Esophageal cancer in golestan province, Iran: a review of genetic susceptibility and environmental risk factors

Esophageal squamousi cell carcinoma [ESCC] is an aggressive tumor that is typically diagnosed only when the tumor has gained remarkable size, extended to peripheral tissues, and led to dysphagia. Five-year survival of advanced cancer is still very poor [19%], even with improved surgical techniques and adjuvant chemoradiation therapy

Therefore, early detection and prevention are the most important strategies to reduce the burden of ESCC

Our review will focus on the studies conducted in Golestan province, an area with a high prevalence of ESCC in northern Iran. We review three aspects of the research literature on ESCC: epidemiological features, environmental factors [including substance abuse, environmental contaminants, dietary factors, and human papilloma virus [HPV], and molecular factors [including oncogenes, tumor suppressor genes, cell cycle regulatory proteins, and other relevant biomarkers]

Epidemiological and experimental data suggest that some chemicals and lifestyle factors, including polycyclic aromatic hydrocarbons [PAHs], cigarette smoking, opium use, and hot tea drinking are associated with the development of ESCC in Golestan

HPV infects the esophageal epithelium, but so far, no firm evidence of its involvement in esophageal carcinogenesis has been provided. Some of these factors, notably hot tea drinking, may render the esophageal mucosa more susceptible to injury by other carcinogens

There are few studies at molecular level on ESCC in Golestan

Increasing awareness about the known risk factors of ESCC could potentially reduce the burden of ESCC in the region. Further studies on risk factors, identifying high risk populations, and early detection are needed

Gastroesophageal reflux disease and overall and cause-specific mortality: a prospective study of 50000 individuals

BACKGROUND Only a few studies in Western countries have investigated the association between gastroesophageal reflux disease [GERD] and mortality at the general population level and they have shown mixed results

This study investigated the association between GERD symptoms and overall and cause-specific mortality in a large prospective population-based study in Golestan Province, Iran

METHODS: Baseline data on frequency, onset time, and patient-perceived severity of GERD symptoms were available for 50001 participants in the Golestan Cohort Study [GCS]

We identified 3107 deaths [including 1146 circulatory and 470 cancer-related] with an average follow-up of 6.4 years and calculated hazard ratios [HR] and 95% confidence intervals [CI] adjusted for multiple potential confounders

RESULTS: Severe daily symptoms [defined as symptoms interfering with daily work or causing nighttime awakenings on a daily bases, reported by 4.3% of participants] were associated with cancer mortality [HR 1.48, 95% CI: 1.04-2.05]

This increase was too small to noticeably affect overall mortality

Mortality was not associated with onset time or frequency of GERD and was not increased with mild to moderate symptoms

CONCLUSION: We have observed an association with GERD and increased cancer mortality in a small group of individuals that had severe symptoms. Most patients with mild to moderate GERD can be re-assured that their symptoms are not associated with increased mortality

gastro-esophageal malignancies in Northern Iran research project: impact on the health research and health care systems of Iran

The Gastro-Esophageal Malignancies in Northern Iran [GEMINI] research project is an example of recent progress in health research in Iran. The original aim of this project was to identify etiologic factors and prevention measures for upper gastrointestinal cancers in Northern provinces of Iran, but its achievements have gone much beyond this initial goal. GEMINI consists of several projects including cancer registries, pilot studies, case-control studies, and the Golestan Cohort Study. GEMINI has been conducted through extensive collaborations between the Digestive Disease Research Center of Tehran University of Medical Sciences with other domestic and international health organizations. The achievements of GEMINI include producing new knowledge, introducing new research methods, developing and expanding health research and health care infrastructures, investing in human resources, and increasing the awareness and knowledge of policy makers and officials at all levels about the importance of chronic diseases in Iran's health priorities. The success of GEMINI reveals the feasibility of large-scale health research studies in developing countries and serves as a successful model not only for health research in Iran, but also for similar research studies in other developing nations

[Celiac disease and esophageal Cancer]

Northeastern Iran has a high incidence for squamous cell esophageal carcinoma [ESCC]. The aim of the study is to the assess relationship between celiac disease [CD] and ESCC. This was a two-part, cross-sectional, case-control study performed during 2006-2011 in Gonbad, Golestan, Iran. Serum IgA anti-tissue transglutaminase antibody levels were measured for all participants in the crosssectional study [adult general population] as well as in ESCC cases and their matched [age and gender] controls. Out of approximately 1.3% of the 2202 individuals selected from the general population, 0.8% of 258 ESCC cases and 0.2% of 457 controls had positive IgA anti-tissue transglutaminase antibody levels. The prevalence of CD in general population of Gonbad district is a little higher than other parts of Iran. Relatively low prevalence of IgA anti-tissue transglutaminase antibody in ESCC cases in northeastern Iran does not support the presumption that CD is a major factor for the high incidence of ESCC in the region. However, as there is little higher prevalence of positivity for the antibody in ESCC cases than in controls, a cohort study of Celiac disease patients is much more suitable study to assess the relation between CD and ESCC.

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

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. 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 _ltration 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. 1557 subjects with a mean age of 56.76 +/- 12.04 years were enrolled in this study. Based on the modi_cation 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]. 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

Quality of drinking water and high incidence rate of esoph-ageal cancer in Golestan Province of Iran: a probable link

Golestan Province in northern Iran is known to be a high-risk area for esophageal cancer [EC]. Of a long list of multiple risk factors, this study focuses on a possible link between the epidemiologic patterns of EC and the anomalous concentration of some ions and elements in the drinking water sources. A total of 183 samples from 45 villages covering a wide range of EC mortality rates are collected and analyzed. The results demonstrate that NO3, SO42, Sb, and Sr exceed the recommended maximum concentration level [MCL] in drinking water. This is more prominent in the villages with high esophageal cancer mortality rate, suggesting a possible link between EC incidence and water quality. Se concentration in drinking water increases from low to the high EC areas, a finding contrary to the expected trend. It is concluded that Se deficiency does not play a major role in the etiology of EC in the Golestan Province. The statistical results obtained from Mann-Whitney and Kruskal-Wallis tests along with cluster analysis are consistent with the observed trend of EC mortality rate in Golestan Province

Prevalence of esophageal cancer risk factors among Turkmen and non-Turkmen ethnic groups in a high incidence area in Iran

Golestan Province in north-eastern Iran has one of the highest incidence rates for esophageal squamous cell carcinoma [ESCC] worldwide. Earlier studies have reported higher incidence rates in the areas of Golestan which are mainly inhabited by individuals of the Turkmen ethnic group. However, it is not clear whether in those areas the incidence among Turkmens is higher in comparison to non-Turkmens. Some previous studies have suggested that environmental factors might play a more essential role in ESCC carcinogenesis in Golestan than a genetic background. If environmental factors instead of a genetic background are the major risk factors, therefore the prevalence of known environmental risk factors would not significantly differ among ESCC cases of different ethnic groups. To investigate the role of environmental factors versus genetic background by using the above concept, we have compared the prevalence of known risk factors for ESCC among Turkmen and non-Turkmen ESCC cases. Study participants were histopathologically proven ESCC cases from Golestan Province. They were recruited in the study from December 2003 to June 2007. The prevalence of the most important known risk factors for ESCC in Turkmen and non-Turkmen ESCC cases was compared using Chi-squared and Fisher's exact tests. Of 300 ESCC cases recruited in the study, 171 [57.0%] and 129 [43.0%] cases were Turkmen and non-Turkmen, respectively. In the majority of the investigated risk factors which included tobacco, nass, and opium use, hot and extremely hot tea consumption, as well as decreased levels of education; there was no significant difference between Turkmen and non-Turkmen ESCC cases in the prevalence of exposure. Our findings support the suggestion that a substantial difference between Turkmens and non-Turkmens in terms of genetic susceptibility to ESCC is unlikely. Nevertheless, the moderate effect of genetic factors cannot be ruled out. Further studies to investigate potential environmental and genetic risk factors of ESCC in Golestan and the interaction between environmental and genetic factors are warranted