• Title/Summary/Keyword: Regulating Control

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Risk Assessment on the Water BOT Business Participation in China : Domestic EPC Contractor's View (해외기업의 중국 수처리 BOT시장 참여 저해 위험요인 분석 : 국내 EPC 건설기업의 관점)

  • Choi, Jae-ho;Li, Shoushuang;Lee, Seungho
    • KSCE Journal of Civil and Environmental Engineering Research
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    • v.28 no.5D
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    • pp.695-703
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    • 2008
  • China water market has huge potential for increased use of BOT mode and one of the most attractive markets of doing business. However, the current China water BOT market shows that many foreign companies are retreating from the market while Chinese water companies fast growing. From the view no domestic companies have track records in China BOT water market, the research identified twenty market access barriers in terms of construction laws, regulations, BOT-related policy and the recent market situation. These are evaluated based on interview results with 10 professionals direct or indirect having a China water BOT experience. All the factors are found to be highly influential to foreign company's decision on the market participation. Among those, no fixed return policy and low water price, difficulty in water price adjustment and approval, and no government guarantees, all directly related to the project viability and under the control of government, were the most critical factors, implying government's role is the key in increasing the market competition by attracting more foreign participation on the market. In addition, new construction law regulating foreign EPC contractor's construction work, namely Decree 113, and requirement of applying competitive bidding in selecting EPC contractor in a BOT project are also considered signigicant barriers on foreign participation, which contradicts international norm and therefore necessitates an adjustment on current decision process in domestic companies.

Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation

  • TaeKyung Nam;Wonku Kang;Sangtaek Oh
    • Journal of Microbiology and Biotechnology
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    • v.33 no.9
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    • pp.1206-1212
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    • 2023
  • The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N6-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

Ten-eleven translocation 1 mediating DNA demethylation regulates the proliferation of chicken primordial germ cells through the activation of Wnt4/β-catenin signaling pathway

  • Yinglin Lu;Ming Li;Heng Cao;Jing Zhou;Fan Li;Debing Yu;Minli Yu
    • Animal Bioscience
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    • v.37 no.3
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    • pp.471-480
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    • 2024
  • Objective: The objective of this study was to investigate the regulation relationship of Ten-eleven translocation 1 (Tet1) in DNA demethylation and the proliferation of primordial germ cells (PGCs) in chickens. Methods: siRNA targeting Tet1 was used to transiently knockdown the expression of Tet1 in chicken PGCs, and the genomic DNA methylation status was measured. The proliferation of chicken PGCs was detected by flow cytometry analysis and cell counting kit-8 assay when activation or inhibition of Wnt4/β-catenin signaling pathway. And the level of DNA methylation and hisotne methylation was also tested. Results: Results revealed that knockdown of Tet1 inhibited the proliferation of chicken PGCs and downregulated the mRNA expression of Cyclin D1 and cyclin-dependent kinase 6 (CDK6), as well as pluripotency-associated genes (Nanog, PouV, and Sox2). Flow cytometry analysis confirmed that the population of PGCs in Tet1 knockdown group displayed a significant decrease in the proportion of S and G2 phase cells, which meant that there were less PGCs entered the mitosis process than that of control. Furthermore, Tet1 knockdown delayed the entrance to G1/S phase and this inhibition was rescued by treated with BIO. Consistent with these findings, Wnt/β-catenin signaling was inactivated in Tet1 knockdown PGCs, leading to aberrant proliferation. Further analysis showed that the methylation of the whole genome increased significantly after Tet1 downregulation, while hydroxyl-methylation obviously declined. Meanwhile, the level of H3K27me3 was upregulated and H3K9me2 was downregulated in Tet1 knockdown PGCs, which was achieved by regulating Wnt/β-catenin signaling pathway. Conclusion: These results suggested that the self-renewal of chicken PGCs and the maintenance of their characteristics were regulated by Tet1 mediating DNA demethylation through the activation of Wnt4/β-catenin signaling pathway.

Active Phytochemicals of Indian Spices Target Leading Proteins Involved in Breast Cancer: An in Silico Study

  • Ashok Kumar Krishnakumar;Jayanthi Malaiyandi;Pavatharani Muralidharan;Arvind Rehalia;Anami Ahuja;Vidhya Duraisamy;Usha Agrawal;Anjani Kumar Singh;Himanshu Narayan, Singh;Vishnu Swarup
    • Journal of the Korean Chemical Society
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    • v.68 no.3
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    • pp.151-159
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    • 2024
  • Indian spices are well known for their numerous health benefits, flavour, taste, and colour. Recent Advancements in chemical technology have led to better extraction and identification of bioactive molecules (phytochemicals) from spices. The therapeutic effects of spices against diabetes, cardiac problems, and various cancers has been well established. The present in silico study aims to investigate the binding affinity of 29 phytochemicals from 11 Indian spices with two prominent proteins, BCL3 and CXCL10 involved in invasiveness and bone metastasis of breast cancer. The three-dimensional structures of 29 phytochemicals were extracted from PubChem database. Protein Data Bank was used to retrieve the 3D structures of BCL3 and CXCL10 proteins. The drug-likeness and other properties of compounds were analysed by ADME and Lipinski rule of five (RO5). All computational simulations were carried out using Autodock 4.0 on Windows platform. The proteins were set to be rigid and compounds were kept free to rotate. In-silico study demonstrated a strong complex formation (positive binding constants and negative binding energy ΔG) between all phytochemicals and target proteins. However, piperine and sesamolin demonstrated high binding constants with BCL3 (50.681 × 103 mol-1, 137.76 × 103 mol-1) and CXCL10 (98.71 × 103 mol-1, 861.7 × 103 mol-1), respectively. The potential of these two phytochemicals as a drug candidate was highlighted by their binding energy of -6.5 kcal mol-1, -7.1 kcal mol-1 with BCL3 and -6.9 kcal mol-1, -8.2 kcal mol-1 with CXCL10, respectively coupled with their favourable drug likeliness and pharmacokinetics properties. These findings underscore the potential of piperine and sesamolin as drug candidates for inhibiting invasiveness and regulating breast cancer metastasis. However, further validation through in vitro and in vivo studies is necessary to confirm the in silico results and evaluate their clinical potential.

Inhibitory Effects of Rubus crataegifolius Leaf Water Extract on Adipocyte Differentiation and Adipogenesis in 3T3-L1 Preadipocytes

  • Mee-Kyung Kim
    • Journal of the Korea Society of Computer and Information
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    • v.29 no.1
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    • pp.187-194
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    • 2024
  • In this study, we examined the effects of Rubus crataegifolius leaf on the inhibition of differentiation and adipogenesis of 3T3-L1 preadipocytes to confirm their potential for use as an anti-obesity functional material. Rubus crataegifolius leaves water extracted using hot water were then concentrated for use, with an extract yield of 4.76%. The result of measuring the rate of 3T3-L1 cell survival of Rubus crataegifolius leaf extract (RCLE) showed growth inhibition of 13% at a concentration of 1,000 ㎍/mL. Thus, in this study, experiments were performed using RCLE treatment concentrations up to 500 ㎍/mL. Production of triglycedie in 3T3-L1 cells showed a dose-dependent decrease, and the rate of reduction was 28.7, 40.8, and 51.6% at concentrations of 100, 300, and 500 ㎍/mL, respectively, compared to the control group. In addition, the results confirmed that suppression of lipogenesis was achieved by suppressing the expression of peroxisome proliferator-activated receptor γ (PPAR γ), CCAAT/enhancer-binding protein α (C/EBP α), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and increasing the expression of p-activated protein kinase (p-AMPK). Based on these results, it is believed that Rubus crataegifolius leaf extract can be used in the effort to manage obesity by regulating factors related to adipocyte differentiation and adipogenesis.

Relationship among porcine lncRNA TCONS_00010987, miR-323, and leptin receptor based on dual luciferase reporter gene assays and expression patterns

  • Ding, Yueyun;Qian, Li;Wang, Li;Wu, Chaodong;Li, DengTao;Zhang, Xiaodong;Yin, Zongjun;Wang, Yuanlang;Zhang, Wei;Wu, Xudong;Ding, Jian;Yang, Min;Zhang, Liang;Shang, Jinnan;Wang, Chonglong;Gao, Yafei
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.2
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    • pp.219-229
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    • 2020
  • Objective: Considering the physiological and clinical importance of leptin receptor (LEPR) in regulating obesity and the fact that porcine LEPR expression is not known to be controlled by lncRNAs and miRNAs, we aim to characterize this gene as a potential target of SSC-miR-323 and the lncRNA TCONS_00010987. Methods: Bioinformatics analyses revealed that lncRNA TCONS_00010987 and LEPR have SSC-miR-323-binding sites and that LEPR might be a target of lncRNA TCONS_00010987 based on cis prediction. Wild-type and mutant TCONS_00010987-target sequence fragments and wild-type and mutant LEPR 3'-UTR fragments were generated and cloned into pmiRRB-REPORTTM-Control vectors to construct respective recombinant plasmids. HEK293T cells were co-transfected with the SSC-miR-323 mimics or a negative control with constructs harboring the corresponding binding sites and relative luciferase activities were determined. Tissue expression patterns of lncRNA TCONS_00010987, SSC-miR-323, and LEPR in Anqing six-end-white (AQ, the obese breed) and Large White (LW, the lean breed) pigs were detected by real-time quantitative polymerase chain reaction; backfat expression of LEPR protein was detected by western blotting. Results: Target gene fragments were successfully cloned, and the four recombinant vectors were constructed. Compared to the negative control, SSC-miR-323 mimics significantly inhibited luciferase activity from the wild-type TCONS_00010987-target sequence and wild-type LEPR-3'-UTR (p<0.01 for both) but not from the mutant TCONS_00010987-target sequence and mutant LEPR-3'-UTR (p>0.05 for both). Backfat expression levels of TCONS_00010987 and LEPR in AQ pigs were significantly higher than those in LW pigs (p<0.01), whereas levels of SSC-miR-323 in AQ pigs were significantly lower than those in LW pigs (p<0.05). LEPR protein levels in the backfat tissues of AQ pigs were markedly higher than those in LW pigs (p<0.01). Conclusion: LEPR is a potential target of SSC-miR-323, and TCONS_00010987 might act as a sponge for SSC-miR-323 to regulate LEPR expression.

The possibility of South Korea to become a member state of APSCO: an analysis from Legal and political perspectives (韓國加入亞太空間合作組織的可能性 : 基于法律与政策的分析)

  • Nie, Mingyan
    • The Korean Journal of Air & Space Law and Policy
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    • v.31 no.2
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    • pp.237-269
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    • 2016
  • Asia-Pacific Space Cooperation Organization (APSCO) is the only intergovernmental space cooperation organization in Asia. Since its establishment to date, eight countries have signed the convention and become member states. South Korea participated actively in the preparatory phase of creating the organization, and one conference organized by AP-MCSTA which is the predecessor of APSCO was held in South Korea. However, after the APSCO Convention was opened for signature in 2005 to date, South Korea does not ratify the Convention and become a member. The rapid development of space commercialization and privatization, as well as the fastest growing commercial space market in Asia, provides opportunities for Asian countries to cooperate with each other in relevant space fields. And to participate in the existing cooperation framework (e.g., the APSCO) by the Asian space countries (e.g., South Korea) could be a proper choice. Even if the essential cooperation in particular space fields is challenging, joint space programs among different Asian countries for dealing with the common events can be initiated at the first steps. Since APSCO has learned the successful legal arrangements from ESA, the legal measures established by its Convention are believed to be qualified to ensure the achievement of benefits of different member states. For example, the regulation of the "fair return" principle confirms that the return of interests from the relevant programs is in proportion to the member's investment in the programs. Moreover, the distinguish of basic and optional activities intends to authorize the freedom of the members to choose programs to participate. And for the voting procedure, the acceptance of the "consensus" by the Council is in favor of protecting the member's interest when making decisions. However, political factors that are potential to block the participation of South Korea in APSCO are difficult to be ignored. A recent event is an announcement of deploying THAAD by South Korea, which causes tension between South Korea and China. The cooperation between these two states in space activities will be influenced. A long-standing barrier is that China acts as a non-member of the main international export control mechanism, i.e., the MTCR. The U.S takes this fact as the main reason to prevent South Korea to cooperate with China in developing space programs. Although the political factors that will block the participation of South Korea in APSCO are not easy to removed shortly, legal measures can be taken to reduce the political influence. More specifically, APSCO is recommended to ensure the achievement of commercial interests of different cooperation programs by regulating precisely the implementation of the "fair return" principle. Furthermore, APSCO is also suggested to contribute to managing the common regional events by sharing satellite data. And it is anticipated that these measures can effectively response the requirements of the rapid development of space commercialization and the increasing common needs of Asia, thereby to provide a platform for the further cooperation. In addition, in order to directly reduce the political influence, two legal measures are necessary to be taken: Firstly, to clarify the rights and responsibilities of the host state (i.e., China) as providing assistance, coordination and services to the management of the Organization to release the worries of the other member states that the host state will control the Organization's activities. And secondly, to illustrate that the cooperation in APSCO is for the non-military purpose (a narrow sense of "peaceful purpose") to reduce the political concerns. Regional cooperation in Asia regarding space affairs is considered to be a general trend in the future, so if the participation of South Korea in APSCO can be finally proved to be feasible, there will be an opportunity to discuss the creation of a comprehensive institutionalized framework for space cooperation in Asia.

Ethanol Extract of Mori Folium Inhibits AICAR-induced Muscle Atrophy Through Inactivation of AMPK in C2C12 Myotubes (C2C12 근관세포에서 상엽에 의한 AMPK의 불활성화와 AICAR로 유도된 근위축 억제의 연관성에 관한 연구)

  • Lee, Yu Sung;Kim, Hong Jae;Jeong, Jin-Woo;Han, Min-Ho;Hong, Su Hyun;Choi, Yung Hyun;Park, Cheol
    • Journal of Life Science
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    • v.28 no.4
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    • pp.435-443
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    • 2018
  • AMP-activated protein kinase (AMPK) functions as a metabolic master through regulating and restoring cellular energy balance. In skeletal muscle, AMPK increases myofibril protein degradation through the expression of muscle-specific ubiquitin ligases. Mori Folium, the leaf of Morus alba, is a traditional medicinal herb with various pharmacological functions; however, the effects associated with muscle atrophy have not been fully identified. In this study, we confirmed the effects of AMPK activation by examining the effects of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, on the induction of atrophy and expression of atrophy-related genes in C2C12 myotubes. We also investigated the effects of the ethanol extract of Mori Folium (EEMF) on the recovery of AICAR-induced muscle atrophy in C2C12 myotubes. It was found that exposure to AICAR resulted in the stimulation of Forkhead box O3a (FOXO3a); an up-regulation of muscle-specific ubiquitin ligases such as Muscle Atrophy F-box (MAFbx)/atrogin-1 and muscle RING finger-1 (MuRF1), and a down-regulation of muscle-specific transcription factors, such as MyoD and myogenin; with the activation of AMPK. In addition, AICAR without cytotoxicity indicated a decrease in diameter of C2C12 myotubes. However, treatment with EEMF significantly suppressed AICAR-induced muscle atrophy of C2C12 myotubes in a dose-dependent manner as confirmed by a decrease in myotube diameter, which is associated with a reversed stimulation of FOXO3a by the inhibition of AMPK activation. These results indicate that the activation of AMPK by AICAR induces muscle atrophy, and EEMF has preeminent effects on the inhibition of AICAR-induced muscle atrophy through the AMPK signaling pathway.

Anti-wrinkle Activity of a Curdrania tricuspidata Extract on Ultraviolet-induced Photoaging (Hairless Mice를 이용한 광노화 모델에서 꾸지뽕나무 추출물의 피부주름 형성 억제효과)

  • Kim, Ok Kyung;Ho, Jin-Nyoung;Nam, Da-Eun;Jun, Woojin;Lee, Jeongmin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.4
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    • pp.608-614
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    • 2013
  • We investigated the anti-wrinkle activity of an 80% ethanol extract of Curdrania tricuspidata leaves (CTL80) on ultraviolet-induced photoaging in hairless mice. Skin wrinkles were induced by 10 weeks of UVB-irradiation on the back of Skh-1 hairless mice three times a week. Mice were divided into ten groups; normal control (-UVB), UVB irradiated control group (+UVB), dietary groups (UVB+ascorbic acid 0.1%, UVB+CTL80 0.1%, UVB+CTL80 0.25%) and topical application groups (-UVB+base lotion (BL), UVB+BL, UVB+ascorbic acid 1%+BL, UVB+CTL80 1%+BL, UVB+CTL80 2%+BL). Wrinkle formation, histological changes, superoxide dismutase (SOD) activities, glutathione peroxidase (GSH-Px), and the expression of matrix metalloproteinases (MMP-1, MMP-3 and MMP-9) were analyzed. Wrinkles for the +UVB groups formed as a pattern of deep furrows and thick crests. Wrinkles with CTL80 treatment formed as a pattern of shallow furrows and thin crests, with wrinkle areas were lower than the +UVB group. In an antioxidant analysis of mouse blood, SOD and GSH-Px activities were significantly higher in the CTL80 topical application group compared to the +UVB group. The mRNA expression of MMPs in the +UVB group was significantly higher than the normal control group, and significantly lower in the CTL80-treated group. In conclusion, CTL80 exerted anti-wrinkle activity on ultraviolet-induced photoaging by regulating antioxidative defense systems and MMPs expression.

DNMT3b Promoter Polymorphism and Risk of Gastric Cancer in the Korean Population (한국인에서 DNMT3b 유전자 다형성과 위암의 감수성)

  • Kim, Sung Geun;Jung, Hun;Kim, Sin Sun;Jeon, Kyung Hwa;Song, Kyo Young;Kim, Jin Jo;Jin, Hyung Min;Kim, Wook;Park, Cho Hyun;Park, Seung Man;Lim, Keun Woo;Kim, Seung Nam;Jeon, Hae Myung
    • Journal of Gastric Cancer
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    • v.7 no.1
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    • pp.9-15
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    • 2007
  • Purpose: DNA methylation is an important epigenetic factor in tumorigenesis. We hypothesized that polymorphism of the promoter of the DNA methyltransferase 3b (DNMT3b) genes, which are responsible for regulating the methylation status of tumor suppressor genes, are associated with increased risk of gastric cancer. Materials and Methods: In this hospital-based case-control study, to determine the role of this polymorphism of the promoter of DNA methyltransferase 3b (DNMT3b) genes in gastric cancer, we genotyped 176 cases and 70 control subjects. To determine the genotype, we used a polymerase chain reaction restriction fragment length polymorphism assay. We compared alleles and genotypes between the two groups and revealed an association of DNMT3b promoter polymorphism with increased risk of gastric cancer in the Korean population. Results: Genotype frequencies were 14.8% (Cytosine-Cytosine), 71.6% (Cytosine-Thymine), and 13.6% (Thymine- Thymine) in the case patients and 40.0% (Cytosine-Cytosine), 42.9% (Cytosine-Thymine), and 17.1% (Thymine-Thymine) in the control subjects, respectively. Compared with CC homozygotes, CT heterozygotes had a 4.523-fold increased risk (OR, 2.13; 95% CI, 2.324~8.803), and the TT homozygotes had a 2.154-fold elevated risk (OR, 1.42; 95% CI, 0.899~85.165). For the T variant genotype (CT+TT), there was a 3.846-fold increased risk (OR, 1.88; 95% CI, 2.040~7.251). However, no significance was observed in the genotype distributions of both polymorphisms according to histopathology, stage of stomach cancer. The Ssame results were observed with Helicobacter infection. Conclusion: DNMT3b promoter polymorphism, especially the T variant genotype, is associated significantly with thean increased risk of gastric cancer.

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