Theses supervised by Doç. Dr. Gülsüm Seda Güleç Yılmaz
13 theses · Yeditepe University
Prostat kanseri hastalarinda epidermal büyüme faktörü reseptörü polimorfizminin incelenmesi
Cancer is associated with increased mortality ratio worldvide while, prostate cancer (PC), possess the most prevalent death ratio among male population. The metastatic form of PC is the second leading cause of cancer-related death. Epidermal Growth Factor (EGF) receptor (EGFR), is one of a member of ErbB family of receptor tyrosine kinases (RTKs) that encodes 170 kD glycoprotein. Studies have revealed that single nucleotide polymorphisms (SNPs) occurring in the EGFR gene cause different types of carcinomas, such as prostate adenocarcinomas and gliomas [1]. For better understanding of how EGFR polymorphism lead to cancer development, case-control study has been conducted in Turkish male population with 61 patient and 62 healty individuals. Genotype analysis was performed with Real-Time PCR method for both patient and control groups and statistical data were obtained from SPSS. Based on the eveluated results, CC homozygous genotype 24 (38.7%), CT heterozygous genotype 53.2(%33), TT homozygous genotype 5 (8.1%) has been detected in patient group. On the other hand, CC genotype 30 (49.2%), CT genotype 26 (42.6%) and TT genotype 5 (8.2%) has been recorded in control group. Consequently, there is a non-significant association between patient and control groups depend on genotype analysis (p=0.475). This study aims to detect EGFR rs1468727 SNP in patient with prostate cancer is Turkish population and improve new aspects to clinical trials. Key words: Cancer, prostate cancer, EGFR
The role of IL1-β gene polymorphism (rs1146327) in non-small cell lung cancer
The goal of this written research is to study the role of IL1-β gene SNP rs1146327 in non-small cell lung cancer (NSCLC). Although the etiology and compulsive mechanisms of NSCLC are unknown, and it is a multifaceted and complex illness, age and inherited factors are supposed to have a part in its growth. Nonetheless, smoking, age, family history, and genetic variables are the most commonly cited factors related with NSCLC. We tested the rs1146327 polymorphism in patients with NSCLC and comparison groups using real-time PCR, and found no statistically big differences in findings between the two groups of affected and control groups. Our data show that the patients' dominant form (GG), heterozygote (GA), and recessive form (AA) rates are 33.3 percent, 43.8 percent, and 22.9 percent, respectively. However, the dominant form (GG), heterozygote (GA), and recessive form (AA) percentages in the comparative group are 16.7 percent, 59.5 percent, and 23.8 percent, respectively. According to our findings, the homozygote mutant type (AA) ratio was larger in controls than in affected persons, despite the change was not significant (p-value = 0.091). The homozygote wild type (GG) ratio was also greater in controls than in patients, with a p-value of 0.951, which was not major.
The role of KLK10 gene (RS7259451) polymorphisms in susceptibility to non-small cell lung cancer
Nowadays, with the COVID-19 disease, the significance of lung cancer specially NSCLC has increased. Moreover, it is also important because it is the second most deadly cancer among other cancers. Kallikrein 10 (KLK10) is one of 15 kallikrein family members. It is a serine endopeptidase and also it has a potential of tumor suppressor protein in prostate and prostate malignant cells. The aim of this study, observation of the impact of KLK10 gene (rs729451) in NSCLC. Blood sample were collected from 48 NSCLC patient and 46 healthy control groups. All DNA isolated from blood samples by using DNA Isolation Robot. Then DNA samples were prepared to make Real-Time PCR (RT-PCR) by using KLK10 detection kit. After RT-PCR, allelic discrimination was obtained from both patient and control groups. Then statistical analyzes were done in SPSS 26.0 by using Fisher's Exact Tests and Chi-square tests and also student's t-test was utilized to get numerical values. P values less than or equals to 0.05 are considered statistically significant. According to analysis, GG wild type homozygote 52.1% (n=25), GT heterozygote 45.8% (n=22) and TT 2.1% (n=1) has been recorded in patient. In addition to this, GG wild type homozygote 60.9% (n=28), GT heterozygote 32.6% (n=15) and TT 6.5% (n=3) has been obtained in control group. Moreover, G allele 80.2% (n=72) and T allele 19.8% (n=24) in patient, and G allele 77.2% (n=71) and T allele 22.8% (n=21) in control group. In the control group, the TT genotype was three times greater (p=356). These findings suggest that the TT genotype is a carrier genotype. Nonetheless, the number of TT genotypes (both control and patient) was extremely low, requiring more research. As a consequence, there is no statistically significant difference in KLK10 polymorphism between the control and patient groups (rs7259451). It's possible that the TT genotype is a carrier gene. More research, on the other hand, is already required. Perhaps this study might be improved by include a broader or diverse population. Otherwise, alternative SNPs in this gene can be investigated. Keywords: Non-small cell lung cancer, NSCLC, polymorphism, KLK10, rs7259451
Association between the interleukin-1 beta (IL 1β) gene polymorphism and ovarian cancer
Ovarian cancer (OC) is a leading cause of mortality and a common type of cancer among women. Due to the difficulty of diagnosis in early stages, the prognosis of ovarian cancer is poor. Many non-modifiable and modifiable risk factors could increase the susceptibility to developing this disease. One of the non-modifiable risk factors that has a great impact on developing OC is the genetic factor. Interleukin-1β (IL-1β), is a cytokine activator that plays a role in different physiological and pathological events, upregulation of IL-1β have been shown in solid tumors, including melanoma, colon, lung, and breast, and high levels of urinary and serum IL-1β have been detected in epithelial ovarian cancer . This thesis study, it is aimed at examining the relationship of the disease with IL-1β (rs16944) polymorphism which is thought to affect the risk of ovarian cancer. We had two groups, patient group with ovarian cancer (n = 41) and control group (n = 41). Genotyping of both groups was determined by Real-Time PCR, and the statistical analysis of the data was performed by SPSS program. According to our results, AA genotype (homozygote wild type) was found in 8 (19.5%), GA genotype (heterozygote type) in 15 (36.6%), GG genotype (homozygote variant type) in 18 (43.9%) in the control group statistically. In the patient group, genotype distributions were determined 4 (9.8%), 16 (39.0%) and 21 (51.2%) respectively. There was no significant relationship in comparison with genotypes between patient and control groups (p=0.450). This study could provide a novel approach for the clinical treatment of ovarian cancer. Key words: Polymorphism, Genotyping, Interleukin-1β (IL-1β), Epithelial Ovarian Cancer, Ovarian Cancer.
Investigation of chemokine ligand12 (Cxcl12) gene polymorphism in ovarian cancer among the turkish population
Ovarian cancer is considered the eighth killer cancer in women globally. In 2021, about 4059 women were identified as ovarian cancer cases, and 2730 of them were reported as cancer deaths in Turkey. It is relatively uncommon, but it has a high death rate among women due to its being hard to detect at early stages when there are no reliable screening methods. Therefore, most of the patients presented at advanced stages with metastasis. Ovarian cancer is a heterogeneous polygenic disease in which there are numerous morphological and molecular types of ovarian cancer. Several gene mutations are involved in the molecular pathogenesis of ovarian cancer.Chemokine ligand 12 (CXCL12) is a chemokine that acts as a ligand for chemokine (C-X-C motif) receptor 4 (CXCR4). The CXCL12 gene is expressed in normal and ovarian cell cancer. Both CXCL12 and CXCR4 are involved in ovarian carcinogenesis through enhanced tumor cell growth, angiogenesis, and metastasis. This thesis study aims to investigate the possible association between SNP rs1801157 in CXCL12gene and susceptibility to ovarian cancer among the Turkish population. The two groups were investigated (n = 40) ovarian cancer patients and the (n = 47) control group, using real-time PCR and statistical analysis of data was performed by the SPSS program. We focused on the genotypic and allelic distribution of this SNP. According to our findings, homozygote wild type (CC), heterozygote (CT), and homozygote mutant type (TT) rates are calculated respectively as 44.7%, 46.8%, and 8.5% in the control group. However, homozygote wild type (CC), heterozygote (CT), and homozygote mutant type (TT) rates are determined respectively as 42.5%, 47.5%, and 10% in the patients' groups. There was no significant relationship between genotypes in patients and the control group subjects under study. We obtained a p-value of (0.962) Keywords: Ovarian Cancer Chemokine ligand 12, CXCL12,SNP, Genotypes
The relation between vitamin D receptors (rs2228570) polymorphism and prostate cancer
AIM: To investigate the association between the vitamin D receptor (VDR) gene rs2228570 polymorphism and prostate cancer (PC) and Reduce risk in the Turkish population. MATERIAL and METHODS: The SNPs of the VDR gene rs2228570 will be genotyped using TaqMan SNP Genotyping Assays and BioScience (ABI) 7500 real-time PCR system. The statistical analysis was carried out using SPSS version 26.0. This research project will be a case-control retrospective study comprising 69 patients with prostate cancer and a control group which consisted of 63 healthy individuals. RESULTS: In this study, VDR gene (rs2228570) polymorphism was analyzed in patients with PC and the control group. There was no significant difference obtained from this study regarding genotype analysis (p=0.475). In the patient group, the genotype frequency of homozygous wild type (AA) was 4.6%, heterozygous genotype (AG) frequency was 41.7%, and homozygous mutant genotype (GG) was 53.9%. In the control group, the genotype frequency of homozygous wild type (AA) was 8.3%, heterozygous genotype (AG) frequency was 40%, and homozygous mutant genotype (GG) was 51.7%. CONCLUSION: It is the first study that investigates the relationship between VDR gene variation (rs2228570) with prostate cancer susceptibility in Turkish populations. The limited sample size could be a limitation of the study. Thus, new studies with larger populations should be conducted with the VDR polymorphism to show the effect of VDR on PC susceptibility. Keywords: Vitamin D, Prostate cancer, (VDR) gene (rs2228570) polymorphism
Investigation of global genome repair genes polymorphism in patients with ovarian cancer in the Turkish population
AIM: Investigate the relation between XPC rs2228001 and DDB2 rs830083 polymorphism with ovarian cancer (OC) susceptibility in the Turkish population. MATERIAL and METHODS: TaqmanR SNP Genotyping Assays and BioScience (ABI) 7500 real-time PCR system will used to genotype the single nucleotide polymorphisms (SNPs) of the XPC and DDB2 genes. Statistical analysis will be performed using SPSS version 27.0. This study will involve a group of 103 OC patients and 104 healthy individuals. RESULT: Through the XPC rs2228001 individuals with the homozygous TT genotype had a lower incidence of OC (OR 0.511, CI 95% 0.261 - 1.003) compared to individuals with the GG polymorphism had a greater risk of OC (OR 1.980, CI 95% 1.044 - 3.754). Also, the T allele was linked to a reduced incidence of OC with significant association (p-value = 0.035). While the DDB2 rs830083 homozygous GC genotype had a lower risk of OC (OR 0.521, CI 95% 0.282 - 0.961) compared to individuals with the CC polymorphism had a higher risk of OC (OR 1.895, CI 95% 1.033 - 3.476). While the G allele was linked to a lower incidence of OC with 2 fold. CONCLUSION: It is the first study that investigating the relation between XPC rs2228001 and DDB2 rs830083 genes with OC susceptibility in Turkish populations. These findings give more insight into the genetic factors associated with OC susceptibility, focusing on the importance of DNA repair systems in diseases. Additional research is required to validate these findings in more diverse and larger populations, allowing for more accurate risk assessment and possibly directing particular treatment options for OC patients. Keywords: Ovarian Cancer, Nucleotide Excision Repair, XPC rs2228001, DDB2 rs830083.
Investigation of DNA damage binding protein 2 (DDB2) gene polymorhism in prostate cancer patient in Turkish population
AIM: To investigate in the Turkish population the gene variation of the DDB2 gene rs830083 polymorphism and prostate cancer (PC). MATERIALS and METHODS: The SNPs of the DDB2 gene rs830083 will be genotyped using TaqmanR SNP Genotyping Assays and BioScience (ABI), real-time 7500 PCR system. The statistical analysis was carried out using SPSS version 26.0. This research project will be a case-control retrospective study comprising 93 patients with prostate cancer and a control group which consisted of 91 healthy individuals. RESULTS: In this study, DDB2 gene (rs830083) polymorphism was analyzed in individuals with Prostate Cancer and control group. Although, there were no significant difference regarding genotype analysis (p=0.216), G allele frequency was significantly higher in the control group 46.2% (p = 0.037). In genotype distribution, of GC was significantly higher in the control group and CC genotype was significantly higher in the patient group, frequency was 26.9% and C 68.8% (p value = 0.048 and 0.037). CONCLUSION: It is the first study investigating the relation between DDB2 gene variations (rs830083) with PC in Turkish populations. Our findings displayed that carrying G allele could be a risk reducing factor for PC susceptibility. Thus, new studies with larger populations should be conducted with the DDB2 polymorphism to show the effect of DDB2 on PC susceptibility. Keywords: DNA Damage Binding Protein, Prostate cancer, (DDB2) gene (rs830083) polymorphism.
Investigation of DNA damage binding protein 2 genetic variation in lung cancer patients in the Turkish population
Lung cancer is one of the main causes of cancer-related fatalities globally worldwide, defined by aberrant cells growing out of control in the lungs. It is primarily linked to smoking, but can also be influenced by genetic, environmental, and occupational factors. DNA repair mechanisms, specifically nucleotide excision repair (NER), are essential for preserving genomic stability and preventing cancer. The purpose of this study was to examine the relationship between polymorphisms in NER-related genes, specifically DDB2 (rs830083), among 96 NSLC patients and 96 controls within the Turkish population. Genotyping was conducted using the Fast Real-Time 7500 system (Applied Biosystems). Results showed that individuals with the homozygous GC genotype of DDB2 rs830083 had an odds ratio (OR) of 0.699 (95% CI: 0.372 - 1.312), whereas those with the CC polymorphism had an OR of 1.267 (95% CI: 0.693 – 2.318). There is no significance correlation between DDB2 polymorphism and LC, according to our research in the Turkish population, highlighting the need for further studies. These findings underscore the importance of continuing research in larger and more diverse populations to better understand genetic factors linked to lung cancer susceptibility, refine risk assessments, and guide potential treatment strategies.
Investigation of angiotensin converting enzyme gene polymorphism in multiple sclerosis patients
Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease that may cause loss of motor function, muscle weakness, spasticity, coordination disorder, vision loss, cognitive disorders, and urinary incontinence, thereby reducing patients' comfort. MS is a multifactorial autoimmune disease where genetic predisposition plays a significant role. Examining the prospective role of the ACE I/D polymorphism as an MS risk factor is the primary motivation for this research. The study involved a total of 183 participants, comprising 90 patients diagnosed with MS from the same neurology clinic and 93 individuals who volunteered for the control group. DNA was extracted from blood samples by employing the real-time polymerase chain reaction (PCR) technique to identify ACE gene I/D polymorphisms. A comparison was made between the genetic characteristics of the polymorphisms in the subjects versus control sections, as well as the demographic and previously collected laboratory data for participant follow-up. There were no substantial variations observed in the abundance of ACE I/D polymorphism genotypes between the MS and healthy comparison groups (X² (2) =0.264, p=0.877). Similarly, there were no significant variations in allele frequency between the control and sick groups (X²(1)=0.07; p=0.777). When examining laboratory data based on genotypic distribution, it was discovered that, with the exception of TSH, the remaining laboratory measures showed no variation between genotypes. Individuals with the DD genotype exhibited considerably lower TSH levels compared to those with II and ID genotypes. As a secondary finding of the study, while comparing the laboratory and demographic data among individuals with MS and the unaffected group, it was noted that MS patients had lower weight, creatinine levels, triglycerides, and HbA1c levels, while having higher HDL and TSH levels (p>0.05). After all, as a primary endpoint, the ACE I/D genetic variation does not have any correlation with the progression of MS. As a secondary endpoint, we suggest that the differences in laboratory parameters between patient and control groups may be due to nutritional problems, autoimmunity, or the effects of medications related to disease severity. Therefore, further studies with a larger number of patients and detailed demographic data analysis would be beneficial.
Investigation of 8q24 (rs6983267) gene polymorphism related to prostate cancer
This thesis explores the rs6983267 gene polymorphism at the 8q24 locus, which is thought that is related with the development of prostate cancer. The study aims to assess the impact of this genetic variation on the development of prostate cancer and its potential biological mechanisms. The research was performed by using real time Polymerase Chain Reaction (RT-PCR) and genotyping analyses on a broad patient population. The study was completed with a total of 171 men. 93 men had PCa therefore formed the "case" group, remaining 78 men formed the control group. Several studies and meta-analysis have been done by various researchers; and showed the relationship between PCa and 8q24 (rs6983267) gene polymorphism. However in our study 39.8 % of the "Case" group has GT genotype. The percentage of GT genotype is 34.5% among the "Control" group. The p-value is 0.352 pointing to a non-significant difference. This association has been examined across different age groups, and environmental factors. Furthermore, the cellular effects of rs6983267 and its role in cancer development have been investigated using molecular biology techniques. This thesis highlights the significance of the rs6983267 gene polymorphism as a potential biomarker for both diagnosis and treatment of prostate cancer. It also suggests new avenues for future research. Key Words: Polymorphism, 8q24, rs6983267, Prostate Cancer
The relation between gpx1 gene polymorphism and ovarian cancer
A common form of cancer and the main cause of death among women is ovarian cancer (OC). Diagnosis in the early stages of the disease is challenging, resulting in a poor prognosis. The risk of ovarian cancer can be increased by both non-modifiable and modifiable factors. Glutathione Peroxidase 1 (GPX1) is a vital enzyme that plays a crucial role as an antioxidant through regulating of reactive oxygen species levels in the cells. The role of GPX1 gene variants in cancer risk is debated. High levels of GPX1 are often present in various types of cancer, but some studies suggest that low levels of circulating GPX1 may increase cancer risk, so GPX1 can act as both a tumor suppressor and promoter. The GPX1 (rs1050450) polymorphism is the most common functional SNP in the human GPX1 gene and is associated with various cancers, including breast, prostate, bladder, lung, leukemia, and colorectal cancers. The aim of this thesis work was to examine how much extent the GPX1 (rs1050450) polymorphism affects the risk of ovarian cancer. There were included two groups, a group of 90 patients with ovarian cancer, and a group of 90 healthy controls. Real-Time PCR was used to genotype both groups, and SPSS was used to analyze the data. According to our result, those with a homozygous CC genotype having a reduced risk (Odds Ratio [OR] 0.304, 95% Confidence Interval [CI] 0.161 - 0.577). Inversely, persons with a TT polymorphism have a higher risk (OR 3.308, 95% CI 1.024 - 10.682). The C allele indicates a substantial relationship to a diminished risk, indicating a potential threefold reduction. However, individuals with the T allele are approximately three times more sensitive to this form of cancer than those without the condition (the odds ratio (OR) of 3.286). The GPX1 gene has a significant P-value of 0.001, suggesting a substantial link between the gene and cancer initiation.
Investigation of catechol-o-methyl transferase (COMT) gene VAL158MET polymorphism and its relationship with prostate cancer
In worldwide, prostate cancer is going to be the second most frequently diagnosed cancer and the fifth leading death object in men. The COMT enzyme hydrolyzes the catechol estrogens especially 2-hydroxyestradiol, resulting to generate 2-methoxyestradiol or 2- ME2, which is an inactive catechol estrogen. The objective of this written research is to investigate if the effects of the COMT gene VAL158MET polymorphism is a possible hazard factor for developing prostate cancer or malignancy. With the accomplishment of real-time PCR, we experimented COMT Val158Met polymorphism in patients with prostate cancer and comparison groups who are healthy men. Rs4680 polymorphism is an A/G transition substitution, as this case (A) allele is the wild type and (G) allele is the mutant type. According to our determination, homozygote mutant type (GG), heterozygote (GA), and homozygote wild type (AA) rates are calculated respectively as 24.5%, 49.3%, and 26.2% in the patient group. Correspondingly the ratio of the homozygote mutant type (GG), p-value was lower than (0.05) p-value = 0.491, so it is not a significant value. The ratio of the homozygote wild type (AA) was also not significant, p-value = 0.365. The ratio of the heterozygote genotype (GA) was also not significant at p-value = 0.174. This sketch has found no statistically significant sense of findings among the two groups of the patient and the comparison groups as well. According to the alleles, we also found no statistically significant findings in COMT gene polymorphism between patients and the controls. We recommend that these studies should be further carried out by increasing the sample size of the study groups to determine more exact knowledge and effect of COMT gene VAL158MET polymorphism for prostate cancer.