Anti-Mullerian Hormone Levels Increase After Bariatric Surgery in Obese Female Patients With and Without Polycystic Ovary Syndrome.

This study was aimed to investigate the effect of weight loss by bariatric surgery on the level of anti-Mullerian hormone (AMH) in morbidly obese female patients with or without polycystic ovary syndrome (PCOS). This prospective study includes 70 females, obese, and fertile patients of reproductive age. All patients were evaluated to determine the changes in weight, body mass index (BMI), serum AMH, and other biochemical parameters at the end of six months. The mean levels of the preop and postop AMH were 1.66±0.87 ng/ml and 5.99±1.39 ng/ml in the PCOS group; 1.35±0.76 ng/ml and 6.23±1.47 ng/ml in the non-PCOS group, respectively. The postop AMH levels were significantly higher than the preop levels for both groups (p<0.001). There were significant differences in the level of glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, total cholesterol, hemoglobin A1c, HOMA-IR, insulin between preop and postop 6th month. A negative correlation was found between postop AMH and body weight in all patients (r=-0.337, p=0.031). Postop AMH levels were negatively correlated with postop BMI levels in the non-PCOS patient group (r=-0.408, p=0.043). No significant difference was observed between the PCOS and non-PCOS groups in terms of all the parameters examined. In conclusion, our study suggests that the significantly increased AMH levels by losing weight with bariatric surgery in patients with morbid obesity with and without PCOS may indicate the improvement of fertilization potential. It could be considered when evaluating fertility in patients with morbid obesity.

Gene variants of TCF7L2 are histopathologically important in colorectal cancers but do not have direct association with MYC expression.

Rapidly accumulating preclinical and clinical studies have helped us to unveil underlying mechanisms of colorectal cancer development and progression. Deregulated signaling pathways play instrumental role in carcinogenesis, drug resistance and metastasis. Wnt signaling cascade has attracted considerable attention in colorectal cancer as many ground-breaking researches have highlighted central role of Wnt pathway in pathogenesis of colorectal cancer. T-Cell Transcription Factors (TCFs) have been shown to work synchronously with ß-catenin to fuel colorectal cancer development and progression. Chromatin immuno-precipitation coupled with high-throughput sequencing (ChIP-Seq) data sets has deepened our knowledge about critical role of risk-associated SNPs. Increasingly it is being reported that many risk-associated SNPs are located within binding sites for transcription factors and consequently risk status of these SNPs may modify binding pattern of transcriptional factors and thus rewire the transcriptional regulation. DNA was extracted from peripheral blood samples of 117 colorectal cancer patients and 127 healthy subjects. TCF7L2 variants (rs6983267, rs7903146) were examined by the PCR-RFLP method. Tumor and the surrounding tissues were dissected from 37 CRC patients and RNA isolation was performed. The gene expression of c-myc was determined by RT-PCR. T allele carriage of rs6983267 variant was found to be associated with CRC (p=0.042). TT genotype of rs7903146 was associated with late tumor stage (T3+T4) (p=0.037) and presence of mucinous component (p=0.031). TTCT haplotype was found to be statistically higher in CRC compared to the control group (p=0.007). There was no statistically significant difference in c-myc gene expression. TCF7L2 gene variants may play an important role in histopathologic aspects associated with CRC and it is independent of c-myc gene expression.

The importance of programmed death ligand 1 gene expression, epidermal growth factor receptor gene mutations and serum epidermal growth factor receptor levels in Turkish non-small cell lung cancer patients.

BACKGROUND: This study aims to investigate the possible relationships between epidermal growth factor receptor gene mutations, serum epidermal growth factor receptor levels, programmed death ligand gene expression levels and the risks and survivals of resectable nonsmall cell lung cancer patients. METHODS: Deoxyribonucleic acid isolation was performed from peripheral blood samples and tumor tissues. The mutation analysis was performed for epidermal growth factor receptor. Programmed death ligand 1 gene expression levels were examined pathologically and histopathologically following the tissue tracing of 36 non-small cell lung cancer patients (29 males, 7 females; mean age 60.1 years; range, 41 to 79 years) and analyzed using real-time polymerase chain reaction. Epidermal growth factor receptor serum levels were assessed in all patients. RESULTS: As a result of mutation analyses in 21 patients (28.5% of all adenocarcinoma patients), epidermal growth factor receptor mutation was determined in at least one exon in six patients. In epidermal growth factor receptor mutation detected patients, programmed death ligand 1 gene expression levels were associated with lymph node metastasis (p=0.036). However, epidermal growth factor receptor mutations were not statistically significantly associated according to histopathological examination (p>0.05). Of patients carrying exon 20 (c.2303G>T) mutations, 25% had tumors with perineural invasion. There was a statistically significant association between exon 20 insertions and c.2303G>T and lymphatic invasion (p=0.02), lymph node metastasis and exon 20 insertions (p=0.03). Patients with lower serum epidermal growth factor receptor levels (<400 pg/mL) had better survival time than those with higher serum epidermal growth factor receptor levels (p=0.04). CONCLUSION: Programmed death ligand 1 gene expression and epidermal growth factor receptor mutation might have a combined effect on non-small cell lung cancer. Programmed death ligand 1 gene expression in tumor pathology may also be a significant feature for tumor progression and tumorigenesis. Serum epidermal growth factor receptor levels seem to be associated with survival.

The assessment of total antioxidant capacity and superoxide dismutase levels, and the possible role of manganese superoxide dismutase polymorphism in acromegaly.

Oxidative status is attributed to endothelial dysfunction and might be one of the key mechanisms of endothelial dysfunction in acromegaly. In this study, we aimed to investigate the effect of acromegaly on superoxide dismutase (SOD) and total antioxidant capacity (TAC) levels, and the possible influence of human manganese superoxide dismutase (MnSOD) polymorphism on these levels. 51 acromegaly patients and 57 age and sex matched healthy subjects were recruited to the study in Bezmialem Vakif University Hospital between 2011 and 2014. The median SOD and TAC levels were 42.7 (33-60) pg/mL and 1,313.7 (155-1,902) µM in acromegaly; and 46.3 (38-95) pg/mL and 1,607.3 (195-1,981) µM in healthy subjects (p < 0.001, p < 0.001). SOD levels were decreased in controlled and uncontrolled patients compared to healthy subjects (p = 0.05 and p = 0.002, respectively). Controlled and uncontrolled acromegaly displayed significantly decreased levels of TAC compared to healthy subjects (p < 0.05 and p < 0.001, respectively). SOD levels were not associated with MnSOD polymorphisms in acromegaly. In conclusion, this study showed that acromegaly was associated with decreased levels of SOD and TAC, and controlling the disease activity could not adequately improve these levels.

The Role of p16 and MDM2 Gene Polymorphisms in Prolactinoma: MDM2 Gene Polymorphisms May Be Associated with Tumor Shrinkage.

AIM: Prolactinomas are thought to arise from clonal expansion of a single mutated cell which is subjected to growth stimuli of several permissive factors, although the pathogenetic mechanisms underlying tumorigenesis remain unclear. The present study aimed to investigate the role of p16 (540C→G and 580C→T) and mouse double minute 2 (MDM2) (SNP309T→G) gene polymorphisms in tumorigenesis and characteristics of prolactinoma. PATIENTS AND METHODS: A total of 74 patients with prolactinoma and 100 age- and gender-matched healthy individuals were enrolled in the study. Serum prolactin levels were measured by enzyme-linked immunosorbent assay (ELISA). p16 and MDM2 polymorphisms were determined by polymerase chain reaction-restriction fragment polymorphism and agarose gel electrophoresis. RESULTS: p16 540C→G genotype distribution was found to be: CC: 66.2%, CG: 28.4%, GG: 5.4%; p16 580C→T genotype distribution was found to be: CC: 82.4%, CT: 17.6%, TT: 0% and MDM2 genotype distribution was found to be: TT: 31.1%, TG: 47.3%, GG: 21.6% in patients with prolactinoma. Tumor diameter before treatment was correlated with prolactin levels before treatment and percentage of prolactin decrease with treatment (r=0.719, p<0.001, p=0.034 r=0.256, respectively). The number of patients with tumor size decrease of more than 50% in those with homozygous genotype (TT+GG) of MDM2 SNP309T→G was significantly higher than in heterozygous genotype (TG) carriers (odds ratio(OR)=0.18, 95% confidence interval(CI)=0.06-0.58; p=0.003). CONCLUSION: This study showed that p16 and MDM2 polymorphisms do not play a decisive role in tumorigenesis, but some genotypes of these polymorphisms might be associated with follow-up characteristics of prolactinoma.

Relationship of CTLA4 and CD28 polymorphisms with lung involvement, HRCT findings and pulmonary function tests in Turkish patients with ankylosing spondylitis.

BACKGROUND AND AIMS: Ankylosing spondylitis (AS) is a multisystem disorder with ocular, pulmonary, and cardiovascular involvement. The incidence of pulmonary involvement varies from 1 to 52%. Abnormal T-cell function-derived immune responses are involved in AS pathogenesis. Numerous genes such as CTLA4 and CD28 control T-cell functions. In this study, we aimed to address the relationship between CTLA4 and CD28 polymorphisms and lung involvement in Turkish patients with AS. METHODS: A cross-sectional evaluation of 80 healthy and 89 AS subjects with no active infection or malignancy was performed to determine the relationship between pulmonary involvement and CTLA4 and CD28 gene polymorphisms. All patients were assessed for clinical, radiological, and spirometric findings. Descriptive statistics, chi-square tests, and independent-sample t-tests were used for statistical analyses. RESULTS: All patients with the CD28 CC genotype (n = 4) had abnormal HRCT, but it was not significant (p = 0.47). All of the normal HRCT patients have CD 28 T alleles. In addition to this data ; 4 patients who have not any T alleles have abnormal HRCT finding. It was significant and was considered that T genotype have protective effect (p= 0,047) on radiologic involvement but no other association was found between CTLA4 and CD28 gene polymorphism with respect to pulmonary function tests (PFT), diffusion capacity, and clinical characteristics in the Turkish patients with AS. CONCLUSION: Our results suggest a possible association of CTLA4 and CD28 variants with AS pulmonary involvement. Furthermore, these results may lead to the development of new therapeutic agents to control more aggressive forms of the disease. However, further studies are needed in larger populations.

Expression of miR-373 and its predicted target genes E-cadherin and CD44 in patients with laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a genomically complex disease that is difficult to target, and efforts have been made to identify new treatment strategies and   molecular markers that might stratify patients and individualize options for treatment. miR-373 has diametrically opposed roles in different stages and types of cancers. miR-373 has been suggested to quantitatively control E-cadherin and CD44 expression. We studied the expression of miR-373, E-cadherin and CD44 in laryngeal squamous cell carcinoma and evaluated the association between the disease and clinical characteristics of patients. Tumor tissues were collected from 24 laryngeal cancer patients. Adjacent normal tissue samples were also obtained as controls. After RNA isolation, we assessed the miR-373, E-cadherin and CD44 levels. As endogenous controls, we used the small RNA U6 and GAPDH TaqMan® to normalize the levels of expression of miR-373, E-cadherin and CD44. The fold change in the expression of the genes in larynx tumor and control tissues was calculated using the 2-ΔΔCT method. miR-373 was significantly upregulated in seventeen tumor samples compared to controls. However, the expression levels of both E-cadherin and CD44 mRNA were found to be significantly downregulated in tumor versus control regions (p=0.026 and p=0.005, respectively). We did not find any significant difference in the expression levels of miR-373, E-cadherin or CD44 and cancer risk factors. miR-373, E-cadherin and CD44 may be involved in the etiopathogenesis of laryngeal cancer. It can be suggested that E-cadherin and CD44 are functional targets of miR-373, but we need further studies to investigate this hypothesis.

Association of CTLA4 and CD28 Gene Variants and Circulating Levels of Their Proteins in Patients with Breast Cancer.

BACKGROUND/AIM: Breast cancer is one of the most common and lethal types of cancer among women. We focused on the importance of the immune system in the etiology of breast cancer by investigating critical polymorphisms of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and cluster of differentiation 28 (CD28) gene, and circulating levels of these proteins. MATERIALS AND METHODS: A total of 79 patients with breast cancer and 76 healthy controls were enrolled. Molecular assessment of CTLA4 (rs231775&rs5742909) and CD28 (rs3116496) variants were determined with polymerase chain reaction restriction fragment length polymorphism techniques. Circulating levels of soluble forms of CTLA4 and CD28 were analyzed by ELISA. RESULTS: Although no significant association was found between study groups, CTLA4 +49AA genotypic frequency, and sCTLA4 and sCD28 levels were higher in patients. Some clinicopathological features were also related with CTLA4 and CD28 variants and blood levels. CONCLUSION: While CTLA4 +49AA genotype is increased in patients with breast cancer, the CTLA4 -318T allele may have a prognostic value. In addition, sCTLA4 and sCD28 can be used for diagnostic purposes in patients with breast cancer.

LGALS3 and AXIN1 gene variants playing role in the Wnt/ ß-catenin signaling pathway are associated with mucinous component and tumor size in colorectal cancer.

The Wnt pathway alterations have been identified in colorectal and many other cancer types. It has been reported that galectin-3 (which is encoded by the LGALS3 gene) alters the signaling mechanism in the Wnt/ ß-catenin pathway by binding to ß-catenin in colon and other cancers. AXIN1 is mainly responsible for the assembly of the ß-catenin destruction complex in the Wnt pathway. This study investigated the relationship of rs4644 and rs4652 variants of the LGALS3 gene and rs214250 variants of the AXIN1 gene to histopathological and clinical properties. Our study included a total of 236 patients, of whom 119 had colorectal cancer (42 women, 77 men) and 117 were healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and allele-specific oligonucleotide (ASO) PCR methods were used. In addition, the serum galectin-3 level was studied with the enzyme-linked immunosorbent assay (ELISA) method. For the rs4644 variant of the LGALS3 gene, the CC genotype a mucinous component was significantly more common than those without a mucinous component (p=0.026). C allele frequency of the rs214250 variant of the AXIN1 gene was significantly correlated to tumor size in the advanced tumor stage (p=0.022). The CCAACT haplotype was more common in colorectal cancer patients (p=0.022). Serum galectin-3 level was higher in the patient group compared to the control group (5.9± 0.69 ng/ml vs. 0.79±0.01 ng/ml; p<0.001). In conclusion, variants of LGALS3 and AXIN1 genes affect tumor sizes and the mucinous component via Wnt/ ß-catenin pathway in the pathogenesis of colorectal cancer.

Does DRD2 polymorphism influence the clinical characteristics of prolactinoma?

OBJECTIVES: Genetic alterations explaining the clinical variability of prolactinomas still could not be clarified and dopamine D2 receptor (DRD2) polymorphism is a putative candidate for the variable response to dopaminergic treatment. The present study was conducted to investigate the influence of DRD2 TaqI A polymorphism on initial and follow-up characteristics of prolactinoma. PATIENTS AND METHODS: Seventy-two patients with prolactinoma and 98 age and gender matched control subjects were recruited to the case-control study. Serum prolactin levels were assessed by enzyme-linked immunosorbent assay and DRD2 polymorphism was determined by polymerase chain reaction and restriction length polymorphism analysis. RESULTS: Decrease of prolactin levels and the tumor shrinkage after cabergoline treatment were 93.9±5.9% and 58.3±33.1% in microadenomas and 96.1±6.1% and 51.7±29.3 in macroadenomas (P=0.02 and P>0.05, respectively). We observed no significant difference for DRD2 genotypes and the alleles between the patients and healthy group (P>0.05). Prolactin levels before treatment were correlated with tumor diameter before and after treatment and the percentage of prolactin decrease with treatment (P<0.001 r=0.58, P<0.001 r=0.40 and P<0.001 r=0.47, respectively). Tumor diameter before the treatment was also correlated with the tumor diameter after the treatment (P<0.001 r=0.64) and the percentage of prolactin decrease (P=0.01 r=0.30). However, no significant association was found between characteristics of prolactinoma and DRD2 genotypes and alleles (P>0.05). CONCLUSION: This study revealed that DRD2 TaqI A receptor polymorphism was not associated with the development of prolactinoma and its clinical characteristics. Future studies are needed to clarify the clinical implications of genetic alterations in prolactinoma.

Analysis of CASP8 D302H Gene Variants in Patients with Primary Brain Tumors.

BACKGROUND: Alteration in cell-cycle control and apoptosis pathways play important roles in tumorigenesis. Caspase-8 (CASP8) is a member of the cysteine protease family, that is implicated in apoptosis regulation. The present study was designed to investigate the possible role of CASP8 D302H gene polymorphism in the tumor development. MATERIALS AND METHODS: A total of 91 patients with brain tumors (including 39 meningioma and 52 glioma cases) and 114 healthy controls were included in the study. We investigated CASP8 D302H polymorphism by using polymorphism chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The CASP8 D302H polymorphism genotypic frequencies were not statistically significantly different between meningioma cases and controls, with frequencies of GG, GC and CC genotypes of 71.2%, 19,2% and 9.6%; and 57.9%, 36.8% and 5.3%, respectively. The GG/CC genotypic frequencies were significantly increased in patients with glioma patients compared to controls (p=0.023) (χ(2)=5.149, odds ratio [OR]=1.27, 95% confidence interval [CI]=1.054-1.551). According to tumor characteristics, there were no statistically significant differences within the groups with astrocytic, oligoastrocytic tumors and oligodentriogliomas. CONCLUSION: D302H polymorphism of CASP8 gene may be associated with increased risk of glioma but larger study groups in different ethnic populations are needed to better elucidate the role of CASP8 gene polymorphism in the pathogenesis of primary brain tumors.

Individual and Combined Effects of CTLA4-CD28 Variants and Oxidant-Antioxidant Status on the Development of Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most frequent cancer worldwide. Research has revealed the contributions of the immune system and anti-inflammatory pathways in the development of cancer. The balance between cluster of differentiation 28 (CD28) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) signaling is important for the regulation of immune responses. The oxidant-antioxidant balance by sustaining redox control via several defense mechanisms is also an important factor for the progression of cancer. The aim of the present study was to determine the distribution of CTLA4/CD28 variants and oxidant-antioxidant status in patients with CRC. MATERIALS AND METHODS: This study enrolled 80 patients with CRC and 115 healthy controls. We used a spectrophotometric assay to detect the levels of lipid peroxidation products malon dialdehyde (MDA) and lipid hydroperoxide (LHP), and measured the concentration of protein damage products, advanced oxidation protein products (AOPP) and protein carbonyl (PCO). Additionally, antioxidant levels were detected by measuring copper, zinc, superoxide dismutase (Zn-Cu SOD) and total thiol (T-SH) levels, and advanced glycation end-products (AGEs). The CTLA4 -318C>T, CTLA4 49A>G and CD28C>T genotypes were determined by using restriction enzymes. RESULTS: AOPP and PCO levels were increased in patients with CRC as well as those of LHP, MDA and AGE, while the levels of antioxidants such as Cu-Zn SOD and T-SH were lower. Lower serum levels of CTLA4 and higher serum levels of CD28 were detected in patients and, an association of the CTLA4 -318C/T polymorphism was found in patients with CRC. CONCLUSION: Our oxidative stress was increased in patients with CRC, suggesting the contribution of this disturbed oxidative status to serum CTLA4 and CD28 levels, and to the pathogenesis of CRC.

Distribution and Effects of CDKN2 p16 540 C>G and 580 C>T, and MDM2 SNP309 T>G Polymorphisms in Patients with Primary Brain Tumors.

BACKGROUND/AIM: Primary brain tumors are unique tumors due to their different pathobiological behavior, while they rarely metastasize outside the central nervous system. Regarding the oncogenesis of primary brain tumors, it was shown that changes in functions of p16 and mouse double minute 2 homolog (MDM2) are related to tumor pathogenesis by enhancing cell proliferation and malign development. The present study aims to evaluate the possible associations between cyclin-dependent kinase 2 (CDKN2) p16 540 C>G and 580 C>T, MDM2 single nucleotide polymorphism 309 (SNP309) T>G polymorphisms and primary brain tumor. MATERIALS AND METHODS: Using polymerase chain reaction-restriction fragment length polymorphism technique, we determined SNPs in 67 patients with primary brain tumors and 71 healthy volunteers without malignancy. RESULTS: The frequency of CC genotype for CDKN2 p16 540 C>G was significantly two-fold higher (p<0.001) and possessing a C allele conferred a ~7-fold increased risk (p=0.005) of primary brain tumor. We also found that the CC genotype produced a higher ~4-fold risk of glioma (p=0.001) and the G allele had a possibly protective role against meningioma (~4.8-fold reduced risk, p=0.001). We found no significant associations for CDKN2 p16 580 C>T and MDM2 SNP309 T>G variants between cases and controls. CGT haplotype was significantly less frequent in patients with primary brain tumors and glioma cases (p=0.009 and p=0.028, respectively) than controls. CGG haplotype was significantly less frequent in patients with meningioma versus the control group (p=0.023). CONCLUSION: These findings show that CDKN2 p16 540 C>G, CDKN2 p16 580 C>T and MDM2 SNP309 T>G variants and their haplotypes may be risk factors for the development of primary brain tumors, especially of glioma.

Possible relationship between the resistin gene C-420G polymorphism and colorectal cancer in a Turkish population.

BACKGROUND/AIMS: In recent years, with improvements in genotyping, a possible relationship between obesity-related gene polymorphisms and colorectal cancer (CRC) has been studied. The promoter region C-420G of the resistin gene is believed to have an important role in the development of malignancy. We prospectively evaluated the possible effect of the resistin C-420G polymorphism on the risk and prognosis of CRC. MATERIALS AND METHODS: One hundred twenty-three patients with CRC and 79 healthy individuals were included in the study. Blood samples were genotyped, and the relationship between the resistin C-420G polymorphism and demographic characteristics and tumor features was evaluated. RESULTS: No statistically significant difference was found in genotype distribution between the patient and control groups and among patients in the means of gender, biochemical findings, and tumor characteristics (p>0.05). CONCLUSION: The relationship between the C-420G polymorphism and various diseases has been evaluated in many studies to date. With the increased importance of obesity in etiopathogenesis, studies have focused on CRC. According to our results, the GG genotype may be associated with a decreased CRC risk. Our 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.

Analyses of EGF A61G Gene Variation and Serum EGF Level on Gastric Cancer Susceptibility and Clinicopathological Parameters.

BACKGROUND: Epidermal growth factor (EGF) induces various biological signaling pathways, including proliferation and differentiation and it is the natural ligand of the epidermal growth factor receptor (EGFR) which is a member of tyrosine kinase transmembrane receptor family. EGF and EGFR control important processes in carcinogenesis and several differences in this signaling pathway are very common in certain types of cancers. In present study, we examined EGF A61G gene polymorphism as a marker of risk and progression in gastric cancer. MATERIALS AND METHODS: A total of 84 patients with gastric cancer and 146 control individuals were enrolled in the current study. EGF A61G gene variation was genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The distribution of EGF A61G genotypes were different between patients with gastric cancer and controls (p=0.039). Serum EGF levels in gastric cancer cases were significantly lower than those in controls (p=0.012). There were no correlations between the serum EGF levels according to EGF A61G genotype and allelic distributions in patients with gastric cancer. CONCLUSION: Our findings suggested that EGF A61G gene variations and EGF serum levels might be associated with the risk of gastric cancer.

Genetic variants in the tumor necrosis factor-related apoptosis-inducing ligand and death receptor genes contribute to susceptibility to bladder cancer.

AIM: The aim of this study was to evaluate the role of polymorphisms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and death receptor (DR4) genes in bladder cancer susceptibility in a Turkish population. MATERIALS AND METHODS: The study group included 91 bladder cancer patients, while the control group comprised 139 individuals with no evidence of malignancy. Gene polymorphisms of TRAIL C1595T (rs1131580) and DR4 C626G (rs4871857) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The frequency of the TRAIL 1595 TT genotype was significantly lower in patients with bladder cancer compared to controls (p<0.001; odds ratios [OR]=0.143; 95% confidence interval [CI]=0.045-0.454). A significantly increased risk for developing bladder cancer was found for the group bearing a C allele for TRAIL C1595T polymorphism (p<0.001; OR=1.256; 95% CI=1.138-1.386). The observed genotype and allele frequencies of DR4 626 C/G in all groups were in agreement with the Hardy-Weinberg equilibrium (p=0.540). However, the frequency of DR4 GG genotype was found to be 2.1-fold increased in the bladder cancer patients with high-grade tumor, when compared to those having low-grade tumor (p=0.036). Additionally, combined genotype analysis showed that the frequency of TRAILCT-DR4GG was significantly higher in patients with bladder cancer in comparison with those of controls (p=0.037; OR=2.240; 95% CI=1.138-1.386). CONCLUSIONS: Our study provides new evidence that TRAIL 1595 C allele may be used as a low-penetrant risk factor for bladder cancer development in a Turkish population. Otherwise, gene-gene interaction analysis revealed that the DR4GG genotype may have a predominant effect on the increased risk of bladder cancer over the TRAIL CT genotype.

Investigation of the vitamin D receptor polymorphisms in acromegaly patients.

OBJECTIVE: The genetic structural alterations in the majority of somatotroph adenomas are not clarified and the search for novel candidate genes is still a challenge. We aimed to investigate possible associations between vitamin D receptor (VDR) polymorphisms and acromegaly. DESIGN, PATIENTS, AND METHODS: 52 acromegaly patients (mean age 45.7 ± 1.9 years) and 83 controls (mean age 43.1 ± 2.6 years) were recruited to the study. VDR polymorphism was determined by polymerase chain reaction-based restriction fragment length polymorphism methods. RESULTS: The distribution of VDR genotypes showed a significant difference in the frequencies of VDR FokI genotypes between patients and controls (P = 0.034). VDR FokI ff genotype was significantly decreased in acromegaly patients (P = 0.035) and carriers of FokI Ff genotype had a 1.5-fold increased risk for acromegaly (OR: 1.5, 95% CI: 1.07-2.1; P = 0.020). IGF1 levels after treatment were significantly higher in patients carrying the Ff genotype compared to carrying ff genotype (P = 0.0049). 25(OH)D3 levels were significantly lower in acromegaly patients (P < 0.001). CONCLUSIONS: Our study suggests that VDR FokI genotypes might affect the development of acromegaly and VDR polymorphisms may play a role in the course of acromegaly as a consequence of altering hormonal status.

Determination of gene expression and serum levels of MnSOD and GPX1 in colorectal cancer.

BACKGROUND/AIM: Oxidative stress plays a role on the development of colorectal cancer. Manganese superoxide dismutase (MnSOD) and glutathione peroxidase 1 (GPX1) are crucial in regulating oxidative balance and its stabilization. Possible mechanisms of action of these enzymes in various types of cancers require further investigation. We aimed to determine expression levels of these genes and their effects on protein levels in serum of patients with colorectal cancer. MATERIALS AND METHODS: Expression levels of genes were determined using Real Time-Polymerase chain reaction in 35 patients with colorectal cancer. We used enzyme-linked immunosorbent assay to determine MnSOD and GPX1 levels. RESULTS: We found significant differences in GPX1 expression between tumor and normal tissues, with a 2-fold decrease in tumor tissues (p<0.05). However, although no significant difference was found between the expression of MnSOD gene in tumor and that in normal tissues, there was a 1.13-fold change in expression. We observed no relationship between expressions of either gene and their levels in serum. CONCLUSION: The GPX1 gene may play a critical role in the development of colorectal cancer.

Hepatocellular carcinoma: targeting of oncogenic signaling networks in TRAIL resistant cancer cells.

Apoptotic response in hepatocellular carcinoma (HCC) cells is impaired because of interconnectivity of proteins into complexes and signaling networks that are highly divergent in time and space. TNF-related apoptosis-inducing ligand (TRAIL) has emerged as an attractive anticancer agent reported to selectively induce apoptosis in cancer cells. Although diametrically opposed roles of TRAIL are reported both as an inducer of apoptosis and regulator of metastasis, overwhelmingly accumulating experimental evidence highlighting apoptosis inducing activity of TRAIL is directing TRAIL into clinical trials. Insights from TRAIL mediated signaling in HCC research are catalyzing new lines of study that should not only explain molecular mechanisms of disease but also highlight emerging paradigms in restoration of TRAIL mediated apoptosis in resistant cancer cells. It is becoming progressively more understandable that phytochemicals derived from edible plants have shown potential in modelling their interactions with their target proteins. Rapidly accumulating in vitro and in-vivo evidence indicates that phytonutrients have anticancer activity in rodent models of hepatocellular carcinoma. In this review we bring to limelight how phytonutrients restore apoptosis in hepatocellular carcinoma cells by rebalancing pro-apoptotic and anti-apoptotic proteins. Evidence has started to emerge, that reveals how phytonutrients target pharmacologically intractable proteins to suppress cancer. Target-based small-molecule discovery has entered into the mainstream research in the pharmaceutical industry and a better comprehension of the genetics of patients will be essential for identification of responders and non-responders.

Functional genetic variants in apoptosis-associated FAS and FASL genes and risk of bladder cancer in a Turkish population.

BACKGROUND: The present study aimed to evaluate the role of functional polymorphisms of apoptosis-associated Fatty acid synthase (FAS) and fatty acid synthase ligand (FASL) genes in bladder cancer susceptibility as first presentation in a Turkish population. PATIENTS AND METHODS: Genotypes of 91 patients with bladder cancer and 101 healthy controls were evaluated for the polymorphism of FAS-1377 G/A and FASL-844 T/C genes by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: The frequency of the FAS-1377 G allele was significantly higher in patients with bladder cancer compared to controls (p<0.001). A significantly increased risk for developing bladder cancer was found for the group bearing a T allele for FASL-844 compared to the homozygous FASL-844 CC genotype (p=0.027). FAS-1377 GG genotype and FASL-844 T allele were found to be independently associated with an increased risk of bladder cancer. Additionally, gene-gene interaction analysis revealed that the frequency of FAS-1377AA with FASL-844TC was significantly lower in patients with bladder cancer in comparison to those of controls (p<0.001). Extensive studies for gene-gene interaction are still needed. CONCLUSION: Our study provides new evidence that FAS-1377 G and FASL-844 T alleles may be used as low-penetrant risk factors for bladder cancer development in a Turkish population.