Polycyclic aromatic hydrocarbons and esophageal squamous cell carcinoma

Esophageal cancer (EC) is the 8th most common cancer and the 6th most frequent cause of cancer mortality worldwide. Esophageal squamous cell carcinoma (ESCC) is the most common type of EC. Exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested as a risk factor for developing ESCC. In this paper we will review different aspects of the relationship between PAH exposure and ESCC. PAHs are a group of compounds that are formed by incomplete combustion of organic matter. Studies in humans have shown an association between PAH exposure and development of ESCC in many populations. The results of a recent case-control study in a high risk population in northeastern Iran showed a dramatic dose-response relationship between PAH content in non-tumor esophageal tissue (the target tissue for esophageal carcinogenesis) and ESCC case status, consistent with a causal role for PAH exposure in the pathogenesis of ESCC. Identifying the main sources of exposure to PAHs may be the first and most important step in designing appropriate PAH-reduction interventions for controlling ESCC, especially in high risk areas. Coal smoke and drinking mate have been suggested as important modifiable sources of PAH exposure in China and Brazil, respectively. But the primary source of exposure to PAHs in other high risk areas for ESCC, such as northeastern Iran, has not yet been identified. Thus, environmental studies to determining important sources of PAH exposure should be considered as a high priority in future research projects in these areas

Modeling the risk of esophageal squamous cell carcinoma and squamous dysplasia in a high risk area in Iran

Background: Identifying people at higher risk of having squamous dysplasia, the precursor lesion for esophageal squamous cell carcinoma (ESCC), would allow targeted endoscopic screening. Methods: We used multivariate logistic regression models to predict ESCC and dysplasia as outcomes. The ESCC model was based on data from the Golestan Case-Control Study (total n = 871; cases = 300), and the dysplasia model was based on data from a cohort of subjects from a gastroenterology clinic in Northeast Iran (total n = 724; cases = 26). In each of these analyses, we fit a model including all risk factors known in this region to be associated with ESCC. Individual risks were calculated using the linear combination of estimated regression coefficients and individual-specific values for covariates. We used cross-validation to determine the area under the curve (AUC) and to find the optimal cut points for each of the models. Results: The model had an area under the curve of 0.77 (95 CI: 0.74-0.80) to predict ESCC with 74 sensitivity and 70.4 specificity for the optimum cut point. The area under the curve was 0.71 (95 CI: 0.64-0.79) for dysplasia diagnosis, and the classification table optimized at 61.5 sensitivity and 69.5 specificity. In this population, the positive and negative predictive values for diagnosis of dysplasia were 6.8 and 97.8, respectively. Conclusion: Our models were able to discriminate between ESCC cases and controls in about 77, and between individuals with and without squamous dysplasia in about 70 of the cases. Using risk factors to predict individual risk of ESCC or squamous dysplasia still has limited application in clinical practice, but such models may be suitable for selecting high risk individuals in research studies, or increasing the pretest probability for other screening strategies

Endoscopic screening for precancerous lesions of the esophagus in a high risk area in northern Iran

Background: Esophageal squamous cell carcinoma (ESCC) is a major health problem in many developing countries, including Iran. ESCC has a very poor prognosis, largely due to late diagnosis. As a first step in developing an early detection and treatment program, we conducted a population-based endoscopic screening for ESCC and its precursor lesion, esophageal squamous dysplasia (ESD), in asymptomatic adults from Golestan Province, northern Iran (a high-risk area for ESCC) to evaluate the feasibility of such a program and to document the prevalence and risk factor correlates of ESD. Methods: This cross-sectional study was conducted among participants of the Golestan Cohort Study (GCS), a population-based cohort of 50,000 adults in eastern Golestan Province. Randomly selected GCS participants were invited by telephone. Those who accepted were referred to a central endoscopy clinic. Eligible subjects who consented were asked to complete a brief questionnaire. Detailed information about selected risk factors was obtained from the GCS main database. Endoscopic examination with was performed with Lugol's iodine staining; biopsies were taken from unstained lesions as well as the normally stained mucosa of the esophagus, and the biopsies were diagnosed by expert pathologists according to previously described criteria. Results: In total, 1906 GCS subjects were invited, of whom only 302 (15.8%) were successfully enrolled. Esophagitis (29.5%) and ESD (6.0%) were the most common pathological diagnoses. Turkmen ethnicity (adjusted OR = 8.61; 95%CI: 2.48-29.83), being older than the median age (OR = 7.7; 95% CI: 1.99-29.87), and using deep frying cooking methods (OR = 4.65; 95%CI: 1.19-18.22) were the strongest predictors for ESD. There were significant relationships between esophagitis and smoking (p-value<0.001), drinking hot tea (P value = 0.02) and lack of education (P value = 0.004). Conclusion: We observed a low rate of participation in endoscopic screening. The overall prevalence of ESD was 6.0%. Developing non-endoscopic primary screening methods and screening individuals with one or more risk factors may improve these rates

Reliability and validity of opiate use self-report in a population at high risk for esophageal cancer in Golestan, Iran

Objective: To assess the reliability and validity of self-reported opium use in a rural Iranian population at high risk for esophageal cancer in preparation for a large cohort study. Method: 1,057 subjects ages 33 to 84 years were recruited from Gonbad city and three surrounding villages in Golestan province of Iran and completed a questionnaire and provided biological samples. The history and duration of using opium, smoking tobacco, chewing nass, and drinking alcohol were measured by questionnaire in the entire cohort. A subgroup of 130 people was reinterviewed after 2 months to assess reliability. Validity of the opium question was assessed by comparing the questionnaire responses with the presence of codeine and morphine in the urine of 150 selected subjects. Results: Self-reported opiate use is reliable and valid in this population. The reliability of ever opium use and duration of opium use had κ′s of 0.96 and 0.74, respectively. The validity of self-reported opium use was also high. Using urine codeine or morphine as the gold standard for use of opium, self-report had a sensitivity of 0.93 and a specificity of 0.89. Conclusions: The self-reported use of opium can provide a reliable and valid measurement in this population and will be useful for studying associations between opium use and occurrence of esophageal cancer and other diseases

Mortality and cancer in relation to ABO blood group phenotypes in the Golestan Cohort Study

Background: A few studies have shown an association between blood group alleles and vascular disease, including atherosclerosis, which is thought to be due to the higher level of von Willebrand factor in these individuals and the association of blood group locus variants with plasma lipid levels. No large population-based study has explored this association with overall and cause-specific mortality. Methods: We aimed to study the association between ABO blood groups and overall and cause-specific mortality in the Golestan Cohort Study. In this cohort, 50,045 people 40- to 70-years old were recruited between 2004 and 2008, and followed annually to capture all incident cancers and deaths due to any cause. We used Cox regression models adjusted for age, sex, smoking, socioeconomic status, ethnicity, place of residence, education and opium use. Results: During a total of 346,708 person-years of follow-up (mean duration 6.9 years), 3,623 cohort participants died. Non-O blood groups were associated with significantly increased total mortality (hazard ratio (HR) = 1.09; 95% confidence interval (CI): 1.01 to 1.17) and cardiovascular disease mortality (HR = 1.15; 95% CI: 1.03 to 1.27). Blood group was not significantly associated with overall cancer mortality, but people with group A, group B, and all non-O blood groups combined had increased risk of incident gastric cancer. In a subgroup of cohort participants, we also showed higher plasma total cholesterol and low-density lipoprotein (LDL) in those with blood group A. Conclusions: Non-O blood groups have an increased mortality, particularly due to cardiovascular diseases, which may be due to the effect of blood group alleles on blood biochemistry or their effect on von Willebrand factor and factor VIII levels. \ua9 Etemadi et al

Familial risks of esophageal cancer among the Turkmen population of the Caspian littoral of Iran

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 × 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. © 2006 Wiley-Liss, Inc

Large body size and sedentary lifestyle during childhood and early adulthood and esophageal squamous cell carcinoma in a high-risk population

Background: Little is known about the association of obesity and physical activity at young ages with subsequent risk of esophageal squamous cell carcinoma (ESCC). Patients and methods: Between 2003 and 2007, we conducted a case-control study in a high-risk population in northeastern Iran. Three hundred ESCC cases and 571 matched controls were recruited. Each individual was shown a standard pictogram, to report body size at ages 15 and 30. Demographic and health-related information, including physical activity at these ages was also collected. Results: In the fully adjusted models, very obese body size (last two pictograms) at age 15 odds ratio (OR) 3.2, 95% confidence interval (CI) 1.3-7.7 and age 30 (OR 3.1; 95% CI 1.1-8.5) were associated with ESCC in women, but not in men. Sedentary work at age 15 (OR 3.3, 95% CI 1.3-8.3) and 30 (OR 18.2, 95% CI 3.9-86.2) were also associated with ESCC risk in women only. The increased risk in women at age 15 remained high after later reduction in body size, while women who became very obese only at age 30 did not show a significantly increased risk. Conclusion: These results highlight the importance of early lifestyle modifications in the context of cancer prevention, particularly in women. © Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved

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

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

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

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

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. © 2013 AACR