Polymorphism of SMAD 7 gene [rs2337104] and risk of colorectal cancer in an Iranian population: a case-control study

The purpose of this study was to evaluate the influence of intronic polymorphism of the SMAD7 [Mothers Against Decantaplegic Homolog 7] gene [rs2337104] on the risk of colorectal cancer [CRC] and clinicopathological features in an Iranian population. SMAD7 has been identified as an antagonist of transforming growth factor beta [TGF-b]-mediating fibrosis, carcinogenesis, and inflammation. Regarding to the recent genome-wide scan, a risk locus for colorectal cancer at 18q21 has been found, which maps to the SMAD7 gene. This case-control study was performed on 109 CRC patients and 109 healthy controls recruited in Taleghani Hospital. The genotyping of all samples were done by TaqMan assay via an ABI 7500 Real Time PCR System [Applied Biosystems] with DNA from peripheral blood. The association of this polymorphism with the risk of CRC and clinico pathological features was investigated. Our results indicated that there were no significant association between genotypic and allelic frequencies of SMAD7 polymorphism [rs2337104] and CRC risk in our population. Although the T allele is the most frequent one in this population and its frequency was 86.7% in patients compared with 91.7% in controls [OR=1.705, 95% CI= 0.916-3.172]. Also, the SMAD7 genotypes were not associated with any clinicopathological characteristics in CRC patients [P>0.05]. For the first time, this study results revealed that this SMAD7 polymorphism couldn't be a potential risk factor for CRC or a prognostic biomarker for prediction of clinicopathological features in an Iranian population. A large-scale case-control study is needed to validate our results

role of Kras mutations and MSI status in diagnosis of colorectal cancer

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. 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. 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. 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. 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

New variations in the promoter regions of human DOCK 4 and RAP1A genes, and coding regions of rap1a in sporadic breast tumors

Breast cancer is the most common cancer among women in developed countries. The prevalence of the disease is increasing in the world. Its annual incidence among Iranian women is about 7000 cases. RAP1A, a tumor suppressor gene, is located at 1p13.3 and plays an important role in the cellular adhesion pathway and is involved in the pathogenesis of breast cancer. The DOCK4 gene, which is located at 7q31.1, specifically activates RAPlA gene. In the present study, DNA samples from 64 cases of sporadic breast tumors [referred to Mehrad Hospital in Tehran] were screened using PCR-SSCP method and the number of observed variations compared with the control group [100 normal women]. Mutation detection for coding exons of RAP1A gene and the 500 bp upstream of transcription initiation site as promoters of both DOCK4 and RAPlA were carried out and compared with the control group. The promoter region of DOCK4 showed a heterozygous mutation with G>A transition at nucleotide -303 in a fibroadenoma case. With regard to RAPlA we found a heterozygous mutation, G>A transition in an adenoid cystic carcinoma case, and another heterozygous mutation, G>T transversion in an intraductal papilloma case both at nucleotide +45. A homozygous variation, T>A transversion was also found at nucleotide +29 of a fibroadenoma case. The differences in the frequency of variations mentioned above were not statistically significant. However Fisher's exact showed significant difference for T>A transversion. Although, the higher frequency of these mutations and variations may be related to the disease, a larger sample size is needed for the confirmation of our findings