Qualitative analysis of Adenomatous Polyposis Coli promoter: Hypermethylation, engagement and effects on survival of patients with esophageal cancer in a high risk region of the world, a potential molecular marker

<p>Abstract</p> <p>Background</p> <p>Squamous cell carcinoma of esophagus (SCCE) occurs at a high incidence rate in certain parts of the world. This feature necessitates that different aspects of the disease and in particular genetic characteristics be investigated in such regions. In addition, such investigations might lead to achievement of molecular markers helpful for early detection, successful treatment and follow up of the disease. Adenomatous Polyposis Coli (<it>APC</it>) promoter hypermethylation has been shown to be a suitable marker for both serum and solid tumors of adenocarcinoma of esophagus. We investigated the status of <it>APC </it>promoter hypermethylation in Iranian patients, compared the results with the former studies, and evaluated its applicability as a candidate molecular marker by examining association between survival of SCCE patients and <it>APC </it>promoter methylation.</p> <p>Methods</p> <p>For evaluating the status of <it>APC </it>promoter hypermethylation and its association with SCCE, a qualitative methylation specific PCR (MSP) was used. DNA was extracted and digested with an appropriate restriction enzyme, treated with sodium bisulfite in agarose beads and amplified in two-step PCR reaction by applying either methylated or unmethylated promoter specific primers. Universally methylated DNA and methylase treated blood DNA of healthy donors were used as positive controls as well. Survival of patients was followed up for two years after treatment and survival rate of patients with methylated <it>APC </it>promoter was compared with that of unmethylated patients.</p> <p>Results</p> <p>Assessment of <it>APC </it>promoter methylation revealed that normal tissues were unmethylated, while twenty out of forty five (44.4%) tumor tissues were hypermethylated either in one or both alleles of <it>APC</it>. Among the tissues in which methylation was detected, seven were hypermethylated in both alleles while the other thirteen were hypermethylated in one of the two alleles of <it>APC</it>. Analyzing two-year survival rate of patients with respect to promoter hypermethylation showed a lower rate of survival for patients with methylated <it>APC </it>promoter following their treatment. Further investigation into the association between promoter hypermethylation and tumor differentiation status indicated that patients with well differentiated tumors were more likely to develop promoter hypermethylation.</p> <p>Conclusion</p> <p>Observing similar level of <it>APC </it>promoter hypermethylation in patients with SCCE in this high risk region and comparing it with other parts of the world could support the hypothesis that a common molecular mechanism might be involved in tumorigenesis of SCCE. In addition, the higher rate of two-year survival for patients with unmethylated <it>APC </it>promoter as well as its relationship with tumor differentiation would suggest that this tumor suppressor could be an appropriate candidate molecular marker for evaluating tumor malignancy and predicting survival of patients subsequent to treatment.</p

Socioeconomic-related inequalities in oral hygiene behaviors: A cross-sectional analysis of the PERSIAN cohort study

Background: Socioeconomic-related inequality in oral hygiene behaviors in Iran is poorly understood. This study aims to measure and decompose socioeconomic-related inequalities in oral hygiene behaviors among middle-aged and elderly adults in Iran. Methods: A cross-sectional analysis was performed using data from the Prospective Epidemiological Research Studies in IrAN (PERSIAN), a large national cohort study. A total of 130,016 individuals aged 35 years and above from 17 cohort centers in Iran were included in the study. The normalized concentration index (C n ) was used to measure the magnitude of inequality in oral hygiene behaviors, i.e. brushing at least twice and flossing once daily, among middle-aged and elderly Iranian adults included in the cohort centers. Decomposition analysis was performed to quantify the contribution of each determinant to the observed inequality in oral hygiene behaviors. Results: Totally, 65.5 of middle-aged and elderly adults brushed their teeth twice a day or more, 7.6 flossed at least once a day and 3.48 had both habits. The estimated C n of the two habits combined, i.e. tooth brushing and dental flossing, for all provinces taken part in the PERSIAN cohort study was 0.399 (95 confidence interval CI: 0.383 to 0.417), indicating that the prevalence of the two habits combined is more concentrated among individuals with higher socioeconomic status. Inequality in oral hygiene behaviors was pro-rich in all cohort centers. The decomposition results suggested socioeconomic status as the main factor contributing to the overall inequality, followed by the level of education, and the province of residence. Conclusion: A low prevalence of oral hygiene behaviors among middle-aged and elderly Iranian adults was observed. There was also a pro-rich inequality in oral hygiene behaviors among middle-aged and elderly adults in all cohort centers. These results suggest an urgent need for targeted policy interventions to increase the prevalence of preventive oral hygiene behaviors among the poor and less-educated middle-aged and elderly adults in Iran. © 2020 The Author(s)

Emerging Epidemic of Inflammatory Bowel Disease in a Middle Income Country: A Nation-wide Study from Iran

BACKGROUND: The burden of inflammatory bowel disease (IBD) hasn't been reported in Iran. We aimed to estimate the prevalence and incidence of IBD and its trend in Iran at national and subnational level from 1990 to 2012. METHODS: We conducted a systematic review of English and Persian databases about the epidemiology of IBD. We also collected outpatient data from 17 provinces of Iran using almost all public and private referral gastroenterology clinics. Prevalence and incidence rate was calculated at national and subnational levels. The Kriging method was used to extrapolate provinces with missing data and GPR model to calculate time trends of rates at subnational level. RESULTS: We found 16 case series, two population-based studies, and two review articles. We collected 11,000 IBD cases from outpatient databases. Among them, 9,269 (84.26%) had ulcerative colitis (UC), 1,646 (14.96%) had Crohn's disease (CD), and 85 had intermediate colitis (IC). A total of 5,452 (49.56%) patients were male. Mean age at diagnosis was 32.80 years (CI: 13 - 61) for UC and 29.98 years (CI: 11 - 58) for CD. Annual incidences of IBD, UC, and CD in 2012 were 3.11, 2.70, and 0.41 per 100,000 subjects respectively. Prevalence of IBD, UC, and CD in 2012 were 40.67, 35.52, and 5.03 per 100,000 subjects respectively. The incidence of UC and CD showed a significant increase during the study period (P for trend < 0.05). CONCLUSIONS: The incidence and prevalence of IBD are increasing in Iran. Establishing a national IBD registry seems necessary for comprehensive care of IBD patients in Iran