Association of the rs2071559 (T/C) polymorphism with lymphatic metastasis in patients with nasopharyngeal carcinoma

Hu,Kai; Xie,Xiujing; Wang,Rensheng; Wu,Fang; Zhang,Yong

doi:10.3892/ol.2017.7209

Association of the rs2071559 (T/C) polymorphism with lymphatic metastasis in patients with nasopharyngeal carcinoma

Authors:
- Kai Hu
- Xiujing Xie
- Rensheng Wang
- Fang Wu
- Yong Zhang
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Affiliations: Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Ultrasonic Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: October 18, 2017 https://doi.org/10.3892/ol.2017.7209
Pages: 7681-7686
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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1	Wee JT, Ha TC, Loong SL and Qian CN: Is nasopharyngeal cancer really a ‘Cantonese cancer’? Chin J Cancer. 29:517–526. 2010. View Article : Google Scholar : PubMed/NCBI
2	Guo XC, Scott K, Liu Y, Dean M, David V, Nelson GW, Johnson RC, Dilks HH, Lautenberger J, Kessing B, et al: Genetic factors leading to chronic Epstein-Barr virus infection and nasopharyngeal carcinoma in South East China: Study design, methods and feasibility. Hum Genomics. 2:365–375. 2006. View Article : Google Scholar : PubMed/NCBI
3	Försti A, Jin Q, Altieri A, Johansson R, Wagner K, Enquist K, Grzybowska E, Pamula J, Pekala W, Hallmans G, et al: Polymorphisms in the KDR and POSTN genes: Association with breast cancer susceptibility and prognosis. Breast Cancer Res Treat. 101:83–93. 2007. View Article : Google Scholar : PubMed/NCBI
4	Folkman J: Tumor angiogenesis: Therapeutic implications. N Engl J Med. 285:1182–1186. 1971. View Article : Google Scholar : PubMed/NCBI
5	Carmeliet P and Jain RK: Angiogenesis in cancer and other diseases. Nature. 407:249–257. 2000. View Article : Google Scholar : PubMed/NCBI
6	Guo P, Xu L, Pan S, Brekken RA, Yang ST, Whitaker GB, Nagane M, Thorpe PE, Rosenbaum JS, Huang Su HJ, et al: Vascular endothelial growth factor isoforms display distinct activities in promoting tumor angiogenesis at different anatomic sites. Cancer Res. 61:8569–8577. 2001.PubMed/NCBI
7	Brenner RM, Nayak NR, Slayden OD, Critchley HO and Kelly RW: Premenstrual and menstrual changes in the macaque and human endometrium: Relevance to endometriosis. Ann N Y Acad Sci. 955(60–74): 86–88, 396–406. 2002.
8	Qi L, Robinson WA, Brady BM and Glode LM: Migration and invasion of human prostate cancer cells is related to expression of VEGF and its receptors. Anticancer Res. 23:3917–3922. 2003.PubMed/NCBI
9	Waltenberger J, Claesson-Welsh L, Siegbahn A, Shibuya M and Heldin CH: Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J Biol Chem. 269:26988–26995. 1994.PubMed/NCBI
10	Iughetti P, Suzuki O, Godoi PH, Alves VA, Sertié AL, Zorick T, Soares F, Camargo A, Moreira ES, di Loreto C, et al: A polymorphism in endostatin, an angiogenesis inhibitor, predisposes for the development of prostatic adenocarcinoma. Cancer Res. 61:7375–7378. 2001.PubMed/NCBI
11	Howell WM, Bateman AC, Turner SJ, Collins A and Theaker JM: Influence of vascular endothelial growth factor single nucleotide polymorphisms on tumour development in cutaneous malignant melanoma. Genes Immun. 3:229–232. 2002. View Article : Google Scholar : PubMed/NCBI
12	Balasubramanian SP, Brown NJ and Reed MW: Role of genetic polymorphisms in tumour angiogenesis. Br J Cancer. 87:1057–1065. 2002. View Article : Google Scholar : PubMed/NCBI
13	Wang Y, Zheng Y, Zhang W, Yu H, Lou K, Zhang Y, Qin Q, Zhao B, Yang Y and Hui R: Polymorphisms of KDR Gene are associated with coronary heart disease. J Am Coll Cardiol. 50:760–767. 2007. View Article : Google Scholar : PubMed/NCBI
14	Thompson L: World Health Organization classification of tumours: Pathology and genetics of head and neck tumours. Ear Nose Throat J. 85:742006.PubMed/NCBI
15	Sobin LH, Gospodarowicz MK and Wittekind C: TNM Classification of Malignant Tumors. 7th edition. Wiley-Blackwell; Oxford: 2009
16	Patterson C, Perrella MA, Hsieh CM, Yoshizumi M, Lee ME and Haber E: Cloning and functional analysis of the promoter for KDR/flk-1, a receptor for vascular endothelial growth factor. J Biol Chem. 270:23111–23118. 1995. View Article : Google Scholar : PubMed/NCBI
17	An SJ, Chen ZH, Lin QX, Su J, Chen HJ, Lin JY and Wu YL: The −271G>A polymorphism of kinase insert domain-containing receptor gene regulates its transcription level in patients with non-small cell lung cancer. BMC Cancer. 9:1442009. View Article : Google Scholar : PubMed/NCBI
18	Zhang W, Sun K, Zhen Y, Wang D, Wang Y, Chen J, Xu J, Hu FB and Hui R: VEGF receptor-2 variants are associated with susceptibility to stroke and recurrence. Stroke. 40:2720–2726. 2009. View Article : Google Scholar : PubMed/NCBI
19	Kariyazono H, Ohno T, Khajoee V, Ihara K, Kusuhara K, Kinukawa N, Mizuno Y and Hara T: Association of vascular endothelial growth factor (VEGF) and VEGF receptor gene polymorphisms with coronary artery lesions of Kawasaki Disease. Pediatr Res. 56:953–959. 2004. View Article : Google Scholar : PubMed/NCBI
20	Kariž S and Petrovič D: Minor association of kinase insert domain-containing receptor gene polymorphism (rs2071559) with myocardial infarction in Caucasians with type 2 diabetes mellitus: Case-control cross-sectional study. Clin Biochem. 47:192–196. 2014. View Article : Google Scholar : PubMed/NCBI
21	Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML and Schuh AC: Failure of blood-island formation and vasculogenesis in Flk-1 deficient mice. Nature. 376:62–66. 1995. View Article : Google Scholar : PubMed/NCBI
22	Duff SE, Jeziorska M, Rosa DD, Kumar S, Haboubi N, Sherlock D, O'Dwyer ST and Jayson GC: Vascular endothelial growth factors and receptors in colorectal cancer: Implications for anti-angiogenic therapy. Eur J Cancer. 42:112–117. 2006. View Article : Google Scholar : PubMed/NCBI
23	Hirakawa S, Kodama S, Kunstfeld R, Kajiya K, Brown LF and Detmar M: VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis. J Exp Med. 201:1089–1099. 2005. View Article : Google Scholar : PubMed/NCBI
24	Nagy VM, Buiga R, Brie I, Todor N, Tudoran O, Ordeanu C, Virág P, Tarta O, Rus M and Bălăcescu O: Expression of VEGF, VEGFR, EGFR, COX-2 and MVD in cervical carcinoma, in relation with the response to radio-chemotherapy. Rom J Morphol Embryol. 52:53–59. 2011.PubMed/NCBI
25	Rydén L, Jirström K, Haglund M, Stål O and Fernö M: Epidermal growth factor receptor and vascular endothelial growth factor receptor 2 are specific biomarkers in triple-negative breast cancer. Results from a controlled randomized trial with long-term follow-up. Breast Cancer Res Treat. 120:491–498. 2010. View Article : Google Scholar : PubMed/NCBI
26	Mele T, Generali D, Fox S, Brizzi MP, Bersiga A, Milani M, Allevi G, Bonardi S, Aguggini S, Volante M, et al: Anti-angiogenic effect of tamoxifen combined with epirubicin in breast cancer patients. Breast Cancer Res Treat. 123:795–804. 2010. View Article : Google Scholar : PubMed/NCBI
27	Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, et al: BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 64:7099–7109. 2004. View Article : Google Scholar : PubMed/NCBI
28	Escudier B, Rini BI, Motzer RJ, Tarazi J, Kim S, Huang X, Rosbrook B, English PA, Loomis AK and Williams JA: Genotype correlations with blood pressure and efficacy from a randomized phase iii trial of second-line axitinib versus sorafenib in metastatic renal cell carcinoma. Clin Genitourin Cancer. 13:328–337. 2015. View Article : Google Scholar : PubMed/NCBI
29	Zheng YB, Zhan MX, Zhao W, Liu B, Huang JW, He X, Fu SR, Zhao Y, Li Y, Hu BS and Lu LG: The relationship of kinase insert domain receptor gene polymorphisms and clinical outcome in advanced hepatocellular carcinoma patients treated with sorafenib. Med Oncol. 31:2092014. View Article : Google Scholar : PubMed/NCBI
30	Novitskiy SV, Csiki I, Huang Y, Johnson DH, Harth EM, Carbone DP and Dikov MM: Anti-vascular endothelial growth factor treatment in combination with chemotherapy delays hematopoietic recovery due to decreased proliferation of bone marrow hematopoietic progenitor cells. J Thorac Oncol. 5:1410–1415. 2010. View Article : Google Scholar : PubMed/NCBI
31	Hlatky L, Hahnfeldt P and Folkman J: Clinical application of antiangiogenic therapy: Microvessel density, what it does and doesn't tell us. J Natl Cancer Inst. 94:883–893. 2002. View Article : Google Scholar : PubMed/NCBI
32	Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP, Gion M, Beliën JA, de Waal RM, Van Marck E, Magnani E, et al: Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer. 38:1564–1579. 2002. View Article : Google Scholar : PubMed/NCBI
33	Park HW, Shin ES, Lee JE, Kwon HS, Chun E, Kim SS, Chang YS, Kim YK, Min KU, Kim YY and Cho SH: Multilocus analysis of atopy in Korean children using multifactor-dimensionality reduction. Thorax. 62:265–269. 2007. View Article : Google Scholar : PubMed/NCBI