Publications by authors named "Ramin Shakeri"

49 Publications

Long-term opiate use and risk of cardiovascular mortality: results from the Golestan Cohort Study.

Eur J Prev Cardiol 2020 Sep 10. Epub 2020 Sep 10.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran 14117-13135, Iran.

Aims: Tens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of long-term opiate use with cardiovascular mortality and whether this association is independent of the known risk factors.

Methods And Results: In the population-based Golestan Cohort Study-50 045 Iranian participants, 40-75 years, 58% women-we used Cox regression to estimate hazard ratios and 95% confidence intervals (HRs, 95% CIs) for the association of opiate use (at least once a week for a period of 6 months) with cardiovascular mortality, adjusting for potential confounders-i.e. age, sex, education, wealth, residential place, marital status, ethnicity, and tobacco and alcohol use. To show independent association, the models were further adjusted for hypertension, diabetes, waist and hip circumferences, physical activity, fruit/vegetable intake, aspirin and statin use, and history of cardiovascular diseases and cancers. In total, 8487 participants (72.2% men) were opiate users for a median (IQR) of 10 (4-20) years. During 548 940 person-years-median of 11.3 years, >99% success follow-up-3079 cardiovascular deaths occurred, with substantially higher rates in opiate users than non-users (1005 vs. 478 deaths/100 000 person-years). Opiate use was associated with increased cardiovascular mortality, with adjusted HR (95% CI) of 1.63 (1.49-1.79). Overall 10.9% of cardiovascular deaths were attributable to opiate use. The association was independent of the traditional cardiovascular risk factors.

Conclusion: Long-term opiate use was associated with an increased cardiovascular mortality independent of the traditional risk factors. Further research, particularly on mechanisms of action, is recommended.
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http://dx.doi.org/10.1093/eurjpc/zwaa006DOI Listing
September 2020

Opium use and subsequent incidence of cancer: results from the Golestan Cohort Study.

Lancet Glob Health 2020 05;8(5):e649-e660

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Digestive Disease Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Evidence is emerging for a role of opiates in various cancers. In this study, we aimed to investigate the association between regular opium use and cancer incidence.

Methods: This study was done in a population-based cohort of 50 045 individuals aged 40-75 years from northeast Iran. Data on participant demographics, diet, lifestyle, opium use, and different exposures were collected upon enrolment using validated questionnaires. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% CIs for the association between opium use and different cancer types.

Findings: During a median 10 years of follow-up, 1833 participants were diagnosed with cancer. Use of opium was associated with an increased risk of developing all cancers combined (HR 1·40, 95% CI 1·24-1·58), gastrointestinal cancers (1·31, 1·11-1·55), and respiratory cancers (2·28, 1·58-3·30) in a dose-dependent manner (p<0·001). For site-specific cancers, use of opium was associated with an increased risk of developing oesophageal (1·38, 1·06-1·80), gastric (1·36, 1·03-1·79), lung (2·21, 1·44-3·39), bladder (2·86, 1·47-5·55), and laryngeal (2·53, 1·21-5·29) cancers in a dose-dependent manner (p<0·05). Only high-dose opium use was associated with pancreatic cancer (2·66, 1·23-5·74). Ingestion of opium (but not smoking opium) was associated with brain (2·15, 1·00-4·63) and liver (2·46, 1·23-4·95) cancers in a dose-dependent manner (p<0·01). We observed consistent associations among ever and never tobacco users, men and women, and individuals with lower and higher socioeconomic status.

Interpretation: Opium users have a significantly higher risk of developing cancers in different organs of the respiratory, digestive, and urinary systems and the CNS. The results of this analysis show that regular use of opiates might increase the risk of a range of cancer types.

Funding: World Cancer Research Fund International, Cancer Research UK, Tehran University of Medical Sciences, US National Cancer Institute, International Agency for Research on Cancer.
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http://dx.doi.org/10.1016/S2214-109X(20)30059-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196888PMC
May 2020

Opiate and Tobacco Use and Exposure to Carcinogens and Toxicants in the Golestan Cohort Study.

Cancer Epidemiol Biomarkers Prev 2020 03 8;29(3):650-658. Epub 2020 Jan 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Background: There is little information on human exposure to carcinogens and other toxicants related to opiate use, alone or in combination with tobacco.

Methods: Among male participants of the Golestan Cohort Study in Northeast Iran, we studied 28 never users of either opiates or tobacco, 33 exclusive cigarette smokers, 23 exclusive users of smoked opiates, and 30 opiate users who also smoked cigarettes (dual users; 21 smoked opiates and 9 ingested them). We quantified urinary concentrations of 39 exposure biomarkers, including tobacco alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC), and used decomposition to parse out the share of the biomarker concentrations explained by opiate use and nicotine dose.

Results: Dual users had the highest concentrations of all biomarkers, but exclusive cigarette smokers and exclusive opiate users had substantially higher concentrations of PAH and VOC biomarkers than never users of either product. Decomposition analysis showed that opiate use contributed a larger part of the PAH concentrations than nicotine dose, and the sum of 2- and 3-hydroxyphenanthrene (∑-phe) resulted almost completely from opiate use. Concentrations of most VOC biomarkers were explained by both nicotine dose and opiate use. Two acrylamide metabolites, a 1,3-butadiene metabolite and a dimethylformamide metabolite, were more strongly explained by opiate use. Acrylamide metabolites and ∑-phe were significantly higher in opiate smokers than opiate eaters; other biomarkers did not vary by the route of opiate intake.

Conclusions: Both cigarette smokers and opiate users (by smoking or ingestion) were exposed to many toxicants and carcinogens.

Impact: This high exposure, particularly among dual opiate and cigarette users, can have a substantial global public health impact.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839071PMC
March 2020

ANTXR1 (TEM8) overexpression in gastric adenocarcinoma makes the protein a potential target of immunotherapy.

Cancer Immunol Immunother 2019 Oct 14;68(10):1597-1603. Epub 2019 Sep 14.

Cell-Based Therapies Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Shariati Hospital, P.O. Box 14117-13135, Tehran, Iran.

Background: Despite the promise of immunotherapy for gastric adenocarcinoma, choices for the selection of effective antigenic targets are very limited. Previously published data and our own in-house computational analysis have suggested that ANTXR1 is a potential target, simultaneously expressed in malignant tumor cells and the endothelial cells of the tumors. However, the expression pattern of ANTXR1 protein in clinical samples of gastric adenocarcinoma has not been fully evaluated.

Methods: Using immunohistochemistry (IHC), we recorded the percentage of ANTXR1 positive cells separately in tumor cells and endothelial cells in the primary tumor, non-tumor gastric tissue adjacent to the primary tumor, and tumor in metastatic sites of 140 gastric adenocarcinoma patients. We also evaluated the association of ANTXR1 expression with the Lauren histological classification of the primary tumors, the patient's history of neoadjuvant chemotherapy and/or radiotherapy, and the patient's overall survival.

Results: ANTXR1 was expressed in a mean of 73.89 ± 30.12% of tumor cells and 13.55 ± 20.53% of endothelial cells in the primary tumors. Intestinal adenocarcinomas had lower ANTXR1 expression in the tumor cells and higher ANTXR1 expression in the endothelial cells of the tumor regions, and a history of neoadjuvant therapy was associated with increased ANTXR1 expression in the endothelial cells of the tumor regions. Finally, above median expression of ANTXR1 in the tumor cells of the tumor regions was associated with significantly lower overall patient survival.

Conclusions: Our findings suggest that ANTXR1 is a promising candidate for preclinical and clinical evaluation for gastric adenocarcinoma immunotherapy.
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http://dx.doi.org/10.1007/s00262-019-02392-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493837PMC
October 2019

Comparing Anthropometric Indicators of Visceral and General Adiposity as Determinants of Overall and Cardiovascular Mortality.

Arch Iran Med 2019 06 1;22(6):301-309. Epub 2019 Jun 1.

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

Background: It is unclear which anthropometric obesity indicator best predicts adverse health outcomes. This study aimed to investigate the association of body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), and hip-adjusted WC with all-cause and cardiovascular mortality.

Methods: 50045 people aged 40-75 (58% women, median BMI: 26.3 kg /m2 ) participated in the population-based Golestan Cohort Study. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for the association of obesity indicators with mortality. We also examined the association of these indicators with intermediate outcomes, including hypertension, blood glucose, dyslipidemia, carotid atherosclerosis, nonalcoholic fatty liver, and visceral abdominal fat.

Results: After a median follow-up of 10.9 years (success rate: 99.1%), 6651 deaths (2778 cardiovascular) occurred. Comparing 5th to the 1st quintile, HRs (95% CIs) for all-cause and cardiovascular mortality were 1.12 (1.02-1.22) and 1.59 (1.39-1.83) for BMI, 1.16 (1.07-1.27) and 1.66 (1.44-1.90) for WC, 1.28 (1.17-1.40) and 1.88 (1.63-2.18) for WHtR, 1.44 (1.32-1.58) and 2.04 (1.76-2.36) for WHR, and 1.84 (1.62-2.09) and 2.72 (2.23-3.32) for hip-adjusted WC, respectively. Hip-adjusted WC had the strongest associations with the intermediate outcomes.

Conclusion: Indicators of visceral adiposity (e.g., hip-adjusted WC) were much stronger predictors of overall and cardiovascular mortality than were indicators of general adiposity (e.g., BMI). The full-strength effect of visceral adiposity becomes apparent only when both WC, as a risk factor, and hip circumference, as a protective factor, are individually and simultaneously taken into consideration.
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June 2019

Urinary Biomarkers of Carcinogenic Exposure among Cigarette, Waterpipe, and Smokeless Tobacco Users and Never Users of Tobacco in the Golestan Cohort Study.

Cancer Epidemiol Biomarkers Prev 2019 02 8;28(2):337-347. Epub 2019 Jan 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.

Background: How carcinogen exposure varies across users of different, particularly noncigarette, tobacco products remains poorly understood.

Methods: We randomly selected 165 participants of the Golestan Cohort Study from northeastern Iran: 60 never users of any tobacco, 35 exclusive cigarette, 40 exclusive (78% daily) waterpipe, and 30 exclusive smokeless tobacco (nass) users. We measured concentrations of 39 biomarkers of exposure in 4 chemical classes in baseline urine samples: tobacco alkaloids, tobacco-specific nitrosamines (TSNA), polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC). We also quantified the same biomarkers in a second urine sample, obtained 5 years later, among continuing cigarette smokers and never tobacco users.

Results: Nass users had the highest concentrations of tobacco alkaloids. All tobacco users had elevated TSNA concentrations, which correlated with nicotine dose. In both cigarette and waterpipe smokers, PAH and VOC biomarkers were higher than never tobacco users and nass users, and highly correlated with nicotine dose. PAH biomarkers of phenanthrene and pyrene and two VOC metabolites (phenylmercapturic acid and phenylglyoxylic acid) were higher in waterpipe smokers than in all other groups. PAH biomarkers among Golestan never tobacco users were comparable to those in U.S. cigarette smokers. All biomarkers had moderate to good correlations over 5 years, particularly in continuing cigarette smokers.

Conclusions: We observed two patterns of exposure biomarkers that differentiated the use of the combustible products (cigarettes and waterpipe) from the smokeless product. Environmental exposure from nontobacco sources appeared to contribute to the presence of high levels of PAH metabolites in the Golestan Cohort.

Impact: Most of these biomarkers would be useful for exposure assessment in a longitudinal study.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-0743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935158PMC
February 2019

Epidemiology of Head and Neck Cancers in Northern Iran: A 10-Year Trend Study From Golestan Province.

Arch Iran Med 2018 09 1;21(9):406-411. Epub 2018 Sep 1.

Omid Cancer Research Center, Omid Preventive Medicine and Health Promotion Center, Gorgan, Iran.

Background: Golestan province, in Northern Iran, is a high-risk area for esophageal squamous cell carcinoma (SCC). SCC is also the most common histological type of cancers of the head and neck region including cancers of oral cavity, oropharynx, hypopharynx and larynx. We aimed to present the incidence rate of head and neck SCC (HNSCC) in Golestan province during 2004 and 2013.

Methods: Data on HNSCC were obtained from Golestan population-based cancer registry (GPCR). Quality control and data analysis were performed using CanReg software. Age standardized incidence rates (ASRs) were calculated using the world standard population. The ASRs were presented per 100000 person-years for different genders, residence places and years.

Results: During the 10-year period from 2004-2013, 434 cases of HNSCC were registered. 327 (75.3%) of these cases were male, 51.2% (222 cases) lived in urban areas and 351 (80.9%) of the total HNSCCs occurred in the larynx. Overall, the ASR of HNSCCs in Golestan province was 4.8. The ASR of HNSCCs was more than two-fold higher in male (6.6) than female (3.0). Our results showed an increasing trend in ASR of larynx cancer during the study period both in male and female.

Conclusion: We found relatively high rates of larynx cancer in Golestan province. Our results also showed higher rates of HNSCC in males and urban population. Considering common risk factors between HNSCCs and esophageal cancer, further studies are needed to clarify different aspects of HNSCCs (including epidemiology and risk factors) in this high-risk population.
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September 2018

Causes of premature death and their associated risk factors in the Golestan Cohort Study, Iran.

BMJ Open 2018 07 18;8(7):e021479. Epub 2018 Jul 18.

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

Objectives: To examine the causes of premature mortality (<70 years) and associated risk factors in the Golestan Cohort Study.

Design: Prospective.

Setting: The Golestan Cohort Study in northeastern Iran.

Participants: 50 045 people aged 40 or more participated in this population-based study from baseline (2004-2008) to August 2017, with over 99% success follow-up rate.

Main Outcome Measures: The top causes of premature death, HR and their 95% CI and population attributable fraction (PAF) for risk factors.

Results: After 444 168 person-years of follow-up (median of 10 years), 6347 deaths were reported, of which 4018 (63.3%) occurred prematurely. Ischaemic heart disease (IHD) accounted for 33.9% of premature death, followed by stroke (14.0%), road injuries (4.7%), stomach cancer (4.6%) and oesophageal cancer (4.6%). Significant risk/protective factors were: wealth score (HR for highest vs lowest quintile: 0.57, PAF for lowest four quintiles vs top quintile: 28%), physical activity (highest vs lowest tertile: 0.67, lowest two tertiles vs top tertile: 22%), hypertension (1.50, 19%), opium use (1.69, 14%), education (middle school or higher vs illiterate: 0.84, illiterate or primary vs middle school or higher: 13%), tobacco use (1.38, 11%), diabetes (2.39, 8%) and vegetable/fruit consumption (highest vs lowest tertile: 0.87, lowest two tertiles vs top tertile: 8%). Collectively, these factors accounted for 76% of PAF in men and 69% in women.

Conclusion: IHD and stroke are the leading causes of premature mortality in the Golestan Cohort Study. Enhancing socioeconomic status and physical activity, reducing opium and tobacco use, increasing vegetable/fruit consumption and controlling hypertension and diabetes are recommended to reduce premature deaths.
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http://dx.doi.org/10.1136/bmjopen-2018-021479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059279PMC
July 2018

Opium Use and Risk of Pancreatic Cancer: A Prospective Cohort Study.

Cancer Epidemiol Biomarkers Prev 2018 03 20;27(3):268-273. Epub 2017 Dec 20.

Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

We examined the association between opium consumption and pancreatic cancer incidence in a large-scale prospective cohort of the general population in northeastern Iran. A total of 50,045 adults were systematically followed up (median of 7.4 years), and incident cases of pancreatic cancer were identified. Self-reported data on opium consumption was collected at baseline. Cumulative use (-year) was defined as number of nokhods (a local unit, approximately 0.2 g) of opium consumed per day multiplied by number of years consuming. Adjusted HRs and 95% confidence intervals (CIs) for the association between opium consumption and pancreatic cancer were calculated using Cox proportional hazards regression models. Overall, 54 confirmed cases of pancreatic cancer were identified. Opium use of more than 81 nokhod-years (high cumulative use), compared with never use, was strongly associated with pancreatic cancer even after adjustments for multiple potential confounding factors [HR = 3.01; 95% CI, 1.25-7.26]. High cumulative consumption of opium was significantly associated with risk of pancreatic cancer after adjusting for cumulative dose of cigarette smoking [HR = 3.56; 95% CI, 1.49-8.50]. In a sensitivity analysis, we excluded participants (including 2 pancreatic cancer cases) who were recruited within the first 5 years of starting opium consumption; high cumulative use of opium was still associated with pancreatic cancer risk [HR = 2.75; 95% CI, 1.14-6.64]. Our results showed a positive association between opium consumption and pancreatic cancer. This is the first prospective large-scale study to show the association of opium consumption with pancreatic cancer as a risk factor. .
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http://dx.doi.org/10.1158/1055-9965.EPI-17-0592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835180PMC
March 2018

Prevalence and determinants of chronic kidney disease in northeast of Iran: Results of the Golestan cohort study.

PLoS One 2017 3;12(5):e0176540. Epub 2017 May 3.

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

Background: The burden of chronic kidney disease (CKD) is increasing globally in particular in fast emerging economies such as Iran. Population-based studies on prevalence of CKD in Iran are scarce. The objective of the current study was to explore the prevalence and determinants of CKD in the setting of Golestan Cohort Study (GCS), the largest prospective cohort in the Middle East.

Methods: In this observational study, 11,409 participants enrolled in the second phase of GCS were included. Sex, age, literacy, residence, anthropometric measurements, smoking, opium use, self-reported history of cardiovascular diseases (heart disease and/or stroke), hypertension, diabetes, and lipid profile were the predictors of interest. The outcomes of interest were eGFR and CKD defined as eGFR< 60 ml/min/1.73m2.

Results: Mean (SD) of GFR was 70.0 ± 14.7 ml/min/1.73m2 among all participants, 68.2 ± 14.2 among women, and 72.0 ± 15.0 among men. Prevalence of CKD was 23.7% (26.6% in women, 20.6% in men). The prevalence of CKD stages 3a, 3b, 4, and 5 were 20.0%, 3.3%, 0.4% and 0.1%, respectively. Female sex, older age, urban residence, history of CVD, hypertension or diabetes, larger body mass and surrogates of body fat and opium use were all associated with CKD. Opium had a significant positive association with CKD in adjusted model. All anthropometric measurements had positive linear association with CKD. Being literate had inverse association. Sex had significant interaction with anthropometric indices, with higher odds ratios among men compared with women. A significantly high association was observed between the rate of change in waist circumference and systolic blood pressure with risk of CKD.

Conclusion: One in four people in this cohort had low eGFR. Obesity and overweight, diabetes, hypertension, and dyslipidemia are major risk factors for CKD. Halting the increase in waist circumference and blood pressure may be as important as reducing the current levels.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176540PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414986PMC
September 2017

Capillary electrophoresis with online stacking in combination with AgNPs@MCM-41 reinforced hollow fiber solid-liquid phase microextraction for quantitative analysis of Capecitabine and its main metabolite 5-Fluorouracil in plasma samples isolated from cancer patients.

J Chromatogr B Analyt Technol Biomed Life Sci 2017 Jan 18;1040:22-37. Epub 2016 Nov 18.

Department of Chemistry, Faculty of Science, Azarbaijan Shahid Madani University, Tabriz, Iran.

The purpose of this study is the development and validation of a simple, novel, selective and fast off-line microextraction technique combining capillary electrophoresis with in-column field-amplified sample injection (FASI) for the simultaneous determination of capecitabine (CAP) and its active metabolite, 5-Fluorouracil (5-FU), in human plasma. At the moment, there is a lack of using cost-effective CE tool combined with novel miniaturized sample clean-up techniques for analysis of these important anti-cancer agents in plasma samples. This paper intends to fill this gap and describe a simple off-line sample pretreatment by means of AgNPs@MCM-41 reinforced hollow fiber Solid/Liquid phase microextraction (AgNPs@MCM41-HF-SLPME) with subsequent quantitation by FASI-CE. The separation of analytes was performed using a BGE containing 60mM phosphate-Tris buffer (pH 7) with 10% methanol as an organic modifier. Before sample loading, a short water plug (50mbar, 3s) was injected to permit FASI for stacking. Various parameters affecting the off-line microextraction efficiency as well as FASI were optimized. Migration time was found to be 6.6 (±0.1)min for 5-FU and 7.4 (±0.2)min for CAP. The linearity, precision, accuracy, recovery, selectivity, specificity, stability as well as the robustness of the method was evaluated from spiked plasma samples during the course of validation. The results revealed that the presented technique demonstrates acceptable accuracy and precision, miniaturized sample preparation and a reduced need for complicated equipment along with an acceptable analysis time. The validated method was successfully applied to determine CAP and 5-FU in patient's plasma samples.
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http://dx.doi.org/10.1016/j.jchromb.2016.11.025DOI Listing
January 2017

Mortality from respiratory diseases associated with opium use: a population-based cohort study.

Thorax 2017 11 24;72(11):1028-1034. Epub 2016 Nov 24.

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

Background: Recent studies have suggested that opium use may increase mortality from cancer and cardiovascular diseases. However, no comprehensive study of opium use and mortality from respiratory diseases has been published. We aimed to study the association between opium use and mortality from respiratory disease using prospectively collected data.

Methods: We used data from the Golestan Cohort Study, a prospective cohort study in northeastern Iran, with detailed, validated data on opium use and several other exposures. A total of 50 045 adults were enrolled from 2004 to 2008, and followed annually until June 2015, with a follow-up success rate of 99%. We used Cox proportional hazard regression models to evaluate the association between opium use and outcomes of interest.

Results: During the follow-up period, 331 deaths from respiratory disease were reported (85 due to respiratory malignancies and 246 due to non-malignant aetiologies). Opium use was associated with an increased risk of death from any respiratory disease (adjusted HR 95% CI 3.13 (2.42 to 4.04)). The association was dose-dependent with a HR of 3.84 (2.61 to 5.67) for the highest quintile of cumulative opium use versus never use (P<0.001). The HRs (95% CI) for the associations between opium use and malignant and non-malignant causes of respiratory mortality were 1.96 (1.18 to 3.25) and 3.71 (2.76 to 4.96), respectively.

Conclusions: Long-term opium use is associated with increased mortality from both malignant and non-malignant respiratory diseases.
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http://dx.doi.org/10.1136/thoraxjnl-2015-208251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759041PMC
November 2017

Opium use, cigarette smoking, and alcohol consumption in relation to pancreatic cancer.

Medicine (Baltimore) 2016 Jul;95(28):e3922

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Digestive Disease Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, MD Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences Gastrointestinal and Liver Disease Research Center, Firoozgar Hospital, Iran University of Medical Sciences Sasan Alborz Biomedical Research Center, Masoud Gastroenterology and Hepatology Clinic, Tehran, Iran Division of Gastroenterology and Hepatology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD American Cancer Society, Atlanta, GA Institute for Transitional Epidemiology and the Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY.

Background And Aims: Although several studies have suggested opium as a risk factor for cancers of the esophagus, stomach, larynx, lung, and bladder, no previous study has examined the association of opium with pancreatic cancer. We aimed to study the association between opium use and risk of pancreatic cancer in Iran, using a case-control design. We also studied the association of cigarette smoking and alcohol consumption with pancreatic cancer, for which little information was available from this population.

Methods: Cases and controls were selected from patients who were referred to 4 endoscopic ultrasound centers in Tehran, Iran. We recruited 316 histopathologically (all adenocarcinoma) and 41 clinically diagnosed incident cases of pancreatic cancer, as well as 328 controls from those with a normal pancreas in enodosonography from January 2011 to January 2015. We used logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: After adjustment for potential confounders, opium use (OR 1.91; 95% CI 1.06-3.43) and alcohol consumption (OR 4.16; 95% CI 1.86-9.31) were significantly associated with an increased risk of pancreatic cancer. We did not find an association between ever tobacco smoking and pancreatic cancer risk (OR 0.93; 95% CI 0.62-1.39).

Conclusion: In our study, opium use and alcohol consumption were associated with an increased risk of pancreatic cancer, whereas cigarette smoking was not.
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http://dx.doi.org/10.1097/MD.0000000000003922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956779PMC
July 2016

Multiplex H. pylori Serology and Risk of Gastric Cardia and Noncardia Adenocarcinomas.

Cancer Res 2015 Nov 17;75(22):4876-83. Epub 2015 Sep 17.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

The reported associations with gastric adenocarcinoma and seropositivity to different Helicobacter pylori antigens using multiplex serology have not been consistent across studies. We aimed to investigate the association between 15 different multiplex serology antigens and the risk of gastric cardia (GCA) and gastric noncardia (GNCA) adenocarcinomas in northeastern Iran, a population with high rates of gastric adenocarcinoma. We included 272 cases of gastric adenocarcinoma (142 GCA, 103 GNCA, and 27 unspecified) and 524 controls who were individually matched to cases for age, sex, and place of residence in a population-based case-control study. Seropositivity to H. pylori was assessed using both multiplex serology and H. pylori IgG ELISA. Ninety-five percent of controls were seropositive to H. pylori. Of the 15 antibodies in the multiplex assay, 11 showed no significant association with gastric adenocarcinomas. CagA and VacA were associated with a significantly increased risk of all gastric adenocarcinoma and GNCA in multivariate models. Surprisingly, GroEL and NapA were significantly associated with a reduced risk of these tumors. Only CagA antigen was associated with significantly elevated risk of GCA. We found no associations between H. pylori seropositivity overall either by whole-cell ELISA test or multiplex serology, likely due to the high prevalence of seropositivity. Individual antigen testing showed that CagA positivity was associated with increased risk of both noncardia and cardia adenocarcinoma, which is similar to some other Asian populations, whereas two antigens were associated with lower risk of gastric cancer. This latter result was unexpected and should be retested in other populations.
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http://dx.doi.org/10.1158/0008-5472.CAN-15-0556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792189PMC
November 2015

Phenotyping and follow up of forty-seven Iranian patients with common variable immunodeficiency.

Allergol Immunopathol (Madr) 2016 May-Jun;44(3):226-31. Epub 2015 Jul 29.

Molecular Immunology Research Center and Department of Immunology, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran; Research Center for Immunodeficiency, Children's Medical Center, TUMS, Tehran, Iran; Universal Scientific Education and Research Network (USERN), Tehran, Iran.

Background: Common variable immune deficiency (CVID) is a heterogeneous syndrome with a wide variety of signs and symptoms. This study describes the phenotyping and survival of the CVID patients in the allergy and clinical immunology department of Rasol-E-Akram Hospital of Iran University of Medical Sciences in Tehran.

Method: We retrospectively reviewed hospital files of CVID patients in our department until January 2014. All patients were diagnosed with standard diagnostic criteria of CVID, treated and visited monthly, during the follow-up period. We divided the patients into four phenotypes; infection only, cytopenia, polyclonal lymphocytic infiltration and unexplained enteropathy. The immunologic, demographic and clinical findings in different phenotypes were analysed.

Results: The study included 47 CVID patients with mean age at onset of symptoms and diagnosis of 11.2 and 20.2 years, respectively. Phenotyping of our patients was: only infection (62%), cytopenia (26%) and PLI (19%) and 94% of cases had only one phenotype. We did not find a significant relation between the clinical phenotypes and immunologic or demographic data. Rate of parental consanguinity in our cases was 47%. Parental consanguinity was related to lower age at onset, lower age at diagnosis and higher baseline IgG levels. Patients with malignancy and autoimmunity had significantly higher age at onset. Our patients were followed-up for 6.9 years and the mortality rate during this time was 6%.

Conclusions: Parental consanguinity and age at onset of CVID symptoms may have important roles in CVID manifestations.
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http://dx.doi.org/10.1016/j.aller.2015.04.005DOI Listing
February 2017

Risk of gastric cancer by water source: evidence from the Golestan case-control study.

PLoS One 2015 29;10(5):e0128491. Epub 2015 May 29.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Dr., Bethesda, MD, 20892, United States of America.

Background: Gastric cancer (GC) is the world's fifth most common cancer, and the third leading cause of cancer-related death. Over 70% of incident cases and deaths occur in developing countries. We explored whether disparities in access to improved drinking water sources were associated with GC risk in the Golestan Gastric Cancer Case Control Study.

Methods And Findings: 306 cases and 605 controls were matched on age, gender, and place of residence. We conducted unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CI), adjusted for age, gender, ethnicity, marital status, education, head of household education, place of birth and residence, homeownership, home size, wealth score, vegetable consumption, and H. pylori seropositivity. Fully-adjusted ORs were 0.23 (95% CI: 0.05-1.04) for chlorinated well water, 4.58 (95% CI: 2.07-10.16) for unchlorinated well water, 4.26 (95% CI: 1.81-10.04) for surface water, 1.11 (95% CI: 0.61-2.03) for water from cisterns, and 1.79 (95% CI: 1.20-2.69) for all unpiped sources, compared to in-home piped water. Comparing unchlorinated water to chlorinated water, we found over a two-fold increased GC risk (OR 2.37, 95% CI: 1.56-3.61).

Conclusions: Unpiped and unchlorinated drinking water sources, particularly wells and surface water, were significantly associated with the risk of GC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128491PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449025PMC
March 2016

Food preparation methods, drinking water source, and esophageal squamous cell carcinoma in the high-risk area of Golestan, Northeast Iran.

Eur J Cancer Prev 2016 Mar;25(2):123-9

aDigestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran bGolestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran cDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda dDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health eSchool of Community Health and Policy, Morgan State University, Baltimore, Maryland fThe Tisch Cancer Institute and Institute for Translational Epidemiology, Mount Sinai School of Medicine, New York, New York, USA gMedical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden hGenetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.

Cooking practices and water sources have been associated with an increased risk of cancer, mainly through exposure to carcinogens such as heterocyclic amines, polycyclic aromatic hydrocarbons, and nitrates. Using data from the Golestan case-control study, carried out between 2003 and 2007 in a high-risk region for esophageal squamous cell carcinoma (ESCC), we sought to investigate the association between food preparation and drinking water sources and ESCC. Information on food preparation methods, sources of drinking water, and dietary habits was gathered from 300 cases and 571 controls matched individually for age, sex, and neighborhood using a structured questionnaire and a semiquantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounders and other known risk factors including socioeconomic status and smoking. More than 95% of the participants reported eating meat, mostly red meat. Red meat consumption above the 75th percentile increased the odds of ESCC by 2.82-fold (95% CI: 1.21-6.57). Fish intake was associated with a significant 68% decrease in ESCC odds (26%, 86%). Among meat eaters, ORs (95% CI) for frying meat (red or white) and fish were 3.34 (1.32-8.45) and 2.62 (1.24-5.5). Drinking unpiped water increased ESCC odds by 4.25 times (2.23-8.11). The OR for each 10-year increase in the duration of drinking unpiped water was 1.47 (1.22-1.78). Our results suggest roles for red meat intake, drinking water source, and food preparation methods in ESCC, even after adjusting for a large number of potential confounders.
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http://dx.doi.org/10.1097/CEJ.0000000000000156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759050PMC
March 2016

Variations of gastric corpus microbiota are associated with early esophageal squamous cell carcinoma and squamous dysplasia.

Sci Rep 2015 Mar 6;5:8820. Epub 2015 Mar 6.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden.

Observational studies revealed a relationship between changes in gastric mucosa and risk of esophageal squamous cell carcinoma (ESCC) which suggested a possible role for gastric microbiota in ESCC carcinogenesis. In this study we aimed to compare pattern of gastric corpus microbiota in ESCC with normal esophagus. Cases were included subjects with early ESCC (stage I-II) and esophageal squamous dysplasia (ESD) as the cancer precursor. Control groups included age and sex-matched subjects with mid-esophagus esophagitis (diseased-control), and histologically normal esophagus (healthy-control). DNA was extracted from snap-frozen gastric corpus tissues and 16S rRNA was sequenced on GS-FLX Titanium. After noise removal, an average of 3004 reads per sample was obtained from 93 subjects. We applied principal coordinate analysis to ordinate distances from beta diversity data. Pattern of gastric microbiota using Unifrac (p = 0.004) and weighted Unifrac distances (p = 0.018) statistically varied between cases and healthy controls. Sequences were aligned to SILVA database and Clostridiales and Erysipelotrichales orders were more abundant among cases after controling for multiple testing (p = 0.011). No such difference was observed between mid-esophagitis and healthy controls. This study is the first to show that composition of gastric corpus mucosal microbiota differs in early ESCC and ESD from healthy esophagus.
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http://dx.doi.org/10.1038/srep08820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351546PMC
March 2015

Correlation of tissue transglutaminase antibody with duodenal histologic marsh grading.

Middle East J Dig Dis 2014 Jul;6(3):131-6

Gastrointestinal and Liver Disease Research Center (GILDRC), Iran University of Medical Sciences, Tehran, Iran.

BACKGROUND Recent guidelines have proposed that there is a correlation between tissue transglutaminase (tTG) antibody titers and degrees of duodenal biopsy, and that duodenal biopsy can be omitted in some patients with high levels of tTG antibody. Using data of registered patients in a gastrointestinal clinic we aimed to assess the correlation between tissue transglutaminase antibody with duodenal histologic Marsh grading in Iranian patients with celiac disease. METHODS We retrospectively reviewed hospital files of registered patients in the gastrointestinal clinic of Firoozgar Hospital, Tehran, Iran. Demographic, laboratory, and histology data of those who had tTG titer and pathology reports of duodenal biopsy based on the modified Marsh classification were extracted and used for the study. RESULTS 159 patients with available tTG titer and pathology reports were enrolled in our study. Mean ±SD of the patients was 35.6±15.2 and 100 (62.9%) of them were women. 133 out of 153 patients had villous atrophy (Marsh IIIa-IIIc). Anemia was the most common sign and bloating, abdominal pain, and diarrhea were the first three common symptoms in these patients. Mean tTG titers was significantly higher in patients graded as Marsh III (p for trend=0.003). Our results showed that tTG titer more than 9 folds higher than the kit's cut-off value was about 97.2% sensitive for Marsh II and more duodenal damage. CONCLUSION There was a correlation between tTG titers and degrees of duodenal damage in patients with celiac disease. Duodenal biopsy is not always necessary for diagnosing celiac disease and when tTG level is more than 9 folds higher than the manufacture's recommended cut-off value it can be avoided. Meanwhile small intestinal biopsy should always be considered in case of high clinical suspicion, regardless of the results of serologic testing.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119669PMC
July 2014

Contact with ruminants is associated with esophageal squamous cell carcinoma risk.

Int J Cancer 2015 Mar 14;136(6):1468-74. Epub 2014 Aug 14.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177, Sweden; Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

The etiology of esophageal squamous cell carcinoma (ESCC) in the high risk area of northern Iran is only partially known. We aimed to investigate prolonged animal contact as a risk factor for ESCC in this population. From 2003 to 2007, we administered a validated questionnaire to 300 ESCC cases and 571 randomly selected controls matched for neighborhood of residence, age (±2 years) and sex. Questions on lifelong exposure to equines, ruminants, canines, and poultry, including duration and level of contact, were asked in a face-to-face interviews. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for potential confounders. A total of 94.7% of cases and 68.7% of controls reported lifelong history of contact with ruminants. After controlling for potential confounders, contact with ruminants was associated with an eightfold increase (95% CI: 3.92-14.86) in risk of ESCC, and increments in duration of contact raised the risk estimates in a dose-dependent manner. Contact with equines and poultry did not significantly change associated OR for ESCC risk and contact with ruminants. OR (95% CI) for contact with canines was 1.99 (1.35-2.93) which after exclusion of contact with ruminants was not significant (OR for contact only with canine: 3.18, 95% CI: 0.73-13.17). These results add to the evidence that contact with ruminants may increase the risk of ESCC.
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http://dx.doi.org/10.1002/ijc.29109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786380PMC
March 2015

Opium use: an emerging risk factor for cancer?

Lancet Oncol 2014 Feb;15(2):e69-77

Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Institute for Transitional Epidemiology, Mount Sinai School of Medicine, New York, NY, USA.

An estimated 16·5 million people worldwide illicitly use opiates, of whom 4 million use raw opium. We did a systematic review to investigate the association between opium use and cancer incidence and mortality. Opium use was associated with an increased risk of cancers of the oesophagus, stomach, larynx, lung, and urinary bladder. Although the present evidence suggests that these associations are possibly causal, further epidemiological studies (particularly prospective studies that collect detailed data about lifetime opium use and control for a broad range of potential confounders) are needed.
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http://dx.doi.org/10.1016/S1470-2045(13)70550-3DOI Listing
February 2014

Photoclinic.

Arch Iran Med 2013 Nov;16(11):691-2

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

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http://dx.doi.org/0131611/AIM.0017DOI Listing
November 2013

Photoclinic.

Arch Iran Med 2013 Jun;16(6):371-2

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

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http://dx.doi.org/013166/AIM.0013DOI Listing
June 2013

Marked increase in the incidence rate of esophageal adenocarcinoma in a high-risk area for esophageal cancer.

Arch Iran Med 2013 Jun;16(6):320-3

Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran.

Background: Esophageal cancer (EC) is the eighth common cancer worldwide. Esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAD) are the most common histologic types of EC. Many recent reports showed an increasing trend in EAD and a decreasing trend in ESCC in many Western countries. Golestan Province in northeastern Iran has been known as a high-risk area for EC. The aim of this study was to describe the time trend of EAD in this area between 2000-2009.

Methods: Data on cancer cases were obtained from Golestan Population-based Cancer Registry. Analysis was done using Joinpoint software. To examine the incidence trends, the annual percent change was calculated. The possibilities of anatomic and histologic misclassification were considered by assessing the trend of ESCC and gastric adenocarcinoma. 

Results: A total number of 1186 histologically-confirmed EC cases were recruited. The incidence rate of EAD showed a significant increasing trend. There was no significant trend in the incidence of ESCC during the study period. A significant increase in the incidence rate of gastric adenocarcinoma   was observed during the period of 2000-2005, followed by a plateau during the period of 2005-2009.

Conclusions: We found a significant increasing trend in the incidence rate of EAD. We find no evidence to support an alternative explanation including anatomic and histologic misclassification. So, the observed rise in the incidence of EAD seems to be real. Therefore, designing and implementation of control programs, including control of preventable risk factors of EAD, should be considered in this high- risk area.
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http://dx.doi.org/013166/AIM.003DOI Listing
June 2013

Solitary huge intrahepatic mass (extramedullary hematopoiesis).

Arch Iran Med 2013 May;16(5):315-6

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

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http://dx.doi.org/013165/AIM.0016DOI Listing
May 2013

Association of tooth loss and oral hygiene with risk of gastric adenocarcinoma.

Cancer Prev Res (Phila) 2013 May 15;6(5):477-82. Epub 2013 Mar 15.

Digestive Disease Research Centre, Tehran University of Medical Sciences, Shariati Hospital, 1411713135, Tehran, Iran.

Poor oral health and tooth loss have been proposed as possible risk factors for some chronic diseases, including gastric cancer. However, a small number of studies have tested these associations. We conducted a case-control study in Golestan Province, Iran, that enrolled 309 cases diagnosed with gastric adenocarcinoma (118 noncardia, 161 cardia, and 30 mixed-locations) and 613 sex, age, and neighborhood matched controls. Data on oral health were obtained through physical examination and questionnaire including tooth loss, the number of decayed, missing, and filled teeth, and frequency of tooth brushing. ORs and 95% confidence intervals (95% CI) were obtained using conditional logistic regression models adjusted for potential confounders. Standard one degree-of-freedom linear trend test and a multiple degree-of-freedom global test of the effect of adding oral hygiene variables to the model were also calculated. Our results showed apparent associations between tooth loss and decayed, missing, filled teeth (DMFT) score with risk of gastric cancer, overall and at each anatomic subsite. However, these associations were not monotonic and were strongly confounded by age. The results also showed that subjects who brushed their teeth less than daily were at significantly higher risk for gastric cardia adenocarcinoma ORs (95% CI) of 5.6 (1.6-19.3). We found evidence for an association between oral health and gastric cancer, but the nonmonotonic association, the relatively strong effect of confounder adjustment, and inconsistent results across studies must temper the strength of any conclusions.
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http://dx.doi.org/10.1158/1940-6207.CAPR-12-0491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644330PMC
May 2013

Opium: an emerging risk factor for gastric adenocarcinoma.

Int J Cancer 2013 Jul 13;133(2):455-61. Epub 2013 Feb 13.

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

Opium use has been associated with higher risk of cancers of the esophagus, bladder, larynx, and lung; however, no previous study has examined its association with gastric cancer. There is also little information on the associations between hookah (water pipe) smoking or the chewing of tobacco products and the risk of gastric cancer. In a case-control study in Golestan Province of Iran, we enrolled 309 cases of gastric adenocarcinoma (118 noncardia, 161 cardia and 30 mixed-location adenocarcinomas) and 613 matched controls. Detailed information on long-term use of opium, tobacco products and other covariates were collected using structured and validated lifestyle and food frequency questionnaires. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were obtained using conditional logistic regression models. Opium use was associated with an increased risk of gastric adenocarcinoma, with an adjusted OR (95% CI) of 3.1 (1.9-5.1), and this increased risk was apparent for both anatomic subsites (cardia and noncardia). There was a dose-response effect, and individuals with the highest cumulative opium use had the strongest association (OR: 4.5; 95% CI: 2.3-8.5). We did not find a statistically significant association between the use of any of the tobacco products and risk of gastric adenocarcinoma, overall or by anatomic subsite. We showed, for the first time, an association between opium use and gastric adenocarcinoma. Given that opium use is a traditional practice in many parts of the world, these results are of public health significance.
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http://dx.doi.org/10.1002/ijc.28018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644384PMC
July 2013

Reproductive factors and risk of esophageal squamous cell carcinoma in northern Iran: a case-control study in a high-risk area and literature review.

Eur J Cancer Prev 2013 Sep;22(5):461-6

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

Several epidemiologic studies have suggested an inverse association between female reproductive factors and the risk of esophageal squamous cell carcinoma (ESCC), but the evidence is not conclusive. We examined the association of the number of pregnancies, live births, and miscarriages/stillbirths in women and the association of the number of children in both sexes with the risk of ESCC in Golestan Province, a high-risk area in Iran. Data from 297 histopathologically confirmed ESCC cases (149 women) and 568 controls (290 women) individually matched to cases for age, sex, and neighborhood of residence were included in this analysis. Conditional logistic regression was used to calculate odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). The average numbers of live births and miscarriages/stillbirths among the controls were 8.2 and 0.8, respectively. Women with six or more live births were at ~1/3 the risk of ESCC as those with 0-3 live births; the OR (95% CI) for having 6-7 live births was 0.33 (0.12-0.92). In contrast, the number of miscarriages/stillbirths was associated with an increase in the risk of ESCC. The OR (95% CI) for at least three versus no miscarriages/stillbirths was 4.43 (2.11-9.33). The number of children in women was suggestive of an inverse association with ESCC, but this association was not statistically significant; in men, no association was observed. The findings of this study support a protective influence of female hormonal factors on the risk of ESCC. However, further epidemiological and mechanistic studies are required to prove a protective association.
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http://dx.doi.org/10.1097/CEJ.0b013e32835c7f87DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731403PMC
September 2013

Is opium a real risk factor for esophageal cancer or just a methodological artifact? Hospital and neighborhood controls in case-control studies.

PLoS One 2012 1;7(3):e32711. Epub 2012 Mar 1.

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

Background: Control selection is a major challenge in epidemiologic case-control studies. The aim of our study was to evaluate using hospital versus neighborhood control groups in studying risk factors of esophageal squamous cell carcinoma (ESCC).

Methodology/principal Findings: We compared the results of two different case-control studies of ESCC conducted in the same region by a single research group. Case definition and enrollment were the same in the two studies, but control selection differed. In the first study, we selected two age- and sex-matched controls from inpatient subjects in hospitals, while for the second we selected two age- and sex-matched controls from each subject's neighborhood of residence. We used the test of heterogeneity to compare the results of the two studies. We found no significant differences in exposure data for tobacco-related variables such as cigarette smoking, chewing Nass (a tobacco product) and hookah (water pipe) usage, but the frequency of opium usage was significantly different between hospital and neighborhood controls. Consequently, the inference drawn for the association between ESCC and tobacco use did not differ between the studies, but it did for opium use. In the study using neighborhood controls, opium use was associated with a significantly increased risk of ESCC (adjusted OR 1.77, 95% CI 1.17-2.68), while in the study using hospital controls, this was not the case (OR 1.09, 95% CI 0.63-1.87). Comparing the prevalence of opium consumption in the two control groups and a cohort enrolled from the same geographic area suggested that the neighborhood controls were more representative of the study base population for this exposure.

Conclusions/significance: Hospital and neighborhood controls did not lead us to the same conclusion for a major hypothesized risk factor for ESCC in this population. Our results show that control group selection is critical in drawing appropriate conclusions in observational studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0032711PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291619PMC
July 2012

Prevalence of chronic kidney disease and its associated risk factors: the first report from Iran using both microalbuminuria and urine sediment.

Arch Iran Med 2012 Feb;15(2):70-5

Nephrology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: The incidence of major risk factors of chronic kidney disease (CKD) in the world is on the rise, and it is expected that this incidence and prevalence, particularly in developing countries, will continue to increase. Using data on urinary sediment and microalbuminuria, we aimed to estimate the prevalence of CKD in northeast Iran.

Methods: In a cross-sectional study, the prevalence of CKD in a sample of 1557 regionally representative people, aged ≥ 18 years, was analyzed. CKD was determined based on glomerular filtration rate (GFR) and microalbuminuria. Life style data, urine and blood samples were collected. Urine samples without any proteinuria in the initial dipstick test were checked for qualitative microalbuminuria. If the latter was positive, quantitative microalbuminuria was evaluated.

Results: 1557 subjects with a mean age of 56.76 ± 12.04 years were enrolled in this study. Based on the modification of diet in renal disease (MDRD) equation, 137 subjects (8.89%) were categorized as CKD stages III-V. Based on urine abnormalities, the prevalence of combined CKD stages I and II was 10.63%, and based on macro- and microalbuminuria it was 14.53%. The prevalence of CKD was significantly associated with sex, age, marital status, education, diabetes mellitus (DM), hypertension (HTN), ischemic heart disease (IHD), waist to hip ratio, myocardial infarction (MI), and cerebrovascular accident (CVA).

Conclusion: CKD and its main risk factors are common and represent a definite health threat in this region of Iran. Using and standardizing less expensive screening tests in low resource countries could be a good alternative that may improve the outcome through early detection of CKD.
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http://dx.doi.org/012152/AIM.003DOI Listing
February 2012