Information to authors
eNOS and VEGF variants might increase the risk of pancreatic cancer
Endothelial nitric oxide synthase (eNOS) is essential in chronic inflammation and carcinogenesis. The association between variants in vascular endothelial growth factor (VEGF) and several cancers still remains uncertain. We studied whether there is a relation between eNOS/VEGF variants and risk of pancreatic cancer (PC). This prospective casecontrol study included 76 PC patients (28 women and 48 men) and 100 healthy controls. Blood samples from all participants were genotyped for eNOS variable number tandem repeat (VNTR) and VEGF insertion/deletion (I/D) variants by PCR. There was a significant difference between groups for the eNOS intron 4 VNTR genotype distributions (p = 0.01). eNOS 4a/4b and 4b/4b genotypes were higher in patients with PC group compared to controls while eNOS 4a/4b genotype was more prevalent in control group than in patient group. Significant differences were observed between groups for the VEGF I/D variant genotype and allele frequencies (p ˂ 0.00, and p ˂ 0.00). VEGF I/D variant I/I genotype and I allele increased in patient group than controls. A statistically significant association was observed when the patients were compared with the controls according to D/D+D/I versus D/D (p ˂ 0.00, OR: 0.094, 95 % CI: 0.03–0.22) We provided evidence that eNOS VNTR and VEGF I/D variants might influence the development of PC.
Key words: pancreatic cancer, eNOS, VEGF, variant
E-mail: hassen hacettepe.edu.tr, serbulent.yigit gmail.com, ozgebostankolu hotmail.com, feyda.nursal gmail.com, emindaldal hotmail.com, nevinbalci hotmail.com
1. Amle, D., Mir, R., Khaneja, A., Agarwal, S., Ahlawat, R., Ray, P.C., and Saxena, A., Association of 18bp insertion/deletion polymorphism, at −2549 position of VEGF gene, with diabetic nephropathy in type 2 diabetes mellitus patients of North Indian population, J. Diabetes Metab. Disorders, 2015, vol. 14, p. 19.
2. Buraczynska, M., Ksiazek, P., Baranowicz-Gaszczyk, I., and Jozwiak, L., Association of the VEGF gene polymorphism with diabetic retinopathy in type 2 diabetes patients, Nephrol. Dialysis Transplant., 2007, vol. 22, pp. 827–832.
3. Carpini, J.D., Karam, A.K., and Montgomery, L., Vascular endothelial growth factor and its relationship to the prognosis and treatment of breast, ovarian, and cervical cancer, Angiogenesis, 2010, vol. 13, pp. 43–58.
4. Chen, J.-B., Zhang, M., Cui, Y., Liu, P.-H., Qi, Y.-W., Li, C., Cheng, X., Ren, W.-B., Li, Q.-Q., and Liu, L.-F., Association between 12 polymorphisms of VEGF/hypoxia/angiogenesis pathway genes and risk of urogenital carcinomas: a meta-analysis based on case-control studies, Front. Physiol., 2018, vol. 9, p. 715.
5. Chien, Y.-H., Bau, D.-T., and Jan, K.-Y., Nitric oxide inhibits DNA-adduct excision in nucleotide excision repair, Free Radicals Biol. Med., 2004, vol. 36, pp. 1011–1017.
6. Diler, S. and Öden, A., The T-786C, G894T, and intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene in prostate cancer cases, Russ. J. Genet., 2016, vol. 52, pp. 220–225.
7. Drobkova, H., Jurečeková, J., Sivoňová, M.K., Mazuchova, J., Škorvanová, M., Šarlinová, M., Halašová, E., and Kliment, J., Associations between gene polymorphisms of vascular endothelial growth factor and prostate cancer, Anticancer Res., 2019, vol. 39, pp. 2903–2909.
8. Erdem, D., Buyuksimsek, M., Gunaldi, M., Isiksacan, N., and Pehlivan, S., Evaluation of the relationship between eNOS and breast cancer, Tıp Fakültesi Klinikleri Dergisi, 2019, vol. 2, pp. 23–27.
9. Ferrara, N., Gerber, H.-P., and LeCouter, J., The biology of VEGF and its receptors, Nat. Med., 2003, vol. 9, pp. 669–676.
10. Fouad, H., Mona, A., Abdel, H., Amira, A., and Abdel, A., Vascular endothelial growth factor (VEGF) gene insertion/deletion polymorphism and diabetic retinopathy in patients with type 2 diabetes, J. Am. Sci., 2011, vol. 7, pp. 199–205.
11. Fukumura, D., Kashiwagi, S., and Jain, R.K., The role of nitric oxide in tumour progression, Nat. Rev. Cancer, 2006, vol. 6, pp. 521–534.
12. Hao, Y., Montiel, R., and Huang, Y., Endothelial nitric oxide synthase (eNOS) 894 G>T polymorphism is associated with breast cancer risk: a meta-analysis, Breast Cancer Res. Treat., 2010, vol. 124, pp. 809–813.
13. He, M., Zheng, K., Tan, D., and Wang, Z., Association between ERCC1 and ERCC2 gene polymorphisms and susceptibility to pancreatic cancer, Genet. Mol. Res., 2016, vol. 15.
14. He, Y., Ni, J., Chen, S., Jiang, Y., Jia, S., and Gao, Y., The vascular endothelial growth factor-2549 insertion/deletion polymorphism is not associated with susceptibility to hepatocellular carcinoma in Chinese, DNA Cell Biol., 2010, vol. 29, pp. 393–396.
15. Hefler, L.A., Ludwig, E., Lampe, D., Zeillinger, R., Leodolter, S., Gitsch, G., Koelbl, H., and Tempfer, C.B., Polymorphisms of the endothelial nitric oxide synthase gene in ovarian cancer, Gynecol. Oncol., 2002, vol. 86, pp. 134–137.
16. Huang, C.-Y., Hsieh, M.-J., Wu, W.-J., Chiang, W.-L., Liu, T.-C., Yang, S.-F., and Tsao, T.C.-Y., Association of endothelial nitric oxide synthase (eNOS) polymorphisms with EGFR-mutated lung adenocarcinoma in Taiwan, J. Cancer, 2018, vol. 9, p. 2518.
17. Jadeski, L.C., Chakraborty, C., and Lala, P.K., Nitric oxide- mediated promotion of mammary tumour cell migration requires sequential activation of nitric oxide synthase, guanylate cyclase and mitogen-activated protein kinase, Int. J. Cancer, 2003, vol. 106, pp. 496–504.
18. Khosroshahi, N.S., Pouladi, N., Shavali, M., Ghafouri, F., Abdolahi, S., and Feizi, M.A.H., Association of –634 G>C VEGF-A polymorphism in thyroid cancer patients in North West of Iran, Meta Gene, 2019, vol. 22, p. 100611.
19. Kim, Y.-J., Chul, W., Jun, K.-H., and Chin, H.-M., Genetic polymorphisms of vascular endothelial growth factor (VEGF) associated with gastric cancer recurrence after curative resection with adjuvant chemotherapy, BMC Cancer, 2019, vol. 19, p. 483.
20. Medeiros, R., Morais, A., Vasconcelos, A., Costa, S., Carrilho, S., Oliveira, J., and Lopes, C., Endothelial nitric oxide synthase gene polymorphisms and the shedding of circulating tumour cells in the blood of prostate cancer patients, Cancer Lett., 2003, vol. 189, pp. 85–90.
21. Medeiros, R., Morais, A., Vasconcelos, A., Costa, S., Pinto, D., Oliveira, J., and Lopes, C., Endothelial nitric oxide synthase gene polymorphisms and genetic susceptibility to prostate cancer, Eur. J. Cancer Prev., 2002, vol. 11, pp. 343–350.
22. Nakamura, M., Abe, Y., and Tokunaga, T., Pathological significance of vascular endothelial growth factor A isoform expression in human cancer, Pathol. Int., 2002, vol. 52, pp. 331–339.
23. Ordóñez, A.G., Carreira, J.F., Franco, A.G., Sánchez, L.M., Alvarez, M., and García, E.C., Two expressive polymorphisms on the endothelial nitric oxide synthase gene (intron 4, 27 bp repeat and − 786 T/C) and the venous thromboembolism, Thromb. Res., 2000, vol. 99, pp. 563–566.
24. Öztürk, E., Dikensoy, E., Balat, Ö., Uğur, M.G., Balcı, S.O., Aydın, A., Kazancı, Ü., and Pehlivan, S., Association of endothelial nitric oxide synthase gene polymorphisms with endometrial carcinoma: a preliminary study, J. Turk.-Ger. Gynecol. Assoc., 2011, vol. 12, p. 229.
25. Polat, F., Turaclar, N., Yilmaz, M., Bingöl, G., and Vural, H.C., eNOS gene polymorphisms in paraffin-embedded tissues of prostate cancer patients, Turk. J. Med. Sci., 2016, vol. 46, pp. 673–679.
26. Rahib, L., Smith, B.D., Aizenberg, R., Rosenzweig, A.B., Fleshman, J.M., and Matrisian, L.M., Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States, Cancer Res., 2014, vol. 74, pp. 2913–2921.
27. Ramírez-Patiño, R., Figuera, L.E., Puebla-Pérez, A.M., Delgado-Saucedo, J.I., Legazpí-Macias, M.M., Mariaud-Schmidt, R.P., Ramos-Silva, A., Gutiérrez-Hurtado, I.A., Gómez Flores-Ramos, L., and Zúñiga-González, G.M., Intron 4 VNTR (4a/b) polymorphism of the endothelial nitric oxide synthase gene is associated with breast cancer in Mexican women, J. Korean Med. Sci., 2013, vol. 28, pp. 1587–1594.
28. Riener, E.-K., Hefler, L.A., Grimm, C., Galid, A., Zeillinger, R., Tong-Cacsire, D., Gitsch, G., Leodolter, S., and Tempfer, C.B., Polymorphisms of the endothelial nitric oxide synthase gene in women with vulvar cancer, Gynecol. Oncol., 2004, vol. 93, pp. 686–690.
29. Song, Y., Yang, Y., Liu, L., and Liu, X., 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, 2019, vol. 698, pp. 186–197.
30. Ungerbäck, J., Elander, N., Dimberg, J., and Söderkvist, P., Analysis of VEGF polymorphisms, tumor expression of VEGF mRNA and colorectal cancer susceptibility in a Swedish population, Mol. Med. Rep., 2009, vol. 2, pp. 435–439.
31. Vincenti, V., Cassano, C., Rocchi, M., and Persico, M.G., Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3, Circulation, 1996, vol. 93, pp. 1493–1495.
32. Wang, X.L., Sim, A.S., Badenhop, R.F., Mccredie, R.M., and Wilcken, D.E., A smoking–dependent risk of coronary artery disease associated with a polymorphism of the endothelial nitric oxide synthase gene, Nat. Med., 1996, vol. 2, pp. 41–45.
33. Wu, X., Wang, Z.-.F., Xu, Y., Ren, R., Heng, B.-L., and Su, Z.-X., Association between three eNOS polymorphisms and cancer risk: a meta-analysis, Asian Pac. J. Cancer Prev., 2014, vol. 15, pp. 5317–5324.
34. Yamamori, M., Taniguchi, M., Maeda, S., Nakamura, T., Okamura, N., Kuwahara, A., Iwaki, K., Tamura, T., Aoyama, N., and Markova, S., VEGF T-1498C polymorphism, a predictive marker of differentiation of colorectal adenocarcinomas in Japanese, Int. J. Med. Sci., 2008, vol. 5, p. 80.
35. Yang, F., Qin, Z., Shao, C., Liu, W., Ma, L., Shu, Y., and Shen, H., Association between VEGF gene polymorphisms and the susc
|Coded & Designed by Volodymyr Duplij||Modified 21.09.21|