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Association of different combinations of four antibodies (CagA, VacA, NapA, and GroEL) with gastric adenocarcinoma and its subtypes.

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. Cancer Res; 75(22); 4876–83. ©2015 AACR.

Supplementary Table 1 from Candidate Gene Association Study of Esophageal Squamous Cell Carcinoma in a High-Risk Region in Iran

Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence that is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. Mutational profiles were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining differences in ESCC incidence. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)-associated mutational signatures single-base substitution (SBS)2 and SBS13 were present in 88% and 91% of cases, respectively, and accounted for 25% of the mutation burden on average, indicating that APOBEC activation is a crucial step in ESCC tumor development.

Background: We aim to present the development and the initial results of the Golestan Cancer Biobank (GoCB), in a low resource setting in northern Iran. Methods: The GoCB protocol and its standard operation procedures (SOP) were developed according to internationally accepted standards and protocols with some modifications considering the limited resources in our setting. The main biological samples collected by the GoCB include blood sample, urine sample, fresh endoscopy tissue sample, fresh surgical tissue sample and formalin fixed paraffin embedded (FFPE) tissue sample. The GoCB collects patients' demographic data, tumor characteristics as well as data on risk factors. We developed a specific GoCB software for management of patient data and biological sample information. The GoCB dataset is annually linked with the Golestan cancer registry dataset to add complementary data (e.g., survival data). Results: The GoCB started collection of data and biological samples in December 2016. By November 2020, a total number of 1217 cancer patients participated in the GoCB. The majority of the GoCB participants (n = 942, 77) were those with gastrointestinal and breast cancers. Data on risk factors were successfully collected in 684 (56.2) of the participants. Overall, 3563 samples were collected from the GoCB participants and 730 samples were used in 7 national and international research projects. Conclusion: We considered specific strategies to overcome major limitations, especially budget shortage, in the development and maintenance of a cancer-specific biological repositories in our setting. The GoCB may be considered as a model for the development of biobank in low- and middle-income countries (LMICs). © 2021 Academy of Medical Sciences of I.R. Iran. All rights reserved.

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients.

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One proposed biological pathway linking poor oral health and ESCC involves the alteration of the microbiome. Thus, we performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors and WGS of synchronous collections of saliva specimens from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella, and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed a similar tumor enrichment of the ESCC-associated bacterial community in these cancers. Because these genera are traditionally considered members of the oral microbiota, we explored if there is a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes are significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of ESCC patients. Longitudinal studies of the pre-diagnostic oral microbiome are needed to investigate whether these cross-sectional similarities reflect temporal associations.

Questionnaire data have linked contact with ruminants to the risk of esophageal squamous cell carcinoma (ESCC) in high-risk Asian populations. To better understand this observed association, we investigated exposure to two major zoonotic ruminant pathogens relative to ESCC risk. Using enzyme-linked immunosorbent assay, immunofluorescence assay, and Brucella microagglutination test assays, we measured immunoglobulin G anti-Coxiella burnetii and anti-Brucella spp. antibodies in patients with ESCC (n = 177) and population-based controls (n = 177) matched by age, gender, and residence area from the Golestan case–control study in Iran. We found a similarly high seroprevalence of C. burnetii in ESCC cases and controls (75% and 80%, respectively), and a similarly low seroprevalence of Brucella spp. (0% and 0.6%, respectively). While documenting a high exposure to one of two zoonotic ruminant infections, this exposure failed to explain the observed association of ruminant contact and ESCC risk in this high-risk population.

Background Bladder cancer (BC) is the 10th most common type of cancer worldwide and the fourth most common type of cancer in Iran. Opium use is considered as one of the risk factors for BC. We aim to assess the association between various parameters of opium use, which in Iran is mainly ingested or smoked in various forms, and the risk of BC. Method In this multi-centre case-referent study in Iran, 717 BC cases and 3477 referents were recruited to the study from May 2017 until July 2020. Detailed histories of opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure adjusted odds ratio (OR) and 95% confidence intervals (CI). The ORs were adjusted for age, gender, place of residence and pack-years of cigarette smoking. Results Regular opium consumption was associated with an increased risk of BC (OR 3.5, 95% CI: 2.8, 4.3) compared with subjects who never used opium. Compared with continuous users, the risk decreased to one-third for those who stopped opium more than 10 years ago. The adjusted OR for those who used both crude opium (teriak) and opium juice was 7.4 (95% CI: 4.1, 13.3). There was a joint effect of opium and tobacco (OR for users of both opium and tobacco 7.7, 95% CI: 6.0, 9.7). Conclusions Regular opium use is associated with an approximately 4-fold risk for BC. The OR decreases along with the increasing time since stopping opium use.

There are unexplained geographical variations in the incidence of kidney cancer with the high rates reported in Baltic countries, as well as eastern and central Europe. Having access to a large and well-annotated collection of “tumor/non-tumor” pairs of kidney cancer patients from the Czech Republic, Romania, Serbia, UK, and Russia, we aimed to analyze the morphology of non-neoplastic renal tissue in nephrectomy specimens. By applying digital pathology, we performed a microscopic examination of 1012 frozen non-neoplastic kidney tissues from patients with renal cell carcinoma. Four components of renal parenchyma were evaluated and scored for the intensity of interstitial inflammation and fibrosis, tubular atrophy, glomerulosclerosis, and arterial wall thickening, globally called chronic renal parenchymal changes. Moderate or severe changes were observed in 54 (5.3%) of patients with predominance of occurrence in Romania (OR = 2.67, CI 1.07–6.67) and Serbia (OR = 4.37, CI 1.20–15.96) in reference to those from Russia. Further adjustment for comorbidities, tumor characteristics, and stage did not change risk estimates. In multinomial regression model, relative probability of non-glomerular changes was 5.22 times higher for Romania and Serbia compared to Russia. Our findings show that the frequency of chronic renal parenchymal changes, with the predominance of chronic interstitial nephritis pattern, in kidney cancer patients varies by country, significantly more frequent in countries located in central and southeastern Europe where the incidence of kidney cancer has been reported to be moderate to high. The observed association between these pathological features and living in certain geographic areas requires a larger population-based study to confirm this association on a large scale. Supplementary Information The online version contains supplementary material available at 10.1007/s00428-020-02986-3.

Circulating cell-free DNA (cfDNA) is emerging as a potential tumor biomarker. CfDNA-based biomarkers may be applicable in tumors without an available non-invasive screening method among at-risk populations. Esophageal squamous cell carcinoma (ESCC) and residents of the Asian cancer belt are examples of those malignancies and populations. Previous epidemiological studies using cfDNA have pointed to the need for high volumes of good quality plasma (i.e., &gt, 1 mL plasma with 0 or 1 cycles of freeze-thaw) rather than archival serum, which is often the main available source of cfDNA in retrospective studies. Here, we have investigated the concordance of TP53 mutations in tumor tissue and cfDNA extracted from archival serum left-over from 42 cases and 39 matched controls (age, gender, residence) in a high-risk area of Northern Iran (Golestan). Deep sequencing of TP53 coding regions was complemented with a specialized variant caller (Needlestack). Overall, 23% to 31% of mutations were concordantly detected in tumor and serum cfDNA (based on two false discovery rate thresholds). Concordance was positively correlated with high cfDNA concentration, smoking history (p-value = 0.02) and mutations with a high potential of neoantigen formation (OR, 95%CI = 1.9 (1.11–3.29)), suggesting that tumor DNA release in the bloodstream might reflect the effects of immune and inflammatory context on tumor cell turnover. We identified TP53 mutations in five controls, one of whom was subsequently diagnosed with ESCC. Overall, the results showed that cfDNA mutations can be reliably identified by deep sequencing of archival serum, with a rate of success comparable to plasma. Nonetheless, 70% non-identifiable mutations among cancer patients and 12% mutation detection in controls are the main challenges in applying cfDNA to detect tumor-related variants when blindly targeting whole coding regions of the TP53 gene in ESCC.

Esophageal squamous cell carcinoma (ESCC) shows a remarkable variation in incidence which is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. The mutational profiles of ESCC were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining the differences in ESCC incidence. APOBEC associated mutational signatures SBS2 and SBS13 were present in 88% and 91% of cases respectively and accounted for a quarter of the mutation burden on average, indicating that activation of APOBEC is a crucial step in ESCC tumor development.

Background There are unexplained geographical variations in the incidence of kidney cancer with the high rates reported in Baltic countries, as well as eastern and central Europe. Analysis of non-neoplastic tissues is a way to better understand the carcinogenesis. Methods Having access to a rich, well-annotated collection of “tumor/non-tumor” pairs of kidney cancer patients from Czech Republic, Romania, Serbia, United Kingdom, and Russia for studying genomics of kidney cancer, we aimed to analyze morphology of non-neoplastic renal tissue. By applying digital pathology, we performed microscopic examination of 1012 frozen non-neoplastic kidney tissues from patients with renal cell carcinoma. Renal parenchyma was evaluated and scored for the interstitial inflammation and fibrosis, tubular atrophy, glomerulosclerosis and arterial wall thickening, globally called chronic renal parenchymal changes. Results Moderate or severe changes was observed in 54 (5.3%) of patients with predominance of occurrence in Romania (OR = 2.67, CI 1.07–6.67) and Serbia (OR = 4.37, CI 1.20-15.96) in reference to those from Russia. Further adjustment for comorbidities, tumor characterstics and stage did not change risk estimates. In multinomial regression model, relative probability of non-glomerular changes were 5.22 times higher for Romania and Serbia compered to Russia. Conclusion Our findings show that the frequency of chronic renal parenchymal changes in kidney cancer patients varies by country, significantly more frequent in countries located in central and southeastern Europe where the incidence of kidney cancer has been reported to be high. We suggest that these parenchymal changes, possibly linked to environmental exposures, may be relevant to renal carcinogenesis in these countries.

Background Oesophageal cancer is a common and often fatal cancer that has two main histological subtypes: oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. Updated statistics on the incidence and mortality of oesophageal cancer, and on the disability-adjusted life-years (DALYs) caused by the disease, can assist policy makers in allocating resources for prevention, treatment, and care of oesophageal cancer. We report the latest estimates of these statistics for 195 countries and territories between 1990 and 2017, by age, sex, and Socio-demographic Index (SDI), using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD). Methods We used data from vital registration systems, vital registration-samples, verbal autopsy records, and cancer registries, combined with relevant modelling, to estimate the mortality, incidence, and burden of oesophageal cancer from 1990 to 2017. Mortality-to-incidence ratios (MIRs) were estimated and fed into a Cause of Death Ensemble model (CODEm) including risk factors. MIRs were used for mortality and non-fatal modelling. Estimates of DALYs attributable to the main risk factors of oesophageal cancer available in GBD were also calculated. The proportion of oesophageal squamous cell carcinoma to all oesophageal cancers was extracted by use of publicly available data, and its variation was examined against SDI, the Healthcare Access and Quality (HAQ) Index, and available risk factors in GBD that are specific for oesophageal squamous cell carcinoma (eg, unimproved water source and indoor air pollution) and for oesophageal adenocarcinoma (gastro-oesophageal reflux disease). Findings There were 473 000 (95% uncertainty interval [95% UI] 459 000-485 000) new cases of oesophageal cancer and 436 000 (425 000-448 000) deaths due to oesophageal cancer in 2017. Age-standardised incidence was 5.9 (5.7-6.1) per 100 000 population and age-standardised mortality was 5.5 (5.3-5.6) per 100 000. Oesophageal cancer caused 9.78 million (9.53-10.03) DALYs, with an age-standardised rate of 120 (117-123) per 100 000 population. Between 1990 and 2017, age-standardised incidence decreased by 22.0% (18.6-25.2), mortality decreased by 29.0% (25.8-32.0), and DALYs decreased by 33.4% (30.4-36.1) globally. However, as a result of population growth and ageing, the total number of new cases increased by 52.3% (45.9-58.9), from 310 000 (300 000-322 000) to 473 000 (459 000-485 000); the number of deaths increased by 40.0% (34.1-46.3), from 311 000 (301 000-323 000) to 436 000 (425 000-448 000); and total DALYs increased by 27.4% (22.1-33.1), from 7.68 million (7.42-7.97) to 9.78 million (9.53-10.03). At the national level, China had the highest number of incident cases (235 000 [223 000-246 000]), deaths (213 000 [203 000-223 000]), and DALYs (4.46 million [4.25-4.69]) in 2017. The highest national-level age-standardised incidence rates in 2017 were observed in Malawi (23.0 [19.4-26.5] per 100 000 population) and Mongolia (18.5 [16.4-20.8] per 100 000). In 2017, age-standardised incidence was 2.7 times higher, mortality 2.9 times higher, and DALYs 3.0 times higher in males than in females. In 2017, a substantial proportion of oesophageal cancer DALYs were attributable to known risk factors: tobacco smoking (39.0% [35.5-42.2]), alcohol consumption (33.8% [27.3-39.9]), high BMI (19.5% [6.3-36.0]), a diet low in fruits (19.1% [4.2-34.6]), and use of chewing tobacco (7.5% [5.2-9.6]). Countries with a low SDI and HAQ Index and high levels of indoor air pollution had a higher proportion of oesophageal squamous cell carcinoma to all oesophageal cancer cases than did countries with a high SDI and HAQ Index and with low levels of indoor air pollution. Interpretation Despite reductions in age-standardised incidence and mortality rates, oesophageal cancer remains a major cause of cancer mortality and burden across the world. Oesophageal cancer is a highly fatal disease, requiring increased primary prevention efforts and, possibly, screening in some high-risk areas. Substantial variation exists in age-standardised incidence rates across regions and countries, for reasons that are unclear. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.

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. © 2016 Wolters Kluwer Health, Inc. All rights reserved.

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.

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. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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.

Background:Gastric fundal atrophy has been hypothesised to increase the risk of oesophageal squamous cell carcinoma (OSCC), but studies have shown inconsistent results.Methods:We measured serum pepsinogen I (PGI) and pepsinogen II (PGII) among 293 incident cases and 524 matched neighbourhood controls in a high-risk area of Northern Iran. Conditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs).Results:After controlling for age, sex, residence area and other potential confounders, gastric atrophy (defined by a validated criterion, PGI

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. Cancer Res; 75(22); 4876–83. ©2015 AACR.

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.

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 8-fold 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 odds ratio for ESCC risk and contact with ruminants. Odds ratio (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.

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.

Background: To establish optimal cutoff values for serologic diagnosis of fundic atrophy in a high-risk area for oesophageal squamous cell carcinoma and gastric cancer with high prevalence of Helicobacter pylori (H. pylori) in Northern Iran, we performed an endoscopy-room-based validation study. Methods: We measured serum pepsinogens I (PGI) and II (PGII), gastrin 17 (G-17), and antibodies against whole H. pylori, or cytotoxin-associated gene A (CagA) antigen among 309 consecutive patients in two major endoscopy clinics in northeastern Iran. Updated Sydney System was used as histology gold standard. Areas under curves (AUCs), optimal cutoff and predictive values were calculated for serum biomarkers against the histology. Results: 309 persons were recruited (mean age: 63.5 years old, 59.5% female). 84.5% were H. pylori positive and 77.5% were CagA positive. 21 fundic atrophy and 101 nonatrophic pangastritis were diagnosed. The best cutoff values in fundic atrophy assessment were calculated at PGI40 pmol/l was 81% sensitive and 73.3% specific for diagnosing fundic atrophy. At cutoff concentration of 11.8 µg/l, PGII showed 84.2% sensitivity and 45.4% specificity to distinguish nonatrophic pangastritis. Exclusion of nonatrophic pangastritis enhanced diagnostic ability of PGI/PGII ratio (from AUC = 0.66 to 0.90) but did not affect AUC of PGI. After restricting study samples to those with PGII

Golestan Province in northern Iran is an area with a high incidence of esophageal squamous cell carcinoma (ESCC). We aimed to investigate prognostic factors for ESCC and survival of cases in Golestan, on which little data were available. We followed-up 426 ESCC cases participating in a population-based case-control study. Data were analyzed using the Kaplan-Meier method and the Cox proportional hazard models. Median survival was 7 months. Age at diagnosis was inversely associated with survival, but the association was disappeared with adjustment for treatment. Residing in urban areas (hazard ratio, HR = 0.70; 95 CI 0.54-0.90) and being of non-Turkmen ethnic groups (HR = 0.76; 95 CI 0.61-0.96) were associated with better prognosis. In contrast to other types of tobacco use, nass (a smokeless tobacco product) chewing was associated with a slightly poorer prognosis even in models adjusted for other factors including stage of disease and treatment (HR = 1.38; 95 CI 0.99-1.92). Opium use was associated with poorer prognosis in crude analyses but not in adjusted models. Almost all of potentially curative treatments were associated with longer survival. Prognosis of ESCC in Golestan is very poor. Easier access to treatment facilities may improve the prognosis of ESCC in Golestan. The observed association between nass chewing and poorer prognosis needs further investigations; this association may suggest a possible role for ingestion of nass constituents in prognosis of ESCC. © 2011 Aghcheli et al.

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. © 2012 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

A region with a high risk for esophageal squamous cell carcinoma (ESCC) in northeast of Iran was identified more than three decades ago. Previous studies suggest that hereditary factors play a role in the high incidence of cancer in the region. Polymorphisms of several genes have been associated with susceptibility to esophageal cancer in various populations, but these have not been studied in Iran. We selected 22 functional variants (and 130 related tagSNPs) from 15 genes which previously have been suggested to be associated with an increased risk of ESCC. We genotyped a primary set of samples from 451 Turkmen (197 cases and 254 controls). Seven of 152 variants were associated with ESCC at the P = 0.05 level; these SNPs were then studied in a validation set of 1668 cases and controls (Turkmen and non-Turkmen) under dominant and recessive models. In the joint sample set, five variants, from five different genes, showed significant associations with ESCC at the P = 0.05 level. For one variant, in ADH1B, the association was strong and was present in both Turkmen and non-Turkmen. The histidine allele at codon 48 of ADH1B gene was associated with a significantly decreased risk of ESCC under a recessive model (OR = 0.41, 95%, CI = 0.19 to 0.49; P = 4×10−4). For four additional variants, an association was present in the Turkmen subgroup, but the statistical significance of these was less compelling than for ADH1B. Two variants showed deleterious effects and two were protective. The G allele of the c.870A>G variant of CCND1 gene was associated with a 1.5-fold increased risk of ESCC under the recessive model (OR = 1.50, 95% CI = 1.14 to 2.16, P = 0.02) and the A allele of the rs1625895 variant of TP53 gene was associated with a 1.5-fold increased risk of ESCC under a dominant model (OR = 1.54, 95% CI = 1.21 to 4.07, P = 0.005). The C allele of the rs886205 variant of ALDH2 was associated with a decreased risk of ESCC under a recessive model (OR = 0.58, 95% CI = 0.34 to 0.87, P = 0.02) and the A allele of the rs7087131 variant of MGMT was associated with a decreased risk of ESCC under the recessive model (OR = 0.26, 95% CI = 0.05 to 0.49, P=0.01). These results confirm that genetic predisposition to ESCC plays a role in high incidence of this cancer among Turkmens who live in northeast of Iran.

Golestan Province, located in the south-east littoral of the Caspian Sea in northern Iran, has one of the highest rates of oesophageal cancer (OC) in the world. We review the epidemiologic studies that have investigated the epidemiologic patterns and causes of OC in this area and provide some suggestions for further studies. Oesophageal squamous cell carcinoma (OSCC) constitutes over 90% of all OC cases in Golestan. In retrospective studies, cigarettes and hookah smoking, nass use (a chewing tobacco product), opium consumption, hot tea drinking, poor oral health, low intake of fresh fruit and vegetables, and low socioeconomic status have been associated with higher risk of OSCC in Golestan. However, the association of tobacco with OSCC in this area is not as strong as that seen in Western countries. Alcohol is consumed by a very small percentage of the population and is not a risk factor for OSCC in this area. Other factors, such as polycyclic aromatic hydrocarbons, N-nitroso compounds, drinking water contaminants, infections, food contamination with mycotoxins, and genetic factors merit further investigation as risk factors for OSCC in Golestan. An ongoing cohort study in this area is an important resource for studying some of these factors and also for confirming the previously found associations. © 2009 Elsevier Ltd. All rights reserved.

Objective To investigate the association between tea drinking habits in Golestan province, northern Iran, and risk of oesophageal squamous cell carcinoma. Design Population based case-control study. In addition, patterns of tea drinking and temperature at which tea was drunk were measured among healthy participants in a cohort study. Setting Golestan province, northern Iran, an area with a high incidence of oesophageal squamous cell carcinoma. Participants 300 histologically proved cases of oesophageal squamous cell carcinoma and 571 matched neighbourhood controls in the case-control study and 48 582 participants in the cohort study. Main outcome measure Odds ratio of oesophageal squamous cell carcinoma associated with drinking hot tea. Results Nearly all (98%) of the cohort participants drank black tea regularly, with a mean volume consumed of over one litre a day. 39.0% of participants drank their tea at temperatures less than 60°C, 38.9% at 60-64°C, and 22.0% at 65°C or higher. A moderate agreement was found between reported tea drinking temperature and actual temperature measurements (weighted κ 0.49). The results of the case-control study showed that compared with drinking lukewarm or warm tea, drinking hot tea (odds ratio 2.07, 95% confidence interval 1.28 to 3.35) or very hot tea (8.16, 3.93 to 16.9) was associated with an increased risk of oesophageal cancer. Likewise, compared with drinking tea four or more minutes after being poured, drinking tea 2-3 minutes after pouring (2.49, 1.62 to 3.83) or less than two minutes after pouring (5.41, 2.63 to 11.1) was associated with a significantly increased risk. A strong agreement was found between responses to the questions on temperature at which tea was drunk and interval from tea being poured to being drunk (weighted κ 0.68). Conclusion Drinking hot tea, a habit common in Golestan province, was strongly associated with a higher risk of oesophageal cancer. Reza Malekzadeh and other authors of this population based case-control study talk about the effect of tea drinking and oesophageal cancer in Golestan province, northern Iran

Background: Cancer registries in the 1970s showed that parts of Golestan Province in Iran had the highest rate of oesophageal squamous cell carcinoma (OSCC) in the world. More recent studies have shown that while rates are still high, they are approximately half of what they were before, which might be attributable to improved socio-economic status (SES) and living conditions in this area. We examined a wide range of SES indicators to investigate the association between different SES components and risk of OSCC in the region. Methods: Data were obtained from a population-based case-control study conducted between 2003 and 2007 with 300 histologically proven OSCC cases and 571 matched neighbourhood controls. We used conditional logistic regression to compare cases and controls for individual SES indicators, for a composite wealth score constructed using multiple correspondence analysis, and for factors obtained from factors analysis. Results: We found that various dimensions of SES, such as education, wealth and being married were all inversely related to OSCC. The strongest inverse association was found with education. Compared with no education, the adjusted odds ratios (95% confidence intervals) for primary education and high school or beyond were 0.52 (0.27-0.98) and 0.20 (0.06-0.65), respectively. Conclusions: The strong association of SES with OSCC after adjustment for known risk factors implies the presence of yet unidentified risk factors that are correlated with our SES measures; identification of these factors could be the target of future studies. Our results also emphasize the importance of using multiple SES measures in epidemiological studies. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2009; all rights reserved.

Our objectives were to investigate patterns of food and nutrient consumption in Golestan province, a high-incidence area for esophageal cancer (EC) in northern Iran. Twelve 24-h dietary recalls were administered during a 1-yr period to 131 healthy participants in a pilot cohort study. We compare here nutrient intake in Golestan with recommended daily allowances (RDAs) and lowest threshold intakes (LTIs). We also compare the intake of 27 food groups and nutrients among several population subgroups using mean values from the 12 recalls. Rural women had a very low level of vitamin intake, which was even lower than LTIs (P < 0.01). Daily intake of vitamins A and C was lower than LTI in 67% and 73% of rural women, respectively. Among rural men, the vitamin intakes were not significantly different from LTIs. Among urban women, the vitamin intakes were significantly lower than RDAs but were significantly higher than LTIs. Among urban men, the intakes were not significantly different from RDAs. Compared to urban dwellers, intake of most food groups and nutrients, including vitamins, was significantly lower among rural dwellers. In terms of vitamin intake, no significant difference was observed between Turkmen and non-Turkmen ethnics. The severe deficiency in vitamin intake among women and rural dwellers and marked differences in nutrient intake between rural and urban dwellers may contribute to the observed epidemiological pattern of EC in Golestan, with high incidence rates among women and people with low socioeconomic status and the highest incidence rate among rural women.

We tested the association between tooth loss and oral hygiene and the risk of esophageal squamous cell carcinoma (ESCC) in people living in a high-risk area of Iran. We used a case-control study of pathologically confirmed ESCC cases (n = 283) and controls (n = 560) matched on sex, age, and neighborhood. Subjects with ESCC had significantly more decayed, missing, or filled teeth (DMFT) with a median (interquartile range) of 31 (23-32) compared with controls 28 (16-32; P = 0.0045). Subjects with ESCC were significantly more likely than controls to fail to practice regular oral hygiene (78% versus 58%). In multivariate-adjusted conditional logistic regression models, having 32 DMFT compared with ≤15 conferred an odds ratio (95% confidence interval) of 2.10 (1.19-3.70). Compared with daily tooth brushing, practicing no regular oral hygiene conferred an odds ratio (95% confidence interval) of 2.37 (1.42-3.97). Restricting the analysis to subjects that had never smoked tobacco did not materially alter these results. We found significant associations between two markers of poor oral hygiene, a larger number of DMFT and lack of daily tooth brushing, and risk of ESCC in a population at high risk for ESCC where many cases occur in never smokers. Our results are consistent with several previous analyses in other high-risk populations. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3062–8)

One etiologic factor for high incidence of esophageal squamous cell carcinoma (ESCC) in Golestan (Northeastern Iran) might be exposure to polycyclic aromatic hydrocarbons. We examined whether food and water are major sources of benzo(a)pyrene (BaP) exposure in this population. We used a dietary questionnaire to assess the daily intake of staple food (rice and bread) and water in 3 groups: 40 ESCC Golestan cases, 40 healthy subjects from the same area, and 40 healthy subjects from a low-risk area in Southern Iran. We measured, by high-performance liquid chromatography combined with fluorescence detection, the BaP concentration of bread, rice, and water in samples obtained from these 3 groups and calculated the daily intake of BaP. Mean BaP concentration of staple foods and water was similar and within standard levels in both areas, but the daily intake of BaP was higher in controls from the high-risk area than in controls from the low-risk area (91.4 vs. 70.6 ng/day, P < 0.01). In the multivariate regression analysis, having ESCC had no independent effect on BaP, whereas residence in the low-risk area was associated with a significant decrease in total BaP intake. Polycyclic aromatic hydrocarbons might, along with other risk factors, contribute to the high risk of ESCC in Golestan.

Background: A recently developed multiplex serology method has been used to identify new virulence factors of Helicobacter pylori. The results of associations with gastric cancer have not been consistent across studies, possibly due to differences in the studied populations and/or the genetic diversity of H. pylori. We aimed to investigate the association between seropositivity to fifteen different H. pylori antigens using the multiplex serology method and the risk of gastric cardia (GCA) and gastric non-cardia (GNCA) adenocarcinomas in northeastern Iran, where the population has both a high prevalence of H. pylori infection and a high incidence of gastric adenocarcinoma. Methods: We included 272 cases of gastric adenocarcinoma (142 GCA, 103 GNCA, and 22 unspecified tumors) and 524 controls who were individually matched to cases for age, sex, and place of residence in this populationbased case-control study. Seropositivity to H. pylori was assessed using both multiplex serology and H. pylori IgG ELISA (BioHit, Finland). Results: H. pylori positivity based on the whole-cell ELISA test and also multiplex serology assay; defined as recognizing antibodies to ≥ 4 antigens; were not significantly associated with any of study groups; and its positivity rate was generally lower in ELISA assay than multiplex serology; GCA cases (79.6% vs. 95.1%), GNCA cases (74.8% vs. 95.2%), and controls (82.4% vs. 94.7%). Of the 15 antibodies in the multiplex assay, 10 showed no significant association with all gastric adenocarcinoma, GCA, or GNCA; while CagA and VacA were associated with a significantly increased risk of these cancers in multivariate adjusted models. Conversely, GroEL and NapA were significantly associated with a reduced risk of all gastric adenocarcinoma and GNCA. Conclusion: Our study showed no association between ELISA test positivity and gastric cancer risk, which implies that this method should not be used for risk stratification and referral for H. pylori eradication. Rather, effective risk stratification would require further characterization of H. pylori strain exposure with virulence factors such as CagA and VacA antigens. Our finding regarding lower risk of gastric adenocarcinoma among GroEL and NapA antigen positive subjects deserves additional investigation.

In northeastern Iran, there is an area of high incidence of esophageal cancer, which is populated by residents of Turkmen ancestry. Several environmental risk factors for esophageal cancer have been proposed, but the roles of familial and genetic factors have not been studied extensively in the Turkmen population. We evaluated the importance of familial risk factors for esophageal cancer by performing a case-control study of 167 cases of esophageal squamous cell carcinoma and 200 controls of Turkmen ethnicity. Detailed family pedigrees of the cases and controls were constructed, which documented all cancers in first- and second-degree relatives. The actuarial risk of cancer was then estimated in 2,097 first-degree relatives of cases and 2,783 first-degree relatives of the controls. A hazard ratio was constructed, based on a comparison of the 2 cumulative incidence curves. The risk to age 75 of esophageal cancer in the first-degree relatives of Turkmen patients with esophageal cancer was 34% versus 14% for the first-degree relatives of the controls (hazard ratio = 2.3; p = 3 x 10(-8)). Cases (9.6%) reported that their parents were related, versus 2.5% of the controls who reported this. (odds ratio = 4.1; p value = 0.006). Familial factors are important in the etiology of esophageal cancer among the Turkmen residents of Iran. The hazard ratio of 2.3 for cancer among first-degree relatives is consistent with an important contribution of heritable factors. It will be of interest to perform marker studies to establish which genes are responsible.

Currently, the buying and selling of kidneys through "transplant tourism" is occurring at an increasing rate, both in developed and developing countries. Since 1988, Iran has adopted a compensated and regulated living-unrelated donor renal transplant program, and by providing financial incentives to volunteer living donors, has eliminated the renal transplant waiting list. In the Iranian model of renal transplantation program, regulations have been put in place to prevent transplant tourism. Foreigners are not allowed to undergo renal transplantation from Iranian living-unrelated donors. They also are not permitted to volunteer as kidney donors for Iranian patients. A study at the transplant unit of Hashemi Nejad Kidney Hospital in Tehran, Iran, showed that of 1881 renal transplant recipients, 19 (1%) were Afghani or Iraqi refugees, 11 (0.6%) were other foreign nationals, and 18 (0.9%) were Iranian immigrants. Renal transplantations seemed ethically acceptable to all refugees and foreign nationals. However, transplantation of Iranian immigrants who had been residing abroad for years constituted true transplant tourism.

Noncompliance with immunosuppressive medications in renal transplant recipients results in higher rate of acute rejection episodes, allograft dysfunction, graft loss and patient death. We studied incidence and risk factors of medications noncompliance in 286 renal transplant recipients who were consecutively seen in our renal transplant clinic between February and April 2002. One hundred and seventy were male, 116 female. Their age ranged from 12 to 70 years (mean 39.1+/-11.6). The length of time since the date of transplantation ranged from 5 to 231 months (mean 76.7+/-53.5). The results of study showed that 70 patients (24.5%) to be noncompliant (7.7% noncompliant minor and 16.8% noncompliant major). The time since the date of transplanation was a significant risk factor in both noncompliant minor and major groups (P0.001 and P0.001). The other risk factors associated with major noncompliance was young age (P0.001), lower level of education (P0.01), lower socioeconomic class (P0.05), addiction and psychiatric disorders (P0.05). Transplant recipients with major noncompliance also had more acute rejection episodes (P0.001) and allograft dysfunction (P0.01). We conclude that noncompliance with immunosuppressive medications is very common in renal transplant recipients and it results to significant acute rejection episodes and allograft failure.

To investigate the incidence of oesophageal cancer (EC) in the Golestan province of North-East Iran, we invited 1349 rural and urban inhabitants of Golestan province aged 35-80 to undergo extensive lifestyle interviews and to provide biological samples. The interview was repeated on a subset of 130 participants to assess reliability of questionnaire and medical information. Temperature at which tea was consumed was measured on two occasions by 110 subjects. Samples of rice, wheat and sorghum were tested for fumonisin contamination. An active follow-up was carried out after 6 and 12 months. A total of 1057 subjects (610 women and 447 men) participated in this feasibility study (78.4% participation rate). Cigarette smoking, opium and alcohol use were reported by 163 (13.8%), 93 (8.8%) and 39 (3.7%) subjects, respectively. Tobacco smoking was correlated with urinary cotinine (? = 0.74). Most questionnaire data had ? > 0.7 in repeat measurements; tea temperature measurement was reliable (? = 0.71). No fumonisins were detected in the samples analysed. During the follow-up six subjects were lost (0.6%), two subjects developed EC (one dead, one alive); in all, 13 subjects died (with cause of death known for 11, 84.6%). Conducting a cohort study in Golestan is feasible with reliable information obtained for suspected risk factors; participants can be followed up for EC incidence and mortality. © 2005 Cancer Research UK.

The age-standardized incidence of esophageal cancer (EC) varies from 3 to >100/100,000 per year in different provinces of Iran. This striking variation of incidence is associated with differences in ethnic backgrounds, raising the possibility that genetic factors are involved in the pathogenesis of EC. We compared the frequencies of polymorphisms in ten genes that have been hypothesized to have a role in risk of EC (CYP1A1, CYP2A6, CYP2E1, GSTM1, GSTP1, GSTT1, ADH2, ADH3, ALDH2, and O6-MGMT) among three Iranian ethnic groups with highly varying rates of EC. These three groups included high-risk Turkomans, medium-risk Turks, and low-risk Zoroastrian Persians. Compared to Zoroastrians, Turkomans had higher frequency of four alleles that are speculated to favor carcinogenesis (CYP1A1 m1, CYP1A1 m2, CYP2A6*9, and ADH2*1); these results are consistent with an influence of these allele variants on the population risk of EC. However, none of these four alleles had a high enough prevalence in Turkomans to explain the high rates of EC in this group. Three of these four alleles (CYP1A1 m1, CYP1A1 m2, CYP2A6*9) were less frequent among Turkomans than in some Asian populations with lower risks of EC. We conclude that it is unlikely that variations in these polymorphic genes are major contributors to the high incidence of EC among Turkomans in Iran.