Fikriye Polat

Combined Germline Variations of Thrombophilic Genes Promote Genesis of Lung Cancer

BACKGROUND A large variety of familiar and non-familiar lung carcinomas (LC) are caused by long term exposure to chemical carcinogens that are present in tobacco smoke. We aimed to investigate the prevalence of 5 thrombophilic germ-line mutations in patients with lung carcinomas. MATERIALS AND METHODS A total of 52 LC patients and 212 healthy controls from same population were analyzed for FV Leiden, factor V H1299R (R2), PAI-1, MTHFR C677T, MTHFR A1298C, ACE I/D, and Apo E genes and compared. RESULTS Overall, heterozygous and/or homozygous point mutations in FV Leiden Apo E2, PAI-1 and MTHFR C677T genes were associated with LC in the current cohort. There was no meaningful association between LC and ACE I/D gene markers. CONCLUSIONS The current results showed that LC is related to combined thrombophilic gene mutations and individuals with homozygosity of 4G in PAI-1 and MTHFR C677T genes and heterozygosity of FV Leiden, Apo E4 genes have a germ-line risk for LC tumorigenesis.

T-786C, G894T, and intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene in bladder cancer cases.

The aim of the present study was to determine whether endothelial nitric oxide synthase (eNOS) gene polymorphisms play a role in development of bladder cancer in the Turkish population. The study was performed on 75 patients (64 men, 11 women) with bladder cancer and 143 healthy individuals (107 men, 36 women) with any kind of cancer history. Three eNOS gene polymorphisms (T-786C promoter region, G894T and intron 4 VNTR 4a/b) were determined with polymerase chain reaction and restriction fragment lenght polymorphism methods. In our study, GT and TT genotypes for eNOS G894T polymorphism were found to significantly vary among patients with bladder cancer and control group (OR: 0.185, CI: 0.078-0.439, p=0.0001 and OR: 0.324, CI: 0.106-0.990, p=0.026). Also, the frequency of the 894T allele was significantly higher in patients with bladder cancer (51%). No association was identified for eNOS T-786C and intron 4 VNTR 4a/b polymorphisms between patients with bladder cancer and control groups in our Turkish population.

Effect of resveratrol on chromosomal aberrations induced by doxorubicin in rat bone marrow cells

This study investigated the effects of resveratrol (RES) on doxorubicin (DXR) induced rat bone marrow cell chromosome aberrations. RES, a polyphenolic compound, has attracted considerable attention because of its antioxidant and antimutagenic effects. DXR, a chemotherapeutic agent, is known to cause chromosomal aberrations in healthy cells in cancer patients. In this study, Wistar albino male rats were divided into 6 groups with 6 animals each. The control group received distilled water i.p. and the DXR group received an i.p. injection of doxorubicin (90mg/kgbw). For the 2 RES dose groups (12.5 and 25mg/kgbw, respectively), RES was injected i.p. 5 times during the 24h study period to coincide with the schedule for the DXR+RES groups. The DXR-RES groups received DXR (90mg/kgbw) and RES at either 12.5 or 25mg/kgbw, i.p. 30min before, concurrently, and then every 6h after DXR administration. Bone marrow collection was timed to coincide with 24h after DXR administration in all groups. RES administration alone did not induce any significant increase in frequency of chromosome aberrations or abnormal metaphases compared with controls (p>0.05) while DXR alone did (p<0.05). In the DXR-RES 12.5mg/kgbw group, frequency of chromosome aberrations and abnormal metaphases were slightly reduced compared to DXR alone, but this was not statistically significant. However, in the DXR-RES 25mg/kgbw group, RES resulted in a statistically significant reduction in the frequency of chromosome aberrations and abnormal metaphases compared to those induced by DXR alone (p<0.05). These results indicate that RES (25mg/kgbw) significantly reduces frequency of DXR induced chromosome damage in bone marrow cells.

The Association of MYNN and TERC Gene Polymorphisms and Bladder Cancer in a Turkish Population

PURPOSE Researchers reported that, MYNN rs10936599 polymorphism is in strong or moderate linkage disequilibrium with SNPs within the 3q26.2 chromosomal regions that also include the TERC gene. In addition, it has been reported that MYNN rs10936599 had a strong cumulative association with bladder cancer risk, and TERC gene suppresses cell growth in bladder cancer cell lines. Therefore, we aimed to determine whether polymorphisms of MYNN rs10936599 and TERC rs2293607 play any roles for bladder cancer in the Turkish population in this study. MATERIALS AND METHODS In this case-control study, 70 patients and 150 controls were investigated. Genotyping analysis was performed by polymerase chain reaction, restriction fragment length polymorphism and DNA sequencing techniques. RESULTS Genotype distribution between study groups for MYNN rs10936599 SNP was significantly different (P = .001); although there was no difference in genotype distribution for TERC rs2293607 SNP. In addition, patients with CT genotype and CT+TT genotype combination of MYNN SNP have a decreased risk for bladder cancer. Two times increased risk ratio on development of bladder cancer was obtained for CC genotype of the SNP (P = .001). Besides, it was found that genotype combination of GG+AG/CC versus AA/CC genotypes (TERC/MYNN)showed stronger correlation. We observed that statistically significant relationship between the C-G haplotypes of two polymorphisms and bladder cancer risk (P = .0001). CONCLUSION At the end of the study, we suggested that there may exist an association between a combination of MYNN rs10936599 and TERC rs2293607 polymorphisms and development of bladder cancer in Turkish population.

Ursodeoksikolik Asit’in İnsan Periferal Kan Lenfositlerindeki in Vitro Genotoksik Etkisi

Kenodeoksikolik asitin 7b epimeri olan ursodeoksikolik asit (UDKA), kolestatik karaciger hastaliklarinin tedavilerinde artan bir sekilde kullanilmaktadir. Bu calismada, Ursodeoksikolik asitin, insan periferal kan lenfositlerindeki in vitro sitotoksik ve genotoksik etkilerinin belirlenmesi hedeflendi. UDKA’nin potansiyel genotoksik ve sitotoksik etkisi, kromozom aberasyon ve mitotik indeks testleri kullanilarak in vitro olarak arastirildi. Insan peripheral kan lenfositleri, 24 ve 48 saat sureyle, 10, 50 ve 100 μg/ml UDKA ile muamele edildi. Veriler SPSS istatistik programinda, Tek Yonlu Anova (Post Hoc Analiz-LSD Test) testi ile analiz edildi. Elde edilen istatistik sonuclari, kontrolle karsilastirildiginda, uygulanan UDKA konsantrasyonlarinin mitotik indeks degerlerini dusurmedigini ve kromozom anomali frekanslarinda da onemli bir artisa neden olmadigini gostermektedir (p>0.05). UDKA’nin insan kromozomlarinda anomalileri artirmamasi bulgusu, bu maddenin az da olsa insan vucudunda fizyolojik olarak uretilen bir safra asiti olmasi ile baglantili olabilir. UDKA’yi kullanan pek cok hasta olmasi, bu calismadan elde ettigimiz bulgularin onemini artirmaktadir.

eNOS gene polymorphisms in paraffin-embedded tissues of prostate cancer patients.

BACKGROUND/AIM The purpose of the present study was to investigate whether endothelial nitric oxide synthase (eNOS) gene polymorphisms play a role in prostate cancer (PCa). MATERIALS AND METHODS We examined three eNOS gene polymorphisms (T-786C promoter region, G894T, and Intron 4 VNTR 4a/b) at extracted DNAs from 50 formalin-fixed paraffin-embedded tissues of PCa patients. For the controls, blood samples obtained from 50 healthy men were studied. Genotyping of molecular variants was performed by PCR-RFLP technique. RESULTS We found that the TC genotype of the T-786C polymorphism was associated with PCa risk (OR: 3.325, CI: 1.350-8.188, P = 0.008). The eNOS G894T polymorphism was also associated with PCa. The frequency of the 894T allele was significantly higher in PCa patients. No association was identified between intron 4 VNTR polymorphism and PCa. CONCLUSION We found significant differences in genotypic and allelic frequencies between PCa patients and controls for eNOS T-786C and G894T polymorphisms. The presence of the T-786C genotype and 894T allele in carriers increased the risk of PCa. No association was found between intron 4 VNTR polymorphism and PCa patients.

Investigation of Mutations in Exon 7,8 and Exon 9 of FHIT Gene in Laryngeal Squamous Cell Carcinoma

The purpose of this study was to assess and explain the relationship between molecular changes occurring in squamous cell laryngeal carcinoma. Furthermore, we were revealed the role of FHIT gene response in the development and progression of squamous cell laryngeal carcinoma, and genes based exons 7,8 and 9 in tumour stage and histopathologic grade. In this study was used 50 blood samples for control and 26 patients with laryngeal squamous cell carcinoma. Briefly, for this purpose, we primarily aimed researching or evaluating exon 7 (C/T), exon 8 (T/C) and exon 9 (A/G) homozygous deletions of FHIT gene exons. Mutations were examined with polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and RT-PCR based HRM technigues. At the end of the HRM analysis, was observed a significant mutation in the groups of patients. L4 and L19 in the number and before the results of SSCP individuals identified as benign according to the results of HRM. In this study, exon 7 and 9 healthy individuals and squamous cell laryngeal carcinoma were observed any difference between individuals in terms of mutation. The pathology of the case was low differentiation. But in addition to this findings, the present findings highlight that the FHIT gene partially related to target for analysis in case with laryngeal squamous cell carcinoma. According to results of analyses, we idendified a link in between the exon 8 and exon 9 of FHIT gene. Abbreviations: SCC: squamous cell carcinoma; PCR-SSCP: polymerase chain reaction single-strand conformation polymorphism; HRM: high-resolution melting