Clinical Phenotype and Disease Course of Inflammatory Bowel Disease in Iran: Results of the Iranian Registry of Crohn's and Colitis (IRCC).

BACKGROUND: Data on the epidemiology of inflammatory bowel disease (IBD) in the Middle East are scarce. We aimed to describe the clinical phenotype, disease course, and medication usage of IBD cases from Iran in the Middle East. METHODS: We conducted a cross-sectional study of registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) from 2017 until 2022. We collected information on demographic characteristics, past medical history, family history, disease extent and location, extra-intestinal manifestations, IBD medications, and activity using the IBD-control-8 questionnaire and the Manitoba IBD index, admissions history, history of colon cancer, and IBD-related surgeries. RESULTS: In total, 9746 patients with ulcerative colitis (UC) (n=7793), and Crohn's disease (CD) (n=1953) were reported. The UC to CD ratio was 3.99. The median age at diagnosis was 29.2 (IQR: 22.6,37.6) and 27.6 (IQR: 20.6,37.6) for patients with UC and CD, respectively. The male-to-female ratio was 1.28 in CD patients. A positive family history was observed in 17.9% of UC patients. The majority of UC patients had pancolitis (47%). Ileocolonic involvement was the most common type of involvement in CD patients (43.7%), and the prevalence of stricturing behavior was 4.6%. A prevalence of 0.3% was observed for colorectal cancer among patients with UC. Moreover,15.2% of UC patients and 38.4% of CD patients had been treated with anti-tumor necrosis factor (anti-TNF). CONCLUSION: In this national registry-based study, there are significant differences in some clinical phenotypes such as the prevalence of extra-intestinal manifestations and treatment strategies such as biological use in different geographical locations.

Diagnostic value of long noncoding RNA SNHG15 in gastric cancer: in vitro and in silico studies.

LncRNA SNHG15 has been recognized as the main factor in the progression of various cancer types. However, the underlying mechanisms are not well clarified. This research aimed to explore the diagnostic potential of SNHG15 in gastric cancer (GC) patients and also the effects of SNHG15-miRNA-mRNA network in GC pathobiology. The expression level of SNHG15 in GC tissues and adjacent normal tissues (ANTs) was evaluated by qRT-PCR and also considered in relation to clinicopathologic factors. The ROC curve was explored to consider the specificity and sensitivity of SNHG15. Gene ontology functional annotation and KEGG pathway analysis were performed in order to predict the effects of SNHG15-miRNA-mRNA network in GC pathobiology. SNHG15 was overexpressed in GC tissues compared to ANTs (fold change= 3.87 and P-value = 0.0022). The SNHG15 expression level was not significantly associated with clinicopathologic factors. ROC curve indicated the specificity of 63.51 and sensitivity of 79.73 and the AUC of 0.744 (P-value < 0.0001). Further gene network analysis revealed that SNHG15 interacts with has-miR-613, has-miR-542-3p, and has-miR-1236-3p, and may be involved in the GC pathobiology by affecting the EGFR tyrosine kinase inhibitor resistance, HIF-1 signaling pathway, and VEGF signaling pathway. It can be concluded that SNHG15 may be a diagnostic factor in GC and may contribute in a variety of cancer-related signaling pathways.

Exploring virulence factors of Helicobacter pylori isolated from gastric biopsy.

BACKGROUND: Helicobacter pylori (H. pylori) colonizes human gastric mucosa and is classified as class one carcinogenic bacteria. In this regard, this study aimed to detect major virulence factors in H. pylori strains recovered from gastric biopsy in patients referred to Aras Clinique in Ardabil, northwest of Iran (2019-2021). MATERIALS AND METHODS: In this descriptive-cross sectional study, 287 dyspeptic patients were included. For bacterial isolation, gastric biopsy specimens (n=287) were taken from gastric antrum, then aseptically were cultured on the selective medium and incubated at 37C in microaerophilic conditions for 3-5 days. RESULTS: 25.18% of all (n = 70) patients were found to be infected with H. pylori upon endoscopy. Of them, 9 patients (12.857%) and 2 patients (2.875%) had peptic ulcer disease and gastric cancer respectively. According to the different patterns of virulence factors, 57 virutypes were identified in which oipA-vacAs1-vacAm2 (3, 4.28% n =) and oipA-vacAs1-vacAs2-vacAm2 (3, 4.28% n =) were the most common patterns. The simultaneous presence of vacAS2, vacAm2 and hopQ2 genes was observed in both patients with gastric cancer. OipA (n = 562.5%), VacAs1 (n = 6.75%), VacAs2 (n = 6.75%), and VacAm2 (n = 787.5%) were found to be the most prevalent virulence factor. CONCLUSION: According previous studies, it is confirmed that the cagPAI gene cluster and vacA gene alleles are strongly correlated with gastritis and gastrointestinal tract adenocarcinomas. Our study indicated that 50% of the indigenous strains of H. pylori harbor these oncogenic genes and they are hypervirulent.

Risk of Gastric Cancer is Highly Dependent on Type of First-Degree Family Member Affected by Cancer: Lessons from a High-Risk Population in Iran.

Background: Family history of gastric cancer (GC) in first-degree relatives may increase the risk of GC. This study aimed to assess how family history of GC in first-degree relatives really affects the risk of GC in an extremely high-risk population. Methods: A large population-based case-control study was carried out on 1222 incident GC cases and 1235 controls in Ardabil Province-a high-risk area in North-West Iran-to assess the associations of GC family history in first-degree relatives with the risk of GC (2003-2017). Results: GC family history did not significantly associate with the risk of GC overall (ORadj=1.09, 95% CI: 0.80-1.47, P=0.589). It found no significant association of GC family history in a parent, and in a father, mother, and sister separately, with the risk of GC. However, GC risk was significantly associated with a history of GC in a sibling (ORadj=1.61, 95% CI: 1.11-2.35, P=0.013), especially brother (ORadj=2.24, 95% CI: 1.41-3.64, P=0.0008). The risk was greatly increased in subjects with two or more affected brothers (ORadj =5.56, 95% CI: 2.33-14.20, P=0.0002). Conclusion: We did not find a familial tendency to cardia GC and non-cardia GC as well as histopathologic features. Determining the type of first-degree relationships with GC may, therefore, be more important than assessing family history alone for predicting the risk of GC in this high-risk area.

Restoration of miR-650 leads to down-regulation of KISS1, a possible route involved in overcoming 5-FU resistance and induction of apoptosis in CRC cells in-vitro.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers and the fourth leading cause of cancer-related deaths worldwide. We aimed to determine the role of miR-650 in CRC pathogenesis. METHODS: In this study, we examined the expression of miR-650 and KISS1 in 80 CRC patients who either received or did not receive chemo agents. For this aim, we assessed the miR-650 and KISS1 expression levels in 80 CRC tissues, 30 of which had no history of chemotherapy. The effect of miR-650 and 5-FU on KISS1 expression was measured using qPCR and Western blotting. Also, the 5- FU effect on miR-650 expression in the CRC cell lines was measured by qRT-PCR. Next, MTT assay and Flowcytometry assays were conducted to determine the role of miR-650 in cell viability and apoptosis. RESULTS: The results showed that miR-650 was down-regulated in CRC tissues. However, patients who received 5-FU before surgery showed increased expression of miR-650. The results for KISS1 were insignificant while administering 5-FU to patients preoperatively increased its expression. In-vitro studies showed that 5-FU led to the up-regulation of miR-650 in the SW480 CRC cell line. Furthermore, the administration of miR-650 and 5-FU downregulated KISS1, especially when combined. Moreover, miR-650 with 5-FU significantly reduced cell viability in CRC cell lines by inducing apoptosis. CONCLUSIONS: These results indicate that miR-650 has a tumor suppressive function, overcoming 5-FU chemoresistance in CRC, and induces apoptosis probably by alleviating KISS1. These results suggest that miR-650 is a potential contributor to CRC pathogenesis.

Comparison of Disease Phenotype and Course among Elderly- and Early-Onset Inflammatory Bowel Diseases in the Middle East.

BACKGROUND: It is unknown if the clinical manifestations and phenotype of disease are comparable between early- and elderly-onset inflammatory bowel disease (IBD). We aimed to seek differences in disease phenotype, course, complications, and treatment between early- and elderly-onset IBD patients. METHODS: This retrospective cohort study on registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) compared demographics, disease phenotype, disease activity, IBD-related surgery and medications between early- and elderly-onset IBD. A generalized linear regression model was used to investigate the relative risk of age at diagnosis adjusted for gender and disease duration for the outcomes. RESULTS: From 10048 IBD patients, 749 with early-onset (7.5%), and 472 (4.7%) elderly-onset IBD were enrolled: 855 (63.1%) ulcerative colitis (UC) and 366 (26.9%) Crohn's disease (CD). Left-sided colitis was more frequent among elderly-onset UC patients (P<0.001). Ileum and ileocolonic locations were the most common types in elderly-onset and early-onset CD patients, respectively. In comparison with elderly-onset UC, early-onset cases more often used prednisolone (22.1% vs. 11.4%, P=0.001), immunomodulators (44.9% vs 25.2%, P<0.001) and anti-tumor necrosis factors (TNF) (20.1% vs 11.9%, P=0.002). Elderly-onset UC patients had 0.7 times lower risk of aggressive phenotype (95%CI:0.6‒0.9, P=0.005). Early-onset CD was associated with higher use of prednisolone (27.7% vs 8.1%, P<0.001), immunomodulators (58.7% vs 41.8%, P=0.005) and anti-TNF (49.6% vs 35.4%, P=0.006). CONCLUSION: Early-onset IBD was associated with a more aggressive phenotype and higher prednisolone, immunomodulators, and anti-TNF use.

Suppression of lncRNA NORAD may affect cell migration and apoptosis in gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is a major malignancy that threatens people's lives worldwide. Long noncoding RNA (lncRNA) non-coding RNA activated by DNA damage (NORAD) is known to be a potential oncogene in many cancers and may promote cell migration and metastasis, and decrease apoptosis rate. MATERIAL AND METHODS: NORAD expression was measured in 70 pairs of GC tissues and their adjacent normal tissues (ANTs) by quantitative real-time polymerase chain reaction. Si-NORAD gene knockdown study and cellular assays were conducted to assess the correlation between NORAD expression and cell viability, apoptosis, migration, and metastasis. RESULTS: NORAD was significantly overexpressed in GC tissues compared to ANTs (P value < 0.0001). The receiver operating characteristic curve indicated the AUC of 0.721 with the sensitivity and specificity of 78.57 and 61.43, respectively (P value < 0.0001). NORAD downregulation leads to decreased cell viability (P value < 0.001) and migration (P value < 0.01), increased apoptosis rate (P value < 0.0001), and increased protein level for PTEN, E-cadherin, and Bax, but decreased protein level for Bcl-2. CONCLUSION: Generally, NORAD may serve as a potential diagnostic biomarker in GC.

Clinical Phenotype and Disease Course of Inflammatory Bowel Disease: A Comparison Between Sporadic and Familial Cases.

BACKGROUND: The role of genetic and environmental factors in inflammatory bowel disease's (IBD) clinical course is not fully clear. We aimed to assess the clinical phenotype, disease course, and prognosis of familial IBD in comparison with sporadic cases. METHODS: We conducted a prospective national matched case-control study of registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) recruited from 2017 until 2020. Sporadic and familial IBD patients were matched based on age, sex, and disease duration. Data on demographics, past medical disease, family history of IBD, disease type, clinical phenotype, extraintestinal manifestations, IBD medications, IBD activity using the IBD-control-8 questionnaire and the Manitoba IBD index, emergency visits in the past 12 months, admissions in the past 3 months, history of colon cancer, IBD-related surgeries, and aggressive phenotype were gathered. Variable distributions were compared between sporadic and familial cases. RESULTS: Overall, 5231 patients with ulcerative colitis (UC, 18.3% familial) and 1438 patients with Crohn's disease (CD, 16.7% familial) were registered in the IRCC. Age at diagnosis was similar between familial and sporadic cases. After matching, 3523 UC patients and 908 CD patients were enrolled in the study. Extraintestinal manifestations, UC extent, CD location and behavior, anti-TNF use, disease activity, colon cancer, IBD-related surgeries and the aggressive phenotype were similar between these sporadic and familial cases. CONCLUSIONS: The prevalence of familial UC and CD cases in Iran was more similar to western countries, and family history did not show a predictive value for disease phenotype, course, and outcomes in our study.

Crosstalk between lncRNAs and miRNAs in gastrointestinal cancer drug resistance.

Gastrointestinal cancers are one of the most prevalent malignancies worldwide. Dysregulation of lncRNAs by epigenetic alteration is crucial in gastrointestinal carcinogenesis. Epigenetic alteration includes DNA methylation, chromatin remodeling, histone modifications, and deregulated-gene expression by miRNAs. LncRNAs are involved in biological processes, including, uncontrolled cell division, migration, invasion, and resistance to apoptosis and drugs. Multiple-drug resistance (MDR) is a crucial obstacle in effective chemotherapy for gastrointestinal cancers. MDR can be associated with the prognosis and diagnosis of patients receiving chemotherapeutic agents (i.e. cisplatin, oxaliplatin, platinum, 5-fluorouracil, gefitinib, methotrexate, taxol, cetuximab, docetaxel, and gemcitabine). In this review, we focused on recently known lncRNAs and their relation with miRNAs and chemotherapeutic drugs, and their modulation in gastrointestinal cancers. Moreover, we mentioned the future prospective and clinical application of lncRNAs as a critical indicator and biomarker in diagnosis, prognosis, staging, grading, and treatment of gastrointestinal cancers.

Cost-effectiveness analysis of two routine therapeutic methods for Helicobacter pylori eradication: a Persian cohort-based study.

AIM: This study aimed to analyze the cost-effectiveness of two routine therapeutic methods for H. pylori eradication in Iran. BACKGROUND: Because of the importance of Helicobacter pylori (H. pylori) eradication on gastric cancer prevalence and costs, an economic analysis of the eradication methods is essential for health systems. METHODS: This cross-sectional study was conducted on 7,496 participants with positive Hepadnaviridae (HPsAg) test results for H. pylori; 6,163 of them were treated with furazolidone (group A), and 1,333 participants were treated with clarithromycin (group B). Data on GP visits, medications, and HPsAg costs as direct costs and absence from work and transportation as indirect costs was collected by researcher-made questionnaire. Indirect costs were calculated based on face-to-face interviews with 365 patients of the Persian Cohort Center. Successful eradication of H. pylori infection (negative HPsAg) was defined as the effectiveness of the interventions. Incremental cost-effectiveness ratio (ICER) was used to compare the overall results. RESULTS: The total direct cost of H. pylori for groups A and B were estimated at 13.7 and 5.83 billion IRR, respectively. The highest and lowest percentages of total costs were the cost of diagnostic services and the time cost, respectively. There was a significant difference between the two groups in drug costs (p<0.001). The effect ratio for groups A and B was 85.93% and 96.54%, respectively. Cost per effectiveness was higher for clarithromycin (CE=3,250,170 IRR) than for furazolidone (CE=2,988,488 IRR), and ICER showed that 5.1 Million IRR per participant is needed to eradicate H. pylori. CONCLUSION: Based on the results, furazolidone was more cost-effective than clarithromycin for H. pylori treatment. Therefore, due to the high prevalence of H. pylori and the economic conditions of the health system in Iran, furazolidone can be a cost-effective choice between the two conventional treatment methods considering the results of further research and possible side effects.

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

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 oipA+vs. oipA- genotype was 67.7% (216/319). The total frequency of the oipA+vs. 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 oipA+vs. oipA- genotype showed a strong direct association with PUs; the ORadj (95% CI) was 18.751 (4.421-79.531), (p = 0.00007). In contrast, it had a significant reverse association with GC; the ORadj (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.

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

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.

Which genotype of Helicobacter pylori-cagA or cagE-Is better associated with gastric Cancer risk? Lessons from an extremely high-risk area in 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 cagA+vs. cagA-, cagE+vs. cagE-, cagA+/cagE-vs. AGCs (all genotype combinations), cagA-/cagE+vs. AGCs, cagA-/cagE-vs. AGCs, cagA+/cagE+vs. AGCs, cagA+/cagE-vs. cagA-/cagE+, and cagA+/cagE+vs. 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 cagE+vs. cagE- (59.6% (65/109) in GC vs. 31.2% (24/77) in non-atrophic gastritis, NAG) and the cagA+/cagE+vs. 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.

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 (Cn) 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 Cn 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.

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

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.

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

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.

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

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.

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

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.

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.

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

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.