-Patterns of food and nutrient consumption in northern Iran, a high-risk area for esophageal cancer.
Islami F, Malekshah AF, Kimiagar M, Pourshams A, Wakefield J, Goglani G, Rakhshani N, Nasrollahzadeh D, Salahi R, Semnani S, Saadatian-Elahi M, Abnet CC, Kamangar F, Dawsey SM, Brennan P, Boffetta P, Malekzadeh R.
Nutr Cancer. 2009;61(4):475-83
Our objectives were to investigate patterns of food and nutrient consumption in Golestan province, a high-incidence area for esophageal cancer (EC) in northern Iran. Twelve 24-h dietary recalls were administered during a 1-yr 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 12 recalls. 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. 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.
-Candidate gene association study of esophageal squamous cell carcinoma in a high-risk region in Iran.
Akbari MR, Malekzadeh R, Shakeri R, Nasrollahzadeh D, Foumani M, Sun Y, Pourshams A, Sadjadi A, Jafari E, Sotoudeh M, Kamangar F, Boffetta P, Dawsey SM, Ghadirian P, Narod SA.
Cancer Res. 2009 Oct 15;69(20):7994-8000. Epub 2009 Oct 13.
There is a region with a high risk for esophageal squamous cell carcinoma (ESCC) in the northeast of Iran. Previous studies suggest that hereditary factors play a role in the high incidence of cancer in the region. We selected 22 functional variants (and 130 related tagSNPs) from 15 genes that have been associated previously with the risk of ESCC. We genotyped a primary set of samples from 451 Turkmens (197 cases and 254 controls). Seven of 152 variants were associated with ESCC at the P = 0.05 level; these single nucleotide polymorphisms were then studied in a validation set of 549 cases and 1,119 controls, which included both Turkmens and non-Turkmens. The association observed for a functional variant in ADH1B was confirmed in the validation set, and that of a tagSNP in MGMT, the association was borderline significant in the validation set, after correcting for multiple testing. The other 5 variants that were associated in the primary set were not significantly associated in the validation set. The histidine allele at codon 48 of ADH1B gene was associated with a significantly decreased risk of ESCC in the joint data set (primary and validation set) under a recessive model (odds ratio, 0.41; 95% confidence interval, 0.29-0.76; P = 4 x 10(-4)). The A allele of the rs7087131 variant of MGMT gene was associated with a decreased risk of ESCC under a dominant model (odds ratio, 0.79; 95% confidence interval, 0.64-0.96; P = 0.02). These results support the hypothesis that genetic predisposition plays a role in the high incidence of ESSC in Iran.
-Downregulation of HLA class II molecules by G1896A pre-core mutation in chronic hepatitis B virus infection.
Mohamadkhani A, Sotoudeh M, Bowden S, Poustchi H, Jazii FR, Sayehmiri K, Malekzadeh R.
Viral Immunol. 2009 Oct;22(5):295-300
Over the past decade, increasing attention has been focused on the contribution of naturally occurring mutations in the hepatitis B virus (HBV) genome to the clinical course of the chronic infection. The aim of this study was to investigate the effect of the HBV pre-core mutation G1896A on the expression of HLA class II molecules and the core protein of hepatitis B in liver biopsies of chronic hepatitis B (CHB) infection. In 30 HBeAg-negative CHB patients the pre-core region of the HBV genome was amplified and sequenced to determine the presence of the mutation G1896A. Liver biopsies were scored based on the Histology Activity Index (HAI) system and immunohistochemistry (IHC) was performed to study the expression of HLA class II molecules on the antigen-presenting cells and the core protein in hepatocytes. We found that 19 of the 30 patients (63%) harbored the G1896A mutation. Compared to the patients without this mutation, those with G1896A had lower HAI scores (5.0 +/- 2.8 versus 7.9 +/- 4, p = 0.03). The study of the expression of HLA-II molecules in our patients revealed that subjects with the G1896A mutation had lower expression of HLA-II compared to wild-type infected subjects (1.87 +/- 0.6 versus 3.27 +/- 1.5, p < 0.01). Core protein expression was present in four patients (13.3%) who had higher HBV DNA levels than patients without core protein expression (3.81 +/- 0.78 versus 2.02 +/- 0.16, p < 0.001). These results suggest that the G1896A pre-core mutation may directly interfere with antigen presentation, most likely by decreasing the availability of HLA class II molecules, and this may result in less aggressive liver disease in HBeAg-negative CHB infection.
-Oesophageal cancer in Golestan Province, a high-incidence area in northern Iran - A review.
Islami F, Kamangar F, Nasrollahzadeh D, Møller H, Boffetta P, Malekzadeh R.
Eur J Cancer. 2009 Oct 1. [Epub ahead of print]
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.
