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Background: A high number of human breast cancers overexpress the murine double minute (MDM2) gene which blocks the p53 protein which plays an important role in arresting the cell growth. The present study aimed to investigate the efficacy of siRNA specific MDM2 in knocking down MDM2 and its subsequent effects on p53 to exert antiproliferative effects on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells. Method: In this in vitro study, we used the specific siRNA of the MDM2 gene to knock down the expression of the MDM2 protein in the MCF-7 cell line. The expression of MDM2, BCL2-associated X (BAX), BH3 interacting-domain death agonist (BID), and B cell lymphoma 2 (BCL2) genes was evaluated using the real-time polymerase chain reaction (PCR) technique. The apoptosis level was also assessed using the flow cytometry technique by the Annexin V test. Results: The results showed that the entry of MDM2 siRNA into MCF-7 cells significantly reduced the mRNA expression of MDM2 gene (P-value < 0.05). Besides, the expression of the antiapoptotic gene of BCL2 significantly decreased (P-value < 0.05) in transfected MCF-7 cells, while that of BAX and BID genes increased (P-value < 0.05). Conclusion: Based on the results, MDM2 inhibition is conducive to prevent cancer metastasis by the induction of cancer cell apoptosis. Moreover, it can be considered in cancer therapy along with chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Several types of cancer have mutations in the tumor suppressor gene p53. Environmental mutagens such as heavy metals play an undeniable role in p53 mutations and leave the mutational fingerprint on the TP53 gene. Therefore, the study of p53 mutation spectra can reflect the past heavy metals exposure. Results: The current study was found interesting results by reviewing the previous data published in the databases. These results were obtained by comparing the common mutational profile between Iran, India, and Pakistan, and the association of these mutations with metals. The mutations in codons 146 (TGG→ TGA, Trp→ Stop), 214 (CAT→CGT, His→ Arg), and 249 (AGG→AGT, Arg→ Ser) were common in both India and Iran, due to the contamination by zinc and arsenic; arsenic and copper; cadmium, arsenic, nickel, and copper poisoning, respectively. Moreover, the mutations in codons 248 (CGG→ CAG, Arg→ Gln), 220 (TAT→ TGT, Tyr→ Cys), 248 (CGG→ TGG, Arg→ Trr), and 273 (CGT→ CAT, Arg→ His) were common among these three countries that could be related to poisoning with arsenic and zinc; arsenic; copper and arsenic; zinc and arsenic, respectively. These results can give a possible explanation for the cause of mutational similarities in these three areas, which can help identify the cause of high rates of p53 mutation and cancer control in these areas. Conclusion: However, concerning the effects of other environmental factors, we definitely cannot explain the cause of these mutations among the heavy metals mentioned, since it requires more detailed studies. [ABSTRACT FROM AUTHOR]

Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. The MDM2 and p53 are interacting proteins that play crucial roles in cell biology. Genetic variations of p53 and MDM2 have been identified in many cancers including CLL; among which are SNP309 in the promoter of MDM2 and SNP codon72 in p53. Materials and Methods: In this study, we sought to find the impact of two SNPs of p53 and MDM2 in the pathogenesis of CLL. A total of 100 CLL patients and 102 healthy controls were recruited. Genomic DNA was extracted, and genotyping was performed using the PCR-RFLP method. The allele and genotype associations were analyzed using the χ2 test. The gene-gene interaction analysis was studied using GMDR v0.9. Results: Our study found the absence of a significant difference between CLL patients and controls related to the allelic frequencies or genotypic distributions for both MDM2 SNP309 and p53 codon72. A significantly higher frequency of p53 C allele was found in patients with disease duration of more than 36 compared to those less than 36 months. However, GMDR analysis suggests genetic interaction between the genes under study. Conclusion: Our findings indicated each polymorphism of p53 codon72 and MDM2 (SNP309) was not a risk factor for CLL but the p53 C allele could be associated with the disease duration. Besides, the interaction between p53/MDM2 genotypes may confer susceptibility to CLL. Our study could be useful in genetic association studies of CLL and the role of gene-gene interactions in the susceptibility to the disease. [ABSTRACT FROM AUTHOR]

Background:Many case-control investigations have showed the correlation of TP53 gene polymorphisms with the risk of breast cancer. However, the findings are not consistent. It has been suggested that the investigation of P53 genotype combinations and haplotypes may be more helpful than the detection of single polymorphisms. In the present study, we investigated the association of P53 intron 3 and codon 72 polymorphisms, as well as their Haplotypes and genotype combinations, with the development of breast cancer among Azeri women of Iran. Methods:A total of 143 Iranian-Azeri females suffering from breast cancer and 160 ethnically and age-matched healthy females participated in this study. Intron 3 genotype was indicated by length analysis of PCR amplicon on polyacrylamide gels and allele specific-polymerase chain reaction (AS-PCR) was applied for genotyping Arg72Pro variation. Data analysis was performed using the JavaStat online statistics package and SHEsis online program. Results: Our findings did not show a significant association of P53 intron 3 and codon 72 polymorphisms with the risk of breast neoplastic tumors among Iranian-Azeri women. However, the (-16ins/+16ins) (Arg/Arg) combined genotype and (+16Ins-Arg) haplotype had a higher frequency in patients in comparison with the control group (OR=3.816; 95%CI: 0.906-18.459; P=0.047 and OR=3.941; 95%CI: 1.583-9.812; P=0.002, respectively). Conclusion:In our study, (-16ins/+16ins) (Arg/Arg) genotype combination and (+16ins-Arg) haplotype showed significant correlation with the increased susceptibility to breast cancer development in Iranian-Azeri females. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer as the fourth most frequent malignancy worldwide was known to have the highest rate among cancer-related disorders in Ardabil province. The product of TP53 gene regulated the cell cycle process and acts as a tumor suppressor factor. The polymorphism P53 Arg72Pro (rs 1042522) has been reported to be associated with many type of cancers. The purpose of the present study was investigating about susceptibility of gaining gastric cancer in which probably conferred by the polymorphism P53 Arg72Pro in Ardabil province. Materials and Methods: Using PCR-RFLP, the polymorphism was assayed among 87 patients affected with gastric cancer and 92 healthy controls selected. The statistical significance was analyzed by logistic regression test. Results: The mean of age for cases and controls were 64.2 and 61.9 years respectively. The frequency of genotypes for cases has been detected as 16.3% for Pro/Pro, 41.9% for Arg/Pro, and 41.9% for Arg/Arg and for controls were 18.5% Pro/Pro, 40.2% Arg/Pro, and 41.3% Arg/Arg respectively. There was not any significant association between this polymorphism and affecting to gastric cancer. Conclusion: Finding shows relationship between susceptibility of gaining gastric cancer in our province and the polymorphism rs 1042522 could be due to genetic and population relationship between Ardabil population and Caucasians, and the selective advantage of the Arg allele in cold climates, as well. On the other hand, considering to the previous studies on the etiology of gastric cancer in Ardabil province shows, environmental factors such as nitrate have more important role bin conferring susceptibility to gain gastric cancer and some genetic changes and affecting to gastric cancer in this study indicates that the role of lifestyle improvement might reduce the huge rate of affected patients in our province. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to evaluate the correlation of P53 and granzyme B (GB) expression, and also the relationship between P53 expression and GB cell density with lymph node metastasis, histologic grade, and inflammation intensity in oral squamous cell carcinoma (OSCC). Methods: Immunohistochemical technique with P53 and GB antibodies were performed on stored paraffin blocks from 48 patients with OSCC (with lymph node metastasis n = 24; without lymph node metastasis n = 24). The density of GB expression was quantified both in invasive front (peritumoral ) and within cancer nests (intratumoral ). Results: P53 positivity was seen in 13 (54.16 %) cases of the nonmetastatic group and 14 cases (58.3 %) in the metastatic group. A significant correlation was seen between P53 immunoexpression and histologic grade (P = 0.047), but there was no significant correlation between P53 expression with lymph node metastasis and inflammation intensity. The density of GB+ cells in the peritumoral zone correlates with a higher intratumoral GB expression (P = 0.001) and was significantly higher in the nonmetastatic group (P = 0.029). No significant correlation between GB and P53 immunoexpression, lymph node metastasis, or inflammation intensity was seen. Conclusion: The present study showed that the presence of a higher density of GB+ cells infiltrating the peritumoral area may have an important role against tumoral cells, prevent lymph node metastasis, and better prognosis in OSCC patients. [ABSTRACT FROM AUTHOR]

Introduction: Gastric cancer remains the second most common cause of cancer-related deaths worldwide. In many malignancies like, lung and breast, multiple prognostic factors are known, such as mutations in Ki-67, HER-2/neu, p53. In this study, we evaluated immunohistochemical protein expression patterns of cell-cycle-regulators p53, proliferation marker Ki-67, surface expression of CD44, HER-2/neu oncogene proposed as useful prognostic factors. Methods: In this descriptive-analytic study, we evaluate 100 patients with gastric cancer who were referred to Shahid Ghazi Hospital or other oncology clinics of Tabriz University of Medical Sciences in 2005-2010. Patients with pathologic confirmation of gastric cancer were selected. Expression of p53, ki-67, CD-44, HER-2/neu were detected by immunohistochemical staining. Results: In this study, 100 patients with gastric cancer participated. 76(76%) were men and 24(24%) were women with mean age of 64.02(8.05) years. Seventy two samples were intestinal type and 28 were diffuse type. CD44 was positive in 27(27%) patients. P53 was positive in 35(35%) patients. Ki-67 was positive in 53(53%) patients. HER-2/neu was positive in 51(51%) patients. Conclusion: The frequency of positive p53, Ki-67, CD44 and HER-2/neu varied in different studies. Positive Ki-67 and HER-2/neu were not associated with changes in survival but positive p53 and CD44 were significantly associated with improved survival. [ABSTRACT FROM AUTHOR]

Background: Hesperidin, a flavanone present in citrus fruits, has been identified as a potent anticancer agent because of its proapoptotic and antiproliferative characteristics in some tumor cells. However, the precise mechanisms of action are not entirely understood. Aim: The main purpose of this study is to investigate the involvement of peroxisome proliferator-activated receptor-gamma (PPARγ) in hesperidin's anticancer actions in human pre-B NALM-6 cells, which expresses wild-type p53. Methods: The effects of hesperidin on cell-cycle distribution, proliferation, and caspase-mediated apoptosis were examined in NALM-6 cells in the presence or absence of GW9662. The expression of peroxisome proliferator-activated receptor-gamma (PPARγ), p53, phospho-IκB, Bcl-2, Bax, and XIAP proteins were focused on using the immunoblotting assay. The transcriptional activities of PPARγ and nuclear factor-kappaB (NF-κB) were analyzed by the transcription factor assay kits. The expression of PPARγ and p53 was analyzed using the RT-PCR method. Results: Hesperidin induced the expression and transcriptional activity of PPARγ and promoted p53 accumulation and downregulated constitutive NF-κB activity in a PPARγ-dependent and PPARγ-independent manner. The growth-inhibitory effect of hesperidin was partially reduced when the cells preincubated with PPARγ antagonist prior to the exposure to hesperidin. Conclusions: The findings of this study clearly demonstrate that hesperidin-mediated proapoptotic and antiproliferative actions are regulated via both PPARγ-dependent and PPARγ-independent pathways in NALM-6 cells. These data provide the first evidence that hesperidin could be developed as an agent against hematopoietic malignancies. [ABSTRACT FROM AUTHOR]

Abstract: Glioblastoma multiform (GBM; World Health Organization (WHO) grade IV) and anaplastic astrocytomas (AA; WHO grade III) are highly aggressive and lethal astrocytic brain tumors. To detect cancer-specific somatic mutations in two hot-spot regions of PIK3CA gene, the helical and kinase domains (encoded by exons 9 and 20, respectively) in GBM and AA, the authors examined the respective sequences 31 paraffin-embedded samples (23 GBM and 8 AA). The samples were obtained from a group of Iranian patients affected with high-grade glioblastoma (HGG). The overall prevalence of PIK3CA mutations was 23% (7/31) for both tumor types (22% in GBM, and 25% in AA). Five mutations were detected in exon 20, p.Arg992Gln (c.2976G→A), p.Met1005Val (c.3014A→G), p.Ile1019→Val (c.3056A→G), p.Ser1008Cys (c.3024C→G), and p.Asn1044Asp (c.3130A→G), and one mutation in exon 9, p.Glu545Ala (c.1634A→C). Additionally exons 4-8 of P53 gene in four unrelated young patients, who showed no mutations in PIK3CA exons 9 and 20, were analyzed. Three mutations were identified: p.Pro72Ala (c.214C→G), g.11608G→T (homozygote splice mutation), and p.Thr170Thr (c.510G→A silent mutation). In conclusion, mutation detection in PIK3CA in patients with a high degree of malignancy and early age at diagnosis should be included in molecular diagnostic protocols, also with regard to possible upcoming therapies. [ABSTRACT FROM AUTHOR]

Purpose: Ulcerative colitis (UC) is a chronic inflammatory condition of the large bowel of unknown etiology, characterized by the presence of bloody diarrhea and mucus associated with a negative stool culture for bacteria, ova, or parasites. The aim of this study was to investigate the association of p53 codon 72 genetic polymorphism with the risk of UC in northern Iran. Methods: We evaluated the association of the p53 codon 72 genetic polymorphism with UC in northern Iran. The genotype of 190 patients with UC (115 men, 75 women; mean age, 32 ± 8.6 years) and 220 healthy control subjects (123 men, 97 women; mean age, 33 ± 2.5 years) were compared. Genomic DNA was extracted from colonic bioptic tissues of patients and blood samples of healthy individuals. Genotypes and allele frequencies were determined in patients and controls using allele-specific PCR (AS-PCR). Results: There were significant differences in the distribution of the polymorphism between the control subjects and the UC patients ( P < 0.0001). Significantly increased frequencies of the Pro allele and the Pro/Pro genotype were observed in patients with UC compared with controls (Pro allele: P < 0.0001; odds ratio, 7.87; 95% confidence interval, 4.03-15.35; Pro/Pro: P < 0.0001; odds ratio, 35.21; 95% confidence interval, 12.56-98.73). Conclusion: The p53 codon 72 genetic polymorphism is associated with UC in northern Iran. [ABSTRACT FROM AUTHOR]

BACKGROUND: The association of a functional single nucleotide polymorphism at codon 72 of the p53 gene (Arg72Pro) with malignancy is a subject of controversy. We analyzed this polymorphism in 224 patients with gastrointestinal cancers (92 with stomach cancer and 132 with colorectal cancer) and in 163 healthy controls. MATERIAL AND METHODS: DNA was extracted from peripheral blood mononuclear cells and amplified with an allele-specific polymerase chain reaction. RESULTS: There was no signifi cant association between p53 alleles and gastrointestinal cancers. The frequency of the Arg allele was 59.7, 58.8, and 59.2% in the stomach cancer patients, colorectal cancer patients, and controls, respectively. Frequencies of the Pro allele were 40.3% in patients with stomach cancer, 41.2% in patients with colorectal cancer, and 40.8% in controls. Likewise, genotype frequencies did not differ signifi cantly between the two patient groups and controls. There were no differences in genotype or allele frequencies by gender, age, or histological grade. CONCLUSIONS: The data do not support the association of the p53 codon 72 polymorphism with stomach or colorectal cancers in Iranian patients. [ABSTRACT FROM AUTHOR]

Abstract: Sulfur mustard (SM), also known as mustard gas, is an alkylating compound used as a chemical weapon in World War I and by Iraqi forces against Iranians and indigenous Iraqi Kurds during the Iran–Iraq War of the 1980s. Although SM is a proven carcinogen there are conflicting views regarding the carcinogenicity of a single exposure. The present study characterizes lung cancers formed in mustard gas victims from the Iran–Iraq War. Methods and materials: Demographic information and tumor specimens were collected from 20 Iranian male lung cancer patients with single high-dose SM exposures during the Iran–Iraq War. Formalin-fixed, paraffin-embedded lung cancers were analyzed by immunohistochemistry for p53 protein. In addition, DNA was extracted from the tissues, PCR amplified and sequenced to identify mutations in the p53 and KRAS genes associated with SM exposure. Results: A relatively early age of lung cancer onset (ranging from 28 to 73 with a mean of 48) in mustard gas victims, particularly those in the non-smoking population (mean age of 40.7), may be an indication of a unique etiology for these cancers. Seven of the 20 patients developed lung cancer before the age of 40. Five of 16 cancers from which DNA sequence data was obtainable provided information on eight p53 mutations (within exons 5–8). These mutations were predominately G to A transitions; a mutation consistent with the DNA lesion caused by SM. Two of the lung cancers had multiple p53 point mutations, similar to results obtained from factory workers chronically exposed to mustard agent. No mutations were detected in the KRAS gene. Discussion: The distinguishing characteristics of lung carcinogenesis in these mustard gas victims suggest that a single exposure may increase the risk of lung cancer development in some individuals. [Copyright &y& Elsevier]

BACKGROUND: It has been reported that the activity of glutathione S-transferase (GST) is over-expressed in plasma and esophagus biopsies in Iranian patients suffering from esophageal squamous cell carcinoma (SCC). The aim of this study was to find out the frequency of GST-P genotypes in these patients. Moreover, the association of GST-P genotypes with p53 protein accumulation in esophageal epithelium was investigated. MATERIALS AND METHODS: DNA isolated from paraffin-embedded tissue biopsies from patients suffering from esophageal SCC (n = 56) were collected. polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using Alw261 enzyme was applied to determine GST-P genotypes (Ile 105 Val). All the samples were also subjected to immunohistochemistry (IHC) for p53. RESULTS: The frequency of GST-P genotypes in Iranian esophagus SCC patients for Ile/Ile, Ile/Val and Val/Val was 73.2, 21.5 and 5.3%. There was no association between GST-P polymorphism and p53 accumulation in esophageal epithelial cells. CONCLUSIONS: The frequency of GST-P polymorphism was not associated with p53 protein accumulation in esophagus epithelium. The frequency of polymorphic variants of GST-P, Ile/Ile, Ile/Val and Val/Val in SCC patients may suggest that Ile to Val substitution in GST-P gene dose not represent susceptibility to SCC in high-risk Iranian population. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is described as age-related progressive skeletal muscle failure that results in marked reduction in the patient's independence and life quality. In this study, we explored the association of TP53 exon 4 Arg72pro (rs1042522) and Intron 3 16-bp Del/Ins (rs17878362) polymorphisms and their haplotypes with sarcopenia, anthropometric, body composition and biochemical parameters., Methods: A total of 254 older individuals (65 sarcopenic and 189 healthy) were recruited in this research and genotyped by PCR-RFLP. Linear regression was applied to find the correlation between TP53 polymorphism, and biochemical and anthropometric parameters. The correlation between TP53 polymorphism and haplotypes and the risk of sarcopenia was investigated by logistic regression., Results: Arg/Pro genotype carriers was at a lower (OR adj  = 0.175, 95% CI = 0.068 - 0.447; P < 0.001) risk of sarcopenia compared to the Arg/Arg group. In haplotypes analysis, Arg-Ins (OR adj : 0.484, 95% CI = 0.231 - 1.011, P = 0.043) and Pro-Ins (OR adj : 0.473, 95% CI = 0.210 - 1.068, P = 0.022) haplotypes showed decreased risk of developing sarcopenia. Moreover, in the case of codon 72 polymorphism, skeletal muscle mass, appendicular lean mass (ALM), skeletal muscle mass index (SMI), hand grip strength and Triglycerides, for Intron 3 16-bp Del/Ins polymorphism, albumin, calcium, cholesterol, and LDL were different, and for the haplotypes, skeletal muscle mass, SMI, ALM, HDL and triglycerides were significantly different between groups., Conclusions: We suggested that the Arg/Pro genotype of the codon 72 polymorphism in exon 4 of TP53, and Arginine-Insertion and Proline-Insertion haplotypes might decrease the risk of sarcopenia in Iranian older adults., (© 2022. The Author(s).)

Although surgery with or without (neo)adjuvant chemo/radiotherapy, as the standard treatments, can be suitable therapeutic strategies for gastric cancer, side effects and drug resistance are two main treatment obstacles. It has been discovered that pomegranate and its natural derivatives, especially ellagic acid (EA), offer significant anti-cancer effects while causing trivial side effects. In this study, we aimed to explore the anti-cancer effects of EA on a human gastric adenocarcinoma cell line (AGS) as well as in immunocompromised mice bearing human gastric tumors, for the first time. HPLC was used for determining EA in samples. MTT assay, apoptosis and scratch assay, gelatin zymography, and quantitative RT-PCR were used to determine the anti-cancer properties of different concentrations of pomegranate fruit juice, pomegranate peel extract, and EA. Furthermore, the effects of these compounds were investigated on immunosuppressed C57BL/6 mice carrying human gastric cancer tumors. EA could inhibit the proliferation and migration of gastric cancer cells. It also had significant effects on reducing both expression and activity of MMP-2 and MMP-9. Further, it was demonstrated that with alterations in the expression of genes involved in apoptosis and inflammation including P53 , BAX , APAF1 , BCL2 , iNOS , NF-κB , IL-8 , and TNF-α , EA treatment led to increased cancer cell death and reduced inflammation. Furthermore, its use in mice bearing gastric tumors resulted in a significant reduction in tumor volume without any obvious side effects. Ellagic acid exhibited anti-cancer effects on gastric adenocarcinoma, and can be considered as a safe anti-cancer agent for further preclinical studies on this cancer.

Background: Aging and obesity are the two major global health concerns. Sarcopenia, an age-linked disease, wherein a progressive loss of muscle volume, muscle strength, and physical activity occurs. In this study we evaluated the association of TP53 rs1625895 polymorphism with the susceptibility to sarcopenic obesity in Iranian old-age subjects., Methods: Total of 176 old individuals (45 sarcopenic and 131 healthy) were recruited in this research and genotyped by PCR-RFLP. BMI, Skeletal Muscle Mass Index, body composition, Handgrip Strength, Gait Speed (GS), and biochemical parameters were measured. Chi-square test was done for genotypes and alleles frequency. Linear regression was applied to find the correlation between TP53 rs1625895 polymorphism, and biochemical and anthropometric parameters. The correlation between TP53 rs1625895 and the risk of sarcopenia and sarcopenic obesity was investigated by logistic regression., Results: G allele was significantly higher in sarcopenic obesity group [P = 0.037, OR (CI 95%) = 1.9 (1.03-3.5)] compared to A allele. BMI (P = 0.049) and LDL (P = 0.04) were significantly differed between genotypes when GG was compared to AA/AG genotype. The results revealed when GG genotype compared to AA/AG genotype in adjusted model for age, the risk of sarcopenic obesity [P value = 0.011, OR (CI 95%); 2.72 (1.25-5.91)] increased. Similarly, GG/AG genotype increased the risk of sarcopenic obesity [P value = 0.028, OR (CI 95%); 2.43 (1.10-5.36)] in adjusted model for age compared to AA genotype., Conclusions: We suggested that TP53 rs1625895 polymorphism may increase the risk of sarcopenic obesity in Iranian population.

The HBV-related hepatocellular carcinoma (HCC) is an important liver malignancy worldwide and carries a poor prognosis. In this regard, an accurate diagnosis is necessary to enable successful treatment. The aim of the current study was to assess the relationship between the expression of certain molecular markers and HCC diagnosis in Iran. Immunohistochemistry and quantitative RT-PCR techniques were used to evaluate the expression patterns of p53 and Ki-67 in liver tissues from 121 HCC and/or HBV-infected patients and 30 healthy volunteers. Patients with HBV+HCC demonstrated increased expression of both p53 and Ki-67 compared to patients with HBV only, highlighting correlation between the p53 and Ki-67 expression levels and HCC diagnosis. The prognostic value of p53 for the diagnosis of HCC was more reliable. The p53 demonstrated higher sensitivity compared to the Ki-67 (sensitivity and specificity, 77.3 and 76.4% for the p53, and 51.0 and 97.9% for the Ki-67, respectively). A panel containing two positive markers had higher specificity and comparable sensitivity to a panel with one positive marker regardless of which one (sensitivity and specificity, 94.8 and 97.9%, for two positive markers and 96.5 and 86.4% for one positive marker, respectively). Taken together the combined analysis of p53 and Ki-67 expression provides a mean to increase the specificity and sensitivity of HBV-related HCC diagnosis to an acceptable level.

This review gives a summary of the important genetic polymorphisms in breast cancer with a focus on people in Iran. Several single nucleotide polymorphisms were considered as breast cancer susceptibility polymorphisms within genes ( STK15, ERRs, ESR1, p53, SEP15, AURKA, SHBG, SRC, FAS, VEGF, XRCC1, GST, NFκB1, XPC, XRCC3 , sirtuin-3, NKG2D ). Cytosine-adenine repeat (IGF-I), rs3877899, G-2548A, GGC (eRF3a/GSPT1), IVS2nt-124A/G have shown an increased risk of breast cancers and a decreased risk has been observed in 4G/5G (PAI-1) , rs6505162 , tri-nucleotide ( GCG   TGFBR1) . We observed that the signaling pathways and antioxidant related genes are the main molecular processes associated with breast cancer progression. Further studies on types of polymorphisms in breast cancer could validate the prognostic value of biomarkers.

Background: Glaucomatous neuropathy is a type of cell death due to apoptosis. The p53 gene is one of the regulatory genes of apoptosis. Recently, the association between the p53 gene encoding for proline at codon 72 and primary open-angle glaucoma (POAG) has been studied in some ethnic groups. This study is the first association analysis of POAG and p53 codon 72 polymorphism in Iranian patients., Methods: A cohort of 65 unrelated patients with POAG (age range from 12-62 years, mean ± SD of 40.16 ± 17.51 years) and 65 unrelated control subjects (without glaucoma, age range of 14-63 years, mean ± SD of 35.64 ± 13.61 years) were selected. In Iranian POAG patients and normal healthy controls, the p53 codon 72 polymorphism in exon 4 was amplified using polymerase chain reaction. The amplified DNA fragments were digested with the BstUI restriction enzyme, and the digestion patterns were used to identify the alleles for the polymorphic site., Results: Comparisons revealed significant differences in allele and genotype frequencies of Pro72Arg between POAG patients and control group. A higher risk of POAG was associated with allele Pro (OR = 2.1, 95% CI = 1.2-3.4) and genotype Pro/Pro (OR = 3.9, 95% CI = 0.13-12.7)., Conclusion: The p53 Pro72 allele was more frequent in Iranian POAG patients than in the control group (P<0.05). The present findings show that the individuals with the Pro/Pro genotype may be more likely to develop POAG. However, additional studies are necessary to confirm this association.