Dariush Nasrollahzadeh

Tea drinking habits and oesophageal cancer in a high risk area in northern Iran: population based case-control study

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 10.1136/bmj.b929V1

Opium, tobacco, and alcohol use in relation to oesophageal squamous cell carcinoma in a high-risk area of Iran

The very high incidence of oesophageal squamous cell carcinoma (ESCC) in Golestan Province in northeastern Iran was suggested by studies in the 1970s as partly due to opium use, which is not uncommon in this area, but based on limited numbers. From December 2003 to June 2007, we administered a validated structured questionnaire to 300 ESCC cases and 571 controls, matched on neighbourhood of residence, age (±2 years), and sex. We used conditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for potential confounders. Compared with those who used neither tobacco nor opium, risk of ESCC was increased in those who used tobacco only (OR, 95% CI: 1.70, 1.05–2.73), in those who used opium only (2.12, 1.21–3.74), and in those who used both tobacco and opium (2.35, 1.50–3.67). All forms of tobacco use (cigarettes, hookah, and nass) were associated with higher ESCC risk. Similarly, use of both crude opium and other forms of opium were associated with higher risk. Alcohol consumption was seen in only 2% of the cases and 2% of the controls, and was not associated with ESCC risk.

Socio-economic status and oesophageal cancer: results from a population-based case–control study in a high-risk area

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.

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. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3062–8)

Validity and reliability of a new food frequency questionnaire compared to 24 h recalls and biochemical measurements: pilot phase of Golestan cohort study of esophageal cancer

Background:A pilot study was carried out to evaluate validity and reproducibility of a food frequency questionnaire (FFQ), which was designed to be used in a prospective cohort study in a population at high risk for esophageal cancer in northern Iran.Methods:The FFQ was administered four times to 131 subjects, aged 35–65 years, of both sexes. Twelve 24-h dietary recalls for two consecutive days were administered monthly during 1 year and used as a reference method. The excretion of nitrogen was measured on four 24-h urine samples, and plasma levels of β-carotene, retinol, vitamin C and α-tocopherol was measured from two time points. Relative validity of FFQ and 24-h diet recall was assessed by comparing nutrient intake derived from both methods with the urinary nitrogen and plasma levels of β-carotene, retinol, vitamin C and α-tocopherol.Results:Correlation coefficients comparing energy and nutrients intake based on the mean of the four FFQ and the mean of twelve 24-h diet recalls were 0.75 for total energy, 0.75 for carbohydrates, 0.76 for proteins and 0.65 for fat. Correlation coefficients between the FFQ-based intake and serum levels of β-carotene, retinol, vitamin C and vitamin E/α-tocopherol were 0.37, 0.32, 0.35 and 0.06, respectively. Correlation coefficients between urinary nitrogen and FFQ-based protein intake ranged from 0.23 to 0.35. Intraclass correlation coefficients used to measure reproducibility of FFQ ranged from 0.66 to 0.89.Conclusion:We found that the FFQ provides valid and reliable measurements of habitual intake for energy and most of the nutrients studied.

Oesophageal cancer in Golestan Province, a high-incidence area in northern Iran – A review

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.

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.

Golestan cohort study of oesophageal cancer: feasibility and first results.

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 (κ=0.74). Most questionnaire data had κ >0.7 in repeat measurements; tea temperature measurement was reliable (κ=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.

Germline BRCA2 mutations and the risk of esophageal squamous cell carcinoma

The incidence of esophageal squamous cell carcinoma (ESCC) is very high among the Turkmen population of Iran. Family studies suggest a genetic component to the disease. Turkmen are ethnically homogenous and are well suited for genetic studies. A previous study from China suggested that BRCA2 might play a role in the etiology of ESCC. We screened for mutations in the coding region of the BRCA2 gene in the germline DNA of 197 Turkmen patients with ESCC. A nonsense variant, K3326X, was identified in 9 of 197 cases (4.6%) vs 2 of 254 controls (0.8%) (OR=6.0, 95% CI=1.3–28; P=0.01). This mutation leads to the loss of the C-terminal domain of the BRCA2 protein, a part of the region of interaction with the FANCD2 protein. We observed nine other BRCA2 variants in single cases only, including two deletions, and seven missense mutations. Six of these were judged to be pathogenic. In total, a suspicious deleterious BRCA2 variant was identified in 15 of 197 ESCC cases (7.6%).

Dietary Intake of Benzo(a)pyrene and Risk of Esophageal Cancer in North of Iran

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.