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Gong AM, Li XY, Xie YQ, Jia ZD, Li YX, Zou YY, Xu CQ, Wang ZY. Association between CD14 SNP -159 C/T and gastric cancer: an independent case-control study and an updated meta-analysis. Onco Targets Ther 2016; 9:4337-42. [PMID: 27486336 PMCID: PMC4958350 DOI: 10.2147/ott.s95807] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
PURPOSE The association between CD14 -159C/T polymorphism and the susceptibility to gastric cancer (GC) has been reported. However, the results were inconclusive. In the present study, a case-control study and a meta-analysis were performed to assess the possible association between -159C/T in the CD14 gene and GC risk. PATIENTS AND METHODS Relevant studies were searched in several databases including PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure database, and Wanfang database (last search was performed on December 30, 2015). In addition, a case-control study involving 164 GC cases and 169 controls was also performed in the analysis. Statistical analysis was performed by the software Revman5.3. RESULTS A total of ten published studies and the present case-control study involving 2,844 GC and 3,983 controls were included for the meta-analysis. The analysis result indicated that the T allele of CD14 -159C/T polymorphism did not confer risk for GC (in our study: [P=0.93]; in the meta-analysis: T vs 2N odds ratio =1.28 and 95% confidence interval (CI) =0.95-1.24, [P=0.24]). However, we found a significant association in the recessive model (in our study: TT vs TC+CC [P=0.04]; in the meta-analysis: TT vs TC+CC odds ratio =1.12 and 95% CI =1.01-1.26, [P=0.04]). Furthermore, a subgroup analysis by ethnicity showed that TT genotype was significantly associated with GC in Asian (odds ratio =1.17 and 95% CI =1.02-1.34, [P=0.02]) but not in Caucasian. CONCLUSION Our results highlight the TT genotype of CD14 -159C/T as a genetic susceptibility factor for gastric cancer, particularly, in Asians and population-based controls.
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Affiliation(s)
- Ai-Min Gong
- Department of Internal Medicine of Traditional Chinese Medicine, Hainan Medical University, Hainan; Department of Pathophysiology, Harbin Medical University, Harbin
| | - Xin-Yuan Li
- Department of Pathophysiology, Harbin Medical University, Harbin
| | - Yi-Qiang Xie
- Department of Internal Medicine of Traditional Chinese Medicine, Hainan Medical University, Hainan
| | - Zhan-Dong Jia
- Department of Nephrology, Ningbo Tradition Chinese Medicine Hospital affiliated to Zhejiang Chinese Medical University, Ningbo
| | | | - Yong-Yan Zou
- Department of Nephrology, Jining Tradition Chinese Medicine Hospital, Jining, People's Republic of China
| | - Chang-Qing Xu
- Department of Pathophysiology, Harbin Medical University, Harbin
| | - Zhen-Yu Wang
- Department of Pathophysiology, Harbin Medical University, Harbin
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Tong X, Li Z, Fu X, Zhou K, Wu Y, Zhang Y, Fan H. The association between CD14-260C/T polymorphism and malignant tumor risk: a meta-analysis of 5,603 participants. Tumour Biol 2014; 35:8707-13. [PMID: 24870592 DOI: 10.1007/s13277-014-2040-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2013] [Accepted: 04/29/2014] [Indexed: 02/05/2023] Open
Abstract
The CD14-260C/T polymorphism has been implicated to be in association with malignant tumor. However, a number of studies have reported inconclusive results. The aim of this study was to investigate the relationship of CD14-260C/T polymorphism and malignant tumor risk by meta-analysis. A search was performed in PubMed, Embase, the Chinese Journals Full-text Database (CNKI), and Wanfang databases up to August 2013. Odds ratio (OR) and 95 % confidence interval (95 % CI) were used to assess the association. Statistical analysis was calculated by STATA 11.0 software. The polymorphism was identified from 11 articles (12 case-control studies), involving 2,660 cases and 2,943 controls. Overall, no significant association between CD14-260C/T polymorphism and malignant tumor risk was found in the dominant model (TT + TC vs. CC: OR = 0.86, 95 % CI = 0.67-1.11). In the subgroup analysis by malignant tumor types, we found that the heterozygote model (TC vs. CC) might reduce the risk of malignant tumor, especially hematological malignance and prostate cancer (OR = 0.67, 95 % CI = 0.47-0.95), but not associated with gastrointestinal cancer susceptibility. In the subgroup analysis by ethnicity, no significant associations were found among different ethnicities. The study suggested that CD14-260C/T polymorphism might be a protective factor for hematological malignance and prostate tumor susceptibility but not an independent risk factor for gastrointestinal cancer susceptibility. To further evaluate the association between the polymorphism and malignant tumor susceptibility, more studies involving thousands of patients are required.
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Affiliation(s)
- Xiang Tong
- West China School of Medicine/West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
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Li K, Dan Z, Hu XJ, Gesang LB, Ze YG, Bianba ZX, Ciren CM, Nie YQ. Association of CD14/-260 polymorphism with gastric cancer risk in Highland Tibetans. World J Gastroenterol 2014; 20:2688-2694. [PMID: 24627605 PMCID: PMC3949278 DOI: 10.3748/wjg.v20.i10.2688] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Revised: 11/09/2013] [Accepted: 01/02/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the relationship between CD14-260 and -651 polymorphisms and the risk of developing gastric cancer.
METHODS: DNA was extracted from peripheral blood samples obtained from 225 Tibetans with gastric cancer and 237 healthy Tibetans, and analyzed using the polymerase chain reaction/ligase detection (PCR/LDR) method to determine the genotypes at -260 and -651 loci of the CD14 promoter. The allele frequencies, genotype frequencies, and haplotypes were analyzed for their association with gastric cancer risk using online SHEsis software. The luciferase reporter assay and point mutation analysis were used to construct in vitro plasmids expressing a C/T homozygote at the -260 locus of the CD14 promoter.
RESULTS: The frequencies of CC, CT and TT genotypes in the CD14-260 C/T locus in gastric cancer patients were 19.1%, 38.7% and 42.2%, respectively, whereas they were 33.3%, 32.5% and 34.2%, respectively, in healthy control subjects. CT genotype carriers were more frequently found among gastric cancer patients than healthy controls (OR = 2.076; 95%CI: 1.282-3.360). Also, TT genotype carriers were more frequently found among gastric cancer patients (OR = 2.155; 95%CI: 1.340-3.466). Compared to the C allele of CD14/-260, the T allele was associated with an increased risk for gastric cancer (OR = 1.574; 95%CI: 1.121-2.045). Furthermore, the frequencies of CC, CT and TT in the CD14-651 C/T locus in gastric cancer patients were 64.4%, 29.3% and 6.2%, respectively, while they were 56.5%, 35.0% and 8.4%, respectively, in the healthy control subjects (P > 0.05). Data obtained using the luciferase reporter assay showed that the p260T homozygote was associated with greater CD14 promoter activity (P < 0.01).
CONCLUSION: CD14/-260 polymorphism is associated with gastric cancer risk in Highland Tibetans and affects CD14 promoter activity, thereby regulating CD14 expression.
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Companioni O, Bonet C, Muñoz X, Weiderpass E, Panico S, Tumino R, Palli D, Agnoli C, Vineis P, Boutron-Ruault MC, Racine A, Clavel-Chapelon F, Travis RC, Khaw KT, Riboli E, Murphy N, Vergnaud AC, Trichopoulou A, Benetou V, Trichopoulos D, Lund E, Johansen D, Lindkvist B, Johansson M, Sund M, Ardanaz E, Sánchez-Cantalejo E, Huerta JM, Dorronsoro M, Ramón Quirós J, Tjonneland A, Mortensen LM, Overvad K, Chang-Claude J, Rizzato C, Boeing H, Bueno-de-Mesquita HB, Bueno de Mesquita HB, Siersema P, Peeters PHM, Numans ME, Carneiro F, Licaj I, Freisling H, Sala N, González CA. Polymorphisms of Helicobacter pylori signaling pathway genes and gastric cancer risk in the European Prospective Investigation into Cancer-Eurgast cohort. Int J Cancer 2014; 134:92-101. [PMID: 23824692 DOI: 10.1002/ijc.28357] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Accepted: 04/16/2013] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori is a recognized causal factor of noncardia gastric cancer (GC). Lipopolysaccharide and peptidoglycan of this bacterium are recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates the transcription of pro-inflammatory cytokines to elicit an immune response. Single nucleotide polymorphisms (SNPs) in these genes have been associated with GC in different populations. We genotyped 30 SNPs of these genes, in 365 gastric adenocarcinomas and 1,284 matched controls from the European Prospective Investigation into Cancer cohort. The association with GC and its histological and anatomical subtypes was analyzed by logistic regression and corrected for multiple comparisons. Using a log-additive model, we found a significant association between SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the multiple comparisons tests only the NOD2 region remained significant (p = 0.009). Analysis according to anatomical subtypes revealed NOD2 and NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with cardia GC, while analysis according to histological subtypes showed that CD14 was associated with intestinal but not diffuse GC. The multiple comparisons tests confirmed the association of NOD2 with noncardia GC (p = 0.0003) and CD14 with cardia GC (p = 0.01). Haplotype analysis was in agreement with single SNP results for NOD2 and CD14 genes. From these results, we conclude that genetic variation in NOD2 associates with noncardia GC while variation in CD14 is associated with cardia GC.
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Affiliation(s)
- Osmel Companioni
- Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, Barcelona, 08908, Spain
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Kim J, Cho YA, Choi IJ, Lee YS, Kim SY, Hwang JA, Cho SJ, Kook MC, Kim CG, Kim YW. Effects of polymorphisms of innate immunity genes and environmental factors on the risk of noncardia gastric cancer. Cancer Res Treat 2013; 45:313-24. [PMID: 24454004 PMCID: PMC3893329 DOI: 10.4143/crt.2013.45.4.313] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2012] [Accepted: 04/09/2013] [Indexed: 12/26/2022] Open
Abstract
Purpose Increasing evidence suggests that polymorphisms in innate immunity genes are associated with Helicobacter pylori-induced inflammation and may influence susceptibility in developing noncardia gastric cancer. Therefore, we investigate the effect of polymorphisms of innate immunity genes and interactions with environmental factors in the Korean population. Materials and Methods We genotyped four polymorphisms of TLR2 (rs1898830), TLR4 (rs10983755 and rs10759932), and CD14 (rs2569190) in a case-control study of 487 noncardia gastric cancer patients and 487 sex- and age-matched healthy controls. Polytomous logistic regression models were used to detect the effects of genetic polymorphisms and environmental factors, which were stratified by the histological type of gastric cancer. Results TLR4 rs10983755 A carriers were found to have higher risk of intestinal-type noncarida gastric cancer than G homozygotes (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.01 to 1.97), but other genetic variants showed no association with the risk of noncardia gastric cancer. Among H. pylori-positive participants, smokers carrying TLR4 rs10983755 A had a higher risk of intestinal-type gastric cancer than nonsmoking TLR4 rs10983755 G homozygotes (OR, 4.28; 95% CI, 2.12 to 8.64). In addition, compared with tap water, other drinking water sources during childhood were found to be associated with the elevated risk of intestinal-type gastric cancer, and these associations were slightly stronger among TLR4 rs10983755 A carriers. Conclusion The genetic polymorphisms of innate immunity genes are associated with the development of intestinal-type noncardia gastric cancer and these associations may differ in accordance to an exposure to certain environmental factors.
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Affiliation(s)
- Jeongseon Kim
- Molecular Epidemiology Branch, National Cancer Center, Goyang, Korea
| | - Young Ae Cho
- Molecular Epidemiology Branch, National Cancer Center, Goyang, Korea
| | - Il Ju Choi
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | - Yeon-Su Lee
- Cancer Genomics Branch, National Cancer Center, Goyang, Korea
| | - Sook-Young Kim
- Cancer Genomics Branch, National Cancer Center, Goyang, Korea
| | - Jung-Ah Hwang
- Cancer Genomics Branch, National Cancer Center, Goyang, Korea
| | - Soo-Jeong Cho
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | | | - Chan Gyoo Kim
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | - Young-Woo Kim
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
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Kim J, Cho YA, Choi IJ, Lee YS, Kim SY, Hwang JA, Cho SJ, Kook MC, Kim CG, Kim YW. Effects of polymorphisms of innate immunity genes and environmental factors on the risk of noncardia gastric cancer. Cancer Res Treat 2013. [PMID: 24454004 DOI: 0.4143/crt.2013.45.4.313] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
PURPOSE Increasing evidence suggests that polymorphisms in innate immunity genes are associated with Helicobacter pylori-induced inflammation and may influence susceptibility in developing noncardia gastric cancer. Therefore, we investigate the effect of polymorphisms of innate immunity genes and interactions with environmental factors in the Korean population. MATERIALS AND METHODS We genotyped four polymorphisms of TLR2 (rs1898830), TLR4 (rs10983755 and rs10759932), and CD14 (rs2569190) in a case-control study of 487 noncardia gastric cancer patients and 487 sex- and age-matched healthy controls. Polytomous logistic regression models were used to detect the effects of genetic polymorphisms and environmental factors, which were stratified by the histological type of gastric cancer. RESULTS TLR4 rs10983755 A carriers were found to have higher risk of intestinal-type noncarida gastric cancer than G homozygotes (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.01 to 1.97), but other genetic variants showed no association with the risk of noncardia gastric cancer. Among H. pylori-positive participants, smokers carrying TLR4 rs10983755 A had a higher risk of intestinal-type gastric cancer than nonsmoking TLR4 rs10983755 G homozygotes (OR, 4.28; 95% CI, 2.12 to 8.64). In addition, compared with tap water, other drinking water sources during childhood were found to be associated with the elevated risk of intestinal-type gastric cancer, and these associations were slightly stronger among TLR4 rs10983755 A carriers. CONCLUSION The genetic polymorphisms of innate immunity genes are associated with the development of intestinal-type noncardia gastric cancer and these associations may differ in accordance to an exposure to certain environmental factors.
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Affiliation(s)
- Jeongseon Kim
- Molecular Epidemiology Branch, National Cancer Center, Goyang, Korea
| | - Young Ae Cho
- Molecular Epidemiology Branch, National Cancer Center, Goyang, Korea
| | - Il Ju Choi
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | - Yeon-Su Lee
- Cancer Genomics Branch, National Cancer Center, Goyang, Korea
| | - Sook-Young Kim
- Cancer Genomics Branch, National Cancer Center, Goyang, Korea
| | - Jung-Ah Hwang
- Cancer Genomics Branch, National Cancer Center, Goyang, Korea
| | - Soo-Jeong Cho
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | | | - Chan Gyoo Kim
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | - Young-Woo Kim
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
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Zeljic K, Supic G, Jovic N, Kozomara R, Brankovic‐Magic M, Obrenovic M, Magic Z. Association of TLR2, TLR3, TLR4 and CD14 genes polymorphisms with oral cancer risk and survival. Oral Dis 2013; 20:416-24. [DOI: 10.1111/odi.12144] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2013] [Revised: 05/12/2013] [Accepted: 05/27/2013] [Indexed: 12/13/2022]
Affiliation(s)
- K Zeljic
- Institute for Medical Research Military Medical Academy BelgradeSerbia
- Faculty of Biology University of Belgrade BelgradeSerbia
| | - G Supic
- Institute for Medical Research Military Medical Academy BelgradeSerbia
- Faculty of Medicine Military Medical Academy University of Defence BelgradeSerbia
| | - N Jovic
- Faculty of Medicine Military Medical Academy University of Defence BelgradeSerbia
- Clinic for Maxillofacial Surgery Military Medical Academy BelgradeSerbia
| | - R Kozomara
- Faculty of Medicine Military Medical Academy University of Defence BelgradeSerbia
- Clinic for Maxillofacial Surgery Military Medical Academy BelgradeSerbia
| | | | - M Obrenovic
- Faculty of Medicine University of East Sarajevo Foca Bosnia and Herzegovina
| | - Z Magic
- Institute for Medical Research Military Medical Academy BelgradeSerbia
- Faculty of Medicine Military Medical Academy University of Defence BelgradeSerbia
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Kim EJ, Chung WC, Lee KM, Paik CN, Kim SB, Oh YS, Lee YW, Kang SG, Noh SJ. Helicobacter pylori Infection Enhances Gastric Mucosal Inflammation in Individuals Carrying the 260-T Allele of the CD14 Gene. Gut Liver 2013; 7:317-22. [PMID: 23710313 PMCID: PMC3661964 DOI: 10.5009/gnl.2013.7.3.317] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2012] [Revised: 09/19/2012] [Accepted: 10/05/2012] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND/AIMS We aim to evaluate the association between promoter polymorphism of the clusters of differentiation 14 (CD14) gene and Helicobacter pylori-induced gastric mucosal inflammation in a healthy Korean population. METHODS The study population consisted of 267 healthy subjects who visited our hospital for free nationwide gastric cancer screening. Promoter polymorphism at -260 C/T of the CD14 gene was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The severity of gastric mucosal inflammation was estimated by a gastritis score based on the sum of the values of the grade and activity of the gastritis. Expression of soluble CD14 (sCD14) was assessed by quantitative sandwich ELISA. RESULTS CD14 polymorphism was not associated with H. pylori infection. There were no significant differences in gastritis scores among the genotype subgroups, but subjects carrying the CD14 -260 CT/TT genotype had significantly higher sCD14 levels than those carrying the CC genotype. Subjects with the 260-T allele of the CD14 gene and H. pylori infection had significantly higher sCD14 levels than those with the same genotype but without infection. CONCLUSIONS In individuals with the T allele at the -260 site of the promoter region of the CD14 gene, H. pylori infection accentuates gastric mucosal inflammation.
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Affiliation(s)
- Eun Jung Kim
- Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea College of Medicine, Suwon, Korea
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Yu L, Wang L, Chen S. Exogenous or endogenous Toll-like receptor ligands: which is the MVP in tumorigenesis? Cell Mol Life Sci 2012; 69:935-49. [PMID: 22048194 PMCID: PMC11114862 DOI: 10.1007/s00018-011-0864-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2011] [Revised: 09/19/2011] [Accepted: 10/14/2011] [Indexed: 12/15/2022]
Abstract
Toll-like receptors (TLRs) are a class of pattern recognition receptors sensing microbial components and triggering an immune response against pathogens. In addition to their role in anti-infection immunity, increasing evidence indicates that engagement of TLRs can promote cancer cell survival and proliferation, induce tumor immune evasion, and enhance tumor metastasis and chemoresistance. Recent studies have demonstrated that endogenous molecules or damage-associated molecular patterns released from damaged/necrotic tissues are capable of activating TLRs and that the endogenous ligands-mediated TLR signaling is implicated in the tumor development and affects the therapeutic efficacy of tumors. Since both exogenous and endogenous TLR ligands can initiate TLR signaling, which is the most valuable player in tumor development becomes an interesting question. Here, we summarize the effect of TLR signaling on the development and progression of tumors, and discuss the role of exogenous and endogenous TLR ligands in the tumorigenesis.
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Affiliation(s)
- Li Yu
- Department of Pathology, The First Affiliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou 510080, People's Republic of China.
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[Single nucleotide polymorphisms and helicobacter pylori-related gastric cancer]. YI CHUAN = HEREDITAS 2011; 33:109-16. [PMID: 21377966 DOI: 10.3724/sp.j.1005.2011.00109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Helicobacter pylori-related gastric cancer is a special-type gastric cancer determined by genetic, environmental, and life style factors. A series of single nucleotide polymorphisms (SNPs) of susceptibility genes, including inflammation-related genes, gastric acid inhibition-related genes, and immune response-related genes, could be specifically involved in the development of Helicobacter pylori-related gastric cancer that consists of three major stages: Helicobacter pylori infection, gastric atrophy development, and carcinogenesis. The aim of the present paper was to review and evaluate the most recently published evidence on the contribution of SNPs to the carcinogenesis of Helicobacter pylori-related gastric cancer in humans.
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-651C/T promoter polymorphism in the CD14 gene is associated with severity of acute pancreatitis in Japan. J Gastroenterol 2010; 45:225-33. [PMID: 19997857 DOI: 10.1007/s00535-009-0163-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2009] [Accepted: 11/05/2009] [Indexed: 02/04/2023]
Abstract
PURPOSE This study aimed to clarify the association of the promoter variants in the CD14 gene with pancreatic diseases in Japan. METHODS Three hundred forty-six unrelated patients with acute pancreatitis (AP) (107 with severe and 239 with mild), 263 patients with chronic pancreatitis (CP), 264 patients with pancreatic neoplasm, and 319 healthy controls were genotyped for the single nucleotide polymorphisms at positions -260 and -651 from the AUG start codon in the CD14 gene by polymerase chain reaction-restriction enzyme digestion. RESULTS The allele and genotype frequencies of the -260C/T and -651C/T polymorphisms did not differ between controls and patients with AP. In subgroup analyses, patients with severe AP had more -651C allele than controls [P = 0.005; odds ratio (OR) 1.71; 95% confidence interval (CI) = 1.18-2.49] or patients with mild AP (P = 0.001; OR 1.95; 95% CI = 1.33-2.85). Genotype -651CC was more common (P = 0.001 vs. controls and P = 0.001 vs. mild AP), and -651CT was less (P = 0.009 vs. controls and P = 0.007 vs. mild AP) in patients with severe AP than in healthy controls or patients with mild AP. The frequencies of pseudocyst development and requirement of surgery were higher in AP patients with -651CC than in those without this genotype. The -260C/T polymorphism was not associated with the severity of AP. The allele and genotype frequencies of both polymorphisms did not differ between controls and patients with CP or pancreatic neoplasm. CONCLUSION -651C/T promoter polymorphism in the CD14 gene was associated with severity of AP in Japan.
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