Abstract
The aim of the study is to study the correlation of genetic polymorphism of vascular endothelial growth factor (VEGF) gene with susceptibility to primary lung cancer. A total of 414 patients with primary lung cancer and 338 healthy volunteers were enrolled in this case–control study from September 2008 to October 2011. Gene identification with PCR-RFLP (polymerase chain reaction-based restriction fragment length polymorphism) was used to detect in white blood cells from the subjects the single-nucleotide polymorphisms (SNP) of VEGF gene, including +405G/C, −460 T/C, −1154G/A, −2578C/A sites. Association of genotypes or haplotypes with susceptibility of lung cancer was analyzed with unconditional logistic regression adjusted by gender and age. Smoking was significantly associated with increased risk of lung cancer. Gene phenotypic analysis demonstrated that C allele of +405G/C in VEGF gene was significantly associated increased risk of lung cancer in males (P=0.0094, odds ratio=1.634.3), as that with carrying GCTC haplotype (odds ratio=1.349), whereas carrying GACG had decreased risk for lung cancer (odds ratio=0.044). No relationship existed between 460 T/C, −1154G/A, −2578C/A alleles of VEGF gene and risk of lung cancer. VEGF gene polymorphism may have a role in the development of lung cancer.
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References
Harris SR, Schoeffner DJ, Yoshiji H, Thorgeirsson UP . Tumor growth enhancing effects of vascular endothelial growth factor are associated with increased nitric oxide synthase activity and inhibition of apoptosis in human breast carcinoma xenografts. Cancer Lett 2002; 179: 95–101.
Watson CJ, Webb NJ, Bottomley MJ, Brenchley PE . Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine 2000; 12: 1232–1235.
Mohammadi M, Bazrafshani MR, Day PJ, Ollier WE . Vascular endothelial growth factor production is regulated by gene polymorphisms. Iran J Immunol 2009; 6: 119–129.
Awata T, Inoue K, Kurihara S, Ohkubo T, Watanabe M, Inukai K et al. A common polymorphism in the 5'-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes 2002; 51: 1635–1639.
Bradbury PA, Zhai R, Ma C, Xu W, Hopkins J, Kulke MJ et al. Vascular endothelial growth factor polymorphisms and esophageal cancer prognosis. Clin Cancer Res 2009; 15: 4680–4685.
Renner W, Kotschan S, Hoffmann C, Obermayer-Pietsch B, Pilger. E . A common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels. J Vasc Res 2000; 37: 443–448.
Maeda A, Nakata M, Yasuda K, Yukawa T, Saisho S, Okita R et al. Influence of vascular endothelial growth factor single nucleotide polymorphisms on non-small cell lung cancer tumor angiogenesis. Oncol Rep 2013; 29: 39–44.
Slatore CG, Sullivan DR, Pappas M, Humphrey LL . Patient-centered outcomes among lung cancer screening recipients with computed tomography: a systematic review. J Thorac Oncol 2014; 9: 927–934.
Hasegawa Y . [Lung cancer: progress in diagnosis and treatments. Topics: I. Epidemiology and pathogenesis; 2. The etiology of lung cancer]. Nihon Naika Gakkai Zasshi 2014; 103: 1261–1266.
Zhao Y, Wei Q, Hu L, Chen F, Hu Z, Heist RS et al. Polymorphisms in microRNAs are associated with survival in non-small cell lung cancer. Cancer Epidemiol Biomarkers Prev 2014; 23: 2503–2511.
Guo Z, Wang H, Li Y, Li B, Li C, Ding. C . A microRNA-related single nucleotide polymorphism of the gene is associated with survival of small cell lung cancer patients. Biomed Rep 2013; 1: 545–548.
Wang G, Wang W, Gao W, Lv J, Fang J . Two functional polymorphisms in microRNAs and lung cancer risk: a meta-analysis. Tumour Biol 2014; 35: 2693–2699.
Xu J, Yin Z, Shen H, Gao W, Qian Y, Pei D et al. A genetic polymorphism in pre-miR-27a confers clinical outcome of non-small cell lung cancer in a Chinese population. PLoS One 2013; 8: e79135.
Ding C, Li C, Wang H, Li B, Guo. Z . A miR-SNP of the XPO5 gene is associated with advanced non-small-cell lung cancer. Onco Targets Ther 2013; 6: 877–881.
Cheng M, Yang L, Yang R, Yang X, Deng J, Yu B et al. A microRNA-135a/b binding polymorphism in CD133 confers decreased risk and favorable prognosis of lung cancer in Chinese by reducing CD133 expression. Carcinogenesis 2013; 34: 2292–2299.
Chen Z, Xu L, Ye X, Shen S, Li Z, Niu X et al. Polymorphisms of microRNA sequences or binding sites and lung cancer: a meta-analysis and systematic review. PLoS One 2013; 8: e61008.
Iacovelli R, Sternberg CN, Porta C, Verzoni E, Braud FD, Escudier B et al. Inhibition of the VEGF/VEGFR pathway improves survival in advanced kidney cancer. A systematic review and meta-analysis. Curr Drug Targets 2014; 16: 164–170.
Cao Y . VEGF-targeted cancer therapeutics-paradoxical effects in endocrine organs. Nat Rev Endocrinol 2014; 10: 530–539.
Park do J, Thomas NJ, Yoon C, Yoon SS . Vascular endothelial growth factor a inhibition in gastric cancer. Gastric Cancer 2015; 18: 33–42.
Datta-Mitra A, Riar NK, Raychaudhuri SP . Remission of psoriasis and psoriatic arthritis during bevacizumab therapy for renal cell cancer. Indian J Dermatol 2014; 59: 632.
Inglis DJ, Lavranos TC, Beaumont DM, Leske AF, Brown CK, Hall AJ et al. The vascular disrupting agent BNC105 potentiates the efficacy of VEGF and mTOR inhibitors in renal and breast cancer. Cancer Biol Ther 2014; 15: 1552–1560.
Cao R, Zhang S, Ma D, Hu. L . A multi-center randomized phase II clinical study of bevacizumab plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) compared with FOLFIRI alone as second-line treatment for Chinese patients with metastatic colorectal cancer. Med Oncol 2015; 32: 325.
Mitry E, Walter T, Baudin E, Kurtz JE, Ruszniewski P, Dominguez-Tinajero S et al. Bevacizumab plus capecitabine in patients with progressive advanced well-differentiated neuroendocrine tumors of the gastro-intestinal (GI-NETs) tract (BETTER trial) - A phase II non-randomised trial. Eur J Cancer 2014; 50: 3107–3115.
Li H, Takayama K, Wang S, Shiraishi Y, Gotanda K, Harada T et al. Addition of bevacizumab enhances antitumor activity of erlotinib against non-small cell lung cancer xenografts depending on VEGF expression. Cancer Chemother Pharmacol 2014; 74: 1297–1305.
Weiss JM, Villaruz LC, Socinski MA, Ivanova A, Grilley-Olson J, Dhruva N et al. A single-arm phase II trial of pazopanib in patients with advanced non-small cell lung cancer with non-squamous histology with disease progression on bevacizumab containing therapy. Lung Cancer 2014; 86: 288–290.
Danciu OC, Rayani S, Michals EA, Villano JL . Prolonged activity of bevacizumab in adenocarcinoma of the lung with multiple brain metastases. Med Oncol 2012; 29: 2619–2622.
Koukourakis MI, Papazoglou D, Giatromanolaki A, Bougioukas G, Maltezos E, Sivridis E . VEGF gene sequence variation defines VEGF gene expression status and angiogenic activity in non-small cell lung cancer. Lung Cancer 2004; 46: 293–298.
Koukourakis MI, Papazoglou D, Giatromanolaki A, Panagopoulos I, Maltezos E, Harris AL et al. C2028T polymorphism in exon 12 and dinucleotide repeat polymorphism in intron 13 of the HIF-1alpha gene define HIF-1alpha protein expression in non-small cell lung cancer. Lung Cancer 2006; 53: 257–262.
Heist RS, Zhai R, Liu G, Zhou W, Lin X, Su L et al. VEGF polymorphisms and survival in early-stage non-small-cell lung cancer. J Clin Oncol 2008; 26: 856–862.
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The study is supported by Hebei Natural Science Funding (Grant # C2009001199).
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Liu, C., Zhou, X., Gao, F. et al. Correlation of genetic polymorphism of vascular endothelial growth factor gene with susceptibility to lung cancer. Cancer Gene Ther 22, 312–316 (2015). https://doi.org/10.1038/cgt.2015.24
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DOI: https://doi.org/10.1038/cgt.2015.24