Publications by authors named "Seyed Reza Fatemi"

33 Publications

A mucinous cystadenoma in rectal cuff of a patient with familial adenomatous polyposis.

Int J Colorectal Dis 2017 Aug 28;32(8):1227-1228. Epub 2017 Feb 28.

Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Introduction: Familial adenomatous polyposis (FAP) may be associated with some extracolonic manifestations which in this vein, it is known as Gardner's syndrome. To our knowledge, so far, there is no report of mucinous cystadenoma in association with FAP.

Case Presentation: We report a 31-year-old woman with FAP who underwent total proctocolectomy with ileal pouch-anal anastomosis 5 years earlier. During endoscopic surveillance, she was found to have a submucosal lesion in rectal cuff.

Results: Endoscopic ultrasound (EUS) revealed a round submucosal anechoic lesion measuring about 3 cm originating from the second layer of the rectal cuff. Surgical resection was performed and a cystic tumor was removed. Histologic examination was consistent with mucinous cystadenoma.

Conclusion: FAP can be associated with mucinous cystadenoma.
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http://dx.doi.org/10.1007/s00384-017-2781-0DOI Listing
August 2017

Recurrence and Five -Year Survival in Colorectal Cancer Patients After Surgery.

Iran J Cancer Prev 2015 Aug 24;8(4):e3439. Epub 2015 Aug 24.

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

Background: Colorectal cancer (CRC) is a common malignancyworldwide and its outcome is most closely related to the extent of disease at presentation. Early diagnosis of an asymptomatic recurrence increases the likelihood of a complete surgical resection.

Objectives: The aim of this study was to evaluate the incidence of colorectal cancer recurrence and survival rate within 5 years, after surgery.

Patients And Methods: During the 9-year period since 21st Mar, 2004 to 20th Mar, 2013, patients whose primary colorectal cancer were resected in Taleghani hospital, Tehran, Iran were selected in a historical cohort. The necessary data such as demographic, age, gender, family history of CRC, site and size of tumor, stage of tumor, operation details, histological results, treatment method, histopathologic, etc. were collected. Then the recurrence and survival of colorectal cancer within 5 years after operation and their risk factors were evaluated. P value less than 0.05 were considered significant. All analysis was done using SPSS software.

Results: A total of 107 patients underwent resection for colorectal cancer during the study period, with mean age of 53.50 ± 12.68 years (range 24 - 76 years), survival rate of 73.8% (rectum 70.0% and colon 75.9%), and mean survival time of 142.17 ± 21.60 month. The recurrence rate of CRC patients, during five years after surgery was 5.7%. Regional lymph nodes, Distance metastasis and Adjuvant therapy were significant prognosis factors of survival after surgery.

Conclusions: The rate of recurrence in Iranian patients was low, which could be due to improvement of exactness and expertise of surgeons or better adjuvant therapy. The significant association between survival and adjuvant therapy clarifies this finding. Early diagnosis and primary detection could increase the rate of survival.
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http://dx.doi.org/10.17795/ijcp.3439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4606369PMC
August 2015

Evaluation of endoscopic characteristics of upper gastrointestinal polyps in patients with familial adenomatous polyposis.

Asian Pac J Cancer Prev 2014 ;15(16):6945-8

Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran E-mail :

Background: Familial adenomatous polyposis (FAP) is a disease inherited in an autosomal dominant fashion. Most FAP patients develop upper gastrointestinal polyps; especially those in the antrum and duodenum are usually neoplastic. The aim of this study was to evaluate the prevalence of gastroduodenal polyps in Iranian FAP patients.

Materials And Methods: 28 patients affected by FAP underwent front-view and side-view endoscopy. Papillary biopsies were performed in all patients. Location of polyps, their number and size, pathology study, patient general information (gender, age, family history of FAP or colorectal cancer and gastroduodenal polyps) were analyzed.

Results: Gastric polyps were seen in 39.3 % of patients. Some 72.7% of the affected individuals had fundic gland polyps and 36.36% had hyperplastic polyps. Duodenal adenoma was observed in 25% of patients. While 57% of patients had tubular adenoma with low grade dysplasia, 42.8% showed tubulovillous adenoma with low grade dysplasia.

Conclusions: Findings of this study indicated that the prevalence of gastroduodenal polyps in FAP patients is high and dysplasia may be evident in duodenal polyps. Therefore, it appears that routine gastroduodenal endoscopy in FAP patients is necessary.
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http://dx.doi.org/10.7314/apjcp.2014.15.16.6945DOI Listing
June 2015

The effect of 5'untranslated region polymorphism in EGF gene, rs4444903, on colorectal cancer.

Gastroenterol Hepatol Bed Bench 2013 ;6(3):129-35

Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran.

Aim: The purpose of this study was to determine the relationship of rs4444903 (EGF+61A/G) SNP genotype with colorectal cancer and tumor stage in an Iranian population.

Background: Epidermal growth factor (EGF) is one of the important proteins that determine survival of cells. EGF binds to its receptor on the cell surface and then activates some of the cell signaling pathway networks within cells that lead to activation or deactivation of factors which are responsible for growth and apoptosis of cells. In this study we assessed the association in EGF polymorphism rs4444903 with colorectal cancer (CRC) in Iranian population.

Patients And Methods: We conducted case-control study to investigate the association of polymorphism rs4444903 in EGF, with colorectal cancer risk in Iranian population. Analyzed Polymorphism of EGF rs4444903 with restriction fragment length polymorphisms (RFLP) among two groups of subjects consisting of including 220 cases with colorectal cancer and 220 healthy individuals as controls. Mutations were confirmed in 10% of the samples by direct sequencing.

Results: The frequencies of AA, AG and GG genotypes among cases with colorectal cancer were 28.2, 46.8, and 25.0 % respectively and in controls genotype frequencies were 23.2, 56.4, and 20.5 %, respectively. Frequency of A allele among case group was 51.6% and for control group was 51.4%. The frequency of G allele in case and control was, respectively 48.4% and 48.6% (OR= 1.009, 95% CI= 0.775-1.315; P= 0.946). The percentage of Stage 0, I, II, III, IV were 5%, 9.35%, 38.84%, 30.21% and 16.54%, respectively, among the cases. However, no significant association between this polymorphism and CRC stage was observed (p=0.626).

Conclusion: Our data suggest a SNP rs4444903 may not represent a risk factor in the development and progression of CRC among Iranian population.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017510PMC
May 2014

Association of co-stimulatory human B-lymphocyte antigen B7-2 (CD86) gene polymorphism with colorectal cancer risk.

Gastroenterol Hepatol Bed Bench 2013 ;6(2):86-91

Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim: This study investigated the role of CD86 +237 G/C polymorphism in intensifying the risk of CRC development.

Background: Colorectal cancer (CRC) is a multi-factorial diseases. Genetic background could affect the susceptibility of individuals to CRC development. CD86 is a co-stimulatory factor on antigen-presenting cells that plays key roles in several cancer related mechanisms such as autoimmunity, transplantation and tumor immunity.

Patients And Methods: A total of 300 individuals, 150 known CRC patients and 150 healthy control individuals, were subjected for the study. CD86 rs17281995 single nucleotide polymorphism (SNP) was genotyped using Allelic Discrimination method.

Results: A statistically significant difference was found among CD86 gene polymorphism (rs17281995) and risk of CRC development. The frequency of GG, GC and CC in control subjects was determined as 38%, 57.3% and 4.7% respectively and in CRC subjects were determined as 42%, 85% and 23% respectively. The data shows a significant association between CC genotype (P = 0.007) and C allele (P = 0.017) of the studied polymorphism and risk of CRC. CC genotype and C allele are also more frequent in female patients when the data is stratified according to gender status.

Conclusion: Our results suggest that CD86 gene alteration could affect the individual's risk for developing CRC among Iranian population and could be used as an important prognostic factor associated with risk of CRC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017506PMC
May 2014

The effect of the treatment of Helicobacter pylori infection on the glycemic control in type 2 diabetes mellitus.

Gastroenterol Hepatol Bed Bench 2013 ;6(1):36-40

Gastroenterology and Liver Disease Research Cancer, Shahid Beheshti University of Medical sciences, Tehran, Iran.

Aim: To evaluate the possible long-term effects of Helicobacter pylori infection on Hemoglobin A1c and fasting blood sugar levels in patients with type 2 diabetes.

Background: Helicobacter pylori causes the gastrointestinal tract inflammation, which it plays an important role in distortion of glucose and lipids absorption that altered lipid metabolism and energy harvesting and develops type 2 diabetes, insulin resistance and has been linked to impaired blood glucose.

Patients And Methods: In this clinical trial, patients with type 2 diabetes and confirmed Helicobacter pylori infection were recruited from the endocrinology clinic of the Shahid Beheshti University Tehran, Iran. Before and after 3 months of eradication therapy fasting blood samples were taken and glycalated hemoglobin levels and fasting blood sugar levels were measured.

Results: 85 (27 male 31.8%, 58 female 68.2%) patients with the mean age of 52.±4.7 years were recruited. 52 (62%) had successful Helicobacter pylori eradication (16 male, 30.8% and 36 female, 69.2%). The mean glycalated haemoglobin levels before successful treatment was 8.7±1.1 and after treatment was 8.3±0.9 and difference was significant (p<0.001). Mean IgG level of serology was 3.3±1.1 and the correlation with glycalated haemoglobin was significant (p=0.02) (r=0.4).

Conclusion: Our results indicate that the Helicobacter pylori treatment can improve the mean glycalated haemoglobin in patients with type 2 diabetes. More investigations will be required to evaluate the effects of Helicobacter pylori eradication among different age groups and in relation to obesity status, diabetes and other disease, and it may be beneficial for patients at risk of diabetes to be checked for the presence of Helicobacter pylori infection.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017496PMC
May 2014

Duodenal adenocarcinoma might be the cause of intractable nausea and vomiting in patient with coeliac disease.

Gastroenterol Hepatol Bed Bench 2012 ;5(4):209-12

Gastroenterology and Liver diseases Research center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Coeliac disease (CD) is an autoimmune disorder which leads to chronic inflammation of the gut. Untreated CD is associated with upper gastrointestinal malignancies, Small-bowel lymphoma and adenocarcinoma are recognized complications of untreated coeliac disease (CD). We report the case of a 43-year-old male suffering from CD who was treated with a gluten-free diet one year, presenting with complaints of intractable nausea and vomiting. After several studies, He underwent push enteroscopy, which identified one large mass lesion in the third part of duodenum. However, histopathological examination showed adenocarcinoma. Subsequently, a duodenal segment resection was performed. After surgery, the patient recovered well and left our hospital in good condition. Clinicians should take into small bowel adenocarcinoma is rare but associated with CD particularly in CD patients with worrying symptoms such as nausea and vomiting unresponsiveness to treatment and these patients should be screened for long term complications like malignancy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017469PMC
May 2014

Association of polymorphisms in microRNA-binding sites and colorectal cancer in an Iranian population.

Cancer Genet 2012 Oct 29;205(10):501-7. Epub 2012 Aug 29.

Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

MicroRNAs (miRNAs) are agents of post-transcriptional gene expression, and they can affect many functions of an individual cell or tissue from extracellular matrix production to inflammatory processes and tumor development. We aimed to determine the possible role of miRNA-binding site polymorphisms located in five cancer-related genes: IL-16, CDKN2A (p16), RAF1, PTGER4, and ITGB4 in colorectal cancer (CRC) risk modification in an Iranian population. This study was performed on 643 individuals (249 CRC cases and 394 healthy controls). We selected five cancer-related genes (IL-16, CDKN2A (p16), RAF1, PTGER4, and ITGB4) and investigated the genotypes of the 3' untranslated region miRNA-binding site polymorphisms in these genes in our study population. The restriction fragment length polymorphism results were confirmed by a direct sequencing method. We found a statistically significant difference between the rs1131445 polymorphism of the IL-16 gene and CRC. The frequencies of the genotypes TT, CT, and CC in controls were 51%, 40.4%, and 8.6%, respectively, and in cases were 41.4%, 44.1%, and 14.5%, respectively, which shows a significant association between the CC genotype of the rs1131445 polymorphism and CRC (P = 0.004). The frequency of the C allele in the CRC group was higher than in the controls, and the C allele of the rs1131445 polymorphism was found to be in association with CRC (P = 0.009). These associations remained significant after Bonferroni's correction for multiple testing. We found that the AA genotype of the rs743554 polymorphism in the ITGB4 gene and the T allele of the rs1051208 polymorphism of the RAF1 gene were associated with the risk of CRC in females; however, after Bonferroni's correction we found that they were non-significant. Finally, we can conclude that a significant relationship exists between the miRNA-binding site polymorphism of the IL-16 gene and CRC risk in the Iranian population.
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http://dx.doi.org/10.1016/j.cancergen.2012.05.013DOI Listing
October 2012

Four years incidence rate of colorectal cancer in Iran: a survey of national cancer registry data - implications for screening.

Asian Pac J Cancer Prev 2012 ;13(6):2695-8

Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran.

Introduction: Design and implementation of screening programs in each country must be based on epidemiological data. Despite the relatively high incidence of CRC, there is no nationwide comprehensive program for screening in Iran. This study was designed to investigate national CRC data and help to determine guidelines for screening.

Methods: Incidence data used in this study were obtained from Iranian annual of National Cancer Registration report. Age standardized rates (ASR)were calculated using world standard population and were categorized by age, sex, anatomic subsite and morphology of tumor. Data were analyzed using SPSS.V.13 and Open Source Epidemiologic Statistics for Public Health software (OpenEpi v.2.3.1).

Results: A quarter of cases were less than 50 years of age. The majority of tumors were detected in the colon. The overall ASR in the four years period was 38.0 per 100000 and was higher for men compared women (P<0.05). Incidence rate of colorectal cancer increased with age.

Conclusion: Results of present study indicated that incidence of colorectal cancer is relatively high in Iran. Incidence of CRC in people under 50 years and in rectum were reported higher than other countries that related etiologic factors should be investigate in further studies. According to the increasing of ASR after age 50 years, it seems that onset of screening at age 50 would be appropriate.
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http://dx.doi.org/10.7314/apjcp.2012.13.6.2695DOI Listing
February 2013

Evaluation of antibody frequency against HBV, HCV and HTLV-1.

Gastroenterol Hepatol Bed Bench 2012 ;5(3):161-5

Gastroenterology and Liver Diseases Research center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim: This study was designed to evaluate the frequency of antibody against these viruses in individuals attending the endoscopy ward of Taleghani hospital Tehran, Iran.

Background: Blood-borne viruses such as hepatitis B and hepatitis C virus and HTLV-1 virus are among the world's public health problems. Hepatitis viruses cause liver problems and HTLV-1 infection can lead to adult T-Cell lymphoma (ATL).

Patients And Methods: Blood samples of 219 individuals attending the endoscopy ward of Taleghani hospital between years 2009-2011 were collected. A questionnaire containing demographic data was completed for each subject. Blood samples were tested for antibody against HTLV-1, HCV and HBc by ELISA (Dia.pro Italy). In case of positive results for anti-HBc, samples were also tested for HBs Ag antigen.

Results: Ninety two subjects were male and 127 were female. Mean age of the population was 39.87 ± 16.47. None of the subjects had anti-HCV antibody, while 4 of them had anti-HTLV-1 antibody and 26 anti-HBc antibody; which only two of these individuals had HBs Antibody.

Conclusion: The results of this study show that frequency of anti-HCV and anti-HTLV-1 antibodies are very low, while the frequency of anti-HBc was higher in the population. Since HTLV-1 is the causative agent of a type of blood cancer, it seems that screening of donated bloods in this region should be considered.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017473PMC
May 2014

Low frequency of human T-cell lymphotropic virus 1 antibodies in Iranian gastric cancer patients in comparison to controls.

Asian Pac J Cancer Prev 2011 ;12(9):2447-50

Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

There is some evidence that human T-cell lymphotropic virus (HTLV-1) infection has a reverse association with gastric cancer (GC). Data about this association in the Iranian population are scarce. In this study we therefore assessed the frequency of anti-HTLV-1 antibody in GC patients and compare it to antibody presence in healthy individuals in Iranian population. This case control study was performed between 2008-2011 on 201 GC patients and 219 control subjects. HTLV-1 antibodies were assessed by ELISA and the positive results were confirmed by western blotting. Totals of 201 gastric cancer patients and 219 controls were enrolled in this study. The tumors in the majority of patients (45.3%) were in the distal (non-cardia) area. Mean age of patients at the time of diagnosis was 59.2±12.5 and mean age of controls was 57.7±11.3. While only one GC patient (0.5%) was positive for HTLV-1 antibody, there were four individuals (1.89%) from the control group with antibodies. In addition, smoking had statistically significant relationship with cancer (P=0.001). Our study showed that the frequency of HTLV-1 antibody in patients was lower than in controls, similar to the results obtained in Japan. Further investigations with a larger sample size are needed in order to determine the association between GC and HTLV-1 infection in Iran.
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September 2012

Simplified MSI marker panel for diagnosis of colorectal cancer.

Asian Pac J Cancer Prev 2011 ;12(8):2101-4

Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Colorectal cancers (CRCs) tumors are diagnosed by microsatellite instability (MSI) due to accumulation of insertion/deletion mutations in tandem repeats of short DNA motifs (1-6 bp) called microsatellites. Microsatellite instability (MSI) is not only a hallmark marker for screening of hereditary nonpolyposis colorectal cancer (HNPCC), but also a prognostic and predictive marker for sporadic colorectal cancer. Our objective was to determine and study of five mononucleotide microsatellite markers status among Iranian patients with HNPCC and sporadic colorectal cancer.

Materials And Methods: In the current investigation 80 sporadic CRC and 80 HNPCC patients were evaluated for MSI. The pentaplex panel including 5 quasimonomorphic mononucleotide repeats (NR-21, BAT-26, BAT-25, NR-27 and NR-24) was used.

Results: Our findings showed that the NR-21 was the most frequent instable marker among the other markers. 53% and 25.6% specimens had instability in sporadic CRC and HNPCC, respectively. Furthermore, the frequencies of instability BAT-25 was determined in 20% sporadic CRC and 23% HNPCC samples. Interestingly our results demonstrated that the frequency of instability NR-24 was similar 20% sporadic CRC and 20.5% HNPCC. Moreover, percentage of NR-27 in HNPCC was 19.2 and 0% in sporadic CRC. Finally, BAT-26 was instable in 21.8% HNPCC patients while we could find 6.6% instability for BAT-26 in sporadic cases.

Conclusion: It seems that among 5 mononucleotides markers NR-21 was the most useful marker for diagnosis HNPCC and sporadic cancer. Following NR-21, BAT-25 and NR-24 are the most reliable markers. Therefore using a triplex panel including 3 aforementioned MSI markers should be more promising markers for identifying MSI status in both patients with HNPCC and/or sporadic colorectal cancer.
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August 2012

Sporadic colorectal polyps and mismatch repair proteins.

Indian J Pathol Microbiol 2011 Oct-Dec;54(4):725-9

Department of Pathology, Research Center for Gastroenterology and Liver disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Colorectal cancers often arise from benign polyps. Adenomatous polyps and serrated polyps progress step by step to adenocarcinoma and change into malignant cancers. Genetic and epigenetic changes have correlation with specific stages of polyp-adenocarcinoma progression and colorectal cancer histopathological changes.

Aims: In this study we used immunohistochemistry (IHC) staining in sporadic colorectal polyps to assay functional status of MLH1, MSH2, MSH6, and PMS2 proteins, to track genetic/epigenetic roles of this issue in our patients.

Materials And Methods: In this cross-sectional study we assessed all patients who were admitted with sporadic colorectal polyps and underwent polypectomy in endoscopy department during 2004-2008.

Result: IHC results were abnormal in 6.8% cases for MLH1, in 4.5% cases for MSH2, in 3% for MSH6, and in 4.8% for PMS2. In all cases with abnormal PMS2, MLH1 was also reported as abnormal. Same results were reported for abnormal MSH2, which is accompanied with abnormal MSH6 in all cases (P values < 0.001). There is no significant difference between IHC staining results, gender, dysplasia grade, adenomatous type, and invasion. On the other hand, there was significant difference between IHC staining results, polyp location, and mean age of patients. The same significant difference was between adenomatous polyps and serrated adenoma polyps by MLH1 and PMS2 (P values < 0.05).

Conclusion: According to our findings, maybe MMR dysfunction is the cause of sporadic colorectal polyps in younger age and its increasing risk of dysplasia progression and malignancy progression is only in serrated adenoma. Sporadic polyps in left colon had a higher risk to progress to malignancies, and abnormal IHC staining for MLH1 and PMS2 in serrated polyps is much more than in other adenomatous polyps.
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http://dx.doi.org/10.4103/0377-4929.91505DOI Listing
April 2012

Interleukin-16 (IL-16) gene polymorphisms in Iranian patients with colorectal cancer.

J Gastrointestin Liver Dis 2011 Dec;20(4):371-6

Research Center for Gastroenterology and Liver Diseases-Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background And Aims: A number of theories have been put forward to clarify the etiology of colorectal cancer (CRC), such as genetic alterations and cytokine production. A combination of inflammatory cytokines has an important role in cancer development. The aim of our study was to screen for alterations located in promoter and exons of IL-16 gene sequence, to determine the distribution of genotypes in individuals with CRC and healthy controls in a sample of Iranian population.

Methods: The case group consisted of 260 individuals with colorectal cancer and the control group included 405 healthy individuals. Three IL-16 gene polymorphisms (rs4072111, rs11556218, rs4778889) were genotyped using PCR-RFLP method. RFLP results were confirmed by direct sequencing.

Results: A significant association between rs11556218 SNP in the IL-16 gene and the risk of CRC was found. The TG genotype of rs11556218 T/G polymorphism showed significant association with a 1.75 fold increased risk of CRC (P=0.005; adjusted OR: 1.759; 95% CI: 1.191-2.598). In addition a significant association between CC genotype of rs4778889 T/C polymorphism and decreased risk of CRC in male subjects (P=0.045; adjusted OR: 0.192; 95% CI: 0.038-0.967) was determined.

Conclusion: This study is the first report of IL-16 gene polymorphisms among CRC patients from Iran. Our results suggest an influence of rs11556218 T > G and rs4778889 T/C polymorphisms on the altered risk of CRC.
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December 2011

Multivariate analysis of prognostic factors in gastric cancer patients using additive hazards regression models.

Asian Pac J Cancer Prev 2011 ;12(7):1697-702

Department of Biostatistics, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.

Background And Objectives: Gastric cancer is the second leading cause of cancer death worldwide and is the most common type of cancer in Iran. The objective of this paper is to apply the additive hazards models to the study of survival of patients with gastric cancer and to compare results obtained by the additive hazards models and the Cox model.

Methods: We retrospectively studied 213 patients with gastric cancer who were registered in one referral cancer registry center in Tehran, Iran. Age at diagnosis, sex, presence of metastasis, tumor size, histology type, lymph node metastasis, and pathologic stages were entered into analysis using the Cox model and additive hazard models. To visualize a covariate effect over time, the estimated cumulative regression function by the Aalen's model is examined.

Results: The five-year survival rate and the median life expectancy in the studied patients were 14.6% and 29.6 months, respectively. Multivariate Cox and Additive hazards models analysis identified that age at diagnosis, tumor size and pathologic stage were independent prognostic factors for the survival of patients with gastric cancer (P<0.05). Moreover, pathologic stage has a late or delayed effect according to the Aalen's plot. Other clinicopathological characteristics were not statistically significant (P<0.05).

Conclusion: Since Cox and additive models give different aspects of the association between risk factors and the study outcome, it seems desirable to use together to give a more comprehensive understanding of data. Our results also suggest that early detection of patients at younger age and in primary stages is important to increase survival of patients with gastric cancer.
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July 2012

Does the prognosis of colorectal cancer vary with tumor site?

Gastroenterol Hepatol Bed Bench 2011 ;4(4):199-209

Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim: The aim of this study was to compare prognostic factors between colon and rectal cancers.

Background: Prognosis of Colorectal Cancer (CRC) may depend on the anatomical site.

Patients And Methods: A total of 1219 patients with CRC diagnosis according to the pathology report of RCGLD cancer registry, from 1 January 2002 to 1 October 2007, were entered into the study. Demographic and clinico-pathological factors were analyzed using survival analysis.

Results: From age at diagnosis, colon cancer had significantly better survival than rectal cancer (Multivariate Hazard Ratio (MVHR)=0.24; 95% Confidence Interval (CI) =(0.074-0.77)). Other factors, including marital status (MVHR =1.78; 95% CI =(0.33-9.62)), body mass index (BMI) (MVHR =1.21 and 1.54; 95% CI =(.30-4.85) and (.44-5.4) respectively for < 18.5 and >30 BMI groups), pathologic stage (MVHR =.64; 95% CI =(.21-1.98)) and alcohol history (MVHR =4.86; 95% CI =(.67-35.14)) were not significantly different between the two patient group but suggested a possible effect upon prognosis. Overall survival in rectum was better than that of colon.

Conclusion: Our findings support this hypothesis that prognosis of CRC varies with tumor site.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017433PMC
May 2014

Association of leptin receptor gene Gln223Arg polymorphism with susceptibility to colorectal cancer.

Gastroenterol Hepatol Bed Bench 2011 ;4(4):192-8

Iranian Ostomy Society, Tehran, Iran.

Aim: Leptin is a 16 kDa polypeptide hormone which secreted by adipose tissue and has an important role in energy balance, insulin pathway and inflammation, because of that it may play an important role in colorectal cancer (CRC). Leptin exerts its effect through the leptin receptor (LEPR) a member of the class I cytokine receptor family.

Background: We have investigated whether glutamine to arginine substitution (Gln223Arg) in exon 6 of the leptin receptor gene, has implications for susceptibility to CRC.

Patients And Methods: Polymerase chain reaction (PCR) and restriction enzyme digestion (RFLP) was performed to evaluate the association between the Gln223Arg polymorphism of the LEPR and CRC risk in a case-control study in 346 subjects involving 173 cases with CRC and 173 controls.

Results: There was no statistically evidence of significant difference in genotype and allele frequencies between the cases with CRC and controls for the Gln223Arg polymorphism of LEPR, before or after adjusting for confounders (age, BMI, sex, and smoking status). Furthermore, no significant difference was observed between the CRC cases and controls by BMI, sex and smoking status.

Conclusion: Our findings suggest that the LEPR Gln223Arg polymorphism is not associated with the risk of CRC in Iranian population.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017430PMC
May 2014

Patterns of survival for anatomical sites of colorectal cancer with shift to advanced lesions in Iran.

Asian Pac J Cancer Prev 2011 ;12(5):1225-31

Department of Nursing Management, Faculty of Nursing and Midwifery, Islamic Azad University, Karaj Branch, Karaj, Iran.

Background: With a background of disparities in colorectal cancer (CRC) incidences/mortality across countries due to differences in exposure to various prognostic factors, this study aimed to evaluate the site-specific pattern for the survival of colon and rectal patients.

Methods: A total of 1,283 patients with CRC diagnosis according to the pathology report of cancer registry of RCGLD from 1 January 2002 to 1 October 2007, were entered into the study. Data were analyzed using univariate and multivariate competing risk survival analysis.

Results: Survival proportion of patients showed a significant trend for 1, 3 and 5 year survival in colon cancer (P< 0.001) but this wasn't significant for rectal cancer (P=0.078). Tumor grade and pathologic stage were the most important factors predicting the survival in colon and rectal cancers with stronger hazard in the rectal site for grade and stronger hazard in the colon site for stage. For colon site, in the well and moderate categories of tumor grade, shifting from early to advance stage and also shifting in tumor grade from well and moderate categories to poor tumor grade had a considerable effect in hazard ratios. For rectum site, well to moderate shifting in tumor grade increased the hazard of death and shifting from early to advance stage increased the hazard equal to 2.54 and 4.36 times within the well and moderate tumor differentiation, respectively. In shifting to advance CRC, colon site had generally worse hazard than the rectum.

Conclusion: Due to the worse conditions of CRC patients as shifting to advance cancer, to improve the effectiveness of treatment and hence the survival of Iranian patients, we should pay more attention to early detection, in particular by implementing population based screening programmes.
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May 2012

Multivariate analysis of prognostic factors in gastric cancer patients using additive hazards regression models.

Asian Pac J Cancer Prev 2011 ;12(4):901-7

Department of Biostatistics, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.

Background And Objectives: Gastric cancer is the second leading cause of cancer death worldwide and is the most common type of cancer in Iran. The objective of this research was to apply additive hazards models to the study of survival of patients with gastric cancer and to compare with results obtained using the Cox model.

Methods: We retrospectively studied 213 patients with gastric cancer who were registered in one referral cancer registry center in Tehran, Iran. Age at diagnosis, sex, presence of metastasis, tumor size, histology type, lymph node metastasis, and pathologic stages were entered into analysis using the Cox model and additive hazard models. To visualize a covariate effect over time, the estimated cumulative regression function by the Aalen's model was examined.

Results: The five-year survival rate and the median life expectancy in the studied patients were 14.6% and 29.6 months, respectively. Multivariate Cox and Additive hazards models analysis identified age at diagnosis, tumor size and pathologic stage as independent prognostic factors for the survival of patients with gastric cancer. Moreover, pathologic stage had a late or delayed effect according to the Aalen's plot. Other clinicopathological characteristics were not statistically significant.

Conclusion: Since Cox and Aalen models give different aspects of the association between risk factors and the study outcome, it seems desirable to use then together to give a more comprehensive understanding of data. Our results also suggest that early detection of patients at younger age and in primary stages is important to increase survival of patients with gastric cancer.
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July 2012

The role of kras mutations and MSI status in diagnosis of colorectal cancer.

Gastroenterol Hepatol Bed Bench 2011 ;4(2):70-5

Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim: The aim of the current investigation was to examine the profile of Kras mutations accompanied with MSI (microsattelite instability) status in polyps and colorectal carcinoma tissues in an Iranian population.

Background: Kras mutations in colorectal cancer cause resistance to anti-Epidermal Growth Factor Receptor (EGFR). So it can be considered as a true indicator of EGFR pathway activation status. Kras mutations can be detected in approximately 30% to 40% of all patients with colorectal cancer. The most hot spot of the gene is located in exons 2 and 3.

Patients And Methods: In this study we examined exons 2 and 3 Kras gene using polymerase chain reactions and subsequent sequencing of the exons in 95 patients with sporadic colorectal cancer including 48 tumors and 47 polyps. This study was performed using biopsy samples from the patients. We sequenced the Kras gene in a panel of human colorectal tumors and polyps in addition to detecting MSI status using fluorescent technique.

Results: We could detect 6 mutations in tumors including 5 mutations in codon 12 and one mutation in codon 13. Moreover, in polyps 2 mutations were determined in codon 13 and one in codon 12. Microsatellite instability assay revealed the presence of 5 and 6 MSI in tumors and polyps, respectively. Among the MSI mononucleotide markers, NR-21 marker demonstrated the most frequency (60%) in the both groups.

Conclusion: Our findings showed that probably the profile of mutations in tumors is not entirely compatible with the pattern of mutations in polyps. However, just one of the mutations, Gly12Asp, was similar in both groups.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017411PMC
May 2014

Colonoscopy screening results in at risk Iranian population.

Asian Pac J Cancer Prev 2010 ;11(6):1801-4

Research Center for Gastroenterology and Liver Disease of Shahid Beheshtee University, Tehran, Iran.

Objectives: To investigate the prevalence of colorectal adenomas and other advanced lesions in first degree relatives of Iranian patients diagnosed with colorectal cancer by colonoscopy and pathologic evaluation.

Methods: Iranian colorectal cancer patients (probands) were identified through pathologic reports of the regional cancer registry. First degree relatives (siblings, parents and offspring) of probands were evaluated for the existence of polyps and precancerous lesions via colonoscopy screening. Control patients were chosen among average risk population with no family history of colorectal cancer who agreed to colonoscopy screening.

Results: A total of 184 subjects underwent colonoscopy screening from April 2007 to March 2009. From 90 cases among families of probands, 70 (77.8%) had a normal colonoscopy result, 18 (20%) demonstrated polyps and 2 (2.2%) were diagnosed with colorectal cancer. Colonoscopy screening in 94 average risk control patients discovered polyps in 4 (4.3%) cases and the other 90 (95.7%) patients had normal total colonoscopy results. Mean age of cases with advanced lesions was 48.4∓10.2 and 41.5∓18.4 in control patients with polyps. The incidence of polyps was significantly higher in males, and in family case patients compared to controls.

Conclusions: Based on colonoscopy screening, the prevalence of colorectal adenoma and precancerous lesions in first degree relatives of patients diagnosed with colorectal cancer is significantly higher than in the average risk population.
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July 2011

Frequent MSI mononucleotide markers for diagnosis of hereditary nonpolyposis colorectal cancer.

Asian Pac J Cancer Prev 2010 ;11(4):1033-5

Science and Research Branch, Islamic Azad University (IAU), and Research Center for Gastroenterology and Liver Diseases, Taleghani Hospital, Tehran, Iran.

Background: Failure in the DNA mismatch repair system is commonly accompanied by microsatellite instability and leads to colorectal cancer. The aim of this study was to find the most frequent of five mononucleotide markers in order to devise the simplest diagnostic strategy for identification of patients with hereditary nonpolyposis colorectal cancer (HNPCC) who were defined by defects in mismatch repair system.

Materials And Methods: 78 patients with colorectal cancer were recruited for this investigation. Five mononucleotide markers, NR-27, NR-21, NR-24, BAT-25 and BAT-26, were used as a pentaplex panel to determine MSI status.

Results: Two out of five mononucleotide markers, NR-21 (25.6%) and BAT-25 (23.1%) showed more instability than the others.

Conclusion: In defining individuals with colorectal cancer, BAT25 and NR-21 may provide diagnostic assistance.
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April 2011

Start codon FokI and intron 8 BsmI variants in the vitamin D receptor gene and susceptibility to colorectal cancer.

Mol Biol Rep 2011 Oct 4;38(7):4765-70. Epub 2010 Dec 4.

Department of Cancer, Research Center for Gastroenterology and Liver Diseases (RCGLD), Shahid Beheshti University of Medical Sciences, Velenjak, Shahid Chamran Highway, 1985711151 Tehran, Iran.

Epidemiological evidence suggests the protective effect of vitamin D against colorectal cancer (CRC) and the polymorphisms in vitamin D receptor (VDR) gene may influence the development of CRC. In this study the possible association of VDR FokI and BsmI gene polymorphisms with CRC risk was examined. A total of 904 subjects, including 452 cases with CRC and 452 controls were enrolled in this study. All 904 subjects were genotyped for VDR FokI and BsmI gene polymorphisms by PCR-RFLP method. We observed no significant difference in genotype and allele frequencies between the cases with CRC and controls for the both FokI and BsmI polymorphisms either before or after adjustment for confounding factors including age, BMI, sex, and smoking status. Furthermore, no evidence for effect modification of the association VDR gene FokI and BsmI variants and CRC by BMI, sex, or tumor site was observed. In addition, there was no significant difference in genotype and allele frequencies between the normal weight (BMI <25 kg/m(2)) cases with CRC and overweight/obese (BMI ≥25 kg/m(2)) cases with CRC for the two SNPs. Our results do not lend support to the hypothesis that VDR gene FokI and BsmI polymorphisms are associated with the risk of CRC. However, further studies are required to confirm this finding.
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http://dx.doi.org/10.1007/s11033-010-0613-1DOI Listing
October 2011

Profile and frequency of p53 gene alterations in gastritis lesions from Iran.

Digestion 2011 29;83(1-2):65-75. Epub 2010 Oct 29.

Research Center for Gastroenterology and Liver Diseases, Shaheed Beheshti Medical University, Tehran, Iran.

Background: It has been frequently shown that p53 alterations have an important role in the development of gastric cancers but there is no data on p53 alteration in gastric cancer and its precancerous lesions from Iran although this country experiences one of the highest gastric cancer incidence and mortality rates in the world. The purpose of this study was to do a comprehensive assessment of p53 alterations in the Iranian population of gastritis patients and to evaluate the association between p53 alterations, microsatellite status and clinicopathological aspects.

Methods: After DNA extraction, PCR sequencing was done for exons 2-7. Also microsatellite status was evaluated using five microsatellite markers: NR-27, NR-21, NR-24, BAT-25 and BAT-26.

Results: The highest rate of alteration was seen in codons 72 (85.6%, SNP) and 248 (30.9%, mutation). Also, we found 2 new mutations in codons 9 and 146. In contrast with previous work, transition at the CpG codons was relatively rare. Nucleotide alterations were more prevalent in the Helicobacter pylori-positive group but not significantly. Neither nuclear staining for p53 protein nor microsatellite instability was seen in gastritis lesions.

Conclusion: p53 alterations might contribute to the pathogenesis of gastritis and perhaps gastric cancer in Iran. However, the different spectrum seen here implies other mechanism(s) in gastritis and gastric cancer development in the Iranian population.
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http://dx.doi.org/10.1159/000320690DOI Listing
March 2011

Mucins in neoplastic spectrum of colorectal polyps: can they provide predictions?

BMC Cancer 2010 Oct 7;10:537. Epub 2010 Oct 7.

Research Institute for Gastroenterology and Liver Diseases, Taleghani Hospital, Shahid Beheshti University, MC, Tehran, Iran.

Background: The significance of expression of different mucins in succession of malignant transformation of colorectal polyps is not determined yet. The aim of the present study was to determine the pattern of expression of MUC1, MUC2, MUC5AC and MUC6 in colorectal polyps and to evaluate the applicability of using mucin expression in predicting the extent of malignant transformation in colorectal polyps.

Methods: A total of 454 polyp specimens comprising 36 hyperplastic polyps, 15 serrated adenomas, 258 tubular adenomas, 114 tubulovillous adenomas, and 31 villous adenomas were included in this study, and were immunostained for MUC1, MUC2, MUC5AC and MUC6 by using mucin specific antibodies.

Results: MUC1 and MUC6 were absent in all hyperplastic polyps and their expression was higher in serrated and traditional adenomas. Only 5 cases including 2 serrated adenomas, 1 tubulovillous adenoma, and 2 villous adenomas stained negative for MUC2. The highest expression of MUC5AC was observed in serrated adenomas followed by tubular adenomas. Binary logistic regression analysis indicated that positive staining for MUC1, and MUC6, and negative staining for MUC2 would increase the risk of invasion to mucosa or the muscularis mucosae in colorectal polyps. Ordinal regression analysis demonstrated a positive association between the level of staining for MUC1 and risk of being of high configuration/grade in colorectal polyps.

Conclusions: MUC1, MUC2, MUC5AC, and MUC6 have the potential to be used as predictors of malignant transformation and invasion to mucosa or the muscularis mucosae in colorectal polyps. The most reliable predictions can be achieved by determining the level of expression of MUC1.
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http://dx.doi.org/10.1186/1471-2407-10-537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958948PMC
October 2010

Impact of EXO1 polymorphism in susceptibility to colorectal cancer.

Genet Test Mol Biomarkers 2010 Oct 20;14(5):649-52. Epub 2010 Sep 20.

Research Center for Gastroenterology and Liver Diseases, Taleghani Hospital, Shaheed Beheshti Medical University, Tehran, Iran.

Background And Aim: One candidate gene for colorectal cancer (CRC) susceptibility is exonuclease 1 (EXO1). It is a member of RAD2 nuclease family, which plays a major role in mismatch repair, DNA replication, and recombination. Single-nucleotide polymorphisms are shown to be related with cancer incidence. The aim of the present study was to examine the association between the L757P polymorphism at exon 13 of the EXO1 gene and the risk of CRC in Iranian patients.

Methods: In this case-control study, 90 cases and 98 healthy control samples were analyzed genetically. The EXO1 polymorphism, P757L, was analyzed by polymerase chain reaction-restriction fragment length polymorphism. The obtained polymorphisms were examined for the relationship with CRC risk and also clinicopathological characteristics.

Results: Our findings showed that patients with the Leu/Leu genotype have a reduced risk of CRC (adjusted odds ratio [OR] = 0.192, 95% confidence interval [CI]: 0.040-0.921) when the Pro/Leu and Pro/Pro genotypes were blended and they were considered as the reference. The Leu/Leu genotype also showed a reduced risk (adjusted OR = 0.168, 95% CI: 0.034-0.816) when the Pro/Pro genotype was a reference; nevertheless, the Pro/Leu genotype did not reveal a significant association with CRC at the same status (adjusted OR = 0.686, 95% CI: 0.367-1.284).

Conclusions: Our results provide evidence diagnosing that the Leu/Leu genotype of EXO1 showed an inverse association with CRC. In addition, despite other investigations, we could define a significant association between the Leu allele and CRC (p = 0.001).
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http://dx.doi.org/10.1089/gtmb.2010.0034DOI Listing
October 2010

Parametric model to analyse the survival of gastric cancer in the presence of interval censoring.

Tumori 2010 May-Jun;96(3):433-7

Department of Biostatistics, Tarbiat Modares University, Tehran, Iran.

Aims And Background: The objective of the study was to assess the impact of prognostic factors on survival of patients with gastric cancer in the presence of interval censoring using parametric models.

Methods And Study Design: In a retrospective cohort study, 178 patients with gastric cancer were studied from February 2003 to January 2008. Gender, age at diagnosis, distant metastasis, tumor size, histology type, tumor grade, lymph node metastasis and pathologic stage were selected as prognostic and entered in the models. Weibull, exponential, log-logistic and log-normal analyses with interval censoring were performed as parametric models, and Akaike Information Criterion (AIC) was used to compare the efficiency of models.

Results: The risk of death for patients at an older age, with tumor size greater than 35 mm, distant metastasis and advanced stage of disease was statistically higher. Other clinical and demographic factors were not significant. According to AIC, the log logistic model is the most efficient of all the models in multivariable analysis.

Conclusions: The results indicated that the early detection of a cancer at a young patient age and in primary stages is important to increase survival from gastric cancer. According to statistical criteria, a parametric model can also be a useful statistical model to find prognostic factors in the presence of interval censoring. Although it seems that all models in this analysis fit well, AIC supported the log logistic regression as the best option.
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September 2010

Prevalence of colorectal cancer in relatives of Iranian patients diagnosed with colorectal cancer.

Asian Pac J Cancer Prev 2010 ;11(1):91-3

Research Center for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Science, Tehran, Iran.

Background: A high rate of colorectal cancer occurrence is established in individuals with a positive family history of this type of cancer.

Objectives: The aim of this study was to investigate the prevalence of colorectal cancer in first degree and second degree relatives of colorectal cancer patients.

Methods: Family medical histories of 489 first degree relatives of colorectal cancer patients were obtained by a questionnaire. 249 average risk patients with no family history of colorectal cancer were included as control patients.

Results: In our study from a total of 489 case patients, 153 (31.3%) had at least one close relative affected by colon cancer. Case-control analysis showed an odd ratio of 3.1 (95% CI, 2.07 to 6.27) for one and 5.7 (CI, 2.39 to 13.56) for two affected relatives. Cases with a positive family history had a 3.006 times greater risk in developing colorectal cancer if a first degree relative was affected comparing with a 4.9 times greater risk if a second degree family member was diagnosed with colorectal cancer. Our study indicated a higher risk for developing colorectal cancer in male family relatives 50 years and older. Rectal area was found the most tumor side affected in case and control patients.

Conclusion: First-degree relatives of patients with colorectal cancer had an increased risk of developing this type of cancer. The risk was greater when diagnosis was in male, elderly patients and other first-degree relatives were affected.
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November 2010

Bayesian analysis for survival of patients with gastric cancer in Iran.

Asian Pac J Cancer Prev 2009 ;10(5):823-6

Department of Biostatistics, Tarbiat Modares University, Tehran, Iran.

Background And Objectives: Gastric cancer is one of the most common cancers in the world. The aim of this study was to evaluate prognostic factors using Bayesian interval censoring analysis.

Methods: This is a historical cohort study of 178 patients from February 2003 through January 2008, admitted with gastric cancer to one referral hospital in Tehran. Age at diagnosis, sex, histology type, tumor grade, tumor size, pathologic stage, lymph node metastasis and distant of metastasis were entered into the analysis using Bayesian Weibull and Exponential models. The term DIC was employed to find best model.

Results: The results showed that as age increased, the risk of death slightly increased significantly in both Weibull and Exponential models with similar results. Patients with grater tumor size were also in higher risk of death followed by advanced pathologic stage. Neither the Weibull nor the Exponential models found sex, distant metastasis, histology type, tumor grade and lymph node metastasis to be prognostic factors. Based on DIC, Bayesian analysis of the Weibull model performed better than the Exponential model.

Conclusion: According to these results the early detection of patients at lower ages and in primary stages is important to increase the survival in cases with gastric cancer.
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May 2010

Vitamin D receptor gene ApaI polymorphism is associated with susceptibility to colorectal cancer.

Dig Dis Sci 2010 Jul 1;55(7):2008-13. Epub 2009 Oct 1.

Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objectives: The purpose of this study was to investigate vitamin D receptor (VDR) gene ApaI and TaqI polymorphisms in relation to the risk of colorectal cancer (CRC) in the Iranian population.

Methods: Two single nucleotide polymorphisms in intron 8 (ApaI) and exon 9 (TaqI) of the VDR gene were genotyped in 160 subjects with CRC and 180 controls by use of the PCR-RFLP method.

Results: The VDR ApaI genotype distribution differed significantly between subjects with CRC and controls. The ApaI "aa" genotype compared with "AA" genotype was associated with a 2.3-fold increased risk of CRC (P = 0.014; OR = 2.25, 95% CI = 1.18-4.28) and the difference remained significant after adjustment for age, BMI, sex, and smoking status (P = 0.014; OR = 2.32, 95% CI = 1.19-4.54). Furthermore, the ApaI "a" allele was significantly overrepresented in subjects with CRC than controls (P = 0.014; OR = 1.48, 95% CI = 1.08-2.02).

Conclusions: These findings suggest that VDR ApaI genotype "aa" is associated with increased risk of CRC in the Iranian population. However, these data remain to be confirmed in larger studies and in other populations.
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http://dx.doi.org/10.1007/s10620-009-0989-8DOI Listing
July 2010