Cytokine Profile in Patients With Maturity-onset Diabetes of the Young (MODY).

BACKGROUND/AIM: High-sensitivity C-reactive protein (hs-CRP) is used in the differential diagnosis of maturity-onset diabetes of the young (MODY)-3, but other inflammatory markers have not been investigated in MODY patients. We aimed to compare the serum levels of anti-inflammatory and proinflammatory cytokines between MODY patients and healthy subjects and show the inflammatory features in MODY subtypes. PATIENTS AND METHODS: Thirty patients with clinically suspected MODY and 34 healthy controls were included in this study. Next-generation sequencing (NGS) was used for the molecular diagnosis of MODY subtypes. Serum levels of cytokines were measured using a multiplexed cytokine assay and hs-CRP concentration was determined by the immunoturbidimetric assay. RESULTS: The hs-CRP levels were higher in both NGS-confirmed (MODY, n=17) (p=0.009) and NGS-unconfirmed (non-MODY, n=13) patients (p<0.001) than those in controls. However, IL-1ß (p=0.001), IL-6 (p=0.018), IL-31 (p=0.003), TNF-α (p<0.001), and sCD40L (p=0.007) levels of MODY patients and IL-1ß (p=0.002), IL-31 (p<0.001), IL-22 (p=0.018), and sCD40L (p=0.039) levels of non-MODY patients were lower than those of controls. While hs-CRP levels were lower in MODY3 patients than non-MODY3 patients (p=0.009), IL-17A (p=0.006) and IL-23 (p=0.016) levels for the first time in this study were found to be higher in patients with MODY3 than in patients with other MODY subtypes (p<0.05). CONCLUSION: MODY patients had lower serum levels of the proinflammatory cytokines IL-1ß, IL-6, TNF-α, IL-31, and sCD40L compared to healthy controls. High IL-17A and IL-23 levels along with low hs-CRP levels may be potential markers to distinguish MODY3 from other MODY subtypes.

The Role of PPAR-gamma C161T Polymorphism in Colorectal Cancer Susceptibility.

BACKGROUND/AIM: This study aimed to determine the role of the peroxisome proliferator-activated receptor-gamma (PPARg) C161T genotype and allele frequencies in predisposition to colorectal cancer (CRC). PATIENTS AND METHODS: PPARg C161T (His447His; rs3856806) gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis in patients with CRC (n=101) and controls (n=238). RESULTS: The T161 allele (CT+TT genotypes) of PPARg C161T polymorphism was associated with CRC development (p<0.001; OR=3.239, 95%CI=1.997-5.252). Subgroup analysis showed that the T161 allele was associated with a 3.056-fold increased risk for colon cancer (CC) (p<0.001; 95%CI=1.709-5.464) and 3.529-fold increased risk for rectal cancer (RC) (p<0.001; 95%C=1.784-6.981). Frequencies of the T161 allele were also higher in total CRC and CC patients with poorly differentiated tumors (p<0.001, c2=30,601, OR=3.109; 95%CI=1.970-4.906 and p<0.001, Fisher exact test, respectively). CONCLUSION: PPARg T161 allele carriers have increased risk for developing CRC.

Investigation of Scavenger Receptor Class B Type I gene variants in patients with coronary heart disease with a history of early myocardial infarction.

OBJECTIVE: The scavenger receptor class B type 1 (SR-BI, SCARB1), which is a high-density lipoprotein (HDL) receptor that mediates selective cholesteryl ester uptake, plays an important role in reverse cholesterol transport. This study investigated the distribution of polymorphic variants of the SR-BI gene in patients with coronary heart disease (CHD) with a history of early myocardial infarction (MI) at an early age and their effects on their serum lipid levels. METHODS: SR-BI rs5888(T>C), rs4238001(C>T), and rs10846744(G>C) were analyzed in 100 male patients with CHD with a history of MI (MI+) who were younger than 50 years and 89 male control subjects without MI history (MI-) using real-time polymerase chain reaction (PCR) and mutant-allele-specific PCR techniques. RESULTS: SR-BI rs4238001 common-CC genotype was found to be more frequent in patients with MI+ than in control subjects (MI-; odds ratio 4.046, p<0.001). The rs10846744 rare-C allele showed a significant association with increased total cholesterol (p=0.014) and triglyceride (p=0.009) levels in the MI+ CHD group. Logistic regression analysis confirmed that there may be an association between the rs4238001-CC genotype (p=0.002), smoking (p=0.026), and MI+ CHD in the presence of other risk factors associated with CHD, whereas haplotype analysis confirmed that patients with MI+ CHD (rs5888-C, rs10846744-G, and rs4238001-C alleles) and CCC (rs5888-C, rs10846744-C, and rs4238001-C alleles) haplotypes were highly frequent (p<0.01 and p=0.027, respectively). CONCLUSION: These results indicated that SR-BI gene variants show different distribution in patients with MI+ CHD compared with that in MI- control subjects, and these variants may have effects in favor of dyslipidemia.

Kallikrein 11 Down-regulation in Breast Carcinoma: Correlation With Prognostic Parameters.

BACKGROUND: Expression of kallikrein-11 (KLK11) has been found to be related to the prognosis of various human cancer types but its physiological functions in the steps of breast cancer (BC) progression are still unknown. MATERIALS AND METHODS: BC and adjacent normal breast tissue samples were collected from 28 patients. KLK11 expression levels were determined by real-time polymerase chain reaction for each sample and associations with known prognostic features were statistically analyzed. RESULTS: Although there was slight up-regulation in tumor tissues overall, significant down-regulation of KLK11 expression in tumor tissue was observed in the elderly and in patients with perineural invasion. Furthermore, tumor size, grade, mitotic score, necrosis, calcification, lymphatic invasion, hormone receptor status and Ki67 expression were associated with altered KLK11 level. CONCLUSION: Changes in expression levels of KLK11, associated with patient characteristics, might be used as complementary data in order to predict clinical outcome and prognosis in BC.

Antiproliferative effects of Turkish pomegranate (Punica granatum L.) extracts on MCF-7 human breast cancer cell lines with focus on antioxidant potential and bioactive compounds analyzed by LC-MS/MS.

In this study, eight different pomegranate (Punica granatum L.) cultivars from Turkey were evaluated for their antioxidant and cytotoxic effects on the MCF-7 breast cancer cell lines and MCF-10A breast fibrocystic epithelial cell lines with a focus on their chemical compositions by LC-MS/MS. Cell lines were treated with pomegranate juice extracts in different doses at selected time intervals (24th, 48th, and 72nd hour). Afterwards, WST-1 cell proliferation assay was performed to investigate the cytotoxicity of the extracts. Accordingly, all extracts decreased the cell viability of MCF-7 breast cancer cell lines and had no cytotoxic effect on the cell viability of MCF-10A cell lines. Among eight extracts, P7 (Izmir 1513), which was rich in anthocyanins such as cyanidin chloride (69.76 ± 8.02 µg/g extract), cyanidin-3-O-glucoside (903.66 ± 101.89 µg/g extract), and punicalagin (992.09 ± 174.53 µg/g extract), was found to demonstrate the strongest cytotoxic activity on MCF-7 breast cancer cell lines by decreasing the cell viability in half at 24th hour with an IC50 value of 49.08 µg/ml. PRACTICAL APPLICATIONS: Eight commercially valuable pomegranate (Punica granatum) cultivars from Turkey were examined. Pelargonidin, cyanidin, cyanidin-3-O-gl, callistephin, and delphinidin-3-O-gl were quantified. Two cultivars (P1 and P3) showed comparatively higher antioxidant effects. A cultivar (P7) showed strongest cytotoxic activity against MCF-7 breast cancer cell line. The cultivars have potential to be used as natural antioxidant and anticancer agents.

Peroxisome Proliferator-Activated Receptor Gamma Pro12Ala/C161T Genotypes and Risky Haplotype Altering Risk of Breast Cancer: A Turkish Case-Control Study.

Breast cancer (BC) has a high incidence rate among women worldwide, and the mechanisms and etiology of this disease are not yet fully understood. The peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor that plays important roles in energy metabolism and cellular differentiation, is also suggested to be effective in cancer development. However, the results of studies investigating the cancer association with PPARgamma are inconsistent, creating a need for further investigation of the effects of this transcription factor on BC risk. We have examined the Pro12Ala-(rs1801282) and C161T-(rs3856806) polymorphisms of the PPARgamma gene in Turkish patients with BC in this case-control study. A total of 95 women diagnosed with BC as cases and 119 controls were genotyped for PPARgamma polymorphisms by polymerase chain reaction and restriction fragment length polymorphism techniques. The ProPro genotype and T161 allele were associated with an increased risk of BC comparing with the Ala12 allele and CC161 genotype, respectively (p < 0.001). The multivariate regression analysis confirmed that the ProPro genotype (p < 0.011), T161 allele (p < 0.001), smoking (p = 0.019), and advanced age (> 60 years) (p = 0.007) are risk factors for breast cancer. We also found that the PPARgamma Pro12Ala and C161T polymorphisms were in linkage disequilibrium (D':0.511, r2:0.099). It was determined that carrying ProPro-T161 risky PPARgamma haplotype was associated with a higher risk of BC compared to protective Ala12-CC161 haplotype (p < 0.01, OR:7.797, 95% CI:3.521-17.263). We concluded that PPARgamma Pro12Ala and C161T polymorphisms are associated with increased BC risk, and ProPro-T161 risky haplotype, which is in linkage disequilibrium, increases this effect.

Local aromatase activity alterations in breast cancer tissues: A potential way of decision support for clinicians.

BACKGROUND AND AIMS: It is becoming evident that local estrogen exposure is important in postmenopausal breast cancer patients. The microenvironment is established by breast stromal cells based on communication with tumor cells that is essential to cancer development, invasion, and metastasis. Here we investigated aromatase activity levels in both tumor and matched stromal tissues by showing their impact on the manufacturing of local estrogen and tumor progression in cases of invasive ductal carcinoma (IDC). METHODS: Tumor (T) and tumor-associated stroma (TAS) neighboring tissues were acquired from each postmenopausal patient, diagnosed with IDC, and categorized as luminal A (n = 20). The control group was formed from tumor-free breast tissue samples (N, n = 12). A microsomal-based technique was created to compare breast tissue aromatase activities using liquid chromatography - mass spectrometry. FINDINGS: We observed that the TAS tissues have the highest aromatase activities (p < 0.05). High progesterone receptor (PR) intensity levels were found to be decreasing the activity level in these tissues significantly (p < 0.05). Tumor tissue specific aromatase activity levels of postmenopausal patients' were tend to be lower compared to healthy premenopausal subjects' (3 fold, p < 0.001). In addition low activity in tumor tissues were associated with low grade and late stage cancers. CONCLUSIONS: Early detection and personalized therapy is essential for postmenopausal breast cancer patients. Together, our in-house tandem mass spectrometry technique has the potential for further development and standardization for the measurement of aromatase activity and may assist clinicians decide on therapy policies for postmenopausal IDC patients which could be an invaluable asset for precise and specific evaluation.

The impact of CYP2D6*4 and GSTP1 Ile105Val polymorphisms on the susceptibility to develop BCR-ABL1 negative myeloproliferative neoplasms.

Inter-individual variations in the genes encoding xenobiotic-metabolizing enzymes have been reported to alter susceptibility to various diseases involving hematological disorders. The purpose of this case-control study was to investigate the relationship between CYP2D6*4 and GSTP1 Ile105Val polymorphisms and the risk of developing BCR-ABL1 negative myeloproliferative neoplasms (MPN). PCR-RFLP was used for genotyping single nucleotide polymorphisms (SNP) in CYP2D6 and GSTP1 in 139 patients with MPN and 126 controls. There was a significantly increased risk for developing BCR-ABL1 negative MPN for the group bearing the CYP2D6*4 variant allele (X2: 4.487; OR 1.738; 95% CI 1.040-2.904; p = 0.034). The platelet count was higher in CYP2D6*4 allele carriers (p = 0.047). There was no association between the GSTP1 Ile105Val polymorphism and the risk of developing MPNs. MPN patients bearing the GSTP1 Ile105Val variant allele had a higher prevalence of bleeding complications (X2: 7.510; OR 4.635; 95% CI 1.466-14.650; p = 0.006). Our study provides new data that the CYP2D6*4 polymorphism may be associated with an increased risk to develop MPNs while the GSTP1 Ile105Val polymorphism does not show such an association. To our knowledge, the current study is the first to investigate the relationship between CYP2D6*4 and GSTP1 Ile105Val polymorphisms and the risk of developing MPNs in the Turkish population. Further studies with more patients and controls are needed to support our data.

Investigation of JAM-A (rs790056) and LFA-1 (rs8058823) gene variants in Turkish colorectal cancer patients.

BACKGROUND/AIMS: Lymphocyte function-associated antigen 1 (LFA-1) is a transmembrane glycoprotein expressed on the surface of leukocytes and containing the binding domain for junctional adhesion molecule-A (JAM-A). The aim of the present study was to evaluate the effects of JAM-A and LFA-1 variants on the formation of colorectal cancer and metastasis. MATERIALS AND METHODS: A total of 82 subjects with colorectal cancer and 67 healthy subjects were studied. DNA was isolated from blood samples, and variations were determined using the polymerase chain reaction and restriction fragment length polymorphism method. RESULTS: JAM-A rs790056 CC genotype and C allele were found to be higher in the colorectal cancer group (p<0.05), and approximately 3-fold increased colorectal cancer risk with CC genotype was determined (p=0.029). Haplotype analysis showed that GC haplotype (LFA-1 rs8058823G and JAM-A rs790056C) frequency was significantly higher in the patient group (p=0.041) than in controls. CONCLUSION: JAM-A rs790056 variation may be effective in the development of colorectal cancer.

Different propolis samples, phenolic content, and breast cancer cell lines: Variable cytotoxicity ranging from ineffective to potent.

Researchers have started focusing on investigating the anticarcinogenic effects of natural products with the slightest side effects possible, because current breast cancer treatment approaches are unable to achieve absolute success especially on aggressive subtypes. Propolis is among these products with its antimicrobial, antifungal, anti-inflammatory, and anticancer effects. Therefore, seven different samples were collected from different regions (Argentina, China, and Istanbul-Turkey) and applied on nonaggressive breast cancer cell line (BCCL) MCF-7 and aggressive cell lines SK-BR-3, and MDA-MB-231. Initially, the phenolic/flavonoid constituents of the propolis ethanol extracts were investigated by liquid chromatography-mass spectrometry-mass spectrometry (LS-MS/MS) and high-performance liquid chromatography (HPLC) analyses. Then, the anticarcinogenic effects of the propolis samples on MCF-7, SK-BR-3, MDA-MB-231 were evaluated by WST1 analysis and only selected ones on MCF-10A and hPdLF. According to the LS-MS/MS and HPLC analysis, Turkey originated propolis (Turkey3) were found to be richer than the other propolis samples in terms of phenolic/flavonoid compounds. Turkey propolis significantly inhibited cell proliferation in both nonaggressive and aggressive BCCL (P < 0.01). Therefore, Turkey3 propolis was selected for further evaluation using Annexin V-PI apoptosis detection assays. In addition, selected compounds among the propolis contents such as galangin, caffeic acid, apigenin, quercetin, and ferulic acid were applied to the MCF-7 cell line to detect cytotoxic and apoptotic effects. Galangin, caffeic acid, apigenin, and quercetin remarkably induced cell proliferation inhibition at all time intervals, whereas ferulic acid was found non efficient on the MCF-7 cell line. Annexin V-PI assay clarified that all cell proliferation inhibitions were markedly apoptotic. Our findings indicated that the inhibition effect of propolis on breast cancer cell proliferation was in a propolis type-, dose- and time-dependent fashion. Turkey3 propolis showed statistically significant cytotoxic effects on both the nonaggressive and aggressive BCCL. These findings were consistent with the effects of its rich phenolic and flavonoid contents, in terms of variety. © 2018 IUBMB Life, 71(5):619-631, 2019.

Anatolian honey is not only sweet but can also protect from breast cancer: Elixir for women from artemis to present.

Natural products with bioactive components are widely studied on various cancer cell lines for their possible cytotoxic effects, recently. Among these products, honey stands out as a valuable bee product containing many active phenolic compounds and flavonoids. Numerous types of multifloral honey and honeydew honey are produced in Turkey owing to its abundant vegetation. Therefore, in this study, we investigated the cytotoxic effects of particular tree-originated honeys from chestnut, cedar, pine, and multifloral honey on cell lines representing different types of the most common cancer of women, breast cancer, MCF7, SKBR3, and MDAMB-231, and fibrocystic breast epithelial cell line, MCF10A as a control. All honey samples were analyzed biochemically. The dose- (1, 2.5, 5, 7.5, and 10 µg/mL) and time (24th, 48th, and 72nd hours)-dependent effects of ethanol/water solutions of the honey samples were scrutinized. Cell viability/cytotoxicity was evaluated by the water soluble tetrazolium Salt-1 (WST-1) method. Apoptotic status was detected by Annexin V-PI assay using FACSCalibur. The statistical analysis was performed using GraphPad Prism 6 and the clustering data analysis with the R programming language. The biochemical analyses of the honey samples showed that the tree-originated honey samples contained more total phenolic compounds than the multifloral honey. Phenolic content of the honey types increases in order of multifloral, pine, cedar, and chestnut, respectively, which is compatible with their cytotoxic affectivity and dark color. In addition, the antioxidant capacity of the studied honey types was observed to increase in order of multifloral < pine < cedar ≅ chestnut. According to the WST-1 data, chestnut honey induced cytotoxicity over 50% on all the cell lines, including the control MCF10A cells, even with low doses (honey concentrations starting from 1 µg/mL) (P < 0.0001). Similarly, Cedar honey was observed to be the second most effective honey in this study. Cedar honey, with the dose of 1 µg/mL, was detected statistically highly significant on MCF10A, MCF7, and SKBR3. In contrast, pine honey showed dramatically significant cytotoxicity only on the MDAMB 231 cells with a 1 µg/mL dose at the same time point (P = 0.018). While pine honey caused an anticancer effect on the MCF-7 and SKBR3 cancer cell lines with a 2.5-5 µg/mL dose (P < 0.0001), like cedar and chestnut honeys, it increased the viability of the MCF10A control cells with the doses of 2.5-5 µg/mL. It only showed cytotoxicity with higher doses (10 µg/mL) on the MCF10A cell line (P < 0.0001). Moreover, we have observed that the multifloral and artificial honey samples were mostly ineffective or increased cell viability with the doses of 1-5 µg/mL. Apoptotic effects of the other honey samples on the MCF-7 cell line were found as chestnut> pine> cedar> multifloral in the Annexin V-propidium iodide (PI) analysis. Chestnut, cedar, and pine honey displayed a remarkably cytotoxic effect on breast cancer cell lines, MCF7, SKBR3, and even on the most aggressive MDAMB 231, representing the triple negative breast cancer, which lacks of targeted anticancer therapy. The chestnut and cedar honeys stand out to be the most cytotoxic on all cell lines, while pine honey was found to be the least toxic on control cells with appropriate toxicity on the cancer cells. © 2017 IUBMB Life, 69(9):677-688, 2017.

Evaluation of Local CYP17A1 and CYP19A1 Expression Levels as Prognostic Factors in Postmenopausal Invasive Ductal Breast Cancer Cases.

There is growing attention focused on local estrogen production in the breast tissue and its possible role in breast cancer initiation and progression. Understanding the underlying mechanisms for estrogen synthesis and the microenvironment consisting of tumor and its surrounding adipose tissue might open new avenues in breast cancer prevention, prognosis and treatment. In order to obtain insight, we compared peritumoral and tumor tissue expressions of CYP17A1 and CYP19A1 genes, which play an important role in estrogen biosynthesis. The paired tissue samples of 20 postmenopausal ER+/PR+ patients diagnosed with invasive ductal breast cancer were studied. In addition, 12 breast tissue samples obtained from premenopausal women without a history of breast cancer were also investigated as representative of normal conditions. Peritumoral adipose tissues expressed CYP19A1 approximately threefold higher than tumor itself (p = 0.001). A nonsignificant trend toward low expression of CYP17A1 was observed in peritumoral compared to tumor tissue (p = 0.687). Clinicopathological parameters and patient characteristics which are accepted as risk factors for breast cancer were also associated with individual and combined expressions of CYP17A1 and CYP19A1. This study offers that evaluation of CYP17A1 and CYP19A1 local expression levels might be useful for deciding on personalized treatment approaches and more accurate diagnosis, when evaluated together with several clinicopathological and disease risk factors. Considering the key role of these CYPs in estrogen synthesis, determining their expression levels may be useful as a postdiagnostic marker and for choosing the right treatment method in addition to the conventional approach.

Preliminary Study: Prominent miRNAs of Breast Malignant Tissues Compared to Normal Tissues in Turkish Patients with Breast Cancer.

miRNA involvement has been observed in almost every type of cancer, including breast cancer. The etiology of abnormal expression of miRNAs in cancer is still not clearly understood. In order to obtain insight into miRNA de-regulation in breast cancer, we analyzed expression levels of five breast cancer-related miRNAs, miRNA21, miRNA155, miRNA19a, miRNA17-5p and let7a miRNA, in both malignant and neighboring non-tumoral paraffin-embedded tissues of 47 patients with invasive ductal breast cancer. The targeted miRNAs, and a reference snRNA, U6, were analyzed by real-time polymerase chain reaction. let7a Levels were significantly lower in patients with lymphatic invasion than in those without (p=0.047). miR21 was down-regulated in 93.3% of patients with necrosis [p=0.017 (Fisher's exact test (FE))], while at least one oncogenic miRNA was up-regulated in 87.3% of the patients with invasive ductal carcinoma [p=0.009 (FE)]. In addition, tumor-suppressor miRNA was down-regulated or unaltered in 65.8% of the patients with tumor grade 2 or 3 and in all with grade 1 [p=0.047 (FE)]. Based on this preliminary study, we suggest that these miRNAs, especially let7a and miRNA21, might be useful markers in follow-up of breast cancer and in prognosis.

Combined effects of collagen type I alpha1 (COL1A1) Sp1 polymorphism and osteoporosis risk factors on bone mineral density in Turkish postmenopausal women.

Identification of risk factors for osteoporosis has been essential for understanding the development of osteoporosis. The collagen type I alpha1 (COL1A1) gene is suggested to be implicated in reduced bone mineral density (BMD) in osteoporosis. In the present study, the investigation of the effects of Sp1 polymorphic variants of COL1A1 gene on BMD values, and the determination of the association between COL1A1 Sp1 gene variants and osteoporosis risk factors in the context of gene-environment interaction in Turkish postmenopausal women were aimed. For the detection of COL1A1 Sp1 polymorphism, PCR-RFLP techniques have been used. BMD for lumbar spine (L1-L4) and hip (femoral neck and total hip) was measured by DXA. This study was carried out using a sample of 254 postmenopausal women. We observed a trend decrease in BMD values in the subjects with "ss" genotype having lower BMD of lumbar spine, femoral neck and total hip than those with "SS" and "Ss" genotype, however the differences did not reach statistical significance (P>0.05). We also found that the frequencies of the BMD under mean values at the femoral neck (57.5%) and total hip (76.2%) increased considerably in the subjects carrying "Ss/ss" genotypes in combination of having family history of osteoporosis (61.5% for femoral neck) and smoking history (90.0% for total hip). This population-based study indicates that COL1A1 Sp1 polymorphism may contribute to the development of osteoporosis in combination of osteoporosis risk factors in Turkish postmenopausal women.

Investigation of BRAF V600E mutation in papillary thyroid carcinoma and tumor-surrounding nontumoral tissues.

The aim of this study was to investigate the association between the BRAF V600E mutation incidence and histopathologic prognostic risk factors for papillary thyroid carcinoma (PTC) on the Turkish population. The contribution of BRAF V600E mutation in both tumor and tumor-surrounding nontumoral tissues of 108 patients with PTC was assessed using mutant allele-specific amplification-polymerase chain reaction. The BRAF V600E mutation was found in 52.8% of the tumor tissues, and 7.4% of the tumor-surrounding nontumoral tissues. The BRAF V600E mutation was significantly higher in the tumor tissues of the classic variant of PTC (CVPTC) cases than the follicular variant of PTC cases (p=0.001). The presence of the BRAF V600E mutation was more frequent in women, but this gender difference was not statistically significant. BRAF V600E mutation was more frequent in patients with either one of adenomatous hyperplasia or diffuse hyperplasia in tumor-surrounding nontumoral tissues (p=0.012). There was no significant difference in the BRAF V600E mutation distribution among tumor-surrounding nontumoral tissues of the two PTC variants, but it was more frequent in the CVPTC. Recent data suggest that BRAF V600E is an important marker, especially, for CVPTC. We propose that patients who had subtotal thyroid resection might have an increased risk of recurrence at the residual thyroid tissue if they have BRAF V600E mutation in their tumor-surrounding nontumoral tissues.

Is the MDR1 C3435T polymorphism responsible for oral mucositis in children with acute lymphoblastic leukemia?

BACKGROUND AND AIM: Although the functional consequences of MDR-1 polymorphisms have been the subject of numerous studies, to the best to our knowledge, associations with clinical side effects of anticancer drugs have yet to be assessed. Our aim was to clarify any role of the C3435T polymorphism of the MDR1 gene in oral mucositis and its relation with elevated reactive oxygen species (ROS) levels, in children with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: The distribution of the MDR-1 C3435T polymorphism in 47 patients with ALL was determined by RFLP and compared with that of 68 healthy controls. RESULTS: There were no association in distribution of genotypes of MDR-1 C3435T polymorphism and the risk of ALL. Oral mucositis were detected in 78.7% (n=37) of the patients and significantly related to the MDR-1 CT genotype (p=0.042), as confirmed by logistic regression analysis. CONCLUSION: Our preliminary data suggest that children carrying the CT genotype are more prone to develop oral mucositis, which might mean that the heterozygous genotype leads to accumulation of more reactive oxygen species. Since a limited number of patients was investigated, further studies are needed to confirm these findings.

Evaluation of ERα and VDR gene polymorphisms in relation to bone mineral density in Turkish postmenopausal women.

It has been suggested that the estrogen receptor alpha (ERα) and vitamin D receptor (VDR) genes as possibly implicated in reduced bone mineral density (BMD) in osteoporosis. The present study investigated the relation of ERα PvuII/XbaI polymorphisms and VDR FokI/TaqI polymorphisms with BMD in Turkish postmenopausal women. Eighty-one osteoporotic and 122 osteopenic postmenopausal women were recruited. For detection of the polymorphisms, polymerase chain reaction-restriction fragment lenght polymorphism techniques have been used. BMD was measured at the lumbar spine and hip by dual-energy X-ray absorptiometry. Distributions of ERα (PvuII dbSNP: rs2234693, XbaI dbSNP: rs9340799) and VDR genotypes (FokI dbSNP rs10735810, TaqI dbSNP: rs731236) were similar in study population. Although overall prevalence of osteoporosis had no association with these genotypes, the prevalence of decreased femoral neck BMD values were higher in the subjects with ERα PvuII "PP" and ERα XbaI "XX" genotypes than in those with "Pp/pp" genotypes and "xx" genotype, respectively (P < 0.05). Furthermore, subjects with VDR FokI "FF" genotype had lower BMD values of femoral neck and total hip compared to those with "Ff" genotype (P < 0.05). In the logistic regression analysis, we confirmed the presence of relationships between the VDR FokI "FF" genotypes, BMI ≤ 27.5, age ≥ 55 and the increased risk of femoral neck BMD below 0.8 value in postmenopausal women. The present data suggests that the ERα PvuII/XbaI and VDR FokI polymorphisms may contribute to the determination of bone mineral density in Turkish postmenopausal women.

PPAR-gamma Pro12Ala polymorphism and gastric cancer risk in a Turkish population.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand dependent transcription factor involved in various processes, including carcinogenesis. We aimed to investigate any possible association of the PPARγPro12Ala (rs1801282) polymorphism with risk of developing gastric cancer (GC). PATIENTS AND METHODS: A hospital based case control study was designed covering 50 patients with GC and 120 healthy controls. The frequencies of PPARγPro12Ala (rs1801282) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: The Ala12 allele of the PPARγPro12Ala G gene was associated with a 1.95 fold increased risk of GC development (p: 0.022; 95% CI: 1.58-2.40). Subgroup analyses showed that the same allele was also associated with metastasis (p: 0.000; OR:4.09; 95%CI:2.273-7.368) and differentiation (p: 0.004; OR:1.95; 95%CI:1.335-2.875) in patients with GC. CONCLUSION: This study suggests that the PPARγPro12Ala G (Ala12) allele might be associated with development, differentiation and metastatic process of GC in the Turkish population. Further studies conducted in larger study groups and in different ethnic populations will be needed to clarify the exact role of the PPARγPro12Ala polymorphism in GC.

Effects of the MTHFR C677T polymorphism on prostate specific antigen and prostate cancer.

Prostate cancer is the most common malignancy and the second leading cause of cancer related deaths among men in many countries. Serum levels of prostate-spesific antigen (PSA) have attracted attention for prediction purposes. The methylenetetrahydrofolate reductase (MTHFR) gene play a critical role in cancer development, but its potential impact on prostate cancer has not been well studied. The C677T variant lies in exon 4 at the folate binding site of the MTHFR gene and results in substitution of an alanine by a valine residue. The present study was carried out 55 cases with prostate cancer and 50 healthy men. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis techniques were employed to determine MTHFR C677T mutation. The frequencies of the CT genotype (p= 0.025) and T allele (p= 0.023) was found to be higher in control subjects when compared with patients group. No statistical difference was found between the alleles of MTHFR and PSA levels after (PSA-BT)/ before (PSA-AT) antiandrogen treatment or tumor stages. We suggest that the heterozygote CT genotype and the 677T allele of the MTHFR polymorphism might be associated with an decreased prostate cancer risk.