Publications by authors named "Abbas Yazdanbod"

32 Publications

Contrasting association of Helicobacter pylori oipA genotype with risk of peptic ulceration and gastric cancer.

Infect Genet Evol 2021 Jan 10;89:104720. Epub 2021 Jan 10.

Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil 5618953141, Iran.

Helicobacter pylori OipA (outer inflammatory protein A) is an outer membrane protein that involves in the binding and colonization of the bacterium in the stomach. The oipA status is associated with the risk of peptic ulcerations (PUs) and gastric cancer (GC) diseases. However, the association trend with PUs compared to GC is often different and highly challenging. We therefore aimed to determine the presence of this genotype in Iranian strains and assess its association with the risk of PUs and GC in a larger number of samples. A total of 319 strains were obtained from 172 patients with non-atrophic gastritis (NAG), 52 with PUs and 95 with GC. The prevalence of the oipAvs. oipA genotype was 67.7% (216/319). The total frequency of the oipAvs. oipA genotypes in NAG, PUs, GC, non-peptic ulceration (including NAG and GC), and non-tumor (including NAG and PUs) groups was 121/172 (70.3%), 50/52 (96.2%), 45/95 (47.4%), 166/267 (62.2%), and 171/224 (76.3%), respectively. In multiple logistic regression analysis, the oipAvs. oipA genotype showed a strong direct association with PUs; the OR (95% CI) was 18.751 (4.421-79.531), (p = 0.00007). In contrast, it had a significant reverse association with GC; the OR (95% CI) was 0.330 (0.179-0.607), (p = 0.00036). In the present study, we interestingly found a contrasting association of the H. pylori oipA genotype with the risk of PUs and GC in Iran. Therefore, the contrasting effect of this genotype may emphasize its independent role in predicting clinical outcomes.
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http://dx.doi.org/10.1016/j.meegid.2021.104720DOI Listing
January 2021

SNP-SNP interactions of oncogenic long non-coding RNAs HOTAIR and HOTTIP on gastric cancer susceptibility.

Sci Rep 2020 10 7;10(1):16763. Epub 2020 Oct 7.

Digestive Disease Research Center, Ardabil University of Medical Sciences, 5618953141, Ardabil, Iran.

Genetic variants within oncogenic long non-coding RNAs HOTAIR and HOTTIP may affect their gene expression levels, thereby modifying genetic susceptibility to gastric cancer (GC). In a hospital-based study in Ardabil-a very high-risk area in North-West Iran, 600 blood samples from 300 GC patients and 300 healthy controls were recruited for genotyping. Seven HOTAIR (i.e., rs17720428, rs7958904, rs1899663, and rs4759314) and HOTTIP (i.e., rs3807598, rs17501292, and rs1859168) 'tag' single nucleotide polymorphisms (SNPs) were genotyped by the Infinium HTS platform. The rs17720428, rs7958904, and rs1899663 tagSNPs significantly increased GC risk under dominant models by 1.5-, 1.57-, and 1.5-fold, respectively. The G-C-T-A haplotype of HOTAIR tagSNPs increased the risk of GC by 1.31-fold. No significant association was found between HOTTIP SNPs and the risk of GC. HOTAIR and HOTTIP variants were also not associated with any clinicopathologic characteristics. The SNP-SNP interaction of HOTAIR rs17720428/rs7958904 with HOTTIP rs1859168 was associated with an increased risk of GC (rs17720428 TG-rs1859168 CC, OR = 1.76; rs7958904 GC-rs1859168 CC, OR = 1.85; rs7958904 CC-rs1859168 CC, OR = 1.86). Interestingly, the SNP-SNP interaction of HOTAIR rs1899663 with HOTTIP rs1859168 strongly increased the risk of GC (rs1899663 GT-rs1859168 CC, OR = 4.3; rs1899663 TT-rs1859168 CC, OR = 9.37; rs1899663 TT-rs1859168 CA, OR = 6.59). We showed that the HOTAIR rs17720428, rs7958904, and rs1899663 tagSNPs and their interactions with the HOTTIP rs1859168 polymorphism significantly increased the risk of GC. Specifically, novel SNP-SNP interactions between HOTAIR and HOTTIP tagSNPs have a larger impact than individual SNP effects on GC risk, thereby providing us with valuable information to reveal potential biological mechanisms for developing GC.
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http://dx.doi.org/10.1038/s41598-020-73682-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541458PMC
October 2020

Which genotype of Helicobacter pylori-cagA or cagE-Is better associated with gastric Cancer risk? Lessons from an extremely high-risk area in Iran.

Infect Genet Evol 2020 Nov 19;85:104431. Epub 2020 Jun 19.

Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.

The association of the H. pylori cagA- /cagE-positive genotypes with the risk of gastric cancer (GC) in Ardabil-a high-risk area in North-West Iran-was assessed. Genotyping was performed in DNA from fresh gastric biopsies (N = 218). Occurrence of H. pylori infection was 85.32% (186/218). The total frequency of the cagAvs. cagA, cagEvs. cagE, cagA/cagEvs. AGCs (all genotype combinations), cagA/cagEvs. AGCs, cagA/cagEvs. AGCs, cagA/cagEvs. AGCs, cagA/cagEvs. cagA/cagE, and cagA/cagEvs. cagA/cagE genotypes was 102/186 (54.8%), 89/186 (47.8%), 38/186 (20.4%), 25/186 (13.4), 59/186 (31.7%), 64/186 (34.4%), 38/63 (38.63%), and 64/123 (52.0%), respectively. The cagEvs. cagE (59.6% (65/109) in GC vs. 31.2% (24/77) in non-atrophic gastritis, NAG) and the cagA/cagEvs. cagA/cagE genotypes (66.7% (40/60) in GC vs. 38.1% (24/63) in NAG) showed an increased association with the risk of GC in Ardabil (odds ratio [OR] = 3.262, 95% confidence interval [CI]: 1.763-6.038, p = .0001 and OR = 3.250; 95% CI: 1.552-6.808, p = .002, respectively). We propose that the H. pylori cagE but not cagA genotype significantly increased the risk of GC in this extremely high-risk population. Therefore, it may play a significant role in determining H. pylori-related clinical outcome.
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http://dx.doi.org/10.1016/j.meegid.2020.104431DOI Listing
November 2020

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

BMC Oral Health 2020 02 28;20(1):63. Epub 2020 Feb 28.

Social Development and Health Promotion Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

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) 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 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.
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http://dx.doi.org/10.1186/s12903-020-1036-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048098PMC
February 2020

Risk factors predisposing to cardia gastric adenocarcinoma: Insights and new perspectives.

Cancer Med 2019 10 25;8(13):6114-6126. Epub 2019 Aug 25.

Digestive Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.

Recent decades have seen an alarming increase in the incidence of cardia gastric adenocarcinoma (CGA) while noncardia gastric adenocarcinoma (NCGA) has decreased. In 2012, 260 000 CGA cases (age-standardised rate (ASR); 3.3/100 000) and 691 000 NCGA cases (ASR; 8.8/100 000) were reported worldwide. Compared with women, men had greater rates for both the subsites, especially for CGA. Recently, four molecular subtypes of GC have been proposed by the Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG); however, these classifications do not take into account predisposing germline variants and their possible interaction with somatic alterations in carcinogenesis. The etiology of adenocarcinoma of the cardia and the gastroesophageal junction (GEJ) is not known. It is thought that CGA is distinct from adenocarcinomas located in the esophagus or distal stomach, both epidemiologically and biologically. Moreover, CGA is often identified in the advanced stage having a poor prognosis. Therefore, understanding the risk and the role of predisposing factors in etiology of CGA can inform clinical practice and counseling for risk reduction. In this paper, we showed that GC family history, lifestyle, demographics, gastroesophageal reflux disease, Helicobacter pylori infection, and multiple genetic and epigenetic risk factors as well as several predisposing conditions may underlie susceptibility to CGA. However, several genome-wide association studies (GWASs) should be conducted to identify novel high-penetrance genes and pathways as well as causal germline variants predisposing to CGA. They must include different ethnic groups, especially from high-incidence countries for CGA, because some risk loci are ancestry-specific. In parallel, statistical methods can be developed to identify cancer predisposition genes (CPGs) from tumor sequencing data. It is also necessary to find novel long noncoding RNAs related to the risk of CGA. Taken altogether, new cancer risk prediction models, including all genetic and nongenetic factors influencing risk, should be developed to facilitate risk assessment, disease prevention, and early diagnosis and intervention of CGA in the future.
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http://dx.doi.org/10.1002/cam4.2497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792520PMC
October 2019

Inverse association of Helicobacter pylori cagPAI genotypes with risk of cardia and non-cardia gastric adenocarcinoma.

Cancer Med 2019 08 5;8(10):4928-4937. Epub 2019 Jul 5.

Digestive Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.

Iran is a high-risk country for cardia gastric adenocarcinoma (CGA) in Central Asia, with an incidence rate five times the average global rate, and shows a high infection rate for Helicobacter pylori (69%). The aim was to examine the associations of multiple H. pylori cagPAI genotypes (ie cagH, cagL, cagG, and orf17) with the risk of CGA, non-CGA, and different histological types of GA in Iran. A large number of H. pylori strains (N = 336) were successfully cultured and genotyped. Histopathological evaluations were performed. The analysis showed an inverse association between the cagH genotype and the risk of CGA and intestinal-type gastric adenocarcinoma (IGA) (adjusted ORs; 0.312 and 0.283, respectively), where the controls were nontumors. The orf17 genotype decreased the risk of non-CGA and diffuse-type gastric adenocarcinoma (DGA)(adjusted ORs; 0.310 and 0.356, respectively). When the controls were those with nonatrophic gastritis, the cagG genotype was negatively associated with the risk of CGA, non-CGA, IGA, and DGA (adjusted ORs; 0.324, 0.366, 0.306, and 0.303, respectively). We did not find such a significant association for the cagL genotype in multiple logistic regression analysis. Combination of the vacA c2 and cagPAI genotypes further decreased the risk estimates for GAs. This study showed the reverse association of H. pylori cagPAI genotypes-cagH and cagG -with the risk of CGA in male patients aged ≥ 55 in Iran. Presence of the vacA c2 genotype in combination with cagPAI genotypes showed strong inverse associations with the risk of CGA and non-CGA. These findings may reveal a coordinated relationship between the vacA c2 and cagPAI genotypes.
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http://dx.doi.org/10.1002/cam4.2390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712521PMC
August 2019

Iranian Registry of Crohn's and Colitis: study profile of first nation-wide inflammatory bowel disease registry in Middle East.

Intest Res 2019 Jul 24;17(3):330-339. Epub 2019 Apr 24.

Digestive Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background/aims: A recent study revealed increasing incidence and prevalence of inflammatory bowel disease (IBD) in Iran. The Iranian Registry of Crohn's and Colitis (IRCC) was designed recently to answer the needs. We reported the design, methods of data collection, and aims of IRCC in this paper.

Methods: IRCC is a multicenter prospective registry, which is established with collaboration of more than 100 gastroenterologists from different provinces of Iran. Minimum data set for IRCC was defined according to an international consensus on standard set of outcomes for IBD. A pilot feasibility study was performed on 553 IBD patients with a web-based questionnaire. The reliability of questionnaire evaluated by Cronbach's α.

Results: All sections of questionnaire had Cronbach's α of more than 0.6. In pilot study, 312 of participants (56.4%) were male and mean age was 38 years (standard deviation=12.8) and 378 patients (68.35%) had ulcerative colitis, 303 subjects (54,7%) had college education and 358 patients (64.74%) were of Fars ethnicity. We found that 68 (12.3%), 44 (7.9%), 13 (2.3%) of participants were smokers, hookah and opium users, respectively. History of appendectomy was reported in 58 of patients (10.48%). The most common medication was 5-aminosalicylate (94.39%).

Conclusions: To the best of our knowledge, IRCC is the first national IBD registry in the Middle East and could become a reliable infrastructure for national and international research on IBD. IRCC will improve the quality of care of IBD patients and provide national information for policy makers to better plan for controlling IBD in Iran.
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http://dx.doi.org/10.5217/ir.2018.00157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667360PMC
July 2019

Are Helicobacter pylori highly cytotoxic genotypes and cardia gastric adenocarcinoma linked? Lessons from Iran.

Cancer Biomark 2017 Dec;21(1):235-246

Gastrointestinal Cancer Research Center, Ardabil University of Medical Sciences, Ardabil 56189-53141, Iran.

Background: Although the most extensive studies revealed the role of H. pylori VacA and CagA toxins in the development of gastric adenocarcinoma, the magnitude of this association and the correlations of vacA mosaicism and cagA status with cardia gastric adenocarcinoma (CGA) still remain controversial.

Objective: We aimed to examine the linkage of H. pylori highly cytotoxic genotypes to CGA in Iranian populations as a model.

Methods: A total of 601 Iranian patients were enrolled. Biopsies were cultured, genotyped, and anatomically and histologically classified.

Results: The vacA c1 genotype, but not cagA status, showed a strong association with the risk of both CGA and non-cardia adenocarcinoma (NCGA), whether the controls were non-tumors, as those with either non-atrophic gastritis or peptic ulcerations, (the OR (95%CI) was 14.11 (4.91-40.52) and 9.59 (4.06-22.65), respectively) or those with NAG (the OR (95%CI) was 10.71 (3.49-32.82) and 8.11 (3.26-20.16), respectively). The vacA c1/cagA+ genotype was significantly associated with an increased risk of NCGA, whether the controls were non-tumors or those with NAG; the adjusted risk was 4.706 (1.41-15.67) and 4.85 (1.42-16.51), respectively.

Conclusions: The H. pylori vacA c1 genotype, but not cagA status, might be the first important bacterial biomarker for predicting the cardia adenocarcinoma risk in male patients aged ⩾ 55 in Iran.
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http://dx.doi.org/10.3233/CBM-170701DOI Listing
December 2017

Helicobacter pylori genotypes determine risk of non-cardia gastric cancer and intestinal- or diffuse-type GC in Ardabil: A very high-risk area in Northwestern Iran.

Microb Pathog 2017 Jun 5;107:287-292. Epub 2017 Apr 5.

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

Frequency of the Helicobacter pylori vacA gene polymorphism and its association with gastric cancer (GC) was assessed in Ardabil, a very high-risk area in Northwestern Iran. We determined the presence of the H. pylori 16S rDNA gene and the vacA s-, m-, i-, and d-region genotypes in DNA from fresh gastric biopsies. Patients with GC were classified based on both the anatomic site and the histopathologic type of tumor Of 135 patients, including 57 with non-atrophic gastritis (NAG) and 78 with GC, 103 were infected by H. pylori. The vacA i1 and d1 genotypes were significantly linked to an increased risk of GC, where both cardia (CGC) and non-cardia GC (NCGC) patients were entered into the analysis. The adjusted OR was 9.59 for i1 and 4.39 for d1. Furthermore, i1 was significantly linked to an increased risk of the intestinal-type adenocarcinoma (OR = 14.04) and d1 to the risk of the diffuse-type adenocarcinoma (OR = 7.71). The presence of the m1-type of vacA in combination with i1 or d1 further increased the risk of GC. When the analysis was restricted to NCGC, the adjusted OR for i1 and d1, was 37.52 and 7.17, respectively. No significant association was found between genotypes and the risk of GC in the cardia site of the stomach. It is proposed that the new types of H. pylori vacA, i1 and d1, might be important determinants of NCGC risk in Ardabil. The m1, not independently, but in combination might further define the risk of GC. i1and d1 might also predict the risk of the intestinal- and diffuse-type adenocarcinomas, respectively.
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http://dx.doi.org/10.1016/j.micpath.2017.04.007DOI Listing
June 2017

Helicobacter pylori babA2 Positivity Predicts Risk of Gastric Cancer in Ardabil, a Very High-Risk Area in Iran.

Asian Pac J Cancer Prev 2016 ;17(2):733-8

Department of Biology, Faculty of Sciences, Ardabil University of Medical Sciences, Ardabil, Iran E-mail :

Background: Ardabil, a Northwestern province of Iran, was found to have the highest rate of gastric cancer (GC) in the country (ASRs = 51.8/100,000 for males and 24.9/100,000 for females) and one of the highest gastric cardia cancer rates in the world. The aim of the present study was to assess the associations of the cagA and babA2 status of Helicobacter pylori with GC in the Ardabil population.

Materials And Methods: A total of 103 patients with non-atrophic gastritis (56) and GC (47), who underwent endoscopy at the Imam Khomeini Hospital in Ardabil, were assessed. The status of 16S rDNA, cagA and babA2 genes was determined using PCR and histopathological assessment was performed.

Results: The following genotypic frequency was observed: cagA+ (50.6%), cagA- (49.4%), babA2+ (26.5%), babA2- (73.5%) cagA+/babA2+ (19.3%), cagA-/babA2+ (7.2%), cagA+/babA2- (31.3%), cagA-/babA2- (42.2%). Although the frequency of the cagA+, cagA+/babA2+ and cagA-/ babA2+ genotypes in patients with GC (55.6%, 25.9%, and 14.8%, respectively) was higher than in those with NAG (48.2%, 16.1%, and 3.6%, respectively), the difference did not reach significance. In contrast, the presence of the babA2 gene (40.7% vs 19.6%) significantly increased the risk of GC; the age-sex-adjusted odds ratio (95% confidence interval) was 5.068 (1.506-17.058; P=0.009), by multiple logistic regression.

Conclusions: It is proposed that the H. pylori babA2 positivity might be considered as an important determinant of GC risk in Ardabil.
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http://dx.doi.org/10.7314/apjcp.2016.17.2.733DOI Listing
January 2017

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

Arch Iran Med 2016 Jan;19(1):2-15

Digestive Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, 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.
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http://dx.doi.org/0161901/AIM.003DOI Listing
January 2016

Relevance of Helicobacter pylori vacA 3'-end Region Polymorphism to Gastric Cancer.

Helicobacter 2016 Aug 27;21(4):305-16. Epub 2015 Nov 27.

Department of Microbiology, School of Biology, University College of Sciences, University of Tehran, Tehran, Iran.

Background: Helicobacter pylori vacA genotypes play an important role in the pathogenesis of severe gastrointestinal disease.

Materials And Methods: We identified a novel polymorphic site in the 3'-end region of H. pylori vacA gene, denoted by c1/-c2 (c1: with deletion of 15 bp), and examined associations of this and the previous four sites as well as cagA status with gastroduodenal diseases, in a total of 217 Iranian H. pylori isolates. Histopathologic evaluations were performed and patients with gastric cancer (GC) were further classified based on the anatomic site of tumor, including cardia and noncardia GC, and the histopathologic type of tumor, including intestinal- and diffuse-type GC.

Results: The vacA m1, i1, d1, c1, and cagA genotypes were significantly associated with an increased risk of GC, the odds ratio (95% confidence interval) was 4.29 (2.03-9.08), 6.11 (2.63-14.19), 3.18 (1.49-6.76), 15.13 (5.86-39.01), and 2.59 (1.09-6.12), respectively. The vacA c1 genotype had an increased age- and sex-adjusted risk for GC by the multiple logistic regression analysis; the OR was 38.32 (95% CI, 6.60-222.29). This association was independent of and larger than the associations of the m-, i-, and d-type of vacA or cagA status with GC. No significant correlation was found between s1, whether independently or in combination, and the risk of GC or peptic ulcer disease (PUD). The vacA i1 and cagA genotypes were linked to an increased risk of PUD; the OR (95% CI) was 2.80 (1.45-5.40) and 2.62 (1.23-5.61), respectively. The presence of both the vacA i1 and cagA genotypes further increased the risk of PUD; the OR was 5.20 (95% CI, 1.92-14.03).

Conclusion: The H. pylori vacA c1 genotype might therefore be one of the strongest risk predictors of GC in male patients aged ≥55 in Iran.
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http://dx.doi.org/10.1111/hel.12284DOI Listing
August 2016

Effect of Helicobacter pylori eradication in Iranian patients with functional dyspepsia: a prospective, randomized, placebo-controlled trial.

Arch Med Sci 2015 Oct;11(5):964-9

Department of Internal Medicine, Imam Khomeini Hospital, Ardabil University of Medical Sciences, Ardabil, Iran.

Introduction: Whether patients with functional dyspepsia (FD) should receive Helicobacter pylori (H. pylori) eradication therapy remains controversial. The objective of this trial was to evaluate the effect of H. pylori eradication therapy on dyspeptic symptoms of patients with FD.

Material And Methods: A prospective, randomized, placebo-controlled trial of H. pylori eradication for FD was conducted. A total of 720 FD patients diagnosed by Rome III criteria were consecutively enrolled. We randomly assigned 186 H. pylori infected patients with FD to receive quadruple therapy for 14 days and 173 such patients to receive identical-appearing placebos. Severity of abdominal symptoms was assessed with the Glasgow Dyspepsia Severity Score (GDSS), and eradication of H. pylori by (13)C-urea breath test was evaluated during one year.

Results: The rate of eradication of H. pylori infection was 87.1% in the treatment group and 2.9% in the placebo group at 6 weeks (p = 0.001). The mean GDSS at 12 months was 4.9 ±2.8 in the treatment group, as compared to 5.2 ±3.4 in the placebo group (p = 0.064). The scores in both groups were lower than those at baseline. According to the intention-to-treat analysis, at 12 months, there was no significant difference between groups in the rate of successful treatment (48.6% in the treatment group and 51.2% in the placebo group; p = 0.84). There was no significant difference in mean symptom scores between the two treatment groups at any point during follow-up.

Conclusions: The results of our study provide no evidence that H. pylori eradication leads to relief of symptoms 12 months after treatment, and there is a need for further studies.
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http://dx.doi.org/10.5114/aoms.2015.54851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624741PMC
October 2015

Relationship between Helicobacter pylori and idiopathic chronic urticaria: effectiveness of Helicobacter pylori eradication.

Postepy Dermatol Alergol 2015 Feb 2;32(1):15-20. Epub 2015 Feb 2.

Department of Dermatology, Imam Khomeini Hospital, Ardabil University of Medical Sciences, Ardabil, Iran.

Introduction: Chronic urticaria (CU) is defined as the presence of urticaria on most days of the week for a period of 6 weeks or longer. Some studies have reported an association between CU and Helicobacter pylori (H. pylori) infection.

Aim: To determine the prevalence of H. pylori infection using the stool antigen test in patients with idiopathic CU and to investigate the infected patients with CU following eradication of H. pylori.

Material And Methods: One hundred patients with idiopathic CU and 100 healthy controls were referred to our clinic between May 2012 and June 2013 and were tested for H. pylori antigen. The patients infected with H. pylori received quadruple therapy for 2 weeks. To assess eradication efficacy, a repeated H. pylori stool antigen test was performed in each patient 6 weeks after the end of anti-H. pylori therapy. The effectiveness of eradication therapy on CU was assessed 3 months after treatment.

Results: Thirty-six percent patients with idiopathic CU were infected with H. pylori while 23% of the controls were infected. Response to eradication therapy was evident in 33 (91.67%) patients in whom H. pylori was eradicated while 3 (8.33%) patients showed no response despite eradication of H. pylori. Clinical follow-up of 33 successfully treated patients 3 months later revealed complete remission of urticaria in 54.5%, partial remission in 18.2%, and no improvement in 27.3%.

Conclusions: The results of our study suggest that H. pylori infection should be included in diagnostic workup of patients with no response to habitual treatment for CU or symptomatic gastrointestinal patients. For the diagnosis of H. pylori infection, one should consider the costs and accessibility of the population to the HpSA(®) stool antigen test and Urea breath test (UBT).
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http://dx.doi.org/10.5114/pdia.2015.48729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360011PMC
February 2015

Successful use of central venous catheters in the management of recurrent malignant pleural effusions: one new option.

Support Care Cancer 2015 Aug 10;23(8):2267-71. Epub 2015 Jan 10.

Department of Internal Medicine, Imam Khomeini Hospital, Ardabil University of Medical Sciences, Ardabil, Iran,

Background: Malignant pleural effusion (MPE) is a common clinical problem in patients with malignancy. To date, placement of various catheters has been suggested as an effective alternative method for traditional treatment of recurrent MPE. In this study, we report our experience in managing treatment of recurrent MPE by placing a central vein catheter without a radiologic guide.

Methods: Patients with recurrent MPE who underwent triple-lumen central vein catheter insertion (2010-2013) were retrospectively reviewed. Clinical, procedural, complication, and outcome details were analyzed. Patients were carefully selected, and the central catheters were inserted as a palliative measure. We assessed the quality of life of patients using the EORTC QLQ-C30.

Results: A total of 84 patients with recurrent MPE were enrolled in this study. Fifty-six males and 28 females with mean age of 57.8 ± 12.4 years old underwent the procedure. There were no preoperative or postoperative complications related to the procedure. The EORTC QLQ-C30 questionnaire showed a significant improvement following catheter placement in symptom scales at 30 days (p = 0.01) and at 60 days (p = 0.002).

Conclusions: Triple-lumen central catheter insertion is a simple, noninvasive option in patients with recurrent MPE that can be performed the patient's bedside. Further research is needed to confirm the results and to assess the impact of central catheter insertion on the quality of life of these patients.
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http://dx.doi.org/10.1007/s00520-014-2595-3DOI Listing
August 2015

Effects of p53 codon 72 and MDM2 SNP309 polymorphisms on gastric cancer risk among the Iranian population.

Asian Pac J Cancer Prev 2014 ;15(17):7413-7

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran E-mail :

Background: Development of gastric cancer (GC) is a multistep process that requires alterations in the expression of oncogenes and tumor suppressor genes, occurring over several decades. The p53 tumor suppressor protein is involved in cell-cycle control, apoptosis and DNA repair. One of the most important regulators of p53 is MDM2, which acts as a negative regulator in the p53 pathway. Based on the key role of p53 and MDM2 in tumor suppression, polymorphisms that cause change in their function might affect cancer risk. We therefore elevated associations of the polymorphisms of p53 (R72P) and MDM2 (SNP309) with GC in Iran.

Materials And Methods: A total of 104 patients with gastric cancer and 100 controls were recruited. Genomic DNA was extracted from fresh gastric samples. Genotyping of the p53 and MDM2 genes was performed using allele specific PCR (AS-PCR).

Results: There was no significant difference between the p53 codon 72 polymorphism distribution in control and patient groups (p=0.54), but the G allele of MDM2 was found to be over-represented in patients (p=0. 01, Odds Ratio=2. 08, 95% Confidence Interval= 1.37-4.34).

Conclusions: The p53 R72P seems not to be a potential risk factor for development of GC among Iranian patients, but our data suggest that MDM2 SNP309 might modify the risk related to GC.
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http://dx.doi.org/10.7314/apjcp.2014.15.17.7413DOI Listing
June 2015

Serum ghrelin; a new surrogate marker of gastric mucosal alterations in upper gastrointestinal carcinogenesis.

PLoS One 2013 30;8(9):e74440. Epub 2013 Sep 30.

Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran ; Department of Epidemiology, University of Groningen, University Medical Center Groningn, Groningen, The Netherlands.

Background: A few studies have indicated inverse relationships between serum ghrelin and gastric and esophageal cancers but those associations have been restricted to specific populations, including smokers and overweight individuals. We examined the association between ghrelin and gastroesophageal cancers and atrophic gastritis in a population-based setting.

Methods: In total 220 gastroesophageal cancers, comprising non-cardia and cardia gastric cancer, esophageal adenocarcinoma, esophageal squamous cell carcinoma (SCC) and age and gender-matched controls were recruited. Serum ghrelin, pepsinogen I/II ratio (PGI/II) and anti-H.pylori IgG antibodies were measured. Relationships between ghrelin and gastroesophageal cancers, after adjustment for PGI/II ratio, H.pylori status and smoking, were tested using logistic regression. Furthermore, in 125 endoscopically normal volunteers, with and without histological atrophic gastritis, the relationship with ghrelin was compared.

Results: Serum ghrelin (lowest vs. highest quintile) was inversely associated with gastric cancer: OR (95% CI) 8.71 (1.70-44.59) for cardia and 6.58 (1.26-34.46) for non-cardia cancer. Lower serum ghrelin was also associated with esophageal SCC: OR (95% CI) 5.69 (1.36-23.78), but not with esophageal adenocarcinoma. A similar association was observed between gastric cancer (cardia and non-cardia) and esophageal SCC when serum ghrelin was analysed as a continuous scaled variable. In endoscopically-normal volunteers, extensive atrophic gastritis was associated with low serum ghrelin [OR (95% CI) 0.25 (0.10-0.64)].

Conclusion: Inverse associations between ghrelin and some gastroesophageal cancers suggest a potential role for serum ghrelin as a biomarker of upper gastrointestinal cancers and atrophic gastritis. In areas with a high incidence of gastric and/or esophageal cancer, screening might be more effectively targeted to individuals with low serum ghrelin in addition to the PGI/II ratio.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0074440PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787044PMC
May 2014

Decrease in gastric cancer susceptibility by MTHFR C677T polymorphism in Ardabil Province, Iran.

Turk J Gastroenterol 2013 ;24(2):117-21

Ardabil University of Medical Sciences, Gastrointestinal Research Center, Ardabil, Islamic Republic of Iran.

Background/aims: Gastric cancer, as the fourth most frequent malignancy worldwide, has the highest rate among cancer-related disorders in Ardabil province, located in North-West Iran. Methylene tetrahydrofolate reductase is one of the cancer susceptibility genes with considerable polymorphisms. Methylene tetrahydrofolate reductase C677T leads to a decrease of about 30% in its product activity and is reported to have an effect on cancer susceptibility.

Materials And Methods: Methylene tetrahydrofolate reductase C677T genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism on peripheral blood DNA from 76 gastric cancer patients and 91 healthy controls. The statistical significance was calculated by logistic regression analysis.

Results: The mean age was 64.2±11.1 and 62.1±9.8 years for cases and controls, respectively. Among tumors, 35.5% were diffuse type and others were intestinal. The frequency of genotypes was 61.8%, 32.9%, and 5.3% among cases and 45.1%, 50.6%, and 4.4% among controls for Ala/Ala, Ala/Val, and Val/Val, respectively. CT heterozygotes had lower susceptibility to gastric cancer (p=0.02). This relationship of significance was detected considering gender and age.

Conclusions: It was found that T allele has a protective association with age in the Ardabil province.
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http://dx.doi.org/10.4318/tjg.2013.0572DOI Listing
May 2014

Neglected role of hookah and opium in gastric carcinogenesis: a cohort study on risk factors and attributable fractions.

Int J Cancer 2014 Jan 5;134(1):181-8. Epub 2013 Aug 5.

Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

A recent study showed an association between hookah/opium use and gastric cancer but no study has investigated the relationship with gastric precancerous lesions. We examined the association between hookah/opium and gastric precancerous lesions and subsequent gastric cancer. In a population-based cohort study, 928 randomly selected, healthy, Helicobacter pylori-infected subjects in Ardabil Province, Iran, were followed for 10 years. The association between baseline precancerous lesions and lifestyle risk factors (including hookah/opium) was analyzed using logistic regression and presented as odds ratios (ORs) and 95% confidence intervals (CIs). We also calculated hazard ratios (HRs) and 95% CIs for the associations of lifestyle risk factors and endoscopic and histological parameters with incident gastric cancers using Cox regression models. Additionally, the proportion of cancers attributable to modifiable risk factors was calculated. During 9,096 person-years of follow-up, 36 new cases of gastric cancer were observed (incidence rate: 3.96/1,000 persons-years). Opium consumption was strongly associated with baseline antral (OR: 3.2; 95% CI: 1.2-9.1) and body intestinal metaplasia (OR: 7.3; 95% CI: 2.5-21.5). Opium (HR: 3.2; 95% CI: 1.4-7.7), hookah (HR: 3.4; 95% CI: 1.7-7.1) and cigarette use (HR: 3.2; 95% CI: 1.4-7.5), as well as high salt intake, family history of gastric cancer, gastric ulcer and histological atrophic gastritis and intestinal metaplasia of body were associated with higher risk of gastric cancer. The fraction of cancers attributable jointly to high salt, low fruit intake, smoking (including hookah) and opium was 93% (95% CI: 83-98). Hookah and opium use are risk factors for gastric cancer as well as for precancerous lesions. Hookah, opium, cigarette and high salt intake are important modifiable risk factors in this high-incidence gastric cancer area.
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http://dx.doi.org/10.1002/ijc.28344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821120PMC
January 2014

Gastric cancer mortality in a high incidence area: long-term follow-up of Helicobacter pylori-related precancerous lesions in the general population.

Arch Iran Med 2013 Jun;16(6):343-7

Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Due to a lack of clear criteria for recognizing subjects at risk of progression to gastric cancer (GC), this cohort study seeks to identify predictors of GC death in a high-risk population.

Methods: During 2000-2001, 1011 randomly selected residents of Ardabil, Iran without a history of gastrointestinal diseases, underwent upper endoscopy with targeted biopsy sampling. Until 2013, cancer mortality data were obtained using cancer and death registry data and verbal autopsy reports. Cox regression was used to estimate hazard ratios (HR).

Results: A total of 3.95% of the participants [mean age: 53.1 ± 9.9 years, 49.8% males, and 88.2% Helicobacter pylori (H. pylori-positive)] died of GC. In the multivariate model, precancerous lesions at the beginning of follow-up were associated with increased GC mortality. The HR [95% confidence interval (CI)] was 7.4 (1.6-33.8) for atrophic gastritis (AG) and 23.6 (5.5-102.3) for intestinal metaplasia (IM). Age over 50 (HR = 4.4; 1.3-14.2), family history of GC (HR = 6.8; 3.3-13.8), smoking (HR = 7.4; 3.2-17.3), and endoscopically confirmed gastric ulcer (GU, HR = 6.5; 2.5-16.4) were independently associated with GC mortality. The concomitant presence of a precancerous lesion increased the HR to 46.5 (10.8-198.6) for a family history of GC, 27.6 (6.5-116.4) for smoking, and 25.1 (6.3-105.3) for age >50 years.

Conclusions: In this population with a high rate of H. pylori infection, age over 50 years, smoking, family history of GC, IM, AG, and in particular, an undiagnosed GU were significant independent risk factors for mortality due to GC. The assessment of a combination of these risk factors might identify individuals at risk of GC who could possibly benefit from regular surveillance.
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http://dx.doi.org/013166/AIM.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812276PMC
June 2013

Helicobacter pylori vacA d1/-i1 genotypes and geographic differentiation between high and low incidence areas of gastric cancer in Iran.

Arch Iran Med 2013 Jun;16(6):330-7

Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran.

Background: Helicobacter pylori (H. pylori)-specific genotypes have been closely correlated with an increased risk of gastric cancer (GC). The present study aimed to determine the distribution of H. pylori pathogenic genotypes amongst Iranians infected with strains representing European ancestry in areas with different GC incidence. 

Methods: A total of 138 H. pylori isolates from ten districts in Iran were used for genotyping. 

Results: The following genotypic frequency was observed: vacA s1 (94.9%), s2 (5.1%), m1 (24.6%), m2 (75.4%), d1 (39.9%), d2 (60.1%), i1 (40.6%), i2 (59.4%), iceA1 (76.8%), iceA2 (52.9%), iceA1/2 (29.7%), babA2 (40.6%), and cagA (65.9%). Hierarchical analyses of molecular variance (AMOVA) for the vacA d1, d2, i1, and i2 alleles and iceA1 and iceA1/2 genes found significant levels of genetic differentiation among populations (P < 0.05). Prevalence of the vacA d1, i1, and iceA1/2 (but not iceA1) genes and vacA d1/i1, vacA d1/iceA1, vacA d1/iceA1/2, vacA d1/cagA+, vacA i1/iceA1, vacA i1/iceA1/2, and vacA i1/cagA+ genotypes were significantly higher (>2- or 3-fold) among H. pylori isolates from high incidence GC areas that had age-standardized rates (ASRs) of >20/105 (max. 51.8/105) when compared with those from low incidence (ASRs <10/105) GC areas (P < 0.005, for the latter, P = 0.016). In contrast, the vacA d2/i2, m2/d2, and m2/i2 genotypes were significantly more prevalent in low compared to high incidence GC areas (P < 0.005). The results of Mantel's test only showed a low correlation between genetic and geographic distances for the iceA1 and iceA1/2 (but not vacA alleles, iceA2, babA2, and cagA) genes among ten districts of Iran (r = 0.098 and 0.074, respectively, P < 0.05). 

Conclusions: We propose that the H. pylori vacA d1/-i1 genotypes, which are new determinants of GC, have tremendous potential for differentiating H. pylori strains from high and low incidence GC areas in Iran.
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http://dx.doi.org/013166/AIM.005DOI Listing
June 2013

Analysis of the relationships between esophageal cancer cases and climatic factors using a Geographic Information System (GIS): a case study of Ardabil province in Iran.

Asian Pac J Cancer Prev 2013 ;14(3):2071-7

Community Medicine, Ardabil University of Medical Science, Ardabil, Iran.

Esophageal cancer is a mjaor health problems in many parts of the world. A geographical information system (GIS) allows investigation of the geographical distribution of diseases. The purpose of the present study was to explore the relationship between esophageal cancer and effective climatic factors using GIS. The dispersion distribution and the relationship between environmental factors effective on cancer were measured using Arc GIS. The highest degree of spread was in Germi town and the least was in Ardabil city. There was a significant relationship between effective environmental factors and esophageal cancer in Ardabil province. The results indicated that environmental factors probably are influential in determining the incidence of esophageal cancer. Also, these results can be considered as a window to future comprehensive research on esophageal cancer and related risk factors.
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http://dx.doi.org/10.7314/apjcp.2013.14.3.2071DOI Listing
January 2014

Are the serum biomarkers pepsinogen I and II good predictors for the detection of subjects with atrophic gastritis in areas that have different gastric cancer incidence?

Arch Iran Med 2013 Apr;16(4):208-12

Digestive Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Northern Iran (Ardabil) is characterized by a high gastric cancer (GC) rate, whereas Southern Iran (Kerman and Yazd) has a low GC rate. The aim of this study is to verify the potential for pepsinogen I and II to detect atrophic gastritis (AG) in both high and low risk populations for GC.

Methods: Sera of blood donors and patients with GC from Ardebil, Kerman and Yazd were used to measure levels of pepsinogen I, II and H. pylori IgG antibody. GC rates in these cities were determined according to the Cancer Registry and upper gastrointestinal (GI) endoscopy results. 

Results: There were 449 subjects with an average age of 45 ± 15 years. The GC rate in the endoscopy units of the hospital in Ardabil was four times higher than Kerman or Yazd. The mean serum pepsinogen I levels did not differ between Ardabil (102 ± 42.6 µg/mL), Kerman (103.3 ± 49.8 µg/mL), and Yazd (111.7 ± 39 µg/mL). Pepsinogen II levels were: 8.1 ± 4.7 µg/mL (Ardabil), 7.5 ± 5.3 µg/mL (Kerman), and 7.6 ± 4.4 µg/mL (Yazd), which were not different. The H. pylori infection rates were: Ardabil (61%), Kerman (55%), and Yazd (73%). A low ratio of pepsinogen I to II (≤3) was seen in Ardabil (1.3%), Kerman (1.9%), and Yazd (0.0%), which was not significant. A total of 51.9% of GC patients from Ardabil had normal pepsinogen I (≥70 µg/mL) levels and pepsinogen I/II ratios that were >5. 

Conclusion: Serum biomarkers pepsinogen I and II and their ratios are probably not sensitive predictors of AG in areas that have either a high or low GC prevalence. This finding is likely related to the lack of an association between GC and advanced AG.
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http://dx.doi.org/013164/AIM.003DOI Listing
April 2013

Epidemiology of peptic ulcer disease: endoscopic results of a systematic investigation in iran.

Middle East J Dig Dis 2012 Apr;4(2):90-6

Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran , Iran.

BACKGROUND Peptic ulcer disease is a multifactorial health problem affecting almost all populations worldwide. Large scale population-based studies are crucial to understanding its scope and specifications in various nations. We aimed to explore environmental risk factors of peptic ulcer disease in the first population based study in Ardabil, Northwest Iran. METHODS This study was a part of a larger survey on upper gastrointestinal tract health conducted in Ardabil and Meshkinshahr with a total catchment area population of 600,000 persons during 2000-01. Using a random sampling proportional to place of residence, 1122 persons aged 40 or elder were selected. 1011 (90.1%) accepted participation and underwent a comprehensive medical examination and a systematic upper gastrointestinal endoscopy. Point prevalence of peptic ulcers was correlated to various life style risk factors. RESULTS Gastric and duodenal ulcers were identified in 33 (3.26%) and 50 (4.94%) participants, making an overall prevalence of 8.20%. Based on multivariable logistic regression analyses, H.pylori infection (OR 3.1, 95% CI: 2.1-4.7), Smoking (OR 1.8, 95% CI: 1.1-6.8), and chronic intake of NSAIDs (OR 2.8, 95% CI: 1.3-4.4) were main risk factors of gastric ulcer. For duodenal ulcer, in addition to H.pylori infection (OR 5.6, 95% CI: 1.9-8.8) and Smoking (OR 2.3, 95% CI: 1.4-6.5), male gender (OR 3.6, 95% CI: 1.2-5.8) and living in an urban area (OR 1.9, 95% CI: 1.1-5.2) were among significant risk factors. CONCLUSION This is the first population-based endoscopic study in North West of Iran reporting accurate point prevalence of peptic ulcer disease. The rate of 3.3% for gastric ulcer and 4.9% for duodenal ulcers are substantially lower than the estimates reported in Asian population-based endoscopic studies but higher than European reports.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017685PMC
April 2012

Epidemiologic profile and clinical characteristics of ulcerative colitis in northwest of Iran: a 10-year review.

Trop Gastroenterol 2010 Oct-Dec;31(4):308-11

Department of Internal Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.

Background And Aim: There are few reports from Iran about the epidemiology and clinical features of inflammatory bowel disease (IBD). In this study, we aimed to determine the epidemiologic profile and clinical features of ulcerative colitis (UC) in Northwest of Iran.

Methods: This retrospective study covered the time period from 1998 to 2008 and included all patients of a private gasteroenterology clinic in the northwest of Iran, who had diagnosis of UC at the time of presentation or those whose diagnosis had been made later. In addition to description of epidemiology and clinical feature of disease, an attempt was made to identify factors associated with severity of disease.

Results: A total of 105 patients including 61 females (58.1%) were evaluated. Mean age of the patients was 33.5 +/- 13.1 years. The median time interval from initiation of symptoms to diagnosis was 9 months. The commonest presentation was proctosigmoiditis. (48.6%). Among extra-intestinal manifestations, sclerosing cholangitis had the highest frequency and was found in 2 (1.9%) patients. Among all evaluated variables, only family income (the higher the income the more severe the disease) and cigarette smoking (inverse association) were find to have significant association with severity of disease.

Conclusion: A case profile of patients with ulcerative colitis from Northwest Iran suggests that the disease is seen most commonly in the third decade of life with a female preponderance. Family income and smoking influenced the course of ulcerative colitis in Iranian patients.
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June 2011

Dietary habits and gastric cancer risk in north-west Iran.

Cancer Causes Control 2011 May 24;22(5):725-36. Epub 2011 Feb 24.

Department of Epidemiology and Biostatistics, School of Health, Yazd Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Objectives: North-west Iran is a high-risk area for gastric cancer (GC). Dietary practices may increase risk of GC. For the first time, the diet-GC association in this area was assessed using a validated food frequency questionnaire.

Methods: Cases and controls were recruited in a population-based study. In addition to collecting dietary data using a food frequency questionnaire, Helicobacter pylori antibody level was measured. Multiple logistic regression models were used to estimate odds ratios for associations between dietary factors and GC among 286 cases and 304 controls.

Results: A positive association was estimated for total fat intake (OR = 1.33/20 g, 95% CI: 1.12-1.57) and risk of GC. Inverse associations were observed for vitamin C, iron, and zinc intake and risk of GC and its subgroups (cardia, non-cardia). Fruits and vegetables consumption and refrigerator use showed inverse associations (OR = 0.72/100 g, 95% CI: 0.65-0.80 and OR = 0.75/10 years, 95% CI: 0.60-0.95, respectively). Positive association was observed among those who preferred fried food (OR = 2.21, 95% CI: 1.45-3.37) or consumed highly salted/roasted seeds (OR = 1.97, 95% CI: 1.13-3.43).

Conclusion: GC in north-west Iran is associated with dietary practices: foods, nutrients and food preparation habits.
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http://dx.doi.org/10.1007/s10552-011-9744-5DOI Listing
May 2011

Mutations in Fanconi anemia genes and the risk of esophageal cancer.

Hum Genet 2011 May 30;129(5):573-82. Epub 2011 Jan 30.

Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, North Kargar Street, Tehran, Iran.

The incidence of esophageal squamous cell carcinoma (ESCC) is very high in northeastern Iran. Previously, we reported a strong familial component of ESCC among Turkmens, who constitute approximately one-half of the population of this region. We hypothesized that the genes which cause Fanconi anemia might be candidate genes for ESCC. We sequenced the entire coding regions of 12 Fanconi anemia genes in the germline DNA of 190 Turkmen cases of ESCC. We identified three heterozygous insertion/deletion mutations: one in FANCD2 (p.Val1233del), one in FANCE (p.Val311SerfsX2), and one in FANCL (p.Thr367AsnfsX13). All three patients had a strong family history of ESCC. In addition, four patients (out of 746 tested) were homozygous for the FANCA p.Ser858Arg mutation, compared to none of 1,373 matched controls (OR = 16.7, 95% CI = 6.2-44.2, P = 0.01). The p. Lys3326X mutation in BRCA2 (also known as Fanconi anemia gene FANCD1) was present in 27 of 746 ESCC cases and in 16 of 1,373 controls (OR = 3.38, 95% CI = 1.97-6.91, P = 0.0002). In summary, both heterozygous and homozygous mutations in several Fanconi anemia-predisposing genes are associated with an increased risk of ESCC in Iran.
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http://dx.doi.org/10.1007/s00439-011-0951-7DOI Listing
May 2011

Gastric cancer in Ardabil, Iran--a review and update on cancer registry data.

Asian Pac J Cancer Prev 2010 ;11(3):595-9

Ardabil University of Medical sciences, Ardabil, Iran.

The incidence rate of gastric cancer in western countries has shown a remarkable decline in recent years while it is still the most common cancer among men in Iran. Ardabil, a North Western province, was found to have the highest rate of GC in Iran and one of the highest gastric cardia cancer rates in the world. We used the most recent data from Ardabil cancer registry to update on the incidence and mortality of GC and performed an extensive search of the English and Persian literature in Pub Med, Embase and all 5 Persian web-based databases, respectively, to summarize all possible risk factors for GC in Ardabil. The age-standardized incidence rate of gastric cancer was 51.8 (95% CI: 47.8-55.8) in men and 24.9 (95% CI: 21.5-27.2) in women per 100,000. Age-standardized mortality rates for gastric cancer in this population were 32.2 (95% CI: 29.1-35.3) and 16.3 (95% CI: 13.9-18.6). The gastric cardia sub-site was the most common location (32.7%) in Ardabil. According to our review H.pylori infection, gastroesphageal reflux symptoms, tobacco smoking, and high intakes of salt, red meat and dairy products increase the risk of GC while diets with a high content of allium vegetables and fruits, especially citrus fruits, and consumption of fresh fish, were significantly protective against GC. We conclude that Ardabil has the highest rate of GC in Iran and one the highest rates of gastric cardia cancer in the world, with no evidence of decline in incidence since 2000. In addition to H.pylori infection, the epidemic of gastroesphageal reflux disease and several dietary factors may be responsible for the very high incidence of gastric cardia cancer in Ardabil.
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March 2011

Epidemiology of upper gastrointestinal cancers in Iran: a sub site analysis of 761 cases.

World J Gastroenterol 2007 Oct;13(40):5367-70

Digestive Disease Research Center, Shariati Hospital, N Kargar St, Tehran 14144, Iran.

Aim: To define the sub site distribution of upper gastrointestinal cancers in three provinces of Iran.

Methods: The study was carried out in three provinces in Iran: Ardabil, Golestan, and Tehran. In Arbabil and Golestan, the data was collected from the sole referral center for gastrointestinal cancers and the local cancer registry. For Tehran province, data from two major private hospitals were used. All gastric and esophageal cancer patients diagnosed during the period from September 2000 and April 2002 were included in the study.

Results: A total of 761 patients with upper gastrointestinal cancers were identified, 314 from Ardabil, 261 from Golestan, and 186 from Tehran. In Tehran, the relative rate of cancer increased from the upper esophagus to the distal stomach. In Golestan, the reverse pattern was observed. In Ardabil, the mid portion (distal esophagus and proximal stomach) was involved most frequently.

Conclusion: There were considerable variations in the sub site of upper gastrointestinal cancers in the three provinces studied. We cannot provide any explanation for this variation. Further research aimed at explaining the discrepancies in sub site distribution of upper gastrointestinal cancers may help identify important risk factors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171328PMC
http://dx.doi.org/10.3748/wjg.v13.i40.5367DOI Listing
October 2007

Survival rate of gastric and esophageal cancers in Ardabil province, North-West of Iran.

Arch Iran Med 2007 Jan;10(1):32-7

Digestive Disease Research Center (DDRC), Tehran University of Medical Sciences, Tehran, Iran.

Background: Upper gastrointestinal cancer is the most common cancer in Ardabil Province, North-West of Iran, accounting for more than 50% of all cancer deaths in this area. We conducted this study to determine the present survival rate of patients with esophageal and gastric cancers before launching interventional studies.

Methods: A prospective follow-up study of 420 biopsy-proven patients (127 females, mean age: 64) with upper gastrointestinal cancer (141 esophageal and 279 stomach cancers) who were initially diagnosed in Aras Clinic, the main gastrointestinal referral center of Ardabil Province, from 2000 through 2004, was performed with collection of data on demographics, tumor characteristics, pathologic stage, treatment methods, complications, survival time, etc. Data were gathered through direct interview with patients or their families in 303 cases and evaluation of death certificates in 55 patients. Follow-up was from cancer diagnosis until death, or immigration. Survival according to stage of disease, Lauren tumor type, tumor location, surgery, and adjuvant chemotherapy was analyzed, and results were compared with those of western series.

Results: Sixty-two cases were lost to follow-up. The one- and five-year survival rates in the patients with upper gastrointestinal cancer in Ardabil Province were 40.5%, and 0.8%, respectively. In the univariate analysis, men had a slightly lower survival rate than women (P = 0.21) and patients with esophageal cancer had a longer survival rate compared to stomach cancer patients (P = 0.15). Patients who had undergone surgery (P < 0.001) and/or chemotherapy (P < 0.001) survived longer than those without such treatments. Tumor morphology, age at diagnosis, radiotherapy, alcohol, and opium consumption did not show any significant effects on the survival rate of patients. In multivariate analysis, only smoking was remained as an independent factor for stomach cancer (P = 0.04) while in esophageal cancer, surgery and grade of differentiation were significant predictors of survival.

Conclusion: Survival rate of stomach and esophagus cancer cases in Ardabil is relatively low. Intervention for early detection and therapy is necessary to increase survival.
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http://dx.doi.org/07101/AIM.009DOI Listing
January 2007