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1.  Frequent occurrence of esophageal cancer in young people in western Kenya 
Esophageal cancer has a strikingly uneven geographical distribution, resulting in focal endemic areas in several countries. One such endemic area is in western Kenya. We conducted a retrospective review of all pathology-confirmed malignancies diagnosed at Tenwek Hospital, Bomet District, between January 1999 and September 2007. Tumor site, histology, sex, age, ethnicity, and location of residence were recorded. Cases were analyzed within and outside a traditional catchment area defined as ≤ 50 km from the hospital. Since 1999, the five most common cancer sites were esophagus, stomach, prostate, colorectum, and cervix. Esophageal cancer accounted for 914 (34.6%) of the 2643 newly diagnosed cancers, and showed increasing trends within and outside the catchment area. Fifty-eight (6.3%) patients were ≤ 30 years old and 9 (1%) were ≤ 20 years old; the youngest patient was 14 at diagnosis. Young cases (≤30) were more common among patients of Kalenjin ethnicity (9.2%) than among other ethnicities (1.7%) (odds ratio (95%CI) 5.7 (2.1–15.1)). This area of western Kenya is a high-risk region for esophageal cancer, and appears unique in its large proportion of young patients. Our findings support the need for further study of both environmental and genetic risk factors for esophageal cancer in this area.
doi:10.1111/j.1442-2050.2009.00977.x
PMCID: PMC3505035  PMID: 19473205
Esophageal cancer; Kenya; age of onset; ethnicity
3.  Aryl hydrocarbon receptor expression is associated with a family history of upper gastrointestinal cancer in a high risk population exposed to aromatic hydrocarbons 
Background
Polycyclic aromatic hydrocarbon (PAH) exposure is a risk factor for esophageal squamous cell carcinoma (ESCC), and PAHs are ligands of the aryl hydrocarbon receptor (AhR). This study measured the expression of AhR and related genes in frozen esophageal cell samples from patients exposed to different levels of indoor air pollution, who did or did not have high-grade squamous dysplasia (HGD), and who did or did not have a family history (FH) of upper gastrointestinal cancer (UGI Ca).
Methods
147 samples were evaluated, including 23 (16%) from patients with HGD and 48 (33%) from patients without DYS who heated their homes with coal, without a chimney (a “high” indoor air pollution group), and 27 (18%) from patients with HGD and 49 (33%) from patients without DYS who did not heat their homes at all (a “low” indoor air pollution group). Nearly half (64 (44%)) had a FH of UGI Ca. RNA was extracted and Quantitative-PCR analysis was performed.
Results
AhR gene expression was detectable in 85 (58%) of the samples, and was more than 9-fold higher in those with a FH of UGI Ca (median expression (IQR) -1964 (-18000, -610) versus -18000 (-18000, -1036) Wilcoxon P = 0.02). Heating status, dysplasia category, age, gender, and smoking were not associated with AhR expression (linear regression, all P-values ≥0.1).
Conclusion
AhR expression was higher in patients with a FH of UGI Ca. Such individuals may be more susceptible to the deleterious effects of PAH exposure, including PAH-induced cancer.
doi:10.1158/1055-9965.EPI-08-1098
PMCID: PMC2796959  PMID: 19690180
Gastrointestinal tract cancer; Esophagus; Aryl hydrocarbon receptor; family history of cancer; gene expression; polycyclic aromatic hydrocarbons
4.  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.
doi:10.1093/ije/dyp195
PMCID: PMC2720396  PMID: 19416955
Oesophageal cancer; socio-economic status; case–control; epidemiology; Iran; factor analysis; correspondence analysis
5.  Vitamin E intake and Risk of Esophageal and Gastric Cancers in the NIH-AARP Diet and Health Study 
We investigated the association of dietary α-tocopherol, γ-tocopherol, and supplemental vitamin E intake with the risk of esophageal squamous cell carcinoma (ESCC; n = 158), esophageal adenocarcinoma (EAC; n = 382), gastric cardia adenocarcinoma (GCA; n = 320), and gastric noncardia adenocarcinoma (GNCA; n = 327) in the NIH-AARP Diet and Health Study, a cohort of approximately 500,000 people. Data on dietary and supplemental vitamin E intake were collected using a validated questionnaire at baseline and were analyzed using Cox regression models. Intakes were analyzed as continuous variables and as quartiles.
For dietary α-tocopherol, we found some evidence of association with decreased ESCC and increased EAC risk in the continuous analyses, with adjusted hazard ratios (HR) and 95% confidence intervals (CI) of 0.90 (0.81 – 0.99) and 1.05 (1.00 – 1.11), respectively, per 1.17 mg (half the interquartile range) increased intake. However, in quartile analyses, the p-value for trend was non-significant for both of these cancers. There was no association between dietary α-tocopherol and GCA or GNCA. We observed no statistically significant associations with γ-tocopherol. For supplemental vitamin E, the results were mainly null, except for a significantly lower risk of GNCA with higher doses of supplemental vitamin E. An increase of 71 mg/day (half the interquartile range) in supplemental vitamin E had an HR (95% CI) of 0.92 (0.85–1.00) and the p-value for trend in the quartile analyses was 0.015.
doi:10.1002/ijc.24342
PMCID: PMC2686122  PMID: 19326432
6.  Serum pepsinogens and risk of gastric and esophageal cancers in the General Population Nutrition Intervention Trial cohort 
Gut  2009;58(5):636-642.
Objective
Low serum pepsinogen I (PGI) and low pepsinogen I/pepsinogen II ratio (PGI/II ratio) are markers of gastric fundic atrophy. We aimed to prospectively test the association between serum PGI/II ratio and risks of gastric noncardia adenocarcinoma, gastric cardia adenocarcinoma, and esophageal squamous cell carcinoma.
Design
Case-cohort study nested in a prospective cohort with over 15 years of follow-up.
Setting
Rural region of the People’s Republic of China.
Subjects
Men and women aged 40-69 at study baseline.
Main outcome measures
Adjusted hazard ratios and 95% confidence intervals for the association between serum PGI/II ratio and caner risk
Results
Compared to subjects with PGI/II ratio of > 4, those with ≤4 had HRs (95%CIs) of 2.72 (1.77-4.20) and 2.12 (1.42-3.16) for noncardia and cardia gastric cancers, respectively. Risk of both cancers were also increased when other cut points ranging from 3 to 6, or when we used quartile models, or nonlinear continuous models. Risk of ESCC was marginally increased in those with PGI/II ratio ≤4, with HR (95% CI) of 1.56 (0.99-2.47), but quartile models and continuous models showed no increased risk. The nonlinear continuous models suggested that any single cut point collapsed subjects with dissimilar gastric cancer risks, and that using cut points was not an efficient use of data in evaluating these associations.
Conclusion
In this prospective study, we found similar and significantly increased risks of noncardia and cardia gastric adenocarcinomas in subjects with low PGI/II ratio, but little evidence for an association with ESCC risk.
doi:10.1136/gut.2008.168641
PMCID: PMC2792746  PMID: 19136509
Gastric cancer; Esophageal cancer; Pepsinogen; Case-cohort
7.  Sex disparities in cancer incidence by time period and age 
Background
Cancer epidemiology manuscripts often point out that cancer rates tend to be higher among males than females, yet rarely is this theme the subject of investigation.
Methods
We used the Surveillance, Epidemiology, and End Results (SEER) program data to compute age-adjusted (2000 US standard population) sex-specific incidence rates and male-to-female incidence rate ratios (IRR) for specific cancer sites and histologies for the period 1975-2004.
Results
The ten cancers with the largest male-to-female IRR were Kaposi sarcoma (28.73), lip (7.16), larynx (5.17), mesothelioma (4.88), hypopharynx (4.13), urinary bladder (3.92), esophagus (3.49), tonsil (3.07), oropharynx (3.06) and other urinary organs (2.92). Only five cancers had a higher incidence in females compared to males: breast (0.01), peritoneum, omentum and mesentery (0.18), thyroid (0.39), gallbladder (0.57), and anus, anal canal and anorectum (0.81). Between 1975 and 2004, the largest consistent increases in male-to-female IRR were for cancers of the tonsil, oropharynx, skin excluding basal and squamous, and esophagus, while the largest consistent decreases in IRR were for cancers of the lip and lung and bronchus. Male-to-female IRRs varied considerably by age, the largest increases of which were for ages 40-59 years for tonsil cancer and hepatocellular carcinoma. The largest decreases in male-to-female IRR by age, meanwhile, were for ages 30-49 years for thyroid cancer, ages ≥70 years for esophageal squamous cell carcinoma, and ages ≥30 years for lung and bronchus cancer.
Conclusion
These observations emphasize the importance of sex in cancer etiopathogenesis and may suggest novel avenues of investigation.
doi:10.1158/1055-9965.EPI-08-1118
PMCID: PMC2793271  PMID: 19293308
Sex; Male; Female; SEER program; Neoplasms; Incidence; Epidemiology
8.  Total and Cancer Mortality After Supplementation With Vitamins and Minerals: Follow-up of the Linxian General Population Nutrition Intervention Trial 
Background
The General Population Nutrition Intervention Trial was a randomized primary esophageal and gastric cancer prevention trial conducted from 1985 to 1991, in which 29 584 adult participants in Linxian, China, were given daily vitamin and mineral supplements. Treatment with “factor D,” a combination of 50 μg selenium, 30 mg vitamin E, and 15 mg beta-carotene, led to decreased mortality from all causes, cancer overall, and gastric cancer. Here, we present 10-year follow-up after the end of active intervention.
Methods
Participants were assessed by periodic data collection, monthly visits by village health workers, and quarterly review of the Linxian Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the cumulative effects of four vitamin and mineral supplementation regimens were calculated using adjusted proportional hazards models.
Results
Through May 31, 2001, 276 participants were lost to follow-up; 9727 died, including 3242 from cancer (1515 from esophageal cancer and 1199 from gastric cancer). Participants who received factor D had lower overall mortality (HR = 0.95, 95% CI = 0.91 to 0.99; P = .009; reduction in cumulative mortality from 33.62% to 32.19%) and gastric cancer mortality (HR = 0.89, 95% CI = 0.79 to 1.00; P = .043; reduction in cumulative gastric cancer mortality from 4.28% to 3.84%) than subjects who did not receive factor D. Reductions were mostly attributable to benefits to subjects younger than 55 years. Esophageal cancer deaths between those who did and did not receive factor D were not different overall; however, decreased 17% among participants younger than 55 (HR = 0.83, 95% CI = 0.71 to 0.98; P = .025) but increased 14% among those aged 55 years or older (HR = 1.14, 95% CI = 1.00 to 1.30; P = .47). Vitamin A and zinc supplementation was associated with increased total and stroke mortality; vitamin C and molybdenum supplementation, with decreased stroke mortality.
Conclusion
The beneficial effects of selenium, vitamin E, and beta-carotene on mortality were still evident up to 10 years after the cessation of supplementation and were consistently greater in younger participants. Late effects of other supplementation regimens were also observed.
doi:10.1093/jnci/djp037
PMCID: PMC2664089  PMID: 19318634
9.  Serum pepsinogens and risk of esophageal squamous dysplasia 
Pepsinogens are a class of endopeptidases that are secreted by the gastric epithelium and released into the circulation. Low serum pepsinogen I (PGI) and low serum pepsinogen I / pepsinogen II ratio (PGI/II ratio) are markers of gastric fundic atrophy, and have recently been shown to be associated with increased risk of esophageal squamous cell carcinoma (ESCC). We conducted the current study to test whether these markers are also associated with esophageal squamous dysplasia (ESD), the precursor lesion of ESCC.
We measured serum PGI and PGII, using enzyme-linked immunosorbent (ELISA) assays, in 125 case subjects (patients with moderate or severe ESD) and 250 sex-matched control subjects (no ESD) selected from an endoscopic screening study in Linxian, China. We used conditional logistic regression models adjusted for age, smoking, and place of residence to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs).
Serum PGI showed no statistically significant association with ESD, whether analyzed as a dichotomous, ordinal (quartiles), or continuous variable. Lower serum PGI/II ratio, however, showed a dose-response association with increased risk of ESD, with an adjusted OR (95% CI) of 2.12 (1.08 − 4.18), comparing the lowest versus the highest quartile. The association between lower serum PGI/II ratio and log OR of ESD was nearly linear, and the p-value for the continuous association was 0.03.
Lower serum PGI/II ratio was linearly associated with higher risk of ESD. This result is consistent with recent findings that gastric atrophy may increase the risk of ESCC.
doi:10.1002/ijc.23918
PMCID: PMC2605159  PMID: 18844222
Esophageal cancer; Squamous dysplasia; Pepsinogen; China
10.  Patterns of food and nutrient consumption in northern Iran, a high-risk area for esophageal cancer 
Nutrition and cancer  2009;61(4):475-483.
Objectives
To investigate patterns of food and nutrient consumption in Golestan province, a high-incidence area for esophageal cancer (EC) in northern Iran.
Methods
Twelve 24-hour dietary recalls were administered during a one year 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 twelve recalls.
Results
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.
Conclusions
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.
doi:10.1080/01635580902803735
PMCID: PMC2796961  PMID: 19838919
esophageal cancer; Iran; Caspian Littoral; Golestan: Turkmen; diet record
11.  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.
doi:10.1136/bmj.b929
PMCID: PMC3269898  PMID: 19325180

Results 1-11 (11)