Let-7a-3p overexpression increases chemosensitivity to carmustine and synergistically promotes autophagy and suppresses cell survival in U87MG glioblastoma cancer cells.

In terms of primary brain tumors, glioblastoma is one of the most aggressive and common brain tumors. The high resistance of glioblastoma to chemotherapy has made it vital to find alternative treatments and biological mechanisms to reduce the survival of cancer cells. Given that, the objective of the present research was to explore the potential of let-7a-3p when used in combination with carmustine in human glioblastoma cancer cells. Based on previous studies, the expression of let-7a is downregulated in the U87MG cell line. Let-7a-3p transfected into U87MG glioblastoma cells. Cell viability of the cells was assessed by MTT assay. The apoptotic induction in U87MG cancerous cells was determined through the utilization of DAPI and Annexin V/PI staining techniques. Moreover, the induction of autophagy and cell cycle arrest was evaluated by flow cytometry. Furthermore, cell migration was evaluated by the wound healing assay while colony formation assay was conducted to evaluate colony formation. Also, the expression of the relevant genes was evaluated using qRT-PCR. Transfection of let-7a-3p mimic in U87MG cells increased the expression of the miRNA and also increased the sensitivity of U87MG cells to carmustine. Let-7a-3p and carmustine induced sub-G1 and S phase cell cycle arrest, respectively. Combination treatment of let-7a-3p and carmustine synergistically increased arrested cells and induced apoptosis through regulating involved genes including P53, caspase-3, Bcl-2, and Bax. Combined treatment with let-7a-3p and carmustine also induced autophagy and increased the expression of the ATG5 and Beclin 1 (ATG6). Furthermore, let-7a-3p combined with carmustine inhibited cell migration via decreasing the expression of MMP-2. Moreover, the combination therapy decreased the ability of U87MG to form colonies through downregulating CD-44. In conclusion, our work suggests that combining let-7a-3p replacement therapy with carmustine treatment could be considered a promising strategy in treatment and can increase efficiency of glioblastoma chemotherapy.

The evaluation of the possibility of Li-Fraumeni syndrome in cancer patients in East Azarbaijan Province of Iran.

INTRODUCTION: In 1969, Li-Fraumeni syndrome (LFS), which is a rare cancer predisposition syndrome, was reported for the first time. The main problem in LFS is the mutation in the TP53 gene, which is a crucial tumor suppressor gene in the cell cycle. A hereditary syndrome is inherited in an autosomal dominant pattern. There is a significant correlation between this syndrome and various cancers such as sarcoma, breast cancer, brain tumors, and different other types of malignancies. This study aimed to identify the possibility of LFS in cancer patients in the East Azarbaijan, Iran. METHODS: In this experimental study, 45 children with cancer in the Northwest of Iran were investigated for LFS. DNA was extracted from the whole blood cells using the salting-out method. The region within the exons 5-8 of the TP53 gene has been replicated via Polymerase Chain Reaction (PCR) method. The PCR products were sent for Sanger sequencing, and finally, the data were analyzed by Chromas software. RESULTS: In the studied probands, in 12 (26.67%) cases, polymorphisms in Exon 6 and Introns 6 and Intron 7 were identified, and no mutation was observed in exons 5-8 of the TP53 gene. CONCLUSION: Our results show that there were no mutations in exons 5-8 of the TP53 gene as an indication of LFS possibility in these families. Further studies are needed to be done in a bigger population, and Next-Generation Sequencing (NGS) needs to be done to evaluate the whole genome of these patients to complete our data.

Evaluating the association of rs6983267 polymorphism of the CCAT2 gene with thyroid cancer susceptibility in the Iranian Azeri population.

Thyroid cancer is the most common malignancy of the endocrine system. LncRNAs play critical role in various cellular processes and are associated with several diseases. CCAT2 is a lncRNA molecule overexpressed in thyroid cancer. Single nucleotide polymorphisms in CCAT2 gene can cause changes in the structure and function of CCAT2 transcripts and susceptibility to several diseases. This study aimed to evaluate the association of rs6983267 in CCAT2 gene with thyroid cancer susceptibility in the Azeri population of Iran. In this "case-control" study, genomic DNA was extracted from peripheral blood of 102 individuals affected by thyroid cancer and 103 healthy individuals as controls. Genotyping was performed using TETRA-ARMS polymerase chain reaction. Statistical analysis showed no significant association between genotypes and/or alleles with the occurrence of thyroid cancer in the studied population, patients' gender, and tumor type. Nevertheless, we found that the allelic and genotypic distribution of this SNP was associated with the size of thyroid tumors in patients. It is assumed that investigating more individuals from both case and control group may further determine the genotypic and allelic frequencies of this SNP locus in Iranian-Azeri population.

An overview on display systems (phage, bacterial, and yeast display) for production of anticancer antibodies; advantages and disadvantages.

Antibodies as ideal therapeutic and diagnostic molecules are among the top-selling drugs providing considerable efficacy in disease treatment, especially in cancer therapy. Limitations of the hybridoma technology as routine antibody generation method in conjunction with numerous developments in molecular biology led to the development of alternative approaches for the streamlined identification of most effective antibodies. In this regard, display selection technologies such as phage display, bacterial display, and yeast display have been widely promoted over the past three decades as ideal alternatives to traditional methods. The display of antibodies on phages is probably the most widespread of these methods, although surface display on bacteria or yeast have been employed successfully, as well. These methods using various sizes of combinatorial antibody libraries and different selection strategies possessing benefits in screening potency, generating, and isolation of high affinity antibodies with low risk of immunogenicity. Knowing the basics of each method assists in the design and retrieval process of antibodies suitable for different diseases, including cancer. In this review, we aim to outline the basics of each library construction and its display method, screening and selection steps. The advantages and disadvantages in comparison to alternative methods, and their applications in antibody engineering will be explained. Finally, we will review approved or non-approved therapeutic antibodies developed by employing these methods, which may serve as therapeutic antibodies in cancer therapy.

Investigating the ACE2 polymorphisms in COVID-19 susceptibility: An in silico analysis.

BACKGROUND: Novel coronavirus (SARS-CoV-2) became an epidemic disease and lead to a pneumonia outbreak first in December 2019 in Wuhan, China. The symptoms related to coronavirus disease-19 (COVID-19) were different ranging from mild to severe lung injury and multi-organ failure symptoms, eventually leading to death, especially in older patients with other co-morbidities. The receptor of this virus in the human cell is angiotensin-converting enzyme 2 (ACE2). METHODS: In this paper, we aimed to perform an in silico analysis of the frequently studied variants of the ACE2 gene and determine the effects of the variants in mRNA secondary structure and binding affinity of cellular factors. Fourteen single-nucleotide polymorphisms were selected based on previous studies and investigated. RESULTS: All of the variants were analyzed in the RNAsnp database and three revealed a significant p-value. The spliceAid2 database prediction showed that 7 out of 14 SNPs caused an alteration in a way that only the wild or mutated form was able to bind to proteins. The latter database also reported that three SNPs produces a dual form in which different specific proteins can bind to the sequence in a specific form (either wild or mutated form). CONCLUSION: Altogether, these estimations revealed the potential of variants in manipulation of the final stable form of ACE2 that can lead to different COVID-19 susceptibility.

Combined Genotype Effects of TP53 and PAI-1 Polymorphisms in Breast Cancer Susceptibility: Multifactor Dimensionality Reduction and in silico Analysis.

INTRODUCTION: Breast cancer is a heterogeneous and multifactorial disease. TP53 and PAI-1 as important tumor suppressor genes are involved in the development, invasion, and metastasis of many cancers. This study's objective was to demonstrate the combined genotype effects of these 2 genes by investigating their single nucleotide polymorphisms. METHODS: In this case-control study, 200 individuals with breast cancer and 179 healthy individuals were studied. The genotypes were determined using the tetra-ARMS method. For data analysis, MDR, online javstat statistics package, and SPSS v.24 software were used. Also, in silico studies on the estimated effects of each of these polymorphisms were performed. RESULTS: We showed a novel gene-gene interaction of these 2 genes and demonstrated a strong synergistic interaction for TP53/PAI-1, moderate synergistic interaction for PAI-1/age, and correlation for TP53/age. On the other hand, there was no association between the allelic and genotype frequency alone and in combination, with case-control status, using the parametric method, between TP53 and PAI-1. DISCUSSION/CONCLUSION: Our findings suggest that the polymorphism of codon 72 of the TP53 gene was significantly associated with tumor stage (p < 0.023). In conclusion, we showed a gene-gene interaction between TP53 and PAI-1, in combination, using the MDR method.

Haplotype and linkage disequilibrium of TP53-WRAP53 locus in Iranian-Azeri women with breast cancer.

Among the cancer susceptibility genes, TP53 is one of the crucial genes involved in cell cycle regulations and, therefore, it greatly affects breast cancer initiation and progression. In addition, WRAP53-a natural antisense transcript-regulates TP53 transcription and, as a protein, modulates the normal cell cycle, which results in breast cancer susceptibility. In this study, we aimed to analyze a haplotype comprising four SNPs, including rs1042522, rs17878362, rs2287499, and rs2287498, which are located at 5' regions of the TP53 and WRAP53 genes, in 118 patients and 110 healthy controls of the Iranian-Azeri population. In silico studies were conducted using the SIFT, Polyphen2, Fanthmm, RNAsnp, and SNP&GO online servers. Linkage disequilibrium (LD) and D' for each combination of the markers were calculated via the Haploview program. Our results showed that the GA1CC haplotype was the most frequent in the studied population. Additionally, no significant LD between any pairwise haplotypes was observed. The GA1CC and CA2GC haplotypes were significantly associated with breast cancer susceptibility. Moreover, the in silico analysis revealed the negative effects of rs2287499 and rs1042522 on WRAP53 and P53, respectively. In conclusion, the CA1GC haplotype was strongly identified as a breast cancer risk factor, and the GA1CC haplotype was assumed to be a protective factor against breast cancer risk. Hence, these markers may potentially be used as molecular prognostic and predictive biomarkers for breast cancer.

Dysregulated KDR and FLT1 Gene Expression in Colorectal Cancer Patients.

BACKGROUND: Colorectal cancer (CRC) is one of the most commonly-diagnosed malignancies throughout the world and the fourth-leading cause of cancer deaths globally. Angiogenesis and the resultant tumor neovascularization is a well-known cancer hallmark. Here we investigated the expression of FLT1 and KDR, the influential genes in angiogenesis regulation, in CRC patients. METHODS: We assessed FLT1 and KDR mRNA expression in 47 CRC samples and matched adjacent noncancerous tissues (ANCT) by quantitative real-time PCR. The Spearmen correlation coefficient and receiver operating characteristic (ROC) curves were also examined. RESULTS: Both genes were expressed at significantly greater levels in CRC tissues than in ANCT (p < 0.05). A significant association was found between KDR expression and disease stage and lymph status in CRC patients. Furthermore, the Spearman correlation demonstrated a moderate correlation between FLT1 and KDR expression in CRC samples. Finally, ROC curve analysis demonstrated that FLT1 had the greatest sensitivity (85.1%), while the greatest specificity was achieved by a combination of the two genes. CONCLUSION: The dysregulated FLT1 and KDR expression, in addition to the observed correlation and ROC curve results, indicate the critical importance of angiogenesis among the cancer pathways in CRC. These data can broaden our current knowledge of angiogenesis in CRC to improve disease diagnosis and patient treatment.

Expression Patterns of CXCL12 and its Receptor in Colorectal Carcinoma.

BACKGROUND: Stromal cell-derived factor-1 (also called CXCL12) and its receptor, CXCR4, have a key role in the pathogenesis and tumorigenesis of various cancers. The aims of the current study were to quantitatively examine the expression of CXCR4 and CXCL12 genes in colorectal cancer and to correlate their expression degree with clinicopathological features. METHODS: Tumor tissue samples were collected from 47 patients with CRC. Total RNA was isolated from resection tissues and real-time PCR analysis was performed to examine mRNA levels of CXCL12 and CXCR4 genes. RESULTS: No significant differences were observed for both CXCL12 and CXCR4 between tumor tissues and the adjacent non-affected tissues, although a borderline significant correlation (p = 0.052) were detected between gene expression of CXCL12 and CXCR4 in tumor tissues. Our results also indicated that there was no significant correlation between expression pattern of CXCL12/CXCR4 and clinicopathological variables. CONCLUSIONS: Our data showed that CXCL12 and CXCR4 are expressed simultaneously in colorectal carcinoma tissues, suggesting that expression of these chemokines and corresponding receptors may play a pivotal role in colorectal tumorigenesis, although it cannot be as a predictive factor for disease progression.

Gene Expression Analyses of HER-2/neu and ESR1 in Patients with Breast Cancer

ABSTRACT Background: Her-2 and ESR1 genes, that interact in the cell signaling pathway, are the most important molecular markers of breast cancer, which have been amplified or overexpressed in 30% and 70%, respectively. This study was performed to evaluate the gene expression levels of Her-2 and ESR1 genes in tumor cells and its adjacent normal tissue of breast cancer patients and compared them whit clinical-pathological features. Methods: In total, 80 tissue specimens from 40 patients, with an average age of 48.47 years, were examined by Real-time PCR technique, and ultimately evaluated the expression level of Her-2 and ESR1genes. The data were analyzed by REST 2009 V2.0.13 statistical software. Results: HER2 and ESR1 overexpression was identified in 19 (48%) and 12 (30%) of 40 patients respectively, which was higher and lower than that recorded in international statistics, respectively. ESR1 overexpression was associated with Stage 3A and lymph node involvement 2 (N2) (P = 0.04 and P = 0.047, respectively). No significant correlation was observed between the expression of HER2 and ESR1 and other clinical-pathological features, however, the relative differences were identified in the expression levels of genes between main group and groups that were classified according to the clinical-pathological features and age. Conclusions: Overexpression of Her-2 and ESR1 genes in the patients of our study are higher and lower than international statistics, respectively, indicating the differences in genetic, environmental and ethnic factors that involved in the developing of breast cancer.

Association of endothelial nitric oxide synthase gene variants (-786 T>C, intron 4 b/a VNTR and 894 G>T) with idiopathic recurrent pregnancy loss: A case-control study with haplotype and in silico analysis.

OBJECTIVE(S): Many lines of evidence suggest that reduced production of nitric oxide (NO) due to single nucleotide polymorphisms in endothelial nitric oxide synthase (eNOS) gene may affect the implantation and maintenance of pregnancy. Accordingly, our objective was to investigate whether the eNOS polymorphisms (-786 T>C, intron 4 b/a VNTR and 894 G>T) and haplotypes may be associated with increased susceptibility to recurrent pregnancy loss (RPL). STUDY DESIGN: A total of 130 women with a history of two or more unexplained consecutive first trimester miscarriages and 110 ethnically matched women with at least two normal pregnancies and no history of pregnancy loss were included in the study as cases and controls, respectively. To identify the genotypes, we used polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods In addition, an in silico analysis was conducted to predict the possible effects of the eNOS 894 G>T polymorphism on the structure and function of eNOS mRNA and protein using prediction servers. RESULTS: Our findings revealed that the prevalence of eNOS -786 T>C polymorphism, eNOS -786C allele and TC+CC genotype in cases were significantly higher than those in healthy controls (p<0.05). Also, the combination genotypes -786TT/4b4a and -786TT/894GG were significantly associated with reduced risk of RPL. We also found that the C-4a-G haplotype of the eNOS gene studied polymorphisms was significantly associated with a predisposition to RPL (odds ratio, 3.219; 95% confidence interval, 1.649-6.282; p=0.0003). The in silico analysis showed that the eNOS 894 G>T polymorphism couldn't affects eNOS mRNA and protein significantly. CONCLUSION: Our findings provide evidence to support the hypothesis that eNOS -786 T>C polymorphism and the -786C-4a-894G haplotype are associated with the high risk of RPL.

Lack of Associations of the MDM4 rs4245739 Polymorphism with Risk of Thyroid Cancer among Iranian-Azeri Patients: a Case-Control Study

Background and Aim: MDM4, a negative regulator of the p53 tumor suppression pathway, has been demonstrated to be overexpressed in a variety of human cancers. Research has revealed that the rs4245739 A>C polymorphism of MDM4 in the 3'-untranslated region makes it a miR-191 target site, leading to lower MDM4 expression. This study aimed to detect if the rs4245739 single nucleotide polymorphism (SNP) impacts on thyroid cancer (TC) development in Iranian-Azeri patients. Materials and Method: Blood samples were taken from 232 healthy controls and 130 TC patients of Iranian-Azeri ethnicity. For genotyping, Tetra-ARMS PCR was performed. SPSS for Windows (version 22.0, IBM SPSS Inc., USA) and the SHEsis online software were used for data analysis. Results: Alleles of MDM4 rs4245739 SNP demonstrated no significant different in frequencies between patients and controls (p>0.05). Additionally, genotypes of MDM4 rs4245739 SNP did not increase or decrease TC risk in patients compared with healthy subjects. Conclusion: Considering the lack of any observed association between the MDM4 rs4245739 polymorphism and TC, we conclude no significant role in the pathophysiology of the disease.

mRNA expression of nuclear factor of activated T-cells, cytoplasmic 2 (NFATc2) and peroxisome proliferator-activated receptor gamma (PPARG) transcription factors in colorectal carcinoma.

Transcription factors are involved in cell cycle and apoptosis regulation and thus have a key role in the carcinogenesis of different tumors. Nuclear factor of activated T-cells, cytoplasmic 2 (NFATc2) and peroxisome proliferator-activated receptor gamma (PPARG) transcription factors are important in the carcinogenesis of colorectal cancer (CRC). In this study, we examined whether the expression of NFATc2 and PPARG genes is significantly altered during the carcinogenesis of CRC. A total of 47 tumor samples and matched normal tissue margins were collected during surgery from patients with CRC. In addition, three CRC cell lines (HCT119, SW480, and HT29) and healthy cell line were used. After total RNA extraction and cDNA synthesis, mRNA expression levels of NFATc2 and PPARG were examined by real-time polymerase chain reaction. The results showed that NFATc2 is overexpressed in the tumor tissues compared with normal tissue margins (p ≤ 0.05). However, the mRNA expression levels of PPARG were not significantly different between the tumor tissues and tissue margins. Our results indicate that NFATc2 may be used as an early diagnostic or predictive biomarker for CRC as well as a therapeutic target, providing that upcoming studies confirm these results.

Gene Expression Analyses of HER-2/neu and ESR1 in Patients with Breast Cancer

ABSTRACT Background: Her-2 and ESR1 genes, that interact in the cell signaling pathway, are the most important molecular markers of breast cancer, which have been amplified or overexpressed in 30% and 70%, respectively. This study was performed to evaluate the gene expression levels of Her-2 and ESR1 genes in tumor cells and its adjacent normal tissue of breast cancer patients and compared them whit clinical-pathological features. Methods: In total, 80 tissue specimens from 40 patients, with an average age of 48.47 years, were examined by Real-time PCR technique, and ultimately evaluated the expression level of Her-2 and ESR1genes. The data were analyzed by REST 2009 V2.0.13 statistical software. Results: HER2 and ESR1 overexpression was identified in 19 (48%) and 12 (30%) of 40 patients respectively, which was higher and lower than that recorded in international statistics, respectively. ESR1 overexpression was associated with Stage 3A and lymph node involvement 2 (N2) (P = 0.04 and P = 0.047, respectively). No significant correlation was observed between the expression of HER2 and ESR1 and other clinical-pathological features, however, the relative differences were identified in the expression levels of genes between main group and groups that were classified according to the clinical-pathological features and age. Conclusions: Overexpression of Her-2 and ESR1 genes in the patients of our study are higher and lower than international statistics, respectively, indicating the differences in genetic, environmental and ethnic factors that involved in the developing of breast cancer.

STC1 and NF-κB p65 (Rel A) is Constitutively Activated in Colorectal Cancer.

BACKGROUND: Stanniocalcin-1 (STC1) and nuclear factor (NF)-κB subunit p65 transcription factor are involved in various types of human malignancies. The roles of STC1 and NFκB-p65 in colorectal cancer (CRC) are still not fully understood. We investigated expression levels of NF-κB p65 and STC1 and also correlations between STC1 and NF-κB p65 expression and clinicopathological features in CRC. METHODS: Tumor tissue samples were collected from 48 patients with CRC. RT-PCR and Real-time PCR analysis was performed to examine mRNA levels of STC1 and NF-κB p65. RESULTS: The relative mRNA levels of STC1 and NF-κB p65 were significantly higher in tumor tissues than in adjacent mucosa (p = 0.025 and p = 0.044, respectively). The data also showed that STC1 and NF-κB p65 mRNA levels were not significantly associated with clinicopathological characteristics. In addition, there was no association between expression levels of STC1 and NF-κB p65 in tumor samples. CONCLUSIONS: Our data indicate that STC1 and NF-κBp65 is activated constitutively in colorectal carcinoma tissues, suggesting that activation of these factors might play an important role in colorectal tumorigenesis. Future studies should examine STC1 and NF-κBp65 as a molecular target for the treatment of CRC.

Analysis of the Association between MDM4 rs4245739 Single Nucleotide Polymorphism and Breast Cancer Susceptibility.

BACKGROUND: MDM4 is a negative regulator of the p53 tumor suppression pathway. Recent studies have revealed that the rs4245739 A>C polymorphism of MDM4 in the 3-untranslated region makes it a miR-191 target site which leads to lower MDM4 expression. This study is aimed to detect if rs4245739 single nucleotide polymorphism (SNP) of the MDM4 gene influences the breast cancer development in Iranian-Azeri women. METHODS: Blood samples were taken from 260 healthy controls and 220 breast cancer women with ethnicity of Iranian-Azeri. Genotyping was done using Tetra-ARMS PCR. RESULTS: Alleles of MDM4 rs4245739 SNP had no significant different frequency between patients and controls (p > 0.05). Additionally, genotypes of MDM4 rs4245739 SNP did not increase or decrease breast cancer risk in patients when compared to healthy women. Also, there was no significant association between the alleles of MDM4 rs4245739 SNP and clinicopathological factors (p > 0.05). CONCLUSIONS: Considering the lack of association between MDM4 rs4245739 polymorphism and breast cancer, rs4245739 polymorphism of this gene seems to have no significant role in the pathophysiology of the disease.

The Central Role for Microenvironment in B-Cell Malignancies: Recent Insights into Synergistic Effects of its Therapeutic Targeting and Anti-CD20 Antibodies.

Most B-cell-related disorders can be cured with conventional agents; however, relapse is common, creating a need for additional therapeutic options. In agreement, recent biomarker studies corroborate the role played by functional crosstalk between malignant B cells and microenvironment which have added texture to clinical outcome. Here we outline the essential role of the tumor-associated niche in B-cell Lymphoma/Leukemia pathogenesis, in an attempt to optimize the use of microenvironment-targeted drugs and anti-CD20 antibodies in the various subsets.

Personalized Gene Expression Analyses of SMAD7 and KLF10 In Breast Cancer

Many cancer researchers use gene expression analysis for differentiation between tumor and normal cells for diagnostic, prognostic and therapeutic purposes. Most of studies compare either tumor cell lines by normal cell lines or tumor tissue of affected individuals by normal healthy control tissue. But expression of each special gene is unique in different individuals and also in different tissue of same individual. For this reason, here we compare the gene expression levels of SMAD7 and KLF10 in tumor cells and its adjacent normal tissue of breast cancer patients and compared them. For this purpose, a total of 40 tumor and matched tumor-free margin samples were obtained during surgery. The SMAD7 and KLF10 mRNA expression levels in tumor and marginal samples were examined by real-time quantitative PCR. Results are not concordant with previous studies and comparison of only SMAD7 or KLF10 is not useful for differentiating between tumor and margin cells, but ratio analysis of these two genes, SMAD7/ KLF10, can be indicative than study of one gene alone. We concluded that gene expression analysis of tumor cells with adjacent normal tissue are essential for precise identification and interpretation of cancer alterations and have important implications for the diagnostic and therapeutic management of cancer patients.

The TP53 intron 6 G13964C polymorphism and risk of thyroid and breast cancer development in the Iranian Azeri population.

BACKGROUND: TP53 mutations are the most common genetic alterations in human cancers. There are also several polymorphisms in both exons and introns of TP53 that may influence its anti-tumor functions and increase the risk of cancer development. Associations of the TP53 intron 6 G13964C polymorphism with increased risk of development of several cancers have been investigated in numerous studies, but the results were controversial and conflicting. In this study, we aimed to investigate the probable association of this polymorphism with risk of both thyroid and breast cancers among the Iranian-Azeri population. MATERIALS AND METHODS: We performed two separate case control studies on associations of the intron 6 polymorphism with two different kinds of cancer. In one case-control study, a total of 75 patients with thyroid carcinoma and 180 controls were analyzed and the other study included 170 patients with breast cancer and 135 healthy women. The intron 6 genotype was determined by RFLP-PCR and the SPSS 16 program was applied for data analysis. RESULTS: For thyroid cancer, the frequencies of GG genotype were 96.0% in patients and 93.3% in controls. The GC genotype had a frequency of 4.0% in patients and 6.7% in controls. In the study on breast cancer, the frequency of GG and GC genotypes in patients were 95.3% and 4.7%, respectively. In breast related control group, the frequency of GG genotype was 93.3% and the frequency of GC genotype was 6.7%. None of the cases and controls had the CC genotype. CONCLUSIONS: There was no significant association between the TP53 intron 6 G13964C polymorphism and risk of development of both thyroid and breast cancer in Iranian-Azeri patients.

Association of p53 (-16ins-pro) haplotype with the decreased risk of differentiated thyroid carcinoma in Iranian-Azeri patients.

Association of P53 polymorphisms with the increased risk of various cancers has been investigated in numerous studies. However, the results were conflicting and no polymorphism has been determined as a definite risk factor. It is likely that the study of P53 combined genotypes and haplotypes may be more useful than individual polymorphisms. Thus, in this study, we analyzed the associations of intron 3 Ins16bp and exon 4 Arg72Pro polymorphisms, as well as their combined genotypes and haplotypes with the risk of differentiated thyroid carcinoma in Iranian-Azeri patients. This case-control study was performed on 84 Iranian Azeri patients with differentiated thyroid carcinoma and 150 healthy subjects. Intron 3 genotype was determined using PCR products analysis on polyacrylamide gels and AS-PCR was used for genotyping Arg72Pro polymorphism. The javastat online statistics package software and SHEsis program were applied for data analysis. There was no significant difference in genotype frequencies of both two polymorphisms between cases and controls. However, the (-16 ins/-16 ins) (Arg/Pro) genotype combination had a noticeable but not significant association with decreased risk of thyroid cancer development (OR = 0.497 95%CI: 0.209-1.168 P = 0.080) and also the frequency of (-16 ins-Pro) haplotype was significantly higher in controls rather than patients (OR = 0.543 95%CI: 0.326-0.903 P = 0.018). In our study, there was association between (-16 ins-Pro) haplotype with decreased risk of differentiated thyroid carcinoma development in Iranian-Azeri patients.