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Mei TTY, Aung HH, Tung WS, Naing C. Association between IL-10 gene polymorphisms (- 1082 A/G, -819 T/C, -592 A/C) and hepatocellular carcinoma: a meta-analysis and trial sequential analysis. BMC Cancer 2023; 23:842. [PMID: 37684564 PMCID: PMC10492326 DOI: 10.1186/s12885-023-11323-1] [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: 12/19/2022] [Accepted: 08/21/2023] [Indexed: 09/10/2023] Open
Abstract
BACKGROUND The carcinogenesis of hepatocellular carcinoma is complicated, and genetic factor may have the role in the malignant transformation of liver cells. IL-10 gene polymorphisms have been investigated for their potential roles in hepatocellular carcinoma This study aimed to investigate the relationship between polymorphisms of IL-10 (-1082 A/G, -819 T/C, -592 A/C), and hepatocellular carcinoma by performing a meta-analysis with eligible individual studies. METHODS This study followed the PRISMA 2020 Checklist. Relevant studies were searched in health-related databases. The Newcastle-Ottawa Scale criteria were used to evaluate the studies quality. Pooled odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and hepatocellular carcinoma using five genetic models. Stratification was done by ethnic groups. Trial sequential analysis (TSA) was performed to determine the required information size. RESULTS Fifteen case-control studies (n = 8182) were identified. Overall, the heterozygous model showed a marginal significant association only between IL-10 (-1082 A/G) and hepatocellular carcinoma risk (OR: 0.82, 95% CI: 0.67-1.00, 9 studies). On stratification, IL-10 (-1082 A/G) was significantly associated with hepatocellular carcinoma risk in the non-Asian population under dominant (OR: 0.62, 95% CI: 0.45-0.86, 4 studies), heterozygous (OR: 0.60, 95% CI: 0.43-0.85) and allelic models (OR: 0.79, 95% CI: 0.64-0.99). IL-10 (-819 T/C) was significantly associated with hepatocellular carcinoma risk only among non-Asians under the dominant (OR: 1.47, 95% CI: 1.02-2.13, 8 studies), recessive (OR: 1.99, 95% CI: 1.03-3.86, and homozygous models (OR: 2.18, 95% CI: 1.13-4.23). For IL-10 (-592 A/C) with 11 studies, there was no significant association with hepatocellular carcinoma in all five genetic models (P values > 0.5). TSA plots indicated that the information size for firm evidence of effect was sufficient only for the analysis of IL-10 (-592 A/C), but not for the - 1082 A/G or -819 T/C. CONCLUSIONS Findings suggest that IL-10 (-1082 A/G and - 819 T/C) polymorphisms are associated with hepatocellular carcinoma in ethnic-specific manner. However, this evidence is not conclusive because the sample size was insufficient. IL-10 (-592 A/C) polymorphism was not associated with hepatocellular carcinoma albeit with sufficient information size. Future well-designed large case-control studies on IL-10 (-1082 A/G and - 819 T/C) with different ethnicities are recommended.
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Affiliation(s)
- Teresa Tan Yen Mei
- School of Medicine, International Medical University, Kuala Lumpur, Malaysia
- School of Medicine, University of Adelaide, Adelaide, Australia
| | - Htar Htar Aung
- School of Medicine, International Medical University, Kuala Lumpur, Malaysia.
| | - Wong Siew Tung
- School of Medicine, International Medical University, Kuala Lumpur, Malaysia
| | - Cho Naing
- Faculty of Tropical Health and Medicine, James Cook University, Queensland, Australia
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Bhatt S, Singh P, Sharma A, Rai A, Dohare R, Sankhwar S, Sharma A, Syed MA. Deciphering Key Genes and miRNAs Associated With Hepatocellular Carcinoma via Network-Based Approach. IEEE/ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS 2022; 19:843-853. [PMID: 32795971 DOI: 10.1109/tcbb.2020.3016781] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Hepatocellular carcinoma (HCC)is a common type of liver cancer and has a high mortality world-widely. The diagnosis, prognoses, and therapeutics are very poor due to the unclear molecular mechanism of progression of the disease. To unveil the molecular mechanism of progression of HCC, we extract a large sample of mRNA expression levels from the GEO database where a total of 167 samples were used for study, and out of them, 115 samples were from HCC tumor tissue. This study aims to investigate the module of differentially expressed genes (DEGs)which are co-expressed only in HCC sample data but not in normal tissue samples. Thereafter, we identified the highly significant module of significant co-expressed genes and formed a PPI network for these genes. There were only six genes (namely, MSH3, DMC1, ALPP, IL10, ZNF223, and HSD17B7)obtained after analysis of the PPI network. Out of six only MSH3, DMC1, HSD17B7, and IL10 were found enriched in GO Term & Pathway enrichment analysis and these candidate genes were mainly involved in cellular process, metabolic and catalytic activity, which promote the development & progression of HCC. Lastly, the composite 3-node FFL reveals the driver miRNAs and TFs associated with our key genes.
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Association of TGF-β1 and IL-10 Gene Polymorphisms with Osteoporosis in a Study of Taiwanese Osteoporotic Patients. Genes (Basel) 2021; 12:genes12060930. [PMID: 34207210 PMCID: PMC8233820 DOI: 10.3390/genes12060930] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/13/2021] [Accepted: 06/15/2021] [Indexed: 01/07/2023] Open
Abstract
Osteoporosis is a rising health threat in the increasingly aging world population. It is a common skeletal disease strongly linked to genetic predisposition. We aim to identify the effects of the anti-inflammatory TGF-β1- and IL-10-specific single-nucleotide polymorphism (SNP) combination on the risk for osteoporosis. We investigated and analyzed the relationships between three TGF-β1 SNPs (-509C/T, +869 T/C and +29T/C), one IL-10 SNP (+1927A/C) and the level of bone mineral density (BMD), as well as the risk of osteoporosis in Taiwanese osteoporotic patients. A total of 217 subjects were recruited, including 88 osteoporotic patients and 129 healthy controls, for SNPs, BMD and clinical characteristics statistical analyses. Females with TGF-β1 SNP (-509 C/C) and IL-10 SNP (+1927 C/C) genotypes showed a great benefit for femoral neck T-scores. However, the combination of TGF-β1 SNP (-509 T/T) and IL-10 SNP (+1927 A/A) genotypes in all subjects showed a significant decrease in total hip BMD T-scores. The TGF-β1 SNP (-509 C/T) genotype in all subjects and TGF-β1 SNP (-509 T/T) and IL-10 SNP (+1927 A/C) genotypes in males showed positive effects on body height. The combination of the many SNPs in the anti-inflammatory TGF-β1 and IL-10 genes may be cooperatively involved in the development of osteoporosis. Our data suggested that the specific SNP combination of TGF-β1 (-509) and IL-10 (+1927) may act as a predictive factor for postmenopausal osteoporosis in Taiwanese women.
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Barooah P, Saikia S, Kalita MJ, Bharadwaj R, Sarmah P, Bhattacharyya M, Goswami B, Medhi S. IL-10 Polymorphisms and Haplotypes Predict Susceptibility to Hepatocellular Carcinoma Occurrence in Patients with Hepatitis C Virus Infection from Northeast India. Viral Immunol 2020; 33:457-467. [PMID: 32352886 DOI: 10.1089/vim.2019.0170] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Chronic hepatitis C virus (HCV) infection leads to variable outcomes, ranging from prolonged slow hepatic damage leading to cirrhosis, and hepatocellular carcinoma (HCC). Polymorphism in cytokines IL-10 and IL-12 that impact the immune response to HCV infection may play a role in determining this outcome. This study was aimed to determine if polymorphisms in IL-10 and IL-12B contribute to HCV susceptibility and the risk of developing HCC in patients from Northeast India. IL-10 - 1082, -819, -592 polymorphisms and IL-12B -1188 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism in a total of 266 HCV-infected patients and 100 age- and sex-matched controls. In the HCV-infected subjects, 110 patients had chronic hepatitis C (CHC), 96 with liver cirrhosis, and 60 with HCC. Serum levels of IL-10 were also measured and correlated with disease severity. Haplotype analysis for IL-10 polymorphisms was carried out. Statistical data were analyzed using SPSS ver. 22.0. The frequency of IL-10 - 592 AA genotype/A allele was significantly higher in HCC patients than in CHC patients. The intermediate IL-10-producing ACC haplotype was significantly more frequent in HCC and cirrhotic patients than in CHC patients. No significant association was found for IL-10 - 819, -592 and IL-12B -1188 polymorphisms with the susceptibility to HCV infection or occurrence of HCC in HCV-infected patients. IL-10 - 592 CA polymorphism and IL-10 ACC haplotype are significant biomarkers of HCC in HCV-infected patients from Northeast India. Higher serum levels of IL-10 were also linked to higher disease severity.
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Affiliation(s)
- Prajjalendra Barooah
- Laboratory of Molecular Virology and Oncology, Department of Bioengineering and Technology, Gauhati University Institute of Science and Technology, Gauhati University, Guwahati, India
| | - Snigdha Saikia
- Laboratory of Molecular Virology and Oncology, Department of Bioengineering and Technology, Gauhati University Institute of Science and Technology, Gauhati University, Guwahati, India
| | - Manas Jyoti Kalita
- Laboratory of Molecular Virology and Oncology, Department of Bioengineering and Technology, Gauhati University Institute of Science and Technology, Gauhati University, Guwahati, India
| | - Rituraj Bharadwaj
- Laboratory of Molecular Virology and Oncology, Department of Bioengineering and Technology, Gauhati University Institute of Science and Technology, Gauhati University, Guwahati, India
| | - Preeti Sarmah
- Department of Gastroenterology, Gauhati Medical College and Hospital, Guwahati, India
| | - Mallika Bhattacharyya
- Department of Gastroenterology, Gauhati Medical College and Hospital, Guwahati, India
| | - Bhabadev Goswami
- Department of Gastroenterology, Gauhati Medical College and Hospital, Guwahati, India
| | - Subhash Medhi
- Laboratory of Molecular Virology and Oncology, Department of Bioengineering and Technology, Gauhati University Institute of Science and Technology, Gauhati University, Guwahati, India
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Goud EVSS, Malleedi S, Ramanathan A, Wong GR, Hwei Ern BT, Yean GY, Ann HH, Syan TY, Zain RM. Association of Interleukin-10 Genotypes and Oral Cancer Susceptibility in Selected Malaysian Population: A Case-
Control Study. Asian Pac J Cancer Prev 2019; 20:935-941. [PMID: 30912418 PMCID: PMC6825797 DOI: 10.31557/apjcp.2019.20.3.935] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background: Interleukin-10 (IL10) genotypes have been closely correlated to the susceptibility for oral squamous cell carcinoma. More than half of oral cancers in the world occur in Asia with estimated 168,850 new cases were diagnosed in this geographical region alone. Considering the rising numbers of oral cancer cases in Malaysia, association of IL10 A1082G gene polymorphism was correlated. Methodology: 41 oral squamous cell carcinoma (OSCC) cases and 48 healthy controls of comparable age, gender, and with habits like smoking, alcohol consumption and betel quid chewing were selected. In this case-control study, samples were collected from the Oral Cancer Research and Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, Malaysia. Genotyping conditions were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The PCR products were subjected to digestion by MnlI enzyme (NEB, UK) to screen for the IL10 A-1082G. Digested DNA products were analyzed by electrophoresis on 4% (w/v) agarose gel, stained with ethidium bromide and imaged under UV illumination. Chi-square test and Fisher’s Exact test were used in statistical analysis. Results: AG genotypes were present in 81.3% and 86.0% of healthy control and OSCC cases respectively (OR=0.468, 95% CI=0.133-1.653). No significant association was found between IL10 A1082G polymorphism with risk habits, clinico-pathological parameters and 5-years overall survival. The findings also show no significant correlation between the IL10 genotype and features of OSCC within the case group as measured by tumor size, lymph node involvement, stage, invasive front, grading, depth, pattern of invasion. Conclusion: This study suggests that functional polymorphism AG of IL10 A1082G may have no influence with OSCC susceptibility. However, further investigation with larger sample sizes can be conducted to provide additional evidence to support the lack of association of IL10 A1082G polymorphism in oral cancer.
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Affiliation(s)
- E V Soma Sekhar Goud
- Department of Oral Maxillo-Facial Pathology and Microbiology, Faculty of Dentistry, MAHSA University, Kuala Lumpur, Malaysia.
| | - Shanthi Malleedi
- Department of Paediatric Dentistry, Faculty of Dentistry, MAHSA University, Kuala Lumpur, Malaysia
| | - Anand Ramanathan
- Department of Oral & Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.,Oral Cancer Research and Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia
| | - Gou Rean Wong
- Oral Cancer Research and Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia
| | - Beatrix Tan Hwei Ern
- Department of Oral Maxillo-Facial Pathology and Microbiology, Faculty of Dentistry, MAHSA University, Kuala Lumpur, Malaysia.
| | - Goh Yin Yean
- Department of Oral Maxillo-Facial Pathology and Microbiology, Faculty of Dentistry, MAHSA University, Kuala Lumpur, Malaysia.
| | - Ho Hui Ann
- Department of Oral Maxillo-Facial Pathology and Microbiology, Faculty of Dentistry, MAHSA University, Kuala Lumpur, Malaysia.
| | - Tan Yuen Syan
- Department of Oral Maxillo-Facial Pathology and Microbiology, Faculty of Dentistry, MAHSA University, Kuala Lumpur, Malaysia.
| | - Rosnah Mohd Zain
- Department of Oral Maxillo-Facial Pathology and Microbiology, Faculty of Dentistry, MAHSA University, Kuala Lumpur, Malaysia. ,Oral Cancer Research and Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.,Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
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Maurya G, Hazam RK, Ruttala R, Karna R, Das BC, Kar P. A study of association between regulatory polymorphism in the IL-10 gene promoter region and acute viral hepatitis, and acute liver failure. Indian J Gastroenterol 2018; 37:293-298. [PMID: 30109600 DOI: 10.1007/s12664-018-0858-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 05/20/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND The level of inflammatory cytokine Interleukin (IL)-10 is increased in patients infected with hepatitis-related acute liver failure (ALF), and this was thought to be because of the regulatory polymorphism in the IL-10 gene promoter region. The present study was designed to analyze the possible association between IL-10 gene promoter polymorphism and acute viral hepatitis (AVH), and ALF. An attempt was made to quantify IL-10 levels at admission, during the hospital stay, and at the final outcome to study its relationship with liver injury among patients with AVH, ALF, and controls. METHODS The study included 40 patients each with ALF and AVH. IL-10 gene promoter polymorphism was detected by the PCR-RFLP method. Quantification of IL-10 was done using commercially available ELISA kits. RESULTS The individuals with -592 AC, -819 TC, -1082 AA genotypes were found to have a significantly higher risk of ALF whereas those with -592 AA and - 819 CC polymorphism were found to be less susceptible. Individuals with - 819 CC were found to be more susceptible to AVH while those with -592 AA and -819 TT were less susceptible as compared to controls. Mean serum IL-10 at admission was significantly elevated in patients with ALF (38.4±11.3 pg/mL) as compared to patients with AVH (16.7±5.4 pg/mL) and control population (8.3±3.6 pg/mL, p < 0.05). CONCLUSION Regulatory polymorphism in the IL-10 gene promoter has a possible and significant association with severity and outcome in patients with AVH and ALF. Raised levels of IL-10 could be predictive of prognosis in patients with ALF.
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Affiliation(s)
- Gaurav Maurya
- Department of Medicine, Maulana Azad Medical College, University of Delhi, E23 Nivedita Kunj, Sector 10, R.K. Puram, New Delhi, 110 002, India
| | - Rajib Kishore Hazam
- Department of Medicine, Maulana Azad Medical College, University of Delhi, E23 Nivedita Kunj, Sector 10, R.K. Puram, New Delhi, 110 002, India
| | - Rajesh Ruttala
- Department of Medicine, Maulana Azad Medical College, University of Delhi, E23 Nivedita Kunj, Sector 10, R.K. Puram, New Delhi, 110 002, India
| | - Rahul Karna
- Department of Medicine, Maulana Azad Medical College, University of Delhi, E23 Nivedita Kunj, Sector 10, R.K. Puram, New Delhi, 110 002, India
| | - Bhudev C Das
- Center for Biomedical Research, University of Delhi, New Delhi, 110 002, India
| | - Premashis Kar
- Department of Medicine, Maulana Azad Medical College, University of Delhi, E23 Nivedita Kunj, Sector 10, R.K. Puram, New Delhi, 110 002, India.
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Interleukin-10 −592C/A, but not −1082A/G promoter single nucleotide polymorphism, is associated with a decreased risk of colorectal cancer in an ethnic Kashmiri population: a case–control study. Eur J Cancer Prev 2017; 26:476-490. [PMID: 28538040 DOI: 10.1097/cej.0000000000000370] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Wang P, An J, Zhu Y, Wan X, Zhang H, Xi S, Li S. Association of three promoter polymorphisms in interleukin-10 gene with cancer susceptibility in the Chinese population: a meta-analysis. Oncotarget 2017; 8:62382-62399. [PMID: 28977953 PMCID: PMC5617513 DOI: 10.18632/oncotarget.18220] [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: 03/15/2017] [Accepted: 04/14/2017] [Indexed: 12/15/2022] Open
Abstract
Numerous studies have examined the associations of three promoter polymorphisms (-1082A/G, -819T/C and -592A/C) in IL-10 gene with cancer susceptibility in the Chinese population, but the results remain inconclusive. To gain a more precise estimation of this potential association, we conducted the current meta-analysis based on 53 articles, including 26 studies with 4,901 cases and 6,426 controls for the -1082A/G polymorphism, 33 studies with 6,717 cases and 8,550 controls for the -819T/C polymorphism, and 42 studies with 9,934 cases and 13,169 controls for the -592A/C polymorphism. Pooled results indicated that the three promoter polymorphisms in IL-10 gene were significantly associated with an increased overall cancer risk in the Chinese population. Stratification analysis showed that the association was more pronounced for hepatocellular carcinoma and low quality studies for the -1082A/G polymorphism, lung cancer and oral cancer for the -819T/C polymorphism. However, the -592A/C polymorphism was associated with a statistically significant increased risk for lung cancer, oral cancer, hospital-based studies and low quality studies, but a decreased risk for colorectal cancer. We further investigated the significant results using the false-positive report probability (FPRP) test. Interestingly, FPRP test results revealed that only IL-10 -1082A/G polymorphism was truly associated with an increased overall cancer risk. In the subgroup analysis, only the low quality studies, lung cancer and colorectal cancer remained significant at the prior level of 0.1. Although this association needs further confirmation by considering large studies, this meta-analysis suggested an association between IL-10 gene polymorphisms and cancer risk in the Chinese population.
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Affiliation(s)
- Ping Wang
- The Key Laboratory of Pharmacology and Medical Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang 471023, Henan, China
| | - Junling An
- The Key Laboratory of Pharmacology and Medical Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang 471023, Henan, China
| | - Yanfeng Zhu
- The Key Laboratory of Pharmacology and Medical Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang 471023, Henan, China
| | - Xuedong Wan
- The Key Laboratory of Pharmacology and Medical Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang 471023, Henan, China
| | - Hongzhen Zhang
- The Key Laboratory of Pharmacology and Medical Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang 471023, Henan, China
| | - Shoumin Xi
- The Key Laboratory of Pharmacology and Medical Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang 471023, Henan, China
| | - Sanqiang Li
- The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang 471023, Henan, China
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Moudi B, Heidari Z, Mahmoudzadeh-Sagheb H. Impact of host gene polymorphisms on susceptibility to chronic hepatitis B virus infection. INFECTION GENETICS AND EVOLUTION 2016; 44:94-105. [DOI: 10.1016/j.meegid.2016.06.043] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Revised: 06/21/2016] [Accepted: 06/22/2016] [Indexed: 12/15/2022]
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Shi YH, Zhao DM, Wang YF, Li X, Ji MR, Jiang DN, Xu BP, Zhou L, Lu CZ, Wang B. The association of three promoter polymorphisms in interleukin-10 gene with the risk for colorectal cancer and hepatocellular carcinoma: A meta-analysis. Sci Rep 2016; 6:30809. [PMID: 27489033 PMCID: PMC4973248 DOI: 10.1038/srep30809] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Accepted: 07/06/2016] [Indexed: 01/10/2023] Open
Abstract
Mounting evidence supports a potent inhibitory role of interleukin-10 (IL-10) in tumor carcinogenesis, angiogenesis and metastasis. This meta-analysis was designed to examine the association of three promoter polymorphisms (−592C > A, −819C > T and −1082G > A) in IL-10 gene with the risk for colorectal cancer and hepatocellular carcinoma. Qualification assessment and data collection were completed by two authors independently. The random-effects model using the DerSimonian and Laird method was fitted by the STATA software. Twenty-five articles involving 5933 cases and 9724 controls were meta-analyzed. Overall comparisons of the mutant alleles (−592A, −819T and −1082A) of three promoter polymorphisms with alternative wild alleles failed to reveal any statistical significance for both colorectal cancer and hepatocellular carcinoma (P > 0.05), and the likelihood of heterogeneity was low (I2 < 50%). For −592C > A polymorphism, a significant risk for colorectal cancer was identified when analysis was restricted to East Asians (odds ratio or OR = 1.41, 95% confidence interval or CI: 1.18–1.68, P < 0.001) and retrospective studies (OR = 1.23, 95% CI: 1.09–1.39, P = 0.001). As weighed by the Egger’s test and the fill-and-trim method, there was a low probability of publication bias for all studied polymorphisms. Our findings collectively suggest that the −592C > A polymorphism in IL-10 gene might be a susceptibility locus for colorectal cancer in East Asians.
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Affiliation(s)
- Yan-Hui Shi
- Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China
| | - Dong-Mei Zhao
- Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China
| | - Yue-Fei Wang
- Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China
| | - Xue Li
- Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China
| | - Man-Ru Ji
- Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China
| | - Dan-Na Jiang
- Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China
| | - Bai-Ping Xu
- Intervention Therapy Department, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China
| | - Li Zhou
- Central Laboratory, Qiqihar Medical University, Qiqihar, Heilongjiang, China
| | - Chang-Zhu Lu
- Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China
| | - Bin Wang
- Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China
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Aroucha DC, Carmo RF, Vasconcelos LRS, Lima RE, Mendonça TF, Arnez LE, Cavalcanti MDSM, Muniz MTC, Aroucha ML, Siqueira ER, Pereira LB, Moura P, Pereira LMMB, Coêlho MR. TNF-αandIL-10polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals. J Med Virol 2016; 88:1587-95. [DOI: 10.1002/jmv.24501] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/13/2016] [Indexed: 12/16/2022]
Affiliation(s)
- Dayse Celia Aroucha
- Instituto do Fígado de Pernambuco (IFP); Recife Brasil
- Faculdade de Ciências Médicas (FCM); Universidade de Pernambuco (UPE); Recife Brasil
| | - Rodrigo Feliciano Carmo
- Colegiado de Farmácia; Universidade Federal do Vale do São Francisco (UNIVASF); Petrolina Brasil
- Rede Nordeste de Biotecnologia (RENORBIO); Recife Brasil
| | - Luydson Richardson Silva Vasconcelos
- Instituto do Fígado de Pernambuco (IFP); Recife Brasil
- Departamento de Parasitologia, Centro de Pesquisas Aggeu Magalhães (CPqAM); Fundação Oswaldo Cruz (FIOCRUZ); Recife Brasil
| | - Raul Emidio Lima
- Instituto de Ciências Biológicas (ICB); Universidade de Pernambuco (UPE); Recife Brasil
| | | | - Lucia Elena Arnez
- Laboratório de Hanseníase, Instituto Oswaldo Cruz; Fundação Oswaldo Cruz (FIOCRUZ); Rio de Janeiro Brasil
| | | | | | - Marcilio Lins Aroucha
- Centro de Ciências da Saúde (CCS); Universidade Federal de Pernambuco (UFPE); Brazil
| | | | | | - Patrícia Moura
- Instituto de Ciências Biológicas (ICB); Universidade de Pernambuco (UPE); Recife Brasil
| | | | - Maria Rosangela Coêlho
- Setor de Virologia do Laboratório de Imunopatologia Keizo-Asami (LIKA); Universidade Federal de Pernambuco (UFPE); Brazil
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Niu W, Pang Q, Lin T, Wang Z, Zhang J, Tai M, Zhang L, Zhang L, Gu M, Liu C, Qu K. A Causal Role of Genetically Elevated Circulating Interleukin-10 in the Development of Digestive Cancers: Evidence from Mendelian Randomization Analysis Based on 29,307 Subjects. Medicine (Baltimore) 2016; 95:e2799. [PMID: 26886630 PMCID: PMC4998630 DOI: 10.1097/md.0000000000002799] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Recent studies have observed a high level of circulating interleukin-10 (IL-10) in patients with digestive cancers, yet whether elevated IL-10 is causally associated with digestive cancers so far remained unresolved. We therefore meta-analyzed available observational studies with Mendelian randomization method to explore this causal association by employing IL-10 gene 3 variants (-592C>A, -819C>T, and -1082A>G) as instruments. Data were available from 52 articles encompassing 29,307 subjects. Subgroup analysis by cancer type indicated that -1082A>G was associated with increased risk of gastric cancer (odds ratio [OR] = 1.19; 95% confidence interval [CI]: 1.05-1.35; P = 0.006), and the association was reinforced for intestinal type gastric cancer (OR = 1.26; 95%CI: 1.09-1.44; P = 0.001). By ethnicity, risk estimate for -1082G allele carriers was increased by 21% for digestive cancers in East Asians (95%CI: 1.05-1.40; P = 0.009). As for the genotype-phenotype association, carriers of -1082G allele had an overall 20.21 pg/mL higher IL-10 level than those with -1082AA genotype (P = 0.023). In further Mendelian randomization analysis, the predicted OR for 10 pg/mL increment in IL-10 was 1.14 (95%CI: 1.01-16.99) in gastric cancer. Our findings provided evidence for a causal role of genetically elevated IL-10 in the development of gastric cancer, especially in East Asians and for intestinal type gastric cancer.
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Affiliation(s)
- Wenquan Niu
- From the State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (WN); Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province (QP, TL, ZW, JZ, MT, LZ, CL, KQ); Department of Hepatobiliary Surgery, The Affiliated Hospital of Qinghai University, Xining, Qinghai (ZW, LZ); Department of Ultrasound Diagnostics, The First Affiliated Hospital of Xi'an Jiaotong University (MT); Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province (LZ); and Chinese Academy of Sciences Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics (MG), Chinese Academy of Sciences, Beijing, China
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Saxena R, Kaur J. Th1/Th2 cytokines and their genotypes as predictors of hepatitis B virus related hepatocellular carcinoma. World J Hepatol 2015; 7:1572-1580. [PMID: 26085916 PMCID: PMC4462695 DOI: 10.4254/wjh.v7.i11.1572] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Revised: 01/30/2015] [Accepted: 03/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC), the predominant type of primary liver cancer, is one of the most serious life-threatening malignancies, worldwide. In majority of the cases, HCC develops after prolonged and persistent chronic liver disease. hepatitis B virus (HBV) or HCV infection is prominent etiological factors, attributing to this condition. It has been well documented that HBV, being the inducer of chronic inflammation, is the main causative agent in causing HCC, particularly in Asian countries. The HBV infection leads to a wide range of clinical symptoms from carrier state to malignancy. Cytokines being immune-modulatory molecules, are the key mediators in the defense mechanism against viral infection. In this regard, this review will detail the substantial role of key Th1: interleukin 1 (IL-1), IL-2, IL-12, tumor necrosis factor-α, interferon-γ; Th2: IL-4, IL-10 and non Th1/Th2: IL-6, transforming growth factor-β1 cytokines genotypes in analyzing the variability in the clinical manifestations in an HBV-afflicted individual, which might finally, culminates into HCC. Since cytokine production is regulated genetically, the cytokine promoter region single-nucleotide polymorphisms induced changes, greatly affects the cytokine production, thus resulting into differential outcome of immune balance.
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Affiliation(s)
- Roli Saxena
- Roli Saxena, Jyotdeep Kaur, Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Jyotdeep Kaur
- Roli Saxena, Jyotdeep Kaur, Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
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Ren H, Zhang TT, Hu WL. A -819 C/T polymorphism in the interleukin-10 promoter is associated with persistent HBV infection, but -1082 A/G and -592A/C polymorphisms are not: a meta-analysis. Arch Virol 2015; 160:747-56. [PMID: 25583543 DOI: 10.1007/s00705-014-2317-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2014] [Accepted: 12/17/2014] [Indexed: 01/30/2023]
Abstract
Single-nucleotide polymorphisms (SNPs) in the interleukin-10 (IL10) gene promoter have been associated with persistent hepatitis B virus (HBV) infection. In particular, the -1082A/G, -819 C/T and -592 A/C polymorphisms have most often been implicated. We performed a meta-analysis of available data to determine the relative importance of these SNPs in persistent HBV infection. We searched available articles in NCBI PubMed, EMBASE, the Chinese National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CBM) and identified 24 studies for inclusion in our meta-analysis. Our results indicated that the presence of the IL10 -819 C allele significantly increased the risk for persistent HBV infection (CC+CT vs. TT: OR = 1.283, 95 % CI 1.023-1.610, P = 0.031; C vs. T: OR = 1.183, 95 % CI 1.001-1.399, P = 0.049). Meanwhile, the -1082A/-819T/-592A haplotype (OR = 0.751, 95 % CI 0.640-0.881, P = 0.000) and the -1082A/-819C/-592C haplotype (OR = 1.568, 95 % CI 1.304-1.884, P = 0.000) were observed to be significantly associated with HBV disease progression in Asians. In contrast, the IL10 -1082A/G and -592A/C polymorphisms were not associated with an increased susceptibility to or outcome of HBV infection. Our meta-analysis supports the growing body of evidence that the presence of the IL10 -819 C/T polymorphism is associated with persistent HBV infection and that the -1082A/-819T/-592A haplotype and the -1082A/-819C/-592C haplotype are associated with HBV disease progression in Asians.
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Affiliation(s)
- Hong Ren
- Department of Dermatology, Lianyungang Municipal First People Hospital, Lianyungang, 222002, Jiangsu, China
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15
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Talaat RM, Dondeti MF, El-Shenawy SZ, Khamiss OA. Association between IL-10 gene promoter polymorphism and hepatitis B viral infection in an Egyptian population. Biochem Genet 2014; 52:387-402. [PMID: 24838671 DOI: 10.1007/s10528-014-9655-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2013] [Accepted: 12/22/2013] [Indexed: 12/17/2022]
Abstract
Cytokines play critical roles in the pathogenesis of hepatitis B virus infection (HBV). This work was designed to study the effect of IL-10 gene polymorphisms (-1082G/A and -819C/T) on susceptibility of Egyptians to HBV. Genotyping was performed using single-stranded polymorphism-polymerase chain reaction in 118 Egyptian hepatitis B patients and 119 healthy controls, and IL-10 serum levels were measured using ELISA. The frequency of IL-10 -1082G/G was significantly higher in HBV patients than in healthy controls, and G/A and A/A were not significantly different between groups. The distribution of IL-10 -819 genotypes was not significantly different between the HBV and healthy control groups. Although AT was significantly different between controls and patients, the distribution of the other haplotypes was not. IL-10 levels were significantly lower among hepatitis B patients. Our data stress the importance of IL-10 gene polymorphism in HBV infection. Depending on our preliminary work, IL-10 -1082G/G may act as a host genetic factor in the susceptibility to HBV infection in Egyptians.
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Affiliation(s)
- Roba M Talaat
- Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City, Egypt,
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Tunçbilek S. Relationship between cytokine gene polymorphisms and chronic hepatitis B virus infection. World J Gastroenterol 2014; 20:6226-6235. [PMID: 24876743 PMCID: PMC4033460 DOI: 10.3748/wjg.v20.i20.6226] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2013] [Revised: 12/09/2013] [Accepted: 01/02/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is still a public health problem worldwide, being endemic in some parts of the world. It can lead to serious liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular cancer. The differences in host immune response can be one of the reasons for the various clinical presentations of HBV infection. Polymorphisms of genes encoding the proinflammatory and antiinflammatory cytokines, which are responsible for regulation of the immune response, can affect the clinical presentation of the infection. Particularly, the polymorphisms of the genes encoding cytokines such as interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, IL-28B, interferon-γ, tumor necrosis factor-α, tumor growth factor-β1, and regulatory molecules like vitamin D receptor and chemokine receptor 5 can be responsible for different clinical presentations of HBV infections. The genomic information about cytokines and other mediators can be important for determining high-risk people for developing chronic hepatitis or hepatocellular cancer and may be used to plan treatment and preventive approaches for these people. In this review, the current knowledge in the literature on the association between cytokine/regulatory molecule gene polymorphisms and clinical course of chronic HBV infection is summarized, and the clinical implementations and future prospects regarding this knowledge are discussed.
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Yu Z, Liu Q, Huang C, Wu M, Li G. The interleukin 10 -819C/T polymorphism and cancer risk: a HuGE review and meta-analysis of 73 studies including 15,942 cases and 22,336 controls. OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY 2013; 17:200-14. [PMID: 23574339 DOI: 10.1089/omi.2012.0089] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
The aim of the present work was to perform a meta-analysis to evaluate the association between the interleukin 10 (IL-10) -819C/T (rs1800871) polymorphism and cancer risk. A total of 73 studies, including 15,942 cancer cases and 22,336 controls, were identified in this meta-analysis. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the random-effects model. Overall, no significant association was identified between the IL-10 -819C/T polymorphism and cancer risk. In the subgroup analyses, the T allele and TT genotype were associated with a moderately reduced cancer risk in the Asian population (T allele vs. C allele: OR=0.93, 95%CI: 0.87, 0.99; TT vs. CC: OR=0.86, 95%CI: 0.76, 0.98; TT vs. CT/CC: OR=0.90, 95%CI: 0.82, 0.98). Individuals who were homozygous for the T allele (TT) were found to be associated with significantly reduced gastric cancer risk in the Asian population. The heterozygous variant (CT) and the dominant model (TT/CT vs. CC) were associated with an increased risk for cervical and ovarian cancer. However, the IL-10 -819C/T polymorphism was not significantly associated with breast cancer, colorectal cancer, lung cancer, hepatocellular carcinoma, prostate cancer, lymphoma, or melanoma. The depressed cancer risk of the TT genotype occurred in the studies of hospital-based case-control studies and the studies recruited less than 500 subjects, but no statistically significant results were found in the stratified analyses using genotyping method. The results suggest that the IL-10 -819TT genotype may be a protective factor for cancer in Asians, especially gastric cancer. In contrast, the CT genotype and the dominant model could be risk factors for cervical and ovarian cancer. The importance of stratifying by ethnicity, cancer type, study design, and sample size needs to be standardized in future studies, together with considering the association between the IL-10 -819C/T polymorphism and cancer risk. Furthermore, the linkage of -819C/T with other polymorphisms of the IL-10 gene may help explain the variability in findings.
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Affiliation(s)
- Zhibin Yu
- Cancer Research Institute, Disease Genome Research Center, Central South University, Changsha, Hunan, China
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Ding Q, Shi Y, Fan B, Fan Z, Ding L, Li F, Tu W, Jin X, Wang J. The interleukin-10 promoter polymorphism rs1800872 (-592C>A), contributes to cancer susceptibility: meta-analysis of 16,785 cases and 19,713 controls. PLoS One 2013; 8:e57246. [PMID: 23460834 PMCID: PMC3584114 DOI: 10.1371/journal.pone.0057246] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2012] [Accepted: 01/15/2013] [Indexed: 01/25/2023] Open
Abstract
Interleukin-10 (IL-10) is a multifunctional cytokine which participates in the development and progression of various malignant tumors. To date, a number of case–control studies were conducted to detect the association between IL-10-592C>A polymorphism and cancer risk in humans. However, the results of these studies on the association remain conflicting. In an effort to solve this controversy, we performed a meta-analysis based on 70 case–control studies from 65 articles, including 16 785 cancer cases and 19 713 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The overall results suggested that the variant homozygote genotype AA of the IL-10-592C>A polymorphism was associated with a moderately decreased risk of all cancer types (OR = 0.90, 95% CI = 0.83–0.98 for homozygote comparison, OR = 0.92, 95% CI = 0.86–0.98 for recessive model). In the stratified analyses, the risk remained for studies of smoking-related cancer, Asian populations and hospital-based studies. These results suggested that the IL-10-592C>A polymorphism might contribute to the cancer susceptibility, especially in smoking-related cancer, Asians and hospital-based studies. Further studies are needed to confirm the relationship.
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Affiliation(s)
- Qi Ding
- Department of Urology, The Changshu Hospital Affiliated to Soochow University, Changshu, China
| | - Ying Shi
- Department of Gastroenterology, The Changshu Hospital Affiliated to Soochow University, Changshu, China
| | - Bo Fan
- Department of Urology, The Changshu Hospital Affiliated to Soochow University, Changshu, China
| | - Zhijiang Fan
- Department of Urology, The Changshu Hospital Affiliated to Soochow University, Changshu, China
| | - Li Ding
- Department of Urology, The Changshu Hospital Affiliated to Soochow University, Changshu, China
| | - Feng Li
- Department of Urology, The Changshu Hospital Affiliated to Soochow University, Changshu, China
| | - Wenjian Tu
- Department of Urology, The Changshu Hospital Affiliated to Soochow University, Changshu, China
| | - Xiaohua Jin
- Department of Urology, The Changshu Hospital Affiliated to Soochow University, Changshu, China
| | - Jing Wang
- Department of Urology, The Changshu Hospital Affiliated to Soochow University, Changshu, China
- * E-mail:
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Yang H, He XX, Song QL, Chen M, Li J, Wang MY, Yu JL, Yao JJ, Liu LF, Lin JS. Association of Ephrin receptor A3 gene polymorphism with susceptibility to chronic severe hepatitis B. Hepatol Res 2012; 42:790-7. [PMID: 22780849 DOI: 10.1111/j.1872-034x.2012.00977.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM Previous research has suggested that Ephrin receptor A3 (EphA3) plays signaling roles in the processes of inflammation by regulating lymphocyte migration and proliferation. In this study, we investigated whether the EphA3 gene polymorphism was associated with disease progression of chronic hepatitis B virus (HBV) infection. METHODS The EphA3 variant rs9310117 was genotyped in 1245 unrelated Han Chinese HBV carriers including 800 cases and 445 controls. χ(2) test was used to examine the difference in allele frequencies and genotype distributions between groups. The association between the polymorphism and disease progression of HBV infection was conducted by unconditional logistic regression analysis. RESULTS Statistical analysis revealed that the genetic variant was significantly associated with the occurrence of chronic severe hepatitis B (CSHB). We observed that subjects bearing at least one T allele (C/T or T/T genotype) had a decreased susceptibility to chronic severe hepatitis B compared with those bearing C/C genotype (P = 0.003, odds ratio = 0.560; 95% confidence interval, 0.381-0.824, recessive model). Genotype C/T had also been confirmed to protect subjects from suffering chronic severe hepatitis B (P = 0.001, odds ratio = 0.498; 95% confidence interval, 0.330-0.752, additive model). CONCLUSION Our results suggest that the genetic alteration at EphA3 locus plays a role in the occurrence of chronic severe hepatitis B.
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Affiliation(s)
- Hong Yang
- Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Ramezani A, Banifazl M, Mamishi S, Sofian M, Eslamifar A, Aghakhani A. The influence of human leukocyte antigen and IL-10 gene polymorphisms on hepatitis B virus outcome. HEPATITIS MONTHLY 2012; 12:320-325. [PMID: 22783343 PMCID: PMC3389357 DOI: 10.5812/hepatmon.6094] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/17/2012] [Revised: 03/18/2012] [Accepted: 04/29/2012] [Indexed: 12/11/2022]
Abstract
CONTEXT The clinical outcome of hepatitis B virus (HBV) infection is variable, ranging from spontaneous recovery to an inactive carrier state, chronic hepatitis, occult HBV infection, liver cirrhosis, or hepatocellular carcinoma. EVIDENCE ACQUISITION This variable pattern and clinical outcomes of the infection were mainly determined by virological and host genetic factors. Since the most of host genetic factors associated with HBV infection have currently focused on human leukocyte antigen (HLA) associations and interleukin (IL)-10 gene polymorphisms, this review focuses on the recent progresses in these issues to provide prognostic markers for the outcome of HBV infection. RESULTS A study on serum levels of IL-10 in occult HBV infected patients reported that the higher level of IL-10 production may suppress function of the immune system against HBV in patients with occult HBV infection. IL-10 promoter polymorphism at position -592 is associated with susceptibility to occult HBV infection. CONCLUSIONS Findings of this study suggest that the host HLA polymorphism is an important factor in determining outcome of HBV infection but regarding IL-10 gene promoter polymorphisms, we are still have a long way to achieve a definite conclusion.
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Affiliation(s)
- Amitis Ramezani
- Clinical Research Department, Pasteur Institute of Iran, Tehran, IR Iran
- Pediatric Infectious Disease Research Center, Tehran University of Medical sciences, Tehran, IR Iran
| | - Mohammad Banifazl
- Iranian Society for Support of Patients with Infectious Disease, Tehran, IR Iran
| | - Setareh Mamishi
- Pediatric Infectious Disease Research Center, Tehran University of Medical sciences, Tehran, IR Iran
| | - Masoomeh Sofian
- TPIRC (Tuberculosis and Pediatric Infectious Research Center), Arak University of Medical Sciences, Arak, IR Iran
| | - Ali Eslamifar
- Clinical Research Department, Pasteur Institute of Iran, Tehran, IR Iran
| | - Arezoo Aghakhani
- Clinical Research Department, Pasteur Institute of Iran, Tehran, IR Iran
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Tomoda T, Nouso K, Sakai A, Ouchida M, Kobayashi S, Miyahara K, Onishi H, Nakamura S, Yamamoto K, Shimizu K. Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus: a case control study. J Gastroenterol Hepatol 2012; 27:797-804. [PMID: 22004425 DOI: 10.1111/j.1440-1746.2011.06948.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIM Chronic hepatitis C virus (HCV) infection is a well known risk factor for hepatocellular carcinoma (HCC). The aim of this study is to elucidate the genetic risk of development and recurrence of HCC in patients with HCV. METHODS A total of 468 patients with HCV, including 265 with HCC were enrolled. We genotyped 88 single nucleotide polymorphisms (SNPs) in 81 genes expected to influence hepatocarcinogenesis using the iPLEX assay. Risk of HCC was clarified by stratifying patients into risk groups based on the multiplied odds ratio (MOR) for SNPs associated with HCC, and the cumulative effects on the development and recurrence of HCC were analyzed. RESULTS Six SNPs associated with risk of HCC were identified (OR range: 0.29-1.76). These included novel SNPs for hepatocarcinogenesis with HCV CCND2 rs1049606, RAD23B rs1805329, CEP164 rs573455, and GRP78rs430397 in addition to the known SNPs MDM2 rs2279744 and ALDH2 rs671. MOR analysis revealed that the highest risk group exerted about a 19-fold higher relative OR compared with the lowest risk group (P = 1.08 × 10(-5)). Predicted 10-year HCC risk ranged from 1.7% to 96% depending on the risk group and the extent of fibrosis. Recurrence-free survival of radiofrequency ablation-treated HCC in the high risk group (n = 53) was lower than that of low risk group (n = 58, P = 0.038). CONCLUSION Single nucleotide polymorphisms of CCND2, RAD23B, GRP78, CEP164, MDM2, and ALDH2 genes were significantly associated with development and recurrence of HCC in Japanese patients with HCV.
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Affiliation(s)
- Takeshi Tomoda
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama city, Japan.
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Wei YG, Liu F, Li B, Chen X, Ma Y, Yan LN, Wen TF, Xu MQ, Wang WT, Yang JY. Interleukin-10 gene polymorphisms and hepatocellular carcinoma susceptibility: A meta-analysis. World J Gastroenterol 2011; 17:3941-7. [PMID: 22025883 PMCID: PMC3198024 DOI: 10.3748/wjg.v17.i34.3941] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2010] [Revised: 04/19/2011] [Accepted: 04/26/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the association between Interleukin-10 (IL-10) gene IL-10-1082 (G/A), IL-10-592(C/A), IL-10-819 (T/C) polymorphisms and hepatocellular carcinoma (HCC) susceptibility.
METHODS: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Database. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for IL-10 polymorphisms and HCC were calculated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate.
RESULTS: This meta-analysis included seven eligible studies, which included 1012 HCC cases and 2308 controls. Overall, IL-10-1082 G/A polymorphism was not associated with the risk of HCC (AA vs AG + GG, OR = 1.11, 95% CI = 0.90-1.37). When stratifying for ethnicity, the results were similar (Asian, OR = 1.12, 95% CI = 0.87-1.44; non-Asian, OR = 1.10, 95% CI = 0.75-1.60). In the overall analysis, the IL-10 polymorphism at position -592 (C/A) was identified as a genetic risk factor for HCC among Asians; patients carrying the IL-10-592*C allele had an increased risk of HCC (OR = 1.29, 95% CI = 1.12-1.49). No association was observed between the IL-10-819 T/C polymorphism and HCC susceptibility (TT vs TC + CC, OR = 1.02, 95% CI = 0.79-1.32).
CONCLUSION: This meta-analysis suggests that IL-10-592 A/C polymorphism may be associated with HCC among Asians. IL-10-1082 G/A and IL-10-819 T/C polymorphisms were not detected to be related to the risk for HCC.
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Li Y, Chang SC, Goldstein BY, Scheider WL, Cai L, You NCY, Tarleton HP, Ding B, Zhao J, Wu M, Jiang Q, Yu S, Rao J, Lu QY, Zhang ZF, Mu L. Green tea consumption, inflammation and the risk of primary hepatocellular carcinoma in a Chinese population. Cancer Epidemiol 2011; 35:362-8. [PMID: 21315679 PMCID: PMC3396119 DOI: 10.1016/j.canep.2011.01.005] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2010] [Revised: 12/27/2010] [Accepted: 01/11/2011] [Indexed: 12/22/2022]
Abstract
OBJECTIVE Green tea has been found to possess anti-inflammatory, anti-oxidative and anti-carcinogenic properties. The present study examines the association between green tea drinking and hepatocellular carcinoma (HCC) and its interactions with other risk or protective factors and single nucleotide polymorphisms (SNP) of inflammation and oxidative stress related genes. METHODS A population-based case-control study with 204 primary HCC cases and 415 healthy controls was conducted in Taixing, China. Epidemiological data were collected using a standard questionnaire. SNPs of genes of the inflammation and metabolic pathways were genotyped at the UCLA Molecular Epidemiology Laboratory. Logistic regression was performed to estimate adjusted odds ratios and 95% confidence intervals. RESULTS Longer duration and larger quantities of green tea consumption were inversely associated with primary HCC. Individuals who drank green tea longer than 30 years were at lowest risk (adjusted OR=0.44, 95% CI: 0.19-0.96) compared with non-drinkers. A strong interaction was observed between green tea drinking and alcohol consumption (adjusted OR for interaction=3.40, 95% CI: 1.26-9.16). Green tea drinking was also observed to have a potential effect modification on HBV/HCV infection, smoking and polymorphisms of inflammation related cytokines, especially for IL-10. CONCLUSION Green tea consumption may protect against development of primary HCC. Potential effect modifications of green tea on associations between primary HCC and alcohol drinking, HBV/HCV infection, and inflammation-related SNPs were suggested.
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Affiliation(s)
- Yanli Li
- Department of Social and Preventive Medicine, The State University of New York (SUNY) at Buffalo, NY, USA
| | - Shen-Chih Chang
- Department of Epidemiology, School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Binh Y. Goldstein
- Department of Epidemiology, School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - William L. Scheider
- Department of Social and Preventive Medicine, The State University of New York (SUNY) at Buffalo, NY, USA
| | - Lin Cai
- Department of Epidemiology, School of Public Health, Fujian Medical University, Fuzhou, Fijian, China
| | - Nai-Chieh Y. You
- Department of Epidemiology, School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Heather P. Tarleton
- Department of Epidemiology, School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Baoguo Ding
- Taixing City Center for Disease Control and Prevention (CDC), Taixing City, Jiangsu, China
| | - Jinkou Zhao
- Jiangsu Center for Disease Control and Prevention (CDC), Nanjing, Jiangsu, China
| | - Ming Wu
- Jiangsu Center for Disease Control and Prevention (CDC), Nanjing, Jiangsu, China
| | - Qingwu Jiang
- Fudan University School of Public Health, Shanghai, China
| | - Shunzhang Yu
- Fudan University School of Public Health, Shanghai, China
| | - Jianyu Rao
- Department of Pathology and Lab Med, School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Qing-Yi Lu
- Center for Human Nutrition, School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Zuo-Feng Zhang
- Department of Epidemiology, School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Lina Mu
- Department of Social and Preventive Medicine, The State University of New York (SUNY) at Buffalo, NY, USA
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Recent advances in the research of hepatitis B virus-related hepatocellular carcinoma: epidemiologic and molecular biological aspects. Adv Cancer Res 2011; 108:21-72. [PMID: 21034965 DOI: 10.1016/b978-0-12-380888-2.00002-9] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, and more than half of HCC patients are attributable to persistent hepatitis B virus (HBV) infections. The best and cheapest way to prevent HBV-related HCC is the implementation of universal hepatitis B vaccination program, by which the incidence rates of childhood HCC have been reduced in several countries, including Taiwan. However, there are still hundreds of millions of HBV carriers in the world that remain a global health challenge. In the past decade, several hepatitis B viral factors such as serum HBV DNA level, genotype, and naturally occurring mutants have already been identified to influence liver disease progression and HCC development in HBV carriers. Several easy-to-use scoring systems based on clinical and viral characteristics are developed to predict HCC risk in HBV carriers and may facilitate the communication between practicing physicians and patients in clinical practice. In addition, the role of nonviral factors in HBV-related HCC has also been increasingly recognized. On the basis of these emerging data, it is recommended that HBV carriers should be screened and monitored to identify those who have a higher risk of liver disease progression and require antiviral treatments. Regarding the molecular carcinogenesis of HCC development, despite some progress in the research of cell biology of HCC in the past decade, aberrant pathways involved in maintaining HCC phenotypes have not been completely elucidated yet. In the future, through comprehensive and integrated approaches to analyze the genomes of human HCC, novel target genes or pathways critically involved in hepatocarcinogenesis may hopefully be identified.
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Zhang TC, Pan FM, Zhang LZ, Gao YF, Zhang ZH, Gao J, Ge R, Mei Y, Shen BB, Duan ZH, Li X. A meta-analysis of the relation of polymorphism at sites -1082 and -592 of the IL-10 gene promoter with susceptibility and clearance to persistent hepatitis B virus infection in the Chinese population. Infection 2011; 39:21-27. [PMID: 21246248 DOI: 10.1007/s15010-010-0075-3] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2010] [Accepted: 12/13/2010] [Indexed: 12/15/2022]
Abstract
BACKGROUND Up to now, many publications about the Chinese population have evaluated the correlation between interleukin-10 (IL-10) -1082 and -592 polymorphisms and persistent hepatitis B virus (HBV) infection. However, the results remain inconclusive. In order to resolve this conflict, a meta-analysis was performed. METHODS Seven studies were included and dichotomous data are presented as the odds ratio (OR) with a 95% confidence interval (CI). RESULTS The results of our study suggest that carriers of the IL-10 -592A allele were more likely to clear HBV spontaneously in the Chinese pooled population (A vs. C: OR = 0.799, 95% CI = 0.678-0.941, P = 0.007; AC vs. AA: OR = 1.343, 95% CI = 1.017-1.684, P = 0.011; AA vs. AC + CC: OR = 0.736, 95% CI = 0.594-0.912; AA + AC vs. CC: OR = 0.588, 95% CI = 0.408-0.848, P = 0.004) and the IL-10 -1082A allele was associated with significantly reduced persistent HBV infection risk in Chinese (A vs. G: OR = 0.701, 95% CI = 0.494-0.996, P = 0.047; AA vs. GG + GA: OR = 0.684, 95% CI = 0.476-0.982, P = 0.040). CONCLUSIONS Persistent HBV infection susceptibility is associated with the gene polymorphism IL-10 -1082GA in the Chinese population and the clearance of HBV is associated with the gene polymorphism IL-10 -592CA in the Chinese population.
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Affiliation(s)
- T-C Zhang
- Department of Epidemiology and Biostatistics, Academy of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China
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Liu JJ, Gao YT, Du Z, Yang B, Jing X, Wang YJ, Wang FM, Liu T. Relationship between IL-10 gene promoter polymorphisms and outcome of hepatitis B virus infection. Shijie Huaren Xiaohua Zazhi 2010; 18:1656. [DOI: 10.11569/wcjd.v18.i16.1656] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Wu JF, Wu TC, Chen CH, Ni YH, Chen HL, Hsu HY, Chang MH. Serum levels of interleukin-10 and interleukin-12 predict early, spontaneous hepatitis B virus e antigen seroconversion. Gastroenterology 2010; 138:165-72.e1-3. [PMID: 19782084 DOI: 10.1053/j.gastro.2009.09.018] [Citation(s) in RCA: 96] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2009] [Revised: 09/10/2009] [Accepted: 09/16/2009] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS This prospective cohort study aimed to determine the effect of cytokines on spontaneous hepatitis B e antigen (HBeAg) seroconversion in patients with chronic hepatitis B virus (HBV) infection. METHODS Polymorphisms in interleukin (IL)-2, IL-4, IL-10, IL-12beta, and interferon-gamma were evaluated in 288 HBeAg-positive chronic HBV patients (median initial age, 8.6 years; median follow-up duration, 19.3 years). Serum cytokine levels were determined in 154 subjects (53.5%) before and after HBeAg seroconversion by enzyme-linked immunosorbent assay analysis. Peripheral blood mononuclear cells (PBMC) were isolated from patients with chronic HBV infection and stimulated with HBV core antigen (HBcAg); data on cytokine genotypes and phenotypes were compared. RESULTS The IL-10-1082 G/G and IL-12beta -10993C/G genotypes predicted early, spontaneous HBeAg seroconversion (hazard ratio [HRs] = 3.43 and 1.54; P < .001, and P < .004, respectively), based on multivariate survival analysis. The IL-10 -1082 G/G genotype was associated with higher serum levels of IL-10 and IL-12; the IL-12beta -10993 C/G genotype predicted higher levels of IL-12 secretion by PBMC after in vitro HBcAg stimulation (P = .04). Higher levels of serum IL-12 (>45 pg/mL) and IL-10 (>70 pg/mL) were associated with early, spontaneous HBeAg seroconversion (HR = 1.52 and 1.48; P = .04 and .02, respectively). CONCLUSIONS The IL-10-1082 G/G is associated with higher serum IL-10 and IL-12 levels and IL-12beta -10993 C/G is associated with increased secretion of IL-12 in response to HBcAg stimulation of PBMC. Both genotypes are associated with early, spontaneous HBeAg seroconversion. Higher serum levels of IL-10 and IL-12 in HBeAg-positive patients are correlated with early, spontaneous HBeAg seroconversion.
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Affiliation(s)
- Jia-Feng Wu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
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Hold GL, Untiveros P, Saunders KA, El-Omar EM. Role of host genetics in fibrosis. FIBROGENESIS & TISSUE REPAIR 2009; 2:6. [PMID: 19961576 PMCID: PMC2796989 DOI: 10.1186/1755-1536-2-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/22/2009] [Accepted: 12/04/2009] [Indexed: 01/18/2023]
Abstract
Fibrosis can occur in tissues in response to a variety of stimuli. Following tissue injury, cells undergo transformation or activation from a quiescent to an activated state resulting in tissue remodelling. The fibrogenic process creates a tissue environment that allows inflammatory and matrix-producing cells to invade and proliferate. While this process is important for normal wound healing, chronicity can lead to impaired tissue structure and function. This review examines the major factors involved in transforming or activating tissues towards fibrosis. The role of genetic variation within individuals affected by fibrosis has not been well described and it is in this context that we have examined the mediators of remodelling, including transforming growth factor-beta, T helper 2 cytokines and matrix metalloproteinases. Finally we examine the role of Toll-like receptors in fibrosis. The inflammatory phenotype that precedes fibrosis has been associated with Toll-like receptor activation. This is particularly important when considering gastrointestinal and hepatic disease, where inappropriate Toll-like receptor signalling, in response to the local microbe-rich environment, is thought to play an important role.
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Affiliation(s)
- Georgina L Hold
- Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
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Yan Z, Tan W, Zhao W, Dan Y, Wang X, Mao Q, Wang Y, Deng G. Regulatory polymorphisms in the IL-10 gene promoter and HBV-related acute liver failure in the Chinese population. J Viral Hepat 2009; 16:775-83. [PMID: 19413695 DOI: 10.1111/j.1365-2893.2009.01139.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Recent reports indicated that high levels of interleukin 10 (IL-10) contribute to the monocytes paralysis and poor clinical outcome in acute liver failure (ALF). Polymorphisms in the promoter region of IL-10 affect IL-10 production and confer susceptibility to inflammatory diseases. The aim of this study was to determine the possible association of the three polymorphisms (A-1082G, T-819C, A-592C) in the IL-10 gene promoter with the susceptibility to hepatitis B virus (HBV)-related ALF in a Chinese population. The IL-10 gene promoter polymorphisms were genotyped in 414 unrelated healthy blood donors, 367 asymptomatic HBV carriers and 345 HBV-related ALF patients. Functional analyses were conducted to verify the biological significances of the associated genetic variations. The allele frequencies of IL-10-592C and -819C were significantly higher in HBV-related ALF patients than in blood donors and asymptomatic HBV carriers. Logistic regression analysis and stratification analysis with adjustment for age and sex indicated that the polymorphisms of A-592C and T-819C were associated with susceptibility to HBV-related ALF (P = 6.9 x 10(-7)), and the -1082A-819C-592C haplotype in the IL-10 gene promoter were associated with an increased susceptibility to ALF in HBV carriers (dominant model, P = 0.0002, odds ratio = 1.60, 95% CI 1.25-2.07). Functional analyses showed that the A-592C polymorphism is a nuclear proteins binding site, and the disease susceptible -592C allele had a higher transcription activity compared with -592A allele. This study emphasizes the importance of IL-10 in the pathophysiology of HBV-related ALF on the population level.
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Affiliation(s)
- Z Yan
- Department of Infectious Diseases, Southwest Hospital, The Third Military Medical University, Chongqing, China
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Maley SN, Schwartz SM, Johnson LG, Malkki M, Du Q, Daling JR, Li SS, Zhao LP, Petersdorf EW, Madeleine MM. Genetic variation in CXCL12 and risk of cervical carcinoma: a population-based case-control study. Int J Immunogenet 2009; 36:367-75. [PMID: 19788587 DOI: 10.1111/j.1744-313x.2009.00877.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
CXCL12 provides a chemotactic signal-directing leucocyte migration and regulates metastatic behaviour of tumour cells. We conducted a population-based case-control study to test the hypothesis that common genetic variation in CXCL12 individual single nucleotide polymorphism (SNP) alleles and haplotypes] is associated with the risk of cervical carcinoma. Cases (n = 917) were residents of western Washington State diagnosed with invasive squamous cell cervical carcinoma (SCC), invasive adenocarcinoma or adenosquamous carcinoma, or adenocarcinoma in situ of the cervix. Control participants (n = 849) were identified from the source population by random digit telephone dialling and frequency matched to cases on county and age. Nine CXCL12 tagSNPs chosen from the SeattleSNPs database were genotyped. The minor allele of intronic SNP rs266085 was inversely associated with cervical cancer under a recessive genetic effects model (OR = 0.74, 95% CI: 0.56-0.98). Among the ten common haplotypes inferred from the nine tagSNPs, one haplotype defined by minor alleles at 5'-flanking SNP rs17885289 and rs266085, and common alleles at the other seven SNPs occurred among 7.8% of cases and 10.6% of controls (dominant model OR = 0.72, 95% CI: 0.56-0.93; recessive model OR = 0.35, 95% CI: 0.12-0.97; and log-additive model OR = 0.72, 95% CI: 0.57-0.90). A stepwise procedure identified rs17885289, rs266085 and 3'-untranslated region (UTR) SNP rs266093 as the most parsimonious subset of SNPs necessary to define the haplotype inversely associated with cervical cancer risk in our study. A 3'-UTR SNP, rs1801157, previously found to be related to HIV pathogenesis, was not associated with cervical cancer risk. Further population-based studies are warranted to confirm these associations between genetic variation in CXCL12 and cervical cancer risk.
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Affiliation(s)
- S N Maley
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA
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Erdogan M, Karadeniz M, Ozbek M, Ozgen AG, Berdeli A. Interleukin-10 gene polymorphism in patients with papillary thyroid cancer in Turkish population. J Endocrinol Invest 2008; 31:750-4. [PMID: 18997484 DOI: 10.1007/bf03349252] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that plays a crucial role in the regulation of the immune system. Chronic inflammation has been reported to be a risk factor for thyroid neoplasia. The propensity to mount an inflammatory response is modified by germ line variation in cytokine and other inflammation-related genes. We hypothesized that a proinflammatory genotype would be positively associated with thyroid cancer. We aimed to evaluate the relation between the genotypic and allelic frequencies of the IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) polymorphisms, and their association with the risk of developing papillary thyroid cancer (PTC) in the Turkish population. RESEARCH DESIGN AND METHODS Forty-two patients with PTC and 113 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for IL-10 gene polymorphism was performed using PCR-restriction fragment length polymorphism method. RESULTS Statistically significant difference IL-10(-1082 G/A) gene polymorphism was determined between 2 (PTC and control) groups. No difference was determined with respect to IL-10(-592 A/C) and IL-10(-819 C/T) gene polymorphisms, and IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) allele frequencies of participating between the control group and the patients with PTC (p>0.05). CONCLUSIONS The polymorphism of IL-10(-1082 G/A) gene was significantly associated with the occurrence of PTC. Such studies will contribute significantly to our understanding of the biological role of IL-10(-1082 G/A) gene polymorphism in PTC development. In conclusion, IL-10(-1082 G/A) gene polymorphism may affect the survival of papillary thyroid carcinoma.
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Affiliation(s)
- M Erdogan
- Department of Endocrinology and Metabolism Disease, Ege University Medical School, Bornova, Izmir, Turkey.
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Zeng Z, Guan L, An P, Sun S, O'Brien SJ, Winkler CA, the HBV study consortium. A population-based study to investigate host genetic factors associated with hepatitis B infection and pathogenesis in the Chinese population. BMC Infect Dis 2008; 8:1. [PMID: 18171470 PMCID: PMC2238742 DOI: 10.1186/1471-2334-8-1] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2007] [Accepted: 01/02/2008] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is a significant public health problem that may lead to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Approximately 30% of the world's population has been infected with HBV and approximately 350 million (5-6%) are persistent carriers. More than 120 million Chinese are infected with HBV. The role of host genetic factors and their interactions with environmental factors leading to chronic HBV infection and its complications are not well understood. We believe that a better understanding of these factors and interactions will lead to more effective diagnostic and therapeutic options. METHODS/DESIGN This is a population-based, case-control study protocol to enroll 2200 Han Chinese from medical centers in northern and western China. Adult subjects in the following groups are being enrolled: healthy donors (n = 200), HBV infected persons achieving virus clearance (n = 400), asymptomatic HBV persistent carriers (n = 400), chronic hepatitis B cases (n = 400), decompensated liver cirrhosis with HBV infection cases (n = 400), and hepatocellular carcinoma with HBV infection cases (n = 400). In addition, for haplotype inference and quality control of sample handling and genotyping results, children of 1000 cases will be asked to provide a buccal sample for DNA extraction. With the exception of adult patients presenting with liver cirrhosis or HCC, all other cases and controls will be 40 years or older at enrollment. A questionnaire is being administered to capture dietary and environmental risk factors. Both candidate-gene and genome-wide association approaches will be used to assess the role of single genetic factors and higher order interactions with other genetic or environmental factors in HBV diseases. CONCLUSION This study is designed and powered to detect single gene effects as well as gene-gene and environmental-gene interactions. The identification of allelic polymorphisms in genes involved in the pathway leading to chronic viral infection, liver cirrhosis and, ultimately, hepatocellular carcinoma would provide insights to those factors leading to HBV replication, liver inflammation, fibrosis, and the carcinogenic process. An understanding of the contribution of host genetic factors and their interactions may inform public health policy, improve diagnostics and clinical management, and provide targets for drug development.
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Affiliation(s)
- Zheng Zeng
- Department of Infectious Diseases, Peking University First Hospital, Beijing, P.R.China
| | - Li Guan
- SAIC/Laboratory of Genomic Diversity, National Cancer Institute-Frederick, National Institutes of Health, Frederick, USA
| | - Ping An
- SAIC/Laboratory of Genomic Diversity, National Cancer Institute-Frederick, National Institutes of Health, Frederick, USA
| | - Shan Sun
- Conservation International (CI) China program, Beijing, P.R.China
| | - Stephen J O'Brien
- Laboratory of Genomic Diversity, National Cancer Institute-Frederick, National Institutes of Health, Frederick, USA
| | - Cheryl A Winkler
- SAIC/Laboratory of Genomic Diversity, National Cancer Institute-Frederick, National Institutes of Health, Frederick, USA
| | - the HBV study consortium
- HBV study consortium: Department of Infectious Diseases, Peking University First Hospital, Beijing, P.R.China (Zheng Zeng, Yanyan Yu, Xiaoyuan Xu, Haiying Lu); Institute of Liver Diseases Research, Beijing Military General Hospital, Beijing, P.R.China (Darong Hu); Beijing Ditan Hospital (Rongbing Wang, Yifan Chen); Department of Surgery, Beijing Institute of Tumor Prevention and Therapy, Beijing, P.R.China (Cunyi Hao); Department of Infectious Diseases, Shanxi Medical University, Taiyuan, P.R.China (Heping Zhou); Department of Infectious Diseases, Qinhuangdao No. 3 Hospital, Qinhuangdao, P.R.China (Zhonghou Han); Department of Surgery, Inner Mongolia Medical College, Hohhot, P.R.China (Lidao Bao, Xiping Zhang); Department of Infectious Diseases, Xuzhou No. 3 Hospital, Xuzhou, P.R.China (Dasi Guo); Department of Infectious Diseases, Xinjian Medical University, Urumoqi, P.R.China (Yaoxin Zhang); Department of Infectious Diseases, the Second Affiliate Hospital of China Medical University, Shenyang, P.R.China (Xiaoguang Dou); Institute of Liver Diseases Research, Peking University Second Hospital, Beijing, P.R.China (Lai Wei); Department of Surgery, Peking Union Medical College, Beijing, P.R.China (Jingan Rui, Qiang Qu)
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Wei YS, Kuang XH, Zhu YH, Liang WB, Yang ZH, Tai SH, Zhao Y, Zhang L. Interleukin-10 gene promoter polymorphisms and the risk of nasopharyngeal carcinoma. TISSUE ANTIGENS 2007; 70:12-17. [PMID: 17559576 DOI: 10.1111/j.1399-0039.2007.00806.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Genetic factors are known to be important in the development of nasopharyngeal carcinoma (NPC). Interleukin-10 (IL-10) is an immunosuppressive cytokine which may facilitate development of cancer by supporting tumor escape from the immune response. Interindividual variations in IL-10 production were genetically contributed to polymorphisms within IL-10 promoter region. The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) at positions -1082 (A/G), -819 (T/C) and -592 (A/C) in the IL-10 gene promoter were involved in predisposing an individual to NPC. One hundred and ninety-eight patients with NPC and 210 age- and sex-matched controls, genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. There were significantly differences in the genotype and allele distribution of -1082 A/G polymorphism of the IL-10 gene among cases and controls. The -1082 AG and GG genotypes were associated with a significantly increased risk of NPC as compared with the -1082 AA genotypes. Haplotype analysis showed that the homozygosity of the GCC haplotype (defined by SNPs at positions -1082, -819 and -592) of IL-10 gene conveys the highest risk for NPC compared with the homozygosity for the ATA haplotype. This study shows for the first time an association between IL-10 gene promoter -1082 A/G polymorphism and its haplotype may contribute to genetic susceptibility to NPC in a Chinese population.
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Affiliation(s)
- Y-S Wei
- Department of Immunology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, Sichuan, China
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You J, Zhuang L, Ma YL, Tang BZ. Research advances in the imbalance of helper T lymphocyte subpopulations and cytokine network in patients with chronic hepatitis B. Shijie Huaren Xiaohua Zazhi 2007; 15:791-799. [DOI: 10.11569/wcjd.v15.i8.791] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Helper T (Th) lymphocytes, important immune regulating cells of organism, could be divided into four functional subsets, Th0, Th1, Th2, Th3, on the basis of the immunoregulatory cytokines that these clones produced. Most of the current work in this field is exploratory and focuses on Th1 and Th2 subsets. Th1 cells secrete interferon-γ (IFN-γ), interkeukin-2 (IL-2) and tumor necrosis factor-β and are principally involved in cell-mediated immunity. They play an important role in the protection against intracellular pathogens, including a variety of viruses. Th2 cells secret interleukin-4 (IL-4), IL-5, IL-6 and IL-10 and regulate the humoral immune response. Th0 cells are naive Th cells, secreting Th1/Th2 phenotype cytokines at low levels. However, Th3 cells, which secrete active transforming growth factor-β, exert a negative immunoregulatory action on the immune response. The cross-regulatory properties of Th1 and Th2 subset cells and relevant cytokines network are very important to maintain normal immunity of organisms. HBV can destroy the balance of Th lymphocytes and cytokines network. The imbalance of pro-inflammatory Th1 and anti-inflammatory Th2 cytokine production play an important role in the immunopathogenesis of hepatitis B virus infection and alter chronic liver disease development, progression and outcome.
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