Investigation of NQO1 genetic polymorphism, NQO1 gene expression and PAH-DNA adducts in ESCC. A case-control study from Iran

We evaluated the effect of NQO1 genetic variation on PAH-DNA adducts in esophageal squamous cell carcinoma (ESCC) in northeast Iran. Golestan Province in northeast of Iran has one of the highest esophageal cancer incidences in the world. The study included 93 ESCC cases and 50 control individuals who were seen at the clinical cancer center in Golestan province. NQO1 C609T genotypes were determined by PCR-RFLP analysis. NQO1 gene expression in tissue samples was determined by quantitative real-time PCR. Immunohistochemical techniques were used to detect PAH-DNA adducts in ESCC and normal esophageal tissues. The distributions of NQO1 genetic polymorphism between cases and the control group were not significantly different. NQO1 gene expression was not higher in tumor tissues than in normal esophageal tissues adjacent to the ESCC; expression was higher in tumor tissues that had the NQO1 T allele. NQO1 gene expression was high in normal esophageal tissues. The level of PAH-DNA adducts was significantly higher in ESCC tissues of cases than in normal tissues adjacent to tumor tissues and in normal esophageal tissues of healthy controls. There were no significant differences between the adduct levels of normal esophageal tissues of patients and controls. There was also no significant relationship between cigarette smoking and PAH-DNA adducts. We concluded that PAHs are a risk factor for ESCC and that PAH-DNA adducts have potential as a biomarker for risk of ESCC

Prognostic factors for esophageal squamous cell Carcinoma-A Population-Based study in Golestan province, Iran, a high incidence area

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

Tooth loss and lack of regular oral hygiene are associated with higher risk of esophageal squamous cell carcinoma

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. Copyright © 2008 American Association for Cancer Research

Epidemiologic features of upper gastrointestinal tract cancers in Northeastern Iran

Previous studies have shown that oesophageal and gastric cancers are the most common causes of cancer death in the Golestan Province, Iran. In 2001, we established Atrak Clinic, a referral clinic for gastrointestinal (GI) diseases in Gonbad, the major city of eastern Golestan, which has permitted, for the first time in this region, endoscopic localisation and histologic examination of upper GI cancers. Among the initial 682 patients seen at Atrak Clinic, 370 were confirmed historically to have cancer, including 223 (60) oesophageal squamous cell cancers (ESCC), 22 (6) oesophageal adenocarcinomas (EAC), 58 (16) gastric cardia adenocarcinomas (GCA), and 58 (16) gastric noncardia adenocarcinomas. The proportional occurrence of these four main site-cell type subdivisions of upper GI cancers in Golestan is similar to that seen in Linxian, China, another area of high ESCC incidence, and is markedly different from the current proportions in many Western countries. Questioning of patients about exposure to some known and suspected risk factors for squamous cell oesophageal cancer confirmed a negligible history of consumption of alcohol, little use of cigarettes or nass (tobacco, lime and ash), and a low intake of opium, suggesting that the high rates of ESCC seen in northeastern Iran must have other important risk factors that remain speculative or unknown. Further studies are needed to define more precisely the patterns of upper GI cancer incidence, to test other previously suspected risk factors, and to find new significant risk factors in this high-risk area. © 2004 Cancer Research UK

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

Background: 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. Methods: 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. Results: 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 nonTurkmen ESCC cases in the prevalence of exposure. Conclusion: 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

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

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