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Objectives: To map the genomic pathways of patients with oral leukoplakia (OLK) which transformed to cancer (progressive) and those which did not (non-progressive), and to compare their exomic profiles., Materials and Methods: Whole exome sequencing was performed on 42 sequential samples from five progressive and eight non-progressive patients. Association of genomic variant frequencies with progression or lesion severity were analysed by non-parametric tests (Kruskal-Wallis and Mann-Whitney-Wilcoxon) and multivariate sparse partial least squares discriminant analysis (sPLS-DA). Enrichment analysis was used to characterise the effect of mutations upon biological pathways. Confirmatory studies used qPCR and immunohistochemistry., Results: Using sPLS-DA, the variant frequency of a small number of genes could be used to classify the samples based on lesion severity or progressive status. Enrichment analysis showed that DNA damage repair gene related pathways were highly impacted in lesions which progressed to cancer. Multivariate analysis of a set of 148 DNA damage repair genes could be used to classify progressive lesions using mutation frequency. BRCA1, BRCA2 and other double strand break (DSB) repair Fanconi anaemia (FA)/BRCA pathway genes were prominent contributors to this classification., Conclusion: Patients with progressive and non-progressive OLK can be differentiated using the frequency of exomic variants, particularly in DNA damage repair pathway genes. To our knowledge, this is the first report of FA/BRCA (DSB) pathway involvement in malignant transformation of OLK to oral squamous cell carcinoma (OSCC)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Approximately 20% of oral squamous cell carcinoma (OSCC) cases arise without any identifiable environmental cause, suggesting involvement of genetic influences in their aetiology. DNA double-strand breaks (DSBs) sever both strands of DNA and pose a potential threat to genomic integrity. A hastened accumulation of somatic mutations consequent to DSB repair is deemed to be a likely event in tumorigenesis of OSCC., Methods: Two discrete chemical approaches, namely hydrogen peroxide and camptothecin, were used to induce DSB in oral cell lines derived from normal through dysplastic to OSCC tissues. After optimization, gamma histone 2Ax (γH2Ax) foci were counted as an indirect measure of kinetics of DSB and confirmed with Western blot of γH2Ax, Nbs1 and ATM., Results: Maximal number of γH2Ax foci was detected 1 and 2 hours post-exposure to camptothecin and hydrogen peroxide, respectively; when adjusted for the baseline number of γH2Ax, neoplastic cell lines showed the lowest number of maximal DSB and slowest rate of repair compared to other cell lines. γH 2 Ax Western blot closely mirrored the trend observed in immunofluorescent staining for γH 2 Ax foci. Changes in the expression level of ATM and Nbs1 were minimal; however, ATM expression showed a slight gradual increase in normal cells which reached its peak at 2 hours after exposure to camptothecin., Conclusions: There is a difference in efficiency of DSB repair pathways in cell lines derived from different stages of oral tumorigenesis with neoplastic cell lines having the most defective DSB repair system., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: This study explored the expression of DNA mismatch repair (MMR) proteins in a range of oral biopsies. We further evaluated the significance of MMR protein expression combined with basic demographic data in differentiating grades of oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC)., Study Design: Immunohistochemical expression of MutSα (hMLH1 and hPMS2) and MutLα (hMSH2 and hMSH6) were compared in 98 formalin-fixed paraffin embedded oral biopsies: 21 normal, 24 mild-dysplasia (MD), 8 moderate-to-severe-dysplasia (SD), and 45 OSCC., Results: Expression of hMLH1, hPMS2, and hMSH2 was reduced in MD, SD, and OSCC compared with the normal. Reduced hMSH2 immunoreactivity discriminated poorly differentiated OSCC from well-differentiated OSCC. The diagnostic model correctly classified 71.4% of cases and revealed that hPMS2-negative biopsies were more likely to be cancerous (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.000-0.813; P = .040)., Conclusion: The results suggested a diagnostic role for MMR proteins in OED and OSCC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Advances in the management of patients with head and neck squamous cell carcinoma (HNSCC) have not significantly changed the prognosis of this tumor over the past five decades. Molecular heterogeneity of HNSCC and its association with HPV, in addition to the increase in the number of cancers arising in traditionally low-risk patients, are among some of the obstacles to the successful management of this group of tumors. Massively parallel sequencing, otherwise known as next-generation sequencing (NGS), is rapidly changing conventional patient management by providing detailed information about each patient's genome and transcriptome. Despite major advances in technology and a significant reduction in the cost of sequencing, NGS remains mainly limited to research facilities. In addition, there are only a few published studies that have utilized this technology in HNSCC. This paper aims to report briefly on current commercially available NGS platforms and discuss their clinical applications, ethical considerations, and utilization in personalized patient care, particularly as this relates to head and neck cancer.

Several studies have indicated the association between intake of foods high in dietary glycemic index (GI) and glycemic load (GL) with an increased risk of digestive tract cancers. We hypothesized that GI and GL may be associated with risk of esophageal squamous cell carcinoma (ESCC) in a high-risk population in Iran. In total, we interviewed 47 cases with incident of ESCC and 96 frequency-matched hospital controls, then calculated the average dietary GI and GL via a validated food frequency questionnaire. Dietary GL was calculated as a function of GI, carbohydrate content, and frequency of intake of certain foods. Dietary GI and GL levels were significantly higher among the ESCC cases compared with the controls (P < .05). After adjustment for potential confounders, those in the highest tertile of dietary GI had 2.95 times higher risk of ESCC compared with those in the lowest (95% confidence interval, 1.68-3.35; P for trend = .002). In addition, being in the highest tertile of dietary GL was positively associated with an ESCC risk (odds ratio, 3.49; 95% confidence interval, 2.98-4.41; P for trend = .001). Findings of the present study indicate that diets with high GI and GL might have potentially unfavorable effects on ESCC risk and suggest a possible role for excess circulating insulin and related insulin-like growth factor 1 in esophageal cancer development., (© 2013.)

Objective: The benefit of adherence to a Mediterranean-style dietary pattern in relation to the risk of esophageal squamous cell carcinoma (ESCC) has not been investigated among non-Mediterranean high-risk populations. The objective of the present study was to examine the association of compliance with the Mediterranean dietary pattern as measured by Mediterranean-Style Dietary Pattern Score (MSDPS) and the risk of ESCC in Iranian population., Methods: This case-control study was conducted on 47 ESCC cases and 96 hospital controls aged 40-75 years. Participants were interviewed using validated questionnaires, and dietary patterns were characterized using the MSDPS., Results: Generally, the mean MSDPS in this population was low (30.84 ± 8.58). MSDPS showed content validity through having expected positive associations with several lifestyle characteristics and dietary intakes. Being in the highest quartile category of MSDPS, compared to the lowest, was independently associated with 37% reduction in risk of ESCC. Two-unit and 3-unit increases in the MSDPS resulted in 41% and 47% reduction in risk of ESCC, respectively. Higher intakes of olive oil (odds ratio [OR] = 0.15, 95% CI: 0.01-0.49), fish and other seafood (OR = 0.48, 95% CI: 0.23-0.98), whole grain (OR = 0.57, 95% CI: 0.28-0.76), and fruits (OR = 0.77, 95% CI: 0.38-0.86) were significantly associated with reduced ESCC risk. In contrast, higher sweet (OR = 1.86, 95% CI: 1.04-2.12) and meat intakes (OR = 1.61, 95% CI: 1.25-2.49) were associated with higher ESCC risk., Conclusion: Consuming a diet in concordance with the principles of the Mediterranean dietary pattern may protect against ESCC. Preventive strategies to reduce ESCC risk in high-risk countries should focus on overall dietary pattern and dietary habits to be effective.

Although Iran is a high-risk country for esophageal squamous cell carcinoma (ESCC), the contribution of overall nutrient intakes to this high incidence rate is not yet clear. The aim of this study was to examine the association between nutrient patterns and risk of ESCC in Iran. Forty-seven patients with ESCC and 96 frequency-matched hospital controls underwent private interviews, and dietary habits were collected using a validated food-frequency questionnaire. Factor analysis was conducted and two major nutrient patterns were retained; factor 1 (high in pantothenic acid, vitamin C, potassium, vitamin B(6), magnesium, folate, thiamin, copper, carbohydrate, vitamin K, niacin, α-tocopherol, zinc, total fiber, fluoride, and polyunsaturated fatty acids) and factor 2 (high in saturated fatty acid, biotin, selenium, monounsaturated fatty acids, riboflavin, sodium, fat, cholesterol, calcium, phosphorus, protein, iron, vitamin E, manganese, vitamin D, and vitamin B(12)). Factor 2 was inversely associated with ESCC (OR = 0.06, 95% CI: 0.01-0.28; P = 0.008), whereas no significant association was found for factor 1 (OR = 0.45, 95% CI: 0.11-1.82). The results of the present study suggested a possible role for a nutrient pattern similar to factor 2 in reducing the risk of ESCC., (© 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Background: Although Iran is a high-risk region for esophageal squamous cell carcinoma (ESCC), dietary factors that may contribute to this high incidence have not been thoroughly studied. The aim of this study was to evaluate the effect of macronutrients, vitamins and minerals on the risk of ESCC., Methods: In this hospital-based case-control study, 47 cases with incident ESCC and 96 controls were interviewed and usual dietary intakes were collected using a validated food frequency questionnaire. Data were modeled through unconditional multiple logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), controlling for age, sex, gastrointestinal reflux, body mass index, smoking history (status, intensity and duration), physical activity, and education., Results: ESCC cases consumed significantly more hot foods and beverages and fried and barbecued meals, compared to the controls (p < 0.05). After adjusting for potential confounders, the risk of ESCC increased significantly in the highest tertiles of saturated fat [OR:2.88,95%CI:1.15-3.08], cholesterol [OR:1.53, 95%CI: 1.41-4.13], discretionary calorie [OR:1.51, 95%CI: 1.06-3.84], sodium [OR:1.49,95%CI:1.12-2.89] and total fat intakes [OR:1.48, 95%CI:1.09-3.04]. In contrast, being in the highest tertile of carbohydrate, dietary fiber and (n-3) fatty acid intake reduced the ESCC risk by 78%, 71% and 68%, respectively. The most cancer-protective effect was observed for the combination of high folate and vitamin E intakes (OR: 0.02, 95%CI: 0.00-0.87; p < 0.001). Controls consumed 623.5 times higher selenium, 5.48 times as much β-carotene and 1.98 times as much α-tocopherol as the amount ESCC cases consumed., Conclusion: This study suggests that high intake of nutrients primarily found in plant-based foods is associated with a reduced esophageal cancer risk. Some nutrients such as folate, vitamin E and selenium might play major roles in the etiology of ESCC and their status may eventually be used as an epidemiological marker for esophageal cancer in Iran, and perhaps other high-risk regions.

Background/aim: The Dietary Guidelines for Americans Adherence Index (DGAI) 2005 was developed to assess the contribution of dietary patterns to chronic disease risk. The objective of this study was to evaluate the association of dietary patterns as measured by the DGAI 2005 with the esophageal squamous cell carcinoma (ESCC) risk in Iran., Methods: This case-control study was conducted on 50 ESCC cases and 100 hospital controls aged 40-75 years. Participants were interviewed using validated food frequency questionnaires and the DGAI score was calculated subsequently., Results: Generally, the mean DGAI 2005 score for this population was low (9.54 ± 1.79) and the control group scored significantly higher compared to the ESCC cases (p < 0.001). Being in the highest tertile of DGAI scores reduced the risk of ESCC by 31%. Consumption of salty, peppery, and sour foods in combination increased the ESCC risk by 7.23%, followed by consumption of fried/barbecued meals (OR 3.79; 95% CI 1.10-5.44; p < 0.001) and high-temperature food/beverages (OR 3.68; 95% CI 1.20-8.99; p < 0.001)., Conclusions: Consumption of a diet in accordance with dietary recommendations was associated with a lower risk of ESCC. Preventive strategies to reduce the ESCC risk in high-risk regions of the world should focus on overall dietary patterns and dietary habits in order to be effective., (Copyright © 2011 S. Karger AG, Basel.)

The authors examined the association of food group intakes and the risk of esophageal squamous cell carcinoma (SCC) in a hospital-based case-control study in Iran. In total, 47 patients with esophageal SCC and 96 controls underwent face-to-face private interviews. Usual dietary intake was assessed using a semiquantitative food frequency questionnaire. Multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals. Cases had higher tobacco consumption and symptomatic gastresophageal reflux, whereas controls had higher mean body mass index (25.3 vs. 20.4) and years of education. A protective independent effect was observed for the highest tertile of total fruit consumption (OR: 0.13, CI: 0.04-0.45, P value = 0.001). Within the group of fruits, a significant inverse association was observed for bananas and kiwis (P for trends: 0.03 and 0.02, respectively). The risk of SCC decreased monotonically with increasing intake frequency of oranges (P value for trend = 0.01). The effect of total vegetable consumption on esophageal SCC was not significant, although a reduction in risk was observed in the highest tertile of intake (OR: 0.66, CI: 0.23-1.87, P value = 0.43). The results of the present study suggest a reasonable association between fruit consumption and esophageal SCC in a Middle Eastern high-risk population.