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1
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Xu B, Yan Y. The Association Between IL-8 Gene Polymorphisms and the Risk of Several Types of Cancer, Especially in Gastric Cancer. Cancer Rep (Hoboken) 2025; 8:e70103. [PMID: 39821721 PMCID: PMC11740087 DOI: 10.1002/cnr2.70103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 11/25/2024] [Accepted: 12/13/2024] [Indexed: 01/19/2025] Open
Abstract
BACKGROUND Changes in functional genetic polymorphisms may increase or decrease the risk of cancer in patients. Nowadays, the association between polymorphisms in the interleukin-8 (IL-8) gene and the susceptibility of cancer risk have been investigated in many studies, however, above relationships remain unclear. AIM The current study aims to comprehensively evaluate the association between IL-8 gene six polymorphisms and the whole cancer risk, especially -251 polymorphism and gastric cancer. METHODS AND RESULTS Six polymorphisms (-251, -353, +678, +1633, +2767, +781) were collected. The expression of serum IL-8 was calculated by ELISA assay. First, 104 case-control studies were conducted. Second, this research has made significant discoveries regarding the -251, -353 and +781 polymorphisms and the potential associations with cancer risk. Finally, the serum IL-8 levels in gastric cancer patients with AA/TT genotypes were significantly higher than those with the same genotypes of healthy controls and TT genotypes in gastric cancer patients. CONCLUSION Overall, the investigation has revealed that IL-8 gene polymorphisms significantly influence vulnerability to cancer development, especially for gastric cancer.
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Affiliation(s)
- Bin Xu
- Geriatrics DepartmentAffiliated Hospital of Jiangnan UniversityWuxiChina
| | - Yidan Yan
- Medical OncologyAffiliated Hospital of Jiangnan UniversityWuxiChina
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2
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Radwan RE, Darwish A, Elsaid AM, El-Kholy WM. Exploring the potential of IL-10 for risk assessment and early intervention in pediatric ALL. BMC Cancer 2024; 24:972. [PMID: 39118076 PMCID: PMC11308622 DOI: 10.1186/s12885-024-12677-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 07/23/2024] [Indexed: 08/10/2024] Open
Abstract
Acute lymphoblastic leukemia (ALL), a leading cause of childhood cancer, targets immune system B and T cells. While understanding its causes is crucial, predicting susceptibility holds immense power for early diagnosis and intervention. This study explored the potential of interleukin 10 (IL-10), a key immune regulator, as a predictive tool in Egyptian children. Investigating 100 ALL patients and 100 healthy controls, we analyzed the IL10 gene polymorphism (-1082 A/G) and serum levels. Strikingly, both the G allele and higher serum IL-10 levels were significantly associated with increased ALL risk (p < 0.05, OR > 1). Moreover, IL-10 emerged as a remarkably accurate predictor, boasting an AUC of 0.995, with a sensitivity of 97% and specificity of 96%. These findings unveil the potential of IL-10 as a powerful predictive tool for pediatric ALL in the studied Egyptian population. Identifying individuals with the GG/AG haplotype and elevated IL-10 levels could enable early intervention and potentially improve outcomes. While further validation in larger and more diverse populations is needed, this study paves the way for personalized risk assessment and potentially revolutionizes how we combat this childhood killer.
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Affiliation(s)
- Roqaia E Radwan
- Physiology Section, Zoology Department, Faculty of Science, Mansoura University, Mansoura, Egypt.
| | - Ahmad Darwish
- Hematology, Oncology and Bone Marrow Transplantation Unit, Pediatric Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Afaf M Elsaid
- Genetics Unit, Children Hospital, Mansoura University, Mansoura, Egypt
| | - Wafaa M El-Kholy
- Physiology Section, Zoology Department, Faculty of Science, Mansoura University, Mansoura, Egypt
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3
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Investigation of roles of IL-8 (+ 781 C/T) and MMP-2 (-735 C/T) gene variations in early diagnosis of bladder cancer and progression. Mol Biol Rep 2023; 50:443-451. [PMID: 36348195 DOI: 10.1007/s11033-022-07881-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 08/12/2022] [Accepted: 08/17/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND The aim of our study is to investigate the roles of IL-8 (+ 781 C/T) and MMP-2 (-735 C/T) gene variations in early diagnosis and progression of BCA. METHODS Polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) methods were used to determine the genotype distributions of IL-8 (+ 781 C/T) and MMP-2 (-735 C/T) gene variations. RESULTS In our study, the genotype distributions of IL-8 (+ 781 C/T) and MMP-2 (-735 C/T) gene variations were not found to be significantly different between the patient and control groups. In addition, C and T allele frequencies for these gene variations were not different from the Hardy-Weinberg distribution in patient and control groups. However, when the combined genotype analyzes for these gene variations were evaluated, CC-CC and CT-CC combined genotypes for + 781 C/T / -735 C/T gene variations were observed significantly more in the patient group compared to other genotypes. CONCLUSION Although IL-8 (+ 781 C/T) and MMP-2 (-735 C/T) gene variations were not found to be genetic risk factors in the Thrace population in our study, CC-CC and CT-CC combined genotypes were determined as genetic risk factors for BCA susceptibility. The combined genotypes obtained as a result of the combined genotype analysis of these genetic variations that are effective in tumor progression may be considered to be important biomarkers for the early diagnosis and progression of BCA.
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4
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Comert S, Sen S, Eryilmaz O, Doruk C, Ulusan M, Demokan S. Evaluation of genetic and epigenetic changes of Tumor Necrosis Factor-Alpha gene in larynx cancer. Pathol Res Pract 2022; 238:154085. [PMID: 36027653 DOI: 10.1016/j.prp.2022.154085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 08/11/2022] [Accepted: 08/18/2022] [Indexed: 11/11/2022]
Abstract
BACKGROUND Tumor Necrosis Factor-Alpha (TNF-α) is a proinflammatory cytokine that plays a role in inflammation, which is one of the hallmarks of cancer, and its polymorphic variants have been associated with disease risk in many cancers in the literature. The aim of this study was to investigate four different polymorphic variants, differential methylation and expression status of the TNF-α gene and to determine the associations between these variants and disease risk, and to evaluate the relationship between the results and clinical parameters. We purposed to investigate the genetic and epigenetic alterations of the TNF-α gene in larynx cancer (LC). MATERIAL AND METHODS After isolation of DNA/RNA from whole blood, tumor and normal tissue, polymorphic variant alleles differrential expression and methylation levels were analyzed by RFLP, semiquantitative RT-PCR, and restriction enzyme digestion, respectively. TNF-α expression and methylation levels were calculated using BIO1D software. The frequencies of the variants c.-238 G>A (rs361525), c.-857 C>T (rs1799724), c.-863 C>A (rs1800630), and c.-1031 T > C (rs1799964) in the promoter region of TNF-α in LC Turkish patients and healthy individuals were examined using the De-Finetti case-control program. Haplotype frequencies and linkage disequilibrium were analyzed using the SNPStats program. RESULTS The frequency of genotype c.-1031 T > C was significantly lower in patients than in healthy individuals [TT vs TC: OR (%95CI) = 7.00 (1.75-27.93), p = 0.003, χ2 = 8.76]. The heterozygous variant of - 857 was associated with recurrence [T vs G: OR (%95CI) = 0.15 (0.02-0.95), p = 0.02, χ2 = 4.86]. For c.-238 G>A, c.-857 C>T, and c.-863 C>A, there was no statistically significant difference between the patient and healthy group in terms of disease risk. A significant association was found between c.-1031 T > C and disease risk of LC. Decreased expression was detected in 46% (23/50) and increased expression in 54% (27/50) of tumor tissue samples compared to the matched normal tissues of patients. Methylation-related loss of expression was detected in 53.3% (16/30) of patients. CONCLUSION Our study is the first investigating four different polymorphic regions of the TNF-α promoter region and the expression/methylation status of TNF-α in the same LC patient and healthy cohort. According to our results, the c.-1031 T > C variant was reported to be significantly associated with a reduced risk of LC. In addition, the TNF-α variant c. -857 C>T suggests that it may be a potential biomarker for predicting the recurrence of LC. An association between c. -857 C>T variant and methylation-based expression status was observed.
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Affiliation(s)
- Sevde Comert
- Department of Basic Oncology, Oncology Institute, Istanbul University, Istanbul, Türkiye; Department of Basic Oncology, Institute of Graduate Studies in Health Sciences, Istanbul University, Istanbul, Türkiye
| | - Sena Sen
- Department of Basic Oncology, Oncology Institute, Istanbul University, Istanbul, Türkiye
| | - Onder Eryilmaz
- Department of Basic Oncology, Oncology Institute, Istanbul University, Istanbul, Türkiye
| | - Can Doruk
- Department of Otorhinolaryngology-Head and Neck Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Murat Ulusan
- Department of Otorhinolaryngology-Head and Neck Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Semra Demokan
- Department of Basic Oncology, Oncology Institute, Istanbul University, Istanbul, Türkiye.
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5
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Abdalhabib EK, Alzahrani B, Saboor M, Hamza A, Elfaki EM, Alanazi F, Alenazy FO, Algarni A, Khider Ibrahim I, Mohamed HA, Hussein Alfeel A, Ali Alshaikh N. IL-10 rs1800896 Polymorphism: A Risk Factor for Adult Acute Lymphoblastic Leukemia. Pharmgenomics Pers Med 2022; 15:809-815. [PMID: 36119849 PMCID: PMC9480578 DOI: 10.2147/pgpm.s377356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Accepted: 08/30/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose Single-nucleotide polymorphism (SNP) in the promoter region of the IL-10 gene can increase susceptibility to tumor development. The current study aimed to explore the genotypic frequency of interleukin-10 (IL-10) rs1800896 polymorphism in newly diagnosed adult patients with acute lymphoblastic leukemia (ALL) and validate whether this SNP is a risk factor for adult ALL. Patients and Methods This case–control study was based on a subset of newly diagnosed 154 adult patients with ALL recruited from the Radiation and Isotope Center in Khartoum (RICK) and 154 healthy controls from the same geographical area. Genomic DNA was used for the genotyping of rs1800896 polymorphism through allele-specific polymerase chain reaction (PCR) assays. Results The genotypic frequencies of rs1800896 showed a statistically significant association of AG and AA genotypes with adult ALL (p<0.001). Combined genotypes AG+GG vs AA also showed a positive association of rs1800896 with adult ALL (OR=4.89). The allelic frequencies of G and A did not show any significant difference in adult patients with ALL compared with the control group. AG rs1800896 genotype showed an increased risk of B and T ALL (OR=2.51 and 4.70, respectively). Age at diagnosis, gender, and immunophenotype (B vs T ALL) did not exhibit any association of rs1800896 with ALL in this patient group. Conclusion rs1800896 polymorphism is associated with an increased risk of ALL in adult patients irrespective of the age at diagnosis, gender, and immunophenotype of ALL.
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Affiliation(s)
- Ezeldine K Abdalhabib
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia
| | - Badr Alzahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia
| | - Muhammad Saboor
- Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
- Medical Research Center (MRC), Jazan University, Jazan, Saudi Arabia
- Muhammad Saboor, Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates, Tel +971 56 443 2008, Email
| | - Alneil Hamza
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia
| | - Elyasa M Elfaki
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia
| | - Fehaid Alanazi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia
| | - Fawaz O Alenazy
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia
| | - Abdulrahman Algarni
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Northern Border University, Arar, Saudi Arabia
| | - Ibrahim Khider Ibrahim
- Department of Hematology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan
| | - Hozifa A Mohamed
- Department of Molecular Biology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan
| | - Ayman Hussein Alfeel
- Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman, United Arab Emirates
- Correspondence: Ayman Hussein Alfeel, Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman, United Arab Emirates, Email
| | - Nahla Ali Alshaikh
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
- Medical Research Center (MRC), Jazan University, Jazan, Saudi Arabia
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6
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Diakite B, Kassogue Y, Maiga M, Dolo G, Kassogue O, Musa J, Morhason-Bello I, Traore B, Traore CB, Kamate B, Coulibaly A, Bah S, Nadifi S, Murphy R, Holl JL, Hou L. Association of the Interleukin-10-592C/A Polymorphism and Cervical Cancer Risk: A Meta-Analysis. Genet Res (Camb) 2022; 2022:2319161. [PMID: 35919032 PMCID: PMC9296312 DOI: 10.1155/2022/2319161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 06/10/2022] [Indexed: 11/17/2022] Open
Abstract
A literature review showed some discrepancies regarding the association of -592C/A with the risk of cervical cancer. To allow more precise analysis of the data by increasing the number of cases studied and more acceptable generalization by considering results from different sources, the present meta-analysis was performed on available published studies that explored the relationship between SNP-592C/A of the IL-10 gene and the risk of cervical cancer. Eleven available studies, including 4187 cases and 3311 controls, were included in this study investigating the relationship between the -592C/A polymorphism of IL-10 and cervical cancer risk. Fixed-effects or random-effects models were performed with pooled odds ratios (ORs). Heterogeneity and bias tests were performed by the inconsistency test and funnel plot, respectively. The overall analysis showed an increased susceptibility to cervical cancer with the -592C/A polymorphism of the IL-10 gene for the recessive model (OR = 1.30, 95% CI = 1.14-1.49), dominant model (OR = 1.36, 95% CI = 1.09-1.70), and additive model (OR = 1.25, 95% CI = 1.09-1.44). Regarding ethnicity, a significant association of the -592C/A polymorphism of the IL-10 gene was linked to an elevated risk of cervical cancer for all genetic models (recessive, dominant, and additive) in the Asian populations and for the recessive and additive models in Caucasians with P < 0.05. The -592C/A polymorphism of the IL-10 gene may be considered a risk factor for cervical cancer.
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Affiliation(s)
- Brehima Diakite
- Centre de Recherche et de Formation sur les Pathologies Moleculaires (CREFPAM), University of Sciences, Techniques and Technologies of Bamako (USTTB), Bamako, Mali
| | - Yaya Kassogue
- Centre de Recherche et de Formation sur les Pathologies Moleculaires (CREFPAM), University of Sciences, Techniques and Technologies of Bamako (USTTB), Bamako, Mali
| | - Mamoudou Maiga
- Centre de Recherche et de Formation sur les Pathologies Moleculaires (CREFPAM), University of Sciences, Techniques and Technologies of Bamako (USTTB), Bamako, Mali
- Preventive Medicine Department, Cancer Epidemiology and Prevention, Northwestern University, Chicago, Illinois 60611, USA
- Institute for Global Health, Northwestern University, Chicago, Illinois 60611, USA
| | - Guimogo Dolo
- Centre de Recherche et de Formation sur les Pathologies Moleculaires (CREFPAM), University of Sciences, Techniques and Technologies of Bamako (USTTB), Bamako, Mali
| | - Oumar Kassogue
- Centre de Recherche et de Formation sur les Pathologies Moleculaires (CREFPAM), University of Sciences, Techniques and Technologies of Bamako (USTTB), Bamako, Mali
| | - Jonah Musa
- Preventive Medicine Department, Cancer Epidemiology and Prevention, Northwestern University, Chicago, Illinois 60611, USA
- Institute for Global Health, Northwestern University, Chicago, Illinois 60611, USA
- Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Jos, Plateau State, Jos, Nigeria
| | - Imran Morhason-Bello
- Department of Obstetrics and Gynecology, Faculty of Clinical Sciences and Institute for Advanced Medical Research and Training (IAMRAT), College of Medicine, University of Ibadan, Ibadan, Oyo, Nigeria
| | - Ban Traore
- Faculty of Sciences and Techniques, USTTB, Bamako, Mali
| | - Cheick Bougadari Traore
- Centre de Recherche et de Formation sur les Pathologies Moleculaires (CREFPAM), University of Sciences, Techniques and Technologies of Bamako (USTTB), Bamako, Mali
| | - Bakarou Kamate
- Centre de Recherche et de Formation sur les Pathologies Moleculaires (CREFPAM), University of Sciences, Techniques and Technologies of Bamako (USTTB), Bamako, Mali
| | - Aissata Coulibaly
- Centre de Recherche et de Formation sur les Pathologies Moleculaires (CREFPAM), University of Sciences, Techniques and Technologies of Bamako (USTTB), Bamako, Mali
| | - Sekou Bah
- Faculty of Pharmacy, USTTB, Bamako, Mali
| | | | - Robert Murphy
- Institute for Global Health, Northwestern University, Chicago, Illinois 60611, USA
| | - Jane L. Holl
- Department of Neurology, University of Chicago, Chicago, Illinois 60611, USA
| | - Lifang Hou
- Preventive Medicine Department, Cancer Epidemiology and Prevention, Northwestern University, Chicago, Illinois 60611, USA
- Institute for Global Health, Northwestern University, Chicago, Illinois 60611, USA
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7
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Cerrato-Izaguirre D, Chirino YI, García-Cuellar CM, Santibáñez-Andrade M, Prada D, Hernández-Guerrero A, Larraga OA, Camacho J, Sánchez-Pérez Y. Mutational landscape of gastric adenocarcinoma in Latin America: A genetic approach for precision medicine. Genes Dis 2022; 9:928-940. [PMID: 35685475 PMCID: PMC9170608 DOI: 10.1016/j.gendis.2021.04.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 04/01/2021] [Indexed: 02/07/2023] Open
Abstract
Latin-America (LATAM) is the second region in gastric cancer incidence; gastric adenocarcinoma (GA) represents 95% of all cases. We provide a mutational landscape of GA highlighting a) germline pathogenic variants associated with hereditary GA, b) germline risk variants associated with sporadic GA, and c) somatic variants present in sporadic GA in LATAM, and analyze how this landscape can be applied for precision medicine. We found that Brazil, Chile, Colombia, Mexico, Peru, and Venezuela are the countries with more published studies from LATAM explicitly related to GA. Our analysis displayed that different germline pathogenic variants for the CDH1 gene have been identified for hereditary GA in Brazilian, Chilean, Colombian, and Mexican populations. An increased risk of developing somatic GA is associated with the following germline risk variants: IL-4, IL-8, TNF-α, PTGS2, NFKB1, RAF1, KRAS and MAPK1 in Brazilian; IL-10 in Chilean; IL-10 in Colombian; EGFR and ERRB2 in Mexican, TCF7L2 and Chr8q24 in Venezuelan population. The path from mutational landscape to precision medicine requires four development levels: 1) Data compilation, 2) Data analysis and integration, 3) Development and approval of clinical approaches, and 4) Population benefits. Generating local genomic information is the initial padlock to overcome to generate and apply precision medicine.
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Affiliation(s)
- Dennis Cerrato-Izaguirre
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Tlalpan, Ciudad de México, CP 14080, Mexico
- Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del I.P.N. (CINVESTAV), Ciudad de México, CP 07360, Mexico
| | - Yolanda I. Chirino
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Reyes Iztacala, Tlalnepantla de Baz, Estado de México, CP 54090, Mexico
| | - Claudia M. García-Cuellar
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Tlalpan, Ciudad de México, CP 14080, Mexico
| | - Miguel Santibáñez-Andrade
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Tlalpan, Ciudad de México, CP 14080, Mexico
| | - Diddier Prada
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Tlalpan, Ciudad de México, CP 14080, Mexico
- Departamento de Informática Biomédica, Facultad de Medicina, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México, CP 04510, Mexico
- Department of Environmental Health Science, Mailman School of Public Health, Columbia University, New York, NY 10027, USA
| | - Angélica Hernández-Guerrero
- Servicio de Endoscopía, Instituto Nacional de Cancerología (INCan), Tlalpan, Ciudad de México, CP 14080, Mexico
| | - Octavio Alonso Larraga
- Servicio de Endoscopía, Instituto Nacional de Cancerología (INCan), Tlalpan, Ciudad de México, CP 14080, Mexico
| | - Javier Camacho
- Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del I.P.N. (CINVESTAV), Ciudad de México, CP 07360, Mexico
| | - Yesennia Sánchez-Pérez
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Tlalpan, Ciudad de México, CP 14080, Mexico
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8
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Mohammadi A, Khanbabaei H, Zandi F, Ahmadi A, Haftcheshmeh SM, Johnston TP, Sahebkar A. Curcumin: A therapeutic strategy for targeting the Helicobacter pylori-related diseases. Microb Pathog 2022; 166:105552. [DOI: 10.1016/j.micpath.2022.105552] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 04/16/2022] [Accepted: 04/19/2022] [Indexed: 12/12/2022]
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9
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Pratap PD, Raza ST, Zaidi G, Kunwar S, Ahmad S, Charles MR, Eba A, Rajput M. Genetic Variants in Interleukin-10 Gene Association with Susceptibility and Cervical Cancer Development: A Case Control Study. Glob Med Genet 2022; 9:129-140. [PMID: 35707782 PMCID: PMC9192188 DOI: 10.1055/s-0042-1743262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Accepted: 12/29/2021] [Indexed: 12/24/2022] Open
Abstract
Objectives
Cervical cancer (CC) is one of the most destructive disease caused by persistent HPV infection which affects women worldwide, especially in developing countries. The genetic basis of host immune response especially cytokine function has been shown to influence CC susceptibility. Studies have demonstrated that IL-10 gene polymorphism have been associated with numerous malignancies, but in context to CC results were inconclusive. Though, aim of our study to investigate the association between IL-10 -1082A/G and -819C/T promoter polymorphism and CC susceptibility.
Material and Methods
This study comprised 192 women with CC and 200 controls. HPV detection was done by RT-PCR and genotyping was assessed through PCR-RFLP method. Serum concentration of IL-10 measured by ELISA.
Results
Women with AG and AG+GG genotypes of IL-10 -1082A/G had two-fold increased risk of CC [OR, 2.35 (95% CI, 1.54–3.58),
p
= 0.005], [OR, 2.03 (95% CI, 1.36–3.04),
p
= 0.0005] compared to controls. Women with G allele of -1082A/G polymorphism had linked with CC susceptibility [OR, 1.39 (95% CI, 1.02–1.88),
p
= 0.036] compared to controls. No significant difference was found between patients and controls in the genotype or allele frequencies of IL–10 -819C/T polymorphism [OR, 1.00 (95% CI, 0.63–1.58),
p
= 0.99]. The level of serum concentration of IL-10 was significantly higher in cases compared to controls.
Conclusion
These findings help to understand that polymorphism of IL-10 -1082A/G gene is associated with increased risk of CC development and can serve as a marker of genetic susceptibility to CC.
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Affiliation(s)
- Pushpendra D. Pratap
- Central Research Laboratory, Molecular Diagnostic Unit, Department of Biochemistry, ERA's Lucknow Medical College, ERA University, Lucknow, Uttar Pradesh, India
| | - Syed Tasleem Raza
- Central Research Laboratory, Molecular Diagnostic Unit, Department of Biochemistry, ERA's Lucknow Medical College, ERA University, Lucknow, Uttar Pradesh, India
| | - Ghazala Zaidi
- Department of Allied Health Sciences, ERA University, Lucknow, Uttar Pradesh, India
| | - Shipra Kunwar
- Department of Obstetrics & Gynecology, ERA University, Lucknow, Uttar Pradesh, India
| | - Sharique Ahmad
- Department of Pathology ERA's Lucknow Medical College, ERA University, Lucknow, Uttar Pradesh, India
| | - Mark Rector Charles
- Central Research Laboratory, Molecular Diagnostic Unit, Department of Biochemistry, ERA's Lucknow Medical College, ERA University, Lucknow, Uttar Pradesh, India
| | - Ale Eba
- Central Research Laboratory, Molecular Diagnostic Unit, Department of Biochemistry, ERA's Lucknow Medical College, ERA University, Lucknow, Uttar Pradesh, India
| | - Muneshwar Rajput
- Central Research Laboratory, Molecular Diagnostic Unit, Department of Biochemistry, ERA's Lucknow Medical College, ERA University, Lucknow, Uttar Pradesh, India
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10
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Gobert AP, Wilson KT. Induction and Regulation of the Innate Immune Response in Helicobacter pylori Infection. Cell Mol Gastroenterol Hepatol 2022; 13:1347-1363. [PMID: 35124288 PMCID: PMC8933844 DOI: 10.1016/j.jcmgh.2022.01.022] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/25/2022] [Accepted: 01/25/2022] [Indexed: 12/30/2022]
Abstract
Gastric cancer (GC) is the fifth most common cancer and the fourth most common cause of cancer-related death worldwide. The intestinal type of GC progresses from acute to chronic gastritis, multifocal atrophic gastritis, intestinal metaplasia, dysplasia, and carcinoma. Infection of the stomach by Helicobacter pylori, a Gram-negative bacterium that infects approximately 50% of the world's population, is the causal determinant that initiates the gastric inflammation and then disease progression. In this context, the induction of the innate immune response of gastric epithelial cells and myeloid cells by H. pylori effectors plays a critical role in the outcome of the infection. However, only 1% to 3% of infected patients develop gastric adenocarcinoma, emphasizing that other mechanisms regulate the localized non-specific response, including the gastric microbiota and genetic factors. This review summarizes studies describing the factors that induce and regulate the mucosal innate immune response during H. pylori infection.
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Affiliation(s)
- Alain P Gobert
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Nashville, Tennessee; Program in Cancer Biology, Nashville, Tennessee.
| | - Keith T Wilson
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Nashville, Tennessee; Program in Cancer Biology, Nashville, Tennessee; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee.
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11
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Wei S, Li X, Wang J, Wang Y, Zhang C, Dai S, Wang X, Deng X, Zhao L, Shan B. Outer Membrane Vesicles Secreted by Helicobacter pylori Transmitting Gastric Pathogenic Virulence Factors. ACS OMEGA 2022; 7:240-258. [PMID: 35036696 PMCID: PMC8756444 DOI: 10.1021/acsomega.1c04549] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 12/03/2021] [Indexed: 06/14/2023]
Abstract
Helicobacter pylori (H. pylori) is known to be a major pathogen causing gastric diseases through its direct localization in gastric epithelium cells. H. pylori releases outer membrane vesicles (OMVs) throughout the growth process. The content, function, and mechanism of H. pylori OMVs in gastric epithelial cells remain unclear. In this study, we extracted and characterized H. pylori OMVs of two strains (standard strain NCTC11637 and clinical strain Hp-400) and analyzed the specific content by proteomic technology. We identified more than 400 proteins in H. pylori OMVs. In addition, we investigated the impact of H. pylori OMVs on cellular functions by detecting proteomic changes in GES1 cells. GES1 cells cocultured with increasing concentrations of H. pylori OMVs were subjected to quantitative proteomic analyses using label-free methods for relative quantitation. The results showed that a total of 4261 proteins were verified, 153 of which were significantly altered in abundance when cocultured with NCTC11637 OMVs, and a total of 4234 proteins in Hp-400 OMVs, 390 of which were significantly altered. Gene ontology analysis and Kyoto encyclopedia of genes and genomes pathway mapping identified significantly altered inflammatory and cancer signaling pathways, including metabolic pathways and the PI3K-Akt signaling pathway. Furthermore, we explored the proteomic changes in GES1 cells induced by H. pylori. Bioinformatics analysis showed that changes in multiple pathways coincided with OMV-mediated proteomic changes. Based on these results, H. pylori induced pathogenicity in epithelial cells at least partially by secreting OMVs that mediated dramatic and specific proteomic changes in host cells. Data are available via ProteomeXchange with identifiers PXD025216, PXD025259, and PXD025281.
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Affiliation(s)
- Sisi Wei
- Research
Center, Hebei Medical University Fourth
Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, Hebei Province 050011, China
| | - Xiaoya Li
- Research
Center, Hebei Medical University Fourth
Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, Hebei Province 050011, China
| | - Jingjing Wang
- Research
Center, Hebei Medical University Fourth
Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, Hebei Province 050011, China
| | - Yaojie Wang
- Research
Center, Hebei Medical University Fourth
Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, Hebei Province 050011, China
| | - Cong Zhang
- Research
Center, Hebei Medical University Fourth
Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, Hebei Province 050011, China
| | - Suli Dai
- Research
Center, Hebei Medical University Fourth
Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, Hebei Province 050011, China
| | - Xian Wang
- Shijiazhuang
Center for Disease Control and Prevention, Shijiazhuang, Hebei Province 050011, China
| | - Xiaoqing Deng
- Research
Center, Hebei Medical University Fourth
Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, Hebei Province 050011, China
| | - Lianmei Zhao
- Research
Center, Hebei Medical University Fourth
Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, Hebei Province 050011, China
| | - Baoen Shan
- Research
Center, Hebei Medical University Fourth
Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, Hebei Province 050011, China
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12
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Association of Interleukin-10 Polymorphisms with Susceptibility to Colorectal Cancer and Gastric Cancer: an Updated Meta-analysis Based on 106 Studies. J Gastrointest Cancer 2021; 53:1066-1082. [PMID: 34694592 DOI: 10.1007/s12029-021-00685-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/01/2021] [Indexed: 01/30/2023]
Abstract
BACKGROUND The purpose of this study was to explore the association of IL-10 polymorphisms with susceptibility to colorectal cancer (CRC) and gastric cancer (GC). METHODS PubMed, Scopus, Embase, SciELO, medRxiv, China Biology Medicine Disc, DeepDyve, CNKI, and Web of Science were used to identify all relevant articles published up to 20th June 2021, without any restrictions on ethnicity. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to determine the strength of the associations. RESULTS A total of 106 case-control studies were included. For CRC, 15 studies with 2772 cases and 3719 controls on -1082A/G, 11 studies with 3259 cases and 4992 controls on -592C/A, and 3 studies with 477 cases and 544 controls on -819 T/C were selected. For GC, 31 studies with 6229 cases and 8666 controls on -1082A/G, 27 studies with 5457 cases and 8381 controls on -592C/A, and 19 studies with 3556 cases and 6218 controls on -819 T/C were included. Pooled data showed a significant association between IL-10-819 T/C polymorphism and CRC susceptibility in overall population, but not for IL-10-1082A/G and -592C/A polymorphisms. However, IL-10-592C/A polymorphism was associated with CRC risk in Asians. A significant association of IL-10-1082A/G polymorphism with the GC risk was found. In the ethnicity subgroup analysis, a significant association was found between IL-10-1082A/G polymorphism and GC risk among Asians. The IL-10-819 T/C was not associated with GC risk in overall population and by ethnicity. CONCLUSIONS Our pooled data show a significant association of IL-10-819 T/C and IL-10-1082A/G polymorphisms with CRC and GC in overall population, respectively. However, other factors may influence these associations, and large-scale studies with adequate methodological quality are necessary to confirm the impact on CRC and GC risk.
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13
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The Role of Tumor Necrosis Factor-α (TNF-α) Polymorphisms in Gastric Cancer: a Meta-Analysis. J Gastrointest Cancer 2021; 53:756-769. [PMID: 34478034 DOI: 10.1007/s12029-021-00688-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/08/2021] [Indexed: 12/12/2022]
Abstract
PURPOSE Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine which may play a role in the development of gastric cancer (GC). This study aimed to investigate the association of five TNF-α polymorphisms including TNF-α-857, TNF-α-1031, TNF-α-863, TNF-α-308, and TNF-α-238 polymorphisms with GC risk. METHODS All eligible case-control studies were collected by searching PubMed, Scopus, and Web of Science. The association of the risk of GC with TNF-α polymorphisms was estimated using odds ratio (OR) and 95% confidence interval (CI). Heterogeneity was assessed via Cochrane's Q and I2 analyses. RESULTS A total of 46 publications involving 16, 715 cases with GC and 27, 998 controls were recruited. The study revealed a significant association for TNF-α 308 (recessive model: OR = 0.646, P = 0.035), TNF-α-1031 (homozygote model: OR = 1.584, P = 0.027), and TNF-α-857 (homozygote model: OR = 1.760, P = 0.001) polymorphisms with the GC risk. The results of subgroup analysis based ethnicity found a significant association between GC risk and TNF-α-857 polymorphism in Caucasian subgroup (P = 0.005) and TNF-α-1031 polymorphism and GC risk in Asians (P = 0.018). CONCLUSIONS This study suggested that TNF-α-857 and TNF-α-1031 polymorphisms may be associated with the increased gastric cancer risk.
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Roshanipour N, Shahriyari E, Ghaffari Laleh M, Vahedi L, Mirjand Gerami S, Khamaneh A. Associations of TLR4 and IL-8 genes polymorphisms with age-related macular degeneration (AMD): a systematic review and meta-analysis. Ophthalmic Genet 2021; 42:641-649. [PMID: 34287094 DOI: 10.1080/13816810.2021.1955274] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND The results of different studies have indicated the possible associations of TLR4 and IL-8 genes polymorphisms with Age-related Macular Degeneration (AMD). A meta-analysis study was designed to evaluate the possible associations of TLR4 (rs4986790/c.896A>G and rs4986791/ c.1196 C > T) and IL-8 (rs4073/c.251A>T and rs2227306/c.781 C > T) genes polymorphisms with AMD. METHOD A systematic literature search was carried out in PubMed, Embase, Web of Science, and Scopus databases to identify relevant publications. Pooled Odds Ratio (OR) with 95% Confidence Interval (CI) was used to evaluate the power of association. RESULTS A total of 12 case-control studies with 4804 AMD patients and 4422 healthy controls were included in this meta-analysis. The analysis of genotypic and allelic models demonstrated significant associations between IL-8 c.781 C > T (CC vs. TT+TC: OR = 0.62 [0.48-0.81], P < .01; CC vs. TC: OR = 0.65 [0.48-0.89], P < .01; TT vs. CC: OR = 1.64 [1.04-2.57], P = .03; and C vs. T: OR = 0.71 [0.65-0.79], P < .01) and risk of AMD, which all of them passed Bonferroni correction for multiple testing (P-value≤0.01), except for TT vs. CC model. In addition, we found associations under the genotypic model of TLR4 c.896A>G (AA vs. AG+GG: OR = 0.73 [0.55-0.97], P = .03; and AA vs. AG: OR = 0.71 [0.53-0.95], P = .02) although after Bonferroni correction (P'-value<0.02) none of these associations remained significant. However, the data from this meta-analysis declined the associations of TLR4 c.1196 C > T and IL-8 c.251A>T polymorphisms with AMD. CONCLUSION The current meta-analysis study suggested that IL-8 c.781 C > T polymorphism is associated with susceptibility to AMD.
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Affiliation(s)
- Nasrin Roshanipour
- Department of Biology, School of Genetic, Islamic Azad University Tabriz Branch, Tabriz, Iran.,Liver and Gastrointestinal Diseases Research Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elham Shahriyari
- Liver and Gastrointestinal Diseases Research Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.,Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Maryam Ghaffari Laleh
- Liver and Gastrointestinal Diseases Research Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.,Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.,Medical Faculty, Research Center for Evidence-Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leila Vahedi
- Liver and Gastrointestinal Diseases Research Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sousan Mirjand Gerami
- Liver and Gastrointestinal Diseases Research Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amin Khamaneh
- Medical Faculty, Research Center for Evidence-Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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15
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Deng F, Weng Y, Li X, Wang T, Fan M, Shi Q. Overexpression of IL-8 promotes cell migration via PI3K-Akt signaling pathway and EMT in triple-negative breast cancer. Pathol Res Pract 2021; 223:152824. [PMID: 34000674 DOI: 10.1016/j.prp.2020.152824] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 12/18/2019] [Accepted: 01/09/2020] [Indexed: 11/20/2022]
Abstract
Triple-negative breast cancer (TNBC) is a type of malignant and heterogeneous tumor in premenopausal females with ineffective therapeutic targets. IL-8 is one of the earliest discovered chemotaxis cytokines which expression is closely related to the progress of various cancers. Previous studies show that IL-8 determines the prognosis of TNBC patients, nevertheless how IL-8 influence the progress of TNBC is unclear. In our studies, we discovered that overexpression of IL-8 promotes TNBC cells (TNBCs) migration and tumor growth via the PI3K-Akt and MAPK signaling pathway. Cell-cycle of TNBCs arrest at S phase by overexpression of IL-8, however, there is no significant difference on the cell viability and cell apoptosis of TNBCs. Besides, overexpression of IL-8 result in the downregulation of E-cadherin and the upregulation of Cyclin B1 in MDA-MB-231 cells. Taken together, our results suggest that IL-8 plays a crucial role in the progress of TNBC, and it could be a novel therapeutic target of TNBC.
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Affiliation(s)
- Fang Deng
- Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China; Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China
| | - Yaguang Weng
- Department of Laboratory Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong, Chongqing 400016, PR China
| | - Xian Li
- Department of Pathology, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong, Chongqing 400016, PR China
| | - Teng Wang
- Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China
| | - Mengtian Fan
- Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China
| | - Qiong Shi
- Department of Laboratory Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong, Chongqing 400016, PR China.
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16
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Agwa SHA, Kamel MM, Elghazaly H, Abd Elsamee AM, Hafez H, Girgis SA, Ezz Elarab H, Ebeid FSE, Sayed SM, Sherif L, Matboli M. Association between Interferon-Lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 Variant Polymorphisms with the Course and Outcome of SARS-CoV-2 Patients. Genes (Basel) 2021; 12:830. [PMID: 34071309 PMCID: PMC8230293 DOI: 10.3390/genes12060830] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 05/26/2021] [Accepted: 05/26/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides a critical host-immunological challenge. AIM We explore the effect of host-genetic variation in interferon-lambda-3 rs12979860, Tolloid Like-1 (TLL1) rs17047200 and Discoidin domain receptor 1(DDR1) rs4618569 on host response to respiratory viral infections and disease severity that may probe the mechanistic approach of allelic variation in virus-induced inflammatory responses. METHODS 141 COVID-19 positive patients and 100 healthy controls were tested for interferon-lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 polymorphism by TaqMan probe-based genotyping. Different genotypes were assessed regarding the COVID-19 severity and prognosis. RESULTS There were statistically significant differences between the studied cases and control group with regard to the presence of comorbidities, total leucocytic count, lymphocytic count, CRP, serum LDH, ferritin and D-dimer (p < 0.01). The CC genotype of rs12979860 cytokine, the AA genotype of TLL1 rs17047200 and the AA genotype of the rs4618569 variant of DDR1 showed a higher incidence of COVID-19 compared to the others. There were significant differences between the rs4618569 variant of DDR and the outcome of the disease, with the highest mortality in AG genotype 29 (60.4%) in comparison to 16 (33.3%) and 3 (6.2%) in the AA and GG genotypes, respectively (p = 0.007*), suggesting that the A allele is associated with a poor outcome in the disease. CONCLUSION Among people who carry C and A alleles of SNPs IFN-λ rs12979860 and TLL1 rs17047200, respectively, the AG genotype of the DDR1 rs4618569 variant is correlated with a COVID-19 poor outcome. In those patients, the use of anti-IFN-λ 3, TLL1 and DDR1 therapy may be promising for personalized translational clinical practice.
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Affiliation(s)
- Sara H. A. Agwa
- Molecular Genomics Unit, Clinical Pathology Department, Medical Ain Shams Research Institute (MASRI), School of Medicine, Ain Shams University, Cairo 11566, Egypt
| | - Marwa Mostafa Kamel
- Medicinal Biochemistry and Molecular Biology Department, School of Medicine, Ain Shams University, Cairo 11566, Egypt;
| | - Hesham Elghazaly
- Oncology Department, Medical Ain Shams Research Institute (MASRI), Ain Shams University, Cairo 11566, Egypt;
| | - Aya M. Abd Elsamee
- Molecular Genomics Unit, Medical Ain Shams Research Institute (MASRI), Ain Shams University, Cairo 11566, Egypt;
| | - Hala Hafez
- Infection Control Unit, Clinical Pathology Department, Ain Shams University Hospitals, Cairo 11566, Egypt; (H.H.); (S.A.G.); (H.E.E.)
| | - Samia Abdo Girgis
- Infection Control Unit, Clinical Pathology Department, Ain Shams University Hospitals, Cairo 11566, Egypt; (H.H.); (S.A.G.); (H.E.E.)
| | - Hoda Ezz Elarab
- Infection Control Unit, Clinical Pathology Department, Ain Shams University Hospitals, Cairo 11566, Egypt; (H.H.); (S.A.G.); (H.E.E.)
| | - Fatma S. E. Ebeid
- Pediatric Department, School of Medicine, Ain Shams University Hospitals, Cairo 11566, Egypt; (F.S.E.E.); (S.M.S.)
| | - Safa Matbouly Sayed
- Pediatric Department, School of Medicine, Ain Shams University Hospitals, Cairo 11566, Egypt; (F.S.E.E.); (S.M.S.)
| | - Lina Sherif
- Department of Clinical Pharmacy, Faculty of Pharmacy, Misr International University, Cairo 11566, Egypt;
| | - Marwa Matboli
- Medicinal Biochemistry and Molecular Biology Department, School of Medicine, Ain Shams University, Cairo 11566, Egypt;
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17
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Liu RY, Li L, Wu T, Zhang ZT. Role of Interleukin-10 Promoter Polymorphisms in Oral Cancer Susceptibility: A Meta-Analysis. Cancer Invest 2021; 39:390-400. [PMID: 33760670 DOI: 10.1080/07357907.2021.1900217] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Role of interleukin-10 (IL-10) promoter polymorphisms in the risk of oral cancer (OC) remains controversial. The present study aimed to explore the relation between IL10 promoter polymorphisms and the progression of oral cancer by performing meta-analysis. Seven studies with a total of 2141 controls and 1928 cases were included in our analysis. Overall results showed significant associations between IL-10-1082A/G gene polymorphism and OC susceptibility under all five models. However, OC was not significantly related to the IL-10-592A/C or -819 T/C polymorphism (p > 0.05).
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Affiliation(s)
- Ru-Yue Liu
- VIP Department, School of Stomatology, China Medical University, Shenyang, China
| | - Lin Li
- VIP Department, School of Stomatology, China Medical University, Shenyang, China
| | - Ting Wu
- VIP Department, School of Stomatology, China Medical University, Shenyang, China
| | - Zhong-Ti Zhang
- VIP Department, School of Stomatology, China Medical University, Shenyang, China
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18
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Moraghebi M, Maleki R, Ahmadi M, Negahi AA, Abbasi H, Mousavi P. In silico Analysis of Polymorphisms in microRNAs Deregulated in Alzheimer Disease. Front Neurosci 2021; 15:631852. [PMID: 33841080 PMCID: PMC8024493 DOI: 10.3389/fnins.2021.631852] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 02/18/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Alzheimer's disease (AD) is a degenerative condition characterized by progressive cognitive impairment and dementia. Findings have revolutionized current knowledge of miRNA in the neurological conditions. Two regulatory mechanisms determine the level of mature miRNA expression; one is miRNA precursor processing, and the other is gene expression regulation by transcription factors. This study is allocated to the in-silico investigation of miRNA's SNPs and their effect on other cell mechanisms. METHODS We used databases which annotate the functional effect of SNPs on mRNA-miRNA and miRNA-RBP interaction. Also, we investigated SNPs which are located on the promoter or UTR region. RESULTS miRNA SNP3.0 database indicated several SNPs in miR-339 and miR-34a in the upstream and downstream of pre-miRNA and mature miRNAs. While, for some miRNAs miR-124, and miR-125, no polymorphism was observed, and also miR-101 with ΔG -3.1 and mir-328 with ΔG 5.8 had the highest and lowest potencies to produce mature microRNA. SNP2TFBS web-server presented several SNPs which altered the Transcription Factor Binding Sites (TFBS) or generated novel TFBS in the promoter regions of related miRNA. At last, RBP-Var database provided a list of SNPs which alter miRNA-RBP interaction pattern and can also influence other miRNAs' expression. DISCUSSION The results indicated that SNPs microRNA affects both miRNA function and miRNA expression. Our study expands molecular insight into how SNPs in different parts of miRNA, including the regulatory (promoter), the precursor (pre-miRNA), functional regions (seed region of mature miRNA), and RBP-binding motifs, which theoretically may be correlated to the Alzheimer's disease.
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Affiliation(s)
- Mahta Moraghebi
- Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Reza Maleki
- Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohsen Ahmadi
- Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Ahmad Agha Negahi
- Department of Internal Medicine, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Hossein Abbasi
- Student Research Committee, Faculty of Para-Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Pegah Mousavi
- Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
- Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
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19
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Zhu Z, Liu JB, Liu X, Qian L. Association of interleukin 10 rs1800896 polymorphism with susceptibility to breast cancer: a meta-analysis. J Int Med Res 2021; 48:300060520904863. [PMID: 32349574 PMCID: PMC7218478 DOI: 10.1177/0300060520904863] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Objective To evaluate the correlation between interleukin 10 (IL-10) −1082A/G polymorphism (rs1800896) and breast cancers by performing a meta-analysis. Methods The Embase and Medline databases were searched through 1 September 2018 to identify qualified articles. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were applied to evaluate associations. Results In total, 14 case-control studies, including 5320 cases and 5727 controls, were analyzed. We detected significant associations between the IL10 −1082 G/G genotype and risk of breast cancer (AA + AG vs. GG: OR = 0.88, 95% CI = 0.80–0.97). Subgroup analyses confirmed a significant association in Caucasian populations (OR = 0.89, 95% CI = 0.80–0.99), in population-based case-control studies (OR = 0.87, 95% CI = 0.78–0.96), and in studies with ≥500 subjects (OR = 0.88, 95% CI = 0.79–0.99) under the recessive model (AA + AG vs. GG). No associations were found in Asian populations. Conclusions The IL10 −1082A/G polymorphism is associated with an increased risk of breast cancer. The association between IL10 −1082 G/G genotype and increased risk of breast cancer is more significant in Caucasians, in population-based studies, and in larger studies.
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Affiliation(s)
- ZiYin Zhu
- Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Ji-Bin Liu
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Xi Liu
- Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - LinXue Qian
- Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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20
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Hamad N, Alzoubi KH, Swedan SF, Khabour OF, El-Salem K. Association between tumor necrosis factor alpha and lymphotoxin alpha gene polymorphisms and migraine occurrence among Jordanians. Neurol Sci 2021; 42:3625-3630. [PMID: 33433759 DOI: 10.1007/s10072-020-04967-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 12/05/2020] [Indexed: 12/31/2022]
Abstract
Inflammatory reactions in the body have been shown to contribute to migraine development. Therefore, genes involved in the inflammatory pathways might play a role in the susceptibility and development of migraine. In this study, polymorphisms in tumor necrosis factor alpha (TNFα) and lymphotoxin alpha (LTA) genes were tested for association with migraine. A total of 398 participants (198 migraine patients and 200 controls) were recruited in the study. Serum TNF level was measured using a sandwich ELISA kit. Lymphocytes' and monocytes' counts were obtained from a differential complete blood count profile. Participants' DNA was extracted and genotyped for rs1800629 and rs1799724 in TNFα, and rs909253 in LTA. Controls had a significantly higher mean lymphocyte count (P = 0.018), while the mean monocyte count and serum TNFα levels did not differ between the two groups (P > 0.05). With respect to gene polymorphisms, the rs1800629 and rs1799724 variants showed significant association with migraine in all subjects, and in males and females when analyzed separately (P < 0.001). The rs909253 did not show any statistical difference in frequencies among the two groups (P > 0.05). Having the A allele in rs1800629 was associated with a higher risk of migraine in both male (OR, 95%; CI, G/A = 3.79 [1.87-7.69]; A/A = 14.22 [1.67-121.14]; P < 0.01) and female (OR, 95%; G/A = 2.54 [1.47-4.38]; A/A = 2.52 [1.12-5.69]; P < 0.001) subjects. In conclusion, rs1800629 and rs1799724 in TNFα showed significant association with migraine among the Jordanian population.
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Affiliation(s)
- Nour Hamad
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, 22110, Jordan
| | - Karem H Alzoubi
- Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, 22110, Jordan.
| | - Samer F Swedan
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, 22110, Jordan
| | - Omar F Khabour
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, 22110, Jordan
| | - Khalid El-Salem
- Department of Neurosciences, Jordan University of Science and Technology, Irbid, 22110, Jordan
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21
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Zhang Y, Chen L, Chen H. Associations between polymorphisms in IL- 10 gene and the risk of viral hepatitis: a meta-analysis. Gut Pathog 2020; 12:36. [PMID: 32742307 PMCID: PMC7385948 DOI: 10.1186/s13099-020-00372-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 06/23/2020] [Indexed: 01/11/2023] Open
Abstract
Background The relationships between polymorphisms in interleukin-10 (IL-10) gene and the risk of viral hepatitis remain inconclusive. Therefore, the authors conducted so far the very first meta-analysis to robustly assess the relationships between polymorphisms in IL-10 gene and the risk of viral hepatitis by integrating the results of previous works. Methods Medline, Embase, Wanfang, VIP and CNKI were searched throughly for eligible studies, and 76 genetic association studies were finally included in this meta-analysis. Results We noticed that rs1800871 (− 819 C/T), rs1800872 (− 592 C/A) and rs1800896 (− 1082 G/A) polymorphisms were all significantly associated with the risk of viral hepatitis in Asians, whereas only rs1800896 (− 1082 G/A) polymorphism was significantly associated with the risk of viral hepatitis in Caucasians. In further analyses by disease subtypes, we noticed that the three investigated polymorphisms were all significantly associated with the risk of both HBV and HCV. Conclusions This meta-analysis demonstrates that rs1800871 (− 819 C/T), rs1800872 (− 592 C/A) and rs1800896 (− 1082 G/A) polymorphisms may influence the risk of viral hepatitis in Asians, while only rs1800896 (− 1082 G/A) polymorphism may influence the risk of viral hepatitis in Caucasians. In further analyses by disease subtypes, we noticed that the three investigated polymorphisms may influence the risk of both HBV and HCV.
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Affiliation(s)
- Yuanyuan Zhang
- Department of Digestive Diseases, Huizhou Municipal Center Hospital, No. 41 of North Yuling Road, Huizhou, 516001 China
| | - Lisha Chen
- Department of Digestive Diseases, Huizhou Municipal Center Hospital, No. 41 of North Yuling Road, Huizhou, 516001 China
| | - Huixin Chen
- Department of Digestive Diseases, Huizhou Municipal Center Hospital, No. 41 of North Yuling Road, Huizhou, 516001 China
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Yu Z, Wit W, Xiong L, Cheng Y. Associations of six common functional polymorphisms in interleukins with tuberculosis: evidence from a meta-analysis. Pathog Dis 2020; 77:5575187. [PMID: 31560754 DOI: 10.1093/femspd/ftz053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 09/26/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Associations of polymorphisms in interleukin-6 (IL-6), IL-8 and IL-10 with tuberculosis (TB) susceptibility were already reported by many publications. The aim of this meta-analysis was to more precisely clarify associations between polymorphisms in IL-6/IL-8/IL-10 and TB by combing the results of all relevant publications. METHODS Eligible publications were searched from PubMed, Embase, Web of Science and CNKI. We used Review Manager to combine the results of individual studies. RESULTS A total of 47 publications were included in this study. IL-6 rs1800795 (1750 cases and 2335 controls, dominant, recessive and allele comparisons), IL-8 rs4073 (1125 cases and 1188 controls, dominant, recessive and allele comparisons), IL-10 rs1800871 (5528 cases and 7671 controls, dominant, recessive and allele comparisons), IL-10 rs1800872 (5269 cases and 7013 controls, dominant and allele comparisons) and IL-10 rs1800896 (7564 cases and 8952 controls, recessive comparison) polymorphisms were all significantly associated with TB in overall combined analyses. In subgroup analyses, we found that the positive results were mainly driven by the pulmonary tuberculosis and Asian subgroups. CONCLUSIONS Collectively, this meta-analysis proved that IL-6 rs1800795, IL-8 rs4073, IL-10 rs1800871, IL-10 rs1800872 and IL-10 rs1800896 may confer susceptibility to TB.
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Affiliation(s)
- Zhen Yu
- School of Public Health, Kunming Medical University, 1168# West Chunrong Road, Chenggong New City, Kunming 650500, China
| | - Wichaidit Wit
- School of Medicine, Prince of Songkla University, Hat Yai 90110, Thailand
| | - Lifen Xiong
- Department of Tuberculosis, Center of Disease Control, 1# North Galan Road, Xishuangbanna, Yunnan 666100, China
| | - Ying Cheng
- School of Public Health, Kunming Medical University, 1168# West Chunrong Road, Chenggong New City, Kunming 650500, China
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Moghimi M, Dastgheib SA, Heiranizadeh N, Zare M, Sheikhpour E, Neamatzadeh H. ASSOCIATION OF IL-8 -251T>A (RS4073) POLYMORPHISM WITH SUSCEPTIBILITY TO GASTRIC CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS BASED ON 33 CASE-CONTROL STUDIES. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:91-99. [PMID: 32294742 DOI: 10.1590/s0004-2803.202000000-16] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 11/04/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND The role of -251A>T polymorphism in the anti-inflammatory cytokine interleukin-8 (IL-8) gene in gastric cancer was intensively evaluated, but the results of these studies were inconsistent. OBJECTIVE Therefore, we performed a meta-analysis to provide a comprehensive data on the association of IL-8 -251T>A polymorphism with gastric cancer. METHODS All eligible studies were identified in PubMed, Web of Science, EMBASE, Wanfang and CNKI databases before September 01, 2019. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were derived from a fixed effect or random effect model. RESULTS A total of 33 case-control studies with 6,192 cases and 9,567 controls were selected. Overall, pooled data showed that IL-8 -251T>A polymorphism was significantly associated with an increased risk of gastric cancer under all five genetic models, i.e., allele (A vs T: OR=1.189, 95% CI 1.027-1.378, P=0.021), homozygote (AA vs TT: OR=1.307, 95% CI 1.111-1.536, P=0.001), heterozygote (AT vs TT: OR=1.188, 95% CI 1.061-1.330, P=0.003), dominant (AA+AT vs TT: OR=1.337, 95% CI 1.115-1.602, P=0.002) and recessive (AA vs AT+TT: OR=1.241, 95% CI 1.045-1.474, P=0.014). The stratified analysis by ethnicity revealed an increased risk of gastric cancer in Asians and mixed populations, but not in Caucasians. Moreover, stratified by country found a significant association in Chinese, Korean and Brazilian, but not among Japanese. CONCLUSION This meta-analysis suggests that the IL-8 -251T>A polymorphism is associated with an increased risk of gastric cancer, especially by ethnicity (Asian and mixed populations) and country (Chinese, Korean and Brazilian).
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Affiliation(s)
- Mansour Moghimi
- Shahid Sadoughi University of Medical Sciences, Department of Pathology, Yazd, Iran
| | | | - Naeimeh Heiranizadeh
- Shahid Sadoughi University of Medical Sciences, Department of Surgery, Yazd, Iran
| | - Mohammad Zare
- Shahid Sadoughi University of Medical Sciences, Department of Surgery, Yazd, Iran
| | - Elnaz Sheikhpour
- Shahid Sadoughi University of Medical Science, Hematology and Oncology Research Center, Yazd, Iran
| | - Hossein Neamatzadeh
- Shahid Sadoughi University of Medical Sciences, Department of Medical Genetics, Yazd, Iran.,Shahid Sadoughi University of Medical Sciences, Mother and Newborn Health Research Center, Yazd, Iran
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Xu G, Wang F. Associations of polymorphisms in interleukins with susceptibility to breast cancer: Evidence from a meta-analysis. Cytokine 2020; 130:154988. [PMID: 32163880 DOI: 10.1016/j.cyto.2020.154988] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 12/11/2019] [Accepted: 01/06/2020] [Indexed: 01/10/2023]
Abstract
BACKGROUND Associations between polymorphisms in interleukins and breast cancer (BC) were already investigated by many studies, yet with controversial findings. The aim of this meta-analysis was to better clarify associations between polymorphisms in interleukins and BC by combing the results of all relevant articles. METHODS Eligible articles were searched from Pubmed, Embase, Web of Science and CNKI. We used Review Manager to combine the results of eligible studies. RESULTS Fifty-seven studies were included in this meta-analysis. We found that IL-6 rs1800796 (dominant comparison: OR = 0.70, 95% CI 0.53-0.92), IL-8 rs4073 (dominant comparison: OR = 0.74, 95% CI 0.61-0.89; over-dominant comparison: OR = 1.16, 95% CI 1.05-1.29; allele comparison: OR = 0.82, 95% CI 0.69-0.89), IL-10 rs1800896 (recessive comparison: OR = 1.28, 95% CI 1.12-1.47) and IL-18 rs1946518 (dominant comparison: OR = 0.80, 95% CI 0.65-0.97; allele comparison: OR = 0.74, 95% CI 0.59-0.93) polymorphisms were all significantly associated with BC in overall combined analyses. In subgroup analyses, we noticed that IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800896, IL-18 rs1946518 and rs187238 polymorphisms were all significantly associated with susceptibility to BC in East Asians from China. CONCLUSIONS Collectively, this meta-analysis demonstrated that IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800896, IL-18 rs1946518 and rs187238 polymorphisms may confer susceptibility to BC for East Asians from China.
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Affiliation(s)
- Guanghua Xu
- Department of Surgery 1, Anji County Third People's Hospital, Huzhou 313300, Zhejiang, China
| | - Fengyong Wang
- Department of General Surgery, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, China.
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Deng F, Weng Y, Li X, Wang T, Fan M, Shi Q. Overexpression of IL-8 promotes cell migration via PI3K-Akt signaling pathway and EMT in triple-negative breast cancer. Pathol Res Pract 2020; 216:152902. [PMID: 32147274 DOI: 10.1016/j.prp.2020.152902] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 01/28/2020] [Accepted: 02/26/2020] [Indexed: 12/17/2022]
Abstract
Triple-negative breast cancer (TNBC) is a type of malignant and heterogeneous tumor in premenopausal females with ineffective therapeutic targets. IL-8 is one of the earliest discovered chemotaxis cytokines which expression is closely related to the progress of various cancers. Previous studies showed that IL-8 determines the prognosis of TNBC patients, nevertheless how IL-8 influences the progress of TNBC is unclear. In our studies, we discovered that overexpression of IL-8 promotes TNBC cells (TNBCs) migration and tumor growth via the PI3K-Akt and MAPK signaling pathway. Cell-cycle of TNBCs arrest at S phase by overexpression of IL-8, however, there is no significant variation on the cell viability and cell apoptosis of TNBCs. Besides, overexpression of IL-8 result in the downregulation of E-cadherin and the upregulation of Cyclin B1 in MDA-MB-231 cells. Taken together, our results suggest that IL-8 performs a crucial role in the progress of TNBC, and it could be a novel therapeutic target of TNBC.
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Affiliation(s)
- Fang Deng
- Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, PR China; Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China
| | - Yaguang Weng
- Department of Laboratory Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong, Chongqing, 400016, PR China
| | - Xian Li
- Department of Pathology, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong, Chongqing, 400016, PR China
| | - Teng Wang
- Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, PR China
| | - Mengtian Fan
- Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, PR China
| | - Qiong Shi
- Department of Laboratory Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong, Chongqing, 400016, PR China.
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Gao J, Ying Y, Wang J, Cui Y, Zhang W. Certain interleukin polymorphisms might influence predisposition to lung cancer: A meta-analysis of 35 published studies. IUBMB Life 2020; 72:957-964. [PMID: 32077194 DOI: 10.1002/iub.2228] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Accepted: 12/28/2019] [Indexed: 11/11/2022]
Abstract
Interleukin polymorphisms might influence predisposition to lung cancer (LC), but the results of already published studies regarding the relationship between interleukin polymorphisms and LC were still controversial and ambiguous. So the authors designed this meta-analysis to more precisely estimate relationship between interleukin polymorphisms and LC by pooling the results of already published related studies. The authors searched Pubmed, Embase, Web of Science, and CNKI for already published studies. Thirty-five already published studies were pooled and analyzed in this meta-analysis. The pooled meta-analyses results showed that distributions of IL-4 rs2243250 polymorphism among patients and controls from Asian countries differed significantly (dominant comparison: OR = 1.29, 95% CI 1.07-1.55; overdominant comparison: OR = 0.83, 95% CI 0.73-0.95; allele comparison: OR = 1.26, 95% CI 1.03-1.54), and distributions of IL-10 rs1800872 polymorphism among patients and controls from Caucasian countries also differed significantly (recessive comparison: OR = 0.54, 95% CI 0.35-0.83; overdominant comparison: OR = 1.26, 95% CI 1.05.1.51). No genotypic distribution differences were observed for IL-4 rs2070874, IL-6 rs1800795, IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800871, and IL-10 rs1800896 polymorphisms in pooled meta-analyses. This meta-analysis suggested that IL-4 rs2243250 might influence predisposition to LC in Asians, whereas IL-10 rs1800872 polymorphism might influence predisposition to LC in Caucasians.
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Affiliation(s)
- Juwei Gao
- Department of Oncology, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yinyin Ying
- Department of Oncology, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Jue Wang
- Department of Oncology, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yiyi Cui
- Department of Oncology, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Weiping Zhang
- Department of Oncology, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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Hong P, Feng WY, Fu LH, Jin J, Fu JP. Associations between genetic polymorphisms in interleukin-10 and hematological oncology: evidence from a meta-analysis. Cancer Biol Ther 2020; 21:372-378. [PMID: 31910710 DOI: 10.1080/15384047.2019.1702404] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Background: Associations between polymorphisms in interleukin-10 (IL-10) and hematological oncology were already explored by many genetic association studies, with controversial findings. The aim of this meta-analysis was to more comprehensively analyze associations between polymorphisms in IL-10 and hematological oncology by combing the results of all relevant studies.Methods: Eligible articles were searched from Pubmed, Embase, WOS and CNKI. The latest literature searching update was performed on 8 October 2019. We used Review Manager to combine the results of eligible studies.Results: Forty-one articles were included in this meta-analysis. IL-10 rs1800890 polymorphism was found to be significantly associated with hematological oncology under AA vs. TT+TA (recessive comparison, OR = 1.12, 95% CI 1.02-1.24), and rs1800896 polymorphism was also found to be significantly associated with hematological oncology under AA vs. AG+GG (dominant comparison, OR = 0.89, 95% CI 0.83-0.95) in overall combined analyses. In subgroup analyses, we observed positive results for rs1800871 (recessive comparison), rs1800872 (dominant, recessive and allele comparisons), and rs1800896 (dominant and allele comparisons) polymorphisms in the non-Hodgkin's lymphoma (NHL) subgroup. Besides, we also detected positive associations between rs1800872 polymorphism and acute leukemia (AL) (dominant and recessive comparisons) and found significant associations between rs1800896 polymorphism and chronic leukemia (CL) (recessive comparison).Conclusion: In summary, this meta-analysis demonstrated that IL-10 rs1800890, rs1800896, rs1800871 and rs1800872 polymorphisms may confer susceptibility to hematology oncology, especially for NHL.
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Affiliation(s)
- Pan Hong
- Department of Hematology, Shaoxing People's Hospital, Shaoxing, China
| | - Wei-Ying Feng
- Department of Hematology, Shaoxing People's Hospital, Shaoxing, China
| | - Lei-Hua Fu
- Department of Hematology, Shaoxing People's Hospital, Shaoxing, China
| | - Jing Jin
- Department of Hematology, Shaoxing People's Hospital, Shaoxing, China
| | - Jia-Ping Fu
- Department of Hematology, Shaoxing People's Hospital, Shaoxing, China
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Chen J, Ma A. Associations of polymorphisms in interleukins with tuberculosis: Evidence from a meta-analysis. Immunol Lett 2020; 217:1-6. [DOI: 10.1016/j.imlet.2019.10.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Revised: 09/23/2019] [Accepted: 10/21/2019] [Indexed: 01/11/2023]
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Lv K, Yang Y. Relationship between interleukin-10 polymorphisms and susceptibility to ischemic stroke: a Meta-analysis. Scandinavian Journal of Clinical and Laboratory Investigation 2019; 80:20-24. [PMID: 31722572 DOI: 10.1080/00365513.2019.1689427] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- Kongdan Lv
- Department of Geriatrics, Zhuji People’ Hospital, Zhuji, China
| | - Yue Yang
- Department of Neurology, Zhuji People’ Hospital, Zhuji, China
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Salvador-Martín S, López-Cauce B, Nuñez O, Laserna-Mendieta EJ, García MI, Lobato E, Abarca-Zabalía J, Sanjurjo-Saez M, Lucendo AJ, Marín-Jiménez I, Menchén LA, López-Fernández LA. Genetic predictors of long-term response and trough levels of infliximab in crohn's disease. Pharmacol Res 2019; 149:104478. [PMID: 31605784 DOI: 10.1016/j.phrs.2019.104478] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 09/16/2019] [Accepted: 10/03/2019] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Several factors, such as trough serum anti-TNF levels, have been associated with response to therapy in Crohn's disease. However, this association is observed after initiation of treatment. Identifying DNA variants may prove useful for predicting long-term response or failure to these drugs before initiation of treatment. OBJECTIVE To identify genetic variants associated with long-term response to infliximab and trough levels in Crohn's disease. PATIENTS AND METHODS An observational, longitudinal study was conducted. We analyzed blood samples from 132 infliximab-treated patients diagnosed with Crohn's disease from 2 hospitals. We genotyped 21 polymorphisms previously related to anti-TNF response in genes involved in the NFkB-mediated inflammatory response, TNFα-signaling and cytokines regulated by NFkB, using real-time PCR. Trough infliximab levels were measured using ELISA. The association between SNPs and time-to-failure (defined as the time from the initiation of induction therapy to the date of treatment withdrawal due to a primary or secondary failure) was analyzed using log-rank test. The association between SNPs and supra-(>7 μg/mL) or infratherapeutic (<3 μg/mL) infliximab trough levels was analyzed using a linear-by-linear association chi-squared test. RESULTS Two SNPs in TLR2, rs1816702 and rs3804099, and 1 SNP in TNFRSF1B, rs1061624, were associated with long-term response (up to ten years follow-up) to infliximab (HR, 0.13 [95%CI, 0.02-1.00], p < 0.05; HR, 0.39 [95%CI, 0.18-0.88], p < 0.05; and HR, 0.04 [95%CI, 0.18-0.92] p > 0.05, respectively). In addition, IL6 rs10499563 C and IL10 rs1800872 A were associated with supratherapeutic trough infliximab levels; IL10 rs3024505 T was associated with infratherapeutic levels (p < 0.05). CONCLUSION Genotyping of the variants identified in the genes encoding TLR2, TNFRSF1B, IL6 and IL10 reported herein represent a promising tool for the identification and selection of those patients who will benefit most from infliximab.
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Affiliation(s)
- Sara Salvador-Martín
- Department of Pharmacy, Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - Beatriz López-Cauce
- Department of Gastroenterology, Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - Olga Nuñez
- Department of Gastroenterology, Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | | | - María I García
- Department of Pharmacy, Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - Elena Lobato
- Department of Pharmacy, Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - Judith Abarca-Zabalía
- Department of Pharmacy, Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - María Sanjurjo-Saez
- Department of Pharmacy, Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - Alfredo J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain; Biomedical Research Network Center for liver and Digestive Diseases (CIBEREHD), Madrid, Spain
| | - Ignacio Marín-Jiménez
- Department of Gastroenterology, Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Biomedical Research Network Center for liver and Digestive Diseases (CIBEREHD), Madrid, Spain
| | - Luis A Menchén
- Department of Gastroenterology, Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Biomedical Research Network Center for liver and Digestive Diseases (CIBEREHD), Madrid, Spain
| | - Luis A López-Fernández
- Department of Pharmacy, Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Spanish Clinical Research Network (SCReN), Spain.
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Chen M, Yang Y. A meta-analysis on associations of IL-6 and IL-10 polymorphisms with susceptibility to ischemic stroke. J Neuroimmunol 2019; 335:577004. [PMID: 31446341 DOI: 10.1016/j.jneuroim.2019.577004] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 06/27/2019] [Accepted: 07/06/2019] [Indexed: 01/11/2023]
Abstract
BACKGROUND Some previous studies already explored associations of interleukin-6 (IL-6) and interleukin-10 (IL-10) polymorphisms with ischemic stroke (IS). However, the results were conflicting. In this meta-analysis, we aimed to better analyze the relationship between IL-6/IL-10 polymorphisms and IS in a larger pooled population. METHODS We performed a systematic search of PubMed, Web of Science, Embase and CNKI. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) to estimate associations between IL-6/IL-10 polymorphisms and IS. RESULTS Totally 37 studies were included for analyses. A significant association with IS was observed for IL-10 rs1800896 polymorphism in AA versus GG + GA (recessive model, p = .001, OR = 1.42, 95%CI 1.15-1.75) in overall population. Further subgroup analyses showed that IL-6 rs1800795 was significantly associated with IS in Asians in GG versus GC + CC (dominant model, p = .0005, OR = 0.74, 95%CI 0.62-0.88), CC versus GG + GC (recessive model, p = .003, OR = 1.61, 95%CI 1.17-2.21) and G versus C (allele model, p = .01, OR = 0.74, 95%CI 0.58-0.93), whereas IL-10 rs1800896 polymorphism was significantly associated with cerebral infarction (CI) in GG versus GA + AA (dominant model, p = .02, OR = 2.04, 95%CI 1.14-3.64), GA versus GG + AA (overdominant model, p = .03, OR = 0.50, 95%CI 0.27-0.93) and G versus A (allele model, p = .01, OR = 1.92, 95%CI 1.16-3.17). CONCLUSIONS Our findings indicated that IL-6 rs1800795 polymorphism was significantly associated with individual susceptibility to IS in Asians, but not in Caucasians. In addition, IL-10 rs1800896 polymorphism was also significantly associated with individual susceptibility to IS, especially for CI.
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Affiliation(s)
- Miao Chen
- Department of Neurology, Zhuji People's Hospital of Zhejiang Province, Zhuji 311800, China
| | - Yue Yang
- Department of Neurology, Zhuji People's Hospital of Zhejiang Province, Zhuji 311800, China.
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Rossi AFT, Contiero JC, Manoel-Caetano FDS, Severino FE, Silva AE. Up-regulation of tumor necrosis factor-α pathway survival genes and of the receptor TNFR2 in gastric cancer. World J Gastrointest Oncol 2019; 11:281-294. [PMID: 31040894 PMCID: PMC6475670 DOI: 10.4251/wjgo.v11.i4.281] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 02/16/2019] [Accepted: 02/28/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Gastric carcinogenesis can be induced by chronic inflammation triggered by Helicobacter pylori (H. pylori) infection. Tumor necrosis factor (TNF)-α and its receptors (TNFR1 and TNFR2) regulate important cellular processes, such as apoptosis and cell survival, and the disruption of which can lead to cancer. This signaling pathway is also modulated by microRNAs (miRNAs), altering gene expression.
AIM To evaluate the mRNA and miRNAs expression involved in the TNF-α signaling pathway in gastric cancer (GC) tissues and its relationship.
METHODS Quantitative polymerase chain reaction (qPCR) by TaqMan® assay was used to quantify the RNA transcript levels of TNF-α signaling pathway (TNF, TNFR1, TNFR2, TRADD, TRAF2, CFLIP, NFKB1, NFKB2, CASP8, CASP3) and miRNAs that targets genes from this pathway (miR-19a, miR-34a, miR-103a, miR-130a, miR-181c) in 30 GC fresh tissue samples. Molecular diagnosis of H. pylori was performed by nested PCR for gene HSP60. A miRNA:mRNA interaction network was construct using Cytoscape v3.1.1 from the in silico analysis performed using public databases.
RESULTS Up-regulation of cellular survival genes as TNF, TNFR2, TRADD, TRAF2, CFLIP, and NFKB2, besides CASP8 and miR-34a was observed in GC tissues, whereas mediators of apoptosis such as TNFR1 and CASP3 were down-regulated. When the samples were stratified by histological type, the expression of miR-103a and miR-130a was significantly increased in the diffuse-type of GC compared to the intestinal-type. However, no influence of H. pylori infection was observed on the expression levels of mRNA and miRNAs analyzed. Moreover, the miRNA:mRNA interaction network showed several interrelations between the miRNAs and their target genes, highlighting miR-19a and miR-103a, which has as predicted or validated target a large number of genes in the TNF-α pathway, including TNF, TNFR1, TNFR2, CFLIP, TRADD, CASP3 and CASP8.
CONCLUSION Our findings show that cell survival genes mediated by TNF/TNFR2 binding is up-regulated in GC favoring its pro-tumoral effect, while pro-apoptotic genes as CASP3 and TNFR1 are down-regulated, indicating disbalance between apoptosis and cell proliferation processes in this neoplasm. This process can also be influenced by an intricate regulatory network of miRNA:mRNA.
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Affiliation(s)
- Ana Flávia Teixeira Rossi
- Department of Biology, São Paulo State University – UNESP, São José do Rio Preto, SP 15054-000, Brazil
| | - Júlia Cocenzo Contiero
- Department of Biology, São Paulo State University – UNESP, São José do Rio Preto, SP 15054-000, Brazil
| | | | - Fábio Eduardo Severino
- Department of Surgery and Orthopedics, Faculty of Medicine, São Paulo State University – UNESP, Botucatu, SP 18618-687, Brazil
| | - Ana Elizabete Silva
- Department of Biology, São Paulo State University – UNESP, São José do Rio Preto, SP 15054-000, Brazil
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Manoel-Caetano FS, Rossi AFT, Calvet de Morais G, Severino FE, Silva AE. Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer. Genes Dis 2019; 6:176-184. [PMID: 31194025 PMCID: PMC6545450 DOI: 10.1016/j.gendis.2019.03.007] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Accepted: 03/28/2019] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer remains one of the leading causes of cancer-related death worldwide, and most of the cases are associated with Helicobacter pylori infection. This bacterium promotes the production of reactive oxygen species (ROS), which cause DNA damage in gastric epithelial cells. In this study, we evaluated the expression of important genes involved in the recognition of DNA damage (ATM, ATR, and H2AX) and ROS-induced damage repair (APE1) and the expression of some miRNAs (miR-15a, miR-21, miR-24, miR-421 and miR-605) that target genes involved in the DNA damage response (DDR) in 31 fresh tissues of gastric cancer. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network. Analysis performed by real-time quantitative PCR exhibited significantly increased levels of the APE1 (RQ = 2.55, p < 0.0001) and H2AX (RQ = 2.88, p = 0.0002) genes beyond the miR-421 and miR-605 in the gastric cancer samples. In addition, significantly elevated levels of miR-21, miR-24 and miR-421 were observed in diffuse-type gastric cancer. Correlation analysis reinforced some of the gene:gene (ATM/ATR/H2AX) and miRNA:mRNA relationships obtained also with the interaction network. Thus, our findings show that tumor cells from gastric cancer presents deregulation of genes and miRNAs that participate in the recognition and repair of DNA damage, which could confer an advantage to cell survival and proliferation in the tumor microenvironment.
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Affiliation(s)
- Fernanda S Manoel-Caetano
- Department of Biology, UNESP, São Paulo State University, Campus of São José do Rio Preto, Rua Cristóvão Colombo, 2265, 15.054-000, São José do Rio Preto, São Paulo, Brazil
| | - Ana Flávia T Rossi
- Department of Biology, UNESP, São Paulo State University, Campus of São José do Rio Preto, Rua Cristóvão Colombo, 2265, 15.054-000, São José do Rio Preto, São Paulo, Brazil
| | - Gabriela Calvet de Morais
- Department of Biology, UNESP, São Paulo State University, Campus of São José do Rio Preto, Rua Cristóvão Colombo, 2265, 15.054-000, São José do Rio Preto, São Paulo, Brazil
| | - Fábio Eduardo Severino
- Department of Surgery and Orthopedics, Faculty of Medicine, UNESP, São Paulo State University, Campus of Botucatu, Av. Prof. Mário Rubens Guimarães Montenegro, s/n, 18.618-687, Botucatu, São Paulo, Brazil
| | - Ana Elizabete Silva
- Department of Biology, UNESP, São Paulo State University, Campus of São José do Rio Preto, Rua Cristóvão Colombo, 2265, 15.054-000, São José do Rio Preto, São Paulo, Brazil
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Tabatabaei-Panah PS, Moravvej H, Sadaf Z, Babaei H, Geranmayeh M, Hajmanouchehri S, Karimi A, Sajjadi F, Arghand F, Ludwig RJ, Witte M, Akbarzadeh R. Proinflammatory Cytokine Gene Polymorphisms in Bullous Pemphigoid. Front Immunol 2019; 10:636. [PMID: 31001258 PMCID: PMC6455081 DOI: 10.3389/fimmu.2019.00636] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Accepted: 03/08/2019] [Indexed: 12/13/2022] Open
Abstract
Bullous pemphigoid (BP) is a rare autoimmune skin blistering disease, characterized by the presence of autoantibodies against hemidesmosomal autoantigens. Cytokine expression is altered in BP patients, and several of these differently expressed cytokines, including IL-1α, IL-1β, IL-8, and TNF-α, contribute to disease pathogenesis. Since genetic polymorphisms in the genes of these cytokines might be implicated in susceptibility to BP disease, we aimed at testing this implication in susceptibility to BP in an Iranian cohort. Blood samples were collected from the subjects and genomic DNA was extracted. To detect the single nucleotide polymorphisms (SNPs), IL-1α (rs1800587), IL-1β (rs1143627, rs16944, rs1143634), IL-8 (rs4073), and TNF-α (rs1799964, rs1800630, rs1799724, and rs361525) genes were genotyped in BP patients and healthy controls as well as IL-8 (rs4073) in pemphigus vulgaris (PV) patients. Quantitative gene expression was evaluated by RT-PCR analysis. A significant difference was observed in the distribution of genotypes or alleles of IL-8 SNP between the BP patients and controls. The A-allele of IL-8 SNP is significantly more prevalent in the control individuals compared to the BP patient. To further validate this observation, we included PV patients as an additional control. Again, the A-allele of IL-8 SNP is significantly more prevalent in the PV compared to the BP patients. While we observed a trend toward significant differences regarding alleles of TNF-α rs1799724 as well as alleles of TNF-α rs1799964, this difference was, however, not evident after correction for multiple analysis. There was no significant difference in all other studied SNPs. In contrast to IL-1α, IL-1β, and TNF-α, IL-8 gene expression levels were significantly higher in the patients than that of controls. The minor allele in IL-8 SNP might play a protective role in susceptibility to BP in Iranian patients. Although higher expression levels of IL-8 gene was found in the patients compared with healthy controls, these levels, however, suggest no association with the examined polymorphism. Moreover, further investigation revealed an elevation in gene expression between wild and polymorphic genotypes of IL-1α rs1800587 and TNF-α rs361525 in the patient group and these SNPs are therefore associated with altering the levels of gene expression.
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Affiliation(s)
| | - Hamideh Moravvej
- Skin Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Sadaf
- Biology Department, East Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Hadis Babaei
- Biology Department, East Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Maryam Geranmayeh
- Biology Department, East Tehran Branch, Islamic Azad University, Tehran, Iran
| | | | - Ahmad Karimi
- Biology Department, East Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Fatemeh Sajjadi
- Biology Department, East Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Fereshteh Arghand
- Biology Department, East Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Ralf J Ludwig
- Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
| | - Mareike Witte
- Department of Dermatology, University of Lübeck, Lübeck, Germany
| | - Reza Akbarzadeh
- Skin Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.,Institute of Anatomy, University of Lübeck, Lübeck, Germany
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Yusupova LF, Nurgalieva AK, Gilyazova IR, Prokofyeva DS, Munasypov FR, Khusnutdinov SM, Rakhimov RR, Abdeev RR, Sakaeva DD, Khusnutdinova EK. The Role of Allelic Variants of Several Genes of Cytokines in the Development of Gastric Cancer. RUSS J GENET+ 2019. [DOI: 10.1134/s1022795419030165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Noto JM, Rose KL, Hachey AJ, Delgado AG, Romero-Gallo J, Wroblewski LE, Schneider BG, Shah SC, Cover TL, Wilson KT, Israel DA, Roa JC, Schey KL, Zavros Y, Piazuelo MB, Peek RM. Carcinogenic Helicobacter pylori Strains Selectively Dysregulate the In Vivo Gastric Proteome, Which May Be Associated with Stomach Cancer Progression. Mol Cell Proteomics 2019; 18:352-371. [PMID: 30455363 PMCID: PMC6356085 DOI: 10.1074/mcp.ra118.001181] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori is the strongest risk factor for gastric cancer. Initial interactions between H. pylori and its host originate at the microbial-gastric epithelial cell interface, and contact between H. pylori and gastric epithelium activates signaling pathways that drive oncogenesis. One microbial constituent that increases gastric cancer risk is the cag pathogenicity island, which encodes a type IV secretion system that translocates the effector protein, CagA, into host cells. We previously demonstrated that infection of Mongolian gerbils with a carcinogenic cag+H. pylori strain, 7.13, recapitulates many features of H. pylori-induced gastric cancer in humans. Therefore, we sought to define gastric proteomic changes induced by H. pylori that are critical for initiation of the gastric carcinogenic cascade. Gastric cell scrapings were harvested from H. pylori-infected and uninfected gerbils for quantitative proteomic analyses using isobaric tags for relative and absolute quantitation (iTRAQ). Quantitative proteomic analysis of samples from two biological replicate experiments quantified a total of 2764 proteins, 166 of which were significantly altered in abundance by H. pylori infection. Pathway mapping identified significantly altered inflammatory and cancer-signaling pathways that included Rab/Ras signaling proteins. Consistent with the iTRAQ results, RABEP2 and G3BP2 were significantly up-regulated in vitro, ex vivo in primary human gastric monolayers, and in vivo in gerbil gastric epithelium following infection with H. pylori strain 7.13 in a cag-dependent manner. Within human stomachs, RABEP2 and G3BP2 expression in gastric epithelium increased in parallel with the severity of premalignant and malignant lesions and was significantly elevated in intestinal metaplasia and dysplasia, as well as gastric adenocarcinoma, compared with gastritis alone. These results indicate that carcinogenic strains of H. pylori induce dramatic and specific changes within the gastric proteome in vivo and that a subset of altered proteins within pathways with oncogenic potential may facilitate the progression of gastric carcinogenesis in humans.
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Affiliation(s)
- Jennifer M Noto
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Kristie L Rose
- Department of Biochemistry, Mass Spectrometry Research Center, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Amanda J Hachey
- Department of Biochemistry, Mass Spectrometry Research Center, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Alberto G Delgado
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Judith Romero-Gallo
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Lydia E Wroblewski
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Barbara G Schneider
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Shailja C Shah
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Timothy L Cover
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee;; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Keith T Wilson
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee;; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Dawn A Israel
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Juan Carlos Roa
- Department of Pathology, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Kevin L Schey
- Department of Biochemistry, Mass Spectrometry Research Center, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Yana Zavros
- Department of Pharmacology and System Physiology, University of Cincinnati, Cincinnati, Ohio
| | - M Blanca Piazuelo
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Richard M Peek
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee;.
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Moghmi M, Arjmandi A, Aghili K, Jafari M, Zare-Shehneh M, Rastegar S, Abolbaghaei SM, Neamatzadeh H. ASSOCIATION OF INTERLEUKIN-10 -592A>C AND -819T>C POLYMORPHISMS WITH GASTRIC CANCER RISK: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 44 CASE-CONTROL STUDIES. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2019; 32:e1415. [PMID: 30624524 PMCID: PMC6323628 DOI: 10.1590/0102-672020180001e1415] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Accepted: 10/11/2018] [Indexed: 12/14/2022]
Abstract
INTRODUCTION A series of studies have evaluated the association between -592A>C and -819T>C polymorphisms in the promoter regions of Interleukin-10 (IL-10) and gastric cancer (GC) risk. However, the results remain inconclusive. OBJECTIVE To better understand the association of the polymorphisms with GC risk, we performed a comprehensive meta-analysis. METHOD An electronic search was performed of several databases to identify relevant studies up to April 2018. RESULTS A total of 44 case-control studies, including 26 studies on IL-10 -592A>C (5,332 cases and 8,272 controls) and 18 studies on IL-10 -819T>C (3,431 cases and 6,109 controls) were selected. Overall, -592A>C polymorphism was associated with the risk of GC under the heterozygote model (OR=1.153, 95% CI=1.020-1.305, p=0.023), but not -819T>C polymorphism. When stratified by ethnicity, significant association was only observed in the Asians under the allele model (OR=1.153, 95% CI=1.007-1.320, p=0.040) and the heterozygote model (OR=1.218, 95% CI=1.076-1.379, p=0.002) for -592A>C. CONCLUSION The current meta-analysis results inconsistent with previous meta-analyses; showed that the IL-10 -592A>C polymorphism, but not -819T>C polymorphism, may be contributed to the susceptibility of GC in overall and Asian populations.
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Affiliation(s)
- Mansour Moghmi
- Shahid Sadoughi University of Medical Sciences, Pathology, Yazd, Yazd
| | - Amir Arjmandi
- Shahid Sadoughi University of Medical Sciences, Medical Genetics, Yazd, Yazd
| | - Kazem Aghili
- Shahid Sadoughi University of Medical Sciences, Radiology, Yazd, Yazd
| | - Mohammadali Jafari
- Shahid Sadoughi University of Medical Sciences, Emergency Medicine, Yazd, Yazd
| | - Masoud Zare-Shehneh
- Shahid Sadoughi University of Medical Sciences, Medical Genetics, Yazd, Yazd
| | - Shohreh Rastegar
- Shahid Sadoughi University of Medical Sciences, Anesthesiology, Yazd, Yazd
| | | | - Hossein Neamatzadeh
- Shahid Sadoughi University of Medical Sciences, Medical Genetics, Yazd, Yazd
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de Brito BB, da Silva FAF, de Melo FF. Role of polymorphisms in genes that encode cytokines and Helicobacter pylori virulence factors in gastric carcinogenesis. World J Clin Oncol 2018; 9:83-89. [PMID: 30254963 PMCID: PMC6153128 DOI: 10.5306/wjco.v9.i5.83] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 06/23/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
The Helicobacter pylori (H. pylori) infection is a determinant factor in gastric cancer (GC) development. However, the infection outcomes are variable and depend on both host and bacterial characteristics. Some host cytokines such as interleukin (IL)-1β, IL-1Ra, IL-8, IL-10 and tumor necrosis factor-α play important roles in the host immune system response to the pathogen, in the development of gastric mucosal lesions and in cell malignant transformation. Therefore, these host factors are crucial in neoplastic processes. Certain polymorphisms in genes that encode these cytokines have been associated with an increased risk of GC. On the other hand, various virulence factors found in distinct H. pylori bacterial strains, including cytotoxin-associated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and blood group antigen binding adhesin, have been associated with the pathogenesis of different gastric diseases. The virulent factors mentioned above allow the successful infection by the bacterium and play crucial roles in gastric mucosa lesions, including malignant transformation. Moreover, the role of host polymorphisms and bacterial virulence factors in gastric carcinogenesis seems to vary among different countries and populations. The identification of host and bacterium factors that are associated with an increased risk of GC development may be useful in determining the prognosis of infection in patients, what could help in clinical decision-making and in providing of an optimized clinical approach.
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Affiliation(s)
- Breno Bittencourt de Brito
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Brazil
| | | | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Brazil
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Sahami-Fard MH. Association between interleukin-10 -592 A/C polymorphism and gastrointestinal tract cancer risk: A meta-analysis. Int J Biol Markers 2018; 33:244-253. [PMID: 29720026 DOI: 10.1177/1724600817747525] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Recent evidence suggests that -592 A/C polymorphism in the interleukin-10 (IL-10) gene may influence risk of gastrointestinal tract cancer; however, individual studies have provided conflicting and inconclusive results. Therefore, this meta-analysis was conducted to assess the association between IL-10 -592 A/C polymorphism and gastrointestinal tract cancer susceptibility. METHODS EMBASE, PubMed, Web of Science, and China National Knowledge Infrastructure databases were searched for case-control studies published before 1 May 2017. A total of 36 studies involving 8069 cases and 13,089 controls were included in the present meta-analysis according to the inclusion criteria. The random- or fixed-effect model was utilized to calculate pooled odds ratio (OR) with 95% confidence interval (CI), and to survey the association. RESULTS By and large IL-10 -592 A/C (rs1800872) polymorphism was not associated with gastrointestinal cancer risk in five genetic models (A vs. C: OR 1.00; 95% CI 0.93, 1.08; POR = 0.960; AA vs. CC: OR 0.98; 95% CI 0.85, 1.14; POR = 0.835; CA vs. CC: OR 1.01; 95% CI 0.94, 1.08; POR = 0.776; AA+CA vs. CC: OR 1.03; 95% CI 0.94, 1.12; POR = 0.592; AA vs. CA+CC: OR 0.98; 95% CI 0.87, 1.10; POR = 0.666). Similar results were also achieved after stratification by the Hardy-Weinberg equilibrium, ethnicity, source of controls, and cancer type. CONCLUSION The results of this meta-analysis indicated that there is no association between the IL-10 -592 A/C promoter polymorphism and gastrointestinal tract cancer susceptibility.
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Li L, Liu J, Liu C, Lu X. The correlation between TNF-α-308 gene polymorphism and susceptibility to cervical cancer. Oncol Lett 2018; 15:7163-7167. [PMID: 29725439 PMCID: PMC5920275 DOI: 10.3892/ol.2018.8246] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Accepted: 02/14/2018] [Indexed: 01/30/2023] Open
Abstract
Tumor necrosis factor-α (TNF-α) is closely related to the occurrence of human cancers. Cervical cancer seriously affects female health. Therefore, our study aimed to investigate the correlation between the polymorphism of TNF-α-308 gene and susceptibility to cervical cancer. Whole blood was collected from 142 patients with cervical cancer and 150 healthy controls. PCR-RFLP was used to detect the polymorphism of TNF-α-308 and the correlation between polymorphism of TNF-α-308 and the susceptibility to cervical cancer was analyzed. The three genotypes of TNF-α-308 were GG, GA and AA, and the distributions of genotypes of TNF-α-308 were consistent with Hardy-Weinberg equilibrium in both cervical cancer group and control group. There were no significant differences in genotype and allele frequency between cervical cancer group and healthy control group (P>0.05). A/A genotype increased the risk of cervical cancer by 1.46 times with 95% confidence interval of 0.32-6.67. Different genotypes were not associated with tumor type (P>0.05). Different genotypes are correlated with cervical cancer TNM stages, tumor differentiation and lymph node metastasis. Proportion of GA+AA genotype in TNM stage III+IV group, low differentiation group and lymph node metastasis group were 28.1, 29.0 and 29.8%, respectively, which were significantly higher than those in stage I+II group, moderate/high differentiation group and non-lymph node metastasis group (P<0.05). The results suggested that TNF-α-308 gene polymorphism is associated with the degree of malignancy of cervical cancer. Female patients with A allele have higher malignant degree of cervical cancer.
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Affiliation(s)
- Liping Li
- Department of Gynaecology and Obstetrics, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China
| | - Jie Liu
- Department of Gynaecology and Obstetrics, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China
| | - Chunjing Liu
- Department of Gynaecology and Obstetrics, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China
| | - Xianghui Lu
- Department of Gynaecology and Obstetrics, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China
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Guo C, Wen L, Song JK, Zeng WJ, Dan C, Niu YM, Shen M. Significant association between interleukin-10 gene polymorphisms and cervical cancer risk: a meta-analysis. Oncotarget 2018; 9:12365-12375. [PMID: 29552317 PMCID: PMC5844753 DOI: 10.18632/oncotarget.24193] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Accepted: 12/04/2017] [Indexed: 12/18/2022] Open
Abstract
Previous studies have suggested that interleukin-10 (IL-10) polymorphisms may be associated with an increased risk of developing cervical cancer. However, the published results on this subject matter are controversial. The aim of this study was to conduct a meta-analysis of published reports to more precisely investigate the relationship between IL-10 polymorphisms and cervical cancer risk. Five online databases (PubMed, Embase, Web of SCI, CNKI and Wanfang) were searched, and seventeen articles with sufficient quantitative information were included in our meta-analysis. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between IL-10 polymorphisms and cervical cancer risk. Publication bias, sensitivity and cumulative analyses were also performed to support our findings. Overall, there was a significant association between the IL-10 -1082A > G polymorphism and cervical cancer risk observed in the total population (G vs. A: OR = 1.60, 95% CI = 1.12–2.29, P = 0.01, I2 = 92.3%; AG vs. AA: OR = 1.34, 95% CI = 1.04-1.74, P = 0.03, I2 = 65.9%; AG + GG vs. AA: OR = 1.58, 95% CI = 1.11–2.25, P = 0.01, I2 = 84.4%), and the same results were obtained in the subgroup analysis. Moreover, the IL-10 -819 T > C polymorphism exhibited a significant, protective effect against cervical cancer. In summary, our meta-analysis suggests that IL-10 polymorphisms may play a variety of roles in regard to cervical cancer risk, especially in Asians.
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Affiliation(s)
- Chong Guo
- Center for Evidence-Based Medicine and Clinical Research, Department of Gynecology and Obstetrics, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China
| | - Li Wen
- Department of Dermatology, Suizhou Central Hospital, Hubei University of Medicine, Shiyan 442000, China
| | - Ju-Kun Song
- Department of Oral and Maxillary Surgery, Guizhou Provincial People's Hospital, Guiyang 550002, China
| | - Weng-Jing Zeng
- Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China
| | - Chao Dan
- Department of Urinary Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China
| | - Yu-Ming Niu
- Center for Evidence-Based Medicine and Clinical Research, Department of Gynecology and Obstetrics, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China.,Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China
| | - Ming Shen
- Jiangsu Key Laboratory of Oral Diseases, Department of Dental Implant, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing 210029, China
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Zhang X, Wang J, Shao H, Zhu W. Function of tumor necrosis factor alpha before and after mutation in gastric cancer. Saudi J Biol Sci 2017; 24:1920-1924. [PMID: 29551945 PMCID: PMC5851903 DOI: 10.1016/j.sjbs.2017.11.040] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Revised: 11/10/2017] [Accepted: 11/12/2017] [Indexed: 01/23/2023] Open
Abstract
Purpose To explore the cause of functional changes of tumor necrosis factor alpha (TNF-α) in development of gastric cancer through the structural changes of each site in TNF-α before and after mutation. Methods Three typical mutant sites (TNF-α-308G/A, 857C/T and 863C/A of TNF-α) were chosen and methods like ab initio modeling was adopted for 3D modeling of TNF-α before and after mutation, besides, the structural changes were also analyzed. Results Mutation of TNF-α-308G/A led to the production of multiple helical structures and that of 863C/A caused the production of one helical structure in its adjacent region. Mutation of 857C/T, however, did not cause the change in the basic structure of TNF-α. Conclusions Structural changes of TNF-α may have a significant effect on development of gastric cancer.
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Affiliation(s)
- Xia Zhang
- Intensive Care Unit, Henan Provincial People's Hospital, Zhengzhou 450000, PR China
| | - Jianjun Wang
- Department of Oncology, Henan University Huaihe Hospital, Kaifeng 475001, PR China
| | - Huanzhang Shao
- Intensive Care Unit, Henan Provincial People's Hospital, Zhengzhou 450000, PR China
| | - Wenliang Zhu
- Intensive Care Unit, Henan Provincial People's Hospital, Zhengzhou 450000, PR China
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Mărginean MO, Mărginean CO, Meliţ LE, Voidăzan S, Moldovan V, Bănescu C. The impact of host's genetic susceptibility on Helicobacter pylori infection in children. Medicine (Baltimore) 2017; 96:e7612. [PMID: 28746216 PMCID: PMC5627842 DOI: 10.1097/md.0000000000007612] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The aim of our study was to investigate the impact of interleukin (IL)-6 190C/T, IL-6 174G/C, IL-6 572G/C, tumor necrosis factor-alpha (TNF-α) 308G/A, and angiotensin-converting enzyme (ACE) I/D gene polymorphisms on Helicobacter pylori (H. pylori) infection in children.A cross-sectional study was performed on 126 children (57 children with H. pylori infection and 69 children without H. pylori infection) aged between 3 and 18 years presenting to a Pediatrics Tertiary Hospital from Romania. Children were assessed clinically, endoscopically, histopathologically, and genetically.In our study, we found that the presence of the CT and CT+TT genotypes of IL-6 190C/T (P < .002 and P = .04), allele G of IL-6 572 G/C polymorphism (P = .01), genotypes GA and AA of TNF-α 308 G/A polymorphism (P = .04, P = .01), and genotype II of ACE I/D polymorphism (P = .02) were associated with H. pylori infection, while the CC genotype of IL-6 174G/C polymorphism was scarcely encountered in children with H. pylori infection [P = .02, odds ratio (OR) = 0.06; 95% confidence interval (95% CI): 0.003-0.128]. Taking under consideration the 4 variant genotypes (IL-6 572G/C, IL-6 190C/T, TNF-α 308G/A, and ACE I/D), we noticed a 2 times higher incidence of H. pylori infection (OR = 6.34; 95% CI: 2.15-25.8).We may consider that the IL-6 190C/T, IL-6 174G/C, IL-6 572G/C, TNF-α 308G/A, and ACE I/D gene polymorphisms may increase the children's susceptibility for acquiring H. pylori infection; therefore, they may contribute to the pathogenesis of H. pylori gastritis.
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Affiliation(s)
| | | | - Lorena Elena Meliţ
- Department of Pediatrics, University of Medicine and Pharmacy Tîrgu Mureş
| | - Septimiu Voidăzan
- Department of Epidemiology, University of Medicine and Pharmacy Tîrgu Mureş
| | - Valeriu Moldovan
- Genetics Laboratory, Center for Advanced Medical and Pharmaceutical Research, University of Medicine and Pharmacy Tîrgu Mureş, Romania
| | - Claudia Bănescu
- Genetics Laboratory, Center for Advanced Medical and Pharmaceutical Research, University of Medicine and Pharmacy Tîrgu Mureş, Romania
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Human and Helicobacter pylori Interactions Determine the Outcome of Gastric Diseases. Curr Top Microbiol Immunol 2017; 400:27-52. [PMID: 28124148 DOI: 10.1007/978-3-319-50520-6_2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The innate immune response is a critical hallmark of Helicobacter pylori infection. Epithelial and myeloid cells produce effectors, including the chemokine CXCL8, reactive oxygen species (ROS), and nitric oxide (NO), in response to bacterial components. Mechanistic and epidemiologic studies have emphasized that dysregulated and persistent release of these products leads to the development of chronic inflammation and to the molecular and cellular events related to carcinogenesis. Moreover, investigations in H. pylori-infected patients about polymorphisms of the genes encoding CXCL8 and inducible NO synthase, and epigenetic control of the ROS-producing enzyme spermine oxidase, have further proven that overproduction of these molecules impacts the severity of gastric diseases. Lastly, the critical effect of the crosstalk between the human host and the infecting bacterium in determining the severity of H. pylori-related diseases has been supported by phylogenetic analysis of the human population and their H. pylori isolates in geographic areas with varying clinical and pathologic outcomes of the infection.
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Genetic association between TNF-α promoter polymorphism and susceptibility to squamous cell carcinoma, basal cell carcinoma, and melanoma: A meta-analysis. Oncotarget 2017; 8:53873-53885. [PMID: 28881857 PMCID: PMC5581156 DOI: 10.18632/oncotarget.17179] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Accepted: 03/16/2017] [Indexed: 01/18/2023] Open
Abstract
Tumor necrosis factor-alpha (TNF-α) is a multifunctional pro-inflammatory cytokine that plays an important role in cancer development. We performed a meta-analysis to assess the relationship between single nucleotide polymorphisms in the TNF-α promoter region (rs1800629 and rs361525) and susceptibility to squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and melanoma. After database retrieval, article selection, data extraction, and quality assessment, 20 articles comprising 4865 cases and 6329 controls were included in this study. rs1800629 was associated with an increased overall risk of SCC, lung SCC, and oral SCC in the AA vs G and AA vs GG+GA genetic models (all OR>1, Passociation<0.05). No increased risk of skin SCC, skin BCC or melanoma was observed (all Passociation>0.05). Rs361525 was not associated with overall SCC risk in the allele, heterozygote, dominant, recessive, or carrier model (all Passociation>0.05). Begg's and Egger's tests (PBegg>0.05; PEgger>0.05) demonstrated there was no significant publication bias. These data indicate that the AA genotype of TNF-α rs1800629, but not rs361525, is associated with an increased risk of SCC, suggesting it could potentially serve as a prognostic marker for predicting SCC risk.
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Tumor Necrosis Factor- α T-857C (rs1799724) Polymorphism and Risk of Cancers: A Meta-Analysis. DISEASE MARKERS 2016; 2016:4580323. [PMID: 28115787 PMCID: PMC5223007 DOI: 10.1155/2016/4580323] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 12/04/2016] [Accepted: 12/06/2016] [Indexed: 01/08/2023]
Abstract
Objectives. To investigate the potential association of tumor necrosis factor-α T-857C polymorphism with susceptibility to the five common malignant tumors. Materials and Methods. A comprehensive search of PubMed/Medline, Embase, and Web of Science databases was performed up to November 2015. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Subgroup analysis, heterogeneity analyses, and publication bias were also texted in the meta-analysis. Results. A total of twenty-two publications involving 5215 cases and 6755 controls were recruited. Overall, the meta-analysis revealed an increased risk between the TNF-α T-857C polymorphism and gastric cancer susceptibility in T versus C model, heterozygote genetic model, and dominant genetic model. An increased risk between the TNF-α T-857C polymorphism and hepatocellular cancer susceptibility in homozygote genetic model and recessive genetic model was also found. No significant association was found between the TNF-α T-857C polymorphism and colorectal cancer, cervical cancer, and prostate cancer. Conclusions. Our meta-analyses suggest that TNF-α T-857C polymorphism may be associated with increased risk of gastric cancer and hepatocellular cancer development. Therefore, the TNF-α T-857C polymorphism could be considered as one possible risk factor of gastric cancer and hepatocellular cancer according to our study.
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Frequency of TNFA, INFG, and IL10 Gene Polymorphisms and Their Association with Malaria Vivax and Genomic Ancestry. Mediators Inflamm 2016; 2016:5168363. [PMID: 27999453 PMCID: PMC5143728 DOI: 10.1155/2016/5168363] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 07/14/2016] [Accepted: 09/27/2016] [Indexed: 02/08/2023] Open
Abstract
Polymorphisms in cytokine genes can alter the production of these proteins and consequently affect the immune response. The trihybrid heterogeneity of the Brazilian population is characterized as a condition for the use of ancestry informative markers. The objective of this study was to evaluate the frequency of -1031T>C, -308G>A and -238G>A TNFA, +874 A>T IFNG and -819C>T, and -592C>A IL10 gene polymorphisms and their association with malaria vivax and genomic ancestry. Samples from 90 vivax malaria-infected individuals and 51 noninfected individuals from northern Brazil were evaluated. Genotyping was carried out by using ASO-PCR or PCR/RFLP. The genomic ancestry of the individuals was classified using 48 insertion/deletion polymorphism biallelic markers. There were no differences in the proportions of African, European, and Native American ancestry between men and women. No significant association was observed for the allele and genotype frequencies of the 6 SNPs between malaria-infected and noninfected individuals. However, there was a trend toward decreasing the frequency of individuals carrying the TNF-308A allele with the increasing proportion of European ancestry. No ethnic-specific SNPs were identified, and there was no allelic or genotype association with susceptibility or resistance to vivax malaria. Understanding the genomic mechanisms by which ancestry influences this association is critical and requires further study.
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Deng K, Wang H, Shan T, Chen Y, Zhou H, Zhao Q, Xia J. Tristetraprolin inhibits gastric cancer progression through suppression of IL-33. Sci Rep 2016; 6:24505. [PMID: 27074834 PMCID: PMC4830935 DOI: 10.1038/srep24505] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Accepted: 03/30/2016] [Indexed: 02/07/2023] Open
Abstract
Tristetraprolin (TTP) is an adenine/uridine (AU)-rich element (ARE)-binding protein that can induce degradation of mRNAs. In this study, we report that TTP suppresses the expression of interleukin-33 (IL-33), a tumor-promoting inflammatory cytokine, and thereby inhibits the progression of gastric cancer (GC). Overexpression of TTP decreased the level of IL-33, whereas knockdown of TTP increased IL-33 levels. We also discovered that TTP inhibited the proliferation, migration, and invasion of GC cell lines through regulation of IL-33. Furthermore, TTP RNA and protein levels were remarkably reduced in GC and inversely correlated with IL-33 level, and they were also closely associated with depth of invasion, lymph node metastasis, advanced TNM stage, as well as survival rate. Taken together, these findings identified TTP as a downregulator of IL-33, and further suggest that TTP can serve as a novel biomarker for the diagnosis of GC and as a potential therapeutic target for GC treatment.
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Affiliation(s)
- Kaiyuan Deng
- Department of General Surgery and Translational Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214002, China
| | - Hao Wang
- Department of General Surgery and Translational Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214002, China
| | - Ting Shan
- Department of General Surgery and Translational Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214002, China
| | - Yigang Chen
- Department of General Surgery and Translational Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214002, China
| | - Hong Zhou
- Department of General Surgery and Translational Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214002, China
| | - Qin Zhao
- Department of General Surgery and Translational Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214002, China
| | - Jiazeng Xia
- Department of General Surgery and Translational Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214002, China
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Major apoptotic mechanisms and genes involved in apoptosis. Tumour Biol 2016; 37:8471-86. [PMID: 27059734 DOI: 10.1007/s13277-016-5035-9] [Citation(s) in RCA: 390] [Impact Index Per Article: 43.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Accepted: 03/28/2016] [Indexed: 12/12/2022] Open
Abstract
As much as the cellular viability is important for the living organisms, the elimination of unnecessary or damaged cells has the opposite necessity for the maintenance of homeostasis in tissues, organs and the whole organism. Apoptosis, a type of cell death mechanism, is controlled by the interactions between several molecules and responsible for the elimination of unwanted cells from the body. Apoptosis can be triggered by intrinsically or extrinsically through death signals from the outside of the cell. Any abnormality in apoptosis process can cause various types of diseases from cancer to auto-immune diseases. Different gene families such as caspases, inhibitor of apoptosis proteins, B cell lymphoma (Bcl)-2 family of genes, tumor necrosis factor (TNF) receptor gene superfamily, or p53 gene are involved and/or collaborate in the process of apoptosis. In this review, we discuss the basic features of apoptosis and have focused on the gene families playing critical roles, activation/inactivation mechanisms, upstream/downstream effectors, and signaling pathways in apoptosis on the basis of cancer studies. In addition, novel apoptotic players such as miRNAs and sphingolipid family members in various kind of cancer are discussed.
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Zabaglia LM, Ferraz MA, Pereira WN, Orcini WA, de Labio RW, Neto AC, Wisnieski F, de Oliveira JG, de Arruda Cardoso Smith M, Payão SLM, Rasmussen LT. Lack of association among TNF-α gene expression, -308 polymorphism (G > A) and virulence markers of Helicobacter pylori. J Venom Anim Toxins Incl Trop Dis 2015; 21:54. [PMID: 26719751 PMCID: PMC4696262 DOI: 10.1186/s40409-015-0054-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 12/21/2015] [Indexed: 12/18/2022] Open
Abstract
Background Tumor necrosis factor plays a critical role in the pathogenesis of gastric diseases such as gastric cancer, and an abnormal inflammatory response has frequently been observed in dyspeptic patients. Helicobacter pylori infection can induce a gastric mucosal inflammatory response that may be influenced by -308 (G > A) polymorphisms and gene expression of the TNF-α gene. Methods One hundred and thirty-four gastric biopsy samples were collected from patients of both genders (61♂ and 73♀, mean age 40.3 ± 24.2 years) with gastric symptoms. The -308 (G > A) polymorphism of TNF-α was characterized using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The expression level was measured using real-time PCR, and relative quantification (RQ) was calculated using the comparative CT method (2-ΔΔCT). Results The analysis revealed an increase in TNF-α gene expression in patients with gastritis; on the other hand, no statistical differences were observed in patients with gastric cancer. In addition, no association was found among -308 polymorphism genotypes, virulence markers, or TNF-α gene expression. Conclusions Helicobacter pylori induces a large increase in TNF-α expression in patients with gastritis, regardless of tissue inflammation, but after the tissue becomes neoplastic, the presence of bacteria did not influence expression. These results suggest that the TNF-α pathway may play an important role in the progression from gastritis to gastric cancer
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Affiliation(s)
- Luanna Munhoz Zabaglia
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | - Mariane Avante Ferraz
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | - Weendelly Nayara Pereira
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | - Wilson Aparecido Orcini
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | | | | | - Fernanda Wisnieski
- Universidade Federal de São Paulo, Rua Sena Madureira, 1500, 04021-001 São Paulo, SP Brazil
| | | | | | - Spencer Luiz Marques Payão
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil ; Faculdade de Medicina de Marília, Rua Lourival Freire 240, 17519-050 Marília, SP Brazil
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