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Vascular endothelial growth factor A (VEGFA) promoter rs2010963 polymorphism and cancer risk: An updated meta-analysis and trial sequential analysis. Meta Gene 2022. [DOI: 10.1016/j.mgene.2022.101017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
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OUP accepted manuscript. Rheumatology (Oxford) 2022; 61:4252-4262. [DOI: 10.1093/rheumatology/keac143] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 02/23/2022] [Accepted: 03/01/2022] [Indexed: 11/13/2022] Open
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Ajaz S, Muneer R, Siddiqa A, Ali Memon M, Firasat S, Abid A, Khaliq S. Association of specific single nucleotide variants (SNVs) in the promoter and 3'-Untranslated region of Vascular Endothelial growth factor (VEGF) gene with risk and higher tumour grade of head and neck cancers. Oral Oncol 2021; 122:105519. [PMID: 34509102 DOI: 10.1016/j.oraloncology.2021.105519] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 08/02/2021] [Accepted: 09/01/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Head and Neck Cancers (HNCs)comprise one of the most frequent cancers in South-Asian region. Vascular Endothelial Growth Factor (VEGF) has a potent role in tumorigenesis and metastasis. Certain common single nucleotide variants (SNVs) in the highly polymorphic VEGF gene are correlated with variations in VEGF functions. The data for these SNVs in HNCs is scarce for South Asian populations. The present study addresses this shortfall. It investigates the association of two VEGF SNVs, -2578C/A (rs699947) in the promoter region and + 936C/T (rs3025039) in 3'-UTR, with the risk of HNCs and tumour characteristics. METHODS The study comprised 323 participants with 121 HNC patients and 202 controls. Germline DNA was isolated from peripheral blood samples. PCR-RFLP methods were optimized and validated by Sanger sequencing. After Hardy-Weinberg evaluation, the independent associations were analyzed under the assumptions of different genetic models. The χ2 test of independence or Fisher's Exact test (significant p-values at < 0.05) were performed and ORs (odds ratios) with 95% confidence interval were tabulated. RESULTS VEGF -2578 A-allele, CA + AA, and AA genotypes had significant protective association against HNCs. The respective ORs were: 0.651 (0.469-0.904), 0.613 (0.381 - 0.985), and 0.393 (0.193-0.804). VEGF + 936 T-allele, CT, and CT + TT genotypes had significantly increased susceptibility for HNCs. The respective ORs were 1.882 (1.001 - 3.536), 2.060 (1.035 - 4.102), and 2.023 (1.032 - 3.966). Additionally, VEGF + 936 CT and CT + TT genotypes showed significant associations with higher tumour grade (p-values < 0.029, and < 0.037, respectively). CONCLUSION The present study is the foremost report of independent and unique associations of the investigated VEGF SNVs with HNCs.
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Affiliation(s)
- Sadia Ajaz
- Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi-75270, Pakistan.
| | - Rabbia Muneer
- Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi-75270, Pakistan
| | - Aisha Siddiqa
- Atomic Energy Medical Centre (AEMC), Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan
| | - Muhammad Ali Memon
- Atomic Energy Medical Centre (AEMC), Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan
| | - Sadaf Firasat
- Centre for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan
| | - Aiysha Abid
- Centre for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan
| | - Shagufta Khaliq
- Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore, Pakistan
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Khajavi M, Zhou Y, Schiffer AJ, Bazinet L, Birsner AE, Zon L, D'Amato RJ. Identification of Basp1 as a novel angiogenesis-regulating gene by multi-model system studies. FASEB J 2021; 35:e21404. [PMID: 33899275 DOI: 10.1096/fj.202001936rrr] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 01/13/2021] [Accepted: 01/15/2021] [Indexed: 01/23/2023]
Abstract
We have previously used the genetic diversity available in common inbred mouse strains to identify quantitative trait loci (QTLs) responsible for the differences in angiogenic response using the corneal micropocket neovascularization (CoNV) assay. Employing a mouse genome-wide association study (GWAS) approach, the region on chromosome 15 containing Basp1 was identified as being significantly associated with angiogenesis in inbred strains. Here, we developed a unique strategy to determine and verify the role of BASP1 in angiogenic pathways. Basp1 expression in cornea had a strong correlation with a haplotype shared by mouse strains with varied angiogenic phenotypes. In addition, inhibition of BASP1 demonstrated a dosage-dependent effect in both primary mouse brain endothelial and human microvascular endothelial cell (HMVEC) migration. To investigate its role in vivo, we knocked out basp1 in transgenic kdrl:zsGreen zebrafish embryos using a widely adopted CRISPR-Cas9 system. These embryos had severely disrupted vessel formation compared to control siblings. We further show that basp1 promotes angiogenesis by upregulating β-catenin gene and the Dll4/Notch1 signaling pathway. These results, to the best of our knowledge, provide the first in vivo evidence to indicate the role of Basp1 as an angiogenesis-regulating gene and opens the potential therapeutic avenues for a wide variety of systemic angiogenesis-dependent diseases.
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Affiliation(s)
- Mehrdad Khajavi
- Department of Surgery, Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Yi Zhou
- Division of Hematology/Oncology, Boston Children's Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA
| | - Alex J Schiffer
- Department of Surgery, Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Lauren Bazinet
- Department of Surgery, Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Amy E Birsner
- Department of Surgery, Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Leonard Zon
- Division of Hematology/Oncology, Boston Children's Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.,Howard Hughes Medical Institute, Boston, MA, USA
| | - Robert J D'Amato
- Department of Surgery, Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.,Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
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Ramírez-Bello J, Cadena-Sandoval D, Fragoso JM, Barbosa-Cobos RE, Moreno-Eutímio MA, Saavedra-Salinas MÁ, Valencia-Pacheco G, López-Villanueva RF, Jiménez-Morales S. The VEGFA -1154G/A polymorphism is associated with reduced risk of rheumatoid arthritis but not with systemic lupus erythematosus in Mexican women. J Gene Med 2018; 20:e3024. [PMID: 29756413 DOI: 10.1002/jgm.3024] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Revised: 05/02/2018] [Accepted: 05/04/2018] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Levels of circulating vascular endothelial growth factor (VEGF) (a potent endothelial-cell-specific angiogenic factor) have been correlated with disease activity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, several single nucleotide polymorphisms (SNPs), including the VEGFA -2578C/A, have been associated with RA in some populations. By contrast, the role of different VEGFA SNPs in the susceptibility to SLE has received little attention. Thus, the present study aimed to determine whether the VEGFA -2578C/A, -1154G/A and -634G/C polymorphisms confer risk or were associated with reduced risk of RA or SLE in a Mexican population. METHODS The present study included 903 women from Mexico: 405 were patients with RA, 282 had SLE and 216 were healthy individuals. The genotypes were obtained with TaqMan probes. RESULTS The data obtained in the present study suggest that the VEGFA -2578C/A and -634G/C polymorphisms are not risk factors for RA or SLE; however, VEGFA -1154G/A was associated with reduced risk in women with RA (odds ratio = 0.6, pc = 0.0051) but not with SLE (odds ratio = 0.7, pc = 0.13). CONCLUSIONS The present study is the first to document an association between VEGFA -1154G/A and reduced risk in women with RA but not with SLE.
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Affiliation(s)
- Julian Ramírez-Bello
- Unidad de Investigación en Enfermedades Metabólicas y Endócrinas, Hospital Juarez de Mexico, Mexico City, Mexico
| | - Daniel Cadena-Sandoval
- Unidad de Investigación en Enfermedades Metabólicas y Endócrinas, Hospital Juarez de Mexico, Mexico City, Mexico
| | - José Manuel Fragoso
- Laboratorio de Biología Molecular, Instituto Nacional de Cardiología 'Ignacio Chávez', Mexico City, Mexico
| | | | | | - Miguel Ángel Saavedra-Salinas
- Servicio de Reumatología, Centro Médico Nacional 'La Raza', Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Guillermo Valencia-Pacheco
- Laboratorio de Hematología, Centro de Investigación Regional 'Dr Hideyo Noguchi', Universidad Autónoma de Yucatán, Yucatan, Mexico
| | - Ricardo F López-Villanueva
- Servicio de Reumatología, Hospital General Regional (ISSSTE), Servicio de Salud de Yucatán, Yucatán, Mexico
| | - Silvia Jiménez-Morales
- Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
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Malecic N, Young HS. Excessive angiogenesis associated with psoriasis as a cause for cardiovascular ischaemia. Exp Dermatol 2018; 26:299-304. [PMID: 28156019 DOI: 10.1111/exd.13310] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/27/2017] [Indexed: 01/09/2023]
Abstract
Psoriasis, a common disease affecting 2%-3% of the UK population, produces significant impairment of quality of life and is an immense burden on sufferers and their families. Psoriasis is associated with significant cardiovascular comorbidity and the metabolic syndrome. Angiogenesis, a relatively under-researched component of psoriasis, is a key factor in pathogenesis of psoriasis and also contributes to the development of atherosclerosis. Vascular endothelial growth factor (VEGF) is a well-established mediator of pathological angiogenesis which is upregulated in psoriasis. It is possible that, in patients with psoriasis, cutaneous angiogenesis may be both a marker for systemic vascular pathology and a novel therapeutic target. In this viewpoint study, the role of VEGF-mediated angiogenesis as a cause for cardiovascular events in patients with psoriasis is explored.
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Affiliation(s)
- Nina Malecic
- Manchester Academic Health Science Centre, Department of Dermatology, The University of Manchester, Manchester, UK
| | - Helen S Young
- Manchester Academic Health Science Centre, Department of Dermatology, The University of Manchester, Manchester, UK
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Hu K, Xie X, Wang R, Wu F, Zhang Y. Association of the rs2071559 (T/C) polymorphism with lymphatic metastasis in patients with nasopharyngeal carcinoma. Oncol Lett 2017; 14:7681-7686. [PMID: 29344214 PMCID: PMC5755165 DOI: 10.3892/ol.2017.7209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2015] [Accepted: 01/12/2017] [Indexed: 11/05/2022] Open
Abstract
Vascular endothelial growth factor (VEGF) and its receptor, VEGFR2, serve a critical role in angiogenesis and lymphangiogenesis, which are involved in the initiation and progression of malignancies. Specific single nucleotide polymorphisms of VEGF and VEGFR2 have been shown to modulate gene expression and influence malignancy aggressiveness. The aim of the present study was to determine whether the VEGFR2 rs2071559 (T/C) polymorphism is associated with the risk of developing nasopharyngeal carcinoma (NPC) and the aggressiveness of NPC in a southern Chinese population. A case-control study comprising 171 NPC patients and 184 healthy individuals was performed. Genotyping of the rs2071559 polymorphism was performed by quantitative polymerase chain reaction using TaqMan probes. Genotype and allele distribution of the rs2071559 polymorphism was not associated with the risk of NPC following adjustment for age, sex and ethnicity by multivariate logistic regression analyses. Regional lymph node metastasis was significantly correlated with the rs2071559 C allele and the related genotypes (OR 0.402, 95% CI 0.193-0.835, P=0.016; and OR 0.347, 95% CI 0.145-0.829, P=0.024, respectively). No correlations between genotype or allele distribution and the primary tumor size, distant metastasis, clinical stage, or histological type were observed. The rs2071559 polymorphism was shown to have an association with lymphatic metastasis in patients with NPC; however, the precise molecular mechanism should be elucidated in additional studies.
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Affiliation(s)
- Kai Hu
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Xiujing Xie
- Department of Ultrasonic Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Rensheng Wang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Fang Wu
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Yong Zhang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
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Kim YR, Hong SH. Promoter polymorphisms of the vascular endothelial growth factor gene are associated with metabolic syndrome susceptibility in Koreans. Biomed Rep 2017; 6:555-560. [DOI: 10.3892/br.2017.886] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Accepted: 03/09/2017] [Indexed: 11/06/2022] Open
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Wang XH, Long ZW. Correlations of EGF G1380A, bFGF C754G and VEGF T460C polymorphisms with malignant melanoma susceptibility and prognosis: A case-control study. Gene 2017; 617:44-53. [PMID: 28219779 DOI: 10.1016/j.gene.2017.02.023] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Revised: 02/14/2017] [Accepted: 02/16/2017] [Indexed: 01/24/2023]
Abstract
This case-control study aims to investigate the correlations of EGF G1380A, bFGF C754G and VEGF T460C polymorphisms with the susceptibility and prognosis of malignant melanoma. A total of 153 patients with multiple primary melanomas were collected as the case group and another 170 healthy individuals were selected as the control group. ELISA and PCR-RFLP were performed to test the serum level of VEGF and to analyze the genotype as well as allele frequencies of VEGF T460C, EGF G1380A, and bFGF C754G, respectively. The patients were assigned into complete remission (CR), partial remission (PR) and non-remission groups after treatment. HE and CD34 staining were conducted in tissue samples of CR and PR patients. Event-free survival (EFS) and overall survival (OS) were measured. AA genotype of EGF G1380A and GG genotype of bFGF C754G had higher frequency distribution in the case group than the control group. Patients with AA genotype of EGF G1380 and GG genotype of bFGF C754G had an elevated VEGF level in comparison to other genotypes. Patients with GA+GG genotypes of EGF G1380A and CG+CC genotypes of bFGF C754G had higher EFS and OS than those with AA genotype and those with GG genotype, respectively. According to the haplotype analysis, the case group had a notably higher frequency of TAG and CAG along with while lower frequency of TGG and CGC compared with the control group. Logistic regression analysis revealed that the polymorphisms of EGF G1380A and bFGF C754G as well as the haploid TAG increased the susceptibility of malignant melanoma. The results indicated that EGF G1380A and bFGF C754G gene polymorphisms were associated with the susceptibility and prognosis of malignant melanoma, and that the polymorphisms of EGF G1380A and bFGF C754G as well as the haploid TAG increased the susceptibility of malignant melanoma.
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Affiliation(s)
- Xin-Hua Wang
- Department of Dermatology, Shigatse People's Hospital, Shigatse 857000, P.R. China
| | - Zi-Wen Long
- Department of Dermatology, Shigatse People's Hospital, Shigatse 857000, P.R. China; Department of Gastric Cancer and Soft-Tissue Sarcoma Sugery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
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do Espírito Santo GF, Galera BB, Duarte EC, Chen ES, Azis L, Damazo AS, Saba GT, de Sousa Gehrke F, Guerreiro da Silva IDC, Waisberg J. Prognostic significance of vascular endothelial growth factor polymorphisms in colorectal cancer patients. World J Gastrointest Oncol 2017; 9:78-86. [PMID: 28255429 PMCID: PMC5314204 DOI: 10.4251/wjgo.v9.i2.78] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Revised: 09/02/2016] [Accepted: 12/14/2016] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the associations of the genetic polymorphisms of vascular endothelial growth factor A (VEGF-A) -1498C>T and -634G>C, with the survival of patients with colorectal cancer (CRC).
METHODS A prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction (PCR) in real-time. The real-time PCR technique was used to identify the VEGF-A -1498C>T (rs833031) and -634G>C (rs2010963) polymorphisms. Genotyping was validated for VEGF-A -1498C>T polymorphism in 129 patients and for VEGF-A -634G>C polymorphism in 118 patients. The analysis of association between categorical variables was performed using logistic regression, survival by Kaplan-Meier method and multivariate analysis by the Cox regression method.
RESULTS In the univariate analysis there was a significant association (OR = 0.32; P = 0.048) between genotype CC of the VEGF-A -1498C>T polymorphism and the presence of CRC liver metastasis. There was no association between VEGF-A -1498C>T polymorphism and VEGF-A -634G>C polymorphism with further clinical or anatomopathologic variables. The genotype CC of the VEGF-A -1498C>T polymorphism was significantly correlated with the 5-year survival (P = 0.032), but not significant difference (P = 0.27) was obtained with the VEGF-A -634G>C polymorphism with the 5-year survival in the univariate analysis. The genotype CT (HR = 2.79) and CC (HR = 4.67) of the polymorphism VEGF-A -1498C>T and the genotype CC (HR = 3.76) of the polymorphism VEGF-A -634C>G acted as an independent prognostic factor for the risk of death in CRC patients.
CONCLUSION The CT and CC genotypes of the VEGF-A -1498C>T and the CC genotype of the VEGF-A -634C>G polymorphisms are prognostic factors of survival in Brazilians patients with sporadic colorectal carcinoma.
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Single nucleotide polymorphisms, haplotype association and tumour expression of the vascular endothelial growth factor (VEGF) gene with lung carcinoma. Gene 2017; 608:95-102. [PMID: 28122267 DOI: 10.1016/j.gene.2017.01.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
VEGF contains several polymorphic sites known to influence its expression. We examined the possible association between+405(-634)C>G,+936C>T,-2578C>A and lung cancer in 199 Kashmiri patients and 401 healthy controls. VEGF+405CG,+936CT+TT and-2578CA genotypes were significantly associated with lung cancer risk compared to VEGF+405CC,+936CC and-2578AA+CC genotypes [OR=0.07 (0.04-0.13), P<0.0001, OR=0.36 (0.25-0.52), P<0.0001 and 0.08 (0.05-0.13), P<0.0001]. Haplotype analysis revealed that CGA and TGA haplotypes of VEGF gene conveys the risk for lung cancer [OR=0.18 (0.10-0.33), P<0.0001 and 0.07 (0.03-0.13), P<0.0001]. VEGF expression revealed non-significant association with the genotypes of the three SNPs. In conclusion, the SNPs examined appear to influence lung cancer susceptibility while as genotypes of the SNPs don't appear to have significant association with VEGF mRNA expression in lung tumours.
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Vaysse A, Fang S, Brossard M, Wei Q, Chen WV, Mohamdi H, Vincent-Fetita L, Margaritte-Jeannin P, Lavielle N, Maubec E, Lathrop M, Avril MF, Amos CI, Lee JE, Demenais F. A comprehensive genome-wide analysis of melanoma Breslow thickness identifies interaction between CDC42 and SCIN genetic variants. Int J Cancer 2016; 139:2012-20. [PMID: 27347659 PMCID: PMC5116391 DOI: 10.1002/ijc.30245] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Accepted: 06/07/2016] [Indexed: 12/23/2022]
Abstract
Breslow thickness (BT) is a major prognostic factor of cutaneous melanoma (CM), the most fatal skin cancer. The genetic component of BT has only been explored by candidate gene studies with inconsistent results. Our objective was to uncover the genetic factors underlying BT using an hypothesis-free genome-wide approach. Our analysis strategy integrated a genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) for BT followed by pathway analysis of GWAS outcomes using the gene-set enrichment analysis (GSEA) method and epistasis analysis within BT-associated pathways. This strategy was applied to two large CM datasets with Hapmap3-imputed SNP data: the French MELARISK study for discovery (966 cases) and the MD Anderson Cancer Center study (1,546 cases) for replication. While no marginal effect of individual SNPs was revealed through GWAS, three pathways, defined by gene ontology (GO) categories were significantly enriched in genes associated with BT (false discovery rate ≤5% in both studies): hormone activity, cytokine activity and myeloid cell differentiation. Epistasis analysis, within each significant GO, identified a statistically significant interaction between CDC42 and SCIN SNPs (pmeta-int =2.2 × 10(-6) , which met the overall multiple-testing corrected threshold of 2.5 × 10(-6) ). These two SNPs (and proxies) are strongly associated with CDC42 and SCIN gene expression levels and map to regulatory elements in skin cells. This interaction has important biological relevance since CDC42 and SCIN proteins have opposite effects in actin cytoskeleton organization and dynamics, a key mechanism underlying melanoma cell migration and invasion.
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Affiliation(s)
- Amaury Vaysse
- INSERM, Genetic Variation and Human Diseases Unit, UMR-946, Paris, France
- Institut Universitaire d’Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Shenying Fang
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Myriam Brossard
- INSERM, Genetic Variation and Human Diseases Unit, UMR-946, Paris, France
- Institut Universitaire d’Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Qingyi Wei
- Duke Cancer Institute, Duke University Medical Center and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Wei V. Chen
- Laboratory Informatics System, Department of Clinical Applications & Support, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
| | - Hamida Mohamdi
- INSERM, Genetic Variation and Human Diseases Unit, UMR-946, Paris, France
- Institut Universitaire d’Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | | | - Patricia Margaritte-Jeannin
- INSERM, Genetic Variation and Human Diseases Unit, UMR-946, Paris, France
- Institut Universitaire d’Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Nolwenn Lavielle
- INSERM, Genetic Variation and Human Diseases Unit, UMR-946, Paris, France
- Institut Universitaire d’Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Eve Maubec
- INSERM, Genetic Variation and Human Diseases Unit, UMR-946, Paris, France
- AP-HP, Service de Dermatologie, Hôpital Avicenne et Université Paris 13, Bobigny, France
| | - Mark Lathrop
- McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada
| | | | - Christopher I. Amos
- Department of Community and Family Medicine, Geisel College of Medicine, Dartmouth College, Hanover, New Hampshire, USA
| | - Jeffrey E. Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Florence Demenais
- INSERM, Genetic Variation and Human Diseases Unit, UMR-946, Paris, France
- Institut Universitaire d’Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
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Dornbusch J, Walter M, Gottschalk A, Obaje A, Junker K, Ohlmann CH, Meinhardt M, Zacharis A, Zastrow S, Schoffer O, Grimm MO, Klug SJ, Wirth MP, Fuessel S. Evaluation of polymorphisms in angiogenesis-related genes as predictive and prognostic markers for sunitinib-treated metastatic renal cell carcinoma patients. J Cancer Res Clin Oncol 2016; 142:1171-82. [PMID: 26935927 DOI: 10.1007/s00432-016-2137-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Accepted: 02/18/2016] [Indexed: 12/31/2022]
Abstract
PURPOSE Single nucleotide polymorphisms (SNPs) in angiogenesis-associated genes might play an important role in activity of the tyrosine kinase inhibitor sunitinib and could affect survival of cancer patients treated with this drug. The aim of this retrospective study was to elucidate the role of 10 known SNPs in VEGFA, VEGFR1, VEGFR2 and VEGFR3 as potential prognostic and predictive markers in an independent cohort of patients with metastatic renal cell carcinoma (mRCC). METHODS DNA from 121 mRCC patients treated with sunitinib was used to analyze SNPs by TaqMan genotyping assays. Disease control rate was evaluated according to RECIST. Adverse effects of sunitinib were registered from medical records. The results of Cox and logistic regression were verified by correction for multiple testing. RESULTS Kaplan-Meier analysis revealed a reduced progression-free survival in patients with the wild-type (WT) allele of the VEGFA SNP rs699947 compared to variant alleles. Patients with the AA/AC-alleles of the VEGFR1 SNP rs9582036 had an improved median overall survival compared to those with the CC-WT allele what could be confirmed by multivariable Cox proportional hazard regression analyses. No statistically significant associations between the analyzed SNPs and higher risk for adverse effects were observed. CONCLUSIONS The results of this study suggest that most of the selected SNPs in angiogenesis-related genes are not associated with survival of mRCC patients after sunitinib therapy or with adverse effects. Only the VEGFR1 SNP rs9582036 showed a statistically significant association with overall survival. The potential of SNPs as prognostic and predictive markers for sunitinib-treated mRCC patients should be finally assessed by prospective studies.
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Affiliation(s)
- Juana Dornbusch
- Department of Urology, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Martina Walter
- Department of Urology, University Hospital of Jena, Lessingstr. 1, 07743, Jena, Germany
| | - Andrea Gottschalk
- Institute for Medical Informatics and Biometry, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Alice Obaje
- Department of Urology, University Hospital of Jena, Lessingstr. 1, 07743, Jena, Germany
| | - Kerstin Junker
- Department of Urology, Saarland University Medical Center, Kirrberger Str. 1, 66424, Homburg, Germany
| | - Carsten-Henning Ohlmann
- Department of Urology, Saarland University Medical Center, Kirrberger Str. 1, 66424, Homburg, Germany
| | - Matthias Meinhardt
- Institute of Pathology, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Aristeidis Zacharis
- Department of Urology, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Stefan Zastrow
- Department of Urology, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Olaf Schoffer
- Cancer Epidemiology, University Cancer Center Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Marc-Oliver Grimm
- Department of Urology, University Hospital of Jena, Lessingstr. 1, 07743, Jena, Germany
| | - Stefanie J Klug
- Cancer Epidemiology, University Cancer Center Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Manfred P Wirth
- Department of Urology, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Susanne Fuessel
- Department of Urology, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
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Yang SM, Huang CY, Shiue HS, Huang SP, Pu YS, Chen WJ, Lin YC, Hsueh YM. Joint Effect of Urinary Total Arsenic Level and VEGF-A Genetic Polymorphisms on the Recurrence of Renal Cell Carcinoma. PLoS One 2015; 10:e0145410. [PMID: 26701102 PMCID: PMC4689502 DOI: 10.1371/journal.pone.0145410] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Accepted: 12/03/2015] [Indexed: 12/21/2022] Open
Abstract
The results of our previous study suggested that high urinary total arsenic levels were associated with an increased risk of renal cell carcinoma (RCC). Germline genetic polymorphisms might also affect cancer risk and clinical outcomes. Vascular endothelial growth factor (VEGF) plays an important role in vasculogenesis and angiogenesis, but the combined effect of these factors on RCC remains unclear. In this study, we explored the association between the VEGF-A -2578C>A, -1498T>C, -1154G>A, -634G>C, and +936C>T gene polymorphisms and RCC. We also evaluated the combined effects of the VEGF-A haplotypes and urinary total arsenic levels on the prognosis of RCC. This case-control study was conducted with 191 RCC patients who were diagnosed with renal tumors on the basis of image-guided biopsy or surgical resections. An additional 376 age- and gender-matched controls were recruited. Concentrations of urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotyping was investigated using fluorescent-based TaqMan allelic discrimination. We observed no significant associations between VEGF-A haplotypes and RCC risk. However, the VEGF-A ACGG haplotype from VEGF-A -2578, -1498, -1154, and -634 was significantly associated with an increased recurrence of RCC (OR = 3.34, 95% CI = 1.03–10.91). Urinary total arsenic level was significantly associated with the risk of RCC in a dose-response manner, but it was not related to the recurrence of RCC. The combination of high urinary total arsenic level and VEGF-A risk haplotypes affected the OR of RCC recurrence in a dose-response manner. This is the first study to show that joint effect of high urinary total arsenic and VEGF-A risk haplotypes may influence the risk of RCC recurrence in humans who live in an area without obvious arsenic exposure.
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Affiliation(s)
- Shu-Mei Yang
- School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan
| | - Chao-Yuan Huang
- Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan
| | - Horng-Sheng Shiue
- Department of Chinese Medicine, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Shu-Pin Huang
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yeong-Shiau Pu
- Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan
| | - Wei-Jen Chen
- School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan
| | - Ying-Chin Lin
- Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, Taipei, Taiwan
- Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yu-Mei Hsueh
- School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan
- Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- * E-mail: (YMH)
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15
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Metzger CS, Koutsimpelas D, Brieger J. Transcriptional regulation of the VEGF gene in dependence of individual genomic variations. Cytokine 2015. [DOI: 10.1016/j.cyto.2015.07.015] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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16
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Metzger CS, Kämmerer PW, Schmidtmann I, Brieger J. Vascular endothelial growth factor polymorphisms as effect modifiers of oral squamous cell carcinoma risk: A systematic review and meta-analysis. Mol Clin Oncol 2015; 3:347-352. [PMID: 25798265 DOI: 10.3892/mco.2014.458] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Accepted: 10/03/2014] [Indexed: 11/06/2022] Open
Abstract
Smoking is one of the main risk factors for the development of oral squamous cell carcinoma (OSCC). Smoking may affect single-nucleotide polymorphism (SNP)-dependent vascular endothelial growth factor (VEGF)-induced angiogenic activity. Therefore, we systematically reviewed the published VEGF-SNP genotype data of OSCC patients and healthy individuals and performed a meta-analysis comparing the VEGF-SNP genotypes of smoking and non-smoking patients in association with OSCC incidence. Prospective and retrospective studies on the clinical comparison of OSCC patients with different VEGF-SNP genotypes were reviewed. The meta-analysis re-pooled studies of smoking and non-smoking OSCC patients with different VEGF-SNPs between 2006 and 2014. The identified articles were reviewed and those reporting pertinent information, assignment to smoking and non-smoking patient groups and sufficient data for estimation of an odds ratio (OR) with a 95% confidence interval (CI) were selected for the meta-analysis. Pooled ORs and CIs for the comparison of SNP distribution in the smoking and non-smoking subgroups were calculated and compared using the random-effects model. A total of 7 studies were included in the systematic review, which was followed by a meta-analysis using 3 pertinent studies. The reviewed studies reported discrepant findings, with differences between Asian and European patients. The meta-analysis demonstrated marginal but not statistically significant differences, suggesting that specific VEGF-SNPs may be OSCC risk modifiers for smokers, depending on the ethnic background. The performed meta-analysis suggested an increased OSCC risk for smokers carrying specific VEGF-genotypes, although the calculated data did not reach the level of significance. However, data have to be interpreted with caution due to the limited sample size. Therefore, further studies, including larger patient samples, are mandatory.
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Affiliation(s)
- Carmen S Metzger
- Department of Otorhinolaryngology, Head and Neck Surgery, Laboratory of Molecular Tumor Biology, University Medical Center of the Johannes Gutenberg University, D-55101 Mainz, Rhineland-Palatinate
| | - Peer W Kämmerer
- Department of Oral, Maxillofacial and Plastic Surgery, University of Rostock, D-18057 Rostock, Mecklenburg-Vorpommern
| | - Irene Schmidtmann
- Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Centre of the Johannes Gutenberg University, D-55131 Mainz, Rhineland-Palatinate, Germany
| | - Juergen Brieger
- Department of Otorhinolaryngology, Head and Neck Surgery, Laboratory of Molecular Tumor Biology, University Medical Center of the Johannes Gutenberg University, D-55101 Mainz, Rhineland-Palatinate
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17
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Kapahi R, Guleria K, Sambyal V, Manjari M, Sudan M, Uppal MS, Singh NR. Association of VEGF and VEGFR1 polymorphisms with breast cancer risk in North Indians. Tumour Biol 2015; 36:4223-34. [PMID: 25604142 DOI: 10.1007/s13277-015-3059-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Accepted: 01/05/2015] [Indexed: 02/07/2023] Open
Abstract
The aim of present study was to evaluate the relationship between vascular endothelial growth factor (VEGF) -2578C/A, -2549I/D, -460T/C and -7C/T and VEGFR1 -710C/T polymorphisms with risk to breast cancer in North Indians. A total of 204 sporadic breast cancer patients and 204 controls were recruited for this case-control study. Significantly increased frequency of II genotype of -2549I/D polymorphism was observed in patients as compared to control individuals (odds ratio (OR) = 2.76, 95 % confidence interval (CI), 1.55-4.92; p = 0.0005). VEGF -2578AA genotype (OR = 2.87; 95 % CI, 1.61-5.10; p = 0.0003) and A allele (OR = 1.65, 95 % CI, 1.25-2.18; p = 0.0004) were found to be associated with increased risk for breast cancer. Individuals carrying CC genotype (OR = 2.23, 95 % CI, 1.25-3.97) and C allele (OR = 1.42, 95 % CI, 1.07-1.87) of VEGF -460T/C polymorphism were at higher risk of breast cancer. There was no significant difference in genotype and allele distribution of VEGF -7C/T and VEGFR1 -710C/T polymorphisms between cases and control individuals (p > 0.05). Linkage disequilibrium analysis showed a strong linkage between VEGF -2549I/D and -2578C/A polymorphisms (Lewontin's [Formula: see text] = 0.99; r (2) = 0.97), -2549I/D and -460T/C ([Formula: see text] = 0.94; r (2) = 0.84), and -2578C/A and -460T/C polymorphisms ([Formula: see text] = 0.93; r (2) = 0.83). In the present study, we concluded that VEGF -2549I/D, -2578C/A and -460T/C polymorphisms are associated with risk to breast cancer in Punjab, North India.
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Affiliation(s)
- Ruhi Kapahi
- Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University, Amritsar, 143005, Punjab, India
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18
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Credidio L, Lima CSP, Leal R, de Ayrizono MLS, Fagundes JJ, Magna LA, Coy CSR. C936T polymorphism of the VEGF gene in relation to the risk and the clinical and biological characteristics of sporadic colorectal adenocarcinoma. BMC Res Notes 2014; 7:768. [PMID: 25361753 PMCID: PMC4223751 DOI: 10.1186/1756-0500-7-768] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2013] [Accepted: 10/02/2014] [Indexed: 01/12/2023] Open
Abstract
Background One of the main glycoproteins responsible for angiogenesis is the vascular endothelial growth factor. It is believed that C936T polymorphism, located in the VEGF gene, is correlated with susceptibility towards development of sporadic colorectal adenocarcinoma. The aim of this study was to identify the frequencies of the genotypes of C936T polymorphism of the VEGF gene in patients with sporadic colorectal adenocarcinoma, in comparison with controls, and whether this correlates with the degree of tumor invasion, lymph node involvement and occurrence of metastases at the time of the diagnosis. The analysis was done on 261 patients with sporadic colorectal adenocarcinoma and 261 controls. The genotypes of C936T polymorphism were evaluated by means of the polymerase chain reaction and enzyme digestion, using peripheral blood samples. Results The occurrences of genotype 936CC were similar in the two groups (80.5% versus 78.5%, p = 0.2288). In relation to tumor location, lymph node involvement, infiltration and tumor metastasis, no statistically significant results were obtained (p = 0.3116, p = 0.8485, p = 0.9408 and p = 0.2861, respectively). Conclusion C936T polymorphism of the VEGF gene did not influence the occurrence of sporadic colorectal adenocarcinoma development and did not correlated with the degree of tumor invasion, lymph node involvement and occurrence of metastases.
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Affiliation(s)
- Laura Credidio
- Department of Coloproctology, University of Campinas, Rua Carlos Chagas, 420, Cidade Universitária, Campinas, SP CEP 13083-878, Brazil.
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Kapahi R, Guleria K, Sambyal V, Manjari M, Sudan M, Uppal MS, Singh NR. Vascular endothelial growth factor (VEGF) gene polymorphisms and breast cancer risk in Punjabi population from North West India. Tumour Biol 2014; 35:11171-81. [PMID: 25106408 DOI: 10.1007/s13277-014-2404-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2014] [Accepted: 07/24/2014] [Indexed: 10/24/2022] Open
Abstract
The purpose of this study was to evaluate the association of seven VEGF promoter polymorphisms with breast cancer risk in Punjabi population from North West India. We screened DNA samples of 102 sporadic breast cancer patients and 102 unrelated healthy, gender, and age-matched individuals for seven VEGF promoter polymorphisms [-417 C/T (rs833062), -172 C/A (rs59260042), -165 C/T (rs79469752), -160 C/T, -152 G/A (rs13207351), -141 A/C (rs28357093) and -116 G/A (rs1570360)] by direct sequencing. The frequency of GG, GA, and AA genotype of -152 G/A polymorphism was 26.47 vs 38.34%, 46.08 vs 51.96%, and 27.45 vs 9.80%, in patients and controls, respectively. VEGF -152 AA genotype was significantly associated with increased risk for breast cancer (OR = 4.04, 95%CI, 1.69-9.68, p = 0.001; recessive model OR = 3.48, 95%CI, 1.59-7.63, p = 0.001). For VEGF -116 G/A polymorphism, G and A allele frequencies were 65.2 vs 76.47% and 34.8 vs 23.53% in patients and controls, respectively. Individuals having -116 AA genotype (OR = 3.40; 95%CI, 1.24-9.37; p = 0.014) and A allele (OR = 1.73; 95%CI, 1.12-2.67; p = 0.012) were associated with increased risk for breast cancer. VEGF -165 C/T and -141 A/C polymorphisms were associated with reduced risk for breast cancer. There was significantly decreased frequency of CT genotype (4.90 vs 18.63%; p = 0.002) and T allele (2.45 vs 9.31%; p = 0.003) of -165 C/T polymorphism among breast cancer patients as compared to controls. VEGF -141 A and C allele frequency were 96.57 vs 91.18% and 3.43 vs 8.82% in patients and controls, respectively. Significant reduced risk for breast cancer was observed with AC genotype (OR = 0.34, 95%CI, 0.14-0.86; p = 0.019) and C allele (OR = 0.37; 95%CI, 0.15-0.89; p = 0.023) of -141 A/C polymorphism. We did not observe association of VEGF -417 T/C, -172 C/A, -160 C/T polymorphisms with breast cancer risk in the studied subjects (p > 0.05). The VEGF -152 G/A and -116 G/A polymorphisms were found to be significantly associated with increased risk for breast cancer while -165 C/T and -141 A/C polymorphisms were found to be associated with decreased risk for breast cancer in Punjabi population from North West India.
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Affiliation(s)
- Ruhi Kapahi
- Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University, Amritsar, 143005, Punjab, India,
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20
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Chen Q, Zhou Z, Shan L, Hua Y, Zeng H, Liu P, Cai Z. Association of the vascular endothelial growth factor -2578C/A polymorphism with cancer risk: A meta-analysis update. Biomed Rep 2014; 2:823-830. [PMID: 25279153 DOI: 10.3892/br.2014.317] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2014] [Accepted: 06/25/2014] [Indexed: 01/23/2023] Open
Abstract
The vascular endothelial growth factor (VEGF) -2578C/A polymorphism has been previously reported to be associated with cancer risk; however, the results have been controversial. Therefore, the aim of the present study was to explore the association between the VEGF -2578C/A polymorphism with the cancer risk. A total of 37 case-control studies were identified. The pooled analysis showed that there was no association between VEGF -2578C/A and the risk of cancer, and the odds ratios (ORs) [with the corresponding 95% confidence intervals (95% CIs)] were 0.97 (0.91-1.04) for C vs. A, 0.94 (0.86-1.02) for CC vs. AA, 0.92 (0.80-1.06) for CA vs. AA, 0.96 (0.89-1.03) for CC/CA vs. AA and 0.97 (0.88-1.08) for CC vs. CA/AA. Subgroup analyses according to ethnicity, source of control and type of cancer showed that the VEGF -2578C/A polymorphism is associated with colorectal and lung cancers. Additionally, the polymorphism may decrease the risk of cancer in the Asian population. This VEGF polymorphism was not associated with a risk of cancer for the Caucasian [0.92 (0.76-1.11) for CC vs. AA] and African populations [1.31 (0.67-2.58) for CC vs. AA], and it was not associated with bladder [1.06 (0.74-1.53) for CC/AA] and breast cancers [1.01 (0.90-1.15) for CC/AA]. Therefore, the present meta-analysis indicates that VEGF -2578C/A may only be associated with the risk of colorectal cancer, lung cancer and the Asian population. More studies with larger sample sizes are required to provide more conclusive evidence.
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Affiliation(s)
- Quanchi Chen
- Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China
| | - Zifei Zhou
- Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China
| | - Liangcheng Shan
- Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China
| | - Yingqi Hua
- Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China
| | - Hui Zeng
- Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China
| | - Pengcheng Liu
- Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China
| | - Zhengdong Cai
- Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China
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21
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Sobjanek M, Zabłotna M, Lesiak A, Michajłowski I, Szczerkowska-Dobosz A, Sokolowska-Wojdylo M, Nowicki R. The -1154 G/A VEGF gene polymorphism is associated with the incidence of basal cell carcinoma in patients from northern Poland. Arch Dermatol Res 2014; 306:539-44. [PMID: 24902660 PMCID: PMC4107281 DOI: 10.1007/s00403-014-1471-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2013] [Revised: 04/10/2014] [Accepted: 05/01/2014] [Indexed: 10/27/2022]
Abstract
Vascular endothelial growth factor (VEGF) is believed to play a crucial role in neoplastic angiogenesis. Although the genetic background of basal cell carcinoma (BCC) has been analyzed in some papers, the mechanism of BCC pathogenesis is not fully understood. To the best of our knowledge, VEGF gene polymorphisms have not yet been explored. The aim of the study was to asses the frequency of three polymorphisms in the VEGF gene (-1154 G/A, -460 T/C and +405 G/C) in patients of Polish origin with BCC and control group. In addition, VEGF serum levels of patients with BCC and controls were measured. The study involved 180 patients (96 women, 84 men) with BCC and a mean age of 68.9 ± 11.8, and 215 healthy age- and sex-matched volunteers. The VEGF polymorphisms at positions -1154 and +405 were analyzed using the amplification refractory mutation system polymerase chain reaction method. To assess the VEGF gene polymorphism at position -460, we used the polymerase chain reaction restriction fragment length polymorphism method. Serum levels of VEGF protein were measured using the ELISA test. The presence of the G allele (GA or GG) in the -1154 VEGF polymorphism was associated with an increased risk of BCC development (OR = 7.28, p < 0.0001). Furthermore, the carriers of the AA genotype in -1154 VEGF polymorphism showed significantly reduced risks of BCC (OR = 0.14, p < 0.0001). It was also shown that the GTC haplotype of VEGF predisposes to BCC development (OR = 1.69, p = 0.013), while the presence of the ATG haplotype significantly reduces this risk (OR = 0.17, p = 0.00001). We have found significantly increased VEGF serum levels among BCC patients, in comparison with the healthy controls (mean 596.7 ± 393.5 pg/ml; range 60.1-931.4 vs. 255.9 ± 174.6 pg/ml; range 42.2-553.0 pg/ml; p < 0.0004). The serum levels of VEGF significantly correlated with tumor size: r = 0.41, p < 0.0001. Our results testify to the importance of -1154 G/A VEGF gene polymorphisms in altering the risk of BCC among the population from northern Poland.
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Affiliation(s)
- Michał Sobjanek
- Department of Dermatology, Venereology and Allergology, Medical University of Gdańsk, ul. Debinki 7, 80-952, Gdańsk, Poland,
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22
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Mishra K, Behari A, Kapoor VK, Khan MS, Prakash S, Agrawal S. Vascular endothelial growth factor single-nucleotide polymorphism in gallbladder cancer. J Gastroenterol Hepatol 2013; 28:1678-85. [PMID: 23962084 DOI: 10.1111/jgh.12343] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/28/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Angiogenesis plays a key role in growth, progression, and metastasis of various cancers. Vascular endothelial growth factor (VEGF) polymorphism has been associated with several cancers. Role of VEGF has not been reported in gallbladder cancer (GBC). Present study was designed to investigate the role of VEGF polymorphism in GBC and in other (benign) gallbladder diseases, that is chronic cholecystitis (CC) and xanthogranulomatous cholecystitis (XGC). METHODS Blood samples were collected from 195 GBC, 140 CC, and 47 XGC patients and 300 normal healthy controls. VEGF polymorphisms were investigated using amplification refractory mutation system polymerase chain reaction for g.43737830A>G and g.3437A>C, polymerase chain reaction-restriction fragment length polymorphism for c.*237C>T, and g.43736418delTinsG amplified by polymerase chain reaction. RESULTS At g.43737830A>G, GA genotype showed susceptibility (odds ratio [OR] = 1.65 and OR = 1.68) and GG genotype showed protective association (OR = 0.58 and OR = 0.50) with GBC and CC. Allele A of VEGF g.43737830A>G was risk associated with GBC and CC (OR = 1.48 and OR = 1.70), while G allele was risk protective for GBC and CC (OR = 0.67 and OR = 0.58). At g.3437A>C, genotype CA was risk protective for GBC (OR = 0.61). TT genotype of c.*237C>T was susceptible for GBC and CC (OR = 2.59 and OR = 3.48), while CC genotype was risk protective for GBC and CC (OR = 0.61 and OR = 0.34). T allele of c.*237C>T polymorphism was risk associated with GBC and CC (OR = 1.63 and OR = 2.90), while C allele was risk protective for GBC and CC (OR = 0.38 and OR = 0.28). Haplotype I-C-A-C was risk protective for GBC (OR = 0.27). CONCLUSION The present study suggests that c.*237C>T and g.43737830A>G polymorphisms are useful markers of susceptibility to GBC.
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Affiliation(s)
- Kumudesh Mishra
- Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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23
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Park JY, Amankwah EK, Anic GM, Lin HY, Walls B, Park H, Krebs K, Madden M, Maddox K, Marzban S, Fang S, Chen W, Lee JE, Wei Q, Amos CI, Messina JL, Sondak VK, Sellers TA, Egan KM. Gene variants in angiogenesis and lymphangiogenesis and cutaneous melanoma progression. Cancer Epidemiol Biomarkers Prev 2013; 22:827-34. [PMID: 23462921 PMCID: PMC3708315 DOI: 10.1158/1055-9965.epi-12-1129] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Angiogenesis and lymphangiogenesis are important in the progression of melanoma. We investigated associations between genetic variants in these pathways with sentinel lymph node (SLN) metastasis and mortality in 2 independent series of patients with melanoma. METHODS Participants at Moffitt Cancer Center were 552 patients, all Caucasian, with primary cutaneous melanoma referred for SLN biopsy. A total of 177 patients had SLN metastasis, among whom 60 died from melanoma. Associations between 238 single-nucleotide polymorphisms (SNP) in 26 genes and SLN metastasis were estimated as ORs and 95% confidence intervals (CI) using logistic regression. Competing risk regression was used to estimate HRs and 95% CI for each SNP and melanoma-specific mortality. We attempted to replicate significant findings using data from a genome-wide association study comprising 1,115 patients with melanoma who were referred for SLN biopsy from MD Anderson Cancer Center (MDACC), among whom 189 patients had SLN metastasis and 92 patients died from melanoma. RESULTS In the Moffitt dataset, we observed significant associations in 18 SNPs with SLN metastasis and 17 SNPs with mortality. Multiple SNPs in COL18A1, EGF receptor (EGFR), FLT1, interleukin (IL)-10, platelet-derived growth factor D (PDGFD), PIK3CA, and toll-like receptor (TLR)-3 were associated with the risk of SLN metastasis and/or patient mortality. The MDACC data set replicated an association between mortality and rs2220377 in PDGFD. Furthermore, in a meta-analysis, 3 additional SNPs were significantly associated with SLN metastasis (EGFR rs723526 and TLR3 rs3775292) and melanoma-specific death (TLR3 rs7668666). CONCLUSIONS These findings suggest that genetic variation in angiogenesis and lymphangiogenesis contributes to regional nodal metastasis and progression of melanoma. IMPACT Additional research attempting to replicate these results is warranted.
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Affiliation(s)
- Jong Y Park
- Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
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Association of vascular endothelial growth factor (VEGF) gene polymorphism and increased serum VEGF concentration with pancreatic adenocarcinoma. Pancreatology 2013; 13:267-72. [PMID: 23719599 DOI: 10.1016/j.pan.2013.02.006] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2013] [Revised: 02/05/2013] [Accepted: 02/20/2013] [Indexed: 12/11/2022]
Abstract
UNLABELLED BACKGROUND &AIM: Pancreatic cancer is related to high mortality rate. The vascular endothelial growth factor (VEGF) has a strong influence in tumor-related angiogenesis having association with the grade of angiogenesis and the prognosis of different solid tumors including pancreatic cancer. The present study was aimed to analyze the genotype and haplotype distribution of VEGF gene single nucleotide polymorphisms (SNPs), -460T/C, +405G/C, +936C/T, in patients with pancreatic adenocarcinoma from South India, and the effect of these SNPs on serum VEGF level. METHODS Total 80 patients with pancreatic adenocarcinoma and 87 controls were recruited. The genotype of VEGF gene polymorphisms was determined in both patients and controls using polymerase chain reaction-restriction fragment length polymorphism method. The serum VEGF protein was estimated by standard enzyme-linked immunosorbent assay. RESULTS The genotype, +405G/G of VEGF gene showed a significant association with the patients with pancreatic adenocarcinoma (P = 0.012, Odds ratio: 2.133), whereas no significant difference was found in the genotype distribution of SNPs, -460C/T and +936C/T between patient and control groups (P > 0.05). Serum VEGF level was found to be significantly high in patients (1315.10 pg/Ml, SD ± 230.79) when compared to controls (591.35 pg/mL, SD ± 92.48) (P < 0.0001), which showed a strong genotype-phenotype correlation between genotype +405G/G and serum VEGF level. Further, the haplotype C-G-T showed a strong association with the disease, and no specific haplotype was associated with increased serum VEGF level. CONCLUSION The polymorphism, +405G/C but not -460T/C and +936C/T, of VEGF gene is strongly associated with pancreatic adenocarcinoma, and this SNP has significant influence on serum VEGF level.
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Naykoo NA, Hameed I, Aasif M, Shaffi S, Yousuf Q, Bhat IA, Andrabi IA, Qasim I, Mir JI, Rasool R, Afroze D, Shah S, Shah ZA. WITHDRAWN: Single nucleotide polymorphisms, haplotype association and tumour expression of the vascular endothelial growth factor (VEGF) gene with lung carcinoma. Gene 2013:S0378-1119(13)00179-0. [PMID: 23458877 DOI: 10.1016/j.gene.2013.01.064] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Revised: 01/22/2013] [Accepted: 01/30/2013] [Indexed: 11/16/2022]
Abstract
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
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Affiliation(s)
- Niyaz A Naykoo
- Department of Immunology & Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir 190011, India.
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Sun M, Fu SM, Dong GY, Wu D, Wang GX, Wu Y. Inflammatory factors gene polymorphism in recurrent oral ulceration. J Oral Pathol Med 2013; 42:528-34. [DOI: 10.1111/jop.12048] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/03/2013] [Indexed: 11/26/2022]
Affiliation(s)
- Mao Sun
- Center for DNA Typing; Fourth Military Medical University; Xi'an China
- Department of Biochemistry and Molecular Biology; Fourth Military Medical University; Xi'an China
| | - Shan-Min Fu
- Department of Orthodontics; Fourth Military Medical University; Xi'an China
- School of Stomatology; Fourth Military Medical University; Xi'an China
| | - Guang-Ying Dong
- Department of Periodontics and Oral Medicine; Fourth Military Medical University; Xi'an China
- School of Stomatology; Fourth Military Medical University; Xi'an China
| | - Dan Wu
- Center for DNA Typing; Fourth Military Medical University; Xi'an China
- Department of Biochemistry and Molecular Biology; Fourth Military Medical University; Xi'an China
| | - Guo-Xia Wang
- Center for DNA Typing; Fourth Military Medical University; Xi'an China
- Department of Biochemistry and Molecular Biology; Fourth Military Medical University; Xi'an China
| | - Yuanming Wu
- Center for DNA Typing; Fourth Military Medical University; Xi'an China
- Department of Biochemistry and Molecular Biology; Fourth Military Medical University; Xi'an China
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Kämmerer PW, Koch FP, Schiegnitz E, Kumar VV, Berres M, Toyoshima T, Al-Nawas B, Brieger J. Associations between single-nucleotide polymorphisms of the VEGF gene and long-term prognosis of oral squamous cell carcinoma. J Oral Pathol Med 2012; 42:374-81. [DOI: 10.1111/jop.12026] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/26/2012] [Indexed: 12/23/2022]
Affiliation(s)
- P. W. Kämmerer
- Harvard Medical School; Boston MA USA
- Department of Oral, Maxillofacial and Plastic Surgery; University Medical Centre; Mainz Germany
- M.R. Ambedkar Dental College and Hospital; Bangalore India
| | - F. P. Koch
- Department of Oral, Maxillofacial and Plastic Surgery; University Medical Centre; Mainz Germany
| | - E. Schiegnitz
- Department of Oral, Maxillofacial and Plastic Surgery; University Medical Centre; Mainz Germany
| | - V. V. Kumar
- Department of Oral, Maxillofacial and Plastic Surgery; University Medical Centre; Mainz Germany
- M.R. Ambedkar Dental College and Hospital; Bangalore India
| | - M. Berres
- Institute of Medical Biostatistics; Epidemiology and Informatics (IMBEI); University Medical Centre; Mainz Germany
| | - T. Toyoshima
- Department of Oral and Maxillofacial Surgery; Kyushu University; Fukuoka Japan
| | - B. Al-Nawas
- Department of Oral, Maxillofacial and Plastic Surgery; University Medical Centre; Mainz Germany
| | - J. Brieger
- Department of Otorhinolaryngology; Johannes Gutenberg-University; Mainz Germany
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Supic G, Jovic N, Zeljic K, Kozomara R, Magic Z. Association of VEGF-A genetic polymorphisms with cancer risk and survival in advanced-stage oral squamous cell carcinoma patients. Oral Oncol 2012; 48:1171-7. [DOI: 10.1016/j.oraloncology.2012.05.023] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2012] [Revised: 05/14/2012] [Accepted: 05/26/2012] [Indexed: 01/30/2023]
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Abstract
A wide variety of diseases have a significant genetic component, including major causes of morbidity and mortality in the western world. Many of these diseases are also angiogenesis dependent. In humans, common polymorphisms, although more subtle in effect than rare mutations that cause Mendelian disease, are expected to have greater overall effects on human disease. Thus, common polymorphisms in angiogenesis-regulating genes may affect the response to an angiogenic stimulus and thereby affect susceptibility to or progression of such diseases. Candidate gene studies have identified several associations between angiogenesis gene polymorphisms and disease. Similarly, emerging pharmacogenomic evidence indicates that several angiogenesis-regulating polymorphisms may predict response to therapy. In contrast, genome-wide association studies have identified only a few risk alleles in obvious angiogenesis genes. As in other traits, regulatory polymorphisms appear to dominate the landscape of angiogenic responsiveness. Rodent assays, including the mouse corneal micropocket assay, tumor models, and a macular degeneration model have allowed the identification and comparison of loci that directly affect the trait. Complementarity between human and animal approaches will allow increased understanding of the genetic basis for angiogenesis-dependent disease.
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Affiliation(s)
- Michael S Rogers
- Vascular Biology Program, Children's Hospital, Boston, Massachusettes, USA.
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Current Evidence on VEGF+405G/C Polymorphism and Malignancy Susceptibility: A Meta-Analysis Involving 30 Studies. Twin Res Hum Genet 2012; 15:496-502. [DOI: 10.1017/thg.2012.34] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The association of VEGF+405G/C (where VEGF is vascular endothelial growth factor) polymorphism and malignancy susceptibility attracts considerable attention because VEGF is one of the most potent angiogenic factors and plays a critical role in the onset and development of malignancy. However, the published findings remain inconclusive. In order to derive a more precise assessment of the association, we performed a meta-analysis including 30 published case-control studies from PubMed, Embase, and Ovid databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. In the pooled analyses, no significant association was found between VEGF+405G/C polymorphism and malignancy susceptibility in different genetic models (G-allele vs. C-allele: OR = 1.00, 95% CI: 0.93–1.07; CC vs. GG: OR = 1.01, 95% CI: 0.88–1.15; GC+CC vs. GG: OR = 1.00, 95% CI: 0.91–1.10; CC vs. GC+GG: OR = 1.01, 95% CI: 0.90–1.13). When stratified by ethnicity, a weak association between this polymorphism and malignancy susceptibility was found in African under allelic frequency comparison (OR = 0.65, 95% CI: 0.43–0.98) and dominant genetic model comparison (OR = 1.95, 95% CI: 1.09–3.50). In summary, although our meta-analysis indicated a weak association of VEGF+405G/C polymorphism with malignancy susceptibility in African, no persuasive evidence of association between the polymorphism and malignancy susceptibility was detected in the pooled analyses. Therefore, more studies with larger scale of participants, especially Africans, are required to further evaluate gene-environment interaction on this polymorphism and malignancy susceptibility.
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Vascular endothelial growth factor A gene (VEGFA) polymorphisms and expression of VEGFA gene in lung cancer patients of Kashmir Valley (India). Tumour Biol 2012; 33:833-9. [DOI: 10.1007/s13277-011-0306-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2011] [Accepted: 12/21/2011] [Indexed: 01/22/2023] Open
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Lee YJ, Lee JS, Kang EH, Lee YK, Kim SY, Song YW, Koo KH. Vascular endothelial growth factor polymorphisms in patients with steroid-induced femoral head osteonecrosis. J Orthop Res 2012; 30:21-7. [PMID: 21710604 DOI: 10.1002/jor.21492] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2010] [Accepted: 06/09/2011] [Indexed: 02/04/2023]
Abstract
To investigate an association between steroid-induced femoral head osteonecrosis (FHON) and functional vascular endothelial growth factor (VEGF) gene (-2578A/C, -1154A/G, -634C/G, and +405C/G) polymorphisms polymerase chain reaction-restriction fragment length polymorphism genotyping was performed in 160 patients (86 idiopathic FHON and 74 steroid-induced FHON) and 160 gender- and age-matched controls. The steroid-induced subgroup had a significantly lower prevalence of -1154A allele (7.4% vs. 18.1%, odds ratio (OR) = 0.363) and genotype carrying -1154A (14.9% vs. 32.5%, OR = 0.333 in a recessive model) than controls. In a dominant model, the frequency of genotype carrying +405G (74.3% vs. 84.4%, OR = 0.492) was significantly lower in steroid-induced FHON than in controls. The distribution of haplotypes was significantly different between controls and FHON patients (p = 0.00011). Especially, when haplotypes were classified into high (CGCG and AAGG) or low (CGGC and AGGC) VEGF inducing haplotypes, patients with steroid-induced FHON had a significantly lower prevalence of high inducing haplotypes (7.4% vs. 15.9%, OR = 0.424) and a significantly higher prevalence of low inducing haplotypes (4.7% vs. 0.6%, OR = 7.894) than controls. Low inducing VEGF haplotypes may confer an increased risk and high inducing haplotypes have a protective effect for the development of steroid-induced FHON in Korea.
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Affiliation(s)
- Yun Jong Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea
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Zablotna M, Sobjanek M, Nedoszytko B, Lange M, Kozicka D, Glen J, Roszkiewicz J. Association of psoriasis with the VEGF gene polymorphism in the northern Polish population. J Eur Acad Dermatol Venereol 2011; 27:319-23. [PMID: 22176586 DOI: 10.1111/j.1468-3083.2011.04393.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Neovascularization plays an important role in pathogenesis of psoriasis and vascular endothelial growth factor (VEGF) seems to be the main angiogenic factor involved in this disease. Published studies which analysed the role of VEGF gene polymorphism in psoriasis were limited and they received controversial results. Objective The aim of our study was to evaluate the association between -1154 G/A, -460 T/C and +405 G/C polymorphisms and the psoriasis susceptibility and to determine whether this genetic variation influence levels of VEGF protein expression. MATERIALS AND METHODS One hundred and eighty-nine patients with psoriasis and 215 ethnically matched controls were genotyped using ARMS-PCR and PCR-RFLP methods. VEGF serum levels were assessed in 47 patients and 40 controls using ELISA test. RESULTS We noted that an increased risk of Type I psoriasis is associated with -1154 G allele (OR = 1.9; P = 0.04), +405 CC (OR = 2.86; P = 0.03) and -460 TT (OR = 1.56; P = 0.05) genotypes and demonstrated that a significantly increased risk of developing disease is related to presence of haplotype GTC among all patients (OR = 1.97; P = 0.001), patients with Type I (OR = 1.87; P = 0.005) and Type II psoriasis (OR = 2.37, P = 0.01). We have found significantly increased serum levels of VEGF in patients with psoriasis compared with those in healthy controls (P = 0.008). Serum levels of VEGF significantly correlated with PASI: r = 0.72, P < 0.00001. Patients with elevated levels of VEGF in the serum showed more frequently: GC genotype (P = 0.04), C allele (P = 0.02) at the locus +405 and TT genotype (P = 0.03) at the locus -460. CONCLUSION Our results strongly support the role of VEGF gene polymorphism in the pathogenesis of psoriasis.
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Affiliation(s)
- M Zablotna
- Department of Dermatology, Wenerology and Allergology, Medical University of Gdansk, Poland
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Hong TT, Zhang RX, Wu XH, Hua D. Polymorphism of vascular endothelial growth factor −1154G>A (rs1570360) with cancer risk: a meta-analysis of 16 case–control studies. Mol Biol Rep 2011; 39:5283-9. [DOI: 10.1007/s11033-011-1326-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2011] [Accepted: 12/03/2011] [Indexed: 10/14/2022]
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Gong ZP, Qiao ND, Gu YX, Song JP, Li PL, Qiu HJ, Fan WW, Mao Y, Chen HY, Zhao Y. Polymorphisms of VEGFA gene and susceptibility to hemorrhage risk of brain arteriovenous malformations in a Chinese population. Acta Pharmacol Sin 2011; 32:1071-7. [PMID: 21706043 DOI: 10.1038/aps.2011.76] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
AIM To evaluate the influence of the vascular endothelial growth factor A (VEGFA) polymorphisms on risk of presentation with intracerebral hemorrhage (ICH). METHODS Nine selected VEGFA single-nucleotide polymorphisms (SNPs) were genotyped in 311 patients with brain arteriovenous malformations (BAVM) in a Chinese population. Associations between individual SNPs/haplotypes and the hemorrhage risk of BAVMs were evaluated using logistic regression analysis. RESULTS In the single-locus analysis, rs1547651 was associated with increased risk of ICH (adjusted OR=2.11, 95% CI=1.01-4.42 compared with the AA genotype). In particular, an increased risk for ICH was associated with this variant in female patients (adjusted OR=3.21, and 95% CI=0.99-10.36). Haplotype-based analyses revealed that haplotype 'GC' in block 1 and haplotype 'ACC' in block 2 were associated with a 30%-38% reduction in the risk of ICH in patients with BAVMs compared to the most common haplotype (P(sim)=0.033 and P(sim)=0.005, respectively). The protective effect of haplotype 'ACC' in block 2 was more evident in male patients and subjects with BAVMs of a size ≥3 cm (adjusted OR=0.57, 95% CI=0.34-0.97 and adjusted OR=0.57, 95% CI=0.31-0.86, respectively). CONCLUSION The results suggest that VEGFA gene variants may contribute to ICH risk of BAVM.
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Association of vascular endothelial growth factor gene polymorphisms with osteoporotic vertebral compression fractures in postmenopausal women. Genes Genomics 2010. [DOI: 10.1007/s13258-010-0013-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Li Y, Wang Y, Kang S, Wang N, Zhou RM, Duan YN, Sun DL, Qin JJ, Zhao W, Zhao L. Association of vascular endothelial growth factor gene polymorphisms with susceptibility to epithelial ovarian cancer. Int J Gynecol Cancer 2010; 20:717-23. [PMID: 20973260 DOI: 10.1111/igc.0b013e3181dbd32b] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Vascular endothelial growth factor (VEGF) is a major angiogenic factor involved in a number of pathological processes, including neovascularization, a crucial step in the development of solid malignancies. The aim of this study was to investigate the association of polymorphisms in the VEGF gene with susceptibility to epithelial ovarian cancer (EOC). METHODS This case-control study included 303 EOC patients and 303 healthy controls. Genotyping of the VEGF gene polymorphisms at j460C/T, j1154G/A, j2578C/A, and +936C/T were performed by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS No significant difference was found in allele and genotype distributions of the -460C/T, +936C/T, and -2578C/A polymorphisms between patients and controls. However, the frequencies of -1154G/A genotype and allele were significantly different between the two groups (P = 0.037, P = 0.013). Compared with the G/A + A/A genotype, the G/G genotype could significantly increase the risk of developing EOC (odds ratio, 1.64; 95% confidence interval, 1.12Y2.39). The haplotype analysis suggested that the -460T/ -1154A/ -2578C haplotype exhibited a decrease in the risk of developing EOC compared with the -460T/ -1154G/ -2578C haplotype (odds ratio, 0.644; 95% confidence interval, 0.415-0.999). CONCLUSIONS The study suggested a possible association between the VEGF -1154G/A polymorphism with susceptibility to EOC, but there is no support for an association of the VEGF -460C/T, +936C/T, and -2578C/A polymorphisms with the risk for EOC.
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Affiliation(s)
- Yan Li
- Department of Molecular Biology, Hebei Cancer Institute, Hebei Medical University, Fourth Hospital, Jiankanglu 12, Shijiazhuang 050011, China.
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Li R, Zhao Y, Fan W, Chen H, Chen Y, Liu Y, Chen G, Zhou K, Huang F, Mao Y, Zhou L, Lu D, Shugart YY. Possible association between polymorphisms of human vascular endothelial growth factor A gene and susceptibility to glioma in a Chinese population. Int J Cancer 2010; 128:166-75. [DOI: 10.1002/ijc.25306] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Cao C, Fang JJ, Ying T, Sun SF, Lv D, Chen ZB, Ma HY, Yu YM, Ding QL, Shu LH, Deng ZC. Vascular Endothelial Growth Factor +936C/T and +405G/C Polymorphisms and Cancer Risk: a Meta-analysis. Arch Med Res 2010; 41:548-57. [DOI: 10.1016/j.arcmed.2010.09.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2010] [Accepted: 09/14/2010] [Indexed: 12/12/2022]
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Wu X, Li D, Liu Z, Wan X, Wu Y, Jiang C, Qian Q. Vascular endothelial growth factor 1498C/T, 936C/T polymorphisms associated with increased risk of colorectal adenoma: a Chinese case-control study. Mol Biol Rep 2010; 38:1949-55. [PMID: 20857215 DOI: 10.1007/s11033-010-0316-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2010] [Accepted: 09/03/2010] [Indexed: 12/25/2022]
Abstract
Single nucleotide polymorphisms in vascular endothelial growth factor gene VEGF, 1498C/T and 936 C/T are associated with colorectal cancer. We sought to determine whether such genetic variability in VEGF contributes to susceptibility of colorectal adenoma (CRA), a presumably precancerous state of colorectal cancer. In this research, two aforementioned polymorphisms were investigated for CRA susceptibility in a Chinese case-control study. The epidemiological risk factors were collected through questionnaire. The plasma VEGF levels were measured via enzyme-linked immunosorbent assay (ELISA). The Taqman-Probe assay was used to determine genotypes in 224 CRA patients and 200 CRA-free controls. The clinicopathological data of each sample were collected for further correlation analysis. According to data analysis males, cigarette smokers, patients who carry metabolic syndrome or familial antecedent of adenomas were significantly associated with CRA risk. Plasma VEGF levels of CRA patients were higher than those of controls (P = 0.003). This difference is independent of genotypes. The carriers with 936CT and CT+TT had higher risk of CRA in comparison with controls (CT vs. CC, OR 2.00, 95% CI 1.23-3.25, P = 0.006; CT+TT vs. CC, OR 2.04, 95% CI 1.28-3.26, P = 0.003). 936-T allele was associated with increased risk of CRA (OR 1.91, 95% CI 1.25-2.91, P = 0.003). Both CRA and control show no difference in the genotype of 1498C/T and the allele frequency of C-/T-. CRA patients with haplotype 1498T+936T presented significantly higher risk than those with wild-type 1498T+936C. Moreover, patients carrying 936CT+TT and 936-T allele demonstrated a tendency for villous adenoma. CRA patients have elevated plasma VEGF levels. The VEGF 936C/T polymorphism and 1498T+936T haplotype were found to be associated with increased CRA susceptibility.
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Affiliation(s)
- Xianglei Wu
- Department of Colorectal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071 Hubei, China
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VEGF polymorphisms are associated with an increasing risk of developing renal cell carcinoma. J Urol 2010; 184:1273-8. [PMID: 20723915 DOI: 10.1016/j.juro.2010.06.009] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2010] [Indexed: 11/23/2022]
Abstract
PURPOSE Vascular endothelial cell growth factor is studied in different malignant tumors as a key endothelial cell mitogen. Many single nucleotide polymorphisms in the VEGF gene have been described. We compared VEGF gene polymorphisms between a control group and a renal cancer group. MATERIALS AND METHODS This study was performed in 202 control, white, healthy blood donors (control group) and in 51 consecutive patients with renal cell carcinoma. We studied VEGF genotype polymorphisms at positions -2549, -460, -1154, +405 and +936 using polymerase chain restriction fragment length polymorphism, and looked for correlations with clinical data. RESULTS No association was found between VEGF gene polymorphism and renal cell carcinoma prognostic parameters. However, in contrast as observed for controls and other polymorphisms the patient group displayed a heterozygote excess (p = 0.0179, 35.9% more than that expected) at the -460 polymorphism. Comparing the control group and the renal cell carcinoma group we detected a significantly increased risk of renal cell carcinoma in subjects with the C-460T polymorphism. T carrier genotypes and the T allele increased the risk of renal cell carcinoma with an OR of 14.15 (95% CI 1.900-105.41, p = 0.0017) and 2.14 (95% CI 1.34-3.419, p = 0.0018), respectively. The genotype at the -2549 polymorphism exhibited a nonsignificant trend for increased risk but the D allele was significantly associated with increased risk (p = 0.0305). CONCLUSIONS Our results suggest that the -460 polymorphism is a risk factor for renal cancer. An individual screening test could be proposed for high risk populations.
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Provinciali M, Re F, Tucci MG, Ricotti F, Lattanzio F. Persistent ex vivo low number and functional in vitro recovery of circulating gammadelta T cells after removal of a cutaneous primary melanoma. Scand J Immunol 2010; 72:142-9. [PMID: 20618773 DOI: 10.1111/j.1365-3083.2010.02413.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
We recently described gammadelta T cells alterations in patients with a cutaneous primary melanoma. To evaluate whether gammadelta T cells alterations persisted after melanoma removal, we performed a follow-up study comparing the number and function of gammadelta T lymphocytes from 19 subjects, 4 years after the removal of a cutaneous primary melanoma, with the data obtained in the same subjects before the surgical intervention and with control donors. The number of circulating gammadelta(+) T cells after melanoma removal was not recovered to the levels found in controls. gammadelta(+) T cells producing TNF-alpha or IFN-gamma were increased after melanoma removal in comparison with the same subjects before surgical intervention or with control donors. After in vitro culture, both the percentage and the expansion of gammadelta T cells were recovered to the values found in controls. In conclusion, the functional capacity of gammadelta T cells was in vitro recovered after melanoma removal, whereas their ex vivo number remained at lower levels than control donors.
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Affiliation(s)
- M Provinciali
- Advanced Technology Center for Aging Research, INRCA-IRCCS, Scientific-Technological Area, Ancona, Italy.
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Cao C, Ying T, Fang JJ, Sun SF, Lv D, Chen ZB, Ma HY, Yu YM, Ding QL, Shu LH, Deng ZC. Polymorphism of vascular endothelial growth factor –2578C/A with cancer risk: evidence from 11263 subjects. Med Oncol 2010; 28:1169-75. [DOI: 10.1007/s12032-010-9613-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2010] [Accepted: 06/19/2010] [Indexed: 11/30/2022]
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Chen MH, Tzeng CH, Chen PM, Lin JK, Lin TC, Chen WS, Jiang JK, Wang HS, Wang WS. VEGF -460T → C polymorphism and its association with VEGF expression and outcome to FOLFOX-4 treatment in patients with colorectal carcinoma. THE PHARMACOGENOMICS JOURNAL 2010; 11:227-36. [PMID: 20531372 DOI: 10.1038/tpj.2010.48] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The -460T → C polymorphism of vascular endothelial growth factor (VEGF) gene significantly increases its promoter activity. A pilot study was conducted to assess the influence of this polymorphism on clinicopathological features of patients with colorectal carcinoma. In total, 228 patients were enrolled, including 100 with stage II/III colorectal carcinoma receiving curative surgery and 128 with metastatic disease. An excellent correlation in VEGF -460 genotypes based on white blood cells and tumor tissues existed, but there was no between-group difference in patients with or without colorectal carcinoma. A marked increase in intratumor and circulating VEGF levels were observed in patients with the T/C or C/C genotypes (P < 0.01), which was associated with increased extent of invasion, nodal involvement, poor histological differentiation, subsequent metastasis and shorter survival in stage II/III patients treated with curative surgery (P < 0.01). For patients with metastatic disease, this polymorphism was associated with a lower response rate to FOLFOX-4 (P = 0.03) and shorter survival (P < 0.001). By multivariate analysis, this polymorphism was identified as an independent prognostic factor (P = 0.01). These data suggest that -460T → C polymorphism of VEGF gene, by increasing VEGF expression and subsequent angiogenesis, could be a key determinant for increased tumor recurrence and a poor prognosis of patients with colorectal carcinoma. However, this study is exploratory and is not adjusted for multiple comparisons, requiring independent replication.
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Affiliation(s)
- M-H Chen
- National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
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Hansen TF, Spindler KLG, Lorentzen KA, Olsen DA, Andersen RF, Lindebjerg J, Brandslund I, Jakobsen A. The importance of -460 C/T and +405 G/C single nucleotide polymorphisms to the function of vascular endothelial growth factor A in colorectal cancer. J Cancer Res Clin Oncol 2010; 136:751-8. [PMID: 19904558 DOI: 10.1007/s00432-009-0714-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2008] [Accepted: 10/19/2009] [Indexed: 01/02/2023]
Abstract
PURPOSE The present study investigated the functional influence of the single nucleotide polymorphisms (SNPs) -460 C/T and +405 G/C at vascular endothelial growth factor A (VEGF-A), mRNA and protein levels in colorectal cancer (CRC) and normal colorectal tissue. METHODS Blood and tissue were collected from 113 patients surgically resected for colorectal cancer. SNPs were analysed from genomic DNA by PCR, the VEGF-A gene expression analysis was performed by RT-PCR and protein analysis by ELISA. RESULTS The T-allele in the -460 C/T SNP and the C-allele in the +405 G/C SNP were associated with significantly lower VEGF-A protein levels in normal colorectal tissue. There were no differences in protein levels in the malignant tissue according to genotypes. No differences were observed at the gene expression levels either. CONCLUSION The results indicate that the two SNPs have a functional influence on the VEGF-A protein levels in normal colorectal tissue. The possible clinical implications of the findings need further investigation.
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Xu B, Li JM, Tong N, Tao J, Li PC, Song NH, Zhang W, Wu HF, Feng NH, Hua LX. VEGFA +936C>T polymorphism and cancer risk: a meta-analysis. ACTA ACUST UNITED AC 2010; 198:7-14. [PMID: 20303008 DOI: 10.1016/j.cancergencyto.2009.11.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2009] [Revised: 11/06/2009] [Accepted: 11/10/2009] [Indexed: 12/17/2022]
Abstract
Vascular endothelial growth factor A (VEGF-A), a major driver of physiological and pathological angiogenesis, plays important roles in the etiology and metastasis of cancers. The +936C>T polymorphism in the 3'-untranslated region of the VEGFA gene has been implicated in cancer risk and is related to VEGF-A protein production; however, published data have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed of 13,293 cancer cases and 12,308 control subjects from 29 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between +936C>T polymorphism and cancer risk. The meta-analysis indicated that individuals with the +936 T had increased risk of oral cancer (OR = 1.39, 95% CI = 1.03-1.88), although no association was found in the contrast of T versus C (OR = 1.00, 95% CI = 0.91-1.10) in the pooled analyses. This meta-analysis supports the idea that VEGFA + 936 T is associated with increased risk of oral cancer. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between VEGFA + 936C>T polymorphism and cancer risk.
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Affiliation(s)
- Bin Xu
- Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
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Lee HH, Hong SH, Shin SJ, Ko JJ, Oh D, Kim NK. Association study of vascular endothelial growth factor polymorphisms with the risk of recurrent spontaneous abortion. Fertil Steril 2010; 93:1244-7. [DOI: 10.1016/j.fertnstert.2008.11.017] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2008] [Revised: 10/15/2008] [Accepted: 11/20/2008] [Indexed: 12/01/2022]
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Ruiz M, Biselli P, Maniglia J, Pavarino-Bertelli E, Goloni-Bertollo E. Genetic variability of vascular endothelial growth factor and prognosis of head and neck cancer in a Brazilian population. Braz J Med Biol Res 2010; 43:127-33. [DOI: 10.1590/s0100-879x2009007500036] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2009] [Accepted: 12/16/2009] [Indexed: 11/22/2022] Open
Affiliation(s)
- M.T. Ruiz
- Faculdade de Medicina de São José do Rio Preto
| | | | - J.V. Maniglia
- Faculdade de Medicina de São José do Rio Preto, Brasil
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Guan X, Zhao H, Niu J, Tang D, Ajani JA, Wei Q. The VEGF -634G>C promoter polymorphism is associated with risk of gastric cancer. BMC Gastroenterol 2009; 9:77. [PMID: 19835575 PMCID: PMC2771032 DOI: 10.1186/1471-230x-9-77] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2009] [Accepted: 10/16/2009] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Both TGF-beta1 and VEGF play a critic role in the multiple-step process of tumorgenesis of gastric cancer. Single nucleotide polymorphisms (SNPs) of the TGFB1 and VEGF genes have been associated with risk and progression of many cancers. In this study, we investigated the association between potentially functional SNPs of these two genes and risk of gastric cancer in a US population. METHODS The risk associated with genotypes and haplotypes of four TGFB1 SNPs and four VEGF SNPs were determined by multivariate logistic regression analysis in 171 patients with gastric cancer and 353 cancer-free controls frequency-matched by age, sex and ethnicity. RESULTS Compared with the VEGF-634GG genotype, the -634CG genotype and the combined -634CG+CC genotypes were associated with a significantly elevated risk of gastric cancer (adjusted OR = 1.88, 95% CI = 1.24-2.86 and adjusted OR = 1.56, 95% CI = 1.07-2.27, respectively). However, none of other TGFB1 and VEGF SNPs was associated with risk of gastric cancer. CONCLUSION Our data suggested that the VEGF-634G>C SNP may be a marker for susceptibility to gastric cancer, and this finding needs to be validated in larger studies.
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Affiliation(s)
- Xiaoxiang Guan
- Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
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Wu GY, Hasenberg T, Magdeburg R, Bönninghoff R, Sturm JW, Keese M. Association between EGF, TGF-beta1, VEGF gene polymorphism and colorectal cancer. World J Surg 2009; 33:124-9. [PMID: 19011936 DOI: 10.1007/s00268-008-9784-5] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Up to the present, EGF 61 A/G, TGF-beta1 -509 T/C, and VEGF 936 T/C gene polymorphisms have been analyzed in other cancer entities than colorectal cancer. We have now investigated the frequency of these gene polymorphisms among colorectal cancer patients. MATERIAL AND METHODS A total of 157 colorectal cancer patients and 117 cancer-free healthy people were recruited at the Surgical Department of the Universitätsklinikum Mannheim. All patients and healthy people are Caucasians. Genomic DNA was isolated from peripheral blood, and gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS The distribution of EGF 61 G/G homozygotes among colorectal cancer patients was more frequent than that in the control group (33.1% versus 11.1%; Odds Ratio [OR]=3.962; 95% Confidence Interval [CI]=2.036-7.708). The frequency of the "G" allele in the colorectal cancer patient group was also higher than that in the control group (51.3% versus 33.3%; OR=2.105; 95% CI=1.482-2.988). No difference could be found for the TGF-beta1 and VEGF genotypes among colorectal cancer patients and healthy controls. CONCLUSIONS The EGF 61 G/G genotype and the G allele are significantly related to colorectal cancer. The TGF-beta1 -509 T/C and VEGF 936 T/C gene polymorphisms are not related to colorectal cancer.
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Affiliation(s)
- Guo-yang Wu
- Department of General Surgery, Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China.
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