Determination of numerical and structural chromosomal changes in skin cancer in rat and finding comparable parts in human

زمینه و هدف: القاء سرطان پوست در موش های صحرایی نژاد SD ایجاد تومورهایی را می نماید که از نظر فیزیولوژیکی و شیمیایی شباهت های زیادی با تومورهای پوستی در انسان دارد. لذا این مطالعه با هدف تعیین ناهنجاری های عددی و ساختاری در مجموعه کروموزوم های موش های صحرایی مبتلا به سرطان پوست و بررسی مناطق متناظر آن ها در کروموزوم های انسانی انجام شد. روش بررسی: در این مطالعه تجربی mg 5/2 ماده ی کارسینوژنیکDMBA (7,12-Dimethylbenzαanthracene) به طریق زیر جلـــدی به موش صحرایی نژاد اسپراگ داولی (SD) تزریق شد. سپس تومورهای ایجاد شده در گروه های مورد آزمایش با روش های هیستوپاتولوژی، ایمنوهیستوشیمی و کشت سلول مورد بررسی قرار گرفتند. با استفاده از سلول های حاصل از کشت سلولی به تهیه کروموزوم های متافازی اقدام و نواربندی گیمسا انجام گردید. با کمک پایگاه های اطلاعاتی، ژن های ساکن در نواحی تغییر یافته شناسایی گردید و همچنین جهت تعمیم نقش احتمالی آنها به انسان از روش مقایسه ی ژنومیک استفاده شد. یافته ها: تغییرات کروموزومی غیر اتفاقی و متداول در بین حداقل 15 سلول متافازی شامل: افزایش عددی کروموزوم‌های شماره 8، 9، 10، 18 و کاهش عددی در کروموزوم‌های شماره 4، 6، 12، 16 و همچنین تغییرات ساختاری از جمله حذف در کروموزوم‌های شماره 1، 4، 5، 6، 17 ثبت گردید. همینطور کروموزوم های مارکر در مدل های کروموزومی دیپلوئیدی و تریپلویدی، مشاهده شد. نتیجه گیری: با توجه به تغییرات ساختاری ویژه مشاهده شده در کروموزوم های متافازی و با در نظر گیری بررسی مقالات مختلف، پیش بینی می گردد ژن های SRD5A2،,BCAM SIRT2، AKT2، MLANA، RHOB، CANX و TERT در بروز سرطان پوست دخالت داشته باشند. همچنین پیشنهاد می گردد که ناهنجاری های ساختاری کروموزومی گزارش شده در این پژوهش که محل استقرار احتمالی ژن های دخیل در این سرطان می باشند مورد کنکاش بیشتری واقع گردد تا ژن های کاندید بیشتری برای بررسی دقیق تر مشخص گردد

Recurrent Regional Allelic Imbalance in Chromosome 15 in Rat Endometrial Adenocarcinomas

Objective: Animals of the inbred BDII rat strain are genetically predisposed to endometrialadenocarcinomas (EAC) and can be used to model human cancer. From our previousstudies, it was obvious that some chromosomes were selectively involved in EAC development;one of them was rat chromosome (RNO) 15, in which there were often losses inthe short arm and gains in the long arm. Since cytogenetic events lead to allelic imbalanceand/or loss of heterozygosity (AI/LoH) in RNO15, it was subjected to a detailed analysiswith polymorphic microsatellite markers spanning the entire chromosome.Materials and Methods: BDII/Han females were crossed to males from two other inbredrat strains known to have low incidence of EAC (BN/Han and SPRD-Cu3/Han). DNA extractedfrom F1, F2 and backcross offspring were used in this studies. Our final markerpanel consisted of 36 markers.Results: The analysis showed that AI/LoH was common in EAC tumors and was concentratedto four well-defined regions along the chromosome. Two of these regions were closeto the distal end of the short arm; one region was in the middle of the chromosome, probablyspanning the centromere; and the fourth region was located distally in the long arm.Conclusion: According to the Rat Genome Project (RGP), the number of genes in these regionsapproached 300. According to a database search, about 80 of these genes could be considered“cancer-related” and they were potential candidates to be targets for the observed chromosomalaberrations. Among the cancer-related genes, there were Anxa7 (Region I), Bmp4, Lgals3, Cdkn3(Region II), Rb1, Ddx26, Clu, Bnip3, Nkx3.1 (Region III), and Gpc5 (Region IV)

Studying the Association between TaqIA polymorphism in ANKK1 Gene and Heroin and Methamphetamine Addiction in Markazi Province

Abstract Background: ANKK1 (ankyrin repeat and kinase domain containing 1) gene is a member of the serine/threonine kinase family. This family involved in signal transduction pathways. This gene contains Taq1A (rs1800497) single nucleotide polymorphism. The A1 allele carriers of TaqIA polymorphism have shown reduced DRD2 (Dopamine Receptor D2) receptors. This decrease predisposes individuals to seek for addictive substances to compensate this deficiency in dopaminergic system. The present study investigated TaqIA (rs1800497) polymorphism in heroin and methamphetamine addiction. Materials and Methods: In this case-control study, 91 male methadone-maintained heroin and methamphetamine addicts and 100 male healthy controls were studied. Genomic DNA extraction was carried out from peripheral blood through salting-out method and individuals were genotyped for TaqIA polymorphism by RFLP-PCR technique and TaqI enzyme was used for RFLP. Results: This survey revealed the significantly higher frequency of the A1 allele of TaqIA polymorphism in patients than control individuals (p<0.001). The frequency of A1 allele in patient and control individuals was %51 and %22.5, respectively. The A1A1 genotype was detected in 25% of patients and 7% of controls (p<0.001, OR=9.7, 95% CI=3.64-25.85). Conclusion: The results of this study revealed that the A1 allele of TaqIA polymorphism is significantly associated with heroin and methamphetamine addiction

Relationship between polymorphisms in the CD40 gene with the prevalence of breast cancer: A case-control study

Background. Breast cancer with a complex inheritance pattern is a major cause of cancer death among women worldwide. Single nucleotide polymorphisms (SNPs), the most common genetic variations, influence interindividual predisposition to disease and treatment outcomes with drugs. Evidence suggests that CD40 polymorphism contributes to pathogenesis of cancer. The co-stimulatory molecule CD40 plays a prominent role in immune regulation. This study aimed to test the association between polymorphisms in the CD40 gene and breast carcinogenesis in Arak, Iran. Methods. In this case-control study, three SNPs (rs1883832, rs4810485, rs3765459) were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We included 80 patients with breast cancer and 80 healthy controls. Statistical analysis was performed by SPSS (version 26) using Chi-Squared test at P˂ 0.05. Results. Our data showed a statistically significant association between the two CD40 SNPs (1s1883832 and rs4810485) and breast cancer risk (P=0.038 and P=0.000, respectively). There was no significant association between rs3765459 and breast cancer risk (P=0.190). Conclusion. We witnessed that CD40 gene polymorphisms (rs1883832 and rs4810485) contributed to breast cancer. So, they are associated with breast cancer risk. Practical Implications. The obtained data revealed a significant relationship between the rs1883832 and rs4810485 polymorphisms and the risk of breast cancer. Thus, these polymorphisms could be used as biomarkers to predict breast cancer

To Investigate the Association of Thr241Met Polymorphisms of the XRCC3 Gene with the Risk of Breast Cancer in Women in Markazi Province

Abstract Background: Biological and epidemiological data suggest that damage induced by endogenous and exogenous factors affects the integrity and stability of DNA and associated with susceptibility to breast cancer. The XRCC3 protein participates in DNA double-strand breaks and recombination repair. The aim of the present study was to evaluate associations between the risk of breast cancer and Thr241Met polymorphism in the XRCC3 gene. Materials and Methods: In this study, the effects of Thr241Met polymorphism of the XRCC3 gene and the risk of breast cancer in a population-based case-control study inclusive 80 patients and 80 healthy individuals of women in Markazi province were evaluated. Genomic DNA was extracted from blood samples using the kit procedure. The genotypes of samples were determined by PCR-RFLP technique. Statistical analysis was done using SPSS software (estimation of χ2 and p-value) and the final results were determined. Results: Statistically significant difference was observed between the two groups of patients and controls for three genotypes of the site rs861539 (p= 0.000). Genotype CT (p= 0.000, OR=2.352, CI= 95%; 2.431 - 39.948) and TT (p = 0.003, OR= 2.352, CI=95%; 0.611 - 9.049) significant associations were showed with risk of breast cancer. Instead, the genotype CC (p= 0.000) showed a protective role against susceptibility to breast cancer. Conclusion: This study identified that there is significant association between Thr241Met polymorphisms of the XRCC3 and the risk of susceptibility to breast cancer, which is in accordance to some of researchers' studies

Lack of the Association between Single Nucleotide Polymorphism (L55M) in PON1 Gene and Susceptibility with Breast Cancer in Markazi Province

Abstract Background: Breast cancer is both the prevailing malignancy and the most common cause of cancer death among women. Many factors may play a role in the susceptibility to the breast cancer and Oxygen Free Radicals may be one of these. There are various known antioxidant systems against oxidative stress, including ParaoxonaseI. The aim of this study was to investigate the association between rs854560 polymorphism in the PON1 gene in patients with breast cancer. Materials and Methods: We performed genotyping analysis using polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) assay in a case–control study of 83 confirmed breast cancer patients and 100 cancer-free controls in Markazi Province. Results: In our study of the PON1 gene L55M polymorphism, the LL genotype was found in 2 (2.40%) patients, whereas the LM genotype was found in 69 (83.13%) patients. The MM genotype was present in 12 (14.45%) patients. In the control group, LL, LM and MM genotypes were found in 4 (4%), 81 (81%), and 15 (15%) subjects, respectively. There was no statistically significant difference between patient and control groups in terms of the PON1 gene L55M polymorphism (p= 0.825). Allele distributions were different but this difference did not reach statistical significance (p= 0.920). Conclusion: We found no association between M55L polymorphism and breast cancer

The Association of Vitamin D Receptor Gene (VDR) ApaI Polymorphism with the Risk of Breast Cancer in Markazi Province Women

Abstract Background: Biological and epidemiological data indicate that the levels of vitamin D maybe affect the breast cancer risk. Vitamin D plays an important role in cell proliferation, apoptosis and tumor growth suppression. Vitamin D receptor is a critical mediator for the cellular reactions of vitamin D. Some of the epidemiological studies, reviewed the relationship between VDR gene polymorphism ApaI and breast cancer, but the controversial findings have been achieved. Materials and Methods: In this study, a population-based case-control study including 140 patients and 160 healthy individuals of women in Markazi Province were evaluated using PCR-RFLP approach. Genomic DNA was extracted from blood samples using the salting-out procedure. Polymorphism of interest was determined by PCR-RFLP method using ApaI enzyme and statistical analysis was performed by SPSS software. Results: Based on the results of this study, distribution of AA genotype in cancer and control groups was, 38.6 and 26.87, for AC genotype 55.00 and 66.87, and finally for CC genotype 6.43 and 6.26 respectively. The results of this study showed no association between ApaI polymorphism of the VDR gene and breast cancer(OR=0.903,CI=95%, 0.29-2.95.) Conclusion: In this study, we found no association between ApaI polymorphism and breast cancer, which are consistent with the findings of some other researchs. It is necessary to examine a larger population to achieve more definitive results

Expression and Methylation Pattern of hsa-miR-34 Family in Sperm Samples of Infertile Men

Production of high-quality spermatozoa is necessary for male fertility. In this regard, post-mitotic stage in spermatogenesis is very important which posttranscriptional microRNAs (miRNAs) playing a key role at this stage. In this research, we evaluated the expression and methylation of hsa-miR-34 family in sperm samples of infertile men. We recruited 102 infertile men (asthenozoospermia, teratozoospermia, asthenoteratozoospermia, and oligoasthenoteratozoospermia) and 52 fertile men as control. The expression of hsa-miR-34a,b,c was determined by quantitative real-time PCR (qRT-PCR) technique. Methylation of hsa-miR34b,c promoter was evaluated by methylation-specific PCR (MS-PCR) method. Our data indicated under-expression of three miRNAs (hsa-miR-34a,b,c) in the sperm samples of infertile men in compared to their fertile counterparts. The highest rate of expression reduction was observed in hsa-miR-34c-5p and in oligoasthenoteratospermic patients (P = 0.011, F = 4.01). The results revealed that the frequency of methylation of the promoter region of hsa-miR-34b,c in infertile men was higher than that of fertile men (82.4% versus 23.3%), and the highest frequency of methylation was observed in patients with asthenoteratospermia (92.9%) and oligoasthenoteratospermia (93.8%). In conclusion, our results indicated lower expression of hsa-miR-34a,b,c and hypermethylation of hsa-miR-34b,c promoter in sperm samples of infertile men. Aberrant under-expression of these miRNAs could be duo to the hypermethylation of the promoter region and indicative of a defect in spermatogenesis