Mutation analysis of the TERT gene in ovarian cancer patients of the Turkish population by next generation sequencing method.

Ovarian cancer (OC) ranks seventh among malignant tumors worldwide. As one of the most common gynecological malignancies, ovarian cancer has the second-highest mortality rate, after cervical and uterine cancer. Next-Generation Sequencing (NGS) technology has enhanced multi-gene panel analysis and its clinical utility for identifying cancer-causing gene mutations. This study aimed to determine the presence of significant and nonsense mutations in telomerase reverse transcriptase (TERT), alpha-thalassemia/mental retardation, X-linked (ATRX), O-6-methylguanine-DNA methyltransferase (MGMT), and isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) genes using the Next-Generation Sequencing (NGS) method. A cohort of 33 patients diagnosed with ovarian cancer was included in this investigation, and peripheral blood samples were collected from all participants. Significant and nonsense mutations in TERT, ATRX, MGMT, IDH1, and IDH2 genes were detected using the Next-Generation Sequencing method. Bioinformatics analysis was conducted using the QIAGEN Clinical Insight system. Twenty-four patients exhibited seven different TERT mutations, occurring in both exonic and intronic regions. One patient displayed a c.699-3delC deletion in the intronic region of the IDH1 gene, and the c.532G > A (p.V178I) mutation observed in three patients was assessed as potentially harmful. Additionally, novel mutations c.881A > G and c.995A > G were observed in the ATRX gene. The heterozygous novel mutation identified in the ATRX gene was confirmed through Sanger sequencing. These mutations were not previously associated with ovarian cancer and are considered novel candidate markers for ovarian cancer susceptibility. Confirmation of these results through larger cohort studies or functional investigations will contribute to a better understanding of the molecular mechanisms underlying ovarian cancer.

The Role of Kallikrein10 (KLK10) Polymorphism in Prostate Cancer Susceptibility.

PURPOSE: The present study aims to investigate the potential role of Kallikrein 10 (KLK10) genotype and allele frequencies in predisposition to prostate cancer. MATERIALS AND METHODS: KLK10 (rs7259451) gene polymorphisms were determined by real-time polymerase chain reaction analysis in patients with prostate cancer (n=69) and controls (n=76). RESULTS: KLK10 gene frequencies were significantly different in the case and control groups (P = .028). GG carriers were significantly higher in the control group (P = .034), whereas TT carriers were higher in the prostate cancer group (P = .033). Furthermore, The patients with GG genotype had the lowest PSA levels while TT carriers had the highest (P = .005). CONCLUSION:  According to the results, we suggested that carrying variant T allele and also carrying homozygote TT genotype could be a potential risk, while ancestral homozygote GG genotype and G allele are risk reducing factors for prostate cancer.

Investigation of Catechol-O-methyltransferase (COMT) gene Val158Met polymorphism in ovarian cancer

Objective: Catechol-O-methyltransferase (COMT), the product of the COMT gene, detoxifies the carcinogenic catechol estrogens. The aim of the present study was to examine the relationship between COMT Val158Met polymorphism and the risk of ovarian cancer. Material and Methods: The study groups consist of 94 individuals as a patients group with ovarian cancer (n=47) and control group (n=47). The allele and genotype frequencies were determined according to Hardy-Weinberg equilibrium (HWE). The allele and genotype frequencies. determined according to HWE. Genetic analysis were performed by real-time-polymerase chain reaction instrument, and the statistical analysis were performed by SPSS program. Results: Although no significant relationship was obtained among groups (p=0.413) regarding COMT gene Val158Met polymorphism, the genotype frequencies for COMT Val158Met (rs4860) polymorphism in groups was homozygote wild type GG genotype 25.5%, heterozygote GA genotype 46.8%, homozygote mutant AA genotype 27.7%. Conclusion: This study is the first to investigate the relationship between ovarian cancer and the Val158Met polymorphism in the COMT gene in a Turkish population. No statistically significant relationship was identified among genotypes belonging to the patient and control groups although sample sizes were relatively small and the analysis should be repeated in a larger cohort.

5-Alfa reductase type 2 (SRD5A2) gene rs523349 polymorphism is not associated with non-obstructive azoospermia in Turkish patients.

Spermatogenesis is an androgen-dependent event, and testosterone is the major androgen source. The enzyme 5-alpha reductase converts testosterone to dihydrotestosterone (DHT) in testicular and peripheral tissues. Polymorphisms in genes encoding 5-alpha reductase may be associated with impaired male fertility. The present study aimed to investigate the relationship between 5-alpha reductase type 2 (SRD5A2) gene rs523349 polymorphism and non-obstructive azoospermia (NOA) in Turkish patients. The study included 75 NOA patients and 43 fertile men from Turkey. No significant relationship was found between SRD5A2 gene rs523349 polymorphism and male infertility (P = 0.071). There was a statistically significant difference in total testosterone level and total testis volume between NOA patients and the control groups, however there was no significant difference between serum follicle-stimulating hormone and luteinizing hormone levels. Our results showed that SRD5A2 gene rs523349 polymorphism was not associated with NOA in Turkish patients.

Potential Protective Role of SDF-1 and CXCR4 Gene Variants in the Development of Dementia.

BACKGROUND: The aim of this study was to evaluate the role of polymorphisms of stromal cell-derived factor-1 (SDF-1) and chemokine receptor-4 (CXCR4) genes in dementia susceptibility in a Turkish population. SUBJECTS AND METHODS: The study group included 61 dementia patients, while the control group comprised 82 healthy individuals. Gene polymorphisms of SDF-1 3'A G801A (rs1801157) and CXCR4 C138T (rs2228014) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: A significantly reduced risk for developing dementia was found for the group bearing an A allele for SDF-1 3'A polymorphism (p=0.009; χ2=6.812; OR=0.626; 95%CI= 0.429-0.913). The frequency of the CXCR4 TT and TC genotype was significantly lower in patients with dementia compared to controls (p=0.028; χ2=5.583; OR=0.215; 95%CI=0.05-0.914); (p=0.027; χ2=4.919; OR=0.484; 95% CI=0.246-0.955). Additionally, combined genotype analysis showed that the frequency of SDF1 GA-CXCR4 CC was significantly lower in patients with dementia in comparison with those of controls (p=0.049; OR=0.560; 95% CI= 0.307±1.020). CONCLUSIONS: Our study provides new evidence that SDF1 A and CXCR4 T alleles may be associated with a decreased dementia risk. The present study is important because to our knowledge, it is the first one to be conducted in a Turkish population to date, but we believe that more patients and controls are needed to obtain statistically significant results.

The Evaluation of Proteoglycan Levels and the Possible Role of ACAN Gene (c.6423T>C) Variant in Patients with Lumbar Disc Degeneration Disease.

BACKGROUND/AIM: The present study aimed to investigate the role of an aggrecan (ACAN) gene variant and proteoglycan levels in the risk of lumbar degenerative disc disease (LDDD). MATERIALS AND METHODS: A total of 108 patients with LDDD and 103 healthy controls were enrolled. Molecular assessment of the ACAN gene (c.6423T>C) variant was determined by real time-polymerase chain reaction. Proteoglycan levels in serum were measured with enzyme-linked immunosorbent assay. RESULTS: The frequency of all alleles and genotypes in all study groups were distributed according to the Hardy-Weinberg equilibrium. In addition, no association between the ACAN gene (c.6423T>C) variant and presence of risk factors for LDDD was detected. However, proteoglycan levels were significantly lower in patients with LDDD compared to the control group (p<0.00001). CONCLUSION: Our findings suggest that proteoglycan has emerged as a potential novel biomarker which might be used for prediction of LDDD risk.

Association between apolipoprotein E genotypes and panic disorder in Turkish population.

AIM: In this study, we aimed to investigate possible interactions among the apolipoprotein E (ApoE) and panic disorder (PD), taking into account serum cholesterol levels and subfractions. METHODS: ApoE genotyping was performed by real-time polymerase chain reaction in DNA samples of PD patient group (n = 45) and healthy control group (n = 50). The serum lipid levels, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) subfraction analysis were examined. RESULTS: There was a significant difference of ApoE genotypes in patient and control groups. The E3/E3 genotypes lower whereas E4 allele carriers were significantly higher in PD group ApoE4allele carriers had 3.2-fold higher risk of PD. PD group had significantly lower LDL and HDL levels. In spite of the decreased levels of total LDL, antiatherogenic large LDL subgroup was significantly lower in a patient with PD. Antiatherogenic large HDL and Intermediate HDL levels were lower, while atherogenic small HDL subfraction was significantly higher in PD group. Furthermore, Apo E3/E3 genotype carriers had significantly higher large LDL, HDL, large HDL, intermediate HDL level, and also had highest HDL between all the groups. ApoE4 allele carriers while they had highest atherogenic small HDL level. CONCLUSION: E4 allele can be associated with PD as an eligible risk factor, the E3/E3 could be a risk-reducing factor for PD. Patients with PD not only had lower LDL and HDL levels but also they have higher atherogenic LDL and HDL subfractions. Also, E3/E3 genotype carriers had convenient but ApoE4 carriers had atherogenic plasma cholesterol levels and subfractions.

Relation of MPO, MnSOD, NQO1 gene variants in endometrial carcinoma in the line of PCR-RFLP methods.

Reactive oxygen species (ROS) have been shown to be responsible for inducing DNA damage leading to mutagenesis, carcinogenesis, and cell death if the capacity of the protective antioxidant system is impaired. Endometrial carcinoma is the primary cancer type in the female genital system. The enhanced cell lipid peroxidation and impaired antioxidant enzyme activities observed in patients with endometrial cancer indicate the potential for oxidative injury to cells and cell membranes in such patients. The aim of the study was to investigate the possible association between gene variants of superoxide dismutase (SOD), myeloperoxidase (MPO), and NADPH quinone oxido reductase (NQO1), and their possible role in endometrial cancer in Turkish patients. According to results, MPO G+ genotype and AG genotype were significantly increased in patients compared with controls (P<0.001). We suggest that the MPO polymorphism might be a risk for endometrial cancer.

Association between fok1 polymorphism of vitamin D receptor gene with uterine leiomyoma in Turkish populations

Objective: The aim of this research was to determine the association between the fok1 polymorphism and uterine leiomyomas. Material and Methods: For genotyping the fok1 polymorphism of the vitamin D receptor, real-time polymerase chain reaction was performed on blood samples of uterine leiomyoma (n=27) and control (n=33) groups. For statistical analyses, SPSS v.23 software (SPSS Inc., Chicago, IL, USA) was used. Results: A statistically significant difference was observed for the frequency of the CC genotype between the uterine leiomyoma and control groups, and the frequencies of the T allele in the uterine leiomyoma groups were significantly higher than in the control group. CONCLUSION: The presence of the fok1 CC genotype may be a risk-reducing factor and the T allele may be a potential risk factor for developing uterine leiomyoma.

Association of CCR2 (+190 G/A) Gene Variants and Ovarian Cancer Severity.

AIM: Chemokines and their receptors play an important role in tumor progression. In the current study, we aimed to determine the association between the CCR2 gene (+190 G/A) polymorphism and ovarian cancer severity. METHODS: CCR2 (+190 G/A) genotyping was performed using real-time polymerase chain reaction for DNA isolated from blood samples from a cohort of patients with ovarian cancer (n = 44) and a control group (n = 45). RESULTS: The CCR2 (+190 G/A) GG genotype frequencies for patients were significantly higher in the stage III-IV cancer group (p = 0.036), and A allele carriers were significantly higher in the stage I-II ovarian cancer group. CONCLUSION: The CCR2 (+190 G/A) GG genotype may be a potential risk factor for the severe forms of ovarian cancer and the A allele may be a risk-reducing factor for severe ovarian cancer.

The effects of PON1 gene Q192R variant on the development of uterine leiomyoma in Turkish patients.

AIM: This study aimed to analyze the relation between uterine leiomyoma (ULM) patients and p.Q192R polymorphism. MATERIALS AND METHODS: ULM patients (n=76) and healthy women (n=103) were recruited from the Yeditepe University, Department of Gynecology and Obstetrics. The genotype and allele distribution of p.Q192R was analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. Genotype and allele frequencies between study groups were calculated by the chi-square (χ(2)) and Fischer's exact test. RESULTS: The frequency of the B allele was lower in patients (p<0.001) and the AB genotype showed a decreased risk for ULM development (p<0.001). The variation was unrelated to ULM size and number. There was no significant difference between p.Q192R genotype frequencies and fibroid size and number. CONCLUSION: The heterogeneous AB genotype of PON1 p.Q192R variation could be recognized as a low-risk parameter for the development of ULM in Turkish women.

Paraoxonase1 192 (PON1 192) gene polymorphism and serum paraoxonase activity in panic disorder patients.

BACKGROUND/AIM: Reactive oxygen species (ROS) are involved in the development of certain neuropsychiatric disorders. Paraoxonase 1 (PON1) activity has been suggested to be adversely related to oxidative stress in plasma. The purpose of the present study was to demonstrate the relationship between serum PON1 activity and PON1 192 polymorphism in panic disorder (PD). MATERIALS AND METHODS: Fourty-two patients with PD and 46 healthy controls were included in this study. PON1 192 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. PON1 activity was measured by spectrophotometric assay of p-nitrophenol production following the addition of paraoxon. RESULTS: PON1 192 AA genotype and A allele in PD were significantly higher than in the control group, whereas the B allele was found to be significantly higher in the control group. Patients with panic disorder have lower PON1 activity than the control group. CONCLUSION: The PON1 192 AA genotype may increase the risk of PD depending on lipid peroxidation.

The relationship between ACE polymorphism and panic disorder.

BACKGROUND: The angiotensin converting enzyme (ACE) gene, which has been found to have an insertion and deletion polymorphism (I/D), is of increasing interest in etiology and treatment of various psychiatric disorders such as panic disorder. The present study aimed to investigate the relationship between ACE polymorphism and panic disorder. MATERIALS AND METHODS: In this study, 43 patients diagnosed with panic disorder at the Erenköy Mental and Neurological Diseases Training and Research Hospital, Istanbul and 41 healthy controls were enrolled. The ACE gene insertion/deletion polymorphism of exon 16 was evaluated using the polymerase chain reaction method. RESULTS: There was a significant association between I/D genotype and panic disorder (p=0.003). However, the frequency of the I allele was found to be significantly higher in patients compared to controls (p=0.002). In addition, we recognized a significant association between I/D polymorphism and respiratory-type panic disorder in patients. Carriers of the D allele also had an increased risk of respiratory type panic disorder patients (p=0.034). Moreover, the result of Spearman correlation analysis showed an association with ACE D allele and severity of panic disorder (p<0.001). CONCLUSION: We suggest that the I/D polymorphism of the ACE gene is associated with panic disorder and particularly respiratory-type panic disorder in patients. The I/D polymorphism of the ACE gene seems to influence therapeutic outcome in patients suffering from panic disorder. Our results indicate that ACE D allele is associated with the severity of panic disorder.

Association between FAS and FASL genetic variants and risk of primary brain tumor.

The purpose of this study was to investigate whether functional polymorphisms of apoptosis pathway genes FAS and FASL are associated with the development of primary brain tumors. The study constituted 83 patients with primary brain tumor and 108 healthy individuals. In the present case-control study, the primary brain tumors were divided into two groups: gliomas and meningiomas. Evaluation of FAS -1377 G/A and FASL -844 T/C gene polymorphisms were performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). To confirm the genotyping, results were examined by DNA sequencing method. Our results were analyzed by SPSS. The frequency of the FAS -1377 AA genotype was significantly lower in meningioma and glioma patients compared to controls (p = 0.023; p = 0.001, respectively). Multivariate logistic regression analysis revealed that FAS -1377 AA genotype was associated with decreased risk of meningioma and glioma (OR = 0.092, 95% CI: 0.012-0.719, p = 0.023 for meningiomas; OR = 0.056, 95% CI: 0.007-0.428, p = 0.006 for gliomas). However, there was no significant differences in FASL -844 T/C genotype frequencies between patients with primary brain tumors and controls (p > 0.05). In this study, combined genotypes were evaluated for association with primary brain tumors. Combined genotype analysis showed that the frequencies of AATC and AACC were significantly lower in glioma patients in comparison with those of controls (p = 0.023; p = 0.022, respectively). This study provides the first evidence that FAS -1377 AA genotype may have a protective effect on the developing primary brain tumor in a Turkish population.