 3, the HR of oral cavity cancer was 1.191(95% CI 1.026-1.383), which was significantly higher than that of 0 metabolic syndrome factors, especially in males (p = 0.0218). When the number of metabolic syndrome factors was ≥ 3, the HR for oral cavity cancer was 1.439(95% CI 1.066-1.942), which was significantly higher than that of 0 metabolic syndrome factors, especially in males aged < 50years (p = 0.0173). Metabolic syndrome increases the risk of oral cavity cancer only in males. In addition, the incidence of oral cavity cancer increased as the number of factors constituting metabolic syndrome increased, only in young males aged < 50years. Thus, metabolic syndrome is an important risk factor for oral cavity cancer, particularly in young males.

Evaluating the reasons for delays in treatment of oral cavity cancer patients

Abstract The growing increase in oral cavity cancer (OSCC) incidence constitutes a severe diagnostic-therapeutic problem – and early diagnosis, as well as medical treatment remain important priorities of maxillofacial oncology. The aim of this paper was to determine the reasons for delays in the diagnostics and treatment of oral cavity cancer patients. The study focused on 248 patients (=56.1 years) post-surgery, in which delays in diagnostics and treatment were reported. As for the causes, most frequently, in 171 cases (69.0%), patient delays were reported, in 56 cases, physician delays were observed, and in 21 cases (8.5%), organizational reasons were to blame. The median time period between the onset of the symptoms and seeking medical attention was 143 days. Time interval between the first contact with a doctor and commencement of oncological treatment was 33.2 days approximately. The majority of the patients were not aware of the oral cavity cancer risk. Misdiagnosis of symptoms as inflammation, as well as prolonged antibiotic therapy and diagnostics constitute main reasons for physician and organization-al/health care system delays. Raising patients’ awareness of cancer risk, as well as educational and promotional programs for physicians are the principal goals of a strategy aiming to enhance oral cancer diagnosis.

Risk and incidence of head and neck cancers in veterans living with HIV and matched HIV-negative veterans.

Persons living with HIV/AIDS have a higher incidence of virus-related and tobacco/alcohol-related cancers. This study is the first to estimate the effect of HIV versus HIV-negative veterans on the risk of head and neck squamous cell carcinoma incidence in a large retrospective cohort study. The authors constructed a retrospective cohort study using patient data from 1999 to 2016 from the National Veterans Administration Corporate Data Warehouse and the VA Central Cancer Registry. This cohort study included 45,052 veterans living with HIV/AIDS and 162,486 HIV-negative patients matched by age, sex, and index visit (i.e., HIV diagnosis date or clinic visit date). The age-standardized incidence rates and estimated adjusted hazard ratios were calculated with a Cox proportional hazards regression for oropharyngeal and nonoropharyngeal head and neck cancer squamous cell carcinoma (HNSCC). The authors also abstracted human papillomavirus (HPV) status from oropharyngeal HNSCC diagnosed after 2010. Veterans living with HIV/AIDS (VLWH) have 1.71 (95% confidence interval [CI], 1.36, 2.14) times the risk of oropharyngeal cancer and 2.06 (95% CI, 1.76, 2.42) times the hazard of nonoropharyngeal cancer compared with HIV-negative veterans. VLWH with oropharyngeal squamous cell carcinoma (OPSCC) were more likely to be HPV-positive (N=30 [81.1%]) than the HIV-negative veterans with OPSCC (N=50 [67.6%]), although this difference was not significant (p=.135). For nonoropharyngeal cancer, the increased risk of oral cavity cancer among VLWH drove the increased risk. The study results suggest that HIV may play a role in virally mediated and nonvirally mediated HNSCC. As the HIV prevalence rises in the United States due to better survival and the incidence of HPV-positive oropharyngeal HNSCC increases, the interaction between HPV and HIV becomes increasingly relevant.

Development and Validation of a Non-Invasive, Chairside Oral Cavity Cancer Risk Assessment Prototype Using Machine Learning Approach.

Oral cavity cancer (OCC) is associated with high morbidity and mortality rates when diagnosed at late stages. Early detection of increased risk provides an opportunity for implementing prevention strategies surrounding modifiable risk factors and screening to promote early detection and intervention. Historical evidence identified a gap in the training of primary care providers (PCPs) surrounding the examination of the oral cavity. The absence of clinically applicable analytical tools to identify patients with high-risk OCC phenotypes at point-of-care (POC) causes missed opportunities for implementing patient-specific interventional strategies. This study developed an OCC risk assessment tool prototype by applying machine learning (ML) approaches to a rich retrospectively collected data set abstracted from a clinical enterprise data warehouse. We compared the performance of six ML classifiers by applying the 10-fold cross-validation approach. Accuracy, recall, precision, specificity, area under the receiver operating characteristic curve, and recall–precision curves for the derived voting algorithm were: 78%, 64%, 88%, 92%, 0.83, and 0.81, respectively. The performance of two classifiers, multilayer perceptron and AdaBoost, closely mirrored the voting algorithm. Integration of the OCC risk assessment tool developed by clinical informatics application into an electronic health record as a clinical decision support tool can assist PCPs in targeting at-risk patients for personalized interventional care.

Life Course Tobacco Smoking and Risk of HPV-Negative Squamous Cell Carcinomas of Oral Cavity in Two Countries

BackgroundTobacco smoking remains one of the major risk factors for oral cavity cancers (OCC), a subgroup of head and neck cancer (HNC) less attributed to human papillomavirus (HPV) infection. Although a strong dose-dependent association between tobacco smoking and OCC exists, several important questions on the age-dependent effects of this habit remain unanswered. We investigated which life course hypothesis best describes the association between tobacco smoking and HPV-negative (HPV−ve) OCC in Canada and India.MethodsWe used data from the HeNCe Life study, a hospital-based case-control study conducted in Canada and India, using similar protocols. Cases were newly diagnosed subjects with primary squamous cell carcinomas of the head and neck region. Control subjects were patients with non-cancer selected from various outpatient clinics in a hospital located in the same catchment area as the cases and frequency-matched to cases according to age and sex. We collected information on an array of life course exposures using a structured questionnaire with the help of a life grid. Tobacco exposure (pack-years) during three life periods (≤ 30, 31−50, and >50 years of age) was calculated from the entire life course history of smoking. We used CDx brushes to collect oral exfoliated cells. Alpha HPV DNA detection and genotyping were performed for 36 HPV genotypes using the linear array. Participants who tested positive for HPV were excluded from the analysis. We used the Bayesian relevant life course exposure model (BRLM) to identify the life course hypothesis that best described the relationship between tobacco smoking and HPV−ve OCC.ResultsWe show evidence for a late-life sensitive period (>50 years of age) for tobacco smoking in relation to the risk of HPV−ve OCC in both Canada and India. An increase of 1 pack-year of tobacco smoking increased the risk of OCC by ~3% in both countries.ConclusionOur findings from the Canadian and Indian data suggest that smoking tobacco after 50 years of age may carry a higher risk of developing oral cancer than earlier in life. Further studies are warranted to confirm the results.

MTHFD1 c.1958G&gt;A and TCN2 c.776G&gt;C polymorphisms of folate metabolism genes and their implication for oral cavity cancer

Abstract Background Cancers of the head and neck can damage the brain, spinal cord, and nerves, as well as the sense organs responsible for contact with the outside world. Oncogenic transformation occurs following mutations that change the function of specific genes, such tumor suppressor genes or oncogenes, and their encoded protein products. Therefore, the aim of this study was to evaluate the relationship between the occurrence of MTHFD1 c.1958G&gt;A and TCN2 c.776G&gt;C gene polymorphisms and the risk of oral cavity cancer. Materials and methods The study population consisted of 439 patients and 200 healthy subjects. Genomic DNA was extracted from peripheral blood and from paraffin-embedded tissue. Analysis of the gene polymorphisms was performed using polymerase chain reaction–restriction fragment length polymorphism. Results Statistically significant differences were found in the distribution of genotypes of the rs2236225 and rs1801198 polymorphisms between patients and controls. Regarding MTHFD1 c.1958G&gt;A, the GA genotype (p&lt;0.0001, OR = 2.91, 95% CI = 1.88–4.49-GA) was more common among patients than healthy subjects. Regarding TCN2 c.776G&gt;C, the frequency of CC genotype (p&lt; 0.0001, OR = 0.17, 95% CI = 0.10–0.33-CC) was significantly less common among patients than healthy subjects. Tobacco smoking, alcohol use, and male gender (p&lt;0.0001) were found to be predictors of the disease. Conclusion The results suggest that the MTHFD1 c.1958G&gt;A polymorphism may be associated with a greater risk of oral cavity cancer, whereas a protective effect has been found for the TCN2 c.776G&gt;C polymorphism.

Association between smokeless tobacco use and oral cavity cancer risk in women compared with men: a systematic review and meta-analysis

BackgroundThe impact of smokeless tobacco (SLT) use on the risk of oral cavity cancer (OCC) has been confirmed; however, the sex-based difference in this association remains inconclusive. Therefore, this study aimed to estimate the association between SLT use and OCC risk in women and compared it to that in men.MethodsPubMed, Embase, and Cochrane Library databases were systematically searched for eligible studies from their inception up to August 2020. Studies reporting the effect estimates of SLT use on OCC risk in men and women, were eligible for inclusion. The relative risk ratio (RRR) was applied to calculate the sex-based difference in the relationship between SLT use and OCC risk, and pooled analysis was conducted using a random-effects model with inverse variance weighting.ResultsNineteen studies reporting a total of 6593 OCC cases were included in the final meta-analysis. The pooled relative risk (RR) suggested that SLT use was associated with an increased risk of OCC in both men (RR, 2.94; 95% confidence interval [CI], 2.05–4.20; P < 0.001) and women (RR, 6.39; 95%CI, 3.16–12.93; P < 0.001). Moreover, the SLT-use-related risk of OCC was higher in women than that in men (RRR,1.79; 95%C, 1.21–2.64; P = 0.003). The risk of OCC related to SLT use in women was still significantly higher than that in men (RRR, 1.75; 95%CI, 1.15–2.66; P = 0.008) after excluding indirect comparison results. Finally, a subgroup analysis suggested significant sex-based differences only in individuals who received chewed smokeless products, regardless of the control definition. Pooled analysis of studies with high design quality confirmed the notably higher risk of OCC in women than in men.ConclusionsThis study found that SLT use was associated with a higher risk of OCC in women than in men. Further large-scale prospective cohort studies should be conducted to verify sex-based differences in the association between use of specific smokeless products and OCC risk.

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.

A Genome-Wide Association Study Identifies Two Novel Susceptible Regions for Squamous Cell Carcinoma of the Head and Neck.

To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which, 434,839 typed and 7,423,250 imputed SNPs were used as the discovery. SNPs with P < 1 × 10-3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from databases of Genotypes and Phenotypes. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96 × 10-9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54 × 10-9 for the leading SNP rs142021700) was identified for hypopharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and expression quantitative trait loci analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of human leukocyte antigen loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN. SIGNIFICANCE: Two novel risk loci for SCCHN in non-Hispanic white individuals highlight the importance of immunologic mechanism in the disease etiology.

Selected CDKN2A and MDM2 polymorphisms in oral cavity cancer.

The head and neck squamous cell carcinoma (HNSCC) is an aggressive human malignancy diagnosed in more than 800 000 new cases worldwide, and mostly arises in the oral cavity, oropharynx, larynx, hypopharynx, and nasopharynx. The study presented here aimed to determine a possible association of rs11515 and rs3088440 gene polymorphisms in the CDKN2A gene (cyclin dependent kinase inhibitor 2A), as well as rs769412 and rs937283 in the MDM2 gene (murine double minute 2), with oral cavity cancer in a sample of Polish population; CDKN2A is crucial in regulating the cell cycle while MDM2 is an oncogene involved in regulating cell proliferation and apoptosis. The study included 95 primary tumor samples following surgical resection from patients, and the control group consisted of 100 healthy individuals. DNA samples were genotyped by employing the 5' nuclease assay for allelic discrimination using TaqMan SNP Genotyping Assays (Applied Biosystems, USA). There was no significant association between any of the polymorphism (rs11515, rs3088440, rs769412 and rs937283) and the oral cavity cancer risk. We found that the AA homozygotes for rs3088440 were significantly more frequent in the control group (OR=0.046, p<0.0001). In addition, the GG genotype of rs769412 was not found in any group. We found no influence of the examined genotypes on clinicopathological parameters, such as T, N and grading values in patients with oral cavity cancer. The results of this study indicate that none of the investigated polymorphisms were associated with the risk of oral cavity cancer in the examined sample of the Polish population.

Smokeless tobacco use and risk of oral cavity cancer

Background/aim Smokeless tobacco has been associated with oral cavity cancer for several decades. The incidence of oral cavity cancer is higher in some parts of the world especially South and South-East Asia including Pakistan. The aim of current study was to evaluate the risk of oral cavity cancer among smokeless tobacco users in our country.Materials and methods A case-control study was conducted between November 2016 and September 2017. Patients diagnosed with oral cavity cancer receiving treatment were included as cases and the attendants of various cancer patients visiting the hospital during the study period were included in the study as controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated and all reported P-values were considered significant at < 0.05. Results The crude OR for the “ever smokeless tobacco users” among cases and controls came out to be 4.98 (95%CI; 2.76–9.01). The OR for snuff users among cases and controls was 4.82 (95%CI; 2.37–9.80) and that for betel leaf users was 4.42 (95%CI; 1.66–11.91) after adjusting for smoking and age.ConclusionOur study provided strong evidence for snuff and betel leaf to be independent risk factors for oral cavity cancer.

Association between coffee intake and the risk of oral cavity cancer: a meta-analysis of observational studies.

The association between coffee intake and the risk of oral cavity cancer has been inconsistent in previous studies. Therefore, we conducted a meta-analysis to summarize the evidence regarding the strength of association between coffee intake and oral cavity cancer. PubMed, Embase, and Cochrane Library were searched to select studies on the relationship between coffee intake and oral cavity cancer conducted up to September 2018. Case-control or cohort studies and those that have reported about the effect estimates with 95% confidence intervals (CIs) of oral cavity cancer according to the different categories of coffee intake were included. The odds ratio (OR) and its corresponding 95% CI were calculated using the random-effects model. Fourteen case-control and five cohort studies that recruited 6456 patients with oral cavity cancer were included in the final quantitative meta-analysis. High versus low coffee intake was associated with a reduced risk of oral cavity cancer (OR: 0.68; 95% CI: 0.56-0.82; P < 0.001) in case-control studies (OR: 0.70; 95% CI: 0.55-0.90; P = 0.006) and cohort studies (OR: 0.65; 95% CI: 0.48-0.87; P = 0.004). Moreover, intermediate coffee intake was significantly associated with a reduced risk of oral cavity cancer (OR: 0.85; 95% CI: 0.77-0.94; P = 0.002), and such associations were mainly observed in case-control studies (OR: 0.86; 95% CI: 0.76-0.98; P = 0.021) but not in cohort studies (OR: 0.83; 95% CI: 0.67-1.02; P = 0.071). High or intermediate coffee intake might have protective effects against oral cavity cancer. However, the underlying mechanisms must be further evaluated in large-scale prospective cohort studies.