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Identification of immune-related mechanisms of cetuximab induced skin toxicity in colorectal cancer patients. PLoS One 2022; 17:e0276497. [PMID: 36269747 PMCID: PMC9586384 DOI: 10.1371/journal.pone.0276497] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 10/08/2022] [Indexed: 11/07/2022] Open
Abstract
Skin rash is a well-known predictive marker of the response to cetuximab (Cmab) in metastatic colorectal cancer (mCRC). However, the mechanism of skin rash development is not well understood. Following exposure to EGFR-targeted therapies, changes in IL-8 levels have been reported. The aim of this study was to evaluate the association between skin rash and inflammatory cytokine levels, including IL-8. Between 2014 and 2017, we prospectively enrolled 38 mCRC patients who underwent chemotherapy with either Cmab or bevacizumab (Bmab) at two hospitals. We performed multiplex cytokine ELISA with 20 inflammatory cytokines including E-selectin, GM-CSF, IFN-alpha, IFN-γ, IL-1 alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IP-10, MCP-1, MIP-1 alpha, MIP-1 beta, P-selectin, sICAM-1, and TNF-alpha at baseline before cycle 1, 24 h after cycle 1, before cycle 2 (= 14 d), and before cycle 3 (= 28 d). Cytokine levels were compared using ANOVA after log-transformation. IL-8 genotypes in 30 patients treated with Cmab were determined using the polymerase chain reaction restriction fragment length polymorphism technique. Depending on the RAS mutational status, 30 and eight patients were treated with Cmab and Bmab-based chemotherapy, respectively. Skin rash developed in 23 (76.6%) of the 30 patients treated with Cmab plus FOLFIRI, after cycle 1. Only the mean log-transformed serum IL-8 level in patients with skin toxicity was statistically lower (2.83 ± 0.15) than in patients who did not experience skin toxicity (3.65 ± 0.27) and received Bmab (3.10 ± 0.26) (ANOVA test, p value = 0.0341). In addition, IL-8 polymorphism did not affect IL-8 levels, skin toxicity, or tumor response in Cmab treated patients. This study suggests that the inflammatory cytokine levels might be affected by Cmab exposure and are associated with the development of skin rash in mCRC patients. Further studies are warranted to evaluate this interaction in Cmab treated patients.
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Yan LR, Lv Z, Jing JJ, Yuan Y, Xu Q. Single nucleotide polymorphisms of whole genes and atrophic gastritis susceptibility:a systematic review and meta-analysis. Gene 2021; 782:145543. [PMID: 33667608 DOI: 10.1016/j.gene.2021.145543] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/29/2021] [Accepted: 02/18/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Atrophic gastritis (AG) is one of the important precancerous lesions of gastric cancer. Single nucleotide polymorphisms (SNPs) are closely related to AG susceptibility. However, the research conclusions on the predictive potential of SNPs are inconsistent. The study aims to retrospect the association between SNPs of whole genes and AG risk by meta-analysis. MATERIALS AND METHODS Up to April 29, 2020, a systematic literature search for the relationship of SNPs with AG susceptibility was performed utilizing PubMed, Web of Science and Chinese National Knowledge Infrastructure. The overall and stratified meta-analyses on extracted data were conducted by Stata11.2. RESULTS 33 case-control studies were enrolled containing 9951 AG patients and 17,252 healthy controls, and 17 SNPs in 12 different genes were systematically reviewed. The results indicated that 12 genes could be categorized based on their functions, including immune response, cell proliferation and apoptosis, and DNA damage repair. For the SNPs in immune response-related genes, the C allele of TLR1 rs4833095 T/C increased AG risk to 1.21-fold and the recessive model of TLR4 rs11536878 in the TLR gene family decreased AG susceptibility to 0.48-fold. The variant alleles of IL-10 rs1800871 (OR = 1.21) and IL-8 rs4073 (OR = 1.22) in the IL gene family were positively associated with AG risk. PSCA rs2294008 enhanced AG risk in all genetic models. SNPs associated with AG susceptibility were mainly focused on immune response-related genes. CONCLUSION These SNPs related to immune response could influence on AG risk and have potential to be AG predictive biomarkers. It is worth noting that the number of studies for each SNPs were insufficient due to the limited published researches and updated meta-analysis needs to be performed based on extensive relevant studies for more reliable results.
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Affiliation(s)
- Li-Rong Yan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang 110001, China
| | - Zhi Lv
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang 110001, China
| | - Jing-Jing Jing
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang 110001, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang 110001, China.
| | - Qian Xu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang 110001, China.
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Hirbod-Mobarakeh A, Shabani M, Keshavarz-Fathi M, Delavari F, Amirzargar AA, Nikbin B, Kutikhin A, Rezaei N. Immunogenetics of Cancer. CANCER IMMUNOLOGY 2020:417-478. [DOI: 10.1007/978-3-030-30845-2_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Association between HLA-DP Gene Polymorphisms and Cervical Cancer Risk: A Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2018; 2018:7301595. [PMID: 30009173 PMCID: PMC6020657 DOI: 10.1155/2018/7301595] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Revised: 04/09/2018] [Accepted: 04/30/2018] [Indexed: 01/21/2023]
Abstract
Objective. We aimed to derive a more precise estimation of the associations between human leukocyte antigens DP (HLA-DP) gene polymorphisms and cervical cancer risk by meta-analysis. Methods. PubMed, EMBASE, ScienceDirect, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases were systematically searched to identify studies investigating the relationship between HLA-DP gene polymorphisms and cervical cancer. The associations between them were evaluated by pooled OR and 95% CI. Results. A total of 11 studies including 5008 cases and 9322 controls with 11 HLA-DP alleles were included in the current meta-analysis. Results. The results showed that HLA-DPB1⁎03:01 was significantly associated with an increased risk of cervical cancer (OR=1.252, 95%CI: 1.116-1.403, Pz=0.001), while HLA-DPB1⁎04:02 and HLA-DP rs3117027 G allele were significantly associated with a decreased risk of cervical cancer (OR=0.744, 95%CI: 0.652-0.848, Pz=0.001; OR=0.790, 95%CI: 0.745-0.837, Pz=0.001), and HLA-DP rs9277535 G allele was significantly associated with a decreased risk of cervical cancer in Asia (OR=0.802, 95%CI: 0.753-0.855, Pz=0.001). Subgroup analyses based on race system showed that HLA-DPB1⁎13:01 was significantly associated with an increased risk of cervical cancer in Asia (OR=1.834, 95%CI: 1.107-3.039, Pz=0.019). No significant association was established for the HLA-DP following alleles: DPB1⁎02:01, DPB1⁎02:02, DPB1⁎04:01, DPB1⁎05:01, rs4282438, and rs3077. Conclusion. HLA-DP gene polymorphisms (HLA-DPB1⁎03:01, DPB1⁎04:02, DPB1⁎13:01, rs9277535, and rs3117027) were significantly associated with cervical cancer.
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López-Cortés A, Guerrero S, Redal MA, Alvarado AT, Quiñones LA. State of Art of Cancer Pharmacogenomics in Latin American Populations. Int J Mol Sci 2017; 18:E639. [PMID: 28545225 PMCID: PMC5485925 DOI: 10.3390/ijms18060639] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2016] [Revised: 03/07/2017] [Accepted: 03/10/2017] [Indexed: 12/22/2022] Open
Abstract
Over the past decades, several studies have shown that tumor-related somatic and germline alterations predicts tumor prognosis, drug response and toxicity. Latin American populations present a vast geno-phenotypic diversity due to the great interethnic and interracial mixing. This genetic flow leads to the appearance of complex characteristics that allow individuals to adapt to endemic environments, such as high altitude or extreme tropical weather. These genetic changes, most of them subtle and unexplored, could establish a mutational profile to develop new pharmacogenomic therapies specific for Latin American populations. In this review, we present the current status of research on somatic and germline alterations in Latin America compared to those found in Caucasian and Asian populations.
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Affiliation(s)
- Andrés López-Cortés
- Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad Tecnológica Equinoccial, Quito 170527, Ecuador.
| | - Santiago Guerrero
- Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Universitat Pompeu Fabra (UPF), Barcelona 08003, Spain.
| | - María Ana Redal
- Instituto de Fisiopatología y Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Centro de Diagnóstico Molecular, MEDgenomica, Buenos Aires 1000-1499, Argentina.
| | - Angel Tito Alvarado
- Unidad de Bioequivalencia y Medicina Personalizada, Facultad de Medicina, Universidad de San Martín de Porres, Lima 12, Peru.
| | - Luis Abel Quiñones
- Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile, Santiago 70111, Chile.
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Yao Y, Zhu L, Li J, Jin Y, He L. Association of HLA-DRB1 Gene Polymorphism with Risk of Asthma: A Meta-Analysis. Med Sci Monit Basic Res 2016; 22:80-6. [PMID: 27503745 PMCID: PMC4989996 DOI: 10.12659/msmbr.900193] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Accepted: 07/13/2016] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The relationship between HLA-DRB1 alleles and asthma is controversial. The purpose of this study was to evaluate the relationship between HLA-DRB1 alleles and risk of asthma. MATERIAL AND METHODS We searched PubMed, Chinese National Knowledge Infrastructure (CNKI), Wan Fang (Chinese) database, and Chinese Biomedical Medical databases (CBM) to find studies on the relationship between HLA-DRB1 alleles and risk of asthma. We calculated the pooled odds ratio (OR) and 95% confidence interval (CI) using STATA 12.0. Finally, a total of 24 studies were included in this meta-analysis. RESULTS The results revealed that DRB1*03 was positively associated with risk of asthma (OR=1.51, 95%CI=1.27-1.80), and DRB1*15 was negatively associated with risk of asthma (OR=0.63, 95%CI=0.42-0.93), but no association was found in other HLA-DRB1 alleles. Subgroup analysis by age revealed that DRB1*03, DRB1*04, DRB1*09, and DRB1*15 were associated with asthma in children. Subgroup analysis by ethnicity showed that DRB1*03 and DRB1*15 were associated with asthma in whites, and DRB1*07 and DRB1*14 were associated with asthma in Asians. CONCLUSIONS This results of this meta-analysis suggest that HLA-DRB1 alleles are associated with asthma.
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Kumar S, Kumari N, Mittal RD, Mohindra S, Ghoshal UC. Association between pro-(IL-8) and anti-inflammatory (IL-10) cytokine variants and their serum levels and H. pylori-related gastric carcinogenesis in northern India. Meta Gene 2015; 6:9-16. [PMID: 26380815 PMCID: PMC4556814 DOI: 10.1016/j.mgene.2015.07.008] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Revised: 06/22/2015] [Accepted: 07/19/2015] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Interleukin (IL)-8 -251 T/A and IL-10 (-1082 G/A and -819/592 C/T) polymorphisms and their expression may influence gastritis, atrophy, intestinal metaplasia (IM) and gastric cancer (GC) following H. pylori infection. METHODS Genotyping of these genes was performed (ASO-PCR) in 200, 182 and 250 with GC, functional dyspepsia (FD) and healthy controls (HC), respectively. Anti-H. pylori IgG-antibody was tested in all and serums IL-8 and IL-10 were measured randomly in 60 subjects of each group by ELISA. RESULTS Pro-(IL-8)-251 AA and anti-inflammatory (IL-10)-819 TT genotypes were commoner among GC than HC (p = 0.023, OR 1.86 [1.09-3.2] and p = 0.020, OR 2.0 [1.11-3.5]) but comparable with FD. IL-8 AA and IL-10-819 T allele carriage was also commoner in H. pylori-infected GC than HC (p = 0.011, OR 2.47 [1.23-5.0], and p = 0.018, OR 2.3 (1.16-4.59). IL-10-1082 G/A genotype and haplotypes (ACC, GCC, ATA and GTA) were comparable in all groups. Circulating levels of IL-8 and IL-10 were higher among GC than HC but comparable to FD (IL-8; 57.64 [6.44-319.46] vs. 54.35 [4.24-318.96] and 26.33 [4.67-304.54] pg/ml, p < 0.001 and IL-10; 15.47 [1.01-270.87] vs. 12.28 [0.96-64.88] and 3.79 [1.24-56.65], p < 0.001 for GC vs. HC). IL-8/IL-10 ratio was lower among GC than HC but higher than FD (3.7 [0.18-38.41] vs. 6.59 [0.98-130.2], p < 0.001 and 4.22 [0.15-61.4], p < 0.01). Circulating levels of IL-8, IL-10 and IL-8/lL-10 ratios were different among H. pylori-infected and non-infected GC than HC (p < 0.001, p < 0.001 and p < 0.01). CONCLUSIONS Pro-(IL-8)-251 T/A and anti-inflammatory (IL-10)-819 C/T gene polymorphisms and their circulating levels may play a role in H. pylori-associated gastric carcinogenesis in northern India.
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Key Words
- ARMS-PCR, Amplification refractory mutation system-polymerase chain reaction
- EDTA, Ethylene diamine tetra acetic acid
- EIU, Enzyme immune unit
- ELISA, Enzyme linked immune-sorbent assay
- FD, Functional dyspepsia
- Functional dyspepsia
- GC, Gastric cancer
- Gastric cancer
- Genetic polymorphism
- H. pylori, Helicobacter pylori
- HC, Healthy control
- Helicobacter pylori
- IL, Interleukin
- IM, Intestinal metaplasia
- Interleukin
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Affiliation(s)
- Sushil Kumar
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Niraj Kumari
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Rama Devi Mittal
- Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Samir Mohindra
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
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Meta-Analysis of the Relationship between XRCC1-Arg399Gln and Arg280His Polymorphisms and the Risk of Prostate Cancer. Sci Rep 2015; 5:9905. [PMID: 25927275 PMCID: PMC4415422 DOI: 10.1038/srep09905] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2014] [Accepted: 03/18/2015] [Indexed: 12/13/2022] Open
Abstract
Prostate cancer is one of the most common noncutaneous malignancies in Western countries. Because there has been a debate regarding the relationship between the XRCC1-Arg399Gln and Arg280His polymorphisms and prostate cancer risk, we therefore performed this meta-analysis. The electronic databases PubMed, EMBASE, and Medline were searched prior to October 1, 2014. An odds ratio and 95% confidence interval were used to calculate association. Heterogeneity was tested by both a chi-square test and I statistic. Funnel plots and Egger's test were used to assess publication bias. All statistical analyses were performed using STATA 12.0 software. A significant association between the XRCC1-Arg399Gln polymorphism and prostate cancer risk was found under a homozygote model and a recessive model. A significant association between XRCC1-Arg280His and prostate cancer risk was found under a heterozygote model and a dominant model [corrected]. Overall, the results of this meta-analysis show that the XRCC1-Arg399Gln polymorphism may be associated with an increased risk for prostate cancer under the homozygote model and the recessive model. And XRCC1-Arg280His polymorphism is likely to be related with prostate cancer risk under the heterozygote model and the dominant model. Additional larger well-designed studies are needed to validate our results.
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Lack of association between leptin G-2548A polymorphisms and obesity risk: Evidence based on a meta-analysis. Obes Res Clin Pract 2015; 9:389-97. [PMID: 25733497 DOI: 10.1016/j.orcp.2015.01.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2014] [Revised: 01/07/2015] [Accepted: 01/13/2015] [Indexed: 01/13/2023]
Abstract
BACKGROUND The prevalence of obesity is increasing in most industrialized and developing countries. We aimed to investigate the association between leptin (LEP) G-2548A polymorphisms and the risk of obesity. METHODS We searched the PubMed, Web of Science, and China National Knowledge Infrastructure databases for studies that evaluated the association between LEP G-2548A polymorphisms and obesity risk prior to March 2014. The odds ratio (OR) and its 95% confidence interval (95% CI) were calculated to estimate the risk of obesity. Meta-analysis of subgroup populations and different control sources was conducted using homozygote (AA vs. GG), allelic (A vs. G), dominant (AA+GA vs. GG), recessive (AA vs. GG+GA), and heterozygote (AG vs. GG) models. The heterogeneity of the studies was assessed using χ(2)-tests based on Q-statistics. The pooled ORs were calculated using a random-effects model if there was no heterogeneity; otherwise, a random-effects model was used. Two authors extracted the data independently. The funnel plots, Begg's and Egger's test were used to assess publication bias. All statistical analyses were performed using STATA 12.0 software. RESULTS Nine case-controlled publications that evaluated the association between LEP G-2548A polymorphisms and obesity risk, which included 2594 subjects (1235 obesity cases and 1359 controls), were included in our meta-analysis. No significant association between this polymorphism and obesity risk was observed (P>0.05). Significant heterogeneity was detected among the studies. The results of subgroup analysis according to ethnicity and different control groups suggested that LEP G-2548A polymorphisms might increase the obesity risk in African populations in the homozygote (AA vs. GG: OR=2.38, 95% CI=1.15-4.93, P=0.020) and recessive (AA vs. GG+GA: OR=2.03, 95% CI=1.34-3.06, P=0.001) models. CONCLUSIONS Overall, this meta-analysis indicated that LEP G-2548A polymorphisms are not associated with obesity risk, although significant associations were observed in the homozygote model (AA vs. GG) and the recessive model (AA vs. GG+GA) in Africa populations. Further studies are still needed to validate and confirm this association.
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Hirbod-Mobarakeh A, Amirzargar AA, Nikbin B, Nicknam MH, Kutikhin A, Rezaei N. Immunogenetics of Cancer. CANCER IMMUNOLOGY 2015:295-341. [DOI: 10.1007/978-3-662-44006-3_17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Ouyang Y, Wu H, Tan A, Yang H, Gao Y, Li H, Lu S, Hu Y, Tang X, Zhang H. E-selectin gene polymorphism (A561C) and essential hypertension. Meta-analysis in the Chinese population. Herz 2014; 40 Suppl 2:197-202. [PMID: 25171839 DOI: 10.1007/s00059-014-4122-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2014] [Revised: 05/21/2014] [Accepted: 05/22/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND The A561C polymorphism of the E-selectin gene (SELE) has been reported to be associated with essential hypertension (EH) in several studies; however, results among these studies were inconsistent. Here, we conducted a meta-analysis to explore the association of the A561C polymorphism with EH. METHODS Publications were retrieved through searching PubMed, Web of Science, the China National Knowledge Infrastructure (CNKI), China Biological Medicine, and the Wanfang database. Odds ratios (OR) and 95 % confidence intervals (CI) were calculated to estimate the strength of association of A561C with EH. Subgroup analysis was also performed to assess ethnic discrepancies. A total of seven studies comprising 2,127 EH patients and 2,078 controls were analyzed. RESULTS In the dominant model analysis, we found significant associations between the A561C polymorphism and EH in all subjects (CC+AC vs. AA, OR = 1.96, 95 %CI 1.57-2.44, P heterogeneity = 0.381), in a Han Chinese subgroup (CC+AC vs. AA, OR = 2.38, 95 %CI 1.73-3.29, P heterogeneity = 0.269), and in non-Han Chinese minorities (CC+AC vs. AA, OR = 1.62, 95 %CI 1.19-2.21, P heterogeneity = 0.84). CONCLUSION The findings suggest that C allele carriers of the SELE gene polymorphism (A561C) might be predisposed to EH in the Chinese population. Further investigations in other ethnic populations should be conducted to verify these findings.
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Affiliation(s)
- Y Ouyang
- School of Public Health of Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, China
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Abstract
BACKGROUND Gastric cancer is a heterogeneous disease with respect to its molecular and histopathological features. Proximal gastric carcinoma (PGC) and distal gastric carcinoma (DGC) are two distinct clinical entities, suggesting the existence of different pathogenic mechanisms. PGC arises in a narrow region of the proximal stomach below the gastroesophageal junction. It accounts for around half of gastric cancers in men, with an increasing incidence worldwide and a predominance in elderly males. SUMMARY At present, the pathogenic mechanisms involved in the onset of PGC remain unknown. This mini-review presents the most recent findings on the pathology and natural history of this widespread and frequently fatal cancer. KEY MESSAGE PGC has unique clinicopathological characteristics distinct from esophageal adenocarcinoma and DGC. PRACTICAL IMPLICATIONS Patients with a high risk for PGC, such as elderly obese men, should undergo upper endoscopy for early detection and appropriate endoscopic therapy in the early stages of disease. Once it has progressed, the cancer is more easily spread, although the current staging systems are not perfectly adapted to the disease. PGC should be staged and treated as a gastric cancer. A separate staging system and genomic studies on this cancer are urgently needed for optimal patient management and appropriate disease prevention.
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Affiliation(s)
- Qin Huang
- Department of Pathology and Laboratory Medicine, Veterans Affairs Boston Healthcare System and Harvard Medical School, West Roxbury, Mass., USA
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Zhang J, Zhan Z, Wu J, Zhang C, Yang Y, Tong S, Wang R, Yang X, Dong W. Association among lifestyle, clinical examination, polymorphisms in CDH1 gene and Traditional Chinese Medicine syndrome differentiation of gastric cancer. J TRADIT CHIN MED 2014; 33:572-9. [PMID: 24660577 DOI: 10.1016/s0254-6272(14)60023-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To explore the association among life-style, clinical examination, polymorphisms in CDH1 gene and Traditional Chinese Medicine (TCM) syndrome differentiation of gastric cancer (GC). METHODS A hospital-based population of 387 GC patients was investigated in Jiangsu province. Relevant information regarding lifestyle and clinical examination were collected by a standard questionnaire. Four known single nucleotide polymorphisms (SNPs) in CDH1 were investigated by polymerase chain reaction-ligation detection reaction methods. Statistical analysis was conducted by SPSS 16.0 software. RESULTS The results showed that meal duration and the status of glutamic pyruvic transaminase were significantly associated with TCM syndrome differentiation of GC (both P < 0.05). None of the four SNPs in the E-cadherin (CDH1) gene achieved significant differences in their distributions among the nine syndrome types of GC (both P > 0.05). However, significant differences were observed in rs13689 genotype distributions between several pairs of syndrome types of GC, suggesting that rs13689 is correlated with the syndrome differentiation of GC. CONCLUSION Integrated analysis of lifestyle, clinical examination and CDH1 gene polymorphisms can contribute to a better understanding of the GC syndrome types and may improve the efficacy of interventions by stratifying disease according to TCM criteria.
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Lee HJ, Song IC, Yun HJ, Jo DY, Kim S. CXC chemokines and chemokine receptors in gastric cancer: from basic findings towards therapeutic targeting. World J Gastroenterol 2014; 20:1681-1693. [PMID: 24587647 PMCID: PMC3930968 DOI: 10.3748/wjg.v20.i7.1681] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2013] [Revised: 10/01/2013] [Accepted: 11/12/2013] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is the fourth most common cancer, and the second-highest cause of cancer-related deaths worldwide. Despite extensive research to identify novel diagnostic and therapeutic agents, patients with advanced gastric cancer suffer from a poor quality of life and poor prognosis, and treatment is dependent mainly on conventional cytotoxic chemotherapy. To improve the quality of life and survival of gastric cancer patients, a better understanding of the underlying molecular pathologies, and their application towards the development of novel targeted therapies, is urgently needed. Chemokines are a group of small proteins associated with cytoskeletal rearrangements, the directional migration of several cell types during development and physiology, and the host immune response via interactions with G-protein coupled receptors. There is also growing evidence to suggest that chemokines not only play a role in the immune system, but are also involved in the development and progression of tumors. In gastric cancer, CXC chemokines and chemokine receptors regulate the trafficking of cells in and out of the tumor microenvironment. CXC chemokines and their receptors can also directly influence tumorigenesis by modulating tumor transformation, survival, growth, invasion and metastasis, as well as indirectly by regulating angiogenesis, and tumor-leukocyte interactions. In this review, we will focus on the roles of CXC chemokines and their receptors in the development, progression, and metastasis of gastric tumors, and discuss their therapeutic potential for gastric cancer.
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Wei LZ, Wang HL, Liu X, Lu YP, Xu F, Yuan JQ, Ling YQ. Meta-analysis on the relationship between HLA-DRBl gene polymorphism and cervical cancer in Chinese population. PLoS One 2014; 9:e88439. [PMID: 24551099 PMCID: PMC3925111 DOI: 10.1371/journal.pone.0088439] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Accepted: 01/12/2014] [Indexed: 02/05/2023] Open
Abstract
Aim To determine the association between HLA-DRB1 haplotypes and risk of cervical cancer in unselected and samples from Chinese ethnicities. Methods A comprehensive search for articles from their inception to April 1st, 2013 was conducted from PubMed, Medline, Elsevier Science, Springer Link, Cochrane Library database, China biology medical literature database (CBM),China National Knowledge Infrastructure (CNKI),VIP,and Chinese literature database(Wang fang). A total of 1596 patients with cervical cancer and 2048 controls from the 12 studies on the relationship between gene polymorphism of HLA-DRB l and cervical cancer were performed and data were analyzed and processed using Review Manager 5.0 and Stata 11.0. Results Among the 13 family alleles, two (DRB1*03 and DRB1*08) were found to be negatively associated with cervical cancer in all studies or in Uighur subgroups, and two (DRB1*10 and DRB1*15) were positively associated with in all studies or in Uighur subgroups. Among the 25 specific alleles, six (DRB1*0301, *0403,*0404, *0803, *1312 and *1502) were associated with an increased risk cervical cancer in all studies. No significant association was established for other HLA-DRB1 family alleles and specific alleles. Ethnicity partially explained the race influence of DRB1*12, DRB1*14, DRB1*0301, DRB1*0403, DRB1*0404, DRB1*0803, DRB1*1312 and DRB1*1502 phenotypes. Conclusion Our results support the hypothesis that the HLA-DRB1 family alleles and specific alleles might influence the susceptibility or resistance to cervical cancer, suggesting that immune regulation may play a key role in this disease, although further investigations are still needed.
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Affiliation(s)
- Lin-zhen Wei
- Department of Obstetrics and Gynecology, Gansu Provincial Hospital, Lanzhou, Gansu, China
- The First Clinical Medicine College of Lanzhou University, Lanzhou, Gansu, China
| | - Hai-lin Wang
- Department of Obstetrics and Gynecology, Gansu Provincial Hospital, Lanzhou, Gansu, China
- * E-mail:
| | - Xin Liu
- Institute of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Ya-peng Lu
- The First Clinical Medicine College of Lanzhou University, Lanzhou, Gansu, China
| | - Fei Xu
- The First Clinical Medicine College of Lanzhou University, Lanzhou, Gansu, China
| | - Jin-qiu Yuan
- Division of Epidemiology, School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong
| | - Ya-qin Ling
- Institute of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
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Pan XF, Wen Y, Loh M, Wen YY, Yang SJ, Zhao ZM, Tian Z, Huang H, Lan H, Chen F, Soong R, Yang CX. Interleukin-4 and -8 gene polymorphisms and risk of gastric cancer in a population in Southwestern China. Asian Pac J Cancer Prev 2014; 15:2951-2957. [PMID: 24815430 DOI: 10.7314/apjcp.2014.15.7.2951] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND Gastric carcinogenesis is a complicated process that involves environmental and genetic factors like interleukin-4 (IL-4) and IL-8. Single nucleotide polymorphisms in their genes are associated with changed levels of gene expression. Here, we investigated the association between IL4-590 C>T and IL8-251T>A and gastric cancer (GC) risk in Sichuan of Southwestern China. MATERIALS AND METHODS We surveyed the research subjects using a self-designed questionnaire with questions on demographic factors and putative risk factors. Approximately 2-5ml of whole blood was collected after field survey to analyze IL4-590 C>T and IL8-251T>A genotypes using MALDI-TOF MS. RESULTS Our study recruited 308 pairs of GC patients and controls, including 224 (72.7%) men and 84 (27.3%) women in each group. There were 99 cardia and 176 noncardia GC patients in the case group. The case and control groups had an average age of 57.7±10.6 (mean±SD) and 57.6±11.1 years. GC patients reported a significantly greater proportion of family history of cancer (29.9% vs 10.7%, p<0.01) and drinking (54.6% vs 43.2%, p<0.01) than did controls. Variant genotypes of IL-4-590 C>T and IL-8-251 T>A were not associated with overall GC risk (adjusted OR, 0.89; 95%CI, 0.61-1.28 for CT or CC vs TT; adjusted OR, 1.14; 95%CI, 0.86-1.79 for TA or AA vs TT). Stratification analysis of two SNPs for risk by subsites only found that variant IL-8-251 TA or AA genotype was associated with increased noncardia GC risk (adjusted OR, 2.58; 95%CI, 1.19-5.57). We did not observe interactions between the IL-8-251 T>A genotype and smoking (adjusted OR, 0.38; 95%CI, 0.08-1.79) or drinking (adjusted OR, 0.36; 95%CI, 0.08-1.65) for risk of noncardia GC. CONCLUSIONS Our data indicate no association between the two SNPs of IL-4-590 and IL-8-251 with overall GC risk, while the IL-8-251 TA or AA genotype conferred risk of cardia GC. Our findings contribute to the evidence body for risk of SNPs associated with the development of gastric cancer in this region.
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Affiliation(s)
- Xiong-Fei Pan
- Department of Epidemiology, West China School of Public Health, Sichuan University, Chengdu, China E-mail :
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Cheng D, Hao Y, Zhou W, Ma Y. Positive association between Interleukin-8 -251A > T polymorphism and susceptibility to gastric carcinogenesis: a meta-analysis. Cancer Cell Int 2013; 13:100. [PMID: 24143859 PMCID: PMC3854499 DOI: 10.1186/1475-2867-13-100] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Accepted: 10/19/2013] [Indexed: 12/14/2022] Open
Abstract
Backgrounds The associations between the polymorphisms of interleukin-8 (IL-8) gene and gastric carcinogenesis have been extensively investigated in recent years. However, the results remain conflicting rather than conclusive. Methods A meta-analysis of 18 eligible studies was performed to evaluate the association of IL-8 -251A > T polymorphism with risk of gastric carcinogenesis. A systematic literature search of MEDLINE, Embase, and Web of Science, CNKI databases was conducted. Statistical analysis was performed by using the Revman 5.1 software and the Stata 12.0 software. Results Of the 293 unique studies identified using our search criteria, 18 studies fulfilled our inclusion criteria and were included in the meta-analysis. These studies cumulatively reported 5,321 cases and 6,465 controls. The combined results based on all studies showed that the IL-8 -251A > T polymorphism was associated with the risk of gastric carciongenesis (A vs. T: OR: 1.14 [1.02, 1.26], P = 0.02), especially gastric cancer (A vs. T: OR: 1.15 [1.03, 1.29], P = 0.02), but not associated with the risk of precancerous lesion (A vs. T: OR: 1.09 [0.99, 1.20], P = 0.08). Analysis stratified by ethnicity may seem that IL-8 -251A > T polymorphism was susceptible to gastric cancer in Asian population, but not in Caucasian population. Conclusions Our meta-analysis results provide evidence that IL-8 -251A > T polymorphism is significantly associated with increased risk of gastric carcinogenesis in Asian population, particularly in gastric cancer. Further large and well-designed studies are required to confirm this conclusion.
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Affiliation(s)
- Daye Cheng
- Department of Transfusion, First Hospital of China Medical University, North Nanjing Street, No, 155, Shenyang 110001, Liaoning, PR China.
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Cai X, Hu W, Zhang B, Dai N, Xu R, Qiu H, Wang D, Li Z, Jiang W. Genotyping of IL-8-251 T > A yields prognostic information in patients with gastric carcinoma. Biomarkers 2013; 18:559-64. [PMID: 23980896 PMCID: PMC3836392 DOI: 10.3109/1354750x.2012.745902] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
This study was designed to investigate the association of the IL-8-251 T > A gene polymorphism with clinicopathological features and the prognostic role of the gene polymorphism in patients with gastric adenocarcinoma. The gene polymorphism was detected by the polymerase chain reaction-restriction fragment length polymorphism method, followed by univariate and multivariate analyses to elicit its prognostic role. The frequency of IL-8-251 A/A, A/T and T/T genotypes were 11.0% (23/210), 43.8% (92/210) and 45.2% (95/210), respectively. The IL-8-251 gene polymorphism was closely correlated with depth of invasion (p = 0.007), grade of differentiation (p = 0.002) and TNM stage (p = 0.009). A/A genotype carriers showed more frequency of serosa involvement, low grade of differentiation and advanced stage of gastric carcinoma. IL-8-251 T > A gene polymorphism have no significant correlation with other clinicopathological features. The 5-year overall survival of IL-8-251 A/A genotype and T allele carriers were 30.8% and 59.2%, respectively. There is a significant discrepancy among the different genotype carriers. Multivariate analysis with the Cox regression model revealed that the IL-8-251 A/A genotype is an independent prognostic indicator (HR = 2.285, 95% Confidence Interval = 1.06-4.93, p = 0.035). We conclude that the IL-8-251 A/A genotype may indicate a poor prognosis for gastric adenocarcinoma patients.
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Affiliation(s)
- Xiuyu Cai
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , GuangZhou , China
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Miyazaki H, Takabe K, Yeudall WA. Chemokines, chemokine receptors and the gastrointestinal system. World J Gastroenterol 2013; 19:2847-2863. [PMID: 23704819 PMCID: PMC3660811 DOI: 10.3748/wjg.v19.i19.2847] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2012] [Revised: 11/13/2012] [Accepted: 04/27/2013] [Indexed: 02/06/2023] Open
Abstract
The biological properties of tumor cells are known to be regulated by a multitude of cytokines and growth factors, which include epidermal growth factor receptor agonists and members of the transforming growth factor β family. Furthermore, the recent explosion of research in the field of chemokine function as mediators of tumor progression has led to the possibility that these small, immunomodulatory proteins also play key roles in carcinogenesis and may, therefore, be potential targets for novel therapeutic approaches. In this review, we will summarize recently reported findings in chemokine biology with a focus on the gastrointestinal tract.
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20
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Yang T, Duan Z, Wu S, Liu S, Zeng Z, Li G, Wang S, Fan D, Ye D, Xu S, Zhang L, Pan F. Association of HLA-B27 genetic polymorphisms with ankylosing spondylitis susceptibility worldwide: a meta-analysis. Mod Rheumatol 2013. [DOI: 10.1007/s10165-013-0836-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Tunceroglu A, Jabbour SK. Gastric cancer: past accomplishments, present approaches and future aspirations. CLINICAL PRACTICE 2013; 10:47-77. [DOI: 10.2217/cpr.12.82] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Xue H, Liu J, Lin B, Wang Z, Sun J, Huang G. A meta-analysis of interleukin-8 -251 promoter polymorphism associated with gastric cancer risk. PLoS One 2012; 7:e28083. [PMID: 22279522 PMCID: PMC3261138 DOI: 10.1371/journal.pone.0028083] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2011] [Accepted: 10/31/2011] [Indexed: 12/16/2022] Open
Abstract
Background Potential functional allele A/T single nucleotide polymorphism (SNP) of Interleukin 8 (IL-8) promoter -251has been implicated in gastric cancer risk. Methods We aimed to explore the role of A/T SNP of IL-8 -251 in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. Eighteen studies were ultimately eligible for the meta-analysis of IL-8 - 251 A/T SNP. We adopted the most probably appropriate genetic model (codominant model). Potential sources of heterogeneity were sought out via stratification and sensitivity analyses, and publication biases were estimated. Results Between IL-8 -251 AA genotype with gastric cancer risk, statistically significant association could be noted with overall gastric cancer, evidently noted in Asians, witnessed in high quality subgroup, and apparently noted in intestinal-type gastric cancer. Conclusions Our meta-analysis indicates that IL-8 -251 AA genotype is associated with the overall risk of developing gastric cancer and may seem to be more susceptible to overall gastric cancer in Asian populations. IL-8 -251 AA genotype is more associated with the intestinal-type gastric cancer. IL-8 -251 AA genotype is not associated with Helicobacter Pylori infection status in our meta-analysis. Impact The analyses suggest that IL-8 -251 AA genotype may be an important biomarker of gastric cancer susceptibility for Asians, especially for Chinese Han population, the assumption that needs to be further confirmed in future well-designed studies in China.
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Affiliation(s)
- Huiping Xue
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Jiaotong University, Shanghai, People's Republic of China
- * E-mail: (GH); (HX)
| | - Jianjun Liu
- Department of Nuclear Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China
| | - Bing Lin
- Division of Nutrition, Zhongshan Hospital, Fudan University School of Medicine, Fundan University, Shanghai, People's Republic of China
| | - Zheng Wang
- Department of General Surgery, Renji Hospital, Shanghai, People's Republic of China
| | - Jianhua Sun
- Department of General Surgery, Renji Hospital, Shanghai, People's Republic of China
| | - Gang Huang
- Department of Nuclear Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China
- * E-mail: (GH); (HX)
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Huang Q, Fan X, Agoston AT, Feng A, Yu H, Lauwers G, Zhang L, Odze RD. Comparison of gastro-oesophageal junction carcinomas in Chinese versus American patients. Histopathology 2012; 59:188-97. [PMID: 21884197 DOI: 10.1111/j.1365-2559.2011.03924.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIMS To compare the clinical and pathological features of gastro-oesophageal junction (GEJ) carcinomas in Chinese and American patients. METHODS AND RESULTS Eighty consecutive patients with a GEJ carcinoma (43 from mainland China, and 37 from the USA) were evaluated for association with Barrett oesophagus (BO), chronic Helicobacter pylori gastritis, intestinal metaplasia, and outcome. GEJ carcinomas were defined as tumours that were located within 20 mm of, and crossed, the GEJ. Overall, GEJ carcinomas from Chinese patients revealed significantly more frequent location in the proximal stomach, higher pathological stage, larger size, younger patient age, and association with chronic H. pylori gastritis. In contrast, GEJ cancers from American patients showed a strong association with distal oesophageal location, BO, and associated intestinal metaplasia and dysplasia. Pathologically, GEJ carcinomas from American patients were predominantly adenocarcinomas, whereas Chinese patients showed a higher proportion of mucinous, adenosquamous, acinar or neuroendocrine tumours. Overall, 3- and 5-year survival rates were statistically similar between both patient groups, but upon multivariate analysis, Chinese patients showed statistically better survival rates for stage III tumours. CONCLUSIONS Most GEJ carcinomas in patients from China represent proximal gastric cancers associated with chronic H. pylori gastritis, and BO-associated carcinomas are rare among this patient population.
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Affiliation(s)
- Qin Huang
- Department of Pathology of the Nanjing Drum Tower Hospital, Nanjing, China
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24
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Verbeke H, Geboes K, Van Damme J, Struyf S. The role of CXC chemokines in the transition of chronic inflammation to esophageal and gastric cancer. Biochim Biophys Acta Rev Cancer 2011; 1825:117-29. [PMID: 22079531 DOI: 10.1016/j.bbcan.2011.10.008] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2011] [Revised: 10/28/2011] [Accepted: 10/29/2011] [Indexed: 12/12/2022]
Abstract
Chronic inflammation may increase the risk to develop cancer, for instance esophagitis or gastritis may lead to development of esophageal or gastric cancer, respectively. The key molecules attracting leukocytes to local inflammatory sites are chemokines. We here provide a systematic review on the impact of CXC chemokines (binding the receptors CXCR1, CXCR2, CXCR3 and CXCR4) on the transition of chronic inflammation in the upper gastrointestinal tract to neoplasia. CXCR2 ligands, including GRO-α,β,γ/CXCL1,2,3, ENA-78/CXCL5 and IL-8/CXCL8 chemoattract pro-tumoral neutrophils. In addition, angiogenic CXCR2 ligands stimulate the formation of new blood vessels, facilitating tumor progression. The CXCR4 ligand SDF-1/CXCL12 also promotes tumor development by stimulating angiogenesis and by favoring metastasis of CXCR4-positive tumor cells to distant organs producing SDF-1/CXCL12. Furthermore, these angiogenic chemokines also directly enhance tumor cell survival and proliferation. In contrast, the CXCR3 ligands Mig/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11 are angiostatic and attract anti-tumoral T lymphocytes and may therefore mediate tumor growth retardation and regression. Thus, chemokines exert diverging, sometimes dual roles in tumor biology as described for esophageal and gastric cancer. Therefore extensive research is needed to completely unravel the complex chemokine code in specific cancers. Possibly, chemokine-targeted cancer therapy will have to be adapted to the individual's chemokine profile.
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Affiliation(s)
- Hannelien Verbeke
- Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven (K.U.Leuven), Belgium
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González CA, Agudo A. Carcinogenesis, prevention and early detection of gastric cancer: where we are and where we should go. Int J Cancer 2011; 130:745-53. [PMID: 21918974 DOI: 10.1002/ijc.26430] [Citation(s) in RCA: 108] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2011] [Accepted: 09/01/2011] [Indexed: 12/15/2022]
Abstract
Helicobacter pylori is the most common cause of gastric cancer (GC), though smoking, alcohol, diet, genetics and epigenetic factors may also have a role in the occurrence of the disease. Why H. pylori cause GC in only a minority of those infected remains unknown. Although mechanisms of H. pylori-induced carcinogenesis are not yet well understood, several genotypes of H. pylori have been associated with strain virulence and disease risk. Primary prevention of GC should be addressed by avoiding exposure to factors that increase the risk and to promote factors associated with decrease risk. Vaccines against H. pylori are an ongoing promise and not yet available. Chemoprevention through vitamin supplementation has shown no benefit. Screening and eradication of H. pylori in the general population is not advised. Given that GC is a multiple-steps process, the identification of patients with preneoplastic lesions with high risk of progression, and periodic endoscopic surveillance of them represents the most effective way for early diagnosis of GC. However, clinical guidelines for surveillance are lacking and there are no clear criteria to classify patients into high or low risk of progressing to GC. No study has shown the potential usefulness of combining the information on the type of preneoplastic lesions, genetic and epigenetic, lifestyle and virulence bacterial factors in order to identify high risk patients who need more intensive surveillance. The integration of all this information, in a prediction model requires further research and could be the most important contribution for reducing the burden of GC.
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Affiliation(s)
- Carlos A González
- Unit of Nutrition, Environment and Cancer, Epidemiology Research Programme, Catalan Institut of Oncology, Hospitalet del Llobregat, Barcelona, Spain.
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−251 T/A polymorphism of the interleukin-8 gene and cancer risk: a HuGE review and meta-analysis based on 42 case–control studies. Mol Biol Rep 2011. [DOI: 10.1007/s11033-011-1042-5 and 3439=3439-- qfut] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/29/2022]
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−251 T/A polymorphism of the interleukin-8 gene and cancer risk: a HuGE review and meta-analysis based on 42 case–control studies. Mol Biol Rep 2011. [DOI: 10.1007/s11033-011-1042-5 and 3439=3439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/29/2022]
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Wang N, Zhou R, Wang C, Guo X, Chen Z, Yang S, Li Y. −251 T/A polymorphism of the interleukin-8 gene and cancer risk: a HuGE review and meta-analysis based on 42 case–control studies. Mol Biol Rep 2011. [DOI: 10.1007/s11033-011-1042-5 and 4855=5113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/29/2022]
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Wang N, Zhou R, Wang C, Guo X, Chen Z, Yang S, Li Y. −251 T/A polymorphism of the interleukin-8 gene and cancer risk: a HuGE review and meta-analysis based on 42 case–control studies. Mol Biol Rep 2011. [DOI: 10.1007/s11033-011-1042-5 and 9408=2840-- oynv] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Wang N, Zhou R, Wang C, Guo X, Chen Z, Yang S, Li Y. -251 T/A polymorphism of the interleukin-8 gene and cancer risk: a HuGE review and meta-analysis based on 42 case-control studies. Mol Biol Rep 2011; 39:2831-41. [PMID: 21681427 DOI: 10.1007/s11033-011-1042-5] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2010] [Accepted: 06/04/2011] [Indexed: 02/07/2023]
Abstract
The -251T/A (rs4073), a single nucleotide polymorphism, has been identified in the promoter region of the interleukin-8 (IL-8) gene. It's presence could influence the production of IL-8 protein by regulating the transcriptional activity of the gene. A large number of studies have been performed to evaluate the role of -251T/A polymorphism on various cancers, with inconsistent results being reported. In this paper, we summarized 13,189 cases and 16,828 controls from 42 case-control studies and attempted to assess the susceptibility of -251T/A polymorphism to cancers by a comprehensive meta-analysis. Pooled odds ratios and 95% confidence intervals were calculated by using the random-effects model. Publication bias, subgroup, and sensitivity analysis were also performed. Results showed that the carriers of the -251A allele had about a 12-21% increased risk for the reviewed cancer, in total. The carriers of -251A had an elevated risk to breast cancer, gastric cancer and nasopharyngeal cancer and a reduced risk to prostate cancer, but no evidence was found to indicate that the -251A allele predisposed its carriers to colorectal and lung cancers. When stratified separately by 'racial descent' and 'study design', it was found that the carriers of the -251A allele among the African group, Asian group and hospital-based case-control study group were at a higher risk for cancer, but not in European group and population-based case-control study. These results show that -251A allele is susceptible in the development of low-penetrance cancers.
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Affiliation(s)
- Na Wang
- Department of Molecular Biology, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang, 050011 Hebei, China
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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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Duan Z, Pan F, Zeng Z, Zhang T, Wang S, Li G, Xu S, Xu J, Zhang L. Interleukin-23 receptor genetic polymorphisms and ankylosing spondylitis susceptibility: a meta-analysis. Rheumatol Int 2011; 32:1209-14. [DOI: 10.1007/s00296-010-1769-7] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2010] [Accepted: 12/30/2010] [Indexed: 12/27/2022]
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Ju D, Sun D, Xiu L, Meng X, Zhang C, Wei P. Interleukin-8 is associated with adhesion, migration and invasion in human gastric cancer SCG-7901 cells. Med Oncol 2010; 29:91-9. [PMID: 21191670 DOI: 10.1007/s12032-010-9780-0] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2010] [Accepted: 12/08/2010] [Indexed: 12/12/2022]
Abstract
Interleukin-8 is known as an important chemokine involved in tumor angiogenesis and progression. Overexpression of interleukin-8 has been detected in a variety of human tumors, including gastric cancer, and is negatively correlated with prognosis. The aim of our study is to determine the effects of interleukin-8 on proliferation, adhesion, migration and invasion abilities and correlated molecular mechanisms in gastric cancer. We made recombinant interleukin-8 ranged from 0 ng/ml to 100 ng/ml interferes in human gastric cancer SCG-7901 cells in vitro. The results shown that interleukin-8 did not change cell proliferation, but promoted cell adhesion to endothelial cell and extracellular matrix components (collagen, laminin and fibronectin) as detected by Cell Counting Kit-8. And it induced migration and invasion ability based on scratch and transwell-chamber assays. Also, interleukin-8 regulated the protein and mRNA expression of matrix metalloproteinase-9, intercellular adhesion molecule-1 and E-cad and there was obviously a dose-dependent relationship, but the protein or mRNA expression of matrix metalloproteinase-2 was not obviously changed under the tested conditions. Our findings indicate that interleukin-8 is associated with adhesion, migration and invasion in gastric cancer and the regulation of matrix metalloproteinase-9, intercellular adhesion molecule-1 and E-cad expression is one of the potential molecule mechanisms. The studies imply interleukin-8 may be an alternative treatment strategy against gastric cancer.
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Affiliation(s)
- Dawei Ju
- Department of Traditional Chinese Medicine, Shanghai Changzheng Hospital, The Second Military Medical University, 415 Fengyang Avenue, 200003 Shanghai, China
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Zhu Y, Wang J, He Q, Zhang JQ. The association between interleukin-10-592 polymorphism and gastric cancer risk: a meta-analysis. Med Oncol 2010; 28:133-6. [PMID: 20087693 DOI: 10.1007/s12032-010-9417-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2009] [Accepted: 01/06/2010] [Indexed: 12/27/2022]
Abstract
Relationship of gastric cancer with the presence of IL-10-592 polymorphism was reported with inconsistent results. The objective of this study was to quantitatively evaluate the association between IL-10-592 allele polymorphism and gastric cancer susceptibility. We performed an extensive search of relevant studies and made a meta-analysis, including 12 studies with 2,285 gastric cancer cases and 4,236 controls. The combined results based on all studies showed that there were no significant differences in genotype distribution between gastric cancer cases and controls, CC versus CA/AA (OR = 1.05, 95% CI: 0.92-1.18), CC/CA versus AA (OR = 1.16, 95% CI: 0.92-1.46), CC versus CA (OR = 1.03, 95% CI: 0.90-1.17), CC versus AA (OR = 1.10, 95% CI: 0.90-1.34), and CA versus AA (OR = 1.16, 95% CI: 0.92-1.45). When stratifying for the race, it was found that gastric cancer cases had a significantly higher frequency of CC/CA versus AA (OR = 1.31, 95% CI: (1.08-1.59) and a significantly upper frequency of CA versus AA (OR = 1.33, 95% CI: 1.09-1.63) than control in Asians. When stratifying for the location and the Lauren's classification of gastric cancer, there were no statistically significant differences in genotype distribution between gastric cancer cases and controls. This meta-analysis suggested that IL-10-592 allele polymorphism might be a risk factor for gastric cancer among Asians.
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Affiliation(s)
- Yu Zhu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China
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