The analysis of Survivin promoter (-31G/C) gene variation in oral squamous cell carcinoma risk and prognosis.

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a malign tumor that associated with smoking and alcohol consumption, eating habits, environmental factors, and genetic susceptibility of the individuals. The Survivin gene, also known as BIRC5, plays important roles in the regulation of the cell cycle and apoptosis. The aim of the present study is to investigate Survivin -31G/C polymorphism in OSCC development and prognosis. MATERIALS AND METHODS: A total of 61 patients with oral squamous cell carcinoma and 133 healthy individuals were genotyped by using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method (PCR-RFLP) to evaluate the role of the Survivin gene promoter region (-31) variation. RESULTS: There were no statistically significant differences in the distribution of Survivin promoter -31 polymorphism genotype and allele frequencies between the cases and controls but we analyzed the clinicopathological characteristics of patients and noticed a significant correlation between the C allele and advanced tumor stage in the patients (p = 0.022). CONCLUSION: The Survivin (-31) gene polymorphism might be associated with advanced tumor stage in oral squamous cell carcinoma but further studies in a larger population are needed most effective evaluation of the Survivin (-31) gene variation in the OSCC risk and prognosis.

The Investigation of MAPK7 Gene Variations in Colorectal Cancer Risk.

BACKGROUND/AIM: Mitogen-activated protein kinases (MAPKs) are important regulatory molecules, which have essential roles in physiology and pathology. In the present study, we examined the possible correlation between the MAPK7 gene and colorectal cancer risk in the Turkish population. MATERIALS AND METHODS: A total of 100 human DNA samples (50 colorectal cancer patients and 50 healthy individuals) were sequenced using next-generation sequencing to define the potential genetic variations in the MAPK7 gene. RESULTS: Five genetic variations (MAPK7; rs2233072, rs2233076, rs181138364, rs34984998, rs148989290) were detected in our study group. The G (variant) allele of the MAPK7; rs2233072 (T>G) gene polymorphism was found in 76% of colorectal cancer cases, and 66% of controls. The prevalence of rs2233076, rs181138364, rs34984998, and rs148989290 gene variations was quite rare in the subjects and no significant association in terms of genotype and allele frequencies was observed between the cases and controls. CONCLUSION: No statistically significant correlation between the MAP7 kinase gene variations and colorectal cancer risk was observed. This is the first investigation in the Turkish population that may initiate additional studies in larger populations to analyze the effect of MAPK7 gene on the colorectal cancer risk.

Predicting the predisposition to colorectal cancer based on SNP profiles of immune phenotypes using supervised learning models.

This study explores the machine learning-based assessment of predisposition to colorectal cancer based on single nucleotide polymorphisms (SNP). Such a computational approach may be used as a risk indicator and an auxiliary diagnosis method that complements the traditional methods such as biopsy and CT scan. Moreover, it may be used to develop a low-cost screening test for the early detection of colorectal cancers to improve public health. We employ several supervised classification algorithms. Besides, we apply data imputation to fill in the missing genotype values. The employed dataset includes SNPs observed in particular colorectal cancer-associated genomic loci that are located within DNA regions of 11 selected genes obtained from 115 individuals. We make the following observations: (i) random forest-based classifier using one-hot encoding and K-nearest neighbor (KNN)-based imputation performs the best among the studied classifiers with an F1 score of 89% and area under the curve (AUC) score of 0.96. (ii) One-hot encoding together with K-nearest neighbor-based data imputation increases the F1 scores by around 26% in comparison to the baseline approach which does not employ them. (iii) The proposed model outperforms a commonly employed state-of-the-art approach, ColonFlag, under all evaluated settings by up to 24% in terms of the AUC score. Based on the high accuracy of the constructed predictive models, the studied 11 genes may be considered a gene panel candidate for colon cancer risk screening.

Precision Diagnosis of Maturity-Onset Diabetes of the Young with Next-Generation Sequencing: Findings from the MODY-IST Study in Adult Patients.

Maturity-onset diabetes of the young (MODY) is a highly heterogeneous group of monogenic and nonautoimmune diseases. Misdiagnosis of MODY is a widespread problem and about 5% of patients with type 2 diabetes mellitus and nearly 10% with type 1 diabetes mellitus may actually have MODY. Using next-generation DNA sequencing (NGS) to facilitate accurate diagnosis of MODY, this study investigated mutations in 13 MODY genes (HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8, and KCNJ11). In addition, we comprehensively investigated the clinical phenotypic effects of the genetic variations identified. Fifty-one adult patients with suspected MODY and 64 healthy controls participated in the study. We identified 7 novel and 10 known missense mutations localized in PDX1, HNF1B, KLF11, CEL, BLK, and ABCC8 genes in 29.4% of the patient sample. Importantly, we report several mutations that were classified as "deleterious" as well as those predicted as "benign." Notably, the ABCC8 p.R1103Q, ABCC8 p.V421I, CEL I336T, CEL p.N493H, BLK p.L503P, HNF1B p.S362P, and PDX1 p.E69A mutations were identified for the first time as causative variants for MODY. More aggressive clinical features were observed in three patients with double- and triple-heterozygosity of PDX1-KLF11 (p.E69A/p.S182R), CEL-ABCC8-KCNJ11 (p.I336, p.G157R/p.R1103Q/p.A157A), and HNF1B-KLF11 (p.S362P/p.P261L). Interestingly, the clinical effects of the BLK mutations appear to be exacerbated in the presence of obesity. In conclusion, NGS analyses of the adult patients with suspected MODY appear to be informative in a clinical context. These findings warrant further clinical diagnostic research and development in different world populations suffering from diabetes with genetic underpinnings.

Monogenic Childhood Diabetes: Dissecting Clinical Heterogeneity by Next-Generation Sequencing in Maturity-Onset Diabetes of the Young.

Diabetes is a common disorder with a heterogeneous clinical presentation and an enormous burden on health care worldwide. About 1-6% of patients with diabetes suffer from maturity-onset diabetes of the young (MODY), the most common form of monogenic diabetes with autosomal dominant inheritance. MODY is genetically and clinically heterogeneous and caused by genetic variations in pancreatic ß-cell development and insulin secretion. We report here new findings from targeted next-generation sequencing (NGS) of 13 MODY-related genes. A sample of 22 unrelated pediatric patients with MODY and 13 unrelated healthy controls were recruited from a Turkish population. Targeted NGS was performed with Miseq 4000 (Illumina) to identify genetic variations in 13 MODY-related genes: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8, and KCNJ11. The NGS data were analyzed adhering to the Genome Analysis ToolKit (GATK) best practices pipeline, and variant filtering and annotation were performed. In the patient sample, we identified 43 MODY-specific genetic variations that were not present in the control group, including 11 missense mutations and 4 synonymous mutations. Importantly, and to the best of our knowledge, the missense mutations NEUROD1 p.D202E, KFL11 p.R461Q, BLK p.G248R, and KCNJ11 p.S385F were first associated with MODY in the present study. These findings contribute to the worldwide knowledge base on MODY and molecular correlates of clinical heterogeneity in monogenic childhood diabetes. Further comparative population genetics and functional genomics studies are called for, with an eye to discovery of novel diagnostics and personalized medicine in MODY. Because MODY is often misdiagnosed as type 1 or type 2 diabetes mellitus, advances in MODY diagnostics with NGS stand to benefit diabetes overall clinical care as well.

Intercellular Adhesion Molecule-1 Lys469Glu Polymorphism, Systemic Redox Homeostasis and Gestational Diabetes Mellitus in Pregnant Women.

OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1) plays an important role in endothelial function. Hyperglycemia-induced impaired redox status is 1 of the well-known pathophysiologic characteristics of gestational diabetes mellitus (GDM), and it plays a crucial role in the causes of disease. Our aim was to clarify any possible relationship between the ICAM-1 Lys469Glu polymorphism and systemic redox status in women with and without GDM. Also, we investigated whether this polymorphism could be associated with a change for better or worse as evidenced by clinical and redox biomarkers. METHODS: The ICAM-1 polymorphism statuses of 89 pregnant women without GDM and 53 pregnant women with GDM were found. Stratifying patients based on GDM and polymorphism status, we investigated various redox homeostasis markers. The independent t test was used. RESULTS: Significantly higher systemic oxidative damage and diminished antioxidant defense were found in pregnant women with GDM. Also, results showed that whether pregnant women were carrying the Lys469Glu polymorphism or not did not seem to be associated with significant differences, as evidenced by comparable systemic oxidative damage. CONCLUSIONS: Although no significant difference was observed between genotypes, the oxidative damage observed in patients with GDM warrants earlier screening and management in the light of new evidence.

The COX2 genetic variants in oral squamous cell carcinoma in Turkish population.

Oral squamous cell carcinoma (OSCC) is a common type of cancer that genetic and environmental factors also lifestyle habits, infections play important roles in the pathogenesis of disease. Cyclooxygenase 2 (COX2) is the inducible isoform of enzyme which convert arachidonic acid to prostaglandins. It was known that alterations in COX2 gene functions contribute to the inflammation process thus induce cancer progression, including cell proliferation, apoptosis, adhesion, invasion and metastasis. A total of 114 cases 165 healthy individuals were included in present study. We aimed to evaluate possible association between the COX2; -765, -1195 polymorphisms and the risk of OSCC. The genotypes were determined by using polymerase chain reaction restriction fragment length polymorphism techniques. In our study group the carriers of COX2 -765 C allele were statistically higher in patients compared with controls and individuals who had CC genotype had a 3,4 fold high risk for OSCC (p <0,05). We also observed the COX2 -1195 AA genotype frequency was higher in cases that of healthy group and individuals who had AA genotype showed a 1,7 fold increased risk for OSCC (p < 0,05). Haplotype analysis confirmed our result and revealed that the frequencies of COX2 -765C, -1195A haplotype frequencies were significantly higher in patients as compared with those of controls. In conclusion we suggest that COX2, -765, -1195 polymorphisms appear to be an important predictive factor and may be a prognostic biomarker for risk of OSCC. Further investigations with larger study groups are needed to fully elucidate the role of COX2 -765, -1195 variations in the development of OSCC.

Investigation of Survivin Gene Polymorphism and Serum Survivin Levels in Patients with Brain Tumors.

BACKGROUND/AIM: The single nucleotide polymorphism -31C/G identified in the survivin gene promoter seems to be associated with over-expression of survivin, an anti-apoptotic protein. In gliomas, increased survivin expression correlated with decreased survival. The aim of the study was to investigate whether survivin gene polymorphism associates with benign and malignant brain tumors and whether it affects survivin serum levels. PATIENTS AND METHODS: Survivin polymorphism -31C>G was genotyped in 82 patients with brain tumors and 65 healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and survivin levels were evaluated by enzyme-linked immuno sorbent assay (ELISA) in patients and controls. RESULTS: Serum survivin levels in patients with malignant tumors were higher than patients with benign tumors (p<0.001). Survivin levels in patients with malignant glial tumors and the frequency of the GG genotype were higher than in patients with benign tumors (p=0.04) and controls (p=0.05). The prevelance of the survivin gene promoter polymorphism -31C>G did not differ between patients and controls. CONCLUSION: Survivin promoter -31C>G gene polymorphism seems to be associated with serum survivin levels in brain tumors of different grades and histologies.

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.

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.

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.

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.

Cyclin D1 gene G870A variants and primary brain tumors.

Alterations of cyclin D1, one of the main regulators of the cell cycle, are known to be involved in various cancers. The CCDN1 G870A polymorphism causes production of a truncated variant with a shorter half-life and thus thought to impact the regulatory effect of CCDN1. The aim of the present study was to contribute to existing results to help to determine the prognostic value of this specific gene variant and evaluate the role of CCDN1 G870A polymorphism in brain cancer susceptibility. A Turkish study group including 99 patients with primary brain tumors and 155 healthy controls were examined. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The CCDN1 genotype frequencies in meningioma, glioma and control cases were not significantly different (p>0.05). No significant association was detected according to clinical parameters or tumor characteristics; however, a higher frequency of AG genotype was recorded within patients with astrocytic or oligoastrocytic tumors. A significant association between AG genotype and gliobilastoma multiforme (GBM) was recorded within the patients with glial tumors (p value=0.048 OR: 1.87 CI% 1.010-3.463). According to tumor characteristics, no statistically significant difference was detected within astrocytic, oligoasltrocytic tumors and oligodentrioglias. However, patients with astrocytic astrocytic or oligoastrocytic tumors showed a higher frequency of AG genotype (50%) when compared to those with oligodendrioglial tumors (27.3%). Our results indicate a possible relation between GBM formation and CCDN1 genotype.

Do CDKN2 p16 540 C>G, CDKN2 p16 580 C>T, and MDM2 SNP309 T>G gene variants act on colorectal cancer development or progression?

CDNK2 p16 plays a pivotal role in G1/S transition by regulating the p53 pathway, which was regulated by a nuclear oncoprotein, mouse double minute 2 (MDM2). Overexpression of the MDM2 gene has been shown in a number of tumor types, its gene amplification is found to associate with accelerated tumor development and failure to treatment in both hereditary and sporadic cancers. Although genetic association studies have revealed the relationship between certain genetic polymorphisms and genes that play important roles in the development and progression of colorectal cancer (CRC), it is still unknown. Therefore, the polymorphisms of p16 540 C>G, 580 C>T, and MDM2 SNP309 T>G designed to investigate the risk of CRC development and progression in a Turkish population. We enrolled 87 patients with CRC and 75 healthy controls into the study. Genotypings were determined using polymerase chain reaction-restriction fragment length polymorphism techniques. Genotype distributions of p16 540 C>G and 580 C>T were found in agreement with the Hardy-Weinberg equilibrium in patients and controls. MDM2 SNP309 T>G was found in agreement with the Hardy-Weinberg equilibrium in controls, but not in patients. The results of our study, the G allele of p16 540 C>G and GG genotype of MDM2 SNP309 T>G were found significantly lower in patients compared with controls (p<0.001, p<0.05, respectively). Haplotype analyses have shown that the C allele of both the CDKN2 p16 540 C>G and 580 C>T variants together indicate a risk haplotype for the patient group; besides, carrying the G allele of p16 540 and G allele of MDM2 also seems a risk haplotype for the patient group. Our study is the first study that investigates the relationship among variants of CDKN2 p16 540 C>G, 580 C>T, and MDM2 SNP309 T>G risk of CRC and the development and progression in the Turkish population.

The vitamin D receptor (VDR) gene polymorphisms in Turkish brain cancer patients.

Objective. It has been stated that brain cancers are an increasingly serious issue in many parts of the world. The aim of our study was to determine a possible relationship between Vitamin D receptor (VDR) gene polymorphisms and the risk of glioma and meningioma. Methods. We investigated the VDR Taq-I and VDR Fok-I gene polymorphisms in 100 brain cancer patients (including 44 meningioma cases and 56 glioma cases) and 122 age-matched healthy control subjects. This study was performed by polymerase chain reaction-based restriction fragment length polymorphism (RF LP). Results. VDR Fok-I ff genotype was significantly increased in meningioma patients (15.9%) compared with controls (2.5%), and carriers of Fok-I ff genotype had a 6.47-fold increased risk for meningioma cases. There was no significant difference between patients and controls for VDR Taq-I genotypes and alleles. Conclusions. We suggest that VDR Fok-I genotypes might affect the development of meningioma.

Possible relation between the NOS3 gene GLU298ASP polymorphism and bladder cancer in Turkey.

Endothelial nitric oxide synthase (eNOS), encoded by the NOS3 gene, has been suggested to play an important role in uncontrolled cell growth in several cancer types. The objective of this study was to evaluate the role of the NOS3 Glu298Asp polymorphism in bladder cancer susceptibility in a Turkish population. We determined the genotypes of 66 bladder cancer cases and 88 healthy controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. A significant association for NOS3 Glu298Asp heterozygotes genotypes and T allely were found between healthy controls and bladder cancer, respectively (p<0.001: p=0.002). There were no significant associations between any genotypes and the stage, grade, and histological type of bladder cancer. Our study suggested an increased risk role of NOS3 GT genotype in bladder cancer susceptibility in our Turkish population.

Association of the Cylin D1 G870A polymorphism with laryngeal cancer: are they really related?

BACKGROUND: Cylin D1(CCDN1) is an important regulator of the cell cycle whose alterations are thought to be involved in cancer development. There have been many studies indicating CCDN1 amplification or over- expression in a variety of cancer types. In addition to gene amplification, the G870A polymorphism may be related with altered CCDN1 activity, and therefore with cancer development. This hypothesis has been tested in different cancer types but results have been contradictory. We therefore aimed to investigate any relationship between CCDN1 A870G genotypes and laryngeal squamous cell cancer development and progression. MATERIALS AND METHODS: A total of 68 Turkish patients with primary laryngeal squamous cell cancer and 133 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the CCDN1 genotypes. RESULTS: No significant association was detected between CCDN1 genotypes and laryngeal squamous cell cancer (LxSCCa) development. Similarly CCDN1 genotypes were not related to clinical parameters of Lx SCCa. However, there was a very significant association between CCDN1 G allele and presence of perineural invasion (p= 0.003; OR: 1.464; CI% 1.073-1.999). CCDN1 G allele frequency was significantly higher in the individuals with perineural invasion (85.7%) when compared to those without (58.5%). The 2 patients who died of disease were both found to possess the GG genotype. CONCLUSIONS: These results pose a controversy in suggesting a protective role of the G allele against LxSCCa development and support the association of CCDN1 gene GG genotype with mortality in patients with LxSCCa.

Association of vitamin D receptor gene polymorphisms with colon cancer.

OBJECTIVE: In this study, we investigated the association of two vitamin D receptor (VDR) polymorphisms BsmI and TaqI with colon cancer in a Caucasian population. METHODS: The VDR gene polymorphisms BsmI and TaqI were detected by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)-genotyping assays by using endonucleases BsmI and TaqI, and an agarose gel electrophoresis technique in a series of 43 colon cancer patients and 42 healthy controls. RESULTS: Allele frequencies and genotype distributions were found to be similar in both cases and controls. When homozygous carriers and heterozygotes were combined for each allele, alleles B and T were found to be more common in the control group (p=0.039, χ(2)=4.276, odds ratio [OR]=0.312, 95% confidence interval [CI]=0.100-0.973 and p=0.039, χ(2)=4.258, OR=0.254, 95% CI=0.064-1.000, respectively). When genotypes were analyzed as pairs, the Bb/TT variant was higher in the control group at a statistically high significance (p=0.001, χ(2)=11.854, OR=0.122, 95% CI=0.032-0.460). CONCLUSION: The alleles B and T and the genotype combination Bb/TT were found to be higher in the control group, and thus BsmI and TaqI polymorphisms of the VDR gene may be possible risk factors for colorectal carcinogenesis.

The role of vitamin D in children with recurrent tonsillopharyngitis.

BACKGROUND: The exact etiology of recurrent tonsillopharyngitis in children is not clear. Recurrent tonsillitis in children has multifactorial etiology like most of the diseases in childhood. In this study, our aim was to determine the potential role of vitamin D in recurrent tonsillitis by measuring serum 25-OH vitamin D levels and determining the vitamin D receptor polymorphism among children with recurrent tonsillitis. METHODS: Eighty-four children with recurrent tonsillitis and seventy-one healthy children aging between 2 and 10 years were enrolled in this study. Serum 25-OH vitamin D level was measured with ELISA and vitamin D receptor gene polymorphism (Apa1, Taq 1, Fok1) was determined by PCR. Serum 25-OH vitamin D level below 50 nmol/L was accepted as deficiency. The vitamin D receptor gene polymorphism in each group was compared. RESULTS: The mean age was 5.6 ± 2.4 and 6.1 ± 2.7 years in study and control group, respectively. The average serum 25-OH vitamin D level was 142.7 ± 68.1 nmol/L in study group and 192.3 ± 56.1 nmol/L in control group. There was significant difference between the groups (p < 0.01). In study group, 4.7% (n = 4) of children had serum 25 OH vitamin D levels below 50 nmol/L. None of the children in control group had serum 25-OH vitamin D level below 50 nmol/L. There was no significant differences in vitamin D receptor gene polymorphisms between groups. CONCLUSION: Serum 25-OH vitamin D levels in recurrent tonsillitis group were lower than those in healthy children. But, there was no difference in the incidence of vitamin D receptor gene polymorphism between the two groups.

Investigation of a possible relationship between EPHX1 gene polymorphisms and colorectal cancer in Turkish society.

Metabolism of chemical carcinogens, including their activation and detoxification, plays a key role in carcinogenesis. Microsomal epoxide hydrolase (EPHX1) has an important role in the metabolism of polycyclic aromatic hydrocarbons and detoxification of procarcinogens. The aim of this study was to investigate the association between colorectal cancer (CRC) development and EPHX1 gene polymorphisms. We investigated the polymorphisms in exon 3 (T>C, Tyr113His) and exon 4 (A>G, His139Arg) of the EPHX1 gene in 68 CRC patients and 116 controls by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of the Try113Try, Try113His, and His113His for EPHX1 exon 3 were 37.9%, 55.2%, and 6.9% in controls and 39.7%, 42.6%, and 17.6% in CRC patients, respectively. Frequencies of EPHX1 exon 4 genotypes were 62.1% His139His, 37.9% His139Arg, and 0% Arg139Arg in the control group and 76.5% His139His, 22.1% His139Arg, and 1.5% Arg139Arg in the patient group. Individuals carrying the EPHX1 exon 3 His113His genotype had a 2.5-fold increased risk (p=0.024), and those carrying the EPHX1 exon 4 His139Arg genotype had decreased risk of CRC compared with controls (p=0.019). Even though exon 3 Tyr113His and exon 4 His139Arg polymorphisms for EPHX1 gene appear to be important factors for CRC risk, further investigations with larger study groups are needed to fully elucidate the role of these polymorphisms in the development of CRC.