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The Relation of VEGFA, VEGFR2, VEGI, and HIF1A Genetic Variants and Their Serum Protein Levels with Breast Cancer in Egyptian Patients

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Abstract

Breast cancer is the most common type of cancer in Egyptian females. Polymorphisms in the angiogenesis pathway have been implicated previously in cancer risk and prognosis. The aim of the current study was to determine whether certain polymorphisms in the genes of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), vascular endothelial growth inhibitor (VEGI), and hypoxia-inducible factor-1α (HIF1A) associated with breast cancer development. The study included 154 breast cancer patients and 132 apparently healthy age-matched females as a control group. VEGFA rs25648 genotyping was performed using (ARMS) PCR technique; while VEGFR2 rs2071559, VEGI rs6478106, and HIF-1α rs11549465 were genotyped by the PCR–RFLP method. Serum levels of VEGF, VEGFR2, VEGI, and HIF1A proteins in breast cancer patients and controls were measured by ELISA. There was a significant association between the VEGFA rs25648 C allele and breast cancer risk (OR 2.5, 95% CI 1.7–3.6, p < 0.001). VEGFA rs25648 C/C genotype was statistically significantly higher in breast cancer patients vs. control (p < 0.001). Participants with the T/T and T/C VEGFR2 rs2071559 genotypes had 5.46 and 5 higher odds, respectively, of having breast cancer than those with the C/C genotype. For the VEGI rs6478106 polymorphism, there was a higher proportion of C allele in breast cancer patients vs. control (p = 0.003). Moreover, the C/C genotype of VEGI rs6478106 was statistically significantly higher in breast cancer patients vs. control (p = 0.001). There was no significant difference in genotypes and allele frequencies of HIF1A rs11549465 polymorphism between breast cancer cases and control individuals (p > 0.05). Serum levels of VEGFA, VEGI, and HIF1A were considerably greater in women with breast cancer than in the control (p < 0.001). In conclusion, the genetic variants VEGFA rs25648, VEGFR2 rs2071559, and VEGI rs6478106 revealed a significant association with increased breast cancer risk in Egyptian patients.

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References

  • Absenger G, Szkandera J, Stotz M, Pichler M, Winder T et al (2013) A common and functional gene variant in the vascular endothelial growth factor a predicts clinical outcome in early-stage breast cancer. Mol Carcinog 52:96–102

    Article  Google Scholar 

  • Albalawi IA, Mir R, Duhier FA (2020) Genetic effects of vascular endothelial growth factor A (VEGF-A) and its association with disease progression in breast cancer population of Saudi Arabia. Asian Pac J Cancer Prev APJCP 21:139

    Article  CAS  PubMed  Google Scholar 

  • Al-Habboubi HH, Sater MS, Almawi AW, Al-Khateeb GM, Almawi WY (2011) Contribution of VEGF polymorphisms to variation in VEGF serum levels in a healthy population. Eur Cytokine Netw 22:154–158

    Article  CAS  PubMed  Google Scholar 

  • Apaydin I, Konac E, Onen HI, Akbaba M, Tekin E et al (2008) Single nucleotide polymorphisms in the hypoxia-inducible factor-1α (HIF-1α) gene in human sporadic breast cancer. Arch Med Res 39:338–345

    Article  CAS  PubMed  Google Scholar 

  • Autiero M, Luttun A, Tjwa M, Carmeliet P (2003) Placental growth factor and its receptor, vascular endothelial growth factor receptor-1: novel targets for stimulation of ischemic tissue revascularization and inhibition of angiogenic and inflammatory disorders. J Thromb Haemost 1:1356–1370

    Article  CAS  PubMed  Google Scholar 

  • Balasubramanian S, Brown N, Reed M (2002) Role of genetic polymorphisms in tumour angiogenesis. Br J Cancer 87:1057–1065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Balasubramanian SP, Cox A, Cross SS, Higham SE, Brown NJ et al (2007) Influence of VEGF-A gene variation and protein levels in breast cancer susceptibility and severity. Int J Cancer 121:1009–1016

    Article  CAS  PubMed  Google Scholar 

  • Bamias G, Siakavellas SI, Stamatelopoulos KS, Chryssochoou E, Papamichael C et al (2008) Circulating levels of TNF-like cytokine 1A (TL1A) and its decoy receptor 3 (DcR3) in rheumatoid arthritis. Clin Immunol 129(2):249–255

    Article  CAS  PubMed  Google Scholar 

  • Bray F, Ren JS, Masuyer E, Ferlay J (2013) Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 132:1133–1145

    Article  CAS  PubMed  Google Scholar 

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  PubMed  Google Scholar 

  • Carmeliet P (2005) VEGF as a key mediator of angiogenesis in cancer. Oncology 69:4–10

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Dawes PT, Mattey DL (2012) Polymorphism in the vascular endothelial growth factor A (VEGFA) gene is associated with serum VEGF-A level and disease activity in rheumatoid arthritis: differential effect of cigarette smoking. Cytokine 58:390–397

    Article  CAS  PubMed  Google Scholar 

  • Cheng K, Shen Y, Liu J, Wang X, Hua Y (2017) The association between the C1772T genetic polymorphism in human HIF-1α gene and breast cancer risk: a meta-analysis. Chemo Open Access 6:2

    Google Scholar 

  • Chew LJ, Pan H, Yu J, Tian S, Huang WQ et al (2002) A novel secreted splice variant of vascular endothelial cell growth inhibitor. FASEB J 16:742–744

    Article  CAS  PubMed  Google Scholar 

  • Cingeetham A, Nanchari SR, Damineni S, Tipirisetti N, Gorre M et al (2015) HIF-1α (1772C>T) polymorphism as marker for breast cancer development. Tumour Biol 36:3215–3220

    Article  PubMed  Google Scholar 

  • Das SK, Vasudevan D (2007) Essential factors associated with hepatic angiogenesis. Life Sci 81:1555–1564

    Article  CAS  PubMed  Google Scholar 

  • De Silva P, Nguyen D, Sauk J, Korzenik J, Yajnik V et al (2012) Long-term outcome of a third anti-TNF monoclonal antibody after the failure of two prior anti-TNFs in inflammatory bowel disease. Aliment Pharmacol Ther 36:459–466

    Article  PubMed  Google Scholar 

  • Fallah A, Sadeghinia A, Kahroba H, Samadi A, Heidari HR et al (2019) Therapeutic targeting of angiogenesis molecular pathways in angiogenesis-dependent diseases. Biomed Pharmacother 110:775–785

    Article  CAS  PubMed  Google Scholar 

  • Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386

    Article  CAS  PubMed  Google Scholar 

  • Ferrara N (2009) Vascular endothelial growth factor. Arterioscler Thromb Vasc Biol 29:789–791

    Article  CAS  PubMed  Google Scholar 

  • Ferrara N, Gerber H-P, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9(6):669–676

    Article  CAS  PubMed  Google Scholar 

  • Fraga A, Ribeiro R, Coelho A, Vizcaíno JR, Coutinho H et al (2017) Genetic polymorphisms in key hypoxia-regulated downstream molecules and phenotypic correlation in prostate cancer. BMC Urol 17(1):12

    Article  PubMed  PubMed Central  Google Scholar 

  • Gao H, Niu Z, Zhang Z, Wu H, Xie Y et al (2019) TNFSF15 promoter polymorphisms increase the susceptibility to small cell lung cancer: a case-control study. BMC Med Genet 20:1–7

    Article  Google Scholar 

  • Goel HL, Mercurio AM (2013) VEGF targets the tumour cell. Nat Rev Cancer 13:871–882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grimaldo S, Tian F, Li L-Y (2009) Sensitization of endothelial cells to VEGI-induced apoptosis by inhibiting the NF-κB pathway. Apoptosis 14:788–795

    Article  CAS  PubMed  Google Scholar 

  • Guba M, Seeliger H, Kleespies A, Jauch K-W, Bruns C (2004) Vascular endothelial growth factor in colorectal cancer. Int J Colorectal Dis 19:510–517

    Article  PubMed  Google Scholar 

  • Han S, Liu L, Xu F, Chen S, Yuan W et al (2016) A case-control study about the association between vascular endothelial growth inhibitor gene polymorphisms and breast cancer risk in female patients in Northeast China. Chin J Cancer Res 28:435

    Article  PubMed  PubMed Central  Google Scholar 

  • Haridas V, Shrivastava A, Su J, Yu GL, Ni J et al (1999) VEGI, a new member of the TNF family activates nuclear factor-κB and c-Jun N-terminal kinase and modulates cell growth. Oncogene 18:6496–6504

    Article  CAS  PubMed  Google Scholar 

  • He P, Han Q, Liu J, Liu D, Zhao X et al (2013) The association between hypoxia-inducible factor-1 α gene C1772T polymorphism and cancer risk: a meta-analysis of 37 case-control studies. PLoS ONE 8:e83441

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  • Hou W, Medynski D, Wu S, Lin X, Li LY (2005) VEGI-192, a new isoform of TNFSF15, specifically eliminates tumor vascular endothelial cells and suppresses tumor growth. Clin Cancer Res 11:5595–5602

    Article  CAS  PubMed  Google Scholar 

  • Hu K, Xie X, Wang R, Wu F, Zhang Y (2017) Association of the rs2071559 (T/C) polymorphism with lymphatic metastasis in patients with nasopharyngeal carcinoma. Oncol Lett 14:7681–7686

    PubMed  PubMed Central  Google Scholar 

  • Ibrahim AS, Khaled HM, Mikhail NN, Baraka H, Kamel H (2014) Cancer incidence in Egypt: results of the national population-based cancer registry program. J Cancer Epidemiol 2014:1–19

    Article  Google Scholar 

  • Ikeda M, Hosoda Y, Hirose S, Okada Y, Ikeda E (2000) Expression of vascular endothelial growth factor isoforms and their receptors Flt-1, KDR, and neuropilin-1 in synovial tissues of rheumatoid arthritis. J Pathol 191:426–433

    Article  CAS  PubMed  Google Scholar 

  • Iovino F, Ferraraccio F, Orditura M, Antoniol G, Morgillo F et al (2008) Serum vascular endothelial growth factor (VEGF) levels correlate with tumor VEGF and p53 overexpression in endocrine positive primary breast cancer. Cancer Invest 26:250–255

    Article  CAS  PubMed  Google Scholar 

  • Iyer NV, Kotch LE, Agani F, Leung SW, Laughner E et al (1998) Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1α. Genes Dev 12:149–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jia W, Sander AJ, Jia G, Ni M, Liu X et al (2013) Vascular endothelial growth inhibitor (VEGI) is an independent indicator for invasion in human pituitary adenomas. Anticancer Res 33:3815–3822

    PubMed  Google Scholar 

  • Jin T, Kim S, Guo F, Howard A, Zhang Y-Z (2007) Purification and crystallization of recombinant human TNF-like ligand TL1A. Cytokine 40:115–122

    Article  CAS  PubMed  Google Scholar 

  • Jubb A, Pham T, Hanby A, Frantz G, Peale F et al (2004) Expression of vascular endothelial growth factor, hypoxia inducible factor 1α, and carbonic anhydrase IX in human tumours. J Clin Pathol 57:504–512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kadiyska T, Tourtourikov I, Popmihaylova AM, Kadian H, Chavoushian A (2018) Role of TNFSF15 in the intestinal inflammatory response. World J Gastrointest Pathophysiol 9:73

    Article  PubMed  PubMed Central  Google Scholar 

  • Kafshdooz L, Tabrizi AD, Mohaddes SM, Kafshdooz T, Akbarzadeh A et al (2015) The polymorphism of hypoxia-inducible factor-1a gene in endometrial cancer. Asian Pac J Cancer Prev 15:10393–10396

    Article  Google Scholar 

  • Karin M (2009) NF-κB as a critical link between inflammation and cancer. Cold Spring Harb Perspect Biol 1:a000141

    Article  PubMed  PubMed Central  Google Scholar 

  • Kariyazono H, Ohno T, Khajoee V, Ihara K, Kusuhara K et al (2004) Association of vascular endothelial growth factor (VEGF) and VEGF receptor gene polymorphisms with coronary artery lesions of Kawasaki disease. Pediatr Res 56:953–959

    Article  CAS  PubMed  Google Scholar 

  • Karsten MM, Beck MH, Rademacher A, Knabl J, Blohmer J-U et al (2020) VEGF-A165b levels are reduced in breast cancer patients at primary diagnosis but increase after completion of cancer treatment. Sci Rep 10:1–8

    Article  Google Scholar 

  • Kerbel RS (2008) Tumor angiogenesis. N Engl J Med 358:2039–2049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kidd LR, Brock GN, VanCleave TT, Benford ML, Lavender NA et al (2010) Angiogenesis-associated sequence variants relative to breast cancer recurrence and survival. Cancer Causes Control 21:1545–1557. https://doi.org/10.1007/s10552-010-9583-9

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim HO, Jo YH, Lee J, Lee SS, Yoon KS (2008) The C1772T genetic polymorphism in human HIF-1α gene associates with expression of HIF-1α protein in breast cancer. Oncol Rep 20:1181–1187

    CAS  PubMed  Google Scholar 

  • Kim YJ, Chul W, Jun KH, Chin HM (2019) Genetic polymorphisms of vascular endothelial growth factor (VEGF) associated with gastric cancer recurrence after curative resection with adjuvant chemotherapy. BMC Cancer 19:483

    Article  PubMed  PubMed Central  Google Scholar 

  • Krippl P, Langsenlehner U, Renner W, Yazdani-Biuki B, Wolf G et al (2003) A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk. Int J Cancer 106:468–471

    Article  CAS  PubMed  Google Scholar 

  • Kushlinskii N, Gershtein E (2002) Role of vascular endothelial growth factor during breast cancer. Bull Exp Biol Med 133:521–528

    Article  CAS  PubMed  Google Scholar 

  • Kuwai T, Kitadai Y, Tanaka S, Onogawa S, Matsutani N et al (2003) Expression of hypoxia-inducible factor-1α is associated with tumor vascularization in human colorectal carcinoma. Int J Cancer 105:176–181

    Article  CAS  PubMed  Google Scholar 

  • Langsenlehner U, Wolf G, Langsenlehner T, Gerger A, Hofmann G et al (2008) Genetic polymorphisms in the vascular endothelial growth factor gene and breast cancer risk. The Austrian “tumor of breast tissue: incidence, genetics, and environmental risk factors” study. Breast Cancer Res Treat 109:297–304

    Article  CAS  PubMed  Google Scholar 

  • Lee JW, Bae SH, Jeong JW, Kim SH, Kim KW (2004) Hypoxia-inducible factor (HIF-1) α: its protein stability and biological functions. Exp Mol Med 36:1–12

    Article  PubMed  Google Scholar 

  • Lee KWC, Lord S, Finn RS, Lim E, Martin A et al (2019) The impact of ethnicity on efficacy and toxicity of cyclin D kinase 4/6 inhibitors in advanced breast cancer: a meta-analysis. Breast Cancer Res Treat 174:271–278

    Article  CAS  PubMed  Google Scholar 

  • Lien CH, Wu WL, Wu CC, Chen YY, Lin TY et al (2019) Association of vascular endothelial growth factor gene rs25648 polymorphism and risk of bladder cancer: a meta-analysis. Tungs’ Med J 13:83–91

    Google Scholar 

  • Lu H, Shu XO, Cui Y, Kataoka N, Wen W et al (2005) Association of genetic polymorphisms in the VEGF gene with breast cancer survival. Cancer Res 65:5015–5019

    Article  CAS  PubMed  Google Scholar 

  • Lu Y, Gu X, Chen L, Yao Z, Song J et al (2014) Interferon-γ produced by tumor-infiltrating NK cells and CD4+ T cells downregulates TNFSF15 expression in vascular endothelial cells. Angiogenesis 17:529–540

    Article  CAS  PubMed  Google Scholar 

  • Madrid-Paredes A, Casado-Combreras MA, Perez-Ramirez C, Segura-Perez AM, Chamorro-Santos C et al (2020) Association of ABCB1 and VEGFA gene polymorphisms with breast cancer susceptibility and prognosis. Pathol Res Pract 216:152860

    Article  CAS  PubMed  Google Scholar 

  • Maisey N (2007) Antitumor necrosis factor (TNF-a) antibodies in the treatment of renal cell cancer. Cancer Invest 25:589–593

    Article  CAS  PubMed  Google Scholar 

  • Manzour AF, Gamal Eldin DA (2019) Awareness about breast cancer and mammogram among women attending outpatient clinics, Ain Shams University Hospitals. Egypt J Egypt Public Health Assoc 94:1–9

    Google Scholar 

  • Marmé D (2018) Tumor angiogenesis: a key target for cancer therapy. Oncol Res Treat 41:164

    Article  PubMed  Google Scholar 

  • Matsumoto Y, Tanaka K, Hirata G, Hanada M, Matsuda S et al (2002) Possible involvement of the vascular endothelial growth factor-Flt-1-focal adhesion kinase pathway in chemotaxis and the cell proliferation of osteoclast precursor cells in arthritic joints. J Immunol 168:5824–5831

    Article  CAS  PubMed  Google Scholar 

  • Metheny-Barlow LJ, Li LY (2006) Vascular endothelial growth inhibitor (VEGI), an endogenous negative regulator of angiogenesis. Seminophthalmol 21:49–58

    Google Scholar 

  • Miettinen M, Rikala MS, Rysz J, Lasota J, Wang ZF (2012) Vascular endothelial growth factor receptor 2 (VEGFR2) as a marker for malignant vascular tumors and mesothelioma–immunohistochemical study of 262 vascular endothelial and 1640 nonvascular tumors. Am J Surg Pathol 36:629

    Article  PubMed  PubMed Central  Google Scholar 

  • Paradowska-Gorycka A, Stypinska B, Pawlik A, Malinowski D, Romanowska-Prochnicka K et al (2019) KDR (VEGFR2) genetic variants and serum levels in patients with rheumatoid arthritis. Biomolecules 9:355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parr C, Gan CH, Watkins G, Jiang WG (2006) Reduced vascular endothelial growth inhibitor (VEGI) expression is associated with poor prognosis in breast cancer patients. Angiogenesis 9:73–81

    Article  CAS  PubMed  Google Scholar 

  • Qi JW, Qin TT, Xu LX, Zhang K, Yang GL et al (2013) TNFSF15 inhibits vasculogenesis by regulating relative levels of membrane-bound and soluble isoforms of VEGF receptor 1. Proc Natl Acad Sci 110:13863–13868

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Rogers MS, D’Amato RJ (2012) Common polymorphisms in angiogenesis. Cold Spring Harb Perspect Med 2:a006510

    Article  PubMed  PubMed Central  Google Scholar 

  • Sahana KR, Akila P, Prashant V, Chandra BS, Suma MN (2017) Quantitation of vascular endothelial growth factor and interleukin-6 in different stages of breast cancer. Rep Biochem Mol Biol 6:33

    Google Scholar 

  • Schäffler A, Schölmerich J, Salzberger B (2007) Adipose tissue as an immunological organ: toll-like receptors, C1q/TNFs and CTRPs. Trends Immunol 28:393–399

    Article  PubMed  Google Scholar 

  • Sharma S, Kapahi R, Sambyal V, Guleria K, Manjari M et al (2014) No association of hypoxia inducible factor-1α gene polymorphisms with breast cancer in North-West Indians. Asian Pac J Cancer Prev 15:9973–9978

    Article  PubMed  Google Scholar 

  • Shibuya M (2011) Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti-and pro-angiogenic therapies. Genes Cancer 2:1097–1105

    Article  PubMed  PubMed Central  Google Scholar 

  • Shibuya M, Claesson-Welsh L (2006) Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp Cell Res 312:549–560

    Article  CAS  PubMed  Google Scholar 

  • Slattery ML, Lundgreen A, Wolff RK (2014) VEGFA, FLT1, KDR and colorectal cancer: assessment of disease risk, tumor molecular phenotype, and survival. Mol Carcinog 53:E140–E150

    Article  CAS  PubMed  Google Scholar 

  • Ślebioda TJ, Stanisławowski M, Cyman M, Wierzbicki PM, Żurawa-Janicka D et al (2019) Distinct expression patterns of two tumor necrosis factor superfamily member 15 gene isoforms in human colon cancer. Dig Dis Sci 64:1857–1867

    Article  PubMed  PubMed Central  Google Scholar 

  • Song Y, Yang Y, Liu L, Liu X (2019) Association between five polymorphisms in vascular endothelial growth factor gene and urinary bladder cancer risk: a systematic review and meta-analysis involving 6671 subjects. Gene 698:186–197

    Article  CAS  PubMed  Google Scholar 

  • Steffensen K, Waldstrom M, Brandslund I, Jakobsen A (2010) The relationship of VEGF polymorphisms with serum VEGF levels and progression-free survival in patients with epithelial ovarian cancer. Gynecol Oncol 117:109–116

    Article  CAS  PubMed  Google Scholar 

  • Sundrani DP, Reddy US, Joshi AA, Mehendale SS, Chavan-Gautam PM et al (2013) Differential placental methylation and expression of VEGF, FLT-1 and KDR genes in human term and preterm preeclampsia. Clin Epigenet 5:1–11

    Article  Google Scholar 

  • Takahashi Y, Kitadai Y, Bucana CD, Cleary KR, Ellis LM (1995) Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res 55:3964–3968

    CAS  PubMed  Google Scholar 

  • Tracey K, Wei H, Manogue KR, Fong Y, Hesse DG et al (1988) Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. J Exp Med 167:1211–1227

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Zheng Y, Zhang W, Yu H, Lou K et al (2007) Polymorphisms of KDR Gene are associated with coronary heart disease. J Am Coll Cardiol 50:760–767

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Liu Y, Ren H, Yuan Z, Li S et al (2011) Polymorphisms in the hypoxia-inducible factor-1α gene confer susceptibility to pancreatic cancer. Cancer Biol Ther 12:383–387

    Article  PubMed  Google Scholar 

  • Watson CJ, Webb NJ, Bottomley MJ, Brenchley PE (2000) Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine 12:1232–1235

    Article  CAS  PubMed  Google Scholar 

  • Wu J, Jiang Y, Yang W, He Z, Meng S et al (2012) Dual function of RGD-modified VEGI-192 for breast cancer treatment. Bioconjug Chem 23:796–804

    Article  CAS  PubMed  Google Scholar 

  • Xu J, Xu L, Li L, You Q, Cha L (2013) HIF-1α C1772T polymorphism and gastrointestinal tract cancer risk: a meta-analysis and meta-regression analysis. Genet Test Mol Biomarkers 17:918–925

    Article  CAS  PubMed  Google Scholar 

  • Xu G-Z, Liu Y, Zhang Y, Yu J, Diao B (2015) Correlation between VEGFR2 rs2071559 polymorphism and glioma risk among Chinese population. Int J Clin Exp Med 8:16724

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yamazaki K, Umeno J, Takahashi A, Hirano A, Johnson TA et al (2013) A genome-wide association study identifies 2 susceptibility loci for Crohn’s disease in a Japanese population. Gastroenterology 144:781–788

    Article  CAS  PubMed  Google Scholar 

  • Yan JD, Liu Y, Zhang ZY, Liu GY, Xu JH et al (2015) Expression and prognostic significance of VEGFR-2 in breast cancer. Pathol Res Pract 211:539–543

    Article  CAS  PubMed  Google Scholar 

  • Yang GL, Zhao Z, Qin TT, Wang D, Chen L et al (2017) TNFSF15 inhibits VEGF-stimulated vascular hyperpermeability by inducing VEGFR2 dephosphorylation. FASEB J 31:2001–2012

    Article  CAS  PubMed  Google Scholar 

  • Ye BD, Choi H, Hong M, Yun WJ, Low HQ et al (2016) Identification of ten additional susceptibility loci for ulcerative colitis through immunochip analysis in Koreans. Inflamm Bowel Dis 22:13–19

    Article  PubMed  Google Scholar 

  • Yu J, Tian S, Metheny-Barlow L, Chew L-J, Hayes AJ et al (2001) Modulation of endothelial cell growth arrest and apoptosis by vascular endothelial growth inhibitor. Circ Res 89:1161–1167

    Article  CAS  PubMed  Google Scholar 

  • Zagouri F, Sergentanis TN, Gazouli M, Tsigginou A, Dimitrakakis C et al (2012) HSP90, HSPA8, HIF-1 alpha and HSP70-2 polymorphisms in breast cancer: a case–control study. Mol Biol Rep 39:10873–10879

    Article  CAS  PubMed  Google Scholar 

  • Zhai Y, Yu J, Iruela-Arispe L, Huang WQ, Wang Z et al (1999) Inhibition of angiogenesis and breast cancer xenograft tumor growth by VEGI, a novel cytokine of the TNF superfamily. Int J Cancer 82:131–136

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Li L-Y (2012) TNFSF15 modulates neovascularization and inflammation. Cancer Microenviron 5:237–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang N, Sanders AJ, Ye L, Jiang WG (2009a) Vascular endothelial growth inhibitor in human cancer. Int J Mol Med 24:3–8

    CAS  PubMed  Google Scholar 

  • Zhang N, Sanders AJ, Ye L, Kynaston HG, Jiang WG (2009b) Vascular endothelial growth inhibitor, expression in human prostate cancer tissue and the impact on adhesion and migration of prostate cancer cells in vitro. Int J Oncol 35:1473–1480

    PubMed  Google Scholar 

  • Zhang N, Sanders AJ, Ye L, Kynaston HG, Jiang WG (2010) Expression of vascular endothelial growth inhibitor (VEGI) in human urothelial cancer of the bladder and its effects on the adhesion and migration of bladder cancer cells in vitro. Anticancer Res 30:87–95

    CAS  PubMed  Google Scholar 

  • Zhang E, Zhu X, Han S, Peng Z, Wang W et al (2013) Increased expression of TNF ligand related molecule 1A and death receptor 3 in bladder tissues of patients with painful bladder syndrome/interstitial cystitis. Exp Ther Med 5:282–286

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Yu D, Lu J, Zhai K, Cao L et al (2014) Functional genetic variants of TNFSF15 and their association with gastric adenocarcinoma: a case-control study. PLoS ONE 9:e108321

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  • Zhang M, Wang X, Jiang X, Yang X, Wen C et al (2019) Polymorphisms of the TNF gene and three susceptibility loci are associated with crohn’s disease and perianal fistula crohn’s disease: a Study among the Han population from south China. Med Sci Monit 25:9637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu X, Wang Y, Xue W, Wang R, Wang L et al (2019) The VEGFR-2 protein and the VEGFR-2 rs1870377 A>T genetic polymorphism are prognostic factors for gastric cancer. Cancer Biol Ther 20:497–504

    Article  CAS  PubMed  Google Scholar 

  • Zidi S, Stayoussef M, Gazouani E, Mezlini A, Yacoubi-Loueslati B et al (2015) Relationship of common vascular endothelial growth factor polymorphisms and haplotypes with the risk of cervical cancer in Tunisians. Cytokine 74:108–112

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt

    Amani A. Abdelgalil, Noha M. Mesbah, Dina M. Abo-Elmatty & Eman T. Mehanna

  2. Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Rehan Monir & Fagr B. Bazeed

  3. Department of Medical Biochemistry, Faculty of Medicine, King Khalid University, Abha, Saudi Arabia

    Rehan Monir

  4. Department of Surgical Oncology, Oncology Center, Mansoura University, Mansoura, Egypt

    Mohamed Elmetwally

  5. Department of Medical Biochemistry, Faculty of Medicine, Port Said University, Port Said, Egypt

    Maivel H. Ghattas

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  1. Amani A. Abdelgalil
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  2. Rehan Monir
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  3. Mohamed Elmetwally
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  8. Eman T. Mehanna
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Contributions

All authors contributed to the study’s conception and design. AAA contributed to conceptualization, methodology, formal analysis, investigation, and writing of the original draft & reviewing and editing of the manuscript. RM, ME, MHG, FBB, NMM, and DMA contributed to supervision & reviewing of the manuscript. ETM contributed to conceptualization, supervision, methodology, investigation, and writing of the original draft & review and editing of the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Amani A. Abdelgalil.

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Abdelgalil, A.A., Monir, R., Elmetwally, M. et al. The Relation of VEGFA, VEGFR2, VEGI, and HIF1A Genetic Variants and Their Serum Protein Levels with Breast Cancer in Egyptian Patients. Biochem Genet 62, 547–573 (2024). https://doi.org/10.1007/s10528-023-10419-4

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